Grainger & Allison's Diagnostic Radiology, 5th Edition

Contributors

†

: deceased

Andy Adam MBBS (Hons), FRCP, FRCS, FRCR, FFRRCSI (Hon)

Professor of Interventional Radiology Department of Radiology St Thomas’ Hospital King’s College London London, UK E. Jane Adam MBBS, MRCP, FRCR Consultant Radiologist Department of Radiology St George’s Hospital London, UK Judith E. Adams MBBS, FRCR, FRCP Chair, Diagnostic Radiology Imaging Science and Biomedical Engineering University of Manchester Honorary Consultant Radiologist Royal Infirmary Manchester, UK David J. Allison BSc, MD, MRCS, LRCP, MBBS, DMRD, FRCR, FRCP

Emeritus Professor of Imaging Imperial College London, UK Sandra Allison MD Assistant Professor of Radiology Director, Radiology Residency Program Director, Ultrasound Georgetown University Hospital Washington DC, USA Philip Anslow FRCR Consultant Neuroradiologist Department of Radiology Radcliffe Infirmary Oxford, UK Susan M. Ascher MD Georgetown University Medical Center Washington DC, USA Zelena A. Aziz MD, MRCP, FRCR Consultant Radiologist Department of Radiology London Chest Hospital London, UK

Clive I. Bartram FRCS, FRCP, FRCR Emeritus Consultant, St Mark’s Hospital and Honorary Professor of Gastrointestinal Radiology Faculty of Medicine Imperial College London, UK Philip P. W. Bearcroft FRCP, FRCR Consultant Radiologist Department of Radiology Cambridge University Hospitals NHS Foundation Trust Addenbrooke’s Hospital Cambridge, UK Anna-Maria Belli DMRD, FRCR Consultant Vascular Radiologist and Reader in Radiology Department of Radiology St George’s Hospital London, UK Anthony R. Berendt BM, BCh, FRCP Consultant Physician-in-Charge Bone Infection Unit Nuffield Orthopaedic Centre Oxford, UK Lol Berman FRCP, FRCR University Department of Radiology Addenbrooke’s Hospital Cambridge, UK Martin J. K. Blomley†

Gisele Brasil Caseiras PhD Research Fellow Insitute of Neurology University College London London, UK Jackie E. Brown BDS, MSc, FDSRCP, DDRRCR Consultant Oral and Maxillofacial Radiologist Kings College London Dental Institute Guy’s Dental Hospital London, UK Dina F. Caroline MD, PhD Professor Emerita Department of Radiology Temple University Hospital Philadelphia Pennsylvania, USA Silvia D. Chang MD, FRCP(C) Assistant Professor University of British Columbia Department of Radiology Vancouver General Hospital Vancouver, Canada W. K. ‘Kling’ Chong BMedSci, MD, MRCP, FRCR Consultant Neuroradiologist Department of Radiology Great Ormond Street Hospital for Children NHS Trust London, UK Bairbre Connolly MBBCh, BAO, FRCSI, MCH, FFRRCSI, FRCP(C)

Carol A. Boles MD Associate Professor of Radiology Associate, Surgical Sciences Orthopedic Surgery Wake Forest University North Carolina, USA Jamshed B. Bomanji MBBS, MSc, PhD Consultant in Nuclear Medicine UCLH Trust Middlesex Hospital London, UK

Medical Director and Division Head of Image Guided Therapy Pediatric Interventional Radiologist Assistant Professor, University of Toronto Department of Diagnostic Imaging The Hospital for Sick Children Toronto, Canada Susan J. Copley MBBS, MD, MRCP, FRCR Consultant Radiologist and Honorary Senior Lecturer Radiology Department Hammersmith Hospital London, UK

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CONTRIBUTORS

David O. Cosgrove MA, MSc, FRCP, FRCR Emeritus Professor Imaging Sciences Department Faculty of Medicine Imperial College Hammersmith Hospital London, UK

Robert J. Eckersley PhD Research Associate Imaging Sciences Department Faculty of Medicine Imperial College Hammersmith Hospital London, UK

Philip C. Goodman MD Professor of Radiology Chief, Thoracic Imaging Division Department of Radiology Duke University Medical Center Durham North Carolina, USA

Nigel Cowan PGDipLATHE, FRCP Oxford, UK

Andrew J. Evans MRCP, FRCR Consultant Radiologist Nottingham Breast Institute Nottingham City Hospital Nottingham, UK

Isky Gordon FRCR, FRCP Professor of Paediatric Imaging Institute of Child Health London, UK

Justin J. Cross MRCP, FRCR Consultant Neuroradiologist Department of Radiology Addenbrooke’s Hospital Cambridge, UK Paras Dalal BSc, MRCP, FRCR Research Fellow in Thoracic Imaging Department of Radiology Royal Brompton Hospital London, UK Maria Daskalogiannaki MD Registrar in Radiology Department of Radiology University Hospital of Heraklion Crete, Greece A. Mark Davies FRCR Consultant Radiologist Royal Orthopaedic Hospital Birmingham, UK Adrian K. Dixon MD, FRCR, FRCP, FRCS, FMedSci, FFRRCSI (Hon), FRANZCR (Hon)

Professor of Radiology Department of Radiology Addenbrooke’s Hospital University of Cambridge Cambridge, UK Rose de Bruyn DMRD, FRCR Consultant Radiologist Department of Radiology Great Ormond Street Hospital for Sick Children NHS Trust London, UK Claudio Defilippi MD Consultant Radiologist Department of Radiology OIRM - S. Anna Hospital Turin, Italy Sujal R. Desai MD, MRCP, FRCR Consultant Radiologist Department of Radiology King’s College Hospital London, UK

Jane Evanson BSc, MBBS, MRCP, FRCR Consultant Neuroradiologist, Barts & The London Hospital NHS Trust The Royal London Hospital London, UK Laura Fender BMedSci, BMBS, MRCP, FRCR Consultant Radiologist Nottingham University Hospital Nottingham, UK Alan H. Freeman MBBS, FRCR Consultant Radiologist Department of Radiology Addenbrooke’s Hospital Cambridge, UK Julia Gates MD Assistant Professor of Radiology Department of Radiology Tufts University School of Medicine Springfield Massachusetts, USA Robert N. Gibson MBBS, MD, FRANZCR, DDU Professor of Radiology Department of Radiology University of Melbourne Royal Melbourne Hospital Victoria, Australia Raymond J. Godwin MA, MB, Bchir, FRCP, FRCR Consultant Radiologist Department of Radiology West Suffolk Hospital Suffolk, UK Karen Goldstone BSc, MSc, Csci, FIPEM Radiation Protection Advisor Acting Head of Department of Medical Physics and Clinical Engineering East Anglian Regional Radiation Protection Service (EARRPS) Addenbrooke’s Hospital Cambridge, UK

Nicholas Gourtsoyiannis FRCR (Hon) Professor of Radiology University of Crete Faculty of Medicine Heraklion, Crete Greece Andrew J. Grainger BM, BS, MRCP, FRCR Consultant Radiologist Chapel Allerton Orthopaedic Centre Leeds Teaching Hospitals Leeds, UK Ronald G. Grainger MB ChB(Hons), MD, FRCP, DMRD, FRCR, FACR(Hon), FRACR(Hon)

Professor of Diagnostic Radiology (Emeritus) University of Sheffield Honorary Consultant Radiologist Royal Hallamshire Hospital and Northern General Hospital Sheffield, UK Philippe Grenier FRCR (Hon) Professor of Radiology Service de Radiologie Polyvalente Diagnostique et Interventionnelle Hôpital Pitié-Salpêtrière Paris, France Roxana S. Gunny BS, BSc, MRCP, FRCR Consulant Neuroradiologist Department of Radiology Great Ormond Street Hospital for Children NHS Trust London, UK Christine M. Hall MBBS, DMRD, FRCR MD Professor of Paediatric Radiology Great Ormond Street Hospital for Children NHS Trust London, UK David M. Hansell MD, FRCP, FRCR, LRSM Professor of Thoracic Imaging Department of Radiology Royal Brompton Hospital London, UK

CONTRIBUTORS

George G. Hartnell FRCR, FRCP Director of Cardiovascular and Interventional Radiology Department of Radiology Baystate Medical Center Springfield Professor of Radiology Tufts University Medical School Boston Massachusetts, USA Hedvig Hricak MD, Dr. Med, SC, Dr. h.c, FRCR (Hon) Chairman, Department of Radiology Carroll and Milton Petrie Chair Professor of Radiology, Weill Medical College of Cornell University Memorial Sloan-Kettering Cancer Center New York, USA James E. Jackson MRCP, FRCR Consultant Radiologist Department of Imaging Hammersmith Hospital London, UK H. Rolf Jäger FRCR, MD Reader in Neuroradiology Institute of Neurology University College London Honorary Consultant Neuroradiologist The National Hospital for Neurology and Neurosurgery and University College Hospital London, UK Jonathan J. James BMBS, FRCR Consultant Radiologist Nottingham Breast Institute Nottingham City Hospital Nottingham, UK Renee M. Kendzierski DO Assistant Professor of Radiology Department of Radiology Temple University Hospital Philadelphia Pennsylvania, USA Dow-Mu Koh MRCP, FRCP Senior Lecturer and Honorary Consultant Department of Radiology Royal Marsden Hospital Sutton, UK Isla Lang MBChB, MRCP, FRCR Consultant Paediatric Radiologist Sheffield Children’s Hospital Sheffield, UK

Adrian K. P. Lim MD, FRCR Consultant Radiologist and Senior Lecturer Imaging Sciences Department Faculty of Medicine Imperial College Hammersmith Hospital London, UK

Stuart E. Mirvis MD, FACR Professor of Radiology Department of Radiology University of Maryland School of Medicine Baltimore Maryland, USA

David J. Lomas MA, MB, BChir, FRCR, FRCP Professor of Clinical Magnetic Resonance Imaging Department of Radiology Addenbrooke’s Hospital Cambridge, UK

Sameh K. Morcos FRCS, FFRRCSI, FRCR Professor of Diagnostic Imaging University of Sheffield Consultant Radiologist Department of Diagnostic Imaging Northern General Hospital Sheffield, UK

Sharyn L. S. MacDonald MBChB, FRANZCR Consultant Radiologist Department of Radiology Christchurch Hospital Christchurch, New Zealand David MacVicar MA, MRCP, FRCP, FRCR Consultant Radiologist Department of Diagnostic Radiology Royal Marsden Hospital Sutton, UK Adrian Manhire BSc, MBBS, FRCP, FRCR Consultant Radiologist Nottingham City Hospital Nottingham, UK Tarik F. Massoud MA, MD, PhD, FRCR University Lecturer and Honorary Consultant in Neuroradiology University Department of Radiology University of Cambridge School of Clinical Medicine Addenbrooke’s Hospital Cambridge, UK Kieran McHugh FRCPI, DCH, FRCR Department of Radiology Great Ormond Street Hospital for Sick Children NHS Trust London, UK James Meaney FRCR, FFRRCSI Director of MRI St James’s Hospital Dublin, Ireland Hylton B. Meire FRCR, DRCOG, DMRD Consultant Radiologist (Retired) King’s College Hospital London, UK Kenneth A. Miles MD, FRCR, MSc, FRCP Clinical Imaging Sciences Centre Brighton and Sussex Medical School University of Sussex Falmar, Brighton, UK

Robert A. Morgan MBChB, MRCP, FRCR Consultant Radiologist Department of Radiology St George’s Hospital London, UK Iain Morrison MBBS, MRCP, FRCR Consultant Radiologist Radiology Department Kent and Canterbury Hospital Canterbury, UK Nestor L. Müller MD, PhD, FRCPC Professor and Chairman Department of Radiology University of British Columbia Head and Medical Director Department of Radiology Vancouver General Hospital Vancouver, Canada Graham Munneke MRCP, FRCR Consultant in Interventional Radiology Department of Radiology St. George’s Hospital London, UK Alison D. Murray MB ChB (Hons), FRCR, FRCP Senior Lecturer in Radiology Department of Radiology University of Aberdeen Aberdeen, UK Richard A. Nakielny FRCR Honorary Clinical Lecturer Directorate of Medical Imaging & Medical Physics Royal Hallamshire Hospital Sheffield, UK Hrudaya Nath MD Professor of Radiology Department of Radiology University of Alabama Hospitals Birmingham Alabama, USA

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xii

CONTRIBUTORS

Tony Nicholson MSc, FRCR Consultant Vascular Radiologist Department of Clinical Radiology Leeds Teaching Hospitals Leeds, UK Amaka C. Offiah BSc, MBBS, MRCP, FRCR, PhD Consultant Radiologist (Academic) Great Ormond Street Hospital for Children NHS Trust London, UK Simon Padley BSc, MBBS, FRCP, FRCR Consultant Radiologist Department of Radiology Chelsea and Westminster Hospital London, UK Martyn N. J. Paley PhD, FInstP Professor of MR Physics Academic Radiology University of Sheffield Sheffield, UK Nickolas Papanikolaou PhD Biomedical Engineer Department of Radiology University Hospital of Heraklion Crete, Greece Jai Patel MBChB, MRCP, FRCR Consultant Vascular Radiologist Department of Clinical Radiology St James’s University Hospital Leeds, UK Anne Paterson MBBS, MRCP, FRCR, FFR RCSI Consultant Paediatric Radiologist Radiology Department Royal Belfast Hospital for Sick Children Belfast, UK Praveen Peddu MRCS, FRCR Specialist Registrar in Radiology Department of Radiology King’s College Hospital London, UK A. Michael Peters BSc, MD, MSc, MRCP, MRCPath, FRCR

Professor of Nuclear Medicine Brighton and Sussex Medical School University of Sussex Brighton, UK William H. Ramsden BM, FRCR Consultant Paediatric Radiologist Department of Clinical Radiology St James’s University Hospital Leeds, UK

Sheila Rankin FRCR Consultant Radiologist Department of Radiology Guy’s and St. Thomas’ Foundation Trust London, UK

John Rout BDS, FDSRCS, MDentSc, DDRRCR, FRCR Consultant Oral and Maxillofacial Radiologist Birmingham Dental Hospital Birmingham, UK

Padma Rao MBBS, BSc, MRCP, FRCR,

Michael B. Rubens MB, DMRD, FRCR Consultant Radiologist Department of Radiology Royal Brompton Hospital London, UK

FRANZCR

Consultant Paediatric Radiologist Royal Children’s Hospital Parkville Melbourne Victoria, Australia Christine Reek BSc, FRCR Consultant Radiologist Department of Radiology Greenfield Hospital Leicester, UK John H. Reynolds DMRD, FRCR, MMedSci Consultant Radiologist Birmingham Heartlands Hospital Birmingham, UK Rodney H. Reznek FRANZCR (Hon), FRCP, FRCR Professor of Diagnostic Imaging The Centre for Cancer Imaging St Bartholomew’s Hospital and The London Queen Mary’s School of Medicine and Dentistry London, UK Philip M. Rich BSc, FRCS, FRCR Consultant Neuroradiologist Department of Neuroradiology Atkinson Morley Wing St George’s Hospital London, UK Andrea Rockall MD, BS, BSc, MRCP, FRCP Department of Radiology St Bartholomew’s Hospital London, UK Giles Roditi FRCP, FRCR Consultant Radiologist Department of Radiology Glasgow Royal Infirmary Glasgow, UK

Asif Saifuddin BSc (Hons), MBChB, MRCP, FRCR Consultant Radiologist Department of Radiology Royal National Orthopaedic Hospital NHS Trust Stanmore, UK Evis Sala MD, PhD, FRCR University Lecturer in Oncology Imaging University Department of Radiology Addenbrooke’s Hospital Cambridge, UK Caron Sandhu FRCR Consultant Radiologist Department of Radiology Guy’s and St. Thomas’ Hospital London, UK Dawn Saunders MD, MRCP, FRCR Consultant Neuroradiologist Department of Radiology Great Ormond Street Hospital for Children NHS Trust London, UK Daniel J. Scoffings MRCP, FRCR Specialist Registrar in Neuroradiology Addenbrooke’s Hospital Cambridge, UK Djilda Segerman MA, MSc, MIPEM Head of Nuclear Medicine Physics Department of Medical Physics Brighton and Sussex University Hospitals NHS Trust Brighton, UK

Lee F. Rogers MD Clinical Professor of Radiology Department of Radiology University of Arizona Health Services Tucson Arizona, USA

Kathirkama Shanmuganathan MD Associate Professor of Radiology Department of Radiology University of Maryland School of Medicine Baltimore Maryland, USA

Giles Rottenberg FRCR Consultant Radiologist Department of Radiology Guy’s and St. Thomas’ Foundation Trust London, UK

Ashley S. Shaw MRCP, FRCR Consultant Radiologist Department of Radiology Addenbrooke’s Hospital Cambridge, UK

CONTRIBUTORS

Mihra S. Taljanovic MD, MA Associate Professor of Clinical Radiology and Clinical Orthopedic Surgery Head - Musculoskeletal Imaging Section Department of Radiology Tucson Arizona, USA

Satinder P. Singh MD, FCCP Associate Professor of Radiology Director Cardiac CT Director, Combined Cardiopulmonary and Abdominal Fellowship Chief of Cardiopulmonary Radiology Department of Radiology University of Alabama Hospitals Birmingham Alabama, USA

FRCR

S. Aslam A. Sohaib MRCP, FRCR Radiology Department Royal Marsden Hospital London, UK

Consultant Radiologist Department of Clinical Radiology Great Ormond Street Hospital for Children NHS Trust London, UK

Alan Sprigg MBChB, DCH, DRCOG, DMRD, FRCR, FRCPCH

Consultant Paediatric Radiologist Sheffield Children’s Hospital Sheffield, UK John M. Stevens MBBS, DRACR, FRCR Lyshom Department of Neuroradiology Radiology Department The National Hospital for Neurology and Neurosurgery London, UK Dennis J. Stoker MB, FRCP, FRCS, FRCR Emeritus Consultant Radiologist Henley-on-Thames, UK Nicola H. Strickland BM BCh, MA (Hons),

Andrew M. Taylor BA (Hons), BM BCh, MRCP

Stuart Taylor BSc, MD, MRCP, FRCR Consultant Radiologist Department of Intestinal Imaging St Marks Hospital Northwick Park Harrow, UK Henrik S. Thomsen MD Professor and Chairman Department of Diagnostic Radiology Copenhagen University Hospital Herlev, Denmark Paolo Toma MD Radiologist-in-Chief Radiology Department G. Gaslini Institute Genoa, Italy

(Oxon), FRCP, FRCR

Consultant Radiologist Imaging Department Hammersmith Hospitals NHS Trust Honorary Senior Lecturer Imperial College London, UK Louise E. Sweeney MBBCH, BAO, DCH, DMRD, FRCR, FFR, RCSI

Consultant Paediatric Radiologist Radiology Department Royal Belfast Hospital for Sick Children Belfast, UK

Peter Twining FRCR, BSc, BS MB Consultant Radiologist Nottingham University Hospital Nottingham, UK John A. Verschakelen MD, PhD Professor of Chest Radiology Department of Radiology University Hospitals Gasthuisberg Leuven, Belgium

Sarah J. Vinnicombe BSc, MRCP, FRCR Consultant Radiologist Department of Radiology St Bartholomew’s Hospital London, UK Gustav K. von Schulthess MD, PhD Professor and Director Department of Radiology University Hospital Zurich, Switzerland Iain D. Wilkinson BSc, MSc, PhD, CSci, ARCP, FIPEM

Reader in Magnetic Resonance & Consultant Clinical Scientist Academic Radiology University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust Sheffield, UK A. Robin M. Wilson FRCR, FRCP(E) Consultant Radiologist King’s College Hospital and Guy’s and St Thomas’ Foundation Trusts London, UK David J. Wilson MBBS, BSc, FRCP, FRCR Consultant Musculoskeletal Radiologist Nuffield Orthopaedic Centre and University of Oxford Oxford, UK Stuart J. Yates MSci, MSc, CSci, MIPEM Principal Physicist Department of Medical Physics & Clinical Engineering Cambridge University Hospitals NHS Foundation Trust Cambridge, UK

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Preface

We hope that this 5th edition of Diagnostic Radiology will continue to build on the original vision of Professors Grainger and Allison who, back in the early 1980s, saw the need for a ‘bible’ for doctors studying for postgraduate examinations in radiology, and to provide a bench book for reporting and reference. The success of the first four editions, which were extremely well received by an increasingly international readership, speaks for the realisation of their dream. Few could have predicted at that stage the extraordinary growth of radiology, or its increasing importance within all aspects of modern medicine. The unprecedented expansion in the imaging repertoire, together with the trend for increasing subspecialisation, have led to changes in training and in the methods used for teaching and learning. This book has had to evolve to reflect these changes, adapting to the perceived needs of those facing postgraduate examinations and also to all radiologists who wish to have an up-to-date basic general textbook for ready reference and illustration. An attempt to cover every subject in detail would have resulted in a huge book that would have been very difficult to use.We have chosen to concentrate on those subjects that most radiologists need to know well, and to pay special attention to the needs of trainee radiologists preparing for examinations. Because training throughout Europe is moving towards a three

year basic course followed by two years of training in selected subspecialties, the factual examination in the UK has moved to an earlier stage in training with less emphasis on some of the diagnostic rarities so beloved by examiners of old. The curriculum is now somewhat less comprehensive and the reduction in size of this 5th Edition reflects that – down from three volumes to two. In this electronic age there are many databases of images available on the internet, with accompanying text. Nevertheless, we believe that well structured textbooks remain an essential part of medical education and practice as they present information in a format that facilitates learning, guiding the reader through an unfamiliar field. We are convinced that Diagnostic Radiology will remain a valuable resource for many years to come. We are again extremely grateful to the distinguished international cast of authors who have all worked hard to deliver fresh and up-to-date material. We are also most grateful to Michael Houston, Gavin Smith and Nora Naughton for their professional skills and publishing expertise and to Jeremy Rabouhans for invaluable help with proof reading. We could never have done it without them! Andy Adam Adrian Dixon

Acknowledgements

This edition could not have occured without the large amount of work done by all the contributing authors and their colleagues. However, the vision and overall planning of Michael Houston at Elsevier have been fundamental in bringing the book to fruition. So, too, has the meticulous gathering and editing of material by Gavin Smith. Finally, the skilful copyediting, and other tasks provided by Nora Naughton, and her remarkable team, must not be forgotten; without them the Editors simply could not have managed. All of these col-

leagues remained remarkably cheerful throughout and kept strong heads even when chapters were late, images missing, and all the other hiccups that can hinder progress in a project of this kind. At a local level, all the Editors would like to thank their various secretaries, technicians and colleagues who have helped proofread, collect material and made various other invaluable contributions. The Editors

CHAPTER

Picture Archiving and Communication Systems (PACS) and Digital Radiology

1

Nicola H. Strickland

The role of PACS Advantages and disadvantages of PACS • Advantages of PACS • Disadvantages of PACS Planning for PACS • The PACS project team • Tendering for a PACS • The PACS contract • Economic considerations • Purchasing versus leasing a PACS • PRE-PACS workflow and preparation • Acronyms: DICOM, HL7 and IHE PACS project implementation • Implementation of digital image acquisition prior to PACS • Integration of PACS ‘Value-added’ PACS Modern PACS architecture • PACS networks • Storage requirements and solutions for PACS PACS workstations • Monitor quality on PACS workstations Conference room design Graphic user interface • Soft-copy tools Software concepts • Prefetching

Compression • Lossless • Lossy • Need for compression Digitization policy Teleradiology • Review of images from home • Teleradiology linkage between two or more hospitals for joint MDTMs • Outsourcing of imaging examinations for reporting • Tele-education Security • User-specific log-in and password • Monitor screen savers • Workstation time-outs • Encryption • Audit trails • Firewalls • Teleradiology security PACS training Quality assurance • Plain radiography • PACS workstations PACS housekeeping • Storage commitment • Modality performed procedure step Current and future directions of PACS

THE ROLE OF PACS A picture archiving and communication system (PACS) aims to replace conventional analogue film and paper clinical request forms and reports with a completely computerized electronic network whereby digital images are viewed on monitors in

conjunction with the clinical details of the patient and the associated radiological report displayed in electronic format. Clearly PACS must replace the functions of traditional X-ray film; i.e. image acquisition, storage, transportation and display.

4

SECTION 1

• IMAGING TECHNIQUES AND GENERAL ISSUES

Were these the only roles of a PACS, it would be an extremely complex and expensive means of replacing traditional film. A PACS must improve upon a film-based system, preferably in a cost-neutral manner. The major added value of a PACS is efficiency of data management. True efficiency benefits can only be realized once a PACS is at least hospital-wide, since any more limited installation means running two systems in parallel, i.e. it entails continuing to produce conventional film and moving it around the hospital, as well as the cost of installing and maintaining a PACS. Thus, even if funds are limited initially, it is advisable at least to aim and plan for growing the PACS installation into a hospital-wide system ultimately. This means decid-

ing upon a potential time scale in which the hospital-wide PACS is to be achieved, and deciding upon a scaleable PACS architecture. Ideally the whole hospital infrastructure should be adapted at the outset so that a hospital-wide PACS can be accommodated at a later stage. This includes providing an uninterruptable power supply (UPS), allowing sufficient cabling space in floors and ceilings, and adapting the air conditioning system for PACS. The hospital information technology (IT) network is likely to need upgrading to enable large amounts of image data to be transported, and it is advisable to install multiple PACS ‘drops’ (workstation outlets) so that more PACS workstations can easily be added at a later date.

ADVANTAGES AND DISADVANTAGES OF PACS Although the concept of PACS has now been in existence for over 20 years, advances in computer hardware technology only enabled it to become a realistic clinical entity in the 1990s. PACS installations are now rising exponentially worldwide, and although most institutions with PACS have achieved a completely filmless working environment, few function in a paperless mode. PACS has proved itself over the last 10 years in the clinical environment, however, and it would now be unthinkable not to implement PACS when installing a new imaging department, or a new hospital.

ADVANTAGES OF PACS There are a number of powerful advantages accruing from a hospital-wide PACS: • Once correctly acquired onto the PACS, no image can ever be lost or misfiled and is always available when needed.This is a major benefit considering that in many hospitals up to 20 per cent of conventional films are missing at the time they are clinically required. In addition to the convenience of always having the appropriate image available when it is wanted for viewing, no patient is re-irradiated simply because a previous key study has been lost. • PACS facilitates the easy comparison of a patient’s current and historical examinations, and of examinations performed on the same body part using different imaging techniques, which is desirable in the interests of optimum clinical practice, and always possible since none of the relevant comparative images is missing1. • All images remain accessible from the PACS archives day and night, every day of the year. • Simultaneous multilocation viewing of the same image is possible on any workstation connected to the PACS network, whereas hard-copy film can manifestly only be in one place at any one time. • Image retrieval is infinitely quicker from PACS than it is using conventional film where someone physically has to go and fetch the film packet2. • The benefits of a computerized system mean that all images correctly and permanently reside under the appropriate

•

•

•

•

imaging study, remain in their correct orientation, and are automatically chronologically ordered. Database searches for a particular patient or study are rapidly effected. Computerized data can easily be duplicated, i.e. ‘backed up’ as a precaution against loss, and cheaply stored in a distant location if desired for disaster recovery purposes. Viewing of images on monitors allows numerous postprocessing soft-copy manipulations: a range of different window width and level settings can be applied to CT images, for example, within a fraction of a second, whereas previously further sheets of film had to be printed with the appropriate settings for soft tissue, lung or bone as desired3,4. There are some direct cost savings due to PACS: there is no longer a film budget, film packet cost or chemical processing. (The ability to print film need not be retained provided a CD burner is linked to the PACS to burn imaging studies for transfer of patients outside the institution, or in the event of a PACS failure or planned downtime). Ancillary staff – filing clerks and darkroom technicians – are no longer needed. The most frequently cited benefit of PACS by nonradiological clinicians is the very substantial time saving incurred by their never having to search for or retrieve films. This time saving represents a considerable indirect financial benefit of a hospital-wide PACS, and should certainly be costed when a business case for PACS is being made. After a hospital-wide PACS has been installed, old films can progressively be removed from the film filing room (film store) starting with the oldest first.The timing of this manoeuvre will depend upon local and national policy, but it has been shown5 that most radiological comparisons are made with studies obtained during the preceding 6 months, although this may be longer in institutions with a large oncological or paediatric practice. Maintenance of a film store, with its associated lighting, heating and cleaning, and the value of the physical space itself, is particularly costly in hospitals located in cities where the space is at a premium. Even off-site film storage at a cheaper location is worth introducing as a cost-saving measure in such institutions in the early years after PACS

CHAPTER 1

•

PICTURE ARCHIVING AND COMMUNICATION SYSTEMS (PACS) AND DIGITAL RADIOLOGY

has been installed, before the film store can be dispensed with altogether. (In the UK it is the radiological report, not the images that are deemed to be the legal document, with certain restrictions for paediatric and educationally challenged patients.) • The installation of a PACS infrastructure in an institution (a local area network [LAN]) sets the stage for the introduction of teleradiology over a wide area network (WAN) if desired. Teleradiology offers the potential for improvements in efficiency, for example in geographically remote areas by centralizing a reporting service, or increasing the referrals to a particular institution. A number of perceived potential benefits of PACS have not been substantiated, or not consistently demonstrated, by audit studies. These include the possibility of a reduced hospital inpatient stay or a greater throughput of outpatients6. It is hardly surprising that such benefits cannot be attributed to PACS since there are so many other variable factors that influence these issues. Also the type of study required to prove any given putative benefit of PACS is fraught with practical difficulties. The classical ‘before’ and ‘after’ study comparing the pre-PACS with the post-PACS era is inevitably complicated by the numerous other concurrent environmental, technological (and often political) changes that have taken place in the interim. These include, for example, changes in the medical personnel and in the type of clinical practice pursued in the hospital under study. Studies comparing a PACS institution with a nonPACS institution may be similarly flawed by the difficulty in adequately correcting for other inherent differences between the two institutions, which may or may not be related to the presence of a hospital-wide PACS7.

DISADVANTAGES OF PACS The advantages of PACS described earlier must be set against its potential disadvantages: • Even though the costs of hardware and storage media continue to reduce in price, PACS remains an expensive technology. Most estimates suggest that a PACS installation should aim at becoming cost-neutral in less than 5 years. Some would argue that PACS should be viewed in the same way as any new imaging technique, and as such it represents an advance in health care management and should not be assessed merely in terms of cost–benefit. • The technological complexity of a PACS and the absolute dependency of a hospital on the PACS once it becomes filmless require a dedicated maintenance programme for the PACS and a carefully devised plan detailing how to supply a minimal clinical service should the whole PACS fail for a significant period of time. This inevitably means that there will be a requirement for new or retrained hospital personnel specializing in computer engineering/information technology, as well as a vendor-provided maintenance service, and these costs must be set against the savings made in respect of less highly paid clerical staff and darkroom technicians. • Once a hospital-wide PACS is in operation and film has been withdrawn, there is no ‘fall-back position’. The hospital is no longer equipped to run a film-based service. This is a daunting prospect that may act as an initial psychological deterrent to embarking upon a large-scale PACS project. • Changing from a hard-copy to a soft-copy imaging environment will raise many issues necessitating a change of work patterns involving: the training of the users, maintenance of the system, action to be taken in the event of a PACS failure and the institution of specific quality assurance protocols (see later).

PLANNING FOR PACS THE PACS PROJECT TEAM The planning and installation of a PACS requires the coordinated input of a multidisciplinary team that might beneficially include representatives from the IT department, computer scientists, physicists, nonradiologist clinicians, radiologists, radiographers, nurses, hospital management, the hospital financial manager and, ultimately, a representative from the chosen PACS vendor. This emphasizes that PACS must have ‘buy in’ from the whole hospital/health care enterprise, and is not a ‘radiological toy’. The project team needs a leader with sufficient time to commit to the project8. This leader need not be a radiologist, or indeed a clinician, but must have a comprehensive practical grasp of the clinical workings of a hospital environment as well as an understanding of basic IT issues and the requirements of imaging.

TENDERING FOR A PACS When tendering for a PACS, a detailed request for tender/ proposal (RFT/RFP) will need to be drawn up9,10. This

document should define the clinical and logistical requirements of the PACS, rather than merely stipulating technical specifications. It is up to the radiologists and other clinicians to specify the current and projected future performance requirements that the PACS must fulfill (including the issues of PACS maintenance, uptime and data migration) and it is the role of the vendors to specify how these clinical requirements are to be met technically.

THE PACS CONTRACT Every PACS project should be based on a firm contract between the institution and the vendor, defining the responsibilities of each in detail. The PACS contract serves as a legal document and requires careful wording. Any subsequent changes or additions to the contract should be made as formal addenda ‘change control notices’ (CCNs) to the original contract, to preserve the legal integrity of the document. This also serves as an audit trail, keeping the contract up to date, and simplifying the situation for both purchaser and vendor.

5

6

SECTION 1

• IMAGING TECHNIQUES AND GENERAL ISSUES

It is important to define what is meant by ‘the life of the system’. This is often taken as being 8–10 years after the completion date.The majority of PACS installations are now based on some form of leasing agreement, rather than an outright capital purchase of the hardware and software. The date at which the maintenance contract will commence, its cost and its terms, all need careful definition. Responsibility must be defined for migration of the PACS archive data at the end of the PACS contract, or in the event of premature termination of the contract. It is advisable to define exactly what is meant by an ‘update’ to the system (generally a minor software release that merely corrects bugs in the system), and what is meant by an ‘upgrade’ (which constitutes a new software installation comprising major new features giving enhanced functionality), whether these are to be included in the purchase price/maintenance agreement, and at what frequency these will occur. An important consideration in negotiation with a vendor is the terms under which the delivered PACS hardware will be replaced if upgrades are released that it cannot support. It is vital to define which party is ultimately responsible for the functioning of the interfaces to the various pieces of imaging equipment, and to other hospital computer systems including the hospital and radiological information systems (HIS and RIS), electronic patient record (EPR), speech recognition dictation system, and electronic remote requesting (order communications) system, if these are already extant in the institution.

ECONOMIC CONSIDERATIONS The main reason for putting in a PACS (ultimately a hospital-wide or larger PACS) is to improve the efficiency of data handling throughout the whole of that health care environment. Much of the benefit will be experienced outside the imaging department itself, which is why PACS must be hospital driven (and funded), not radiology driven. PACS should be part of the hospital-wide information management and technology strategy, with the aim of achieving cost neutrality over about 3 years.

PURCHASING VERSUS LEASING A PACS The options for PACS procurement are broadly 2-fold11: 1 Capital purchase, using the hospital’s capital allowance, or 2 Some form of leasing arrangement. The fundamental difference between the two is that with capital purchase the hospital owns the assets (the PACS), whereas with any leased arrangement the hospital procures a service that contractually provides agreed functional outcomes (the output-based specification [OBS]). The vast majority of PACS installations nowadays are on a leasing scheme with a managed service provided by the PACS vendor. A leasing arrangement means that all the PACS equipment (hardware and software) is provided as a service from

a private company (with a maintenance contract). Nothing is owned by the hospital, i.e. the private company retains all the assets. The advantage of a leasing arrangement is that it allows hospitals with no hope of ever having the large capital sum necessary to purchase a hospital-wide PACS to make a quantum leap in technology to move to a PACS solution, and it transfers the risk to the company. It has to be appreciated, as with renting a house, that the hospital would be left with nothing if it were to stop paying the lease. At the end of the contractual term, the hospital does not own anything. However, in these circumstances the hospital is usually given an option to buy the installed assets (the PACS hardware and software) at ‘a fair market value’, as negotiated with the provider. In a leased service the PACS company provides the PACS hardware and software necessary to meet the workload and performance requirements stipulated by the hospital, both at the time of leasing and in the future. For example, such requirements might include the need to perform 400 000 imaging examinations per year, with a short-term storage of a year, and a display time for these examinations (first image to screen) of 3 s or less.The PACS company is responsible for maintaining a PACS with an agreed level of technology throughout the contractual term. The technological risk rests with the provider. The risk covers the following three areas: • Utilization of the system • Availability of the system to users • Future planning and implementation of new technology into the hospital’s system. The risk is transferred to the service provider by linking their revenues to agreed performance targets for the above. In addition the hospital should be provided with a guaranteed programme of equipment replacement and a guarantee to keep pace with technology. Leasing arrangements vary from about 8–30 years, with some planned ‘built-in’ equipment replacement ‘hardware swap-out’ at 5-yearly intervals, or 3–4-yearly technological reviews with ‘technology refreshments’ of software and/or hardware as may be necessary to provide greater productivity or capability. This technology refreshment may be a chargeable issue depending upon the contract and/or negotiations. Companies generally expect to recoup their capital outlay in approximately 3–5 years in a leased arrangement, but this will of course depend upon the financial model being used.

PRE-PACS WORKFLOW AND PREPARATION A number of careful and detailed preliminary pre-PACS studies of the workload and workflow pattern within the hospital/ health care facility will need to be conducted before the clinical requirements to be met by the PACS can be specified12.This includes documenting how many imaging examinations in each modality are performed annually, the average (and maximum) number of images per examination for each modality, and making a prediction of the rate of growth of the imaging workload.This prediction will be influenced by the expectation,

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for example, of acquiring a new 64-slice (or greater) multidetector CT machine, the intention to start performing high image acquisition studies in MR such as cardiac or breast imaging and so forth. The predicted image storage requirement should always be an overestimate to allow for unexpected demand. It is also advisable to know which outpatient clinics are performed when, and how many film packets are pulled for each, to give some estimate of the network traffic to be expected. It is also important to define the role of the imaging department in other imaging-related activities, such as the radiological steps involved in conducting multidisciplinary team meetings (MDTMs) and radiological presentations at staff rounds, and undergraduate and postgraduate teaching sessions. PACS must be able to fulfill all these functions. The Imaging Directorate would be wise to know before PACS is installed, exactly how many imaging studies are never reported (for various reasons such as: the film packets are never returned to the department for reporting), the time between image examination acquisition and dictation of a report by a radiologist for each investigation and the time delay (if any) between dictation of the report and the availability of the verified report to other clinicians. These workflow deficiencies need to be addressed and corrected prior to the installation of a PACS, since the PACS will not ameliorate the situation but instead will expose these issues by making such information available in computerized form throughout the PACS institution. Seamless integration with other IT systems, and with imaging acquisition devices, is absolutely vital for a PACS to function successfully, and every modern PACS depends upon adherence to DICOM and HL7 standards and IHE (see next paragraph for an explanation of each) workflow processes to achieve this integration13. Before installing PACS, old equipment and old data information systems will need to be upgraded to a minimum level of DICOM and HL7 compliance, respectively. Often it is cheaper to replace such products with modern versions, rather than to pay to upgrade them. A full inventory must be made of the equipment and IT systems to be connected to the PACS with a precise description of the level (if any) of DICOM or HL7 compliance supported, before a PACS project can be properly planned and costed. The full DICOM conformance statement of every piece of DICOM-compliant equipment (e.g. a computed tomography [CT] scanner, an ultrasound [US] machine, a workstation etc.) is available on the Internet. It is generally the users’

responsibility to list the make and model of all the equipment possessed by the hospital/health care facility, and the PACS vendor’s responsibility to look up and interpret the DICOM conformance statements and to make it clear which pieces of equipment will need upgrading/replacing, and to explain the connectivity limitations if such DICOM upgrades are not undertaken. One of the major causes of interoperability problems when linking equipment from different vendors to a PACS is the use of ‘private DICOM attributes’ by many vendors, which, in simple terms, means that information stored in these particular private DICOM fields is not available to be shared with other apparatus, manufactured by a different vendor, which may be linked to it on a network. This leads to a loss of functionality on the recipient apparatus, for example not being able to post-process scanner images received on a workstation from a different vendor.

ACRONYMS: DICOM, HL7 AND IHE DICOM stands for digital communication in medicine and refers to a worldwide multipart standard to which all modern imaging equipment and PACS must adhere, and has now been extended to other disciplines, including cardiology, endoscopy, and ophthalmology. The DICOM conformance statement of every piece of modern imaging equipment is obligatorily available on the Internet, and the description of the various DICOM attributes possessed by each appliance will predict its connectivity with another piece of equipment. All apparatus is described as being a ‘user’ or a ‘provider’ of services such as storage.The DICOM standard is continuously under development, but each new part of the DICOM standard has to be backwardly compatible with the current DICOM standard. HL7 stands for health level 7 and refers to a worldwide standard for data information systems such as HIS and RIS. It is a less rigorous standard than DICOM. HL7 messages from data information systems are conveyed to DICOM apparatus (including PACS) by a ‘broker’, which acts as an integrating and translation device. IHE stands for integrating the health care enterprise and is not a standard, but a comprehensive workflow descriptor of how processes, such as reporting, for example, are achieved in imaging. Its use of integration profiles eliminates the need to reconcile the details of HL7 messages and DICOM conformance statements among multiple vendors. It is now being expanded outside the discipline of imaging.

PACS PROJECT IMPLEMENTATION The PACS project should be treated as a major IT project and divided into stages (milestones) with specific dates set for the completion of each stage. It may be useful in the UK to base the project management on the PRINCE guidelines published by the HMSO14 for major IT equipment contracts. Only after each consecutive milestone is satisfactorily completed and assessed is the next milestone embarked upon.

Each milestone requires conformance testing and clinical acceptance15. These are distinct entities: conformance testing should be carried out independently by hospital employees as well as by the vendor company itself. Payment is best deferred until after clinical acceptance at each stage. Final payment is only made after agreed satisfactory functioning of the system under loaded conditions, in a clinical setting.

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A realistic definition of the expected dates of completion of each milestone (including installation dates), with penalty clauses written into the contract to come into effect if these dates are overrun, protects the institution from major delays since penalties can be extracted from the vendor if such delays occur.

IMPLEMENTATION OF DIGITAL IMAGE ACQUISITION PRIOR TO PACS Plain radiography (chest, abdominal and skeletal plain images) still constitute the majority (usually 60 per cent) of imaging examinations in most general radiology departments. These examinations therefore need to be acquired in a digital format in order to be transferred to PACS. This represents a considerable challenge since conventional plain film work is still such a significant part of the total departmental workload. The other imaging investigations (computed tomography [CT], magnetic resonance [MR], nuclear medicine [NM], positron emission tomography [PET], US, digital subtraction angiography, and fluoroscopy) are either already digital in nature at acquisition or can be rendered so by screen capture/frame grabbing from the acquisition device, and can thus be easily transferred to PACS. There are three basic means of rendering plain radiographic images digital: 1 Digitizing conventional analogue film 2 Photostimulable phosphor plate technology, commonly known as computed radiography (CR). 3 Direct digital radiography. There is considerable new technology associated with acquiring plain radiographic images digitally, whichever method is chosen. In situations other than the opening of a new hospital/health care facility, it is circumspect not to introduce this new technology concurrently with a PACS to avoid the risk of ‘technology overload’ for the users. Once the bulk of the imaging studies (i.e. the plain radiography) is being acquired and stored digitally, the introduction of PACS and the complete withdrawal of film is a less daunting task. The overlap period, in which a digital archive is being built up whilst continuing to distribute film outside the imaging department, should be kept to a minimum for financial reasons: it is obviously expensive to run hard- and soft-copy systems concurrently. A period of <3 months is a reasonable timescale for the phasing in of PACS after digital plain radiography has been introduced. The digital archive acquired during this time is sufficient for the majority of comparisons with previous plain images4, and obviates the need for a great deal of retrospective digitization of conventional film.

Digitization of analogue film This is a time-consuming process that requires relatively skilled operators who are able to differentiate the various imaging modalities and body parts and orientate the films correctly for digitization and storage on PACS. Digitization must take place in a nondusty environment. A digitized image retains any intrinsic limitations present in the analogue film: areas that

were underexposed on the original film remain underexposed when digitized; areas that were overexposed on the original film would normally yield more information when viewed over a bright light, but tend just to look black when digitized. Digitization on a large scale is not a practical option and combines the expense of a film budget with the cost of digitization and maintenance of a soft-copy archive. Digitization may be a viable solution in a very-low-throughput teleradiology service, and is necessary in a PACS environment to allow hardcopy films acquired at a nonPACS institution to be entered onto the PACS for comparison with subsequent digital images acquired at the PACS institution. Since digitization is a costly and labour-intensive process, yielding digital images of suboptimal quality, a sensible minimalist digitization policy should be adopted when PACS is installed. A reasonable compromise is only to digitize one previous ‘key’ image in patients for whom it is regarded as clinically highly desirable to have a comparison image available long term on the PACS archive (for example, oncology patients on chemotherapy, or patients with slow-growing tumours or chronic disease). Some institutions choose not to digitize any previous films, but undertake to make past hardcopy imaging available on request (from off-site storage) for over a year. It is clear that unselective ‘blind’ digitization of batches of previous films is a waste of time and money considering how few previous imaging studies are ever subsequently reviewed4.

Photostimulable phosphor plate technology/ computed radiography This is the commonest means of acquiring plain radiographic images in a digital format. Photostimulable phosphor plates replace the conventional film/screen combination in a cassette and can be used with standard X-ray equipment (although not for fluoroscopy). X-ray photons falling on the phosphor plate produce a latent image by promoting electrons to metastable traps of higher energy level. When the plate is ‘read out’ in raster fashion by a scanning laser beam in the plate reader, these electrons gain sufficient energy to fall back to their basal energy level, and in so doing, emit photons of visible light that is converted to a final digital signal (Fig. 1.1). Phosphor plates have a flatter, more linear, optical density versus radiation exposure response curve than the classic sigmoid-shaped curve of the conventional film/screen combination (Fig. 1.2). This technology thus gives a greater latitude of exposure, which is useful under challenging radiographic circumstances, such as in the intensive care unit, and allows structures of widely differing radiographic density to be well visualized on the same image, such as the area behind the cardiac silhouette and the lung vessels, or the soft tissues of the neck and the cervico-thoracic junction. This feature allows a reduction, compared with film, in the number of repeat images taken due to errors in selecting the correct exposure. The spatial resolution of CR is lower (approximately 2½ line-pairs per mm) than that of film (approximately 5 line-pairs per mm), but its superior contrast resolution more than compensates for its limited spatial resolution.

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Xray -photons Exposure

Caesium Iodide

Photostimulable phosphor plate

Light Selenium

Laser

Latent image

Luminescence

Read out

Amorphous silicon panel (photodiode/transistor array)

Amorphous silicon panel (photodiode/transistor array)

Electrons

Electrons

Read out electronics

Read out electronics

Digital signal

Digital signal

Figure 1.1 Diagrammatic representation of digital image acquisition by photostimulable plate technology (CR).

Phosphor plates are repeatedly reusable for a thousand or more exposures, although they do have a finite life after which they start to crack and need replacement (and this is a cost that must be allowed for in the departmental budget). CR apparatus is cheaper than direct digital radiography (DR) equipment, especially for mobile radiographic units.

Direct digital radiography Current direct DR apparatus (other than in dental work) uses amorphous silicon with a digital detector. Different systems on the market use different detectors to capture the X-ray photons: caesium iodide or rare earth scintillators, which emit light photons, or selenium, which produces an electrical signal (i.e. a direct digital signal) (Fig. 1.3).The amorphous silicon is used to make plates consisting of an array of photodiodes/transistors, each acting as a single pixel to amplify the incoming light or electrical signal and give a digital electronic output. When it became technically possible to construct flat-panel detectors large enough, they started to be used in plain radiography.The detector plates are fragile, heavy and fixed, and have only very recently been adapted for use in mobile direct DR apparatus (which remains much more expensive than the phosphor Film/screen 3.0 CR or DR

Dark

2.0 Linear density range Lungs 1.0 Heart

Light 0.0 0.0

Xray-photons

X-rays

1.0

2.0 log Relative radiation exposure

3.0

Figure 1.2 Optical density versus radiation exposure response curves. The phosphor plate has a more linear response than the sigmoidshaped curve of the film/screen combination. Photostimulable phosphor plates have a wider latitude than film/screen.

Figure 1.3 direct DR.

Diagrammatic representation of image acquisition by

plate alternative).Thus at present there is a continuing concurrent need for CR using the much cheaper phosphor plates for mobile radiography and to provide redundancy. The spatial resolution of direct DR equals that of film and it has better detective quantum efficiency (DQE) – giving a guaranteed possible dose reduction per exposure – and better contrast resolution. Unlike photostimulable phosphor plates, a direct digital signal is produced and there is no manual processing of plates involved. The current higher cost of direct DR apparatus still favours its use mainly in mammography and in very-high-throughput radiology units16.

INTEGRATION OF PACS The seamless integration of the PACS with existing image acquisition systems and with other hospital computer systems is the most important and challenging aspect of any PACS project.This is why the person/vendor with ultimate responsibility for the various planned interfaces must be clearly identified and involved in the PACS contract.

HIS–RIS–PACS integration It is crucial to have seamless integration between PACS and RIS9 and HIS. No PACS installation should be contemplated unless there are already integrated HIS and RIS systems within the institution, or they are being installed simultaneously with the PACS. It is most unwise to implement a PACS before a HIS/RIS since the PACS database will stand alone, isolated, and the retrospective merger of databases is time consuming and expensive. It could be argued that it is unnecessary to integrate HIS with PACS (even if this is done indirectly via the RIS) (Fig. 1.4). However it is only the HIS, not the RIS, that is aware of all the patients known to the hospital/health care enterprise irrespective of whether they have previously had imaging studies. If such a patient attends for an imaging study, his or her demographic details need to be automatically transferred from the HIS to RIS and PACS. Furthermore it is only the HIS that

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HIS HIS

RIS

RIS PACS

Figure 1.5

PACS

Bi-directional integration between PACS, HIS and RIS.

Figure 1.4 Unidirectional interfaces between HIS, RIS and PACS. Here HIS is only connected to PACS via RIS. Scanner

is aware of the patients who have been scheduled to attend particular outpatient clinics, and this information can be used directly by the PACS to prefetch the imaging studies for these patients from a long-term archive prior to their attendance at the outpatient clinic. There are three main reasons in favour of having bidirectional integration between these three systems (Fig. 1.5): • There is input of demographic data only once, minimizing human error. • Any update to a patient’s demographic data on HIS, RIS or PACS is propagated to all systems automatically, ensuring that all systems contain accurate information. • Any scheduling or status data is distributed to all systems automatically, providing all systems with advanced notice of events and allowing them to prepare to play their roles in these events. A good example of this is the concept of pre-fetching, whereby pertinent historical examinations are fetched to the PACS short-term storage unit in advance of a patient’s attendance at an outpatient clinic, hospital admission or imaging examination; these data are known to the HIS and/or RIS and passed to the PACS prior to the event concerned.

Radiology information system The RIS may be a stand-alone computer platform, or may be a module of the HIS12. It stores information specific to the radiology department, including the registration of patients attending only the imaging department for an imaging investigation, but not otherwise under the care of the hospital (e.g. general practitioner referrals); schedules examinations, including date, time and room allocation; may track the patient’s progress through the imaging department; and stores radiological reports and produces statistics concerning imaging workflow. A modern RIS will incorporate some DICOM features such as DICOM modality worklist (DMWL), (Fig. 1.6).

RIS Single data entry

Figure 1.6

DICOM modality worklist.

whereby the demographic data of a scheduled list of patients is downloaded directly to the imaging apparatus (e.g. CT system) due to perform the studies (provided the imaging modality also supports DMWL). This obviates the need to retype the demographic details of patients on the imaging equipment or the PACS, and thereby eliminates work and human typographical errors, which would otherwise cause the images not to be recognized when later sent to a mismatched entry for that patient on PACS. A reference number (an ‘accession number’) is assigned by the RIS to each study and communicated to the imaging room as part of the DMWL to obtain a one-to-one correspondence between the DICOM data set and the RIS-related information.

Hospital information system or electronic patient/ medical record The HIS (or in some health care institutions, the EPR) is the most important computer system in a hospital. It constitutes the patient master index that stores demographic (textural) data on all patients known to the hospital, whether or not they have ever had any imaging procedures performed. In addition to this demographic data, e.g. patient name, identification number and date of birth, the HIS also records admission and discharge dates, outpatient appointments, clinician(s) responsible for the patient’s care and so forth. Other modules of the HIS document laboratory data, usually including haematology, biochemistry and histopathological test results. Ultimately a true EPR should contain all the case notes for a patient in digital format, but most systems are a long way from achieving this goal.

‘VALUE-ADDED’ PACS Once hospitals have PACS installed, it will gradually become clear to them that having a PACS, whereby imaging studies and their reports are electronically stored and transmitted, is only the first step in achieving a fully integrated, seamless, electronic system of health care workflow. Becoming filmless is not enough: all health care systems are a long way off the aim of also becoming paperless. In order fully to achieve the latter, there can be no paper request forms, and no paper copies of reports.

Paper request forms can be integrated into the PACS environment using a work-around solution, such as digitizing the paper request forms prior to acquisition of the imaging study, or using a bar code hand-held laser reader on the patient label on the request form at the time of imaging and reporting to locate the electronic entry on RIS, PACS and the speech recognition system. Such processes have a number of drawbacks, do not produce a streamlined workflow and, most importantly, they do not eliminate the existence of a paper request. It is only by

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ceasing to be dependent upon the physical existence of a paper request that health care institutions can function as virtual hospitals, and become location independent with respect to the sites of generation of the imaging study request, the acquisition of its imaging study, and the generation of its report17. To eliminate paper requests, imaging studies must be booked using a remote electronic requesting system (sometimes known as ‘order communications [order comms]’). The image study request details must be entered electronically at the time of booking (either by directly typing them into the system or by using speech recognition to enter them). The booking of imaging studies is rather more demanding of such electronic requesting systems than the booking of other investigative studies, such as haematology or biochemistry profiles or histopathology examinations. Radiologists in the UK are legally bound by IRMER (ionizing regulations in medicine regulations), whereby studies using ionizing radiation must be clinically justified and therefore the clinicians’ requests for such imaging studies must be vetted by a radiologist to ensure they are indeed clinically indicated. An electronic requesting system for radiological studies must allow this vetting step to take place electronically, with an audit trail of the person who changed an imaging request and the reason for the change; the details of the new procedure scheduled must be made known to the referrer and his/her team, and to the patient. The generation of the radiology reports should ideally be via an electronic speech recognition system fully integrated with both the RIS and the PACS. In this way when an imaging study is displayed on the PACS monitors for reporting, the integration means that both the RIS and the speech recognition system will automatically ‘know’ which imaging study is being reported. The speech recognition system immediately converts the dictated report into text, which is corrected there and then by the radiologist author, and is electronically signed. This report is permanently stored in the RIS (the location where radiological reports are conventionally stored long term) and is visible on the PACS and in the HIS/EPR. Speech recognition adds considerable value to the PACS since imaging workflow efficiency is markedly improved, by eliminating any delays between dictation and typing, and between typing and verification by the radiologist. Once a report is dictated

and signed by the radiologist it is instantaneously available to any authorized user accessing the study on the PACS. The ‘imaging loop’ should be closed by installing electronic feedback of results, whereby the relevant clinician(s) are electronically shown the reports on imaging studies they have requested on their patients. Returned results therefore have to be grouped by referring clinician, or preferably, by referring clinical firm (team). There needs to be a means whereby the reporting radiologist can, at the time of dictating the report, electronically add an ‘alert’ flag to a report revealing an unexpected or urgent clinical finding to draw it urgently to the attention of the referring clinician and his/her team. The imaging loop is closed by the clinician (or his/her team) responsible for the health care of the patient reading the report on the imaging study and taking responsibility for it. There needs to be a robust audit trail to record who read the report, and, more importantly, who took responsibility for understanding and acting upon it to avoid imaging reports being overlooked, and also for medico-legal purposes should an important imaging result be missed. It is not adequate to rely upon communication of urgent results by telephone in case (as often happens nowadays) the relevant clinician is no longer on duty or is unable to be contacted for some reason. Paper reports sent by conventional mail or fax can also be unreliable and there is no confirmation that they have reached their destination and been read by the relevant clinician. Thus the electronic communication of results system must incorporate a two-step receipt procedure whereby the reader must actively click twice (e.g. in two different check boxes), once to acknowledge reading and again to indicate understanding of (i.e. taking responsibility for) the result of the imaging procedure. These steps must be traceable by the system’s audit trail. If this form of verification is not followed then an electronic result may appear to have been read (for example, as with an email programme, by changing from bold to normal type font) whereas in fact it has merely been opened, or opened by a medical student or junior doctor who will not take responsibility for dealing with the consequences of the report findings. Unfortunately these electronic requirements for closing the imaging loop have yet to be implemented on current commercial system software.

MODERN PACS ARCHITECTURE Today’s high-speed computers and networks mean the hardware architecture is no longer an issue; it is the logical architecture that matters. For large PACS, everybody builds essentially the same hardware architecture today (multiple servers on fast networks); the only real difference is whether the systems present a logically centralized view or a distributed (autorouting) view to the user.

PACS NETWORKS The network is the critical link for all the individual components in a PACS. Its performance is a major factor in determining the ability of a PACS to support the examination volume of the hospital/health care institution.

Most PACS products are industry-standard networks, usually consisting of a high-speed network, often called a backbone, which spans the entire institution, with branches that connect individual components or groups of components to the backbone. Networks can be differentiated in several ways, including cable type, speed, communication protocols and topology. Data are transmitted over the physical network using a protocol.The performance of the PACS, i.e. its response time (judged by the radiologist as the speed with which an image appears on the PACS monitor after the display command is activated on the workstation) is determined by the cable quality and speed, and by the protocols used for carrying imaging data.

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It is the quality and speed (bandwidth) of the enterprisewide network that determines the rapidity with which images are displayed on the PACS workstation and web browser computer monitors. The quality of the PACS hardware and software is immaterial if image delivery is rate limited by an inadequate portion of the network. Radiological images contain very large amounts of data: a single plain chest radiograph contains from 8–10 megabytes of data, and there are considerably more data in the very large (around 1000–2000 individual images) thin-section CT and MR cross-sectional image datasets often now acquired for a single study. Networks nowadays run standard ethernet protocol, with TCP/IP (Transmission Control Protocol/Internet Protocol) of the Internet. At least 100 megabit ethernet is needed to transmit radiological images and some institutions are now running 1 gigabit ethernet throughout the health care enterprise. The core of many PACSs still run propriety network protocols to achieve greater speed of transmission. Modern hospitals have a switched network rather than a hub network because a switched network allows the whole bandwidth (e.g. 100 Mbps ethernet) to be available to each switch in the network (whereas in a hub network the entire hub accommodates the total bandwidth (e.g. the 100 Mbps) and all the attached items have to share a portion of that bandwidth).

STORAGE REQUIREMENTS AND SOLUTIONS FOR PACS The PACS requires two basic different types of storage for: • Image data • Indexing data.

PACS image data storage The PACS requires a very large amount of storage for the images (which includes associated objects such as presentation states), but the requirements are fundamentally different from the types of storage used by other large data users such as banks. The peculiar features of PACS image storage are: • There is an ever-increasing need for more storage space • The data once written are rarely (if ever) changed • Images tend only to be accessed a few times during their entire life and normally by only one user at a time • Required disk access speed is not actually very high, as enduser access is more limited by network speed than by disk limitations.

PACS indexing data storage The PACS has more ‘conventional’ requirements for its indexing data storage where: • The total volume of data is tiny by modern standards (a few gigabytes at most) • Data are constantly being updated and changed • Concurrent access by multiple users (for queries) is required.

Historically, the costs of image data storage were the main determinant of the cost of a PACS, but nowadays, they should only be a minor component, as disk costs have fallen so dramatically, and PACS software costs are much higher than its hardware costs (although vendor mark-up for hardware can skew this ratio).

Storage volumes and types In the early days of PACS, storage volumes were mainly determined by the size and number of CR images, but multi-slice CT and large MR studies are now overtaking CR, and required data volumes are still increasing, such that even after applying lossless compression, an average district general hospital will need about 2 Tbyte and a major teaching hospital about 5 Tbyte per year18. There have been many types of storage used over the years for PACS to handle such large volumes, including optical disks (magneto-optical disks, MOD or compact disk/digital versatile disk, CD/DVD), tape-drives and jukeboxes containing both of these. All these mechanical devices, with their attendant reliability issues, are now obsolete, and the only sensible method of storing images for normal use is Redundant Array of Inexpensive Disks (RAID) – a system that spreads data across many disks, providing the following advantages: • The data are still accessible if one (or, in some configurations, more than one) drive fails • The speed of the system as a whole is faster than the individual disks, because they work in parallel. RAID itself can be used in multiple different configurations and ways of connecting the PACS server, with widely different pricing, but the main categories are: 1 Directly attached to the server. This is cheap and simple, but expansion then requires the whole system to be stopped and restarted, and expansion is also limited. 2 Attached to a network using file servers (network attached storage [NAS]). This is mature standard technology that offers an excellent choice of products as fully supported ‘off-the-shelf ’ hardware, to which any competent server should be able to connect.

Storage area networks SANs are basically RAID, but connected to their servers using special connections (normally optical fibre). They provide extensive facilities for management, backup, flexible use of space and sharing of disk space across multiple servers, but this flexibility comes at a price, as they are much more expensive than equivalent space bought in the form of file servers, normally being 5–10 times as expensive per Gbyte.

Proprietary storage systems It is possible to replace the above ‘open’ and standard connection methods by proprietary equivalents, which are claimed to have unique special features, but costs are high and there is then ‘lock-in’ to the particular vendor concerned.

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Mirrored storage It is possible to have duplicate copies of the data held on two or more devices, preferably in physically separate locations. In theory this is possible for any of the above basic types, but in practice it is difficult to do for directly attached storage, and for SANs and proprietary methods it can be prohibitively expensive, so it is most commonly applied to NAS devices.

Backup Whilst it is useful to have all the institution’s PACS data immediately available on RAID, there is always the risk that it could be lost, through any of the following: • Disk failure (RAID should be robust, if the fault is spotted and the disk replaced before another fails) • Other hardware failure (RAID is not immune from this) • Fire, flood and malicious physical damage • Software errors and viruses (which can even affect mirrored RAID). Therefore, disaster recovery backup onto media that are not on-line and therefore not accessible to viruses etc. is important, and tape is perfect for this. Note that there is no requirement for a jukebox, merely a good fire- and flood-proof safe to isolate and protect the tapes! Backup of PACS image data is very different from the backup needed in most industries, due to the ‘static’ nature of the images, and therefore it is important that the backup strategy is properly designed around this pattern. In particular: • Regular backing up of the whole set of images stored is a waste of time (since once acquired, the images are not going to change) • Each image probably only needs to be on two tapes • Those tapes should be ‘refreshed’ every year or two depending on the manufacturer’s stated data life • Conventional ‘tape rotation’ must be avoided, as it could cause good (original) data to be over-written by errors.

Compression implications for storage It is important to check that an appropriate compression strategy is used, as properly managed lossless (reversible) compression with the same compression used over the network can: • Reduce required storage space by about 60 per cent • Decrease image access times (as less data need to be read off the disk and moved over the network).

These benefits have no significant downsides, and money spent on uncompressed storage space is simply wasted. There are academic arguments in favour of moderate lossy (irreversible) compression, which could probably reduce longterm storage space by a further 75–85 per cent (90–95 per cent overall) but this is a more contentious subject, and is not as clear-cut as the incontrovertible arguments in favour of lossless compression.

Optimal PACS storage Bearing in mind all the points mentioned earlier, there are two very different requirements for PACS data storage: 1 Indexing data. These are the sort of data well understood by industry, requiring the highest speed, most robust and manageable disk available, combined with regular complete backups.The cost per Gbyte is obviously high, but the actual space required is very small. 2 Image data. These data do not require fast, over-managed, repeatedly backed-up storage – merely large quantities of ‘cheap and cheerful’ storage – preferably duplicated RAID for which network-attached storage or similar is ideal. Furthermore, by buying only what is needed as required, prices decline over time in line with commodity storage advances.

Commercial considerations Clearly, the arguments given earlier can only be put into practice if it is possible to specify the type of storage used for a PACS, and this is not possible if decisions have been made elsewhere precluding such choice, or if it is not possible to buy the ‘core PACS’ and the storage independently. At least one of the major PACS vendors has however been known to allow such independent purchase in some areas of the world, enabling the purchase of PACS software and integration expertise from those best able to supply it (the PACS companies) whilst at the same time, buying the storage itself from those best able to supply that component – the commercial storage solution providers. Nevertheless, if the PACS storage is not purchased (at a premium) from the PACS vendor, there must be sufficient highly competent in-house expertise available to manage this storage independently from the PACS vendor, and the PACS contract will need to make special reference to the responsibility for maintaining and managing the PACS storage separately from the core PACS software and integration.

PACS WORKSTATIONS MONITOR QUALITY ON PACS WORKSTATIONS Fitness for purpose ‘Diagnostic quality’ monitors means that the monitor used for viewing the digital image should be capable of showing the image at its maximum spatial and contrast resolution (i.e. the spatial and contrast resolution at which the image was acquired). The spatial and contrast resolution of images from the various imaging modalities differs, for example: plain

radiography (such as a digitally acquired chest X-ray) has a higher intrinsic data content than a single image from a CT, MR, or US scan, and therefore would need a better quality monitor to show all the data it contains. The key issue in every part of a PACS specification, including the question of monitor quality, is fitness for purpose. The following questions have to be answered, with respect to image display monitors: ‘Why am I looking at the image in this particular location?’ Is it to make a final diagnostic report

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(as issued by a radiologist)? Is it to identify urgently treatable pathology before the image has been seen and reported by a radiologist (as might be the case for a clinician on the intensive care ward, or in the Accident and Emergency [A&E] department), trying to diagnose a pneumothorax or pneumonia)? Is it as a reminder of the imaging findings on this patient by reviewing his/her imaging studies, generally also with access to the definitive radiological report (as might be the case in the outpatient clinic or on a ward round)? The monitor requirements in all these scenarios differ. It is perfectly acceptable for a nonradiological clinician to make a diagnosis from an image that is not displayed at its maximum resolution, and to go on to treat the disease displayed (e.g. a pneumonia or a fracture) before the image is seen and reported by a radiologist viewing the image on a fullresolution monitor. Fitness for purpose is the key here: it would not be appropriate for the clinician to base patient management upon such an image viewed solely upon a mobile phone screen, but conversely most lesions requiring urgent treatment can be well seen on a 1 megapixel monitor, with access to a soft-copy magnification tool, and do not have to be seen on a 3 megapixel monitor to be detected19. It is also important to bear in mind that many subtle radiological signs seen on plain radiographs (such as early interstitial lung disease, or subperiosteal bone resorption) relate to diagnoses that are generally not nowadays made clinically by the plain radiographic appearance. In the cases cited, the early interstitial lung disease would be suspected clinically and on lung function tests and confirmed radiologically by high-resolution CT; the subperiosteal resorption would occur in gross hyperparathyroidism already diagnosed biochemically. In any case most subtle plain radiological appearances do not require immediate treatment before the images can be further reviewed on a higher resolution monitor, and other investigations using different imaging modalities and various clinical tests to confirm the diagnoses, will be carried out before any treatment is commenced. A digital chest radiograph acquired using either CR (phosphor plate technology), or direct digital technology, displayed at full size at its acquisition resolution, requires a monitor with the following minimum specification: • 3 megapixels (for spatial resolution) • 700 cd/m2 brightness (high luminance) • Greyscale, not colour • 256 linear-sized levels of greyscale (DICOM part 14 compliant display), usually of 10 bit depth (for contrast resolution). Diagnostic quality monitors of the specification cited earlier are only necessary for viewing ‘plain radiography’ (such as a chest radiograph) i.e. CR, or direct DR, at their full spatial and contrast resolution. Other images (e.g. CT, MR, US, NM, angiography or fluoroscopy) will be displayed at their maximum acquisition resolution on a 1 megapixel monitor (that is ~ 1200 × 1600 pixel monitor with a 19-inch diagonal). Digital mammograms, however, require a 5 megapixel monitor to be displayed in their entirety at full resolution.

A portion of a digital chest radiograph (or other plain radiograph) can be displayed at its full acquisition spatial resolution by use of a pan-zoom or a magnifying glass soft copy tool on a lower resolution monitor (such as a 1 megapixel monitor), provided the soft copy tool truly does show more pixels within its magnified area and does not just ‘stretch out’ the existing pixels already displayed on the 1 megapixel display (Fig. 1.7). When comparing plain radiography images (such as chest radiographs), it is essential to be able to see at least the current and a previous radiograph simultaneously. Only a dualmonitor workstation will enable two chest radiographs to be simultaneously compared at full size. A single monitor will enable two chest radiographs to be compared simultaneously, but they will inevitably be of reduced size, and this is not satisfactory in circumstances where the operator is trying to detect subtle sequential changes in pathology (such as resolving/worsening respiratory distress syndrome in the intensive care setting).

Ambient lighting The ambient lighting conditions in the area where the image monitor is placed need to be optimal for image viewing, and the importance of this cannot be overemphasized. This means that complete blackout should be possible, with dark (black or navy) blackout blinds fitted to the windows, and a variable level of low ambient lighting should be achievable with dimmer switches fitted to the room lighting. The workstation monitors should not be placed opposite a window, to avoid daylight reflecting from the screen. On the wards, the workstations should, if possible, be sited in a recess off the main ward so that independent dimming of the lights is possible in the recessed area. Flat-screen monitors are preferable to cathode ray tube screens since they do not reflect light, or show parallax (but do have to be viewed directly en face), and they take up less desktop space. Monitor resolution less than image resolution

True magnification

Pixel stretching

Figure 1.7 Diagrammatic illustration of true magnification. The monitor shows an image at less than its full resolution. The middle monitor illustrates a true magnification tool where more image data (more pixels) are displayed within the area of the magnification tool. The right-hand monitor shows a ‘magnification tool’ that merely expands the displayed data (stretches the pixels) and does not display more image data.

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It is clearly pointless installing high-quality monitors without optimizing the ambient lighting for image viewing. It is important to appreciate that high monitor luminance and good low-light viewing conditions are at least as important as (and some would argue, more important than) the absolute screen resolution of the monitor.

Location and type of PACS display devices The introduction of a PACS inevitably imposes some changes on the location where images are viewed around the hospital. One of the disadvantages of film was that it could only be viewed by one user, or group of users all in the same location, at any one time. PACS allows multilocation viewing simultaneously of the same image at the same time by numerous users all at different PACS display devices (dedicated PACS workstations and/or PACS web browser computers).

‘PACS workstations’ versus ‘web browsers’ The only difference between a so-called ‘PACS workstation’ and a PACS ‘web browser’ is their software. It has nothing to do with the resolution of the viewing monitors used, since any resolution of hardware monitor can be used to show any type of software package. Unfortunately the terminology has led to considerable confusion and misunderstanding because, apart from the software differences, there are often other associated differences, depending upon: • The manufacturer’s products • The type of hardware used for the PACS workstation and that used to run the web browser software • The network used to connect the PACS workstations and the PACS web browser to the on-line image storage device • The type and degree of compression (if any) applied to images displayed on the PACS workstation and on the PACS web browser. In general, the term ‘PACS workstation’ refers to a highspecification computer that runs proprietary sophisticated software dedicated to image diagnosis and review, whereas a ‘PACS web browser’ depends upon a public domain web browser (usually Internet Explorer) to display images for review purposes, and can be loaded on any off-the-shelf computer. Any computer running PACS web browser software can be used to review PACS images and thus could be called a ‘PACS workstation,’ but since it is an off-the-shelf computer it can also perform numerous other functions (e.g. making slides, writing documents, accessing the Internet etc.) depending upon which software packages have been loaded onto it, and to which networks it is connected. The PACS images viewed using a web browser are not necessarily inferior to those viewed on a dedicated PACS workstation. The resolution of the images depends upon: 1 The quality (resolution, size and luminance) of the monitor(s) fitted to the computer upon which the web browser software is running 2 Whether the images are compressed 3 The ambient lighting conditions where the monitor is viewed.

Thus the uncompressed images viewed on a PACS web browser could be of the highest diagnostic quality if a 3 megapixel (or even a 5 megapixel) monitor were fitted to the computer. An important, relatively new hardware development is the manufacture of dual-monitor computers (with the appropriate circuitry to run from one central processing unit (CPU), one graphics card and use one keyboard). If PACS web browser software were run on such a computer, then two chest radiographs from the same patient could be compared simultaneously, at large size, one on each monitor. The potential ‘drawback’ of a PACS web browser in some circumstances is the relative simplicity of its software compared with that found on a proprietary PACS workstation dedicated to image display for diagnostic or comparative review purposes. Again this issue is one of fitness for purpose, since in the majority of clinical settings such sophisticated software is unnecessary and never used, and the web browser software is entirely adequate for displaying the images (and reports) of a particular patient, and for comparing different studies on the same patient. Thus web browser software is entirely appropriate and sufficient for viewing patients’ images in the ward or clinic setting. The monitors chosen for the computer upon which the PACS web browser is to be run should also be fit for purpose, so that if it is deemed necessary that the images to be viewed in that location should be displayed at a resolution fit for primary diagnosis (i.e. the same resolution as would be seen by a radiologist reporting in the Imaging department), then very-high-resolution, highluminance, large (possibly dual) monitors will have to be chosen, and adjustable low ambient lighting and blackout facilities will have to be installed.

Requirements for sophisticated PACS software The indications for using the sophisticated (expensive) proprietary PACS workstation software (rather than the simpler web browser software) are as follows: 1 For the radiologist performing daily lists of primary diagnostic reporting and issuing definitive reports. The sophisticated software allows the radiologist seamlessly (by a single mouse click/key stroke) swiftly to work through a reporting worklist of imaging studies on patients whose names are not known. This software is particularly useful for reporting plain radiographs where there is a rapid throughput of work, and the radiologist should not be wasting time typing in the name of every patient whose images are to be reported. The current images of the next patient in the worklist to be reported are automatically displayed on the PACS workstation monitor, in conjunction with a configurable number of previous relevant imaging studies (of the same modality and body part) in sequential reverse chronological order. This automatic display of current and past images in the required format across the monitors is known as default display protocols (DDPs) or hanging protocols. When the report is complete, the software will mark the study dictated, thereby changing its status on the PACS. None of this software is necessary for the nonradiologist clinician, who is not involved in formal radiological report generation,

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does not have to work rapidly through a reporting worklist, and who is usually seeking the PACS images of a particular patient whose name and/or other demographic details are known to them. 2 For PACS database searching not based upon specific patient name or other demographic details. This is particularly useful to radiologists who often need to find a particular imaging study, or examples of certain imaging studies, which showed specific features, but they frequently do not know/ cannot remember the patient name or other demographic details. Currently web browser software generally does not allow searches of this nature, for example finding all cardiac MR examinations performed in January 2007. Nonradiological clinicians are almost always searching for images and reports on individual specific patients for clinical review, whose demographic data (be that name, date of birth, hospital number, or all of these) are known to them. These are exactly the data used by web browsers to search for specific imaging studies and their reports. 3 For any activity that benefits from the use of multipatient or single patient folders. Folders are useful for compiling and conducting MDTMs or other clinico-radiological conferences. Sophisticated PACS software (generally not available on web browsers) is required to add and remove patient studies or images to and from folders.Thus an MDTM folder of all the specific studies to be reviewed at a specific MDTM can be compiled electronically on PACS in advance of the meeting. This allows the radiologist who will be responsible for commenting upon the radiology in the MDTM to review the relevant imaging studies of the selected patients in advance of the meeting, with the benefit of the DDPs for automated display of the latest relevant preceding images. During the MDTM the conference folder can be progressively emptied of the studies already discussed, whilst some may be retained: for example, if they are to be discussed again the following week after additional imaging or other tests have been carried out, or if an addendum needs to be added to a report. Folders are useful for direct display from PACS (without having to make up a separate PowerPoint slide presentation) at hospital staff/grand rounds. This is especially true if the software allows anonymity with removal of the patient demographic details in the header bar across the top of the screen, so the folder can be displayed in a potentially public setting without breech of patient confidentiality. Multipatient folders are of benefit in the academic and research settings.They can be used to filter images directly from PACS into a particular group of images also stored and able to be displayed on PACS. Examples include images of patients involved in a particular research study, images selected for a book chapter or lecture, or teaching cases for specific tutorials. In summary therefore, sophisticated dedicated PACS software needs to be located in areas with the above requirements for use, i.e.: • The imaging department for diagnostic reporting • Seminar and conference rooms where teaching, MDTMs and staff rounds take place.

It is only in the imaging department (or any other area where final diagnostic image report generation takes place) that highresolution monitors need to be installed.

Location of PACS web browser computers Physicians’ ward rounds often follow a format of discussing all the patients first, with their case notes and X-rays, in a seminar room, followed by a ward visit of all the patients.This working practice can easily be adapted to PACS by holding the discussion phase of the ward round in a seminar room where there is access to a PACS web browser. Surgical, intensive care and physicians’ business ward rounds are often conducted at the bedside where the clinical charts are located, sometimes with the notes trolley being pushed round with the ward round, and any relevant X-rays being looked at ‘on the fly’, on the nearest viewing box (or, regrettably, by holding the radiograph up to the window!). Unless PACS viewing facilities are provided at the bedside, these ambulant ward rounds will have to detour to view the patients’ images on the nearest web browser as each patient is visited. Citing the ward-based PACS web browser computers is important: they should be easily accessible from the bedside, but in an alcove or area of the room where there are blackout facilities, lighting that can be dimmed, and no reflected light. Bedside viewing of the PACS images is possible, but is generally an expensive option. There are battery-powered mobile PACS trolleys/carts, rechargeable from mains electricity. They need a long battery life to last the entire ward round, and pose a security problem since theft of a mobile computer is much easier than a standard, fixed computer. One option for bedside viewing of PACS images is to make them available on the TV monitor located at each patient’s bedside for watching regular television (usually on a fee-paying basis). However this may lead to patient complaints if the ward round timing happens to coincide with a patient’s favourite TV programme, especially when the patient is paying for the privilege of watching it at the bedside! Hand-held personal digital assistants (PDAs) is another potential solution. Such wireless devices can be used to view a patient’s images at the bedside as a miniature prompt reminder of the imaging study in question. Obviously this assumes that the hospital is running a wireless network (unusual in the UK) and PDAs are considered far too expensive to be provided by the NHS! In each operating theatre web browser access to PACS is necessary. In theatres, use of wall- or ceiling-mounted computer monitors has been advocated by some, whilst others favour mobile carts. Wall- or ceiling-mounted monitors are more cumbersome to adjust and repair if they malfunction, and mobile cart computers raise issues of possible transfer of infection from one theatre to another if moved between theatres. The most important consideration is to ensure acceptable viewing monitor(s) (19 in) are installed, with a relatively long logout time and no screensaver, so that the images remain displayed for a sufficiently long time period and do not keep ‘disappearing’ during the surgical operation. Images viewed in theatre will already (hopefully!) have been studied in detail elsewhere by the operating surgeon, and

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their display in theatre is as an ‘aide-mémoire’ for review purposes only. Clearly the bright ambient lighting necessary in the operating theatre will render the image viewing conditions suboptimal anyway, so the monitors chosen for the PACS web browser computer do not have to be of particularly high specification. In the outpatient clinic access to a PACS web browser will be necessary in each clinic room for the majority of clinics. Since outpatient clinic rooms are often small, desktop integration of the PACS with the hospital information system/

patient archive system (HIS/PAS) on one computer (preferably using the same login for each system) is essential to allow sufficient desktop space. This is an additional reason for seamless integration between hospital IT systems. In addition there is the obvious need to be able to click directly from the imaging study to its report, and vice versa. Ideally it should be possible to view the patient’s other electronic data (e.g. blood test results) with the same user login, on the same computer, and without having to launch another software package from scratch.

CONFERENCE ROOM DESIGN Good overhead display of PACS images is essential in rooms used for MDTMs, staff rounds, teaching and other presentations.The overhead displays need not be of high resolution since they are for demonstration purposes only. The PACS workstation monitor(s) should be slaved to overhead projector(s) for projection on the wall, so that the whole audience can see the images well and are involved in the conference. It is not satisfactory (even with a small group) to attempt to run conferences from the PACS monitors themselves since visibility, even in the second row, is not good enough. Colour landscape-style monitors (maximum dimension in the horizontal plane) are preferable to portrait-style monitors (maximum dimension in the vertical plane) for linking to an overhead projector, since the latter were developed for the film industry and their technology is designed for colour landscape projection. Such projectors only synchronize well to the refresh rates of landscape-style monitors. Although a PACS web browser can be used to run conferences, more sophisticated PACS software is highly preferable for the reasons cited earlier. For example, PACS web browsers generally do not permit the use of software such as conference folders into which the examinations to be reviewed at the conference can be placed in advance of the conference. When

a PACS web browser is used, every patient to be reviewed has to be called up manually in real time by typing in their demographic details. This is time consuming, and does not allow easy pre-conference review of the images by the radiologist. The PACS requirements for a hospital staff round or teaching presentation differ from those of an MDTM since staff rounds and teaching merely require demonstration of the salient features in an image and, unlike MDTMs, have no diagnostic review purpose. Thus a single PACS monitor is adequate and can be of low specification. The PACS software permitting the use of PACS folders is, however, highly desirable for staff round and teaching presentations. Conversely, in an MDTM the radiologist should have two PACS workstation monitors (even if only one monitor is projected for the audience to see) to allow comparison of full-size current and previous chest radiographs simultaneously, or to compare and contrast different imaging modality studies simultaneously on the two monitors. Obviously the considerations of good blackout facilities and room lighting that can be dimmed also apply to the conference room. The relatively low luminance of the projected overhead image demands almost full blackout, and certainly there must at least be the facility fully to switch off the lights at the front of the room nearest the overhead screen(s).

GRAPHIC USER INTERFACE Whatever the specification of the PACS workstation, it is to be expected that its graphic user interface (GUI) should be intuitive and user friendly. The GUI is the screen layout and computer tools presented to the user.The ability to manipulate and post-process soft-copy images on monitors represents a major change in working practice for radiologists and other clinicians used to working with hard-copy film and now migrating to working with soft-copy images on PACS monitors20.

SOFT-COPY TOOLS All PACS vendors now offer a variety of soft-copy tools for image display and manipulation. User preference for the tools varies and many users now like the option to be able to configure their own customized toolbar/tool palette for their most frequently used soft-copy tools, some of which will be modality dependent.

Contrast width and level The contrast window width and level tool is the most frequently used soft-copy tool, and is often allocated to one of the mouse buttons for easy accessibility. Alteration of the contrast width and level allows soft tissue and bony structures to be well seen on a single exposure. For example, it often permits the left lower lobe to be assessed behind the left cardiac silhouette, whereas this information is not available on a relatively underexposed hard-copy chest radiograph. There is thus an increase in the amount of information that can be extracted from an image, and this is particularly noticeable for plain radiography. In addition to the contrast tool for continuous manipulation of greyscale width and level, there is generally a facility to enter personalized contrast width and level presets so that these can be rapidly applied to displayed images. This is particularly useful for instantly flipping from soft tissue to lung to

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bone windows on CT images (whereas previously different window settings had to be printed onto film by the radiographers).

CT density values A pixel tool will measure Hounsfield unit values on CT images. A region of interest (ROI) tool will give a mean density value.

Greyscale inversion A greyscale inversion tool causes video inversion of the image from the more conventional white-on-black presentation to black on white and vice versa. Many users prefer to use the black-on-white presentation for viewing barium work, angiography, hepatobiliary fluoroscopy and for identifying the tips of indwelling lines and catheters on plain radiography.

Stack/cine mode The ability to demonstrate images in stack-mode display leads quickly to a change in practice when viewing cross-sectional images (and angiographic images) on PACS monitors21. The stacking facility allows images to be demonstrated either on an automatic cine (useful in cardiac MR, dynamic US or MR contrast studies), or in a manual-scroll mode whereby the user can scroll up and down through a stack of images at a speed directly controlled by the speed of mouse movement (Fig. 1.8). All PACS vendors now provide software to link image stacks so that they run synchronously after matching for corresponding anatomical level. This is particularly useful for comparing new and old studies in the follow up of oncology patients, and for examining a chest CT simultaneously on lung and mediastinal window settings. An additional useful GUI tool is the ability to cross-link series in different anatomical planes (or scout views). This is mostly used in MR simultaneously to pinpoint a particular structure in, say, the transverse, coronal and sagittal planes. It is the exploitation of stack-mode display on a PACS monitor that allows diagnostic workstations with only two monitors (or even one monitor) still to be suitable for reporting cross-sectional imaging modalities. This viewing mode is so useful that it is desirable to have stack-mode display available

on the web browser review stations as well as on the diagnostic workstations.

Image orientation Image rotation and a left–right inversion tool will flip the orientation of an image (although if the radiographers have performed their quality assurance correctly, this should very rarely be necessary)22. It can also be of use in CT or MR procedures in which the patient has been examined in a lateral or prone position.

Magnification Magnifying glass functions include both the ability to magnify a segment of the image (preferably with a variable size to this magnified segment and a continuously variable degree of magnification within it) and the provision of a pan zoom tool that allows magnification of the entire image with a roam facility. Not all PACS vendors provide both tools, but each does have its individual uses. The magnification glass tool enables a segment of the image to be magnified, whilst retaining an overall view of the entire image, at its original size. The pan zoom tool enlarges the entire image, and is most useful for enlarging extremities (digits) and small paediatric images. If the magnification tool displays the original data at full resolution (Fig. 1.7), its presence can obviate the need to have 3 megapixel display monitors on workstations used for occasional diagnostic plain radiographic reporting, which greatly reduces the cost of the diagnostic workstations.

Annotation Annotation tools for teaching and labelling purposes include text, a scaleable arrow, the ability to paste measurement and density value data directly onto the image (and store it there as part of the overlay), and a freehand draw tool that is a useful adjunct for real-time teaching purposes. A closed-loop freehand draw tool will provide a cross-sectional area measurement of an irregular shape and is particularly useful for drawing round the tumour mass on radiotherapy planning scans.

Significant images It is highly desirable to have a means of designating selected images in an examination as ‘significant’ (‘key’ or ‘flagged’). The recall and display and/or printing of only these selected images can be useful under certain circumstances, such as for: • Nonspecialist clinicians • For demonstration purposes • As an aide-mémoire when referring to a historical examination.

Measurement Ti l e

Sta c k / cine

Figure 1.8 Diagram illustrating ‘tile’-mode display (left) and ‘stack-’ or ‘cine’-mode display (right). (Reproduced from Strickland N H, Allison D J 1995. Default display arrangements of images on PAC monitors. Br J Radiol 68:252–260 with permission).

Measurement functions include tools for making linear, area and angle measurements. There is also a requirement for certain computed measurements for particular specialties. In orthopedics the scoliotic curve is often assessed using the Lippman-Cobb angle. Dedicated orthopedic templating software packages are available to facilitate the planning

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required to predict the requisite joint prosthesis to be inserted at surgery.

Format The image format changes the number (upcount) of tile images displayed per monitor, and determines whether the examination will be displayed in tile or stack mode.

Linked cursors A linked cursor tool (dual user arrows) allows interactive conferencing between two distant users on different PACS workstations, communicating either by telephone, audio conferencing or by typing into dialogue boxes on their workstations. The two arrow cursors have a physically distinct appearance and one is assigned to each of the two workstations conferencing with one another. This feature is particularly important in the teleconference setting.

White masking/shuttering It is desirable to have a means of eliminating the glare from the white nonexposed area surrounding images acquired on phosphor plates or by fluoroscopic devices. This can currently be achieved by manual shuttering with a black frame, in some cases at the review workstation of the acquisition device, in others on the PACS workstation itself. This is a suboptimal solution because it is time consuming and it generally only allows rectangular shuttering frames to be applied. Such frames are unhelpful when an image, such as of the tibia and fibula, has been acquired in a diagonal orientation across the imaging plate, or when multiple exposures have been made on the same plate. The process ought to be achieved electronically such that the edge of the exposed area is automatically recognized and the white surround masked.

Save option The ‘save’ command should be a password-based user privilege. It is undesirable to have images saved on the PACS with inap-

propriate settings and therefore the save privilege is often made available only to radiologists and radiographers, who, with their specialist knowledge of how an image should appear, ought to be sufficiently responsible to leave an image so that it looks acceptable for viewing by the next PACS user. The save privilege may be made available to other users only in their private folders. An alternative approach is to have the image reappear as last saved by that specific user according to log in, and to default to how it was saved by the radiographer who first verified its appearance on PACS if not previously accessed by that user. It is sometimes useful to be able to display the original version of the image, as it was acquired onto PACS before any soft-copy manipulations were performed on it by other users. The problem with having this version of the image appear as the default is that frequently the plain radiography images will have required subsequent adjustment for orientation by the radiographer prior to verification on PACS, and will thus appear the wrong way up or inverted.

Some other desirable features An ‘undo’ command is useful for reversing the last configurable number of commands (as in a normal word processing package). It is useful to have a pull-down menu allowing easy access to the last viewed examinations so that the user can navigate back to them quickly and easily. It is important to be able to display the clinical details or report associated with any active examination by a one-step procedure. An ‘abort’ button is an extremely useful feature if a lengthy search or command has been instituted in error. The display of a progress bar in addition to a time cursor on the screen is desirable psychologically for the user, and indicates how far the task is towards completion. It also allows the user to distinguish whether the workstation has in fact ‘frozen/crashed/hung’ or whether the command is merely taking a long time to implement.

SOFTWARE CONCEPTS Sophisticated PACS software is essential to the radiologist (and to a lesser extent the nonradiological clinician in certain settings, as discussed in the section on workstations) to allow the PACS to be used efficiently in the clinical environment. It is the PACS software that is the discriminatory feature determining whether or not hospital-wide functioning using a PACS will be sustainable in a busy clinical environment23. Four main software concepts are considered in this section: 1 Prefetching 2 Worklists and folders 3 Default display protocols (DDPs) or hanging protocols 4 Reporting/dictation macros or worklists.

PREFETCHING Prefetching is the process whereby previous images on a patient are automatically retrieved from the long-term archive

onto the short-term storage device, either for review when the patient is due to attend the hospital as an in- or outpatient, or prior to the acquisition and viewing of a new imaging examination on that patient. Now that the cost of RAID storage has reduced, local ‘on line’ storage devices are often huge, with effectively all imaging studies kept there, immediately accessible to PACS users. Under such circumstances there is no call for prefetching of any imaging studies from a long-term archive. However, where numerous PACS facilities are sending their imaging studies to shared long-term archives (as in the English Connecting for Health countrywide PACS project, where there are five large long-term PACS cluster stores serving the whole country), the software concept of prefetching is again becoming a very important issue. Prefetching is commonly sufficiently sophisticated to take the form of an ‘intelligent’ prefetch. This means that only a

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be accessed in different ways (e.g. by body part or by referring clinician) according to the clinical setting. Depending upon the nature of the workflow in a particular institution the precise requirements for various worklists and folders will differ, and the pertinent software needs to be tailored and made site specific. One example is reporting worklists: some sites may prefer to divide up their plain radiographic work into body part specific worklists to be reported by specialized radiologists – chest radiographs, skeletal, skull and spine etc.; others may have radiologists who are happy to work from one general plain radiography reporting worklist. Direct integration of both HIS and RIS to PACS means that any ‘tag’ (or header field) in these systems can be used to construct a customized worklist or folder on PACS. (If only the RIS is directly interfaced to PACS then HIS fields cannot be used to construct PACS worklists or folders).

configurable number of past examinations, from the same modality and/or the same body part as that currently being imaged or reviewed, are retrieved from the long-term archive. It is usually only examinations of the same body part (and often of the same technique) that will be of relevance in making a diagnostic comparison, and there is no point in unnecessarily overloading the network and PACS short-term storage device with data irrelevant to the current clinical problem. Prefetching is essential to reduce the number of ad hoc fetches of examinations to a minimum and is usually scheduled to take place during the night before the next booked patient attendance or imaging study, since traffic on the network is slackest during the night.This is important because retrieval of examinations from the long-term storage (whatever its nature) takes much longer than the almost instantaneous display from short-term storage, and therefore needs to be kept to a minimum during clinical practice. Current hardware enables prefetched images to appear on the workstation monitor in <3 s, this being the time between the execution of the command to display an examination and the appearance of the first image of that examination on the monitor. Any subsequent re-display of this examination will be even quicker since it will already be in the random access memory (RAM) of the individual workstation. This contrasts markedly with the time taken to fetch an examination from the long-term archive, which is generally 2–3 min if that archive is local or even much longer (5–10 min) if it is far away on a wide-area network. Prefetching algorithms rely upon connections with the HIS and RIS to trigger prefetches for inpatients, outpatients, patients booked to have radiological examinations without a hospital attendance (referred from general practitioners), and patients due to be reviewed at MDTMs24. All these events (except the MDTM patient list) are known to the HIS and/or RIS, since this is where the booking for such events takes place, and this information needs to be transmitted to the PACS to trigger the prefetch. This is one of the key reasons why integration between the HIS, RIS and PACS databases is so crucial. If the HIS and RIS are governed by a master patient index, then it is this master patient index that communicates with the PACS database. It can be useful to have the PACS itself able to trigger prefetching; an example of this requirement is when patients have to be reviewed at a MDTM. Many such patients may not be current in- or outpatients and may not have had recent imaging examinations performed in the hospital, so there will be no trigger outside the PACS for the studies relating to these patients to be prefetched prior to the conference.

These are software algorithms for ordering and displaying the images of current and a configurable number of past related examinations in a predetermined arrangement on the workstation monitors, so that they appear as the radiologist and/or other clinician wishes to view them25–27. DDPs display only previous imaging studies of the same body part (and usually the same modality) for comparison with the current study, and they display these studies in the correct chronological order by default. All these features save the user time since the images do not have to be rearranged on the monitors prior to reporting or viewing. DDPs can now frequently be made user specific (based on login) and user configurable, and may be configured to suit different modalities or different body parts. Most PACS software allows specialized DDPs to be constructed, for example for cardiac MR, and for 3D reconstructions associated with cross-sectional imaging.The introduction of multi-slice spiral CT, large MR angiograms and dynamic MR contrast studies (e.g. in the breast) produce vast numbers of images at acquisition. Some centres consider it more appropriate to store these images on a local archive directly linked to the acquisition device, and only to send definitively to the PACS some selected reconstructed images for review. Some PACS vendors sell workstations with a third monitor, which is a colour, relatively low-resolution monitor (approximately 1 megapixel) linked to their high resolution (3 megapixel, greyscale) diagnostic monitors, on which a post-processing package, such as multiplanar reformatting, can be run simultaneously for cross-sectional imaging studies displayed on the diagnostic PACS monitors.

Worklists and folders

Reporting/dictation macros/worklists

These software concepts are a means of subdividing the vast amount of imaging data acquired onto the PACS into clinically relevant, easily accessible subgroups. Although ‘worklists’ and ‘folders’ are generally identical from the engineering viewpoint, worklists usually refer to ‘work that has to be done’ (such as lists of patients’ examinations that are to be acquired or reported), whereas folders are designated groupings of examinations that have generally been reported but need to

These terms refer to software mechanisms that provide the reporting radiologist with a means of working through a reporting worklist (equivalent to the old ‘reporting pile’ with film) in a manner that is efficient and thus time saving. This is achieved by minimizing the number of commands necessary to accomplish various necessary steps. For example, a single keystroke or mouse click might be expected to display the next examination in the reporting worklist with a predeter-

Default display protocols or hanging protocols

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mined number of previous related examinations, generally of the same body part and modality, in the correct chronological order and format according to the appropriate (or chosen) DDP. The same single keystroke or mouse click should also save the changes made to the displayed examination, if any, after dictation, and mark that examination reported when closed, by changing its status and thereby removing it from the worklist. The reporting macro will then automatically display the next unreported examination in the worklist, with its relevant previous examinations for comparison and so forth. Automated reporting/dictation macros or worklists are essential to the radiologist for rapid, efficient plain radiographic reporting work. This software can only work if the pertinent clinical details associated with the imaging study request appear automatically in electronic format with the imaging study displayed on PACS. Ideally this should be achieved by the integration of remote electronic requesting (order communications) with the PACS and the RIS; however a less satisfactory work-around can be achieved either by typing the clinical requesting details onto PACS or RIS, or by scanning in the paper request form. A highly desirable feature of some reporting macros is that the software automatically skips displaying the next exam in the reporting worklist if it has already been opened in reporting macro mode by another radiologist, working at a different workstation. This allows numerous radiologists to work from the same reporting worklist, at physically distant locations within the same or different institutions (as in a virtual hospital environment), and protects them from simultaneous dictation of the same exam. A useful (but rarely present) refinement of such reporting macros is to have an intermediate status assigned to examina-

tions if they have been reported by a junior radiologist and require checking at a later time. Such an intermediate status will temporarily protect these examinations from being subsequently reported by a more senior radiologist, and will allow their easy retrieval for checking after dictation by the junior.

Proprietary software It is important to realize that there is no standard for PACS software analogous to the DICOM standard for PACS and imaging hardware. All PACS software is thus proprietary, and vendor specific. This being said, one can ‘mix and match’ the hardware from different vendors when constructing a PACS, but a PACS workstation from one particular vendor will only display images according to the software programs that it is running. Some progress in this area has been made due to Clinical Context Object Workgroup (CCOW), which is a HL7 standard protocol designed to enable disparate applications to synchronize in real-time, and at the user-interface level. It is vendor independent and allows applications to present information at the desktop in a unified way. PACS databases are also not covered by the DICOM standard and so the only way for a workstation made by one particular vendor to obtain an examination from another vendor’s database is for that workstation to send a query/ retrieve DICOM format message to the database supplied by the different vendor. Such query/retrieve DICOM messages, although effective in being able to accomplish the task of displaying the desired images, will inevitably be slower than a proprietary query/retrieve between a workstation and a PACS database supplied by the same vendor. At present there is, unfortunately, no prospect of a universal software standard being developed.

COMPRESSION There are two major categories of image data compression28: lossless (reversible) and lossy (irreversible).

to be employed without the irreversible data loss being visibly detectable in the image.

LOSSLESS

NEED FOR COMPRESSION

Lossless compression techniques can currently achieve a maximum compression ratio of 3:1. As the name implies, lossless compression reversibly compresses the data so that no data are permanently lost from the image, which is restored to its original state when decompressed.

The main requirement for image data compression arises in connection with teleradiology. Compressed (reduced amounts of ) data can be transmitted more quickly, and therefore more cheaply, over long distance transmission lines. There is currently no British legislation regarding whether or not radiological images may be irreversibly compressed and used for diagnosis or archived in a compressed form. The British Royal College of Radiologists’12 recommend that if a definitive diagnostic report is to be made on an image then it should be viewed in an uncompressed form, although it may be subsequently archived in a lossily compressed form. Thus only lossless compression would be acceptable for an image that is to be definitively diagnostically reported on the receiving workstation. It has been argued in some countries (e.g. Germany) that only the ‘original’ (uncompressed) image should be archived. This argument is spurious, however, in that there is no clear definition of what constitutes the

LOSSY Lossy compression techniques irreversibly compress the image and data are permanently lost, although the aim is that this should not be detectable to the observer when the image is subsequently viewed29. Several types of compression algorithm exist, for example joint photographic expert group (JPEG) compression, and wavelet compression. The latter is currently employed by many companies in their web browser technology since it permits higher compression ratios (of up to 60:1)

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‘original’ image. Even the images as first acquired, be they CT or on phosphor imaging plate, have already been modified in some way, by the application of various image-processing algorithms. Now that long-term archiving media are becoming cheaper and of higher density (i.e. greater capacity) the need irreversibly to compress imaging data on a local area network (LAN) has diminished. The lossless compression of images being transferred from a short-term storage device to diagnostic workstations is of benefit, however, since even a 3:1 lossless compression ratio will noticeably increase the speed of transmission and thereby reduce the lag time between requesting the display of an image and seeing it appear on the PACS workstation monitors. Lossy compression of images transmitted to PC review workstations significantly reduces their transmission time30.

Many web browsers operate intelligent ‘streaming’ of data transmission such that reversibly compressed data are transmitted and the degree of decompression is tailored to fit the maximum display resolution of the monitors of each workstation/computer, thereby saving on unnecessary decompression time overhead, allowing the images to be displayed faster on the monitors. Progressive image decompression of all the images in the study takes place in the background whilst the first image(s) are displayed for viewing. A display time of 3 s between the keyboard display command and the appearance of the first image of the study on the display monitor is required for effective clinical workflow. In the diagnostic teleradiology setting it is useful to be able to view the data initially in a lossily compressed form (so that it arrives quickly) and subsequently in an uncompressed form to check that nothing that may be of diagnostic relevance has been missed.

DIGITIZATION POLICY Digitization is a laborious and time-consuming process, and needs to be performed by someone who is able to recognize the difference between the various imaging techniques (such as distinguishing CT from MR) and different body parts (for example someone who is able to differentiate films belonging to a barium meal, a small bowel enema and a barium enema). It therefore needs to be performed by personnel with some radiographic training, generally radiographers, and not filing clerks. Every study needs to have an entry sent from the RIS to the PACS prior to digitization; and needs to have the report, which resides in the RIS, made visible via the PACS. Digitized film will always be inferior to the original film, or to direct digital acquisition, however good the quality of the digitizer. Institutions differ in their approach to digitization of historical hard copy films when PACS is installed. It would be a total waste of resources to digitize large numbers of historical films, especially since so few historical films are ever referred to again. Many institutions digitize no previous films, but continue to send film packets to the outpatient clinics, and keep their film store on site, for a period of at least 3 months, and undertake rapidly to retrieve any requested hard copy for a further more prolonged period of, say, 2 years, when the film store is moved to an off-site storage facility. Some PACS sites (for example, Hammersmith Hospital in 1995/1996) allowed nonradiological clinicians to select films from a single previous imaging study for digitization prior to PACS ‘going live’. Such a film(s), deemed crucial for future reference, can be selected by the clinician from a particular patient’s film packet prior to refilling, after the patient has attended the outpatient clinic, or been discharged from hospital. (The examination for digitization was placed in a temporary plastic outer film jacket that also contained the patient’s normal cardboard film packet.) An additional policy, which is very effective, is to start building up a soft-copy PACS archive of digital images (from CR and DR, as well as the more traditional digital modalities of CT, MR etc.), some time before the institution withdraws film and goes live with PACS.This means that there will already be a substantial number of historical digital images on the PACS

for comparison when the institution becomes filmless. Clearly it is expensive to run this overlap period for too long, since any cost benefits of PACS can only start to be realized when film is withdrawn, and a period of approximately 3 months would be a reasonable compromise. Modalities that are already acquiring digital images (such as CT, MR many US and NM machines etc.) can easily send any configurable number of historical studies to PACS from the local modality storage medium. It is important that the reports of these examinations should also accompany the images and be visible on PACS. Every PACS institution will need to have the facility to digitize film and to upload CDs of digital images (and preferably also of their reports) onto PACS in order to deal with the images of patients referred to the hospital from elsewhere, so that these historical images can be easily viewed in conjunction with the subsequently acquired imaging studies performed on the patient when under the care of the PACS hospital. This requirement will clearly be greater for tertiary referral centres than for district general hospitals. In England the amount of digitization/uploading of digital images should reduce as the whole of England’s hospitals have a PACS installed and are able to send their images to the central cluster stores. It will always be necessary for the institution to have a means of burning imaging studies, with their reports, onto a CD for sending with patients returning from referral from abroad (outside England). This CD burner should automatically burn the images onto the CD in DICOM format, with a self-launching DICOM viewer, and also automatically burn the report associated with the imaging study. PACS vendors generally sell their own CD burners, but it is possible to use cheaper freeware versions available on the Internet, such as that supplied by efilm. In addition it is useful to be able to read CDs brought by the patient in the outpatient clinic or in the MDT room. Thus the computers in clinic rooms etc. (those also running the PACS web browser) should have a CD drive and should have sufficient RAM to be able to run a large cross-sectional imaging study in stack mode. If the CD files are copied

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to the hard drive of the computer the imaging studies will obviously run faster than trying to play them directly from the CD. After reviewing the images on the CD it may be decided that they are not of relevance to the current problem and therefore do not require uploading to the institution’s PACS. Such CDs containing images from a referring hospital should have been burnt in DICOM format with a DICOM viewer that self-launches when the CD is opened.

Unfortunately this is not always the case: sometimes the DICOM format of the images is incomplete, sometimes no DICOM viewer is included on the CD, and sometimes the images may be sent in JPEG, or other, format31. All these problems can make the CD unreadable on a normal PC, and thus it is advisable to have DICOM and JPEG reader software programs installed on these PCs to attempt to read such CDs.

TELERADIOLOGY Teleradiology is radiology at a distance (from the Greek, tele, meaning distance). It has more stringent requirements than other types of telemedicine because of the vast amount of data in radiological images and, if a definitive primary diagnosis is to be made at the receiving site, the requirement is to see this data at its original resolution. Teleradiology has many forms, but the most commonly used types of teleradiology are: 1 Review of images from home when on call 2 Teleradiology linkage between two or more hospitals for joint MDTs 3 Out-sourcing of imaging examinations by understaffed hospitals for reporting elsewhere by a private company 4 Tele-education whereby a digital image teaching library is accessed remotely by users. Again, the key here is that the hardware and software should be ‘fit for purpose’.

REVIEW OF IMAGES FROM HOME This is to allow the on-call radiologist or physician/surgeon to review plain radiographs (such as the intensive care chest Xray) or emergency CT to decide upon immediate medical or surgical management. It is not intended to provide the quality of image upon which the final definitive diagnostic report will be issued. These types of management issues generally depend upon observing fairly gross pathology, such as lobar lung collapse, free intraperitoneal gas, or intracranial haemorrhage.Veryhigh-resolution monitors are therefore not required, and a single 17 in PC monitor will suffice. It is, however, important to have a timely transfer of images (it would be medically negligent to wait for more than 2 or 3 min to receive a CT study showing a dissection of the aorta, for example), and for this a reliable broadband connection and streamed image compression (tailored to the resolution of the receiving PC monitor) will be necessary. Use of a virtual private network (VPN) minimizes the amount of data encryption necessary, which reduces the time overhead required for the encryption and decryption process.

TELERADIOLOGY LINKAGE BETWEEN TWO OR MORE HOSPITALS FOR JOINT MDTMS The complexity of the hardware requirements will vary depending upon the nature of the teleconference, for example, one site may always be the dominant site transmitting to vari-

ous satellite sites, or bidirectional links may be required so that either site can send or receive data. If one site wishes to send images whilst the other simultaneously transmits microscopy data for example, then two independent lines of transmission will be needed. Most clinicians prefer to use their screens for receiving as much medical data as possible, rather than reserving one for a photographic image of their colleagues in the other location(s), which is a concept video conferencing companies, used to installing equipment for business teleconferencing, often have difficulty in understanding. Large overhead projection onto a wall screen is preferable to smaller plasma screens that are not well seen from the back of a conference room. Some PACS software products include linked or sitespecific cursors to be used simultaneously on images during a teleconference. If a company different from the PACS vendor is used to install the teleradiology conferencing equipment, then the same stringent contract requirements for equipment service, maintenance (including a helpline facility and dial in troubleshooting), uptime and updates/upgrades should be incorporated into the contract signed as is used for the PACS project itself or for any medical IT project.

OUT-SOURCING OF IMAGING EXAMINATIONS FOR REPORTING This service constitutes diagnostic primary reporting remote from the site where the imaging examinations were acquired.This demands exactly the same hardware and software requirements (including access to the patients’ previous imaging examinations with their reports) as if the diagnostic reporting were being carried out in the primary hospital contracting out the service.

TELE-EDUCATION The hardware requirements for remote access of a digital image teaching library are minimal. The user’s home PC will be adequate. Software for such teaching libraries will be of variable sophistication. The better teaching modules will allow the user to perform basic manipulation of the images, including altering contrast width and level, magnification, viewing in stack mode. Flexible use of the teaching material is desirable, with the possibility for the user to review cases on one particular topic, or to work through a random selection of cases in ‘exam mode’, and to use bookmarking in order to be able to return to the same place in the teaching programme after an interruption, and so forth.

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SECURITY Any PACS and teleradiology installation must incorporate security measures to protect patient confidentiality32. These operate at several levels in a PACS: • User-specific log in and password • Monitor screen savers • Workstation time-outs • Encryption • Audit trails • Firewalls.

USER-SPECIFIC LOG-IN AND PASSWORD Users of the PACS should be registered with the system administrator and provided with a personal log-in and password. It is becoming more common for passwords to have to contain special characters and numbers as well as letters. Some institutions implement an enforced password change every few months in order to maintain an updated list of currently approved users.

MONITOR SCREEN SAVERS Screen savers on PACS workstations guard against the risk of a patient’s data being inadvertently left displayed on an unattended workstation.

AUDIT TRAILS A PACS, like any other multi-user computerized system, should have an audit trail mechanism that logs to a specific user all actions they carry out on the system.This audit trail can be used to trace any inappropriate data viewing, or any action that could potentially pose a risk to the security of the system and the integrity of its data. Such actions on a PACS include the deletion of images and the merger of patients. There are legitimate reasons for occasionally wishing to carry out such procedures, usually to correct human error, for example, the image(s) of one patient may erroneously have been acquired into the wrong patient’s folder; the same patient may inadvertently be entered onto the PACS twice with different identification numbers or different name spellings.The privilege to make such changes on the PACS is generally restricted to the system administrator(s).

FIREWALLS A firewall is a configuration that protects a computer system from unauthorized access from outside the institution. It only allows access from specified Internet protocol (IP) addresses and ports using certain protocols. It will protect a PACS from access by unauthorized users.

TELERADIOLOGY SECURITY WORKSTATION TIME-OUTS An automatic time-out feature for every workstation minimizes the risk of workstations in use being left unattended after a user has logged in. Different time-out settings can be applied to the various workstations throughout the hospital based upon their intensity of clinical use.

ENCRYPTION Encryption is not generally deemed necessary for an intranetbased PACS, but is essential when teleradiology, with data transmission over public networks, is being employed. There are numerous different types and levels of encryptions. Commonly encryption involves private and public encryption keys (codes) to encrypt the data and to access it once encrypted.

When patient data are transmitted over public networks, as with teleradiology, security measures must be undertaken to ensure confidentiality. Thus an encryption program must be part of any teleradiology installation to codify the textural data. Generally the images per se cannot be recognized as patient specific and therefore image data need not be encrypted, unless there is identifiable textural patient information burnt into the image itself, as occurs with screen-captured images or images digitized from hard-copy film. Many would argue that it is safer and simpler to encrypt both image and textural data sent over a public network. Alternatively a VPN can be used for teleradiology instead, obviating the need for encryption and thus saving on the time overhead taken for encryption and decryption of large volumes of data. A VPN is accessed by designated users via a randomly generated code on a digital keypad.This code changes for every log-on session, and allows the user to be connected to the network.

PACS TRAINING PACS training is part of the PACS installation and is carried out in the first instance by the PACS vendor, as will be specified in the PACS contract. PACS training (as for any IT installation) is provided on a cascade basis, so that the vendors’ applications specialists train key personnel, who are then responsible for cascading that training to other members of staff. It is important to keep a formal permanent record of

the names of these ‘core trainers’ who attended the training sessions, so that they can later be held responsible for training other members of their teams. One of the challenges in any hospital is to disseminate information to its staff. The times and locations of the training sessions need to be well publicized, with sufficient choice of times to allow the maximum number of users to attend. Since

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attendance at such training sessions is often given a low priority by busy clinicians, it can be very valuable to schedule the training sessions just prior to the PACS go-live date (or PACS upgrade). It is also very good for applications specialists to be present in key locations, such as the outpatient clinics and the A & E department, immediately after the PACS (or major PACS upgrade) is introduced, to help users in the clinical setting when they have no choice but to use the PACS. On-line computerbased training and help menus are useful adjuncts to training. Basic PACS training and information on how to obtain a PACS password must be included in new hospital doctors’ induction day instructions and be available on the hospital intranet.

The training required by a nonradiological clinician to use the PACS is relatively modest: merely to learn how to call up the required imaging study, display it with any relevant historical imaging study, manipulate the image with respect to simple soft-copy tools including changing the contrast settings and magnification, and display the report. Most clinicians also like to be able to display large cross-sectional imaging studies (CT and MR) in stack mode and to scroll through them manually. Clinicians also need to be taught how to add imaging studies to folders so they can populate the MDTM folders with the imaging studies they wish to have reviewed in advance of the meetings.

QUALITY ASSURANCE A thorough programme of quality assurance must be instigated to maintain a PACS. This will generally be undertaken by in-house specialists, such as radiation physicists and IT personnel, as well as input from the PACS vendor as part of the maintenance contract. Technical support via a modem connection is not sufficient. The tasks involved in a quality assurance programme for a PACS hospital differ substantially from those previously required in a conventional-film-based hospital.

PLAIN RADIOGRAPHY The acquisition of plain radiographic images in digital format so they can be transferred to the PACS still constitutes the major workload in the imaging departments of most general hospitals (see ‘Implementation of Digital Image Acquisition Prior to PACS’). The quality assurance of these images, which are still largely acquired by CR, is an important task integral to the PACS project. Quality assurance is a topic that, unfortunately, has been largely ignored by PACS and CR manufacturers. The radiographic technique required for CR and direct DR differs in a number of respects from the procedure required with conventional film, for example, the correct body part algorithm must be applied to the image. In order effectively to run a quality control program it is essential that ‘rejected’ unsatisfactory images should not be lost from the system. This can be avoided if a mechanism is introduced whereby such inadequate images are sent to PACS by default and then, by ‘rejection’ on the PACS, made invisible to the clinical user, but visible to the physicist who is performing the quality control analysis. The same mandatory send to PACS of all unsupervised fluoroscopic and angiographic images acquired by junior radiologists in training allows their work to be assessed for quality assurance purposes. It is helpful to make certain fields on the CR device mandatory, including: • Entry of the radiographer’s identification, so that quality control issues can be discussed with the appropriate person • A record of the exposure factors (mAs and kVp) used on each image, since the wide latitude of CR and DR will ‘salvage’ an overexposed image that would have looked

black on film, but will appear acceptable on digital imaging after appropriate contrast adjustment, resulting in even gross overexposure passing undetected.

PACS WORKSTATIONS Regular quality assurance of the monitors on diagnostic PACS workstations ensures they are functioning optimally33. Their brightness, fidelity of greyscale range, and number of dead pixels (on flat-panel monitors) need surveillance. An image should have the same greyscale appearance whatever the device upon which it is displayed, including monitors of differing qualities and makes, film, CDs, and even paper prints. DICOM definition of greyscale display conformance greatly facilities this task by making it amenable to automation. Even trivial quality assurance tasks are important and monitors need regular cleaning to remove finger marks and dust, and keyboards also need cleaning. Laser mice do not suffer from mechanical failure seen in mice containing roller balls.

PACS failure The day-to-day maintenance, percentage uptime, fault-fixing times, and the software and hardware upgrades and ‘refreshes’ of the dedicated PACS workstations and the web browser computers must form part of the PACS contract. Responsibility for the dedicated PACS workstations and their software normally lies with the PACS vendor company, whereas the hospital IT department is usually responsible for the web browser computers, their software and antivirus programs, and for the PACS and hospital networks. The amount of out-ofhours cover is predicated by cost. Often this emergency cover is channelled via the in-house IT helpline. It is vital that these IT helpdesk workers understand that a PACS breakdown has dire clinical consequences (culminating in the total breakdown of all clinical practice), due to the fundamental dependence of all-modern clinical practice upon imaging. Any PACS problem must be given the highest priority by the IT helpdesk, with immediate escalation, unlike a reported email system failure, for example. It is essential to have a robust protocol in place to deal with major potential failures of the integrated PACS, including knowing what to do in the event of failure of:

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The RIS Sending from the modality to PACS The PACS itself, or part of the PACS The network Any other IT systems that may be integrated with the PACS, such as remote electronic requesting, speech recognition and the EPR.

Every major PACS upgrade will currently be associated with planned PACS downtime (although in future it is likely that even large upgrades will be mainly conducted in the background, thereby not disturbing the user), and these upgrades need careful advance planning and hospital-wide coordination34.There has to be a mechanism (by printing film or burning CDs for example) of maintaining an emergency imaging service during the PACS downtime.

PACS HOUSEKEEPING PACS does not run itself and needs daily housekeeping to keep the database tidy. This task is best performed by a dedicated team to provide redundancy (for sickness and holiday leave), although only one full-time equivalent (FTE) is necessary per PACS site producing 80–100 000 examinations per year. Radiographers are best suited to this task (after special training) since they are already familiar with radiological workflow, and understand the difference between the various imaging modalities and body parts imaged. A team of four such radiographers for one FTE post avoids the risk of boredom arising if they were to perform solely PACS housekeeping duties for much longer than a week at a time, and enables them also to maintain their radiography skills by working on a rota basis. PACS housekeeping is an ongoing task that will last throughout the life of the PACS and it is essential that provision be made for such posts at the time of PACS implementation. If the appointment of such posts is delayed, huge backlogs of PACS housekeeping tasks develop, which are difficult to clear. Housekeeping tasks can be summarized according to the resultant problems visualized on the PACS, for each of which there may be several different causes: 1 There is a study entry on PACS but no images 2 The study entry appears as ‘unspecified’ (or similar nomenclature) on PACS 3 The study has a dictated status on PACS but there is no associated report visible on the PACS 4 The study has a nondictated status on PACS and no report 5 The study has a verified state on PACS but needs to be reopened to add more images to it 6 The study is unretrievable from the long-term archive 7 There are CR/direct DR errors 8 Burning imaging studies and their reports to CDs and uploading imaging studies from external CDs/digitizing external films. There will be a large amount of extra housekeeping work generated every time there is an upgrade to the PACS or to any of the IT systems integrated to PACS (such as RIS, speech recognition or HIS/EPR).

1. There is a study entry on PACS but no images Possible causes • The patient was expected for the study at a set time (booked appointment on RIS) but did not attend (DNA), or defaulted from the study before images could be acquired

for some other reason, such as claustrophobia in the MR scanner. The RIS entry automatically generated an order entry on PACS, but no images were generated to go into the study. This situation requires deletion of the RIS entry and of the PACS entry (although it is advisable to keep a permanent record somewhere [usually on the RIS] of the fact that the patient DNA). • The modality on which the images were acquired is not connected to the PACS, such as a mobile US machine printing paper images, or a mobile fluoroscopy unit used in the operating theatres, and therefore the images taken could not be transferred to PACS. However since the study was performed, a report should be generated, and it is often valuable to have such reports accessible on the PACS, despite the lack of images, for later comparative purposes when subsequent studies are performed that are acquired onto the PACS. Clearly such genuine studies, with zero images on PACS but a generated or pending report, should not be deleted.

2. The study entry appears as ‘unspecified’ (or similar nomenclature) on PACS Main possible causes • No RIS entry was made for the study: the demographic details of the patient were entered directly on the imaging modality and the images were then sent to PACS. • The link between RIS and PACS is down so there is no entry on PACS to receive the sent images. • The DICOM modality worklist between RIS and the modality is down (or has not been implemented). The demographic details of the patient therefore have to be entered again, manually, directly on the modality. Also due to typographical errors, there is a mismatch of demographical data sent to PACS from the modality acquiring the images and that from the RIS entry sent to PACS. • Extra images are sent to PACS for an exam that has already been closed on PACS, for example, post-micturition US images, or CT/MR reformatted images. This is not a problem for equipment where DICOM modality performed procedure step (MPPS) has been implemented, whereby individual steps of an imaging study can be closed without closing the whole study. • The imaging plate (or image acquisition) was not assigned to any patient, i.e. no name was supplied. This could arise, for example, if different CR plates containing images from

CHAPTER 1

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PICTURE ARCHIVING AND COMMUNICATION SYSTEMS (PACS) AND DIGITAL RADIOLOGY

the same examination on the same patient were put through different CR readers, if these readers are not networked and so do not communicate with one another. The problem in any of these scenarios is that the PACS is regarding these ‘unspecified’ images as belonging to a study on a separate patient. This means that none of the previous imaging studies on the patient is available for comparison with the unspecified examination, which is not only undesirable but could be medically dangerous. The first bullet scenario should never arise, since it must be made compulsory policy for a RIS entry to be made first before any imaging examination is carried out (and this must apply in the emergency situation and out of hours too). The solution for the next three bullets is to merge the ‘unspecified’ images into the correct PACS folder. In the case of the fifth bullet, no demographic data were supplied at all yet the images were still sent to PACS. Under these circumstances it is essential for the correct patient to be identified, and to reassign the image(s) to the correct patient demographic data on the CR plate reader, and then for the ‘no name supplied’ images to be merged into one folder, bearing the correct demographic details, on PACS.

3. The study has a dictated status on PACS but there is no associated report visible on the PACS Possible causes • Human error: the study is erroneously marked dictated on PACS, by a keystroke or mouse click, by a radiologist (or other reporter). • The dictation is ‘lost’. This can be due to the loss or corruption of a tape (if cassette tapes are being used to record verbal dictation), or to malfunction of a speech recognition or digital dictation system. Action required to remedy this problem is to decide upon a date range to be investigated (choosing an end-point where the report would have been expected to reach PACS), and to check whether a report exists on the RIS or speech recognition/digital dictation system. If it does, then this report needs to be resent to RIS and/or PACS and the failure in this pathway corrected. If no report exists, then the status of the examination needs to be restored to ‘unreported’ status on PACS so that it will reappear in an unreported worklist for a report to be dictated by a radiologist. If the examination is of a ‘special’ type, such as an angiogram, a specific radiologist may need to be alerted and so made aware that this ‘recycled’ study exists and requires a report. It may be necessary to resend the study entry from RIS to PACS, depending upon the type of integration implemented between PACS, RIS and the speech recognition system (if in use). If there is no backward connection from PACS to RIS and/or the speech recognition system, merely changing the status of the study to ‘unreported’ on PACS will not affect its status on RIS or on the speech recognition system. These systems will still view the study as having a reported status, and will therefore block the study from being re-reported.

4. The study has a nondictated status on PACS and no report This refers to studies on PACS that have been ‘missed’ and not reported. In some PACS where there is a relatively small short-term archive, when such studies become old they ‘fall off ’ the short-term archive, their status changes from ‘unreported’ to some different intermediate status, and they are then only present on the long-term archive, but have still not been reported. There are various reasons for examinations to be missed in reporting, including: • The study was performed out of hours on call by a junior radiologist. A verbal report and/or hand-written report in the case notes was issued, but no definitive report was issued awaiting discussion with a consultant radiologist (this never took place). • If cross-sectional imaging work is allocated to radiologists on a sessional basis, a study may be missed at hand-over between, say, morning and afternoon sessions, with each of the radiologists responsible thinking the other is going to report the study. • A particular type of imaging examination may be unpopular to report either because it requires specialist expertise, such as a temporo-mandibular joint MR, or because it is tedious and time consuming, such as a bone age study. Such studies may be left for prolonged periods of time in the hope that they will be reported by another colleague! The solution is as in item (3) above in addition to recalling it to the short-term PACS archive.

5. The study has a verified state on PACS but needs to be reopened to add more images to it This problem arises simply due to the current lack of implementation of DICOM storage commitment (SC) and DICOM MPPS on the modality, the PACS, or commonly both (see later for a description of SC and MPPS). A study may be closed on PACS by a radiographer verifying that all the images have been transferred to PACS, or by a radiologist (or other reporter) reporting the study and marking it ‘dictated’. At a later stage it is realized that further images need to be added to the study. This may arise in a number of circumstances, for example: • Post-processing reconstructions were performed on a specialist workstation after the study was completed. • Dedicated radial head views were being performed at the request of a different radiologist from the one reporting the study, who did not realize that further views had been requested. • The study was reviewed by the reporting radiologist working on a specialist dedicated workstation (e.g. for crosssectional imaging studies), who then reported the study on PACS without opening it, not realizing that not all the images had yet arrived on PACS. • Delayed images were later acquired on an IV urogram. In these circumstances the study status needs to be ‘re-opened’ on PACS, i.e. its status needs to be changed on PACS to

27

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• IMAGING TECHNIQUES AND GENERAL ISSUES

‘unverified’ (or the equivalent nomenclature), and the additional images need to be sent to the study folder on PACS and the verified/reported status of the study reinstated. Obviously if a radiologist has already reported the study without being aware that additional images exist, they must be alerted to the presence of these extra images in case the images alter the validity of the report already issued, requiring a report addendum to be added.

6. The study is unretrievable from the long-term archive If a study cannot be fetched from the long-term store back onto the local short-term archive this usually requires investigation by a PACS engineer, who needs to be alerted. Robust mechanisms will need to be set in place to deal with this problem when linked regional cluster stores are in widespread use nationally (as planned for the Connecting for Health, CfH project in England).

7. Computed radiography/direct digital radiography problems These are various and could reasonably be classified as radiographic and radiographic equipment problems rather than PACS problems, but since plain radiography forms such an integral part of any PACS, they are best dealt with by the PACS housekeeping team. One such example, when the imaging plate (or image acquisition) is not assigned to any patient, i.e. no name was supplied, has already been detailed earlier in item 2. Other examples include: • An image is assigned to the wrong exam of the same, or a different patient. • The wrong processing algorithm is used on the image, which might cause the image to look too grainy or poorly defined. • The imaging plate is cracked, scratched or dirty. The first bullet scenario is an emergency situation for the PACS housekeeper if an image is assigned to the wrong patient, since it could potentially have medically dangerous consequences. The immediate visibility of PACS images to users throughout the health care institution theoretically means that the wrong management could be started on the wrong patient (e.g. a chest drain placed in a patient who did not have a tension pneumothorax), before the fault was rectified by reassigning the image to the correct patient. The very first housekeeping step when an image has been assigned to the wrong exam is to write and save a warning annotation on the image (such as ‘Error: beware this image does not belong to this patient’), which will be immediately visible as an alert to all PACS users. This incorrectly assigned image must then be deleted on PACS. Then, on the CR reader (or other modality), the image must be un-assigned from the wrong patient/study and re-assigned to the correct patient/study and resent to PACS. When the wrong processing algorithm has been used, the suboptimal appearance of the image cannot be corrected merely by changing the contrast window width and level.The

raw data needs to be reprocessed on the CR or DR console using the correct algorithm, and resent to PACS such that the new image resides in the correct PACS study folder. Cracked, scratched or dirty imaging plates need to be identified and replaced or cleaned as appropriate.

8. Burning imaging studies and their reports to CDs and uploading imaging studies from external CDs/ digitizing external films Transfer of imaging studies to institutions outside England (not linked by a shared long-term archive) requires the burning of the images and their associated report onto a CD for physical transfer. Private patients are entitled to a copy of their imaging study and report for future reference. The images should be burnt to the CD in DICOM format with a self-launching DICOM viewer so that the imaging studies can be easily viewed on the recipient’s PC, and can be uploaded to another PACS without having to convert their format. There is now no place for printing images to film, which is more expensive than a single CD and is not amenable to image manipulation (such as changing contrast window width and level, or magnification). CDs (or films) containing imaging studies from outside hospitals/health care centres may be accepted for uploading (or digitizing) onto the institution’s PACS, if a patient is being considered/has been accepted for continuing care at that institution. All such studies will require a RIS entry, and, ideally, a study report, associated with the imaging study transferred to the PACS for review. The amount of uploading of imaging studies from external CDs is escalating exponentially as more institutions implement PACS. (In England it is hoped that adequate implementation of the cluster stores, the Englandwide National spine and the N3 network should alleviate this problem.) Unfortunately many institutions are burning CDs without a DICOM viewer, or with images in non-DICOM format that pose problems for the recipients in reading them and transferring them to their own PACS. The PACS housekeepers should be responsible for trying to resolve these issues in a timely manner, since no one else has been delegated to take on this unexpected extra work.

STORAGE COMMITMENT (Fig. 1.9) SC is a relatively recent DICOM service and a major advance for PACS. It provides for the first time a way for the modality and the PACS to confirm that images sent by the modality are safely stored in the PACS. The PACS sends a message back n images sent Modality

PACS

n images sent

Figure 1.9

DICOM storage commitment.

CHAPTER 1

•

PICTURE ARCHIVING AND COMMUNICATION SYSTEMS (PACS) AND DIGITAL RADIOLOGY

to the sending modality when it has successfully received and committed to storage the expected ‘n’ number of images. On receipt of this message from the PACS, the modality operator (e.g. a CT superintendent) will know that all the images in a study have been successfully acquired onto PACS, and it is now safe to delete those images from the acquisition modality (the CT scanner in this case) without risk of any unarchived images being ablated.

MODALITY PERFORMED PROCEDURE STEP (Fig. 1.10) In MPPS, the modality sends a message to the RIS (and to the PACS as well) whenever a defined part of an imaging acquisi-

PACS RIS Modality

Figure 1.10

DICOM modality performed procedure step.

tion process has been accomplished, so that the RIS and the PACS can progress the case on to the next step (which may be to store the case in the PACS, or to move the case to the reporting stage).

CURRENT AND FUTURE DIRECTIONS OF PACS PACS has now proved itself in sustained filmless clinical practice in numerous sites around the world. The acceptance and implementation of the DICOM standard for imaging equipment and PACS, and of the HL7 standard for RIS and HIS, and the introduction of the EPR, has promoted easier integration of systems from different vendors. The introduction of fast standard (nonproprietary) protocols and the application of web browser technology have enabled PACS installations to become open systems using commercial offthe-shelf hardware, which in turn is reducing the overall cost of PACS. Now that PACS is accepted into routine clinical practice in modern medical institutions, it is the ‘added value’ of PACS in improving clinical workflow efficiency that must take priority. Seamless integration of PACS with other electronic systems in the health care enterprise implies a single log in, using a single workstation, with easy ‘point and click’ navigation between the various software packages. PACS is merely one part of the ultimate total EPR where electronic requesting and booking, speech recognition, electronic feedback and acknowledgement of results, digital recording of the entire case notes, electronic pharmacy, stocktaking and ordering etc. all form a part of the whole. Radiology has led the way in developing PACS to its current high standard and ubiquitous deployment. Other disciplines using clinical images (such as cardiology, obstetric US, endoscopy and bronchoscopy, ophthalmology, dermatology, histopathology etc.) must show the same rigor in workflow process to achieve the PACS equivalent, which requires as priorities: (A) an information system like RIS to book the studies, send the demographic data to PACS and the image acquisition device, and store the reports; and (B) extensive IT support and active housekeeping on a daily on-going basis. There is no technical reason why all clinical images and other clinical digital records should not be integrated into the elusive EPR: it is merely the process and discipline of implementation that is still currently lacking outside the domain of radiology.

ACKNOWLEDGEMENT The author thanks Dr David Harvey for writing the subsection on ‘Storage Requirements and Solutions for PACS’.

REFERENCES 1. Reiner B I, Siegel E L, Hooper F, Protopapas Z 1998 Impact of filmless imaging on the frequency of clinician review of radiology images. J Digit Imaging 11(suppl 1):149–150 2. Redfern R O, Kundel H L, Polansky M, Langlotz C P, Horii S C, Lanken P N 2000 A picture archival and communication system shortens delays in obtaining radiographic information in a medical intensive care unit. Crit Care Med 28:1006–1013 3. Reiner B I, Siegel E L, Hooper F J, Glasser D 1998 Effect of film-based versus filmless operation on the productivity of CT technologists. Radiology 207:481–485 4. Reiner B I, Siegel E L, Hooper F J, Pomerantz S, Dahike A, Rallis D 2001 Radiologists’ productivity in the interpretation of CT scans: a comparison of PACS with conventional film. Am J Roentgenol 176:861–864 5. Siegel E L, Reiner B I 1998 Recommendations for image prefetch or film digitization strategy based on an analysis of an historic radiology image database. J Digit Imaging 11:94–99 6. Bryan S, Weatherburn G, Buxton M, Watkins J, Keen J, Muris N 1999 Evaluation of a hospital picture archiving and communication system. J Health Serv Res Policy 4:204–209 7. Mariani C, Tronchi A, Oncini L, Pirani O, Murri R 2006 Analysis of the Xray work flow in two diagnostic imaging departments with and without a RIS/PACS system. J Digit Imaging 19(suppl 1):18–28 8. Strickland N H 1998 Role of a project leader implementing a hospitalwide PACS. In: Horrii S C, Blaine J G (eds) Proceedings of SPIE Medical Imaging 3339: PACS design and evaluation: engineering and clinical issues, pp 476–478 9. Pilling J 1999 Problems facing the radiologist tendering for a hospital wide PACS system. Eur J Radiol 32:101–105 10. Perry J H 2000 PACS: A PACS RFP Toolkit, www.dejarnevtte.com/ efinegan/pacsprim.htm 11. Reiner B, Siegel E, McKay P 2000 Adoption of alternative financing strategies to increase the diffusion of picture archiving and communication systems into the radiology marketplace. J Digit Imaging 13(suppl 1):108–113 12. The Royal College of Radiologists 2007 Guide to information technology in radiology. BFCR (in preparation). Royal College of Radiologists, London

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13. Boochever S S 2004 HIS/RIS/PACS integration: getting to the gold standard. Radiol Manage 26:16–24 14. CCTA 1998 Managing successful projects with PRINCE (PRINCE 2 reference manual). Central Computing and Telecommunications Agency, London 15. Lewis T E, Horton M C, Kinsey T V, Shelton P D 1999 Acceptance testing of integrated picture archiving and communications systems. J Digit Imaging 12(suppl 1):163–165 16. Andriole K P 2002 Productivity and cost assessment of computed radiography, digital radiography, and screen-film for outpatient chest examinations. J Digit Imaging 15:161–169 17. Graschew G, Roelofs T A, Rakowsky S, Schlag P M, Heinzireiter P, Kranzlmuller D, Volkert J 2006 New trends in the virtualization of hospitals – tools for global e-Health. Stud Health Technol Inform 121:168–175 18. Meenan C, Daly B, Toland C, Nagy P 2006 Use of a thin-section archive and enterprise 3D software for long-term storage of thin-slice CT data sets. J Digit Imaging 19(suppl 1):84–88 19. Brem M H, Bohner C, Brenning A et al 2006 Evaluation of low-cost computer monitors for the detection of cervical spine injuries in the emergency room: an observer confidence-based study. Emerg Med J 23:850–853 20. Strickland N H 2000 PACS (picture archiving communications systems): filmless radiology. Arch Dis Childhood 83:82–86 21. Mathie A G, Strickland N H 1997 Comparison between ‘stack’ and ‘tile’ mode CT image display on PACS. Radiology 203:207–209 22. Luo H, Luo J 2006 Robust online orientation correction for radiographs in PACS environments. IEEE Trans Med Imaging 25:1370–1379 23. Strickland N H 1997 Implications of a filmless hospital for a radiological service. In: Proceedings of the 5th International Conference on Image Management and Communication (IMAC) ‘97. Seoul, Korea. Proceedings of the PakMedTek Symposium 24. Strickland N H, Deshaies M J, Reynolds R A, Turner J E, Allison D J 1997 Short term storage allocation in a filmless hospital. In: Horii S C, Blaine J (eds) Proceedings of SPIE Medical Imaging 3035: PACS design and evaluation: engineering and clinical issues, pp 509–514

25. Strickland N H, Allison D J 1995 Default display arrangements of images on PACS monitors. Br J Radiol 68:252–260 26. Strickland N H, Allison D J, Reynolds R A, Crowell J, Schuurmans M D, Keller S A 1995 Organization of intensive therapy unit images on PACS monitors. In: Jost R G, Dwyer S J (eds) Proceedings of SPIE Medical Imaging 2435: PACS design and evaluation: engineering and clinical issues, pp 278–285 27. Strickland N H, Allison D J, Deshaies M J 1997 Design for the optimal arrangement of magnetic resonance images on PACS monitors. In: Kim Y (ed.) Proceedings of SPIE Medical Imaging 3031: Image display, pp 432–439 28. Okkalides D 1998 Assessment of commercial compression algorithms, of the lossy DCT and lossless types, applied to diagnostic digital image files. Comput Med Imaging Graph 22:25–30 29. Toney M O, Dominguez R, Dao H N, Simmons G 1997 The effect of lossy discrete cosine transform compression on subtle bone fractures. J Digit Imaging 10:169–173 30. Bennett W F, Spigos D G, Tzalonikou M T, Terrell J E, Augustyn M A 1999 Web-based viewing of picture archiving and communications systems images – Part II: the effect of compression on speed of transmission. J Digit Imaging 12(suppl 1):116–118 31. van Ooijen P M, Roosjen R, de Blecourt M J, van Dam R, Broekema A, Oudkerk M. 2006 Evaluation of the use of CD-ROM upload into the PACS or institutional web server. J Digit Imaging 19(suppl 1):72–77 32. Doupi P, Ruotsalainen P, Pohjonen H 2005 Implementing interoperable secure health information systems. Stud Health Technol Inform 115:187–214 33. Crespi A, Bonsignore F, Paruccini N, Macchi I 2006 Grayscale calibration and quality assurance of diagnostic monitors in a PACS system. Radiol Med (Torino) 111:863–875 34. Strickland N H, Allison D J, Beam K W et al 1998 Implementation of a major hardware and software upgrade in a hospital-wide PACS during clinical use. In: Horii S C, Blaine J G (eds) Proceedings of SPIE Medical Imaging 3339: PACS design and evaluation: engineering and clinical issues, pp 496–499

CHAPTER

Intravascular Contrast Media for Radiology, CT and MRI

2

Ronald G. Grainger, Henrik S. Thomsen, Sameh K. Morcos, Dow-Mu Koh, Giles Roditi

INTRAVASCULAR RADIOLOGICAL IODINATED CONTRAST MEDIA Ionic monomers (high osmolar contrast media [HOCM]) Non-ionic monomers (low osmolar contrast media [LOCM]) Ionic dimers Non-ionic dimers Quantity of iodine required Informed consent Adverse reactions to radiological contrast media Types of adverse reaction Complications Principles of investigating patients at increased risk Contrast media related to specific clinical areas Renal Tract Nervous system Cardiovascular System Contrast media, blood coagulation and the endothelium Prevention of adverse reaction to RCM Ethical, financial and cost–benefit considerations High- versus low-osmolar contrast media Conclusion MRI CONTRAST MEDIA Extracellular MRI contrast agents Pharmacokinetics Clinical use of extracellular MRI contrast agents

Safety of extracellular MRI contrast agents Contrast medium-induced nephropathy Nephrogenic systemic fibrosis (NSF) Prevention of adverse reactions Use of extracellular MRI contrast agents in special groups of patients Interaction between extracellular MRI contrast agents with clinical tests Use of extracellular MRI contrast agents for radiographic examinations CONTRAST-ENHANCED MR IMAGING OF THE LIVER AND PANCREAS Non-specific extracellular gadolinium chelates Arterial phase Portovenous phase Interstitial phase Hepatocyte-selective gadolinium chelates Non-gadolinium contrast media CONTRAST-ENHANCED MR IMAGING OF THE PANCREAS Gadolinium contrast-enhanced imaging Mn-DPDP-enhanced MR imaging MRI CONTRAST AGENTS AND TECHNIQUES FOR CONTRASTENHANCED MR ANGIOGRAPHY Concepts of contrast medium administration Peripheral run-off and whole-body CE-MRA Blood pool contrast agents

INTRAVASCULAR RADIOLOGICAL IODINATED CONTRAST MEDIA Ronald G. Grainger Iodine (atomic weight 127) is the only element that has proved satisfactory for general use as an intravascular radiological contrast medium (RCM).The iodine provides the radio-opacity: the other elements of the RCM molecule provide no radio-opacity but act as carriers of the iodine, greatly increasing the solubility and markedly reducing the toxicity of the total molecule.

The problem has always been how to package the iodine so that it may be delivered safely into very sensitive arterial systems (e.g. brain, heart, kidney) in the very large amounts required to produce adequate film-screen radio-opacity1 (see later). Organic carriers of iodine will probably remain the basis of all intravascular RCM for the foreseeable future. Since the 1950s,

32

SECTION 1

• IMAGING TECHNIQUES AND GENERAL ISSUES

Structural formulae of contrast media

Iodine atoms +

Cation

particles

Osmolality osmols/kg H2O 280 mg I2/ml

— Coo

A. Ionic monomer (HOCM) Conventional contrast medium salt e.g. sodium iothalamate (Conray)

3:2

1500

3:1

600

6:2

560

6:1

300

I

I R5

R3 I

B. Nonionic monomer (LOCM) Substituted amide e.g. iohexol (Omnipaque), iopamidol (Niopam)

CONH-R I

I R5

R3 I Cation

+ —

C. Ionic dimer (LOCM) Mono-acid dimeric salt e.g. sodium ioxaglate (Hexabrix)

R

Coo I

I R

R I

D. Nonionic dimer (LOCM) e.g. iodixanol (Visipaque) iotrolan (Isovist)

I

I

I

R

R I

I

I

I

R

IONIC MONOMERS (HIGH OSMOLAR CONTRAST MEDIA [HOCM])

R I

there are four chemical varieties of iodinated RCM in clinical use (Fig. 2.1,Tables 2.1, 2.2). All four are tri-iodo benzene ring derivatives with three atoms of iodine at 2,4,6 positions (in monomers) and six atoms of iodine per molecule of the ring anion (in dimers); they are very hydrophilic, have low lipid solubility, low toxicity, low binding affinities for protein, receptors or membranes, and have molecular weights less than 20002 (Table 2.1). On intravascular injection, all of these four products are distributed rapidly because of high capillary permeability into the extravascular, extracellular space (except in the central nervous system [CNS]). They do not enter the interior of blood cells or tissue cells and they are rapidly excreted, with over 90 per cent being eliminated by glomerular filtration by the kidneys within 12 h. None of these four chemical types of RCM have marked pharmacological actions. This is highly desirable as they are used purely as imaging and not therapeutic agents.

I

Figure 2.1 Structural formulae of the four different types of iodinated intravascular contrast media: osmolalities and ratio of iodine atoms to osmotically active particles.

All ionic monomers are salts with sodium or meglumine (Nmethyl glucamine) as the non-radio-opaque cation and a radioopaque tri-iodinated fully substituted benzoic acid ring as the anion. These anions include diatrizoate (Urografin, Hypaque), iothalamate (Conray), ioxithalamate, metrizoate – the first two

Table 2.1 IODINATED CONTRAST MEDIA: CHARACTERISTICS, IODINE CONTENT AT 300 mosmols kg-1 WATER (PHYSIOLOGICAL) (MODIFIED AFTER MORRIS 19932) Classification iodine per particle ratio

Molecular weight

Iodine content mg ml−1 at 300 mosmol kg−1 water

Osmolality mosmol kg−1 water at 300 mgl ml−1

Classification of RCM generic names

Iodine atoms per molecule

Osmotic particles per molecule

Ionic monomer HOCM

3

2

3:2

600–800

70

1500–1700

3

1

3:1

700–800

150

600–700

6

2

3:1

1269

150

560

6

1

6:1

1550–1626

300

300

Diatrizoate Iothalamate Metrizoate Ioxithalamate Non-ionic monomer LOCM Iohexol Iomeron Iopamidol Iopromide Ioversol Ioxilan Xenetix Ionic dimer LOCM Ioxaglate Non-ionic dimer LOCM isotonic Iodixanol Iotrolan

CHAPTER 2

being by far the most frequently used. Each molecule completely dissociates in water solution into two ions – one non-radioopaque cation and one tri-iodinated radio-opaque anion, giving an iodine:particle ratio of 3:2 (1.5) (Table 2.1 and Figure 2.1). They are very hypertonic – 1600 mosmols kg−1 water at 300 mg iodine kg−1 compared to physiological osmolality of 300 mosmol kg−1 water.

NON-IONIC MONOMERS (LOW OSMOLAR CONTRAST MEDIA [LOCM]) Almén introduced the concept of non-ionic (and therefore low osmolar) contrast media in 1969 with metrizamide. The 2nd generation non-ionic monomers in 2006 include iohexol, iopamidol, iopromide, ioversol, ioxilan, etc. (Tables 2.1 and 2.2) and are much more stable, much more soluble, much less toxic and much less expensive than metrizamide. None of these molecules dissociate in solution. They are tri-iodinated non-ionizing compounds and therefore in solution they provide three atoms of iodine to one osmotically active particle (the entire molecule), producing an iodine: particle ratio of 3:1 (Tables 2.1, 2.2, Fig. 2.1). They have less than half of the osmolality of HOCM. They have an osmolality of about 600 mosmol kg−1 water at a concentration of 300 mg I /ml-1 compared with the physiological osmolality of 300 mosmols.

IONIC DIMERS Ioxaglate is the only compound in this group. It is a mixture of the sodium and meglumine salts of a monoacidic double benzene ring with each benzene ring having three atoms of iodine at C2, 4, 6 positions. The total molecule therefore contains six atoms of iodine and in solution each molecule dissociates into one radio-opaque hexa-iodinated anion and one non-radio-opaque cation (sodium and/or meglumine). Ioxaglate therefore has an iodine:particle ratio of 6:2 or 3:1 (Tables 2.1, 2.2, Fig. 2.1).

Table 2.2

•

INTRAVASCULAR CONTRAST MEDIA FOR RADIOLOGY, CT AND MRI

NON-IONIC DIMERS Iotrolan (Schering) and iodixanol (Nycomed) are both examples of non-ionizing chemicals. They do not ionize or dissociate in solution. Each molecule contains two non-ionizing tri-iodinated benzene rings linked by a bridge (Tables 2.1, 2.2, Fig. 2.1). Each molecule therefore provides in solution six atoms of iodine for one molecule, i.e. an iodine:particle ratio of 6:1. Non-ionic dimers are physiologically isotonic (300 mosmol kg−1 water) in solution at 300 mg I/ml-1. Iotrolan has been recently voluntarily withdrawn for intravascular use because of unexpected delayed reactions – usually with allergic and skin manifestations that are rarely serious but seem to be more severe and frequent in the Japanese. These delayed adverse reactions may also apply to other dimers. There are recent but unconfirmed reports that non-ionic dimers may be less nephrotoxic than non-ionic monomers3,4 (see renal toxicity later).

QUANTITY OF IODINE REQUIRED Very large amounts of iodine are necessary because of the low sensitivity inherent in conventional photographic film-screen radiography. This low sensitivity to iodine is not an inherent property of the X-ray beam but is due to the low sensitivity of the photographic process in distinguishing minor differences in radio-opacity. Alternative nonphotographic X-ray detection recording systems, such as photodetectors with electronic amplification, like those used in CT scanning and in digital subtraction angiography (DSA), are very much more sensitive to minor differences in iodine concentration as demonstrated by 95 per cent tumour blush in all cerebral tumours on CT after IV injection of RCM compared to about 20 per cent blush after intra-arterial injection using photographic film-screen radiography.

REPRESENTATIVE LOW-OSMOLAR MEDIA (LOCM)

Generic name

Registered trade name

Iodine mg ml−1 water

Osmolality mosmols kg−1 water

Viscosity cps at 3.7°C

320

580

7.5

Ionic LOCM Dimer Meglumine ioxaglate 32.9% (Sodium ioxaglate 19.65%)

Hexabrix 320 Non-ionic monomer

Iopamidol 61%

Niopam 300

300

616

4.7

Ioversol 64%

Optiray 300

300

645

5.5

Iopromide 62.3%

Ultravist 300

300

620

4.6

Iobitridol 65.8%

Xenetix 300

300

695

6.0

Iohexol 64.6%

Omnipaque 300

300

640

6.1

Non-ionic dimer Iodixanol 65%

Visipaque 320

320

290

11.4

Iotrolan 64%

Isovist 300

300

320

8.1

33

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The average daily physiological turnover of iodine is 0.0001 g. The total iodine content in the body (mainly in the thyroid) is 0.01 g. The requirement for a 2-, 3- or 4vessel angiogram (with conventional film-screen photographic recording) may be 70 g iodine, delivered in, say, 30 min into the arterial supply trees of very sensitive organs, for example, the brain, kidney, or heart. This is 700 000 times the daily body turnover of iodine and it is testimony to the low toxicity of RCM (either HOCM or LOCM) that this huge quantity of iodine can be accepted into the arterial tree of the most sensitive organs of the body with very rare evidence of severe toxicity. In complicated cases, these massive quantities may have to be increased by 100 per cent or even more, involving more than 200 g of iodine (400++ g of RCM) being injected intravascularly for film-screen radiographic angiography, probably the largest quantity of any drug used in the whole of clinical medicine.

INFORMED CONSENT Informed consent is essential for any invasive procedure (angiography, angioplasty, vascular embolization, biopsy, etc.), but probably is not essential in many countries for uncomplicated procedures (e.g. intravenous urography [IVU]) in a reasonably fit patient, as it may alarm the pvatient to learn that there is a risk (however small) of a severe or fatal ADR. In some countries, e.g. the USA, informed consent may well be necessary, even in these patients. Like every other drug, contrast agents should be administered only when there are clear and defensible clinical indications and when the prospects of benefit to the patient outweigh the risks and discomfort that may occur. With modern contrast agents (either HOCM or LOCM), it is more likely that a complication occurring during a radiological arterial procedure will be due to the consequences of the instrumentation (e.g. vessel damage, thromboembolism) rather than to the contrast agent, if the latter is used in an appropriate dose and manner.

ADVERSE REACTIONS TO RADIOLOGICAL CONTRAST MEDIA6–12 An excellent (1999) review of adverse reactions, their mechanism, prophylaxis and treatment is presented by Sidhu and Dawson6. In clinical medicine, every technical procedure and every drug given to a patient by whatever route (oral, rectal, IV, IA, intrathecal) may cause adverse drug reactions (ADRs), which are sometimes fatal. Radiographic procedures and drugs are no exceptions. It is inevitable that even when administered appropriately, RCM will very occasionally result in a severe or even fatal ADR, sometimes leading to litigation. It has become increasingly difficult to defend inappropriate indications, inadequate resuscitation facilities and inappropriate experience, especially in small imaging departments, in either private or public hospitals.

TYPES OF ADVERSE REACTION Adverse reactions to RCM may be divided into: 1 Idiosyncratic anaphylactoid reactions 2 Non-idiosyncratic reactions 3 Combined 1 and 2 reactions.

Idiosyncratic anaphylactoid reactions These ADRs are the most dreaded and most serious and fatal complications of RCM injection as they occur without warning, cannot be reliably predicted and are not preventable in the present state of our knowledge. These reactions usually (85 per cent) begin either during or immediately after the injection of contrast medium. ADRs are more frequent in patients who have had a previous adverse reaction to contrast medium, asthmatics, allergic and atopic patients, patients with impaired cardiovascular and renal systems, diabetics (Table 2.3), and patients on beta-adrenergic blockers and possibly on nonsteroidal analgesics. Idiosyncratic reactions vary greatly in severity and clinically may closely mimic true anaphylactic and allergic reactions, although there is no confirmatory evidence of a true antigen IGE antibody immunological reaction to contrast media. Some possible mechanisms5,6,10,11 involved in causing these reactions are: 1 Inhibition of enzymes such as cholinesterase (which de-activates and hydrolyses acetylcholine), resulting in increased concentration of acetylcholine; this may result in symptoms of vagal overstimulation, e.g. cardiovascular collapse, bradycardia, bronchospasm. 2 Release of vasoactive substances such as histamine, serotonin or bradykinin may result in vasomotor collapse. 3 Activation of physiological cascade systems including the complement activation system, the kinin system with bradykinin release, the coagulation system inducing intravascular coagulation and the fibrinolytic system causing lysis of fibrin and blood clots. 4 The immune system disturbances. 5 Anxiety, apprehension and fear of the radiological procedure probably plays a significant part in adverse reactions by activating a hypothalamic reaction resulting in cardiovascular and respiratory collapse and even death. It is probable that many of these mechanisms are inter-related and that a self-perpetuating vicious circle is established, resulting in severe and perhaps fatal cardiovascular collapse. Unlike the chemotoxic and hyperosmolar reactions, the earlier mentioned anaphylactoid reactions are not dose dependent and death has been known to occur following a 1 ml IV test dose, or after the full dose of RCM has been given after a negative test dose.

Non-idiosyncratic reactions Unlike the idiosyncratic reactions, these non-idiosyncratic reactions are dose dependent and therefore relate to the chemical composition, osmolality and concentration of contrast medium and the volume, speed and multiplicity of the injection.

CHAPTER 2

Table 2.3 ADVERSE DRUG REACTIONS TO IV INJECTION OF HOCM (IONIC) AND LOCM (NON-IONIC) MONOMERIC CONTRAST MEDIA (MODIFIED FROM KATAYAMA ET AL 19907) Ionic HOCM

Patients

Non-ionic LOCM

169 284

Total number of patients

163 363

12.66%

Total adverse reactions

3.13%

0.22%

Severe ADR

0.04%

(1)

Deaths (uncertain cause) (1)

(1)

All ADR% ionic HOCM

Symptoms

All ADR% non-ionic monomeric LOCM

4.58

Nausea

1.04

2.29

Heat

0.92

2.97

Vomiting

0.36

3.16

Urticaria

0.47

1.12

Flushing

0.16

0.40

Vascular pain

0.05

0.58

Coughing

0.15

0.17

Dyspnoea

0.04

Ionic HOCM, severe ADR (%)

Clinical history

Non-ionic LOCM, severe ADR (%)

1.88

Asthma

0.23

0.18

Without history of allergy

0.03

0.53

With history of allergy

0.10

0.13

Without history of previous ADR to RCM

0.03

0.73

With history of previous ADR to RCM

0.18

0.53

Heart disease

0.10

0.20

Renal disease

0.04

0.22

Diabetes mellitus

0.05

1 Chemotoxic reactions. Chemotoxic adverse reactions are probably due to toxicity to the contrast medium anion rather than to its iodine content, as the iodine is very firmly bound to the benzene ring. Some patients with a low iodine intake (often geographical), have an increased incidence of endemic goitre, are very sensitive to an increased intake of iodide, and may develop thyrotoxicosis after injection of RCM contrast agents. Presumably in these patients this is due to the very small amount of free iodide ions, which is known to be present in contrast medium solutions. Special care should be taken with patients who are thyrotoxic or goitrous. Chemotoxic side effects include cardiac, neurological and renal toxicity as well as vascular manifestations. Cationic toxicity may result from changes (either greater or lesser) in sodium or calcium ion concentration induced by injection of large amounts of RCM. 2 Hyperosmolar reactions. The very high osmolality of high concentrations of HOCM (ratio 3:2) is 5–8 times

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INTRAVASCULAR CONTRAST MEDIA FOR RADIOLOGY, CT AND MRI

the physiological osmolality (300 mosmol kg−1 water) of every cell in the body (Table 2.1, Fig. 2.1). It is not surprising therefore that adverse reactions may occur due to the marked hyperosmolality that develops when large volumes of concentrated HOCM are injected into the circulation. The degree of hyperosmolality is much reduced if non-ionic ratio 3:1 (LOCM) and (even more) if ratio 6:1 products isotonic non-ionic dimeric LOCM are injected instead of injecting HOCM of ratio 3:2 (Tables 2.1, 2.2). The adverse reactions due in part to hyperosmolality of the contrast medium include: 1 Erythrocyte damage due to the loss of intra-erythrocytic water, leading to rigidification and reduction of the vital essential deformability of red cells, which is necessary for the erythrocytes (7 µm diameter) to pass through capillaries (diameter 2–4 µm). 2 Endothelial damage. All RCMs, especially HOCM injure the endothelium by virtue of their chemotoxicity, ionicity and osmolality. The normal endothelium permits passage of molecules less than 50 000 molecular weight (HOCM or LOCM [even dimers] have molecular weights less than 20 000) by freely diffusing through intercellular pores and by transcytosis. Thus all RCMs are readily passed through the endothelium into the tissue fluid except in the CNS (blood–brain barrier – see later). Damage to the capillary wall of the injected arterial territory (perhaps by RCM) leads to its increased permeability and the passage of toxic substances from the blood into the extravascular tissue fluid that bathes the tissue cells. In addition to its semi-permeability membrane function, the endothelial cells of the capillaries also constitute a highly significant and very sensitive pharmacological tissue and they are stimulated to produce several active substances such as Factor XII, arachidonic acid, phospholipids, prostacyclins, angiotensin-converting enzymes, nitric oxide, pro-coagulants and anti-coagulants etc., which have considerable effects in vasoregulation and coagulation6,10. 3 Blood–brain barrier damage is a specific example of endothelial damage. The central nervous system is the only tissue in the body that is normally protected from the passage of contrast medium molecules through the capillary wall, because the capillaries of the central nervous system are relatively impervious and have very tight intercellular connections. If this capillary blood–brain barrier is damaged, the molecules or ions of RCM may pass through the capillary wall into the extravascular neurological tissue fluid and exert a direct toxic effect on the delicate nerve tissue cells. A pathological increase of permeability of the blood–brain barrier occurs in several conditions, e.g. many cerebral and meningeal tumours, cerebral infarcts and in some infections. This is the basis of the very useful diagnostic sign of tumour staining, which is particularly well seen on CT, even after IV injection of contrast medium.

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4 Vasodilatation of the arteriolar and capillary bed of the injected artery is closely related to the hyperosmolality of the contrast medium solution. It may lead within a few seconds to a rapid increase in blood flow to several times the physiological flow rate. This is associated with a local uncomfortable feeling of warmth, heat, discomfort, or severe pain during peripheral arteriography. Systemic generalized vasodilatation following injection of large quantities of hyperosmolar contrast medium may lead to severe systemic hypotension, peripheral venous pooling and a diminished venous return to the heart, resulting in cardiovascular failure that may be extremely severe and even fatal. 5 Hypervolaemia results from the osmotic attraction of extravascular tissue fluid into the circulation induced by the hyperosmolality of RCM. This may increase the blood volume by about 10 per cent within a few minutes, thus reducing haemoglobin concentration and increasing the demand on cardiac output and stress on the left ventricle. 6 Cardiac depression with systemic hypotension, diminished venous cardiac return, myocardial ischaemia and the direct depression of myocardial contractility, particularly after coronary angiography. All of these hyperosmolar reactions are closely related to the hyperosmolality of RCM and therefore depend on the dose, concentration and volume of RCM injected and are consequently considerably reduced by substituting LOCM for the very hypertonic HOCM.

Vasomotor reactions These vasomotor ADRs may occur following either idiosyncratic (not dose-dependent) or non-idiosyncratic (dosedependent) reactions induced by RCM, or may develop independent of other ADRs. There may be severe hypotension, tachycardia or bradycardia with marked apprehension, anxiety, sweating and disturbance, and depression of myocardial contraction with a markedly reduced cardiac output, leading to unconsciousness and cardiopulmonary collapse and possibly death. Vaso-vagal reactions may also occur, characterized by bradycardia, whereas the vasomotor collapse states mentioned earlier are usually accompanied by tachycardia.

COMPLICATIONS Minor reactions7 Flushing, nausea, arm pain, pruritus, mild urticaria, vomiting and headache7 (Table 2.3) occur in 5–10 per cent of patients injected with HOCM but less than 1 per cent when LOCM is injected. These are usually mild in severity, of short duration, self-limiting and generally require no specific treatment other than reassurance and restoration of the patient’s confidence. Occasionally an oral antihistamine (e.g. chlorpheniramine [Piriton] 4 mg) for urticaria, a tranquillizer (e.g. diazepam [Valium] 5 mg) or a mild analgesic (e.g. aspirin 300 mg or paracetamol 500 mg) may be helpful. Arm pain may be due to a small unrecognized extravasation, but venous spasm on entirely intravascular injection may also

occur, especially with HOCM. There may be local oedema, very rarely resulting in cellulitis, compartment syndrome, or tissue necrosis. A major problem may arise if there is a large extravasation such as in powered injections of RCM for dynamic CT. A major recent advance is an automatic device to electrically stop the pump5. The electrical skin impedence changes if there is significant extravasation. Electrodes over the site of injection are connected by cable to the power injector, which is automatically immediately cut off if significant extravasation occurs. This is an important safety device that has been adopted by several manufacturers of powered injectors, and permits higher IV flow rates with considerably increased safety5.

Intermediate reactions More serious degrees of the above generalized symptoms, including moderate degrees of hypotension and bronchospasm occur in 0.5–2 per cent of IV injections of HOCM and is probably reduced to one-quarter of that frequency following IV LOCM7 (Table 2.3). These intermediate reactions disturb both the patient and the doctor but do not cause alarm. They usually respond readily to appropriate therapy – reassurance, chlorpheniramine (Piriton) (4–10 mg orally, intramuscularly or intravenously) for urticaria or angioneurotic oedema, diazepam (5 mg) for anxiety, salbutamol β2 agonist inhalation for bronchospasm, hydrocortisone 100–500 mg IM or IV, adrenaline 0.1–0.5 ml of 1/1000 solution intramuscularly or subcutaneously (children 0.01 ml kg−1 body weight up to 3 mg max.) for more severe bronchospasm – repeated if necessary.

Severe life-threatening reactions These include severe manifestations of all of the above symptoms and occur in about 0.2 per cent after HOCM and about 0.04 per cent following LOCM7 (Table 2.3). Severe reactions include convulsions, unconsciousness, laryngeal oedema, severe bronchospasm, pulmonary oedema, severe cardiac dysrhythmias and cardiac arrest, cardiovascular and respiratory collapse.Treatment is urgent: the patient is very alarmed and the doctor is seriously worried about the patient’s possible demise. The responsible clinician (usually the radiologist) must be well trained in emergency treatment as these severe ADRs are unpredictable in occurrence and in response to treatment. Treatment6,10–12 must be urgently and expertly administered according to a pre-arranged well-practised schedule. Additional medical (including anaesthetic) assistance should be immediately available. A crash trolley complete with oxygen cylinders, flow valves, suction equipment, oral airways, nasal tubes, endotracheal tubes, face masks, ambu-type bag, stethoscope, sphygmomanometer, syringes, needles, cannulae and tracheotomy set is essential. A suction machine, electrocardiogram (ECG), blood pressure monitor and DC defibrillator must also be readily available. There must be a comprehensive selection of drugs and IV fluids necessary for resuscitation and

CHAPTER 2

the means and the personnel for their safe administration must be readily available. The airway must be secured and oxygen, artificial respiration, external cardiac massage and electrical DC defibrillation must be administered as and when required. IV fluid infusion (normal saline, lactated Ringer's solution) through an indwelling IV catheter is essential to restore blood volume and to administer IV drugs, such as: • a powerful diuretic such as frusemide (Lasix) 20–40 mg IV slowly or IM for pulmonary oedema • diazepam and barbiturates for convulsions • adrenaline (see later) • salbutamol (β2 agonist metered dose inhaler) • hydrocortisone or methyl prednisolone (100–1000 mg) • aminophylline (very slowly, 250–500 mg) intravenously for intense bronchospasm • chlorpheniramine for allergic or anaphylactic symptoms • vasopressors, e.g. noradrenaline (or metaraminol [Aramine] 0.5–5 mg slow IV infusion) • dihydroxyphenylaline (or dopamine) infusion (2.5–5 µg kg−1 min−1) for hypotension with monitoring of the blood pressure Sodium bicarbonate infusion should be administered to correct any acidosis, and atropine 0.6–1.0 mg IV or IM repeated if necessary (children 0.02 mg kg-1 repeated if necessary to 2 mg total) is used for vasovagal reactions, bradycardia and cardiac failure. Adrenaline (recently prepared solution and in date) is much more rapidly effective than steroids: it is the main therapeutic agent and should always be readily available for it is the essential treatment. In severe anaphylactoid reactions it should be administered as soon as possible and may be life-saving. Adrenaline (epinephrine) (0.3–0.5 ml, 1/1000 solution [children 0.01 ml kg−1 body weight] by deep SC or IM injection repeated at 10–20-minute intervals) provides the most rapid and reliable relief for bronchospasm, angioneurotic oedema and other anaphylactoid symptoms. Adrenaline has occasionally precipitated ventricular fibrillation when given by IV injection, but in very severe anaphylactoid reactions, even this route should be considered, injecting 1–5 ml, 1/10 000 solution, very slowly, preferably under ECG control. Corticosteroids take several hours to become fully effective, even when given intravenously, but they should be administered immediately and intravenously in severe anaphylactoid reactions.

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INTRAVASCULAR CONTRAST MEDIA FOR RADIOLOGY, CT AND MRI

cized (reasonably) on methodological grounds, they are very useful contributions to the international literature and knowledge of RCM.They both found that deaths due to LOCM are no fewer than to HOCM6. A very interesting analysis of Deaths Related to Iodinated Contrast Radiological Media (ICRM) reported to the United States Federal Drugs Administration between 1979 and 1994 (estimated 170 million IRCM studies) was published in 19979 and concluded that despite the increasing availability and usage of the safer LOCMs in the USA in 1978–1994, the data do not show a decrease in RCM-related deaths to LOCM as opposed to HOCM injection.

Factors significantly predisposing to adverse drug reactions (Table 2.4) All ADRs are significantly more frequent with HOCM (12.66 per cent) than with LOCM (3.13 per cent)7 (Table 2.3). Previous adverse reactions to RCM and a history of asthma are the two most dangerous adverse predisposing factors.These and others include: 1 Previous adverse reaction. A previous adverse reaction to contrast medium increases the risk factor of a reaction to a second LOCM injection (severe ADR 0.18 per cent)7 (Table 2.3). 2 History of asthma or bronchospasm. Patients with a previous history of bronchospasm, however mild, have an increased risk of an adverse reaction to RCM (0.23 per cent severe ADR, Table 2.3). Subsequent reactions to a second RCM injection may be very severe and even fatal. 3 History of allergy or atopy. Patients with known allergy, particularly to foodstuffs and perhaps especially to iodides have an increased incidence of an ADR (0.10 per cent severe ADR)7 (Table 2.3). 4 Cardiac disease. The risk of severe ADRs in severe cardiac disease is 0.10 per cent severe ADR following LOCM7 (Table 2.3). A high sodium load caused by a large volume of HOCM containing sodium salts should be avoided, as this may exacerbate cardiac decompensation due to hypervolaemia and myocardial depression.

Table 2.4 PATIENTS CONSIDERED TO BE AT GREATER THAN USUAL RISK OF A SEVERE ADVERSE REACTION TO IODINATED RADIOLOGICAL CONTRAST AGENTS 1. Patients with a previous ADR to RCM (excluding mild flushing, nausea)

Deaths

2. Asthmatics

The earlier mentioned severe adverse reactions may not respond even to expert, rapidly administered treatment and the patient may die. Death may however be immediate and without warning. It usually results from intractable cardiopulmonary collapse, pulmonary oedema, or intense bronchospasm. The death rate following IV injection of contrast medium is not known with accuracy. One death in 40 000 IV injections of HOCM is often quoted as a medium figure. Both the Katayama7 (in Japan) and Cashman (in Australia) papers were unblinded large surveys, but despite being criti-

3. Allergic and atopic patients 4. Cardiac patients with decompensation, unstable arrhythmia, recent myocardial infarction 5. Renal patients in failure, diabetic nephropathy, on metformin 6. Feeble infants and aged patients 7. Patients with a severe general debility 8. Very nervous, anxious patients 9. Patients with various metabolic and haematological disorders 10. Thyrotoxic: goitrous patients

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5 Renal disease6. Mild temporary renal dysfunction may occur in around 5 per cent; serious renal impairment occurs in about 0.1 per cent7 (Table 2.3). The most important safeguard against RCM-induced renal failure is adequate hydration, given orally or intravenously. 6 Dehydration. All patients must be well hydrated (if necessary by IV) before and after contrast medium is injected. The previous practice to dehydrate the patient deliberately for IVU (in order to produce an improved image of the renal calices) is very dangerous and must be abandoned in all patients. 7 Haematological and metabolic conditions. Patients with sickle cell anaemia may react adversely, particularly to HOCM, which may cause an increase in sickling, with potentially serious or even fatal complications following selective cerebral and coronary angiography. 8 Anxiety and apprehension. Anxiety and apprehension definitely predispose to adverse reactions. 9 Other conditions. Manifest hyperthyroidism is a contraindication to RCM administration. Neonates and aged and infirm patients are probably at increased risk because of their associated morbidities. 10 Delayed adverse reactions. Serious adverse reactions usually begin during or within 15 min of IV injections of RCM. In the last few years it has become apparent that some patients (perhaps as much as 10–20 per cent) experience reactions that may be delayed for a few days.These delayed reactions are usually uncomfortable, time-limited and not dangerous. Patients with a thrombotic tendency such as severe polycythaemia may have an increased risk, especially after arterial injections of non-ionic LOCM. HOCM inhibits thrombosis more than LOCM. Patients with myelomatosis may develop renal failure after contrast medium injection, with proteinaceous casts and precipitation of Bence-Jones protein and Tamm-Horsfall protein possibly causing renal tubular obstruction. These reactions are now much less frequent because LOCMs are much less toxic and less protein binding, and the previous practice to dehydrate the patient before IV urography is now completely reversed. Patients with phaeochromocytoma may develop a hypertensive crisis during angiography or IV urography as a reaction to the contrast agent, to abdominal compression or to manipulation of the tumour. Whenever phaeochromocytoma is suspected, these patients should be prepared with preliminary alpha- and beta-adrenergic blockade before angiography. Patients with pre-existing renal disease, particularly the renal complications of diabetes mellitus, have an increased risk of an adverse reaction to RCM, which may precipitate renal failure. LOCM is preferred especially if the patient has pre-existing renal impairment6,10–12. Recent evidence3 suggests that iso-osmolar dimer (iodixanol) LOCM may be even less nephrotoxic than monomeric LOCM (iohexol), which has twice the physiological osmolality. In a multicentred trial of diabetics with pre-existing renal

impairment (serum creatinine 115–308 mmol-1) 129 patients underwent angiography3. There was a significant increase in contrast-induced nephrotoxicity with increased serum creatinine in 26.2 per cent of the iohexol (non-ionic monomer) group compared to 3.1 per cent in the iodixanol (non-ionic dimer) group. This important finding is being strongly challenged partially because of the large size of the dimer molecule (which may itself impose a renal problem) and the possibility of an increase in delayed ADRs. In 2005 an in vitro study considered the cytotoxic adverse effects on renal tubular cells of non-ionic dimers (iodixanol and iotrolan) compared with monomer LOCM (ioversol and iomeprol). This study demonstrated significantly more toxic effects of the dimers when compared on an equi-molar concentration with the monomers4. The authors conclude that their in vitro research indicates considerable caution in accepting the advantages of the dimers reported in the previous paper3. Metformin (phenoformin), an oral biguanide hyperglycaemic therapy for diabetes mellitus Type 2, is primarily excreted by the kidney. In patients with severe renal impairment, intravascular accumulation of the biguanide may occur after RCM, and this may precipitate biguanide lactic acidosis (vomiting, diarrhoea, somnolence) – a potentially fatal complication. RCM-related lactic acidosis is extremely rare in diabetics receiving metformin if the patient has normal renal function before RCM. It is therefore recommended12 that metformin need only be discontinued if there is pre-existing renal impairment and it may be recommenced 48 h later after re-assurance of good renal function after RCM. These delayed reactions are more common in women: arm pain (7 per cent), delayed rash (5 per cent), flu-like symptoms (headache, skin lesions, salivary gland swelling – ‘iodide mumps’ (9 per cent) probably due to ‘iodism’) are the more important late manifestations. Presumably the reaction is idiosyncratic and not dose dependent. A few cases (including deaths) of delayed vasculitis, disseminated lupus erythematosis and Stevens–Johnson syndrome have been reported after injection of LOCM. Delayed reactions in general may be more frequent with LOCM than with HOCM and with dimers compared to monomers. Iotrolan – a non-ionic dimer – has been voluntarily withdrawn from intravascular clinical usage because of a worryingly high incidence of delayed adverse reactions, mainly reported in Japan. It is possible that similar delayed ADRs may occur after other similar dimeric LOCMs.

PRINCIPLES OF INVESTIGATING PATIENTS AT INCREASED RISK Manifest active hyperthyroidism is an absolute contra-indication to RCM administration. The following suggestions should be noted: 1 Despite the above extensive list of those patients who have a known predisposition to adverse reactions, many com-

CHAPTER 2

2

3

4

5

6

7

8 9

10 11

plications of contrast medium injections are unpredicted and unpredictable. The radiologist must always weigh the possible advantages to the patient of the diagnostic procedure against the very small but ever-present risk of a severe adverse reaction (and even death) to the contrast medium and the technique of its administration. In many patients deemed to be at increased risk of an adverse reaction, the RCM procedure may be replaced by other imaging investigations, such as ultrasound (US), computed tomography (CT) or magnetic resonance imaging (MRI), often not requiring injections of any contrast agent but producing equal or improved diagnostic information. The referring clinician should be consulted and advised if the patient is thought to be at increased risk. The patient should be informed, consulted and reassured as necessary. The discussion and result should be recorded in the patient's notes. Although a routine test dose is generally not necessary, it is advisable to perform a 1 ml or smaller test dose, either by IV or mucosal testing in patients considered to be at increased risk of an ADR. The smallest dose of RCM that will give reliable, comprehensive diagnostic results should be used. This is especially important in patients with pre-existing renal impairment or diabetes, those who are poorly hydrated, infants and those who may require further RCM procedures. All patients receiving RCM, particularly if there is previous renal impairment and those patients receiving large quantities of RCM, must be very well hydrated (if necessary intravenously) before and after the injection in order to excrete the RCM as completely and quickly as possible. Do not leave the patient unattended for the first few min after the injection. Premedication is strongly advised for previous adverse reactors, especially in asthmatic and allergic patients, who should be given pre-injection and post procedure 24 h of oral corticosteroids and possibly antihistamines. In all patients considered to be at increased risk, LOCM should be administered in preference to HOCM. Before administering the injection, the emergency trolley, alarm system and availability of experienced assistance must be confirmed.

CONTRAST MEDIA RELATED TO SPECIFIC CLINICAL AREAS RENAL TRACT6,10–12 There is no doubt that high doses of contrast media impair renal function, usually peaking at 3–5 d, causing a decrease in urine output and an increase in serum creatinine and urea levels, decreased creatinine clearance and reduced glomerular filtration rate (GFR). In some patients this may proceed to renal failure with anuria, uraemia and death. Renal dialysis (either intravas-

•

INTRAVASCULAR CONTRAST MEDIA FOR RADIOLOGY, CT AND MRI

cular or peritoneal) is very effective and may be life-saving as an alternative method of excreting RCM and uraemic metabolic products. These severe adverse reactions are very unlikely to occur if the patient is well hydrated and has normal renal function before the RCM injection. Particularly important adverse factors are pre-existing renal failure and oliguria, diabetic nephropathy, nephrotoxic drugs, patients who are not well hydrated and patients who are liable to be injected with very high doses of RCM for multiple sequential examinations repeated within a few days. Alternative imaging procedures must always be considered. The usual recommended dose for IV urography in the normally well-hydrated adult with normal renal function is 15–25 g iodine; this dose may be increased provided the patients are well hydrated (by IV normal saline if necessary before, during and after RCM injection). A maximum of about 70 g of iodine (1 g iodine kg-1 body weight in adults) is generally advisable even in patients with good renal function, but considerably larger quantities (up to 200 g or even 300 g of iodine, i.e. up to 600 g of RCM) may be required, particularly in difficult angiographic and interventional procedures. Nephrotoxic drugs (diuretics, antibiotics, non-steroidal anti-inflammatory drugs, cytotoxic therapy) may enhance the adverse effects of RCM. Diabetic patients receiving metformin should be given special attention (see earlier). After early uncertainty, it is now established that HOCMs are more nephrotoxic, and LOCMs are preferred for all patients considered to be at increased risk, especially with diabetic nephropathy. There is increasing evidence that RCM (particularly HOCM and large doses) may induce damage to the tubules in the renal medulla and reduce intra-medullary blood flow in patients with acute calculus renal colic. It is not yet established whether monomer LOCM or dimer LOCM have the lower renal toxicity (see earlier)3,4.

NERVOUS SYSTEM LOCMs are much more comfortable for cerebral arteriography in the conscious patient and are always preferred. Cerebral RCM photographic arteriography is being strongly challenged and partially displaced by CT and MR angiography (MRA).

Cerebral angiography Adverse reactions to RCM include dilatation of the external carotid arterial territory causing facial pain and heat. Damage to the blood–brain barrier may cause dangerous cerebral oedema, bradycardia and hypotension.

Myelography Myelography is being rapidly replaced by MRI (and to a lesser extent by CT) and very few myelograms are now performed in well-equipped imaging departments. If contrast medium myelography is essential, then non-ionic LOCM must be injected, for ionic contrast media (both HOCM and LOCM) are very toxic and often fatal when injected into the subarachnoid space.

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Myelography with oily products, such as iophendylate (Myodil, pantopaque – standard products in the 1940s–1980s) have been completely abandoned as it is now known that severe chronic adhesive arachnoiditis may follow their injection, sometimes causing considerable pain, disability and compression of the lumbosacral nerve roots with severe neurological deficit.

CARDIOVASCULAR SYSTEM Peripheral Arteriography The usual iodine concentration required for conventional film–screen angiography is about 300 mg I ml−1 contrast medium. Conventional HOCM (1500 mosmol kg−1 water) has been completely displaced for peripheral arteriography by LOCM (600–700 mosmol kg−1 water), because the latter causes much less warmth, discomfort, pain and movement. LOCM (Table 2.3) permits almost painless angiography in all territories, usually eliminating discomfort, movement and the need for general anaesthesia.

Aortography Injections of LOCM at the 300–400 mg ml−1 iodine concentration are greatly preferred as they cause much less discomfort and vasodilatation. Coronary angiography HOCMs (e.g. Urografin 76 per cent) with physiological levels of sodium and which do not bind avidly to serum calcium (related to buffer agents) had a good reputation for selective coronary angiography, but LOCMs are even safer for they cause less marked haemodynamic, myocardial and physiological changes and depression. Coronary angioplasty (PTCA) and stent placement During therapeutic coronary angioplasty, the intima and the arterial wall are deliberately torn and stretched by the intra-arterial balloon considerably increasing the risk of local arterial occlusion. The most important controllable factor in reducing this risk is the expertise of the operator (see later). Many investigators utilize full heparinization of the patient and LOCM injections.

Peripheral Venography Venography of the leg for possible deep vein thrombosis (DVT) is the most frequent venographic study. The procedure is performed by injecting RCM into a small vein of the foot, with the leg dependent and tourniquets restricting peripheral venous return. If the deep veins are already compromised and partly thrombosed, peripheral venography of the leg is a potentially dangerous procedure, as both deep and superficial venous return from the leg are compromised, and some cases of venous gangrene due to venous endothelial damage and thrombosis have been induced by attempted venography. LOCM is strongly advised because of its lower osmolality and its less irritant effect on the venous endothelium. Endothelial contact time should be reduced to the minimum by washing out with saline, massaging and exercising the leg immediately after satisfactory radiographs have been obtained. Termination of the injection of contrast medium must be seriously considered if the injection causes pain or if the deep veins are seen to be extensively thrombosed, for all RCM may induce thrombophlebitis. Although leg venography is still the ‘gold standard’ for imaging DVT, it is being increasingly replaced by compression ultrasound (without contrast medium).

Cardiac and Coronary Angiography Intracardiac injections LOCM injections are much preferred as they cause less disturbance of cardiac function, depression of myocardial contractility, peripheral vasodilatation, hypervolaemia, systemic hypotension and ECG changes. They are also much better tolerated subjectively than HOCM. Pulmonary angiography LOCM injections should be used for pulmonary angiography as they cause less elevation of the pulmonary artery pressure, coughing, movement and discomfort. Separate unilateral pulmonary artery injections should replace main stem pulmonary artery injection.

CONTRAST MEDIA, BLOOD COAGULATION AND THE ENDOTHELIUM6 In the 1990s it was confirmed that unlike ionic LOCM, non-ionic contrast media do not strongly inhibit thrombin formation or fibrin polymerization (with the consequent coagulation of blood), nor do they significantly inhibit platelet activity and aggregation. LOCMs do not inhibit blood coagulation as markedly as do HOCMs. Despite this disadvantage, LOCMs are now utilized for almost all angiographic and angioplasty procedures. Meticulous care must be taken to prevent catheter/guide wire thrombosis or sludging by constant perfusion of heparinized saline, continuous trans-catheter pressure recording and preventing blood entering the syringe (preferably plastic, not glass). Some angiographers routinely heparinize the patient for angiography and most angiographers do so during angioplasty. The production of many vaso-active physiological agents by the endothelium when exposed to RCM is discussed earlier6,11.

PREVENTION OF ADVERSE REACTION TO RCM There is no known premedication regimen that can be relied upon to eliminate completely the risk of a severe adverse reaction to RCM. Several strategies for prophylactic premedication have been suggested, usually involving the use of (some or all of ) corticosteroids, antihistaminics, H1 and H2 antagonists and ephedrine. The present author (Grainger) strongly recommends that in all patients considered to be at increased risk of adverse reactions (Table 2.4), alternative imaging should always be considered; premedication with corticosteroids (and possibly with antihistaminics) should be administered for the 12–24 h

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before and after injection of RCM, and that LOCM (rather than HOCM) should be used in all these patients in whom further administration of contrast medium is considered to be essential.

ETHICAL, FINANCIAL AND COST–BENEFIT CONSIDERATIONS HIGH- VERSUS LOW-OSMOLAR CONTRAST MEDIA The incidence of mild, moderate and severe adverse reactions is markedly less frequent with LOCM than with HOCM7 (Table 2.3). In the late 1990s, the only factor inhibiting the total abandonment of HOCM and its replacement by LOCM was financial, because LOCM was considerably more expensive. Recent major reduction in LOCM prices (industrial competition, expiration of patent protection, improved manufacturing techniques and user pleadings) has markedly changed this late 1990s position. The strong recommendation must be that LOCM should be used for intravascular injection in all patients, especially those at increased risk. Unfortunately there are still many impoverished countries where total conversion to LOCM is not a major medical requirement and is not financially justified, and they reasonably continue to use HOCM.

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INTRAVASCULAR CONTRAST MEDIA FOR RADIOLOGY, CT AND MRI

CONCLUSION Both HOCM and LOCM are probably the safest drugs used in clinical medicine. It is not yet proven that LOCM reduces the fatality rate compared to HOCM. There is no doubt that LOCMs produce less discomfort on IV injection, less pain on intra-arterial injection, less physiological and haemodynamic disturbance and fewer adverse reactions to contrast agents than does HOCM. Recent major reduction in cost has encouraged the use of LOCM in about 80–90+ per cent of all intravascular radiographic injections in Europe, North America, Australasia, Japan and many other countries. Because of the concern about the ill-effects of radiation exposure, it is probable that in the next few years, radiological methods will be progressively replaced by MRI using blood pool and other specific contrast agents. The Manual on Contrast Media, 4th edition, published by the American College of Radiology in 1999 and The European Society Guidelines on Contrast Media (2003) Version 3.0 are excellent practical handbooks. Two encyclopaedic textbooks (Dawson, Cosgrove and Grainger6 and Thomsen, Muller and Mattrey11) dealing exclusively with contrast agents (radiological, US and MRI) with contributions from internationally respected clinicians and industry scientists were published in 1999 and are recommended if further information is required.

MRI CONTRAST MEDIA EXTRACELLULAR MRI CONTRAST AGENTS Henrik S. Thomsen and Sameh K. Morcos Extracellular MRI contrast agents are diagnostic pharmaceutical compounds containing paramagnetic metal ions that affect MR signal properties of surrounding tissues. Paramagnetic agents are mainly positive enhancers that reduce the T1 and T2 relaxation times and increase tissue signal intensity on T1-weighted MR images and have almost no effect on T2-weighted images. Initially it was thought that MRI did not need contrast media due to the excellent soft tissue contrast compared to CT. However, in 2005, up to 40 per cent of all MRI examinations worldwide were performed with contrast agents. The majority of contrast-enhanced MRI examinations are performed with extracellular, not organ-specific agents. However, organ-specific agents (e.g. liver, lymph nodes) have recently become available (see later section). Almost 25 years ago, copper (Cu2+), manganese (Mn2+) and gadolinium (Gd3+) were considered as potential paramagnetic ions to be used for MRI. However, Gd is the most powerful, with seven unpaired electrons, but unfortunately gadolinian is the most toxic of those ions and therefore it is necessary to encapsulate it by a chelate. The first agent to be introduced into clinical practice was the gadolinium diethylene triamine pentacetic acid salt (GdDTPA). The chelate DTPA was already known from its use in nuclear medicine (99mTc-DTPA). Several extracellular Gd

chelate MRI contrast agents are currently available for clinical use in addition to Gd-DTPA. Some of these agents are ionic with high osmolality; others are non-ionic with osmolality twice that of the blood (Table 2.5). All the extracellular MRI contrast agents have a high tolerability in animal studies and good relaxation properties. In this chapter the pharmacokinetics, clinical use and safety of these agents will be discussed, including possible interaction with clinical tests and their use for radiographic examinations.

PHARMACOKINETICS The pharmacokinetics of all extracellular MRI contrast agents with the exception of gadobenate dimeglumine (Gd-BOPTA) are similar to iodinated water-soluble contrast media. They have low molecular mass and after IV injection they are rapidly diffused into the interstitial extravascular space. Reverse diffusion into the intravascular compartment also occurs and a state of equilibrium between diffusion in and out is usually reached within 2 h. Gd chelates are eliminated unchanged from the intravascular compartment by passive glomerular filtration and by 24 hours >95 per cent of the injected dose is excreted in urine with normal renal function. A very small amount (<0.1 per cent) is eliminated via faeces. The biological half-life is approximately 1.5 h. Extracellular MRI contrast agents do not cross the intact specialized vascular blood–brain barrier. They do not bind to proteins or receptors and there is no intracellular penetration.

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Table 2.5 CURRENTLY AVAILABLE EXTRACELLULAR MRI CONTRAST AGENTS

Generic agent name

Gadopentate Gadoterate dimeglumine meglumine (Gd-DPTA) (Gd-DOTA)

Gadodiamide (Gd-DPTA-BMA)

Gadoteridol (Gd-HP-DO3A)

Gadobenate dimeglumine (Gd-BOPTA)

Gadobutrol (Gd-BT-DO3A)

Gadovesetamide Gd-DTPA-BMEA

Year of introduction

1988

1989

1993

1994

1998

1998

2000

Molecular structure

Liner, ionic

Cyclic, ionic

Linear, non-iconic

Cyclic, non-ionic

Linear, ionic

Cyclic, non-ionic

Linear, non-ionic

Molecular concentration

0.5 mmol/L

0.5 mmol/L

0.5 mmol/L

0.5 mmol/L

0.5 mmol/L

1 mmol/L

0.5 mmol/L

Osmolality mosmol/kg H2O

1960

1350

650

630

1970

1600

1110

Viscosity (mPas at 37°C)

2.9

2.0

1.4

1.3

5.3

4.96

2.0

*Thermodynamic stability constant

22.1

25.8

16.9

23.8

22.6

21.8

16.6

*Conditional stability

18.1

18.8

14.9

17.1

18.4

N/A

15

*Kinetic stability (dissociation T ½ *t pH 1.0)

10 min

>1 month

35 s

3h

N/A

24 h

N/A

**Amount of excess chelate (mg/ml)

0.40

None

12.00

0.23

None

N/A

28.40

*The higher the figure, the higher is the stability of the contrast agent. **The presence of excess chelate is an indirect marker of the instability of the contrast agent. The higher the figure, the higher the instability of the agent. N/A, not applicable.

Unlike all other Gd chelates, gadobenate dimeglumine has a capacity for weak and transient protein binding and is eliminated through both the renal and hepatobiliary pathways. The hepatic uptake represents 2–4 per cent of the injected dose. It behaves as a conventional extracellular contrast agent in the first minutes following IV administration and as a liver-specific agent in a later delayed phase (40–120 min after administration) when it is taken up specifically by normal functioning hepatocytes.13

CLINICAL USE OF EXTRACELLULAR MRI CONTRAST AGENTS These agents accumulate in tissues with abnormal vascularity (malignant and inflammatory lesions) and in regions where the blood–brain barrier is disrupted. Owing to their rapid equilibration in the interstitial space of both normal and tumour/ inflammatory tissues, the use of dynamic MR imaging after bolus injection makes the best use of the narrow imaging window with a transiently increased tumour/inflammatory to normal tissue contrast. Generally the recommended dose for clinical use is 0.1 mmol kg-1 body weight but up to 0.3 mmol kg-1 may be used, particularly in MRA.13–15

anaphylactoid reaction, which are observed with radiographic iodinated contrast media, may also be seen with extracellular MRI contrast agents but the incidence is much lower. The incidence of mild adverse effects is less than 5 per cent. Life-threatening reactions are very rare, with an incidence around 1:100 000. Fatal reactions may however occur but are extremely rare.13

CONTRAST MEDIUM-INDUCED NEPHROPATHY Extracellular MRI agents are more nephrotoxic than iodinated contrast media in equimolar doses. However, nephrotoxicity after contrast-enhanced MRI examinations is not common even in patients with renal disease as the dose of Gd-based contrast medium required for a diagnostic MRI examination is small in comparison to the doses of iodinated contrast media that are routinely used for CT or other radiographic examinations. However, in patients with marked reduction in renal function (particularly due to diabetes mellitus), contrast medium-induced nephropathy may occur even at the standard doses of extracellular MRI contrast agents (see later section on NSF).16

SAFETY OF EXTRACELLULAR MRI CONTRAST AGENTS

NEPHROGENIC SYSTEMIC FIBROSIS (NSF)

Extracellular MRI contrast agents are well tolerated with a low incidence of adverse effects. There are no differences in the safety of the various agents except when it comes to extravasation in soft tissue; then the osmolality is important and high osmolar agents are likely to induce more local damage. In blood, the osmotic load of all Gd-based contrast media is very low, compared to iodinated contrast media, because only a small amount of the contrast agent is required to produce a diagnostic MRI examination. Adverse reactions such as nausea/vomiting, urticaria, bronchospasm, laryngeal oedema, hypotension and generalized

Recently (2006 and 2007) several reports have suggested that the administration of extracellular gadolinium based contrast agents (Gd-CA) may trigger the development of NSF in patients with advanced renal impairment (GFR < 30 ml/ min) or on dialysis. The incidence of this condition in this group of patients is around 3–5% and the onset varies from a few days to 3 months after administration of Gd-CA. The disease is characterised by scleroderma- like skin changes that mainly affect the limbs and trunk. The induration of the skin can progress to cause flexion contracture of joints. The fibrotic changes may also affect other organs such as mus-

CHAPTER 2

cles, heart, liver and lungs. The disease can be aggressive, in some patients leading to serious physical disability or even death. The considerable majority of reported NSF complications followed the administration of non-ionic gadodiamide, but in a few patients NSF followed injection of gadopentate dimeglamine, gadovestomide and other gadolinium contrast agents.18–21 The stability of the binding of the gadolinium ion (Gd+++) within the chelate could be an important factor in the pathogenesis of NSF and may explain the strong association between gadodiamide and this condition. The stability of the Gd-chelates is influenced by the configuration of the molecule whether linear or macrocyclic and ionicity. Macrocyclic chelates offer better protection and binding to Gd+++ in comparison to the linear molecules. Replacement of carboxyl group by a less strongly coordinating group to produce a non ionic Gd-CA also weaken the binding of the chelate to Gd+++ particularly in the non ionic linear molecule. Stability measurements (Table 2.5) indicate that the least stable molecules are the non ionic linear chelates, and most stable is the ionic cyclic chelate. In vivo, transmetallation with endogenous ions leading to the release of the highly toxic gadolinium ions (Gd+++) is likely to occur with unstable Gd-CA particularly if they remain in the body for a long period, as is the case in patients with advanced renal impairment or on dialysis. Recent reports demonstrated gadolinium in the skin lesions of patients with NSF strengthening the hypothesis that free gadolinium play an important role in triggering this condition. It is advisable at this stage of our understanding to *avoid the administration of non-ionic linear chelates in patients with advanced renal impairment (GFR <30ml/min) including those on dialysis. A more stable Gd-CA such as macrocyclic Gd-chelates might prove less hazardous if contrastenhanced MRI examination is thought to be necessary in such a group of patients, including pregnant and lactating women with end-stage renal failure. There is no evidence that immediate haemodialysis after administration of Gd-CA protects the patient against NSF*.20, 21

PREVENTION OF ADVERSE REACTIONS It is not recommended to give any prophylaxis before administering extracellular MRI agents. However, if there has been a previous hypersensitivity-like reaction to a gadolinium-based compound, an alternative imaging investigation should be considered. If the administration of a Gd-based contrast agent is deemed essential, a different MRI contrast agent to the one incriminated in the previous reaction should be used and corticosteroid prophylaxis might offer some protection. There is no cross-reaction between extracellular MRI contrast agents and radiographic iodinated contrast media. Patients with multiple allergies may react to both iodinated and gadolinium-based contrast media.13

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USE OF EXTRACELLULAR MRI CONTRAST AGENTS IN SPECIAL GROUPS OF PATIENTS Patients on dialysis Extracellular MRI contrast agents are easily removed by haemodialysis or continuous ambulatory peritoneal dialysis. There is no need to schedule the MRI examination in relation to the dialysis session.

Pregnancy and lactation Mutagenic and teratogenic effects have not been described after administration of gadolinium-based contrast media.Therefore, if the MR examination is deemed necessary, an extracellular MRI contrast agent may be given to a pregnant female. Only tiny amounts of gadolinium-based contrast media given to a lactating mother reach the milk and only a minute proportion is absorbed from the baby’s gut. Therefore, stopping breast-feeding for 24 h following administration of a gadolinium-based contrast media is not warranted.13

INTERACTION BETWEEN EXTRACELLULAR MRI CONTRAST AGENTS WITH CLINICAL TESTS Extracellular MRI contrast agents may cause spurious hypocalcaemia as they can interfere with the assay method of calcium measurement. Awareness of this effect on calcium measurements by some MRI contrast agents is important in order to avoid incorrect and potentially hazardous treatment. Caution should be exercised when using colorimetric assays for angiotensin-converting enzyme, calcium, iron, magnesium, total iron binding capacity and zinc in serum samples of patients who have recently received Gd-based contrast media. Therefore, biochemical assays are better performed before contrast media injection, or delayed for at least 24 h afterwards or longer in patients with renal impairment. Urgent laboratory tests performed on specimens collected shortly after contrast media injection should be carefully assessed. Accuracy of unexpected abnormal results should be questioned and discussed with colleagues from the hospital laboratories.22

USE OF EXTRACELLULAR MRI CONTRAST AGENTS FOR RADIOGRAPHIC EXAMINATIONS Gadolinium attenuates X-rays and hence their use for radiographic examinations instead of iodinated contrast media has been advocated in patients with history of serious adverse reactions to iodinated contrast media and in patients who shall undergo imminent thyroid treatment with radioactive iodine, providing the renal function of these patients is normal. In patients with renal impairment, Gd-based contrast media should not be used for radiographic examinations as they can induce nephrotoxicity at the doses required to produce adequate radiographic enhancement. It is also important to point out that Gd-based contrast agents have not been approved for radiographic examinations or intra-arterial injection and the doses approved for MRI examinations will provide only a limited enhancement of radiographic examinations.16

* NB: The drug safety authorities in Europe have recently recommended that the non-ionic linear chelate gadodiamide agents should not be used in patients with GFR < 30 ml/min, on dialysis or those who have had or who are waiting for liver transplantation. Gd-based agents should be used in neonates and infants up to one year of age, only after careful consideration.

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CONTRAST-ENHANCED MR IMAGING OF THE LIVER AND PANCREAS Dow-Mu Koh The IV contrast media currently available for MR imaging the liver can be classified into three broad categories. The types, actions and common side effects of these contrast media are summarized in Table 2.6.

NON-SPECIFIC EXTRACELLULAR GADOLINIUM CHELATES These contrast compounds distribute freely in the extracellular space and shorten the T1-relaxation time, resulting in T1 signal enhancement. Dynamic MR imaging of the liver is performed after bolus IV contrast injection. The use of fat-saturated three-dimensional (3D) volume interpolated MR imaging (e.g. VIBE, THRIVE, FAME) allows high spatial resolution imaging of the entire liver to be acquired in a 20-second breath hold. Imaging is repeated in the arterial, portovenous and parenchymal phases of liver enhancement.

ARTERIAL PHASE In the hepatic arterial phase (typically 20–30 s after IV injection), both benign (e.g. focal nodular hyperplasia, adenoma and haemangiomas) and malignant lesions (e.g. hepatocellular carcinoma and metastases arising from neuroendocrine tumours) may appear hypervascular. Further differentiation depends on the pattern and rate of contrast medium change within the lesion. For example, haemangiomas typically dem-

Table 2.6

onstrate peripheral nodular enhancement23 (Fig. 2.2), while focal nodular hyperplasia shows intense uniform enhancement. Heterogeneous irregular enhancement is typical of hepatocellular carcinoma.

PORTOVENOUS PHASE The portovenous phase occurs at 60–90 s after IV contrast medium administration during which maximum liver parenchymal enhancement is achieved.This increases conspicuity of hypovascular (e.g. hypovascular metastases) and non-vascular (e.g. hepatic cysts) lesions. During this period, benign lesions such as adenoma and focal nodular hyperplasia may fade to isointensity with the liver. Hypervascular metastases can also appear isointense. The pseudo-capsule and internal septae associated with hepatocellular carcinoma become more prominent.

INTERSTITIAL PHASE This phase occurs from approximately 90 s to 5 min after administration of IV contrast agent. Differential washout of contrast agent from the hepatic parenchyma and focal liver lesions aids lesion characterization. In this phase, haemangiomas continue to enhance centripetally (Fig. 2.2); adenomas and focal nodular hyperplasia are typically isointense with the liver, although late enhancement of the central scar of focal nodular hyperplasia may be visible24. Small hepatocellular carcinoma fades to contrast hypointensity. Delayed enhancement of cholangiocarcinoma becomes apparent.

SUMMARY OF CONTRAST MEDIA AVAILABLE COMMERCIALLY FOR MR IMAGING OF THE LIVER

Classes Examples

Nonspecific extracellular gadolinium chelates

Hepatocyte selective gadolinium chelates

Magnevist™ Omniscan™

Multihance™ Primovist™

Teslascan™ (Manganese based)

Endorem™ (Iron oxide based)

Resovist™ (Iron oxide based)

Non-gadolinium-based contrast media

Dotarem™ Prohance™ Gadovist™ Constituents

Low molecular weight gadolinium chelates

Low molecular weight gadolinium chelates: Gd-BOPTA Gd-EOB-DTPA

Magafodipir trisodium (MnDPDP)

Superparamagnetic iron oxide particles (ferrumoxides 80–150 nm in size)

Superparamagnetic iron oxide particles (ferucarbotran 60 nm in size)

Administration

Intravenous bolus

Intravenous bolus

Intravenous infusion

Intravenous infusion

Intravenous bolus

Action

Distributes freely in the extracellular space

Initially distributes freely in extracellular space but undergoes hepatic excretion

Selective uptake by hepatocytes and excreted into bile ducts

Selective uptake by Kupffer cells

Selective uptake by Kupffer cells

Imaging

T1-weighted imaging

T1-weighted imaging

T1-weighted imaging

T2*-weighted ± T1-weighted imaging

T2*-weighted ± T1-weighted imaging

Common side effects

Rash

Rash

Nausea and abdominal discomfort

Back pain

Back pain

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INTRAVASCULAR CONTRAST MEDIA FOR RADIOLOGY, CT AND MRI

Figure 2.2 Dynamic T1-weighted MR images obtained using a 3D volume interpolated technique after IV bolus of non-specific extracellular gadolinium chelate. Imaging was performed in the (A) arterial, (B) portovenous, (C) interstitial and (D) delayed (10 min) phases of hepatic enhancement. Note the discontinuous peripheral nodular enhancement of the lesion (arrows) in segment VI of the right lobe, which increases centripetally, typical of a haemangioma. Lesion characterization is possible by evaluating the rate and pattern of contrast enhancement.

HEPATOCYTE-SELECTIVE GADOLINIUM CHELATES These are also administered intravenously as a bolus. However, a proportion of the contrast medium is selectively excreted by hepatocytes into the bile ducts. The percentage of hepatic uptake is 5 per cent for MultiHance and up to 50 per cent for Primovist. Dynamic T1-weighted MR imaging is performed in the arterial, portal and interstitial phases after injection, similar to

the nonspecific extracellular gadolinium contrast media. However, a delayed hepatic enhancement phase is observed (Fig. 2.3).This occurs at 15–30 min for Primovist and approximately 1–3 h for MultiHance. MultiHance has been used to distinguish between adenomas and focal nodular hyperplasia25. As adenomas do not contain normal biliary radicals, they appear hypointense at delayed T1weighted imaging. Metastases (nonhepatocellular) and hepatocellular carcinoma (poorly functioning hepatocytes) also frequently appear hypointense. By comparison, focal nodular

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Figure 2.3 Dynamic T1-weighted MR images using a 3D volume interpolated technique after IV bolus of hepatocyte selective gadolinium chelate (Gd-EOB-DTPA) in a normal liver. Imaging was performed in the (A) arterial, (B) portovenous and (C) interstitial phases of contrast enhancement, similar to the use of non-specific extracellular gadolinium chelates. However, a (D) delayed hepatic phase (15–30 min) was observed with intense hepatic parenchymal enhancement accompanied by clearance of contrast medium from hepatic vasculature due to hepatocyte contrast excretion. Lesions of non-hepatocellular origin (e.g. metastases) would increase in conspicuity during this phase

hyperplasia appears hyper- or isointense at delayed imaging. Primovist results in a much more intense parenchymal enhancement due to increased biliary excretion. However, its role in detection and characterization of focal liver lesions is still under investigation.

NON-GADOLINIUM CONTRAST MEDIA Unlike the gadolinium-based contrast media, dynamic imaging is not performed with the use of these MRI agents. These

contrast media are actively transported into liver and can be divided into two subcategories: 1 Hepatocyte-selective manganese-based contrast medium. Teslascan (MNDPDP) is infused intravenously and its selective uptake by hepatocytes results in intense T1 liver signal enhancement at approximately 30 min, which persists for several hours.26 There is normally complete clearance of contrast agent from the liver by 24 h. The contrast medium is also taken up by the pancreas, adrenal glands and the pituitary.

CHAPTER 2

2 Cysts, haemangiomas and metastases from non-neuroendocrine primary tumours remain hypointense at T1-weighted imaging. There is variable enhancement of focal nodular hyperplasia, adenomas and hepatocellular carcinomas.26 Metastases from neuroendocrine tumours also show enhancement by an uncertain mechanism. It has been found that delayed imaging at 24 h may be useful for detection and characterization of colorectal hepatic metastases due to delayed clearance of contrast material surrounding the metastases27 (Fig. 2.4).

Reticulo-endothelial system targeted iron-based contrast media These comprise small paramagnetic iron oxide particles that are administered intravenously. The iron accumulates within

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INTRAVASCULAR CONTRAST MEDIA FOR RADIOLOGY, CT AND MRI

Kupffer cells in the normal liver, resulting in reduction in signal intensity of the liver at T2*-weighted gradient-echo imaging. Lesions containing Kupffer cells demonstrate signal reduction whereas lesions that are Kupffer cell depleted would remain high signal. Immediately following IV administration, the contrast agent also causes T1 relaxation and early T1-weighted imaging may be performed. Iron oxide-based contrast media have been shown to increase the detection of small hepatic metastases prior to surgery.28 (Fig. 2.5). The contrast agent can also be used to demonstrate the extent of cholangiocarcinomas in the liver. However, its role in distinguishing between hepatocellular carcinoma, focal nodular hyperplasia and adenomas is less certain, as variable amounts of Kupffer cells in these lesions results in considerable overlap of their imaging appearances.

Figure 2.4 T1-weighted MR imaging of the liver obtained in two different patients with colorectal hepatic metastases at 24 h after MnDPDP contrast (selective hepatocytic) administration. Note the clearance of contrast medium from the normal liver. However (A) geographic enhancement and (B) rim enhancement can be seen adjacent to metastases believed to be related to delayed clearance as a result of regional cholestasis.

Figure 2.5 Gradient T2*-weighted MR imaging of liver obtained (A) before and (B) after paramagnetic iron oxide (Kupffer cell) contrast medium injection. The metastasis (no Kupffer cells) in the right lobe of the liver increases in conspicuity after contrast agent administration due to signal reduction in the normal liver.

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CONTRAST-ENHANCED MR IMAGING OF THE PANCREAS An MR cholangio-pancreaticogram (MRCP) is usually performed in conjunction with MR imaging of the pancreas.

GADOLINIUM CONTRAST-ENHANCED IMAGING Low molecular weight extracellular gadolinium chelates are most frequently used to characterize pancreatic lesions. Before contrast enhancement, unenhanced MR imaging should be carefully reviewed for focal signal abnormalities. In particular, fat-suppressed T1-weighted imaging is useful for identifying low signal intensity foci within the pancreas. T2-weighted imaging is helpful for visualizing high signal cystic lesions. Most solid pancreatic tumours appear hypointense or isointense on T1-weighted imaging, and isointense or mildly hyperintense on T2-weighted imaging. Following bolus contrast injection, T1-weighted MR imaging is performed. The use of a fat-suppressed 3D volume interpolated T1-weighted imaging sequence, performed in repeated breath-holds, is particularly useful for detecting small focal lesions29,30 and for assessing vascular involvement.

In the arterial phase, there is enhancement of hypervascular neuroendocrine tumours of the pancreas. Both cystic and solid hypovascular pancreatic carcinomas are also well demarcated in the arterial phase (Fig. 2.6). In the portovenous phase, hypervascular tumours usually fade to isointensity. Despite the superior contrast resolution of MR imaging, it is still controversial whether the technique is better than multi-detector CT for the detection and characterization of focal pancreatic lesions. However, there is gathering enthusiasm for using MR imaging to assess for tumour resectability.31

Mn-DPDP-ENHANCED MR IMAGING Mn-DPDP is also excreted by the normal pancreatic parenchyma. Anecdotal reports have demonstrated the potential utility of the technique in detecting pancreatic carcinoma as relative hypointense lesions against the enhancing pancreas at T1-weighted imaging4. However, no studies have shown a clear advantage over the extracellular gadolinium chelates. Furthermore, the uptake of the contrast agent (Mn-DPDP) by neuroendocrine tumours can result in reduction of contrast between the tumour and the enhancing pancreatic tissue.

Figure 2.6 Carcinoma of the pancreas (A) T2-weighted axial image showing a mildly hyperintense lesion within the pancreatic tail (arrows), which appears hypointense (arrows) on the (B) fat-suppressed T1-weighted MR image. (C) Immediately following IV extracellular gadolinium contrast administration, the mass is well seen as a hypointense mass (arrows) against the enhancing pancreatic parenchyma using a fat-suppressed T1-weighted imaging sequence.

MRI CONTRAST AGENTS AND TECHNIQUES FOR CONTRAST-ENHANCED MR ANGIOGRAPHY Giles Roditi The flow-sensitive MRA techniques of time-of-flight and phase contrast imaging first developed in the 1980s rely on maximization of signal difference between flowing blood in the vessel lumen versus static vessel wall and surrounding tissues. These have now in large part been superseded by contrast-enhanced MRA (CE-MRA) techniques, wherein gadolinium-based paramagnetic contrast agents increase the

blood pool signal by causing a profound shortening of the T1 relaxation time. A fast T1-weighted gradient-echo pulse sequence is used, specifically designed with short TR, short TE and RF spoiling to produce an image with low background signal while vascular contrast depends on T1 shortening due to the gadolinium rather than flow effects. Since CE-MRA is not susceptible to in-plane flow saturation, it

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INTRAVASCULAR CONTRAST MEDIA FOR RADIOLOGY, CT AND MRI

Blood T1(msec)

T1 (msec)

can be performed in the plane of the vessel, increasing the practicable field of view and reducing acquisition time32,33. Breath-hold techniques are desirable (i.e. a volume acquired in 30 s or less) as they improve diagnostic accuracy for branch vessels. Most modern MRI machines are now capable of imaging a clinically useful MRA volume in a comfortable breath-hold, and parallel imaging techniques are starting to allow time-resolved imaging.

•

1200

Fat T1 (270 msec)

1000

Gadofosveset Steady state (150 msec)

800 Contrast Bolus First pass 0.2 mmol/kg (50 msec)

600 400

CONCEPTS OF CONTRAST MEDIUM ADMINISTRATION Delivery of contrast agents (Gd-CA) for CE-MRA by IV injection is more complex than for ‘simple’ MRI studies and necessitates an understanding of their mode of action and kinetics to maximize contrast effect and minimize artefacts. In order to provide contrast, a sufficient concentration of gadolinium contrast agent must be achieved in the vessels of interest to reduce the T1 of blood to less than 270 ms (equivalent to the T1 of fat for a 1.5 T system). The effect of a contrast agent on a tissue is given by the equation:

200 0 0

1

2

3

4

5

6

7

8

9 10

[Gad] (mMolar) Figure 2.7 Graph of whole blood T1 value as a function of gadolinium concentration compared to T1 of fat (highest signal background). Note how T1 of blood falls from 1200 ms to below that of fat (270 ms) above 0.5 mmolar gadolinium concentration. Approximate T1 of blood during first pass contrast bolus passage (50 msec) and in steady state for Gadofosveset BPCA (150 msec) is also shown.

R' = R + rC where R is the original relaxation rate (1/relaxation time), r is the agent’s specific relaxivity rate, C its concentration and R' the resultant new relaxation rate (Fig. 2.7). Blood has a T1 of 1200 ms, hence with a conventional extracellular fluid (ECF) gadolinium contrast agent with a T1-specific relaxivity rate of 4 mmol-1 s−1 a concentration of 1 mmol l-1 will reduce this to approximately 200 ms, and 2 mmol l-1 will reduce it to 100 ms – a useful contrast difference. Unfortunately, at concentrations above 5 mmol l−1 the T2* shortening effects of gadolinium come to predominate and signal on a T1w (T1-weighted) sequence rapidly declines. These T2 and T2* effects also act over a wider region than the T1 effects that are very local to the agent; this explains the artefacts seen from residual ‘neat’ venous contrast after arm injection, resulting in loss of signal in adjacent arteries on aortic arch and subclavian studies. To help combat this and ensure efficient contrast use, IV contrast medium should be immediately flushed with a suitable volume of saline (e.g. 30 ml) at the same injection rate to move the bolus into the central venous pool, where it is propelled on to the right heart, maximizing efficiency of the dose. To further minimize these effects, it is recommended that contrast agents are administered via a vein in the right arm since any artefact from the left brachiocephalic vein (where flow tends to be sluggish) across the origins of the aortic arch branches may seriously degrade their depiction. A right arm injection is also beneficial even when studying territories remote from the arch, since the route is shorter with less contrast travel time variability than with left arm intravenous injections (Fig. 2.8). Contrast agent injection for MRA studies is simplified by the use of an MRI compatible pump injector ensuring reproducibility while allowing medical and radiographic staff

Figure 2.8 First-pass arterial phase MRA aortic arch and subclavian arteries – normal study. Note the signal dropout in the right axillary artery where the axillary vein crosses and more medially in the right subclavian artery where the subclavian vein is directly adjacent due to T2* effect of residual concentrated gadolinium contrast in veins.

to remain in the MRI control room. The phenomenon of signal abolition at high agent concentrations also informs the use of contrast for ‘direct’ MR venography when injecting into the relevant veins, e.g. pedal injection for a lower limb study or for arteriovenous fistula studies. For this, an injection of diluted contrast is required and this also applies for direct MR arteriography studies.

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Peak arterial blood pool contrast concentration after IV injection is proportional to contrast agent flux (which is the product of agent concentration and rate of injection) and inversely proportional to cardiac output. The effect of differing cardiac output is lessened at injection rates over 1 ml s−1 and so, on modern systems, apart from trying to minimize patient anxiety, cardiac output is generally not directly manipulated (reduced) and varying the rate of contrast administration is used to maximize contrast efficacy. ‘Double dose’ (0.2 mmol kg−1) is usually employed for single station examinations (e.g. carotid, thoracic aortic, renal arteries etc.) and to maximize efficient use of contrast medium, the bolus should last for the duration of the CE-MRA sequence covering central and peripheral k-space data acquisition. For example, for a typical 20-second breath-hold sequence then 30 ml of a 0.5 mol l−1 ECF agent could be injected at a rate of 1.5 ml s−1. In practice somewhat higher rates are used as the bolus injected peripherally becomes ‘stretched’ as it passes through the pulmonary circulation and heart, hence rates of 2.0–2.5 ml s−1 are used. For a 1.0 mol l−1 agent (such as gadobutrol) half the volume is required for the same gadolinium flux at any given rate. If this reduced volume is injected at the same rate as a 0.5 mol l −1 medium, this will result in a higher intra-arterial concentration at the bolus peak. However, this may adversely affect image quality if the bolus no longer covers the whole of the acquisition in terms of peripheral k-space lines, hence a 30 per cent lower rate is recommended. Optimum timing of the data acquisition is required to ensure peak concentration in the vessel of interest, and therefore the most profound T1 shortening of blood, coincides with the contrast medium defining central lines of k-space data. Most MRI systems are now supplied with automated triggering and/ or fluoroscopic monitoring simplifying timing with centrically encoded pulse sequences acquiring low frequency contrast defining k-space profiles at the beginning of data acquisition34. These doses have generally been shown to be safe, particularly in terms of nephrotoxicity, even in renal impairment35,36 though the potential of some agents (Gadodiamide and Gadoversetamide) to interfere with assays for serum calcium may result in a spurious ‘pseudohypocalcaemia’ and this phenomenon is potentiated/prolonged in patients with chronic kidney disease. However, the recent reports of an association between Gd-CA (Contrast Agent) use in patients with severe renal impairment (particularly those on dialysis) and the subsequent development of nephrogenic systemic fibrosis (NSF) introduces a note of caution. Whether gadolinium is the specific and sole necessary factor triggering NSF is not yet resolved at the time of writing. Most patients with renal impairment do not develop the disorder, following Gd-CA,with an incidence of 3–5% in dialysis patients administered Gd-CA.37 While the exact relationship and any causality are not yet determined this is a particularly important issue for CE-MRA, which has hitherto been embraced as a safe means of investigation in these patients who are prone to vascular problems. This is especially so since there appears to be a dose-response relationship with

development of NSF more likely with high dose examinations. Despite no conclusive evidence of protection, the current ACR guidelines advise dialysis where practicable in such patients promptly after contrast administration.38,39 (Please see preceding section by Thomsen and Marcos).

PERIPHERAL RUN-OFF AND WHOLE-BODY CE-MRA CE-MRA is not restricted to a single station field of view with the use of stepping table techniques (analogous to those used in conventional angiography) and that allow scanning of the lower body arterial tree from abdominal aorta to feet40 with extended tables and whole body MRA. Mask images are used to allow subtraction of regions of high signal pre-contrast (such as subcutaneous and marrow fat) from the post-contrast images. Image subtraction is particularly crucial for the tibial station as the image scaling effect of high signal due to contrast agent is negligible within small crural arteries while both the subcutaneous and marrow fat are in close proximity to the vessels. Whereas a total dose of 0.2 mmol kg−1 standard (0.5 mol l−1) ECF gadolinium contrast is used for single station studies, this is increased to 0.3 mmol kg−1 for multiple-station CE-MRA of the aorta and lower limb arterial run-off. Biphasic injection protocols are also recommended, for example a rate of 1.5 ml s−1 for the first phase dropping to 0.8 ml s−1 for the second phase. This second phase lower rate helps to prolong the bolus and also reduce venous enhancement. The main problems with peripheral run-off CE-MRA revolve around the classic MRI trade-offs of spatial resolution versus signal-to-noise ratio (SNR) versus image acquisition time. There is also the drawback of so-called ‘venous contamination’ whereby the crural arteries may be obscured by early enhancement of calf veins. High spatial resolution is particularly critical for the small tibial arteries yet this is also the region where venous contamination is most likely, particularly in patients with Fontaine class III and IV critical ischaemia who demonstrate rapid arteriovenous shunting bypassing tissue diffusion/extraction. IV contrast agent travel time variability depends on passage from the venous compartment through the pulmonary circulation and heart. Once in the abdominal aorta, the leading edge of the contrast bolus travels at approximately 6 s per station down the lower limbs (groin, popliteal, ankle). However, the arterial-venous transit times at the calf vary depending on disease status with much more rapid transit in those with critical ischaemia and/or cellulitis compared to simple claudication.41 This has led to different strategies to optimize tibial arterial imaging. 1 Imaging the crural arteries first with a dedicated injection of contrast and a centric-encoded sequence designed for venous suppression, e.g. elliptic centric, CENTRA. Aortoiliac and femoral levels are subsequently imaged with standard stepping table technique and a second injection of contrast medium. 2 The imaging time window at the calf can be prolonged by venous compression techniques, whereby compression

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Table 2.7

•

INTRAVASCULAR CONTRAST MEDIA FOR RADIOLOGY, CT AND MRI

SUMMARY OF CONTRAST AGENTS AVAILABLE COMMERCIALLY SUITABLE FOR MR ANGIOGRAPHY43

Generic name

Trade name

Protein binding

Dose for MRA – mmol kg-1

T1 specific relaxivity in blood at 1.5 T – mmol−1 s−1

Gadopentate dimeglumine

Magnevist

Negligible

0.2–0.3

4.3

*

Gadobutrol*

Gadovist

Negligible

0.2–0.3

5.3

Gadoteridol

Prohance

Negligible

0.2–0.3

4.4

Gadoterate meglumine

Dotarem

Negligible

0.2–0.3

4.2

Gadodiamide

Omniscan

Negligible

0.2–0.3

4.6

Gadoversetamide

Optimark

Negligible

0.2–0.3

5.2

Gadobenate dimeglumine

Multihance

Weak

0.1–0.3

6.7

Gadofosveset trisodium

Vasovist

Strong

0.03–0.05

19

*Gadobutrol is formulated as a 1.0 mol l-1 preparation compared to 0.5 mol l-1 for the other ‘standard’ ECF gadolinium contrast agents with negligible or weak protein binding.

cuffs around the thighs inflated to subdiastolic pressures prolong arterial and venous transit times and also increase the venous volume of dilution (reducing contrast conspicuity in the venous compartment). 3 Another strategy is to image the calf vessels first with either fast thick slab 2D subtraction imaging or 3D time-resolved imaging, followed by a standard bolus chase 3D acquisition for the aortoiliac and femoropopliteal stations. 4 The use of parallel imaging and phased array coils at all stations with variable acquisition parameters can allow tailored and more rapid bolus chase such that venous contamination is minimized, e.g. following the aortoiliac station, the femoral segment is rapidly acquired with lower resolution and then highest resolution for the tibial station.42 These techniques listed are not mutually exclusive and the strategy used will depend upon MR machine capability, coil availability and operator experience/preference.

BLOOD POOL CONTRAST AGENTS Blood pool contrast agents (BPCAs – also known as persistent vascular agents) are specifically designed for vascular imaging through persistence in the intravascular space without the passage to extravascular interstitial extracellular fluid spaces that is the hallmark of conventional ECF agents (i.e. their vascular half-life is much greater than ECF agents). Blood pool persistence is achieved either by high molecular weight preventing diffusion through the capillaries or through protein binding to serum albumin, which has the same effect. BPCAs are either based on gadolinium compounds or ultrasmall paramagnetic iron oxides (USPIOs) though these latter iron based agents are as yet not commercially available for blood pool imaging. Gadobenate dimeglumine is predominantly an ECF fluid agent but its weak protein interaction provides higher relaxivity compared with standard 0.5 mol l−1 ECF agents and this weak (but still positive) protein binding also helps prolong blood pool residency. This results in a relatively higher signal intensity peak and longer duration of enhancement compared with standard agents for similar dose and injection rates. The safety profile of gadobenate dimeglumine is similar to the conventional ECF agents.

Gadofosveset has been specifically designed for CE-MRA as a blood pool agent with strong protein binding to albumin, up to 20 molecules of gadofosveset can bind to one molecule of albumin but in clinically used doses it is usually only one or two per albumin molecule. Binding to albumin is rapid with 75 per cent bound 1 min after IV injection, reaching a steady state with approximately 88 per cent bound. The high protein binding has two effects; firstly it markedly increases relaxivity (hence the lower doses/concentrations required) and secondly it results in the agent effectively being confined to the vascular space with little passage to extracellular fluid spaces and an increased half-life in the blood pool. This binding is reversible and the agent is ultimately excreted unchanged by the kidneys through glomerular filtration; it is also eliminated by routine renal dialysis, with 92 per cent cleared after three sessions. Gadofosveset has a safety profile similar to other gadolinium contrast compounds with a low rate of adverse reactions consisting of transient mild tingling sensations (particularly in the perineum), pruritus, flushing, headache and taste perversion. One possible serious adverse anaphylactoid event to gadofosveset was reported, resolving within 5 min. There is apparently no potential nephrotoxicity at clinically used doses nor interference with proper binding drugs such as warfarin. As a commercial BPCA for CE-MRA, gadofosveset provides currently unique properties, particularly through the very prolonged time window available for imaging as with a T ½ of 28 min (compared to 90s for Gad-DTPA) diagnostic imaging can be performed up to 1 h post injection. Arterial first-pass CE-MRA can be performed just as with the ECF agents, perhaps even with greater signal through the increased specific relaxivity of the agent. It is the possibilities of delayed imaging performed with high intravascular signal that are intriguing since this is not limited to the short time of a first-pass bolus and can therefore be performed at very high spatial resolution. Steady state imaging can start from 2 min after injection up to approximately 1 h. Imaging should be designed for high spatial resolution, ideally to create an isotropic dataset to allow for reformatting of images in any plane. In order to obtain best contrast, the sequence used should be optimised with a reduced f lip angle of 20°–25°, increased TR of 10–12 msec, TE of 2–4 msec and appropriately reduced bandwidth (increased water-fat shift). Since imaging is no longer confined

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Figure 2.9 CE-MRA detail of right calf in patient with critical lower limb ischaemia and tibial arterial disease using the blood pool agent Gadofosveset trisodium (Vasovist) in steady state phase with high spatial resolution - 1024 matrix reconstruction on 520 mm field of view with 0.6 mm slice thickness = voxel size of 0.5 × 0.5 × 0.6 mm = 0.15 mm3 voxel volume. (A) Overview MIP where overlying veins tend to obscure detail, (B) representative coronal slice from acquisition and (C) subvolume MIP of right calf showing clear separation of arteries and veins acheived through high spatial resolution. Note satisfactory peroneal artery but heavily diseased posterior tibial artery with irregular wall thickening seen between paired posterior tibial veins.

to a brief period of contrast enhancement, these high spatial resolution sequences can be used with phase oversampling for wrap suppression, increased signal averages for improved SNR etc. However, since these will now be longer sequences than usual MRA, they should be used with respiratory gating and/ or cardiac pulsatility compensation in appropriate body regions (Fig. 2.9). For imaging of systemic and portal venous disorders, as well as arteriovenous malformations, this prolonged time window and excellent contrast are a major advantage over the rapidly excreted conventional agents. Gadofosveset or similar products may well become the optimum agent in suspected pulmonary embolism for it will demonstrate both the pulmonary areterial tree in the early phase and the pelvic and leg veins (where the thrombus may arise) in the later phase of the same examination. The use of blood pool agents in coronary MRA may boost signal from the coronary vessels with respect to myocardium and might dramatically improve image quality. With its high relaxivity and long imaging window gadofosveset may well more reliably detect endoleak after aortic stent grafting than conventional imaging with ECF gadolinium agents and CT techniques. It is also thought that the use of a blood pool agent may allow the detection and localization of occult gastrointestinal haemorrhage. The downside to the use of a blood pool agent is that during later phase imaging, arteries and veins will now be equally conspicuous. Software programs are being developed to isolate arterial structures from the veins though these are currently not commercially available. An interesting further observation with gadofosveset is that late imaging reveals uptake in atherosclerotic plaques: no doubt this will provide fertile ground for further research as regards plaque activity and morphology.

REFERENCES 1. Grainger R G 1982 Intravascular contrast media. The past, the present and the future. Br J Radiol 55:1–18 2. Morris T W 1993 X-ray contrast media. Where are we now and where are we going? Radiology 188:11–16 3. Aspelin P, Aubrey S G, Fransson S G et al 2003 Nephrotoxic effects in high risk patients undergoing angiography. N Engl J Med 348:491–499 4. Heinrich M C, Kuhlmann M K, Grgic A et al 2005 Cytotoxic effects of ionic high-osmolar, nonionic monomeric and non-ionic iso-osmolar dimeric iodinated contrast media on renal tubular cells in vitro. Radiology 235:843–849 5. Nelson R C, Anderson F A Jr, Birnbawm B A et al 1988 Contrast medium extravasation detection accessory. Radiology 209:837–843 6. Dawson P, Cosgrove D O, Grainger R G 1999 Textbook of Contrast Media. Ch. 11 (Nephrotoxicity), Ch 15 (Endothelium and Blood) Isis Medical Media, Oxford 7. Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P, Matsuura K 1990 Adverse reactions to ionic and non-ionic contrast media. A report from the Japanese committee on the safety of contrast media. Radiology 175:621–628 8. Yoshikawa H 1992 Late reactions to non-ionic contrast media. Radiology 183:737–740 9. Spring D B, Bettman M A, Barkan H E 1997 Deaths related to iodinated contrast media reported spontaneously to US Food and Drug Administration 1978–1994: Effect of availability of low osmolality contrast media. Radiology 204:333–337 10. American College of Radiology 1999 Manual on Contrast Media, 4th edition. American College of Radiology. Reston, Virginia, USA 11. Thomsen H S, Muller R N, Mattrey R F 1999 Trends in Contrast Media. Springer-Verlag, Germany 12. European Society of Urogenital Radiology 2003 Version 3.0 13. Thomsen H S 2006 Contrast media, safety issues and ESUR guidelines. Springer, Berlin Heidelberg New York 14. Prince M R, Grist, T M, Debatin J F 2003 3D Contrast MR Angiography, 3rd edn, Springer, Berlin Heidelberg New York 15. Schneider G, Prince M R, Meaney J F M, Ho V B 2005 Magnetic Resonance Angiography – Techniques, Indications and Practical Applications. Springer, Berlin Heidelberg New York

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16. Thomsen H S, Almén T, Morcos S K and the members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR) 2002 Gadolinium-containing contrast media for radiographic examinations: A position paper. Eur Radiol 12:2600–2605 17. Grobner T 2006 Gadolinium - a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 21:1104–1108 18. Marckmann P, Skov L, Rossen K et al 2006 Nephrogenic systemic fibrosis: Suspected etiological role of gadodiamide used for contrastenhanced magnetic resonance imaging. J Am Soc Nephrol 17: 2359–2362 19. Sadowski EA, Bennett LK, Chan MR, Wentland AL, Garrett AL, Garrett RW, Djamali A 2007 Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology Jan 31; [Epub ahead of print] 20. Thomsen H S 2006 Nephrogenic Systemic Fibrosis: a serious late adverse reaction to gadodiamide. Eur Radiol 16:2619–2621 21. Morcos SK 2007 Nephrogenic systemic fibrosis following the administration of extracellular gadolinium based contrast agents: Is the stability of the contrast agent molecule an important factor in the pathogenesis of this condition? Br J Radiol 80:73–76 22. Morcos S K, Thomsen H S, Exley C M and members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR) 2005 Contrast Media: Interactions with Other Drugs and Clinical Tests. Eur Radiol 15:1463–1468 23. Quillin S P, Atilla S, Brown J J, Borrello J A, Yu C Y, Pilgram T K 1997 Characterization of focal hepatic masses by dynamic contrastenhanced MR imaging: findings in 311 lesions. Magn Reson Imaging 15:275–285 24. Ba-Ssalamah A, Schima W, Schmook M T et al 2002 Atypical focal nodular hyperplasia of the liver: imaging features of nonspecific and liver-specific MR contrast agents. Am J Roentgenol 179:1447–1456 25. Grazioli L, Morana G, Kirchin M A, Schneider G 2005 Accurate differentiation of focal nodular hyperplasia from hepatic adenoma at gadobenate dimeglumine-enhanced MR imaging: prospective study. Radiology 236:166–177 26. Wang C 1998 Mangafodipir trisodium (MnDPDP)-enhanced magnetic resonance imaging of the liver and pancreas. Acta Radiol Suppl 415:1–31 27. Koh D M, Brown G, Meer Z, Norman A R, Husband J E. Diagnostic accuracy of rim and segmental MRI enhancement of colorectal hepatic metastasis after administration of mangafodipir trisodium. Am J Roentgenol. 2007 Feb; 188(2):W154–61 28. Ward J, Naik K S, Guthrie J A, Wilson D, Robinson P J 1999 Hepatic lesion detection: comparison of MR imaging after the administration of superparamagnetic iron oxide with dual-phase CT by using alternativefree response receiver operating characteristic analysis. Radiology 210:459–466

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29. Birchard K R, Semelka R C, Hyslop W B et al 2005 Suspected pancreatic cancer: evaluation by dynamic gadolinium-enhanced 3D gradient-echo MRI. Am J Roentgenol 185:700–703 30. Obuz F, Dicle O, Coker A, Sagol O, Karademir S 2001 Pancreatic adenocarcinoma: detection and staging with dynamic MR imaging. Eur J Radiol 38:146–150 31. Smedby O, Riesenfeld V, Karlson B et al 1997 Magnetic resonance angiography in the resectability assessment of suspected pancreatic tumours. Eur Radiol 7:649–653 32. Prince M R, Yucel E K, Kaufman J A, Harrison D C, Geller S C 1993 Dynamic gadolinium-enhanced three-dimensional abdominal MR arteriography. J Magn Reson Imaging 3:877–881 33. Prince M R 1994 Gadolinium-enhanced MR aortography. Radiology 191:155–164 34. Riederer S J, Bernstein M A, Breen J F et al 2000 Three-dimensional contrast-enhanced MR angiography with real-time fluoroscopic triggering: design specifications and technical reliability in 330 patient studies. Radiology 215:584–593 35. Tombach B, Bremer C, Reimer P et al 2002 Using highly concentrated gadobutrol as an MR contrast agent in patients also requiring hemodialysis: safety and dialysability. Am J Roentgenol 178(1):105–9 36. Prince M R, Arnoldus C, Frisoli J K 1996 Nephrotoxicity of high-dose gadolinium compared with iodinated contrast. J Magn Reson Imaging 6:162–166 37. Collidge T A, Thomson P C, Mark P B et al 2007 Gadolinium-Enhanced Magnetic Resonance Imaging and Nephrogenic Systemic Fibrosis – A Retrospective Case-Control Study. Radiology, in press 38. Kuo P H, Kanal E, Abu-Alfa A K, et al 2007 Gadolinium-based MR contrast agents and nephrogenic systemic fibrosis. Radiology. 242(3):647–9 39. Kanal E, Barkovich J A, Bell C et al 2007 ACR Guidance Document for Safe MR Practices: 2007 AJR 188: 1–27 40. Meaney J F, Ridgway J P, Chakraverty S et al 1999 Stepping-table gadolinium-enhanced digital subtraction MR angiography of the aorta and lower extremity arteries: preliminary experience. Radiology 211:59–67 41. Wang Y, Chen C Z, Chabra S G et al 2002 Bolus arterial-venous transit in the lower extremity and venous contamination in bolus chase threedimensional MRA. Invest Radiol 37:458–463 42. Bezooijen R, van den Bosch H C, Tielbeek A V et al 2004 Peripheral arterial disease: sensitivity-encoded multiposition MR angiography compared with intraarterial angiography and conventional multiposition MR angiography. Radiology 231:263–271 43. Rohrer M, Bauer H, Mintorovitch J, Requardt M, Weinmann H J 2005 Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths. Invest Radiol 40:715–724

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CHAPTER

Ultrasound: General Principles

3

David O. Cosgrove, Hylton B. Meire, Adrian Lim and Robert J. Eckersley

• • • • • • • • •

Nature of ultrasound Imaging methods Artefacts: clinical insights into ultrasound physics Interpretative principles Doppler ultrasound Volume flow measurement Doppler artefacts, errors and pitfalls Safety of ultrasound Developments in ultrasound

Ultrasound is an important technique for tomographic imaging of soft tissues. It provides images in real-time and so can also be used to interrogate the movement of structures such as cardiac valves, interactive guidance of biopsies and drainage procedures and, using the Doppler mode, the patterns of blood flow in both large and small vessels. Although ultrasound contrast agents are now available, images are generally obtained without them and thus are not dependent on organ function. As far as is known, ultrasound used at diagnostic intensities is harmless and it can be used without concern for injury to sensitive tissues such as the eye and the developing fetus. Ultrasound technology continues to improve; even low-end and portable systems are now digital and new transducer and beam-forming technologies allow higher frequencies to be used at depth. Although ultrasound has found major applications in the heart, abdomen and pelvis, as well as in the neck, breast, peripheries and neonatal brain, perhaps its most important clinical impact is in obstetrics, where the combination of safety and tomographic imaging of the fetus has rendered it indispensable. The parts of the body that can be imaged with ultrasound are, however, limited because it does not readily cross a tissue– gas or tissue–bone boundary, so they and deeper-lying structures cannot be studied.Thus, ultrasound is not generally useful for the lungs and is difficult to use in the head—except in the neonate, when the open fontanelles provides an excellent ‘window’. In other areas, overcoming the barrier caused by the

bony skeleton and gas-containing viscera requires technical expertise. Ultrasound is also subject to many artefactual signals which complicate interpretation and add to the operator skills required. Patients readily accept an ultrasound examination because the procedure requires only light pressure on the skin and preparation is minimal: bladder filling is required for pelvic ultrasound and fasting is necessary for the gallbladder, but otherwise the patient may be examined with this technique as and when convenient, a major advantage for emergency uses. In addition, mobile ultrasound systems that can be taken to the bedside, to intensive care and into the operating room are widely available.

NATURE OF ULTRASOUND Ultrasound is simply sound with a frequency above the limits of human hearing. In most diagnostic applications, frequencies in the 2–20 MHz (megahertz = million cycles per second) range are used, corresponding to wavelengths of 1–0.1 mm in tissue.

Ultrasonic transducers Ultrasound is generated by piezoelectric materials, which have the property of changing thickness when a voltage is applied across them. Lead zirconate titanate (PZT) is the most widely used. Its piezoelectric effect derives from movements of the heavy charged lead atom that is loosely bound within a complex crystal: when an electrical field is applied, the atom moves and distorts the crystal. PZT is a ceramic that is cast as a thin plate that may be disc shaped or, more usually, is formed into a strip that is then sliced into several hundred tiny elements as an array, with metal electrodes on the two surfaces. It is polarized by heating it above a critical temperature and then allowing it to cool in an electric field.When electrically pulsed, the crystal rings at a resonant frequency that is mainly determined by its thickness. Higher frequency crystals are thinner and thus more difficult to manufacture. The piezoelectric effect is reversible, so the same or a similar crystal is used as the receiver to

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produce small electrical signals when struck by an ultrasound wave. The crystal is mounted in a conveniently shaped holder, which contains the electrodes and any associated electronics, as well as the lenses and matching layers required to improve the beam shape. The whole assembly is known as the probe, transducer or head. An interesting new approach to designing transducers relies on photo etching, as used in semiconductor construction, to produce arrays of capacitance elements in which a pair of electrodes is separated by a small air gap; these capacitative microfabricated ultrasound transducers (CMUTs) are easily mass produced and integration of the associated electronics is simple (MEMS and Nanotechnology Clearinghouse website: www.memsnet.org/mems/what-is.html).

Propagation in tissue Ultrasound travels through tissue as a beam that is usually focused to improve lateral resolution. It propagates as a sequence of compression and rarefaction waves, transmitted by the elastic forces between adjacent tissue particles. The particles move in the same direction as the wave—thus ultrasound is a longitudinal wave in comparison to the transverse wave that occurs at the surface of water where the particles move up and down as the wave travels horizontally. The frequency of the oscillations is inversely proportional to the wavelength ( f = c/λ, where f is frequency, c is the velocity of ultrasound and λ is the wavelength). The way in which the ultrasound wave is transmitted varies with the strength of the elastic forces between adjacent particles (which relates to the elasticity of the tissue and thus to the velocity of ultrasound) and the masses of the particles (which determine density). These two factors determine the acoustic impedance (Z ) of the tissue (Z ≅ ρc, where ρ is density and c is the velocity of ultrasound). When the particles are heavy, a given amount of energy is transmitted with small movements of the particles: when they are light, larger excursions are involved; however, the actual distance a particle is moved at diagnostic ultrasound intensities is only a few Ångstroms. In clinical practice, since the velocity of ultrasound in tissue is almost constant (at 1540 m s−1), changes in impedance are mainly attributable to differences in density. The constant speed of ultrasound in soft tissues allows the depth of reflecting structures to be calculated by measuring the delay in the return of echoes after the ultrasound pulse has been transmitted.This is the essence of the pulse-echo method used in both ultrasound imaging and most forms of Doppler ultrasound. The position of reflecting structures across the image is determined by the direction in which the ultrasound beam is transmitted.

Attenuation Provided that the constituent particles of a tissue are small enough to move as a single entity, the acoustical vibrations are transmitted in an orderly and efficient manner. However, when very large molecules are involved, the vibrations become disorganized, one part of the molecule responding more or

less than another. While coherent vibration is what we know as sound, chaotic vibration is heat. This loss of coherence, the most important cause of dissipation of ultrasound energy, is known as absorption and is approximately proportional to the concentration of large molecules which correlates with viscosity. Absorption is also highly dependent on the ultrasound frequency, higher frequencies being more strongly absorbed. For average soft tissues, the loss amounts to approximately 1 dB per cm tissue depth for each MHz.Thus, when using a 3 MHz probe, for every 2 cm of tissue penetration there will be a loss of 6 dB, which is a halving of the signal’s strength. The noise floor (produced by random vibrations in the tissue and the transducer as well as by imperfections in the scanner electronics) typically lies some 60–90 dB below the peak signal, so the penetration of such a probe would be limited to about 20 cm depth. Ultrasound energy is also lost to the receiving transducer if it is reflected or refracted away from the returning line of sight or if the beam diverges. The total loss from all these mechanisms is called attenuation. High-frequency ultrasound gives good resolution because of its short wavelength, but the rapid attenuation of highfrequency ultrasound by tissue is the limiting factor to the maximum frequency that can be used in any given clinical application. Frequencies as high as 20 MHz can be used when only a few millimetres of tissue are to be traversed, such as for imaging the eye and skin, and for intravascular ultrasound (IVUS). For superficial tissues, 10–15 MHz is appropriate. For the heart, abdomen and second and third trimester obstetrics, 3–7 MHz is optimal; however, for some difficult applications, such as the abdomen in obese subjects, and for transcranial studies (most of which use Doppler), it is necessary to resort to 1 or 2 MHz transducers, with consequent reduction in spatial resolution. This frequency limitation can be mitigated by the use of coded transmit pulses, which impose a signature on the pulse (e.g. by making its frequency rise during the pulse, so called chirp encoding); long pulses are used and the scanner contracts them back to a short pulse using a matched decoding filter. Thus, the spatial resolution is regained but more acoustic energy can be transmitted without an increase in acoustic pressure so that the signal-to-noise ratio is improved. Compensation for the loss of signal with depth is achieved by applying progressively increasing amplification (gain) to later echoes using a time-varying amplifier that is triggered when each ultrasound pulse is sent. This is the time gain compensation (TGC), an important user control that must be set to equalize the image brightness for superficial and deep structures. Many modern ultrasound machines incorporate automatic TGC software that simplifies image optimization. This trade-off between depth and resolution is the chief reason for the development of intracavitary probes. Examples are transrectal probes for the prostate and transvaginal probes for gynaecology and early obstetrics, as well as transoesophageal probes for echocardiography. These can operate at 7–15 MHz to give good quality images and, as the barriers caused by

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impenetrable overlying structures are obviated, high-quality images are reliably achieved. Intracavitary probes can be combined with endoscopes for transoesophageal and transgastric data acquisition to evaluate the submucosal and deeper layers of the viscera and to provide high-resolution images of adjacent structures such as regional lymph nodes.

Reflection The other important ultrasonic interaction with tissue is reflection. Some of the transmitted energy is reflected whenever the beam crosses an interface where the transmission properties change, the proportion depending on the degree of impedance mismatch (change of Z ). The phenomenon is similar to that occurring in a rope that is fixed at one end and made to oscillate by shaking the free end up and down: provided the rope is of uniform construction, waves travel along it until they die out or reach the fixed end. However, if a part of the rope is thicker or more rigid, then the waves are partly reflected back when they reach this ‘obstruction’. The intensity of the reflection mainly depends on the degree of change in the tissue density. Ultrasound that is not reflected passes through and is available for imaging deeper tissues. Only a small fraction (2–10%) is reflected at each soft tissue interface but almost total reflection occurs at tissue–gas interfaces, and some two-thirds of the incident ultrasound is reflected at a tissue–bone or tissue–calculus interface so that an acoustic ‘shadow’ is produced deep to these surfaces. They are essentially opaque to ultrasound, which therefore cannot be used to interrogate aerated lung, and imaging through bone is difficult. Two main types of echo are encountered clinically, depending on the structure of the reflecting surface (Table 3.1). Where the interface is smooth compared with the ultrasonic wavelength (i.e. the surface is flat over an extent of several millimetres), the reflected wave obeys Snell’s law just as in optics and is reflected at an angle equal to the angle of incidence. By analogy, these echoes are known as specular or mirrorlike echoes. In the usual arrangement for ultrasound imaging, when the transducer is used both for generation and reception of the ultrasound, only those smooth surfaces that lie at right angles to the sound beam return specular echoes. The directed reflection means that the echo is of high intensity: strength and directionality are the cardinal features of these echoes from flat surfaces.They arise from the linings of hollow viscera and blood vessels, from the valves of the heart, from organ capsules and fascial planes, from the skin and from gas and bone surfaces. When the irregularities in the surface are similar in size as the ultrasound wavelength itself, i.e. 0.01–1 mm, a different mechanism, known as scattering, produces echoes; here each small

Table 3.1

ECHO-PRODUCING MECHANISMS

Specular: mirror-like reflections from flat surfaces

Strong, directional echoes

Scattered: interference patterns from small parenchymal discontinuities

Weak, nondirectional echoes

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interface (e.g. a lobule of an organ, arterioles, venules, etc.) is vibrated by the mechanical shock it has received from the incident ultrasound pulse. The energy is re-radiated more or less equally in all directions, so that each discontinuity behaves as an isolated point source of ultrasound.The echoes are isotropic and potentially detectable from any direction but, because the energy is distributed across the surface of an expanding sphere, the signal received by the transducer from any single vibrating particle is extremely weak and, in practice, is only detectable when several wavelets from adjacent particles happen to be superimposed and produce an additive effect. Low intensity and detectability from any angle are the cardinal features of these scattered echoes. They arise from soft tissue parenchyma and thus are important diagnostically.The texture in the resulting image is an interference pattern, known as speckle and, although deterministic, is not a one-to-one representation of the histological reality. This is why tissues of very different composition (e.g. liver and spleen) can produce indistinguishable echo textures. Many body tissues actually display properties intermediate between specular and scattered echoes. If the beam is sent into a tissue region from several angles and the echoes combined, the speckle pattern is reduced and specular echoes are more likely to be picked up.This approach, known as compounding, can improve image contrast and is widely used in high-end machines. Ultrasound is generally considered to be conducted in a linear manner whereby the waveform of the pulse is preserved with depth. In fact, this is not quite true and nonlinear propagation is an important phenomenon in which the wave of the original pulse from the transducer becomes distorted so that it comes to contain higher frequency components or harmonics. This occurs because the speed of sound increases with increasing density of the conducting medium so that the compression part of the cycle travels slightly faster than the rarefaction part; this distorts the wave much the same way that an ocean wave builds and breaks as it approaches the shore. The development of these harmonics depends on the sound intensity: higher acoustic powers produce stronger harmonics and therefore they are weak in the parts of the sound beam away from the central, desired portion. They are also weak for the first few millimetres of tissue depth because they take a few cycles to build up.These facts have been exploited in machines that use filters to select for the harmonics in the returning echoes by transmitting at, say, 1.5 MHz and tuning the receiver to 3 MHz to remove the fundamental echoes. In doing so, the beam aberrations from side lobes and from reverberations in the superficial tissue layers are suppressed (see below, Resolution). The tissue harmonic image is cleaner with higher contrast: this has been especially useful in echocardiography and in abdominal data acquisition (Fig. 3.1).

IMAGING METHODS Pulse-echo method In conventional pulse-echo ultrasound imaging, signals are displayed according to the depth calculated from the time

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Figure 3.1 Harmonic imaging. (A) Conventional grey scale image through the gallbladder hints at an echogenic mass within it. (B) In harmonic mode the image has much higher contrast and the gallstones (arrowhead), together with the shadowing they produce, are clearly visualized. Note also the thickened gallbladder wall that was not obvious on the fundamental image.

elapsed between transmission and receipt of the echoes, using the speed of sound in tissue to convert from time to depth; the same principle is used in radar and sonar. In the simplest system, only the depth of the interface is determined. It is displayed as a vertical deflection on a monitor and is known as A-mode (A for amplitude). It has one spatial dimension and the strength of the echoes is indicated by the height of the deflection (Fig. 3.2). If the transmitted pulse is repeated rapidly, then the position and intensity of any interfaces that arise from moving structures change with time. A simple way to display these changes is to modulate the intensity of the spot on the monitor in proportion to the intensity of the echoes and then to sweep the line of echoes across the screen. The resultant trace shows depth versus time and is known as an M-mode display (M for movement). It is especially useful in echocardiography for evaluating the rapid movements of valve leaflets (Fig. 3.3). A two-dimensional tomographic ultrasound image is formed by sweeping the beam through a slice of tissue and mapping the echogenicity of the reflectors as shades of grey to form a B-mode image (B for brightness), also known as a grey scale display. This is the commonest mode used for ultrasound imaging. While the depth of the reflectors is determined by the delay in the return of the echoes to the transducer (the

pulse-echo principle), their lateral position is determined by the direction in which the ultrasound beam was sent. Combining a series of B-mode images swept through a volume provides a three-dimensional display and, if the sweeping is sufficiently rapid, a real-time 3D display can be achieved, known as 4D. This has proved to be valuable in echocardiography and obstetrics.

Figure 3.2 A-mode trace. The A-mode is a trace indicating echo intensity tissue with depth. In this example, there is a fluid space (6–10 cm) from which no echoes arise. Tissues superficial and deep to this produce echoes of varying intensities and there is a particularly strong echo from the skin (0–5 cm). The time gain compensation (TGC) curve is also shown.

Figure 3.3 M-mode trace. The echo intensity is displayed as brightness and the trace is swept across the screen so that the x-axis represents time. This is an M-mode echocardiogram showing the rapid movement of the mitral valve apparatus within the left ventricle (LV), with thicker proximal and distal moving bands representing the myocardium. RV = right ventricle.

Beam steering The direction in which the beam is sent can be determined mechanically or electronically. Mechanical steering systems are used in intracavitary examinations where their small size is an advantage. They use a simple, single crystal transducer, which is mechanically swept through an arc (typically of 360 degrees) by spinning it on a wheel (Fig. 3.4). The resulting image has a circular shape, with the transducer itself at the centre and the tissues arranged around it, with the mucosa or intima closest to the transducer. Electronic sector systems (also known as phased arrays) have replaced mechanical systems for other applications. The beam direction is controlled by building up interference patterns between the waves transmitted from an array of a large number of small transducer elements.The usual arrangement consists of numerous PZT crystals (512 in stateof-the-art systems), each 1 mm or less in width and 5–10 mm in length, stacked up in a block. Each has separate electrical contacts and the pulses to each element are serially delayed from one end of the array to the other. These minute differences in timing occur within the short time needed to form

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Delay lines Pulser

128

Array elements

Figure 3.4 Mechanical transducer. (A) Diagram of a mechanical endoprobe transducer. A motor rotates the transducer assembly to sweep out a circular path. (B) A transrectal image covering a 2.2 cm axial section showing the layers of the rectal wall with defects of both the internal and the external sphincter (arrowheads) anteriorly. This is a classic sphincter tear that resulted from a forceps delivery. A = anterior, ES = external sphincter, IS = internal sphincter, M = mucosa, R = right, Tx = transducer. (Courtesy of Professor Clive Bartram, St Mark’s Hospital, London.)

an individual pulse and they produce interference patterns in which the troughs and peaks of the pressure waves add where they coincide and subtract where they are out of phase (hence the title ‘phased array’) (Fig. 3.5). This results in a beam that is angled away from the straight-ahead direction. For the next pulse, a slightly different set of delays is applied to adjust the steering. During receipt of the returning echoes, the electrical signals from the individual elements are delayed before they are summed in the beam former, exploiting the same summing and cancelling approach; the resulting signal is the electronic equivalent of angling the transducer face in the required direction. Although the concept is easy to understand, the underlying mathematics is complex and its implementation generally requires dedicated hardware, although software emulations have been developed so that beam forming can be performed on a PC, thus opening the way to cheaper and more flexible scanners. The resulting image has a triangular or sector shape, which has the important practical advantage of requiring only a small skin-contact area (or ‘footprint’), although it provides only a limited display of the superficial tissues. It is widely used in echocardiography. The operation of electronic linear array transducers is a little simpler.They are made longer than phased arrays and the beam is moved across the scanned plane by firing the elements in groups, starting from one end of the array and stepping along to the other (Fig. 3.6). This produces an image with a

Bea m

ep swe

A

Figure 3.5 Phased array. (A) Diagram illustrating the steering of an ultrasound beam with a phased array transducer. The delay lines introduce small timing differences in the pulses driving the elements so that those at one end are fired earlier than those further along the array. This has the effect of steering the beam away from the centre line, rather as if the transducer face had been tilted. (B) Right lobe of the liver in a patient with a pleural effusion imaged with a phased array ultrasound system. D = diaphragm, E = effusion, k = kidney.

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Figure 3.7 Breast carcinoma (arrows). Image obtained with a 14 MHz linear array probe. The rectangular format is particularly suitable for superficial structures. F = fatty tissue, G = glandular tissue, P = pectoralis muscle.

Array elements

Beam sweep

Figure 3.6 Linear array. Diagram of a linear array showing the formation of one ultrasound beam by triggering a set of elements at one end of the probe. The next beam would be formed by the adjacent or partially overlapping set of elements so that the beam is swept along the transducer face to give a rectangular image.

rectangular shape, best suited for the superficial structures that are of prime interest in small parts imaging (Fig. 3.7). In a simple variant, the linear array is curved so that the field of view is trapezoidal, as with a sector scanner, but with a longer skin line. This compromise is particularly useful when both superficial and deeper structures need to be imaged, for example in obstetrics (Fig. 3.8). An important limit to the rate at which ultrasound information can be acquired is set by its speed in tissue (average in soft tissue, 1540 m s−1). It is necessary to wait for each pulse

Figure 3.8 Convex array. (A) Image of a fetal skull obtained using a 3.75 Hz convex array. (B) Transvaginal image of a uterus with a fibroid (arrows) obtained using a tightly curved array at 7 Hz. The convex format is a compromise between the footprint requirements of sector and linear probes and has the advantage of giving a wide field of view for deeper structures. M = midline, P = placenta, S = skull, U = uterus.

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to have faded away before the next is transmitted because, if the second pulse is sent too early, the last echoes from the first overlap early echoes from the second and are falsely registered on the image as superficial structures. To avoid this range ambiguity artefact, the pulse repetition frequency (PRF) must allow a delay of at least the time taken for the most distant echoes to return. In practice, this limits the PRF to about 1000 pulses per second. The clinical application dictates the way these pulses are distributed in time and space. They are spread apart and the field of view restricted to maximize the frame rate for echocardiography but the sacrifice in spatial resolution and the small image size are not ideal for general applications in which image quality is paramount. Here, the low frame rate is generally less of a sacrifice, so a high line density and wider field of view provide a reasonable compromise.

Resolution Ultrasound resolution must be considered separately for the two dimensions, along and across the beam. Depth or range resolution is simply determined by the length of the ultrasound pulse, which is kept as short as possible, usually about two wavelengths in length; this equates to a shorter pulse if higher frequencies can be used and this is the main reason for the improved resolution of high-frequency systems. Lateral resolution, in contradistinction, depends on the width of the ultrasound beam. This is mainly controlled by mechanical or electronic lenses. The ultrasound emitted from a point source spreads in a hemisphere; however, as the source is enlarged, it forms a beam with near-parallel sides for several centimetres before the beam diverges again (Fig. 3.9). The changeover is the transition between the near (Fresnel) and far (Frauenhofer) fields. In fact, it is the point beyond which the ultrasound waves from the edge of the transducer arrive less than a wavelength later than those from the transducer’s centre, and this is why larger aperture transducers have a longer near field. The beam is actually formed by the same interference effects that are exploited to steer the beam in electronic transducers and which occur because the compression and rarefaction phases of the ultrasound pulse summate in the direction of the beam but cancel elsewhere. Adding a converging lens (usually a curved layer of plastic bonded to the front of the piezo material), or simply shaping the transducer face into a shallow dish, acts to narrow the beam. This can be thought of as working in the same way as an optical lens, i.e. by beam refraction, but a more useful concept is based on the fact that the lens conducts ultrasound more rapidly than tissue, so that waves emanating from the transducer edge are fractionally ahead of those from the centre as they enter the body. Thus, interference patterns are set up across the sound field that emphasize the centre region of the ultrasound beam and cancel ultrasound waves that would otherwise spread laterally. The same effect can be produced with a multi-element array by sending the transmit pulses to the outer elements fractionally ahead of those to more central elements; this is the

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Figure 3.9 Ultrasound beam shapes. The shapes of the ultrasound beam from four transducers are indicated. All are of the same frequency (3.5 MHz). The beam from the 10 mm probe in (a) has a complex region close to the transducer face, then a mid portion with near parallel sides, before the beam spreads out in the far field. The white lines indicate the half-power limits. Increasing the probe diameter (b) improves the overall beam width. In (c), weak focusing has been added by concave shaping of the crystal. This further improves the beam shape in the focal zone but causes it to spread more severely further out. This would be a useful compromise for general abdominal data acquisition. Stronger focusing (d) exaggerates these effects, producing a fine beam but only over a short distance. This would be useful for data acquisition in superficial structures.

electronic equivalent of shaping the transducer surface into a dish (Fig. 3.10). Focusing also occurs on receipt of the echoes, in a reciprocal fashion. While electronic focusing is complex, it confers two benefits. First, the focal position can be altered by changing the delays within the transmit pulse so that the probe can be optimized for each clinical situation. Secondly, on receipt of the echoes, the focus can be set close to the transducer initially (to optimize resolution of superficial tissues) and then be progressively refocused deeper into the body to track the train of echoes returning from deeper interfaces. This dynamic focusing optimizes resolution over the entire depth of the image. Tight focusing of the ultrasound beam has the undesired effect of accentuating its divergence in the far field, so that the beam is only optimal over a short depth (Fig. 3.9d).While such a transducer would be appropriate for structures where only a narrow strip of tissue is of interest (e.g. the eye), generally a better compromise is to use weak focusing together with as large an aperture as can reasonably be maintained in contact with the skin. In practice, the ultrasound beam achieved is far from perfect (Fig. 3.11). Not only is the optimum beam width achieved over only a relatively short focal depth, but its profile also leads to smearing of signals from strong reflectors because they are detected from some distance off-axis (Fig. 3.12). In addition, any real beam has side lobes that are emitted at steep angles from the main beam so that unwanted echoes may be received from interfaces that lie a long way off-axis. These signals further smear the image, particularly when strong reflectors such as gas bubbles lie in their direction.These limitations also apply across the imaging plane, so that out-of-plane reflectors may

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also interfere. Minimizing the loss of spatial and contrast resolution that results from these deficiencies is a major emphasis of the art and science of transducer design and is an area in which marked progress continues to be made (e.g. by using tissue harmonic imaging).

Delay lines Pulser

ARTEFACTS: CLINICAL INSIGHTS INTO ULTRASOUND PHYSICS

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Array elements

Focal zone

Figure 3.10 Electronic focusing. Diagram to illustrate the principle of electronic focusing. The delay lines are set to send the pulses from the outer elements fractionally ahead of those from more central elements. The resulting interference patterns accentuate the central part of the beam and cancel the off-axis portions. The effect is greatest at the focal zone.

The assumptions made in generating ultrasound images are that ultrasound travels at a constant speed in tissue and that the beam is ‘well behaved’. Artefacts arise whenever these principles are violated. The speed of ultrasound varies by only a few per cent in watery soft tissues but fat conducts approximately 20% more slowly. This means that the depth of echoes arising beyond large fatty regions is overestimated so that they are depicted as being further away from the skin than they actually are. It may be seen as a shelf in the diaphragm behind a fatty tumour in the liver (e.g. a lipoma). An even more dramatic illustration of this same artefact occurs with silicone implants, in which the ultrasound velocity is about half that of soft tissue (Fig. 3.13).The chest wall deep to a breast prosthesis, for example, can appear to be twice its true distance from the skin. The difference between the velocity in adipose and watery tissues can refract the ultrasound beam so that it deviates from its straight-line path. A gross version of this artefact occurs in the hypogastrium, where the fatty wedge lying between the lower ends of the two rectus abdominis muscles acts like an optical prism. The refraction of the ultrasound beam in transverse suprapubic images can produce double outlines of pelvic structures and even, in extreme cases, complete double images. This artefact may well be the cause of the ‘vanishing twin’ phenomenon (when one of a pair of twin embryos disappears early in pregnancy), described when ultrasound was first introduced in obstetrics. More generally, the different velocities at multiple small tissue–fat interfaces produce minor deviations of the ultrasound beam that defocus and disperse it. The clinical effect of this is loss of contrast, the image appearing noisy and blurred

Figure 3.11 Ultrasound beam plot. The complexity and marked deviation from the ideal of a practical diagnostic ultrasound beam is shown in this intensity plot. The beam is very complex for the first few millimetres from the transducer face (on the left of the figure) but improves towards the focal zone, where it reaches an effective diameter of a few millimetres, before spreading out again in the far field. Unfortunately, some ultrasound energy is also sent out as side lobes at angles to the main beam, further complicating the effective beam shape. These divergences from the ideal narrow shape limit both the spatial and contrast resolution of ultrasound images. (Beam plot kindly supplied by Dr Adam Shaw of the National Physical Laboratory, Teddington.)

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Figure 3.12 Beam width artefact. In this abdominal image in a patient with ascites, the intense echoes from gas in a loop of bowel have spread across into the fluid (arrowhead). This artefact results from the finite width of the ultrasound beam. A = ascites, B = bowel.

Figure 3.14 Beam dispersion by fat. Deep to this fatty renal hilum, the retroperitoneal tissue layers (arrowheads) are less clear than adjacent tissue planes because the hilar fat has defocused the beam. S = renal sinus.

(Fig. 3.14).The problem is worse when there is marked admixture of fatty and watery tissues, as may occur in fatty infiltration of muscle, a feature that may explain why poor images may be obtained from an out-of-training athlete. The degradation of ultrasound images and its variability from patient to patient are two of the most important limitations to the diagnostic use of ultrasound: strenuous efforts are being made by equipment manufacturers to investigate and minimize these problems. The use of tissue harmonics has greatly reduced this interpatient variability and thereby the number of unsuccessful examinations. A ‘well-behaved’ beam would be laser-thin and travel directly through the tissues to and from the transducer. The real-life situation is far from this ideal: the effects of beam spreading, side lobes, refraction and diffraction on spatial and contrast resolution have been mentioned. Multiple reflections are another common artefact that produces a series of

parallel false images of flat interfaces that happen to lie parallel to the skin. They are the result of repeated reflections of the incident ultrasound pulse between the transducer and the flat surface or between two such surfaces within the body. A common example is seen as parallel lines deep to the superficial fascia produced by the ultrasound being reflected from the transducer back into the tissue a second time. Similar linear artefacts are commonly seen in the superficial portions of the lumen of viscera such as the bladder and gallbladder and in blood vessels. The difficulty in measuring the thickness of the superficial intima–media layer of the carotid artery results from this artefact (Fig. 3.15). Rereflection from the transducer surface is reduced by applying matching layers which make it less reflective by reducing the impedance mismatch between the transducer and the skin, resulting in much less noisy images. A similar situation is produced by the closely packed bubbles in the foam that may occur in bowel gas. Here, the intense reflections repeat in near-random sequence, depending on the precise arrangement of the bubbles, to produce a train of echoes that fades over a few millimetres as the ultrasound energy dissipates. On the screen, a bright streak, the ‘comet tail’ artefact, is seen extending for a few millimetres deep to the gas. The same effect may occur deep to foci of calcification and behind metallic or plastic foreign bodies. Where a flat reflector lies at an angle to the ultrasound beam, ultrasound may be sent back into the tissue at an angle and then be reflected back from any interface it encounters. These echoes retrace the incident pathway and are picked up by the transducer, to be depicted as though lying deep to the angled reflector, exactly as objects are seen ‘through’ an optical mirror. This ‘mirror image’ artefact is commonly encountered at the air–pleura interface above the diaphragm: the echoes apparently above the diaphragm actually arise from the hepatic or splenic parenchyma (Fig. 3.16). They are quite different from the appearance of the lung examined intercostally when a very strong linear echo is seen, usually followed by strong reverberation echoes that fade over a few millimetres.

Figure 3.13 Velocity artefact from a silicone prosthesis. On this breast scan, the echofree ovoid is a prosthesis (S) inserted following removal of a tumour. The low speed of sound within it has distorted the pleural line (P) so that it appears to lie deeper behind the prosthesis (arrows) than to either side.

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Figure 3.15 Reverberation artefacts. (A) Multiple internal reflections within tissue layers give rise to false repeated signals which are most obvious where they fall over echo-free fluid spaces such as the gallbladder (arrowheads). (B) Although the intima–media layer is well delineated at the deeper surface of this normal common carotid artery (arrow), the superficial layer is mostly obscured by reverberation artefact. C = common carotid artery.

Figure 3.16 Mirror image artefact. Structures in the liver, such as cysts (arrowhead) in this patient with dominant polycystic kidney disease, are mirrored at the air–pleura interface and appear in the position of the lower lobe of the lung. When this surface is absent, for example when a pleural effusion is present, the effect does not occur (compare Fig 3.5).

INTERPRETATIVE PRINCIPLES Shadowing and increased through transmission Acoustic shadowing and increased through transmission of sound (often referred to as enhancement, a term better reserved for the signal-augmenting effects of microbubble contrast agents) are important components of the ultrasound image. Shadowing occurs when little or no ultrasound can penetrate an interface and results in a dark band over the deeper tissues, bounded by the ultrasound beam lines, which are parallel for a linear transducer and radiating for a curved or sector transducer (Fig. 3.17). Shadowing is reduced when compounding is used. Absorption and reflection are the two main causes of shadowing. If a portion of the tissue being imaged absorbs ultrasound faster than the background for which the TGC is adjusted, tissues deeper to the highly attenuating region are undercorrected and appear darker than adjacent tissue. Fibrous tissue and, to a lesser extent, fat attenuate more than average and are common causes of acoustic shadowing (e.g. in a fatty liver, behind scars, and behind scirrhous breast carcinomas). High attenuation also partly accounts for the shadows seen deep to calcific lesions such as biliary and renal stones; note that in this case the intense reflection is the main factor. Whatever proportion of the incident ultrasound is reflected is not available to continue through

for imaging. For stones, this amounts to about 60% of the incident energy, but for tissue–gas interfaces almost all the incident ultrasound is reflected and these produce dense shadows. In this case, the shadows are often partially filled in by reverberant echoes caused by the efficiency of these gas–tissue boundaries as reflectors, so that reverberation artefacts commonly occur. This noise in gas shadows has given rise to their designation as ‘dirty shadows’, as compared to the ‘clean shadows’ behind stones, and this is a useful differential diagnostic feature. Whether a stone or gas bubble actually casts a shadow depends on its size because about three-quarters of the beam must be obstructed to cause a shadow. If a stone is smaller than this, or lies away from the central axis of the beam, enough ultrasound passes beside it to insonate the deeper tissues. In practice, shadowing is usually apparent behind renal and biliary stones of 5 mm or more in diameter; much smaller calcifications may shadow if high-resolution transducers are used. Groups of fine calcifications can also shadow if their aggregate size and density is high enough (e.g. in nephrocalcinosis). A third important type of shadowing is ‘edge shadows’, sometimes known as ‘refractive shadows’, a description based on one explanation of their origin. They are seen as fine, dark lines extending deep to strongly curved surfaces. Cysts and the fetal skull are typical examples and fascia is often also responsible; for example, the fine shadows seen beyond Cooper’s ligaments in the breast and those caused by the neck of the

Figure 3.17 Acoustic shadowing. The dark band (arrows) deep to the gallstones (G) is an example of shadowing produced by a combination of high absorption and reflection. L = liver.

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gallbladder. These edge shadows must be recognized as being different from attenuating and reflective shadows to avoid errors in their interpretation. Increased through transmission is the opposite of attenuation shadowing: a region of tissue has a lower than average attenuation and so the TGC (which is adjusted to compensate for the average attenuation) is inappropriately high for that region so that echoes from deeper tissues are overamplified. The phenomenon is the hallmark of cystic spaces and the ‘bright up’ is often accentuated by the darker banding lines of the edge shadows typically formed from the cyst wall (Fig. 3.18). Even those fluid cavities that contain echogenic material, such as suspended crystals in the gallbladder, pus, blood or necrotic tissue, usually still produce increased transmission, depending largely on the proportion of fluid present. However, some solid tissues also show increased sound transmission, usually because they have a high proportion of fluid. Many tumours fall into this category, especially fibroadenomas in the breast, while lymphomatous deposits and inflammatory masses may behave in the same way.

Echogenicity The prime determinant of the strength of ultrasonic echoes is the impedance mismatch (Z ) between adjacent tissue components. At the risk of being somewhat simplistic, in practical clinical terms this may be understood as interfaces between tissues of different densities.The larger the mismatch, the stronger the echo, so that interfaces between soft tissues and bone, for example, give very strong echoes; however, within soft tissues, the most significant components are fibrous tissue (often in the form of the perivascular microskeleton) and fatty tissue. Thus, while uniform regions of fibre or fat are echo-poor (subcutaneous fat and retroperitoneal fibrosis are examples), admixtures between them and watery tissues give stronger echoes. A second important factor is the concentration of the scatterers: for a given impedance mismatch, a region that contains a large number of scatterers is more echogenic than one where they are spread out. Commonly, the ‘dilution’ of scatterers is caused by high water content. The low reflectivity of the

Figure 3.18 Increased sound transmission. The echoes (arrowheads) deep to this liver cyst (C) appear brighter than those from the rest of the liver; this is because the cyst fluid attenuates less than the solid liver and so signals from beyond it are relatively overamplified.

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Figure 3.19 Prostatic carcinoma. Small malignant tumours are usually relatively echo poor, as in this example (arrowheads). More advanced tumours have complex echo patterns as necrosis, fibrosis and calcification develop. This transverse image was obtained using a transrectal endoprobe.

congested liver in right heart failure is an example. Malignant tumours are a general case: until they grow large enough to undergo necrosis or calcification they tend to be echo-poor (Fig. 3.19). Similarly, the oedematous tissues in acute inflammation give low-level echoes (e.g. the echo-poor pancreas in acute pancreatitis). On the other hand, the high concentration of reflectors is the cause of the echogenic kidneys in recessive (infantile) polycystic renal disease—the interfaces between the innumerable cysts cause strong echoes (Fig. 3.20). Strong echoes are also obtained from the multiple interfaces of the vessel walls of haemangiomas, and even stronger ones from angiomyolipomas in which there is also admixed fatty tissue.

DOPPLER ULTRASOUND The Doppler principle has been utilized in diagnostic ultrasound since 1954. Colour Doppler is a refinement of the technique whereby the regions of blood flow are displayed

Figure 3.20 Echogenic kidney in recessive polycystic renal disease. The multiplicity of interfaces between the numerous small cysts results in high-intensity echoes from what would otherwise be expected to be an echo-poor process. k = kidney, L = liver.

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in colour as an overlay on the grey scale 2D image. ‘Duplex’ is used to imply that two types of information are being collected simultaneously: typically 2D imaging (possibly with colour Doppler) and spectral Doppler. The Doppler effect is a change in the frequency of sound being reflected from a moving target. In its simplest form in diagnostic ultrasound equipment, it is used to detect the beating fetal heart lying anywhere in the sound field of a large, unfocused and continually transmitting transducer.With these systems there is no way of determining either the direction of motion or depth of the fetal heart beneath the transducer, an advantage in this clinical application because the fetal heart beat can be detected successfully without accurate positioning of the transducer. In vascular applications, a wide, continuous ultrasound beam might result in confusing signals being received from several vessels simultaneously. This limitation is overcome by utilizing a narrow beam, similar to that used for imaging, and by transmitting the ultrasound in short pulses and processing only the information returning from a specific depth. Accurate positioning of the sensitive area of the beam (the sample volume) is achieved by positioning an electronic marker in the 2D image. Array transducers permit the collection of Doppler information while continuing with real-time imaging, albeit at a reduced frame rate since the machine has to share the pulses between the modes.

near the vessel wall so blood can be considered as flowing in a series of concentric layers (laminae), the blood in adjacent laminae having different velocities (Fig. 3.21). This type of flow is termed ‘laminar flow’ which is assumed in many of the calculations made from Doppler data. However, flow is nonlaminar in many vessel segments, including near bends, branches and junctions, and around plaques of atheroma. Values derived from Doppler signals in these circumstances may be inaccurate. If flow is not pulsatile and the velocity is not high, the ‘velocity profile’ across the vessel is approximately parabolic (Fig. 3.22). If the blood is flowing fast or is being accelerated rapidly, it tends to move with the same velocity, so-called ‘plug flow’ (Fig. 3.23). In a major artery the flow usually approximates to plug flow during systole and to parabolic flow during diastole.Venous flow is normally parabolic. The term turbulent flow is frequently misused to imply any form of flow disturbance: strictly speaking, it should only be applied to describe the complex flow disturbance that results from blood being forced at high velocity through a

Theoretical basis of Doppler studies

Figure 3.21 Laminar flow. Diagrammatic representation of the concentric layers of blood flowing at different velocities with the highest velocity in the centre of the vessel.

An ultrasound beam insonating a blood vessel is partially reflected by red blood cells. If these are moving, there is a change in the frequency of the reflected pulse: an increase in frequency if the flow is towards the probe and a decrease if it is away from it. This is the Doppler effect and the changes in frequency, referred to as the Doppler shift, may be calculated from the equation:

ƒd =

2ƒo ν cos θ c

This indicates that the Doppler frequency shift ( fd) depends on the transmitted frequency ( fo), the velocity of the blood (v) and the angle between the ultrasound beam and the direction of flow (θ).The speed of ultrasound (c) is constant. If the angle is known and the frequency shift measured, the blood flow velocity may be calculated by the scanner’s computer. The operator places a cursor appropriately in the vessel and marks the direction of the vessel axis. It is necessary to achieve an angle of considerably less than 90 degrees between the direction of blood flow and the direction of the ultrasound beam, as no Doppler signal results if the beam/vessel angle is 90 degrees (cos 90° = 0 in the above equation). The accuracy of the calculated velocities is inversely proportional to the beam/vessel angle. At an angle of zero degrees the error is up to 3%, at 70 degrees it is 30% and at 80 degrees it may approach 100% (see Fig. 3.38).

Figure 3.22 Parabolic velocity profile. The fastest flow is in the centre of the vessel, with a progressive reduction in velocity towards the vessel wall.

Characteristics of blood flow When blood is flowing in a straight vessel, the drag effects of the vessel wall and the viscosity of blood slow the flow

Figure 3.23 Plug flow. The flow velocities are almost equal across the whole vessel diameter.

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small orifice. The mildest form of flow disturbance (usually encountered near a moderate stenosis) results in an increase in the range of velocities present, giving rise to spectral broadening in the Doppler trace. More severe lesions may be accompanied by ‘disturbed flow’ in which eddies or vortices of flow occur beyond the lesion, giving rise to simultaneous forward and reverse flow components in the Doppler signal. The flow velocity waveform through the cardiac cycle depends on cardiac function, the type of blood vessel and the state of the distal vascular bed. Elastic arteries such as the femoral, supplying high-resistance beds, exhibit a pronounced triphasic flow pattern (Fig. 3.24). There is a rapid systolic upstroke but, because of the combination of elasticity and high peripheral resistance (if the supplied muscles are at rest), almost immediate flow reversal occurs, resulting in a transient negative Doppler component. There may be no forward flow during diastole. However, if the peripheral resistance is low, as in the internal carotid, hepatic and renal arteries, a uniphasic pattern is seen with forward flow throughout diastole (Fig. 3.25). A switch from the former to the latter occurs in the limb vessels with exercise and in the mesenterics with digestion. The waveform of the display may also be modified by many factors above, at, or below the sampling site. In a major artery the waveform is determined by cardiac contractility, aortic valve function, the proximal arterial tree, the state of the vessel at the examination site and disease in the distal arterial tree supplied by the vessel. When quantifying the severity of a stenosis, it is important to be clear as to whether a reduction in cross-sectional area (CSA) or diameter is being described; for example, a 70% diameter reduction gives rise to a 90% area reduction (Table 3.2). When the CSA of an artery is narrowed by up to 50% (diameter reduction 30%) there is no reduction in the volume of blood flowing and there must therefore be an increase in the peak flow velocity. This is usually accompanied by an increase in the range of velocities present (spectral broadening) (Fig. 3.26). If the stenosis is greater than 50%, there is a much greater increase in the velocity, and the flow beyond the steno-

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Figure 3.25 Low resistance flow. The flow is continuously forward throughout the cardiac cycle with moderately high flow throughout diastole. There is very little low-velocity flow throughout most of the cardiac cycle (compare with Figs 3.26 and 3.27).

sis forms eddies (disturbed flow) that give rise to 100% spectral broadening with small amounts of simultaneous reverse flow (Fig. 3.27). The disturbed flow propagates for a few centimetres beyond the lesion. Narrowing of the CSA by more than 75% (50% diameter reduction) reduces volume flow, which produces a fall in flow velocity in the proximal vessel segment. Stenoses of more than 90% CSA reduction (70% diameter reduction) give rise to a severe reduction in volume flow, very high jet velocities through and beyond the lesion and turbulence beyond the lesion (Fig. 3.28). In addition, there is an increase in the pulsatility of the flow proximal to the lesion and a decrease beyond. These indirect signs may be the only available indicators of disease in some clinical situations; for example, in renal artery stenosis, where the stenotic segment may not be accessible to ultrasound examination.

Information in the Doppler signal The spectral Doppler signal consists of a mixture of continually varying frequencies that, by chance, fall in the audible range so that the signal may be evaluated simply by amplifying it and feeding it to a loudspeaker. The frequency content and

Table 3.2 RELATIVE VALUES FOR AREA AND DIAMETER REDUCTION IN STENOSES

Figure 3.24 Normal common femoral artery flow. There is triphasic flow with early diastolic flow reversal.

Diameter reduction (%)

CSA reduction (%)

10 20 30 40 50 60 70 80 90

20 36 51 64 75 84 91 96 99

95

99.75

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Figure 3.26 Moderate spectral broadening. The spectrum throughout late systole and most of diastole has been filled in by an increased range of blood flow velocities.

waveform of the signal, however, contain a wealth of information about the nature of the blood flow in the vessel and it is easier to appreciate and interpret these if a visual display is created. This is derived from a ‘spectrum analyser’ which determines the strength of components in the Doppler signal that fall into each of numerous frequency bands during a time interval of typically 5–20 ms. The resultant display represents frequency on the vertical axis and time on the horizontal axis. The brightness of the tracing at any point indicates the amount of signal at each specific frequency over each time interval and is proportional to the number of red cells in the sample volume that are moving at each velocity (Fig. 3.29). The outline of the spectral display gives information about the direction of the flow, the maximum Doppler frequency at any time, and the nature and magnitude of any pulsations or other periodic changes in flow velocity. By convention, flow towards the transducer is displayed above the baseline and away from the transducer below. Clearly there is a great deal of information in the Doppler signal and currently we do not have techniques for extracting it all. There are, however, several simple observations that permit the diagnosis and grading of disease, and some of these can be supported by simple mathematical calculations.

Pulsatility measurements Many indices of waveform analysis have been devised but only two are in regular clinical use. These are the resistance index (RI) (also known as the Porcelot index) and the pulsatility index (PI) (also known as the Gosling index). Because they are ratios, they are independent of the beam/vessel angle (although obtaining a good quality Doppler trace from which to make the measurement does require a beam/vessel angle of < 60 degrees). Their derivations are:

Figure 3.27 Complete spectral broadening. There is now complete filling of the spectrum throughout the cardiac cycle, with brief periods of simultaneous reverse flow during systole.

Figure 3.28 Turbulence beyond a stenosis. There is high-velocity flow beyond this portal vein stenosis, with simultaneous forward and reverse velocities.

Figure 3.29 Close-up view of the spectral trace. The spectral trace is composed of increments on both the vertical and horizontal axes. The horizontal increments indicate the individual time intervals during which Doppler sampling occurs, 20 ms in this example. The vertical increments indicate increasing frequency. The brightness of the trace within each pixel indicates the number of blood cells moving with that velocity at that time.

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Resistance index =

Pulsatility index =

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maximum velocity − minimum velocity maximum velocity maximum velocity − minimum velocity time-averaged maximum velocity over a cardiac cycle

The PI was devised to characterize the triphasic flows typically seen in the femoral artery. Its main disadvantage is that it requires calculation of the mean peak frequency, whereas the RI only requires the measurement of two values. The RI is particularly sensitive to changes in downstream flow resistance and was devised to assess changes in diastolic flow in lowresistance vascular beds. The resistance may be increased by vascular stenosis or by disease in the organ supplied by the vessel. However, as it also depends on the ‘end diastolic’ velocity, the RI increases as the heart rate decreases, allowing a longer duration for the diastolic flow to fall (Fig. 3.30). In theory, it is possible to correct the RI for a normalized heart rate; in practice, however, this is seldom done.

Spectral content The distribution of the shades of grey in each time slot indicates the range of flow velocities present in the vessel at that time. If there is plug flow, this distribution is very narrow (Fig. 3.31A), whereas parabolic flow gives rise to a wider range of frequencies (Fig. 3.31B). The spectral broadening produced by a stenosing lesion is shown in Figure 3.28.

Colour Doppler With this form of display, areas of blood flow are represented as colour within the image. It has become common practice to represent flow towards the transducer as red and flow away as blue (Fig. 3.32). The operator can reverse these assignments and select alternative colours.The velocity information used is a cruder estimate of the mean velocity in each location compared to the spectral information described above. For some clinical applications the colour may be set to vary with the variance of the velocity rather than mean velocity; this may be helpful for the detection of flow disturbance or turbulence as an indication of the site of significant vascular disease. The Doppler

V

1

2

T

Figure 3.30 Dependence of RI on heart rate. The value of enddiastole is relatively high if the heart rate is rapid (1). A slower heart rate allows a greater time for diastolic deceleration, leading to a lower enddiastolic velocity (2) and an apparently higher resistance index. V = velocity, T = time.

Figure 3.31 (A) Spectral distribution in plug flow. A very narrow band of velocities is present throughout the cardiac cycle in this artery. (B) Spectral distribution in parabolic flow. The slower flow in this wide portal vein gives rise to a wide range of velocities during each time interval.

information is collected in rapid sequence from a large number of discrete picture elements. The derived velocity information displayed at each pixel is built up from a number of consecutive ultrasound echoes, and this necessarily reduces the number of complete frames of Doppler information that can be acquired in any time period.The frame rate for colour Doppler is therefore about one-quarter of that for grey scale imaging, although this problem can be alleviated by reducing the width of the Doppler gate and by increasing the size of each pixel. In practice, a compromise between frame rate, image area spatial resolution and accuracy of the colour velocity information has to be accepted. The main advantages of colour Doppler are the ease with which vessels can be detected and their patency confirmed. In many applications this may be all that is required for confirming that a structure is a vessel, or that a known vessel is patent. Where relevant, the direction of flow can also be easily confirmed (e.g. in the portal vein). The wealth of information contained in the Doppler spectrum is not available in the colour image, however, and it is often necessary to perform a conventional spectral Doppler study as well. The positioning

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Power Doppler is useful for depicting slow flow in smaller vessels—for example, in the kidney (Fig. 3.33)—and in malignancies.The reduction in signal strength when a volume element is only partially within a vessel gives an apparent improvement in vessel wall definition (Fig. 3.34). A further practical advantage is the reduced dependence on the beam/vessel angle. This is mainly because the direction information is averaged in colour Doppler and cancels out if the beam/vessel angle is close to 90 degrees (Fig. 3.35A). In power Doppler the direction information is ignored and the signal amplitudes are averaged. As these are all positive, a strong signal results (Fig. 3.35B).

VOLUME FLOW MEASUREMENT

Figure 3.32 Colour convention in colour Doppler. Fetal circle of Willis. The flow in the right middle cerebral artery, the left anterior communicating artery, the left posterior communicating artery and the right posterior cerebral artery are displayed in red as the flow is towards the transducer. The flow in the other vessels is passing away from the transducer and is therefore represented by blue.

of the Doppler gate is greatly facilitated by colour Doppler and made more accurate. In addition, colour Doppler readily shows up vessels that are too small to be resolved in the 2D image and that otherwise could not be studied. The major clinical applications of colour Doppler are the same as those for conventional spectral Doppler, although the ease of examination is improved and the operator’s confidence enhanced. In addition, colour Doppler permits the detection of very small vessels and the assessment of the number and distribution of vessels within a tissue volume. This is of relevance when attempting to record blood flow signals from vessels such as the renal arcuate arteries or the uterine arteries, and in the assessment of the vascularity in and around focal lesions. For example, the colour Doppler-detected vascular pattern around malignant breast lesions shows more numerous vessels, often with abnormal courses, than are seen in benign lesions, and primary hepatomas appear more obviously vascular than metastases in the liver.

It is theoretically possible to measure the volume of blood flowing within a vessel using Doppler ultrasound. This requires calculation of the mean blood velocity in the vessel

Figure 3.33 Power Doppler display of a right kidney. This extended field of view (Siemens ‘Siescape’) shows the flow in the IVC, main renal vessels and the intrarenal vessels right out to the capsule. The loss of directional information prevents differentiation of arteries from veins. (Courtesy of Siemens.)

Power Doppler The Doppler information used in power Doppler is the same as for colour Doppler but the velocity information is discarded and usually also the direction information.The colour hue is modulated by the strength of the Doppler signal, which, in turn, is proportional to the number of red cells moving within the sample volume.The display is thus a map of the distribution of moving red cells above the sensitivity threshold of the system. Large vessels give high signals, while the presence of both tissue and small vessels in the sensitive region gives a weaker signal. Fortunately, the random noise that impairs conventional velocity colour Doppler is self cancelling with this form of display, thus enabling higher gains (around 10 dB) to be used and increasing the sensitivity for vessel detection.

Figure 3.34 Vessel wall definition. Normal carotid artery. The power Doppler display colour intensity decreases near the vessel wall owing to the volume elements lying partly outside the vessel. This gives an apparent improvement in the definition of the intimal surface.

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Figure 3.35 (A) Colour Doppler with 90-degree beam-to-vessel angle. There is poor flow detection and direction ambiguity throughout the vessel. (B) Power Doppler display with 90-degree beam-to-vessel angle. As direction information is not used in the display, uniform flow detection is achieved throughout the vessel segment.

and the cross-sectional area of the vessel. The product of these two values should be the volume of blood flowing. In practice, there are significant uncertainties about both values, which may lead to errors in excess of 100%. Calculation of the mean velocity should take into consideration the distribution of velocities across the vessel in each time interval and the average of these over several cardiac cycles (Fig. 3.36). It is also assumed that the vessel is uniformly insonated and that signals are detected from all the blood in the cross-section of the vessel. In practice, slow-moving blood is missed and the range gate or beam width may encompass only a fraction of the cross-sectional area. These errors may not be obvious from visual inspection of the spectral display. If the crosssectional area of a vessel is calculated from a single diameter, any error is squared. Measuring the area from an image at right angles to the vessel axis may be more accurate, but this information cannot be obtained at the same time and site as

Figure 3.36 Calculation of time-averaged mean velocity. The weighted mean velocity during each time interval has been calculated. The average of these throughout the trace is a close estimate of the true mean velocity.

the Doppler signal, owing to the inappropriate beam/vessel angle. Volume blood-flow measurement in the carotid and femoral vessels and in the abdomen has not been shown to be of clinical value.

DOPPLER ARTEFACTS, ERRORS AND PITFALLS Doppler examinations are subject to a range of artefacts and potential errors that are not encountered in 2D imaging.

Sample volume size and position The shape of the sample volume is determined by the length of the range gate and the width of the ultrasound beam at the depth of the gate. The depth and length of the sample volume are determined by the operator and should be matched to the size of the vessel under investigation. If the sample volume is too small or does not encompass the whole cross-section of the vessel, the resulting spectrum underestimates the range of velocities present in the vessel. In scanners with array transducers, the beam width can be altered and many automatically focus the beam at the depth of the range gate. This is seldom advisable since, although it may improve sensitivity, it leads to undersampling in large vessels such as the portal vein. Similarly, if the sample volume is small and the vessel to be studied is mobile, a discontinuous Doppler signal results. If the movement of the vessel is due to respiration, the cause for the changes in the spectral display can usually be recognized. If, however, an artery moves as a result of intrinsic pulsations it may move in and out of the beam with each cardiac cycle. This can give rise to loss of the diastolic signal in each cycle, resulting in falsely high PI and RI values (Fig. 3.37). If the range gate is too large or the beam width too great, more than one vessel may lie in the beam at the same time and give rise to a confusing spectral display, especially if flow in both vessels is in the same direction. Sometimes such a feature is of positive advantage; for example, when searching for a

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Figure 3.37 (A) Normal superior mesenteric arterial trace. The vessel has remained within the range gate throughout the cardiac cycle, giving a satisfactory Doppler trace. (B) Artefactually abnormal SMA trace. Same case as Figure 3.37A. The range gate is too small and is misplaced. The vessel is moving out of the range gate during diastole, giving rise to the false appearance of increased vascular resistance.

renal vein signal alongside the renal artery.The actual length of the sample volume is usually greater than that displayed on the image. This has led to the false assertion that it is acceptable to have a sample volume smaller than the vessel diameter.

Velocity information An important source of error when attempting a velocity calculation is the effect of the beam/vessel angle. This shows the percentage error in velocity calculation that may be expected for different angles. At angles greater than 50 degrees there is a rapid increase in error that approaches 100% at 80 degrees (Fig. 3.38). Major errors may also arise from the way the mean velocity is calculated: calculating the mean value of the peaks is only accurate for pure plug flow (Fig. 3.39). Strictly, the mean velocity should be calculated for each time interval, taking into account the distribution of velocities in that time interval.The mean of a large number of these values over several cardiac cycles should then be calculated (Fig. 3.36). For a vessel with true laminar flow and a parabolic profile, this more accurate method produces a value half that of the mean peak method. The pulse repetition frequency (PRF) of the ultrasound system imposes limitations on the range of Doppler frequencies that can be measured. The maximum value of the PRF is limited by the depth from which echoes are to be recorded. In abdominal diagnosis this may be up to 15 cm. In order to allow time for the echoes to be received before the next pulse is transmitted, about 250 µs must elapse between pulses.Thus, the pulses can only be repeated at about 4000 s−1 (4 kHz).The Doppler detectors can only measure frequencies accurately if they are less than half of the PRF (the Nyquist limit), i.e. less than 2 kHz in this example. Doppler shift frequencies above this level are frequently encountered in the abdomen, are misinterpreted by the apparatus, and displayed on the wrong side of the baseline, giving rise to a characteristic discontinuous waveform display (Fig. 3.40A). The technical term for this phenomenon is ‘aliasing’ and it may sometimes be overcome by viewing the vessel from a steeper angle, using a lower ultrasound frequency,

a higher PRF or continuous Doppler beam, or by electronic correction (Fig. 3.40B).

Wall filters The pulsating walls of arteries give rise to high-amplitude, low-frequency Doppler signals that may overload the spectrum analyser and appear in the spectral display as high-intensity spikes. This ‘wall thump’ can be filtered out by rejecting the

100 90 80 70 Error in velocity

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60 50 40 30 20 10

10

20

30

40

50

60

70

80

Degrees

Figure 3.38 Dependence of velocity error on beam-to-vessel angle. The error in velocity calculation is less than 10% for angles of less than 50 degrees. There is a rapid and unacceptable rise in the error rate for angles greater than 70 degrees.

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of colour reversal are contiguous (Fig. 3.43). If the flow reversal is genuine, the forward and reverse flow colours are separated by a black margin.

SAFETY OF ULTRASOUND

Figure 3.39 Mean peak velocity calculation. Automatic software has calculated the peak instantaneous velocity for each time interval throughout the cardiac cycle. The mean of these values is the mean peak velocity.

very low frequencies in the Doppler signal. If the ‘wall filter’ is set too high, however, true flow information may be lost (Fig. 3.41). For abdominal venous studies, a filter value as low as 25–50 Hz is appropriate. In some makes of scanner, settings up to 800 Hz are available for arterial studies and would eliminate the Doppler information from many veins.

Colour artefacts The most common problem with colour Doppler is failure to appreciate that the colours represent flow direction with respect to the transducer. If a vessel curves or bifurcates in the image plane, the flow in different segments will be represented in different colours.The same artefact may result if a straight vessel is imaged with a curvilinear or sector transducer (Fig. 3.42). As with spectral Doppler, aliasing also occurs in colour flow imaging and results in reversal of colour and thus apparent flow reversal. Aliasing can be identified by noting that the areas

An important feature of diagnostic ultrasound, especially in obstetric applications, is its apparent safety. No study has shown any damaging effect of pulsed ultrasound at diagnostic intensities when applied to the intact fetus in utero. These studies include follow-up assessments of growth, the development of cataracts and hearing loss, and the induction of childhood malignancies. Occasional reports of effects (usually unimportant and found on searching the data collected for other purposes, a statistically unacceptable methodology) have failed to be substantiated on repeat studies. One curiosity that does seem to be statistically sound was the unexpected finding in a Norwegian study that male fetuses imaged with ultrasound were less likely to be right-handed (23% were left-handed or without a dominant hand, compared with 17% in controls). While unimportant in itself, this suggests that ultrasound can induce changes in cell migration at an early developmental stage. There have been several reports of biochemical alterations to cells in suspension, including changes to DNA and surface membrane behaviour, both of which are obvious at high intensities but are demonstrable also (at least in some studies) at diagnostic power levels. It is debatable whether these effects are significant for the intact animal and it is notable that many of them have proved to be elusive when repeat studies have been attempted.They do, however, inject a note of caution and reinforce the importance of using common sense in restricting the use of high-power modes and long imaging durations to situations in which the clinical benefit outweighs any possible ill effects: there is no place in medicine for a quick (i.e. inadequate) ultrasound or for ‘just to have a look’ (e.g. at a fetus).

Figure 3.40 Frequency aliasing. (A) The frequencies above the Nyquist limit have appeared on the wrong side of the baseline. (Note that no beam-tovessel angle has been set so the velocity values are uncorrected and therefore meaningless.) (B) The aliased peaks have been electronically transposed to their correct locations.

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Figure 3.41 Inappropriately high wall-thump filter. The wall-thump filter has been set at 200 Hz and has removed all the low velocity information in this venous study.

The entire subject of safety is under continuous review and up-to-date information is available from the European Federation of Societies for Ultrasound in Medicine and Biology (www.efsumb.org). Ultrasound intensity is the energy flowing across a surface in unit time; the usual units are watts per square centimetre. For pulsed ultrasound, a peak or average value may be taken. Because of focusing, the energy distribution along and across the beam is nonuniform, and the peak intensity at the maximum point is usually quoted. Mean spatial peak temporal average intensities for B-mode imaging are ~175 mWcm−2, and for spectral Doppler ~1600 mWcm−2. High intensities of ultrasound are capable of causing significant biological effects. These are used to therapeutic benefit

Figure 3.42 Artefactual flow reversal on colour flow imaging. Flow within the splenic vein (arrowheads) is from left to right. In this transverse epigastric scan, on the left side of the image the flow is towards the curvilinear array probe and is therefore displayed as red. On the right side, the flow is away from the probe and is therefore displayed as blue. There is a thin black area at the point where the colour changes, indicating a true flow direction reversal, rather than aliasing, as the cause of the colour change. A = aorta, I = inferior vena cava.

Figure 3.43 True and artefactual colour flow reversal. The highvelocity jet through this portal vein stenosis has given rise to aliasing. The aliased green signal passes through yellow to red in a continuous gradation (in the vertical limb of the vessel in this display). The coarse vortex within the poststenotic dilatation gives rise to a true area of flow reversal, colour-coded blue, which is separated from the forward flow red component by a black margin.

both in physiotherapy, when the changes sought (mainly local heating) are often reversible in nature, and in ultrasound surgery, when cell killing is the aim. The primary mechanism inducing biological change is thermal. The ultrasound beam is attenuated during its passage through tissue, some of the lost energy (20–40%) being scattered by tissue structures and the remainder absorbed, thus leading to heating. In the case of B-mode imaging and Doppler examinations of soft tissue, this phenomenon results in a biologically insignificant temperature rise. Significant temperature rises may, however, be induced when a Doppler beam at its highest power is incident on a bone surface because of the high absorption at this interface where the impedance changes markedly. The problem is worst in the case of spectral Doppler, in which the beam is held over one tissue region for long periods of time. It is therefore recommended that Doppler exposures should be performed at the lowest power level consistent with obtaining the desired information and that the time the beam is held stationary is kept to a minimum. Particular care is advised when Doppler is used during late pregnancy, when the skull has begun to calcify, and in examining the neonatal brain in the vicinity of the skull. The vibration of particles caused by a high-intensity ultrasound beam may produce mechanical disruption of intracellular membranes, and the pressures can cause fluids to flow in streaming movements. Extreme ultrasound powers can produce regions of such low pressure during the rarefaction phase of the cycle that dissolved gases (mainly nitrogen) can come out of solution, or water may vaporize to produce minute gas

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bubbles that pulsate in the sound field. This process, known as cavitation, can cause mechanical damage to the tissue and even lead to ionization. Cavitation is unlikely to occur at diagnostic imaging intensities in vivo but has been demonstrated with the higher powers and continuous-wave conditions used in ultrasound therapy. Safety-related information as presented to the operator is regulated by the FDA’s output display standards (ODS) which are calculated predictions of the possible effects in tissue. There are two indices, one of which, the mechanical index (MI), indicates the probability of mechanically induced damage: an MI of 1 warns of the possibility of mechanical effects in tissue. The second is the thermal index (TI), which is related to possible heating of tissues. Separate indices have been defined for soft tissue and for bone (TIS and TIB, respectively) because heating at a bone surface is likely to be higher. A TIS of 1 suggests that, in the worst case, tissue could be heated by 1°C; since damage is unlikely until temperature rises of 1.5°C or more are achieved (and maintained for some time), this is a conservative estimate, as is the MI indication. Although rather vague in their real-life meaning, the ODS does provide guidance to users, who can then decide whether any possible risk to, for example, the fetus, is outweighed by the potential benefit of the examination.

DEVELOPMENTS IN ULTRASOUND High frequencies, 3D, elastography Three-dimensional ultrasound (3D US) has become available on many machines and the data can be acquired rapidly enough to allow display in real-time at low frame rates (called 4D). It has found niche applications, mainly for the display of complex anatomy such as the fetal face and the heart. In most parts of the body the clean surfaces that are required for true 3D rendering are not present; however, reslicing in otherwise unobtainable planes has proved useful in some situations; for example, to display the uterus in the coronal plane for depicting developmental anomalies. Elasticity imaging (or elastography) is a new imaging method that is promising because of the very high contrast it offers between masses, especially tumours, and the host tissue. The principle is simple: obtain signals before and after applying a distorting force (stress) that moves the tissues by a few millimetres, and create an image of the tissue’s response (strain) by comparing the two. In principle, any imaging method can be used: ultrasound has the advantage that the transducer can be used to apply the stress and of working in real-time; magnetic resonance imaging has also been used successfully. The information used to create the elastograms is similar to clinical palpation except that it is much more sensitive, especially to deeper structures. It has been applied to the breast and the prostate and is an active research area. A commercial device that estimates liver elasticity as a measure of fibrosis to assess the need for antiviral therapy in hepatitis has been developed.

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Contrast agents An important development has been the introduction of microbubble agents to enhance ultrasound signals. They exploit the very high reflectivity of microbubbles small enough to cross the lung capillary bed, so that systemic (including myocardial) ultrasound enhancement can be achieved following an intravenous injection. Their gas content makes them very reflective, even at high dilution, and initially this was exploited using Doppler to enable signals to be obtained from small vessels and from those where the signals are attenuated by overlying tissue such as the intracranial arteries under the skull. However, by virtue of their compressibility, microbubbles display unique properties in an ultrasound beam, which sets them into resonance when there is a match between their diameter and the ultrasonic wavelength. Fortuitously, for microbubbles in the 2–7 µm range (needed to allow transcapillary passage) this occurs at ultrasound frequencies of 2–10 MHz. As the acoustic pressure increases and still well within diagnostic levels, the compression and expansion phases become asymmetrical because it is harder to compress a bubble than to expand it.This nonlinear behaviour produces echoes that contain frequencies not present in the transmitted pulses. Many of these are higher frequency harmonics at twice the transmitted frequency. An elegant way to extract these nonlinear signals is to send a series of pulses down each line, varying their phase and amplitude; the returning signals are combined to cancel the linear signals from tissue and the remaining bubble-specific signals are used to form an image that can be presented as a colour overlay on the B-mode image or shown on a side-by-side display, all in real-time. As these contrast-specific methods are exquisitely sensitive, low transmit powers can be used (MIs of 0.1 or 0.2) such that the fragile microbubbles are not destroyed, allowing continuous imaging for their life of around 5 min after injection. Since they do not depend on microbubble motion, they can be detected even in the microcirculation, a major advantage over Doppler techniques. A major technical difficulty with making small bubbles is that their surface tension is so high that they collapse and dissolve within a few seconds of formation.To produce enhancement of useful duration, the microbubbles must be stabilized by encapsulating them in a membrane such as denatured albumen or a phospholipid. The gas is also critical to achieving good resonance (and therefore echogenicity) as well as providing a useful duration after injection. Air or inert gases such as perfluorocarbon compounds are the most frequently used (Fig. 3.44). Microbubbles extend to ultrasound many of the features of angiography, such as demonstrating tissue perfusion where infarction is a clinical question and demonstrating bleeding points (the microbubbles are confined to blood vessels unless there is active haemorrhage). The temporal filling patterns of focal lesions such as liver masses can be studied in similar ways to dynamic CT and MRI methods and this has become an important clinical application. Contrast-enhanced ultrasound is now incorporated into European guidelines for hepatoma detection in cirrhosis. They have proved invaluable in monitoring the extent of liver ablation using ultrasound-guided

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the arterialization of the hepatic blood flow in cirrhosis and in malignancy by timing the delay from injection to the appearance of microbubbles in the hepatic veins: a long delay of around 40 s is normal and reflects the fact that three sets of microcirculation have to be crossed by portal blood. Arterialization, however, leads to a much earlier arrival (< 25 s) and this seems to be a sensitive marker for these diseases. An approach that may be especially important for the myocardium depends on the fragility of many types of microbubble such that they are destroyed by the ultrasound beam at the higher ranges of permitted intensity. If, after such

Figure 3.44 Fibrous nodular hyperplasia: enhancement after intravenous administration of a microbubble contrast agent. The baseline longitudinal section through the right lobe of the liver (A) shows a subtle subcapsular lesion (arrowheads). The system was then reset to display the contrast image on the left (using Contrast Pulse Sequences) and the B-mode image on the right, both with low MIs. SonoVue (2.4 ml) was given IV and the haemodynamics of the flow through the lesion observed in real time. At 19 s (B), the lesion had enhanced markedly—the ‘light bulb sign’ of a hypervascular lesion—and its feeding vessel was apparent (arrowhead). By 35 s (C), the liver had enhanced to the same extent as the lesion, which therefore disappeared, indicating that it contains normal liver tissue. This sequence is pathognomonic of focal nodular hyperplasia. (With thanks to Siemens Medical, Mountain View, CA for provision of the CPS software and Bracco, Milan for supply of SonoVue.)

RF or laser techniques because remaining perfused tumour can be detected immediately and treatment extended to complete ablation in the same session; previously, contrast CT was required and the patient would have to return for a second ablation session. In addition, using these agents as tracers to measure time– intensity curves analogous to those used in dynamic radioisotope studies is now possible, launching ultrasound into a new functional era of great potential. One promising approach reveals

Figure 3.45 Reperfusion study. (A) With an infusion of a microbubble (in this case SonoVue) to produce a steady blood level, a high-intensity power Doppler pulse has been used to inactivate the agent in this renal transplant; this is the first frame after the ‘flash’ whose position is indicated by the green box. (B) After a few seconds interrogation with a low intensity beam (an MI of < 0.2 was used here) in the pulse inversion mode, the hilum of the transplant has reperfused and is again returning a signal. (C) Several seconds later the entire cortex has filled with contrast agent. The rate of recovery of these signals relates to the speed of blood flow, an important physiological measurement. (With thanks to Siemens Medical, Mountain View, CA for provision of the PI software and Bracco, Milan for supply of SonoVue.)

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a destructive pulse (or ‘flash’), the tissue is interrogated with a low-power, nondestructive beam, the speed with which microbubbles (and therefore red blood cells) reperfuse the slice can be measured (Fig. 3.45). The slope of this refill curve relates to flow rate, while its peak level relates to the fractional vascular volume, the two measurements needed to estimate true perfusion. Although its potential importance in ischaemic heart disease is obvious, it also illustrates the innovative ways that the special properties of microbubbles can be used—in this example to create a ‘negative bolus’ for haemodynamic measurements. Microbubbles can be modified as vehicles to carry useful compounds such as therapeutic agents, including DNA and oligonucleotides, as well as ligands for biochemical processes such as activated endothelium. This opens up possibilities for molecular imaging and for directed drug/gene delivery. Physiotherapy-level ultrasound can be used not only to release the payload but also to create transient pores in cell membranes that facilitate cell uptake. The therapeutic applications of microbubbles could overtake their diagnostic uses.

Ultrasound therapy Ultrasound also seems likely to find a role in tissue ablative therapy, particularly in oncology. Therapeutic ultrasound uses the thermal effects of high-power ultrasound beams that are tightly focused so that very small target tissue regions can be heated and coagulated, and dedicated transrectal therapy systems have been marketed. There is also considerable research interest for the treatment of hepatic and renal lesions. Although the general approach is similar to radiotherapy, ultrasound therapy has the advantages of being much more precise, rapid (the entire process could be completed in one session), easy to handle and of not damaging adjacent tissues. It is also possible to monitor its effects in real-time with diagnostic ultrasound. The physical limitations to accessible anatomical regions are the same as for diagnostic ultrasound.

SUGGESTED FURTHER READING Physics Evans D H, McDicken W N 1999 Doppler ultrasound: physics, instrumentation and signal processing. Wiley, Chichester Hill C R (ed.) 2001 Physical principles of medical ultrasound, 2nd edn. Wiley, Chichester

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Hoskins P R, Thrush A, Whittingham T 2000 Diagnostic ultrasound: physics and equipment. Greenwich Medical Media, London Hykes D L, Starchman D E, Hedrick W R 2004 Ultrasound physics and instrumentation. Mosby, St Louis Kremkau F W 1997 Diagnostic ultrasound: principles and instruments. W B Saunders, Philadelphia

Clinical Baxter G M, Allan P L, Morley P (eds) 1999 Clinical diagnostic ultrasound. Blackwell, Oxford Bluth E I, Peter H, Arger P, Carol B, Benson C B 2000 Ultrasound: a practical approach to clinical problems. Thieme, Stuttgart Callen P W 2000 Ultrasonography in obstetrics and gynecology. Elsevier, Philadelphia Rumak C M, Wilson S R, Charbonneu J W (eds) 2005 Diagnostic ultrasound, 3rd edn. Mosby-Year Book, St Louis Zwiebel W J, Pellerito J S 2004 Introduction to vascular ultrasonography. Elsevier-Saunders, Philadelphia

Safety Abbott J G 1999 Rationale and derivation of MI and TI: a review. Ultrasound Med Biol 25: 431–442 Barnett S B, ter Haar G R, Ziskin M C, Duck F A, Maeda K 2000 International recommendations and guidelines for the safe use of diagnostic ultrasound in medicine. Ultrasound Med Biol 26: 355–366 ter Haar G, Duck F A 2000 The safe use of ultrasound in medical diagnosis. British Institute of Radiology, London

New developments Albrecht T, Cova L, Frauscher F, Solbiati L, Thorelius L 2005 Contrastenhanced ultrasound in clinical practice. Springer, Berlin Goldberg B B (ed.) 2001 Ultrasound contrast agents, 2nd edn. Martin Dunitz, London Nelson T R, Downey D B, Pretorius D 1999 Three-dimensional ultrasound. Lippincott Williams & Wilkins, Philadelphia Quaia E (ed.) 2005 Contrast media in ultrasonography. Springer, Berlin

Acknowledgements Dr Gail ter Haar (Royal Marsden Hospital, London) kindly reviewed the section on Safety.

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Ashley S. Shaw and Adrian K. Dixon

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Computed tomography: a brief history Technical overview of MDCT Image reconstruction and analysis Clinical applications of MDCT Whole body MDCT in asymptomatic adults Radiation dose considerations Radiotherapy Future directions

COMPUTED TOMOGRAPHY: A BRIEF HISTORY The first CT machine used for clinical purposes, developed by the late Sir Godfrey Hounsfield, was installed at the Atkinson Morley Hospital, London, in the early 1970s1. Each axial image of the head took several minutes to acquire and days to reconstruct at the EMI laboratories. Over the next decade, CT machines became faster as the processing power of computers improved. In the mid-1980s, the development of slip-ring technology enabled continuous revolution of the X-ray unit, which reduced the acquisition time and allowed helical data to be acquired2. Since the late 1990s, the focus of development has been on reducing the size of the detectors in order that they could be arranged in multiple rows along the z-axis.This permits the acquisition of multiple ‘slices’ simultaneously, thus reducing acquisition time yet further. At the time of writing, ‘state of the art’ CT systems have up to 64 rows of detectors, allowing up to 4 cm to be imaged per revolution, a revolution time around 0.4 s, and with a resolution of approximately 0.4 mm.

TECHNICAL OVERVIEW OF MDCT Before multidetector CT, imaging protocols and patient throughput were frequently limited by the time taken for the tube to cool between exposures. Refinements in tube design now ensure that multiple phases of imaging can be performed without overheating, as the tube cools faster than the throughput of patients. These design improvements also allow increas-

ingly complex studies of small structures, which require the focal spot to be kept to an absolute minimum even when the mA is increased. For example, one manufacturer offers a focal spot measuring 0.6–0.9 mm, depending on the mA used. The X-rays are detected by various forms of detector. A ceramic scintillator, for example, absorbs the X-rays and produces visible light. This stimulates a photodiode to produce an electrical signal from which the image can be constructed. In order to reach the spatial resolution, detectors have become smaller (typically around 0.6 mm), more sensitive (allowing some dose reduction) and react faster (allowing increased gantry rotation speeds). In short, the smaller each detector is, the smaller the possible collimation, whereas the wider the bank of detectors, the greater the potential coverage per rotation. Some manufacturers arrange detectors of varying width such that the smallest are positioned centrally and the largest positioned peripherally, whereas others use identically sized detectors across the array.The majority of machines in use are characterized by the number of detectors (e.g. 16-, 40- or 64-slice) and use a single focal spot on the tube. By contrast, one 64-slice machine has a 32-detector array with two rapidly alternating focal spots in the tube. In effect, this produces overlapping projections that are acquired and processed simultaneously. The end result of these advances is that the latest technology from all manufacturers is able to produce isotropic images with sub-mm resolution in all planes with ever-increasing rapidity.

IMAGE RECONSTRUCTION AND ANALYSIS The rapid acquisition of such large datasets has necessitated a change in radiologists’ approach to CT reporting. As a bare minimum, both thick and thin section axial images should be produced and stored. Images need to be viewedwon a workstation capable of producing images in all planes, with the ability to change window level and width. When viewing images, our experience has shown that, in addition to standard lung or soft tissue windows, review of the data on bone windows (preferably in the sagittal plane) often demonstrates unsuspected abnormalities (Fig. 4.1).The optimal

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Figure 4.1 Sagittal MPR imaged on bone windows, demonstrating multiple sclerotic lesions throughout the vertebrae in a patient presenting with lymphoma.

slice thickness will depend on the clinical question posed. Cardiac imaging, for example, will require sub-mm images, whereas renal calculi will be reliably visualized on images up to 3 mm thick, and the detection of lung nodules can be enhanced by scrolling through overlapping 10 mm images (allowing differentiation from branching blood vessels). For 3D viewing of datasets, there are four principal postprocessing techniques: multiplanar reconstructions (MPR), maximum intensity projection (MIP), surface shaded display (SSD) and volume rendered (VR) images (Fig. 4.2). MPR— and associated curved planar reconstruction (CPR)—simply allows the image to be viewed in any plane chosen, including a curved plane with CPR (Fig. 4.3). MIP displays the highest attenuation voxels in an image only, thus allowing visualization of structures (usually vessels) not in a single plane. However, visualization of arterial wall calcification can be difficult and vessels near to bony structures may be obscured. SSD gives 3D representations of the anatomy in grey scale, but is prone to noise and artefacts. VR allows visualization of the vessels distinct from the surrounding anatomy and is of particular value in cerebral angiography, where the vessels pass through and lie in close proximity to the skull base. Computer aided detection (CAD) of lung nodules is currently under development by a number of groups. Preliminary results indicate that, while more nodules can be detected,

Figure 4.2 (A) Coronal MPR demonstrating renal cell carcinoma at the lower pole of the left kidney extending to the hilum. (B) Coronal MIP demonstrating renal cell carcinoma at the lower pole of the left kidney extending to the hilum. (C) Coronal SSD demonstrating renal cell carcinoma at the lower pole of the left kidney extending to the hilum. (D) Coronal VR demonstrating renal cell carcinoma at the lower pole of the left kidney extending to the hilum.

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Dynamic perfusion CT (PCT)5 evaluates regional blood flow within the brain by serially imaging a limited area following the infusion of intravenous contrast medium.The resulting images give a computerized map of relative cerebral blood flow, mean transit time and cerebral blood volumes, albeit with limited coverage of the brain (Fig. 4.4)6. In the context of patients presenting with acute stroke, PCT is significantly more accurate than non-enhanced CT in detecting stroke

Figure 4.3 artery.

CPR demonstrating a normal calibre right coronary

there is a significant rise in the number of false-positive nodules. Although not current routine clinical practice, CAD may become a useful prompt in the evaluation of resectable metastases and on lung cancer screening programmes (should they prove to be of clinical value).

CLINICAL APPLICATIONS OF MDCT Neuroradiology In many areas, CT has been superseded by magnetic resonance imaging (MRI) for the evaluation of neurological disease as it gives superior differentiation of the soft tissues. However, CT remains the initial imaging investigation for many patients, particularly those presenting following trauma or with acute neurological syndromes. Digital subtraction angiography (DSA) has long been regarded as the gold standard for detection of an intracranial aneurysm. Single row detector helical CT could not acquire data sufficiently quickly to obtain reliable diagnostic angiographic studies. MDCT has been shown to be highly accurate in the detection of aneurysms, with a sensitivity of over 96% and specificity of 100% on a 16-detector row machine, identical to the DSA results3. Even for small aneurysms (< 3 mm), sensitivity remained over 90%. This has led to a significant change in neuroradiological and neurosurgical practice, enabling treatment to be planned from 3D images at a workstation, with a consequent reduction in the number of diagnostic angiograms performed. Furthermore, it is now possible to perform multiple phases of vascular imaging within the brain, obtaining both an arterial and a venous phase4. This may provide additional information in patients with an arteriovenous malformation, but needs further evaluation.

Figure 4.4 (A) Unenhanced CT of the head in a patient presenting with acute aphasia. (B) Cerebral perfusion map demonstrating delayed perfusion in the left middle cerebral artery territory. Images courtesy of Rosie Farmer, Addenbrooke’s Hospital, Cambridge, UK.

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(75–86% versus 66%), the extent of stroke (94% versus 43%), and has a high interobserver agreement7. This may prove to be of clinical use in those patients in whom thrombolysis or other novel therapies are being considered. Potentially, the technique can differentiate the ischaemic penumbra from infarcted tissue, identifying patients who would benefit from revascularization and those in whom unnecessary treatment could be avoided. The data obtained from this technique are very similar to that obtained with perfusion and diffusion-weighted MRI but CT is considerably easier in the acute situation. It is likely that routine clinical use will be guided by developments in therapy for acute stroke. Similarly, the use of perfusion CT following severe head trauma has been reported to yield independent prognostic information regarding functional outcome8, although again this is not part of current routine clinical practice.

Cardiac The rapid acquisition times and increased spatial resolution of MDCT probably holds the greatest potential for cardiac imaging. Imaging of the coronary arteries with CT has two major components: unenhanced coronary artery calcium scoring and contrast-enhanced coronary artery angiography. Electron-beam CT (EBCT) has been used for coronary calcium scoring for approximately two decades and is a highly sensitive method of detecting coronary artery atherosclerosis. A number of authors have shown there to be a high correlation between EBCT and MDCT. However, there is a well-recognized high interscan, interobserver and intraobserver variability and the consensus of the American Heart Association/American College of Cardiology is that the incremental value of calcium scores over traditional risk assessments has not been proven and that its use could only be justified in selected groups at intermediate risk9. CT coronary angiography is typically performed in a single breath-hold, with ECG gating, during a rapid (≤ 5 ml/s) infusion of iodinated contrast material (Fig. 4.5). The sensitivity and specificity of 16-detector row CT for detection of ≥ 50% luminal stenosis is around 90%10,11, although a significant proportion of the arteries (12%)11 were not demonstrated sufficiently well to be evaluated. However, the negative predictive value (NPV) of a normal study is reported to be 95%12 and thus could be potentially used to exclude cardiac disease in patients with chest pain.There are, of course, limitations: problems occur in patients with arrhythmias (e.g. atrial fibrillation), the heart rate should ideally be 60 beats per minute or below13, and beta-blockers may be necessary for optimal imaging. In order to detect a 10–20% change in stenosis, imaging will require an isotropic spatial resolution of 0.3 mm and an acquisition time of approximately 0.1 s—technical specifications that, as detailed above, are becoming possible with double tube 64-slice systems CT. It is anticipated that this development will further enhance the accuracy and reproducibility of coronary artery angiography and, importantly, give an overview of cardiac morphology and function. By using all the data during the various phases of the cardiac cycle, cine loops can provide ejection fractions and other objective measurements.

Figure 4.5 VR image of the heart depicting the coronary arteries.

Assessment of perfusion can be made on delayed imaging.The potential impact of noninvasive coronary imaging on clinical practice is clearly enormous, and will depend on the results achieved with newer MDCT technology.

Thoracic The imaging of patients with suspected pulmonary venous thromboembolism (PE) had, for many years, relied on either ventilation–perfusion (VQ) studies or pulmonary angiography. However, once CT became sufficiently fast to image the thorax with thin collimation (≤ 2 mm) in a single breath-hold, CT pulmonary angiography (CTPA) rapidly became the test of choice for many clinicians. Indeed, the number of patients referred for CT with suspected PE has increased dramatically since its introduction. This is likely to be due to increased awareness of the diagnosis in combination with easy access to an accurate noninvasive study. VQ studies expose the patient to a significantly lower radiation dose than CTPA, but have a number of drawbacks. There is a significant proportion in which the result will be indeterminate due to cardiorespiratory disease or an abnormal radiograph14. Once these are taken into account, the overall radiation burden to the population is only slightly (approximately 4%) higher using CTPA for all15. Moreover, the greater specificity of a positive CTPA, compared with a ‘high probability’ of PE, gives the clinician greater confidence in the diagnosis. The negative predictive value of a CTPA for PE is 99.4% in patients at 3-month follow-up, with a mortality attributable to PE within this time period of 0.01%16. The current generation of MDCT machines produces consistently high quality images of the pulmonary arteries down to the subsegmental level. However, the clinical significance of tiny peripheral emboli is unclear

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as they may not affect outcome17. Consequently, CTPA is now widely considered to be the equal of pulmonary angiography in terms of accuracy without the associated risks. Imaging of the venous system 2 min postinjection from the iliac crests to the popliteal fossa has been advocated by several groups for all patients undergoing CTPA. The evidence suggests that 20% of patients with a negative CTPA will have venous thrombosis in the legs18. However, it is difficult to justify replacing a highly accurate, noninvasive and radiationfree test (ultrasound) with CT, particularly as the gonads are unavoidably included in the imaging.

Vascular The high resolution and speed afforded by MDCT has a number of potential applications in the assessment of the vascular system elsewhere. The increased speed allows a ‘pure’ arterial phase study to be obtained; however, the faster the machine, the less forgiving it is. It is imperative that all such studies are either triggered by the arrival of contrast medium at a defined site or are based on a test bolus. In our practice, unenhanced and arterial-phase images are acquired. This aids detection of intramural haematoma or haemorrhage in acute patients and differentiates calcification from endoleak in treated patients. The commonest vascular application clinically is the assessment of aortic aneurysms, both before and after treatment.The enhanced resolution, particularly in the z-axis, together with multiplanar reconstruction (Fig. 4.6), allows accurate planning of endovascular or surgical repair. Following endovascular aneurysm repair (EVAR), MDCT is regarded by the Society of Interventional Radiology (SIR) as the gold standard for monitoring the aorta. Particular attention should be paid to the presence of any fractures or kinking of the stent on the unenhanced study. Following intravenous contrast medium,

Figure 4.6 Colour volume rendered image of the aorta demonstrating an infrarenal aneurysm extending down to the bifurcation.

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the presence of an endoleak will be seen as contrast medium within the aorta tracking into the thrombus and implies failure of the stent graft. Enlargement of the aneurysmal sac without an apparent endoleak is termed endotension. Visceral infarction, particularly involving the kidneys, should also be apparent on the arterial study. When using MDCT to investigate patients with peripheral vascular disease, it is important to appreciate that the flow rate down both normal and atherosclerotic peripheral vessels can be highly variable. Consequently, it is our practice to perform two test bolus studies: one in the lower aorta and a second in the popliteal fossa. We then subtract the time delay between the two and set the table speed accordingly. Post-processing of the data can be time consuming and the images in the distal vessels can be variable, as with all forms of peripheral vascular imaging. In our experience, the results from 16-detector row and above are comparable with magnetic resonance angiography (MRA) and have the advantage of providing bony landmarks to help treatment planning. Both of these techniques yield a 3D dataset, unlike conventional arteriography, and have the advantage of being noninvasive. It would seem likely that the role of MDCT in this field will grow in coming years, with arteriography increasingly reserved for therapeutic cases.

Trauma Accurate assessment of the cervical spine is of critical importance in trauma cases: the consequences of missing a significant injury are potentially devastating. The reported accuracy of plain radiographic studies is highly variable, but approximately 10–20% of significant cervical spine injuries will be missed through a combination of suboptimal radiographs, interpretation error and absence of radiographic signs19. In the obtunded patient, these problems are compounded by the absence of any clinical information from physical examination. Single detector row CT is superior to plain radiography, but the relatively poor resolution in the z-axis could prove problematic in identifying fractures in the axial plane. MDCT has overcome this with increased speed and resolution, such that the entire cervical spine can now be imaged and viewed in any plane within a matter of seconds. The sensitivity, specificity and NPV of MDCT are reported to be 98.1%, 98.8% and 99.7%, respectively, with many major trauma centres now using MDCT as the primary imaging method for evaluating the cervical spine in the obtunded trauma patient20,21. Imaging of the thorax and abdomen following trauma is usually performed with MDCT; ultrasound may be of use in confirming the presence of a haemoperitoneum in the unstable patient before laparotomy, but cannot reliably assess the full extent of solid organ or GI tract injuries. In addition to the non-enhanced imaging, the speed of image acquisition with MDCT allows the radiologist to perform each phase of the study at an appropriate delay following intravenous enhancement. The thorax should be imaged in the arterial phase, as deceleration injuries may lead to shearing injuries of the aorta (most commonly occurring at the isthmus, just distal to the origin of the left subclavian artery). The abdomen should ideally be imaged in the arterial and portal venous phases, in order

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that both vascular injuries (dissection, pseudoaneurysm, avulsion) and parenchymal injuries may be assessed. The pelvis is usually imaged in the portal venous phase. The sensitivity and specificity of CT for detecting bowel and mesenteric injury are approximately 80%22, while for solid organ injuries these approach 100%.

Gastrointestinal CT colonography (CTC) has been extensively investigated over the past decade, with the ultimate goal of providing an accurate, minimally invasive screening test for detecting colonic polyps before they become frankly malignant. The evolution of MDCT has enabled the development of CTC. Current best practice involves thin collimation (≤ 3 mm) and low dose imaging of the insufflated colon in both prone and supine positions following either purgative or faecal tagging with multiple doses of oral contrast media for 48–72 h23. The use of intravenous hyoscine is recommended by some authors. Reporting is usually, though not always, performed from the axial and MPR images with 3D endoluminal fly-through views used for problem solving. However, the precise techniques employed are as variable as the results achieved, which range from as low as 59% sensitivity for polyps > 10 mm24 to 93% (outperforming colonoscopy) in the detection of polyps > 8 mm25. CTC outperforms double contrast barium enema (DCBE) in all studies. The clinical significance of ‘missed’ and diminutive polyps has also been questioned, given the slow progression of polyps over time26. Moreover, there is wide variation in the reporting of polyps even among ‘expert’ readers27, illustrating that this truly is a technique in evolution from a technical perspective, with a steep learning curve for the radiologist. Multicentre trials are currently underway in the USA (ACRIN) and the UK (SIGGAR 1) to evaluate the use of CTC in the context of a screening programme, but at present the majority view is that colonoscopy should be viewed as the gold standard, with CTC likely to replace the DCBE in the future. Again CAD techniques are under evaluation.

identifying the arterial and venous anatomy of the donor for surgical planning. Following transplantation, we have found MDCT to be particularly useful in evaluating the vascular supply to the graft in cases of suspected ischaemia where US is nondiagnostic (Fig. 4.7).

Genitourinary The evaluation of a patient presenting with haematuria may involve intravenous urography, ultrasound, CT or MRI in combination with cystoscopy. Increasingly, MDCT is being used as the primary imaging investigation as it has a high sensitivity for detecting malignant lesions, calculi and traumatic injuries. The other major causes (infection, coagulopathy, instrumentation) may be diagnosed on clinical history and blood and urine testing.The technique employed should encompass an unenhanced study (to detect calculi), a nephrographic phase (approximately 100 s, to assess the renal parenchyma) and an excretory phase (8–10 min, to assess the ureters). The latter two stages may be combined by giving the intravenous contrast medium in two parts, 8–10 min apart, and then imaging 100 s after the second dose. This will significantly reduce the radiation dose to the patient. As MDCT may not depict flat tumours of the bladder wall, cystoscopy must not be omitted. The increased anatomical resolution and multiplanar reconstructions possible with MDCT have enabled its use for surgical planning. In particular, urologists are able to accurately assess whether resection of a malignant lesion requires partial or complete nephrectomy, whilst potential organ donors may be noninvasively evaluated with an accurate depiction of the renal vasculature.

Paediatric Imaging children with CT poses a number of problems. It requires cooperation with instructions and the need to remain still, requires a high degree of spatial resolution to depict smaller organs and their vessels and exposes patients to a relatively high dose of radiation. Some hold that around 1 per

Hepatobiliary The use of multiple phases of contrast-enhanced imaging has probably had the greatest impact in liver imaging, which is reflected in the extensive US, CT and MR literature on the subject. The detection and characterization of focal liver lesions is largely based on patterns of vascular enhancement, with the hypervascular lesions—hepatocellular carcinoma (HCC), regenerative nodules, focal nodular hyperplasia and adenoma—in particular providing diagnostic dilemmas. In order to optimize contrast enhancement, our practice is to trigger the CT study from the arrival of contrast in the abdominal aorta. CT-based surveillance programmes for early detection of HCC with cirrhosis consist of an arterial and portal venous phase study at the very least, with many centres also obtaining unenhanced images. Both early and late arterial phase imaging can be performed, but no additional benefit for this has yet been shown. In living related liver transplantation, MDCT may be used to determine liver volumes and is increasingly utilized for

Figure 4.7 Coronal MIP image demonstrating hepatic artery thrombosis with collateral arteries in a patient following liver transplantation.

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1200–2000 patients undergoing CT might develop cancer because of the effects of the CT radiation, and these risks are greater in children28. Advances in MDCT have led to a significant reduction in acquisition time, which has been shown to reduce the need for sedation of paediatric patients29. Simultaneously, it has become possible to reduce the collimation below 1 mm, dramatically improving the resolution, and thereby not only aiding the diagnosis but also enabling accurate assessment of congenital abnormalities and surgical planning, particularly in patients with malignancy. Unlike in adult patients, imaging in different vascular phases is discouraged because of radiation issues. Therefore it is important to select a single optimal imaging sequence whenever possible (e.g. in a Wilms’ tumour, the late arterial phase will also opacify the renal veins and upper IVC). Optimizing an MDCT study for a paediatric patient should also include reducing the radiation dose as much as is possible while maintaining diagnostic quality. Reducing the kV and/or mAs will significantly reduce the dose to the patient30, and this can now be modulated automatically during imaging on newer machines, giving a constant image signal-to-noise ratio throughout the study. Additionally, increasing the pitch reduces the radiation dose significantly without loss of diagnostic quality30.

WHOLE BODY MDCT IN ASYMPTOMATIC ADULTS Whole body CT imaging of asymptomatic patients is controversial, yet is becoming commonplace in several countries, particularly the United States. Clearly, the potential benefits of identifying early stage malignant lesions or coronary heart disease with one noninvasive test could be enormous, but as yet the case for whole body CT screening is far from proven. When considering these studies, it should be borne in mind that a single CT examination cannot be optimized for looking at all organs at once. Consequently, the sensitivity and specificity of a whole-body study is likely to be significantly lower than with the dedicated organ-specific studies currently being evaluated. Inevitably, further follow-up investigations will be required for incidental findings, resulting in anxiety and distress for the patient and occasionally lead to morbidity and mortality. Moreover, the radiation dose is nontrivial. A recent publication exploring the hypothetical situation of a 45-year-old man undergoing annual screening CT until the age of 75 calculated the overall estimated lifetime attributable risk of cancer mortality to be approximately 1.9% (1 in 50)31. This combination of high cost, low specificity and high risk indicates that it is unlikely that whole body CT screening would be of benefit to the population. In the UK, such CT examinations are not recommended by the National Screening Committee32.

RADIATION DOSE CONSIDERATIONS In the late 1980s, CT represented approximately 2% of radiological investigations and 20% of the collective dose to the

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population. In 2003–2004, it is estimated that this has increased to 9%, with the dose from CT contributing around half of all radiation from medical exposures33. Since 1997, CT has been designated a high-dose procedure by the European Union, along with interventional radiology and radiotherapy. The reasons for this expansion in practice have been outlined above, with MDCT able to perform increasingly complex diagnostic procedures noninvasively and, in some instances, requiring multiple phases of imaging. Furthermore, unlike conventional plain radiography, where the radiation dose from each exposure is to some extent regulated by automatic detectors (increasing the dose will result in an overexposed, dark radiograph of little diagnostic value), increasing the exposure factors (and patient dose) for a CT study will provide the user with higher quality images. More difficult to assess is the effect that an increasingly litigious society has had on the practice of medicine and in particular the number of requests for studies ‘to rule out’ underlying tumour, pulmonary embolism, etc., even when these are clinically unlikely. The responsibility for reducing patient dose should be shouldered by all parties. The referring clinician should ensure that the radiologist is given full clinical information to ensure that CT is indeed the most appropriate test. The radiologist should ensure that each study is justified, that the imaging protocols are optimized to answer the clinical question and that the dose to the patient follows the ALARA (as low as reasonably achievable) principle. CT manufacturers also play a key role in this area through the continued development of dose modulation and the installation of low-dose preset protocols. In order to maximize patient safety, it is essential that all these issues are addressed in each case.

RADIOTHERAPY Over the past decade, significant advances have been made in the planning and delivery of radiotherapy. The introduction of MDCT enabled the oncologist to map the extent of tumour in three planes, allowing accurate dose planning of irregular shapes while minimizing the dose to the surrounding normal tissues. This 3D conformal radiotherapy (CRT) results in a significant reduction in side-effects. However, there were limitations in corrections that could be made to the delivered dose. More recently, intensity modulated radiotherapy (IMRT) has been developed, whereby each radiation beam is divided into 1-cm2 ‘beamlets’, each delivering a different prescribed dose. This has reduced even further the dose delivered to the surrounding normal tissues through increasing accuracy of delivery. Current research in radiotherapy includes the development of techniques to account for movement during radiotherapy, particularly respiration, with 4D CRT. Moreover, techniques are being developed which take account of the changes to the patient and tumour (weight loss and tumour shrinkage) that occur during a course of radiotherapy, so-called adaptive radiotherapy. It is anticipated that both of these will again further the accuracy of radiotherapy with more precise dose delivery and reduced side-effects. The increasing use of functional imaging of tumours with 18FDG-PET is also beginning to impact on

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radiotherapy planning. The co-registration of anatomical and physiological images using CT-PET has resulted in significant advances in lung tumour radiotherapy in particular, as it is now possible to differentiate between the central obstructing tumour and distal collapse.

10.

11.

FUTURE DIRECTIONS The gantry speeds and coverage currently achieved in MDCT are more than adequate for almost all clinical applications. The most notable exception, cardiac imaging, will undoubtedly drive manufacturers to produce yet faster machines with greater coverage until high-quality,‘real-time’ images are achieved, which could potentially directly replace all diagnostic coronary angiography. A significant improvement in resolution will be more difficult to achieve using the current technology with up to 64 banks of detectors.This would require significant improvements in detector efficiency and size reduction. However, the next generation of CT machines may instead employ flat panel detectors. Early reports of prototype machines indicate that spatial resolution is greatly improved, with isotropic voxels of the order of 0.25 mm, with coverage of approximately 20 cm in the z-axis per revolution. However, contrast resolution is relatively poor and data acquisition is still slow on these machines at present. One of the most important potential applications for such high-resolution studies, in addition to those described above, would be imaging of the breast. Early reports indicate that the technique is feasible at a dose comparable to that from 2-view mammography, with the added advantages of better tumour localization and potentially better detection of tumours. The tumour detection and dose characteristics will clearly be of greater importance than the speed of data acquisition for breast work, but increased speed will be crucial for cardiac applications.

REFERENCES 1. Ambrose J, Hounsfield G N 1973 Computerized transverse axial tomography. Br J Radiol 46: 148–149 2. Kalender W A, Seissler W, Klotz E, Vock P 1990 Spiral volumetric CT with single-breath-hold technique, continuous transport, and continuous scanner rotation. Radiology 176: 181–183 3. Tipper G, U-King-Im J M, Price S J et al 2005 Detection and evaluation of intracranial aneurysms with 16-row multislice CT angiography. Clin Radiol 60: 565–572 4. Matsumoto M, Kodama N, Sakuma J et al 2005 3D-CT arteriography and 3D-CT venography: the separate demonstration of arterial-phase and venous-phase on 3D-CT angiography in a single procedure. Am J Neuroradiol 26: 635–641 5. Miles K A, Hayball M, Dixon A K 1991 Colour perfusion imaging: a new application of computed tomography. Lancet 337: 643–645 6. Gillard J H, Minhas P, Hayball M P et al 2000 Evaluation of quantitative computed tomographic cerebral perfusion imaging with H215O positron emission tomography. Neurol Res 22: 457–464 7. Wintermark M, Fischbein N J, Smith W S, Ko N U, Quist M, Dillon W P 2005 Accuracy of dynamic perfusion CT with deconvolution in detecting acute hemispheric stroke. Am J Neuroradiol 26: 104–112 8. Wintermark M, van Melle G, Schnyder P et al 2004 Admission perfusion CT: prognostic value in patients with severe head trauma. Radiology 232: 211–220 9. O’Rourke R A, Brundage B H, Froelicher V F et al 2000 American College of Cardiology/American Heart Association Expert Consensus document

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on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. Circulation 102: 126–140 Nieman K, Cademartiri F, Lemos P A, Raaijmakers R, Pattynama P M, de Feyter P J 2002 Reliable noninvasive coronary angiography with fast submillimeter multislice spiral computed tomography. Circulation 106: 2051–2054 Ropers D, Baum U, Pohle K et al 2003 Detection of coronary artery stenoses with thin-slice multi-detector row spiral computed tomography and multiplanar reconstruction. Circulation 107: 664–666 Schuijf J D, Bax J J, Salm L P et al 2005 Noninvasive coronary imaging and assessment of left ventricular function using 16-slice computed tomography. Am J Cardiol 95: 571–574 Cademartiri F, Mollet N R, Runza G et al 2006 Diagnostic accuracy of multislice computed tomography coronary angiography is improved at low heart rates. Int J Cardiovasc Imaging 22: 101–105; discussion 107–109 Cross J J L, Kemp P M, Walsh C G, Flower C D R, Dixon A K 1998 A randomized trial of spiral CT and ventilation perfusion scintigraphy for the diagnosis of pulmonary embolism. Clin Radiol 53: 177–182 O’Neill J, Murchison J T, Wright L, Williams J 2005 Effect of the introduction of helical CT on radiation dose in the investigation of pulmonary embolism. Br J Radiol 78: 46–50 Quiroz R, Kucher N, Zou K H et al 2005 Clinical validity of a negative computed tomography scan in patients with suspected pulmonary embolism: a systematic review. JAMA 293: 2012–2017 Prologo J D, Gilkeson R C, Diaz M, Cummings M 2005 The effect of single-detector CT versus MDCT on clinical outcomes in patients with suspected acute pulmonary embolism and negative results on CT pulmonary angiography. Am J Roentgenol 184: 1231–1235 Cham M D, Yankelevitz D F, Henschke C I 2005 Thromboembolic disease detection at indirect CT venography versus CT pulmonary angiography. Radiology 234: 591–594 Tins B J, Cassar-Pullicino V N 2004 Imaging of acute cervical spine injuries: review and outlook. Clin Radiol 59: 865–880 Brohi K, Healy M, Fotheringham T et al 2005 Helical computed tomographic scanning for the evaluation of the cervical spine in the unconscious, intubated trauma patient. J Trauma 58: 897–901 Griffen M M, Frykberg E R, Kerwin A J et al 2003 Radiographic clearance of blunt cervical spine injury: plain radiograph or computed tomography scan? J Trauma 55: 222–226 Elton C, Riaz A A, Young N, Schamschula R, Papadopoulos B, Malka V 2005 Accuracy of computed tomography in the detection of blunt bowel and mesenteric injuries. Br J Surg 92: 1024–1028 Taylor S A, Halligan S, Bartram C I et al 2003 Multi-detector row CT colonography: effect of collimation, pitch, and orientation on polyp detection in a human colectomy specimen. Radiology 229: 1–2 Rockey D C, Paulson E, Niedzwiecki D et al 2005 Analysis of air contrast barium enema, computed tomographic colonography, and colonoscopy: prospective comparison. Lancet 365: 305–311 Pickhardt P J, Choi J R, Hwang I et al 2003 Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 349: 2191–2200 Macari M, Bini E J, Jacobs S L et al 2004 Significance of missed polyps at CT colonography. Am J Roentgenol 183: 127–134 Johnson C D, Harmsen W S, Wilson L A et al 2003 Prospective blinded evaluation of computed tomographic colonography for screen detection of colorectal polyps. Gastroenterology 125: 311–319 Brenner D J, Elliston C D, Hall E J, Berdon W E 2001 Estimated risks of radiation-induced fatal cancer from pediatric CT. Am J Roentgenol 176: 289–296 Pappas J N, Donnelly L F, Frush D P 2000 Reduced frequency of sedation of young children with multisection helical CT. Radiology 215: 897–899 Donnelly L F, Emery K H, Brody A S et al 2001 Minimizing radiation dose for pediatric body applications of single-detector helical CT: strategies at a large children’s hospital. Am J Roentgenol 176: 303–306 Brenner D J, Elliston C D 2004 Estimated radiation risks potentially associated with full-body CT screening. Radiology 232: 735–738 Dixon A K 2004 Whole-body CT health screening. Br J Radiol 77: 370–371 Shrimpton P C, Hillier M C, Lewis M A, Dunn M 2005 Doses from computed tomography (CT) examinations in the UK—2003 review. National Radiation Protection Board, Oxon, UK

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Magnetic Resonance Imaging: Basic Principles

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Iain D. Wilkinson and Martyn N. J. Paley

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Historical perspective Spin physics Excitation and relaxation: free induction decay and echoes Signal localization: techniques for building images Instrumentation: magnets, coils and computers Physical parameters that provide contrast Pulse sequences Safety considerations Conclusion

This chapter considers the basic principles of the MRI technique. Magnetic resonance imaging (MRI) is a noninvasive method of mapping the internal structure and certain aspects of function within the body. It uses nonionizing electromagnetic radiation and appears to be without exposure-related hazard. It employs radiofrequency (rf) radiation in the presence of carefully controlled magnetic fields in order to produce high quality cross-sectional images of the body in any plane. It portrays the distribution of hydrogen nuclei and parameters relating to their physical surroundings in water and lipids. MRI has progressed over 30 years from being a technique with great potential to one that has become the primary diagnostic investigation for many clinical problems. Its application, initially limited to the neuro-axis, now covers all regions of the body and an increased knowledge base has provided a better understanding of how it can best be utilized, either alone or in conjunction with other techniques, in order to maximize diagnostic certainty. Technical advances have included improvements in spatial resolution, types of contrast and, in particular, speed of imaging. The range of information that can be obtained from a multitude of different types of image contrast is one of its biggest selling points: modern MR is truly multimodal, capable of depicting function as well as anatomy with a high sensitivity to the presence of disease.

HISTORICAL PERSPECTIVE The phenomenon of ‘nuclear induction’, later to be termed nuclear magnetic resonance (NMR), was described independently but almost simultaneously by Bloch1 and Purcell2 and their colleagues in 1946 and for this they were jointly awarded the Nobel Prize for Physics in 1952. Much later, for some reason the term ‘nuclear’ was dropped. In applications to medicine, it is now commonly referred to as magnetic resonance (MR). Since its discovery, NMR has been used extensively as a laboratory method for studying the properties of matter at the molecular level (NMR spectroscopy). In 1971, Damadian noted that in vitro, animal tumours had elevated MR relaxation times when compared to normal control tissue, and in the following year he filed a US patent: ‘apparatus and method for detecting cancer in tissue’. The application of MR to imaging required a method of spatial localization. Published in 19733, Lauterbur’s paper showed how this could be done by applying a linearly varying magnetic field across a liquid. In the same year, Mansfield and Grannell reported revealing structure within a solid by the use of a linear magnetic field gradient4. Human in vivo images were first published in 1977 by Mansfield and Maudsley5, Damadian et al6 and Hinshaw et al7. Multiplanar imaging ability was first demonstrated by Hawkes et al in 1980, who also reported the first demonstration of intracranial lesions8, and 1980 also saw the introduction of the basis of the most common spatial encoding method – spin-warp imaging by Edelstein et al9.The introduction and subsequent improvements in diffusion, perfusion, flow and spectroscopy from a large number of groups have been providing fascinating new insights into cerebral and cardiac pathology10–16. Functional MRI (fMRI) of the brain, which uses endogenous blood oxygen level dependent (BOLD) contrast, was introduced by Ogawa et al in 199217 and developed by Rosen et al18. Methods have been developed that have enabled areas that have previously been difficult to assess, such as pulmonary ventilation, to be imaged with the aid

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of hyperpolarized helium gas19. New parallel encoding methods used with phased-array rf coils, such as SMASH introduced by Sodickson et al in 199720 and SENSE introduced by Pruessmann et al in 199921, are changing the rules of imaging speed, particularly when coupled with the introduction of 3T whole-body systems.

SPIN PHYSICS MR describes the phenomenon whereby the nuclei of certain atoms, when placed in a magnetic field, absorb and emit energy of a specific or resonant frequency. Nuclei suitable for MR are those which have an odd number of protons or neutrons and therefore possess a net charge distribution. They also exhibit the property of nuclear spin, which gives them angular momentum. The combination of charge and angular momentum causes these nuclei to behave as magnetic dipoles. Almost all medical images produced to date have used the simplest of all nuclei, that of hydrogen (a single proton), which is present in virtually all biological material and exhibits relatively high MR sensitivity. Other relevant naturally occurring nuclei include phosphorus (31P), sodium (23Na), carbon (13C) and potassium (39K). Noble gases such as helium (3He) and xenon (129Xe) can also be made sufficiently sensitive by laser pre-polarization techniques. The proton can be regarded as a small, freely suspended bar magnet spinning rapidly about its magnetic axis. Place a group of protons in a uniform magnetic field and their magnetic moments experience a torque, tending to line them up with the applied field. Due to thermal energy not all of the spins line up and at body temperatures the difference in numbers between those that do and those that do not (the net magnetization) is small. The stronger the applied magnetic field, the larger the net magnetization and the higher the available MR signal.The direction of the applied magnetic field conventionally defines the z-axis, which is generally in the craniocaudal direction in the common cylindrical imaging magnet configuration. Because the nuclei are spinning, they respond to the magnetic torque like a gyroscope and their axes are tilted so they rotate about the magnetic field’s axis in a movement termed ‘precession’. The frequency of precession is directly proportional to the applied magnetic field. For protons in a field of 3T, it is almost 128 MHz. This relationship is expressed by the Larmor equation: f0 = γB0 where f0 is the resonant frequency, γ is the gyromagnetic ratio (constant for a nuclear species) and B0 is the applied magnetic field.

EXCITATION AND RELAXATION: FREE INDUCTION DECAY AND ECHOES If rf energy is then applied, there is a strong interaction or resonant effect, providing that the frequency of the rf is equal

to the proton precession frequency. This is called magnetic resonance (MR) and manifests itself in the following way: rf energy is absorbed by the nuclei causing the motion of the nuclear dipoles to be disturbed (they become ‘excited’). Their net magnetization along the z-axis deviates through an angle that depends upon the amount of rf energy absorbed. Once the applied rf is turned off, the magnetization gradually returns to its equilibrium position. As it does so, the changing magnetization induces a small voltage in a receiver coil. In its simplest form, the electrical signal detected following an rf pulse is known as the free induction decay (FID), the size and length of which is determined by the sample’s proton density and relaxation times. The time it takes for the net magnetization to revert back to its equilibrium position along the longitudinal z-axis is governed by the longitudinal or T1 relaxation time. In this way, energy is given up by the spins to the overall structure or lattice (T1 can be called the spin–lattice relaxation time) and once the energy associated with a given excitation pulse has decayed away by this mechanism, it cannot be retrieved: you have to start again by applying another rf excitation pulse, imparting more energy to the system. In addition to the transfer of energy to the overall structure, the spins interact with each other. As this occurs, their net magnetization in the x–y plane (perpendicular to the z-axis) becomes less coherent or dephases. The rate at which it does so is governed by T2, the transverse or spin–spin relaxation time. As will be described below, for a given rf excitation pulse, part of the T2 decay or dephasing can be reversed, leading to the production of echoes. Due to the different nature of T1 and T2 decay, T2 can never be longer than T1. In liquids, T2 starts to approach the value of T1 and in human tissue, T2 is approximately a tenth of T1.The spin–spin interaction (T2 decay) can be hastened by the presence of local changes in magnetic field homogeneity. When this occurs, the transverse magnetization decays with time constant T2*, which is shorter than its intrinsic T2. So far, the production of a FID has been described, occurring after termination of an rf excitation pulse.To facilitate the spatial encoding process and to enable ‘weighting’ of the signal by various contrast mechanisms in differing proportions, it is necessary to delay the production of the signal. Within the overall decay envelope given by T2 relaxation, a signal echo (or echoes) can be formed in different ways. The two most common types of echo are the spin echo and the gradient echo (or field echo) (Fig. 5.1). Both cause rephasing or refocusing of the transverse magnetization (in the x–y plane) at an echo time (TE) following the excitation pulse. Spin echoes are produced by an 180-degree, second rf pulse which flips the spins over in the x–y plane: instead of spreading further apart, they refocus, moving into phase with each other again, pass through a maximum and then dephase once more. Gradient echoes are, as the name suggests, produced by the introduction of a magnetic field gradient: the gradient causes the spins to realign in the x–y plane while they are ‘pointing’ in the same direction (i.e. without flipping them over). At sufficiently long TE, spin echoes and gradient echoes produce signals that are

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90
rf

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Echoes

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Figure 5.1 Schematic depiction of signal formation: (A) application of a 90-degree rf pulse leads to the production of the free induction decay (FID); (B) a spin echo (SE) is produced at the echo time (TE) by the application of a 180-degree rf pulse at TE/2; (C) a gradient echo (GE) is produced by the application of a magnetic field gradient (G).

T2-weighted and T2*-weighted, respectively; that is, different tissues having different T2 and T2* relaxation times yield different signals that depend on the values of those relaxation times. There are other echo types: Hahn (or partial) echoes and stimulated echoes. The former will be briefly mentioned in the section outlining gradient-echo sequences.

SIGNAL LOCALIZATION: TECHNIQUES FOR BUILDING IMAGES The physical relationship that makes building up an image possible is the proportional relationship of the resonant frequency to the strength of the magnetic field (Larmor equation again). In understanding the MR spatial-encoding process, two concepts need to be separated: that of resonant frequency (as given by the Larmor equation: spins precessing at a high resonant frequency when in a high magnetic field) and spatial frequency (the high spatial frequency components of an image corresponding to the fine detail in that image). Imaging is performed using the properties of the Larmor relationship but, in addition to this, the data are encoded in the spatial frequency domain! The latter refers to the sampled signal being in the wonderful world of k-space. Different gradient schemes have been devised to traject through k-space in different ways but most images are acquired using a two-dimentional (2D) encoding technique which samples kspace as a set of rectangular Cartesian coordinates (like the regular spacing in a tight climbing net). The beauty of this method is that the image is then just the 2D Fourier transform of the sampled signal (Fig. 5.2). The basic components of this strategy can be split into three parts: 1 Slice selection is performed during the rf excitation process. The excitation pulse consists of a narrow bandwidth of frequencies. A linearly increasing field (field gradient) is applied across the object in the slice-select direction; the combination of the limited excitation bandwidth in the

Figure 5.2 (A) Two-dimensional (2D) ‘k-space’ magnitude data array and (B) corresponding sagittal T1-weighted proton density image formed after 2D Fourier transformation.

presence of the gradient means that only spins within a finite distance in the slice-encode direction (i.e. a 2D slice) will resonate and be excited. The slice position and thickness can be altered by adjusting the rf centre frequency, pulse bandwidth and/or gradient strength (rate of change of magnetic field across the object). A negative gradient lobe is added after excitation so that once slice selection has been accomplished, the spins across the chosen slice precess in-phase with one another. 2 Phase encoding is performed following excitation and prior to the formation of the signal echo. A second gradient is applied along one direction within the plane of the excited slice. While it is on, the presence of the gradient causes a linear change in spin precession frequency along its direction. As with slice selection, once it has been switched off, all spins within the slice revert to precessing at the static field’s resonance frequency. However, the phase-encoding gradient will have introduced an incremental phase shift along its direction, the size of which depends upon its magnitude. This corresponds to one sampled spatial frequency (one value of ky) along the phase-encode direction. In order

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to sample other spatial frequencies in that direction, the excitation process is repeated to fill the desired matrix size. During each repeat, which occurs every repeat time (TR), the strength of the phase-encode gradient is altered, so that a different phase shift is introduced, thereby encoding a different spatial frequency in the phase-encode direction. 3 Frequency encoding is performed during data sampling of the signal echo. A third linear field gradient is applied in the imaging plane, perpendicular to the phase-encode and slice-selection directions. At different positions along the frequency-encoding direction, spins will be resonating at different resonant frequencies as the signal is sampled. As the echo evolves, successive spatial frequencies of the object are encoded along this third dimension. Thus, in a basic spin-echo or gradient-echo technique (Fig. 5.3), during any one TR, the slice is selected, the total number of spatial frequencies (say 256 or 512) is sampled along the frequency-encode direction at one spatial frequency along the phase-encode direction. This process is repeated for the total number of spatial frequencies required in the phase-encode direction (say 256 or 512). This can lead to inappropriate, excessive imaging times if high spatial resolution is required (> 25 min for 512 phase encodes with a TR of 3 s). However, developments in sequence design have enabled multiple phase-encoding steps to be performed within each TR, speeding up the process using, for example, fast spin-echo (FSE) techniques (Fig. 5.4). It is important to realize that individual elements in k-space do not correspond on a one-to-one basis with individual pixels in the final image, but rather that each k-space element contains information about that spatial frequency component throughout the image. An alternative method to slice selection is to use an additional (secondary) phase-encoding gradient along the slice selection axis, yielding true three-dimensional (3D)-encoded datasets that typically have high spatial resolution in all three directions (often submillimeter). Putting together phase and frequency encoding plus slice selection has introduced the concept of a pulse sequence that consists of a series of applied rf and gradient pulses that lead to

TR 90


90


RF Slice Phase Frequency TE Signal

Figure 5.3 Basis of the gradient-echo (spin-warp) pulse sequence. Three orthogonal gradients are used for: slice selection (while the rf excitation pulse is applied); phase encoding (the amplitude of which is iterated every repeat time [TR]) and frequency encoding (leads to echo formation at the echo time [TE]). The process is repeated after time TR for the total number of required phase-encoding steps.

RF

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Figure 5.4 Train of 180-degree refocusing rf pulses that form the basis of the fast spin-echo (FSE) sequence. Each 180-degree rf pulse has a different magnitude phase-encoding gradient. A whole train of 2, 4, 8, etc. echoes are produced per TR, reducing the number of TRs required for a given total number of phase-encoding steps.

the production of the signal in the form of an echo which has been encoded in k-space.Variations in the timing of the component parts of these pulse sequences can be used dramatically to alter image contrast; this being one of the major advantages of MR, helping to identify anatomy and characterize normal and pathological tissue types. Adjustments to the building blocks and parameters that define a pulse sequence can be used to manipulate image contrast. Most sequences in use today are based on variants of the above. There are several other methods of moving or trajecting through k-space that have potential advantages. Of these, the most commonly used is echo-planar imaging (EPI). EPI was one of the first imaging schemes to be proposed. It requires very rapid gradient switching and is thus technically demanding and, in its early forms, prone to various artefactual complications (such as Eddy current effects). Technical developments have enabled its introduction on commercial clinical systems over the last 10 years. Its speed is a great asset, being capable of yielding an image in under 100 ms, and has led to its use in areas such as imaging of water diffusion and brain function. It is important to note that MRI is a true digital imaging technique as discrete data points are sampled which, when transformed, form an image made up of 2D picture elements (pixels) or 3D volume elements (voxels).

INSTRUMENTATION: MAGNETS, COILS AND COMPUTERS The major parts of an imaging system comprise (A) the magnet subsystem to produce a spatially and temporally constant B0; (B) the gradient subsystem to produce time-varying magnetic field gradients primarily for spatial encoding; (C) the rf subsystem to transmit and receive the rf energy; and (D) the associated microprocessors/computers to specify and control the pulse sequence, calculate, process, display, store and transfer the resultant images. The magnet, gradient and rf coils are all situated within an rf-shielded examination or magnet room. This shielding (a Faraday cage) consists of a conductive metal lining (copper or aluminium) through which rf electromagnetic radiation will not pass. It serves to keep external electrical noise out and the generated rf energy within the examination room. All electrical connections into the room must be filtered appropriately as they pass through this shield. Most screened rooms possess wave guides or tubes (with a high length-to-diameter ratio; > 5:1) fixed into the wall of the

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screened room, through which nonconductive tubing may be passed (plastic gas tubing or fibre-optic cabling).The examination room door should be shut while acquiring data to enable the shield to work effectively.

Static magnetic field (Fig. 5.5) Although it is possible to perform MR experiments within the earth’s magnetic field (being approximately 0.00004T!), most clinical MRI systems are constructed around magnets which produce fields in the range 0.2–3T. Research systems capable of human in vivo imaging at 8T and above are available. There has been much debate over the optimum B0 for clinical imaging and this debate continues.The vast majority of installed systems operate at 1.5T, although there is presently a surge in systems operating at the new high-field strength of 3T. Low-field, reduced cost systems (0.2–0.5T) are often marketed for various ‘niche’ applications (e.g. musculoskeletal extremity imaging). At this low end of the range, permanent ferromagnetic composites or room temperature electromagnets tend to be utilized. Above 0.5T, superconducting windings (a niobium–tin alloy embedded in a copper matrix) are supercooled in a bath of liquid helium (at 4.2 K or −269°C) such that they offer zero resistance to the high currents required to produce high magnetic flux densities. Superconducting magnets, which are constantly ‘on’ or ‘at field’, are mostly cylindrical in geometry, especially at 1.5T and above, although more ‘open’ designs are becoming available at 1T and below. Developments in magnet technology have meant that, provided the helium refrigeration pump remains in operation (usually a rhythmical thud can be heard while the system is not acquiring data), one fill of liquid helium should last several years. The overall size of these superconducting magnet systems has decreased substantially in recent years, yielding friendlier designs with reduced levels of patient anxiety/claustrophobia. Why buy a high B0 system? The protons’ net magnetization increases with B0, leading to an overall increase in imaging signalto-noise ratio (approximately a linear relationship). Various other parameters also change with increasing B0, leading to

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potential benefits such as increased magnetic susceptibility contrast (useful for depicting nuclei within the brainstem or fMRI responses), greater resolution between resonance peaks in spectroscopy (potentially helpful for water/fat imaging) and an increase in tissue T1s (prolonged blood signal and better background suppression for time-of-flight angiography). However, higher is not automatically better as the aforementioned can also produce increased metallic foreign-body artefact, increased chemical shift artifact and changed T1 contrast. At high resonant frequencies, rf homogeneity also provides greater technical challenges. A high degree of homogeneity of the main magnetic field together with gradient linearity are essential for correct geometrical representation, this being especially pertinent when MR is used directly for therapy (e.g. in stereotactic radiosurgery to the trigeminal nerve or the placement of deep-brain stimulators). To maximize B0 homogeneity, a combination of passive and active shimming is employed. The former can take the form of a series of metallic coin-like discs or nougats, the configuration of which is usually site specific, determined and placed during installation. In high-end systems, active shimming can be computer optimized on each imaging volume for each patient episode.

Magnetic field gradients In cylindrical systems, the gradient coil sets required to produce the three orthogonal, linear gradient fields (gradients), are located adjacent to the inner surface of the magnet cryostat. The maximum gradient amplitude that can be generated (given in milliTesla per metre) has a significant effect on the minimum slice thickness and field of view and, thereby, the highest spatial resolution that can be achieved. The rate at which the gradients can achieve the desired amplitude is known as the gradient slew rate (given in milliTesla per metre per second). This sets a limit to the minimum TR and TE values that can be achieved, and thereby the minimum scan acquisition time. Applications such as fast cardiac, MR-digital subtraction angiography (MR-DSA), or high sensitivity diffusion tensor imaging require high amplitude gradients with a

Figure 5.5 MRI systems: (A) Modern system based on a cylindrical cryogenic magnet; (B) open magnet for interventional MRI; (C) low-field system for niche applications.

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fast slew rate. Fast gradient switching can lead to the induction of artefact-producing eddy currents within the conductive structures of the system. Improvements in gradient coil design and compensation methodology have significantly reduced this problem, although correct set-up during installation is essential for artefact-free use of gradient-intensive sequences such as echo-planar diffusion or sensitive techniques such as gradient localized spectroscopy. Powerful gradient amplifiers are an essential component of the gradient subsystem and are sited in a room with restricted access, adjacent to the magnet room.

Radiofrequency field Many of the rf transmit and receive subsystem components (digital-to-analogue converters, frequency mixers, power amplifiers, analogue-to-digital converters, etc.) are also sited within the electronics/cabinet room. These comprise all but the rf coils and associated receiver pre-amplifiers, which are placed close to the anatomical area under investigation in order to maximize their effectiveness. A typical system will have been purchased with a number of signal-detecting rf ‘receive’ coils, each dedicated to investigating a particular anatomical area (Fig. 5.6); often used in conjunction with the main rf transmitter body coil located adjacent to the gradient coil sets. The body coil is designed to provide a homogeneous rf excitation field throughout the required imaging volume. Many of the receiver coils will comprise several coil ‘elements’. Coil sensitivity needs to be maximized and the best signal-to-noise ratio can be obtained from a small volume adjacent to a close

fitting coil, but small coils only detect from a limited volume. To achieve high sensitivity over a large volume or area, several coil elements can be used in ‘phased-array’ configurations (e.g. for imaging the entire length of the spinal cord) or signals from multiple coils themselves (e.g. a coil ‘matrix’ covering the whole body) can be used in tandem.To facilitate this multicoil technology, many rf channels are used to pipe the detected signals away from the examination room. Thirty-two channel systems are available as standard product while those under research development can contain over 100. The number of coils/elements used is likely to grow substantially over the next few years. In addition to signal-to-noise ratio considerations, the inherent spatial information provided by arrays of coils/elements can be put to good use in parallel imaging techniques, where SENSE and SMASH technology can reduce the number of required phase-encoding steps and hence imaging time to yield a prescribed resolution. This is particularly pertinent to high-field strength systems where there is sufficient signal-to-noise ratio.

Pulse sequence control, data manipulation and image handling MR depends on highly sophisticated computing. The relentless increase in computing power has had a direct beneficial effect upon performance. Real-time image reconstruction is common without noticeable delay following data acquisition, which is important when hundreds (e.g. tissue perfusion studies) or thousands of images (e.g. BOLD fMRI studies) are acquired during a single examination. It is also now possible to

Figure 5.6 Examples of dedicated rf receive coils: (A) ‘CTL’ phased-array coil for imaging the whole spine plus typical anatomical coverage (B).

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Figure 5.6 cont’d (C) a neurovascular coil that allows MR angiography from the circle of Willis to the aortic arch (D); (E) a dedicated wrist coil designed to produce high-resolution imaging of the wrist joint (F).

register two or more datasets accurately with each other using complex computationally intensive algorithms. Slice positions can be prescribed automatically using such image registration techniques. Highly accurate comparisons between images from the same examination can be obtained ‘on the fly’ (e.g. statistical analysis of BOLD fMRI data) or from different examinations (e.g. subtraction of images to determine parenchymal volume changes in dementia or slowly evolving lesions such as meningioma). The real-time manipulation of 3D datasets (maximum intensity projections, surface rendering or general multiplanar reformatting) enables complex interactive postacquisition viewing strategies to be employed by the radiologist, which is particularly important when assessing complex vascular structures such as arteriovenous malformations or visualizing intracranial cortical developmental malformations. Digital data processing speeds will become even more critical if

ultra-high resolution imaging at very high field strengths (≥ 3T) with acquisition matrices of at least 2048 × 2048 becomes widespread. The common PC–user interface can be found on the majority of new MR systems. The introduction of picture archiving and communications systems (PACS) and the data standard, DICOM, has been evident. Local archive is still possible (commonly to DVD in new systems), but the provision of a central PACS archive is often assumed. The introduction of soft copy reviewing and reporting has meant that the radiologist is no longer confronted with fixed viewing parameters on sheets of film, but has the advantage of being able to interact with window widths and levels during the review process, enabling the interrogation of features that may be outside the acuity of the human visual system when observed on hard copy format. The incorporation of a plethora of functional investigative techniques into clinical practice (perfusion,

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exogenous contrast medium uptake, water diffusion, etc., and not just BOLD fMRI) often benefits from representation in colour overplayed on high resolution anatomical images. The rapid cinematic presentation of multiple contiguous sections can facilitate integration of information across several sections. Ciné presentations are frequently used in the analysis of dynamic studies, particularly of the vasculature.

PHYSICAL PARAMETERS THAT PROVIDE CONTRAST MR offers a vast range of possible image contrasts (Fig. 5.7), which, in turn, provides high sensitivity about the presence of many abnormalities. However, pixel values do not represent an absolute measure (e.g. absolute T2, in milliseconds). They are only absolute on the rare occasions when specialist quantitative techniques are invoked (e.g. calculation of absolute T2 of the hippocampal structures for the definition and lateralization of sclerosis in temporal lobe epilepsy). Rather, they reflect various physical parameters, including proton density, T1, and T2, and their scaling is influenced by factors such as body size (which affects rf coil loading and hence the induced voltage in the receiver coil). This is unlike CT, where pixel values in Hounsfield units correspond directly to X-ray attenuation (electron cloud density). When a particular physical parameter, e.g. the spin–spin relaxation time T2, dominates the relative pixel intensities in the image (i.e. the image contrast mostly reflects differences in T2), that image is said to be T2 weighted. The diversity of available weightings can lead to difficulties assessing what is the optimum amount of information to gather. As well as in-depth anatomical knowledge, interpretation requires knowledge regarding the type of weighting present in an image, how that relates to a particular physical contrast mechanism and how that contrast varies in the normal population and with disease. This section outlines the most common contrast mechanisms in common clinical use and emphasizes how they can manifest as artefacts or false image information if not properly analysed. Some examples are given.

Proton density It seems intuitive that the proton density (PD or ρ) of an object will fundamentally be linked to the size of the signal returned by that object. Indeed, this is the case; the higher the number of ‘MR visible’ protons, the greater the potential signal becomes. To provide image weighting so that the PD dominates pixel intensity, the effects of other potential influences should be minimized. This approach to providing the majority weighting by one factor is common practice in sequence design and protocol implementation (see ‘sequence’ section below). It is useful to rank body components according to their relative PDs. Highest are cerebrospinal fluid (CSF) and other fluids. These are followed in order by various soft tissues such as liver, kidney, spleen, grey matter and white matter, then articular cartilage, fibrocartilage, membranes, cortical bone and, lowest of all, air. It is important to recognize that the ‘MR visible’ proton pool consists of mobile protons. Hydrogen nuclei that form part of large molecular structures or are immobilized in solids have tight chemical bonds that ensure that they interact with each other so rapidly (i.e. have very short T2 values) that they provide no detectable signal over the timescales involved in standard clinical MR technique, and appear to have a PD of zero. PD is increased in some lesions.These include oedema, infection, inflammation, acute demyelination, acute haemorrhage, various tumours and cysts. Since the formation of oedema is a common response to a wide variety of insults, an increase in PD is a frequent occurrence. A decrease in PD may be seen in scar formation, fibrosis, some tumours, capsule and membrane formation, as well as with calcification. The changes in PD are often relatively small in comparison to the changes seen on T2-weighted images.

T1 (longitudinal relaxation time or spin–lattice relaxation time) This time constant characterizes the rate of the protons’ recovery from their excited state to their resting or equilibrium state, in the longitudinal or z-direction (parallel to the main field), for each component of the object. It relates to the transfer of energy from the protons to the tissue’s overall structure. Body

Figure 5.7 Patient with multiple sclerosis with plaques of demyelination shown on (A) fast spin-echo (FSE) proton density; (B) FSE T2; and (C) FSE FLAIR. There is no discernible abnormality on T1-weighted images without contrast medium (D).

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fluid T1 is long (typically 1500–2500 ms) compared to soft tissues (typically 300-1200 ms), while those of fatty structures are shorter still (100–150 ms). T1 increases with B0, requiring an alteration in sequence parameters to provide equivalent T1 image contrast at different field strengths. For any tissue, T1 is always longer than T2. Although the relaxation processes characterized by T1 and T2 are physically different, both tend to increase with most disease processes, primarily due to the accumulation of fluid associated with oedema, inflammation and infection. Despite an overall increase in T1 with pathology, T1-weighted images are often favoured for the depiction of anatomical structure. Standard T1-weighted spin-echo images can be acquired in less time than their corresponding T2-weighted counterparts, due to the reduction in TR used to introduce the degree of T1 weighting. Images with T1 weighting are heavily influenced by the presence of the most common exogenous contrast agent, chelated gadolinium (Gd) (see section below on ‘exogenous contrast media’), which can cause a dramatic increase in signal on T1-weighted imaging (Fig. 5.8).

T2 (transverse relaxation time or spin–spin relaxation time) This time constant characterizes the rate of phase dispersion of the spins’ magnetization in the transverse plane (perpendicular to the main field). This fanning out of the x–y magnetization occurs as the protons exchange energy (or quantum, mechanical chatter) with each other. For a given tissue, the dependence of T2 on B0 is small when compared to that of T1. Fluids have long T2 values (typically 600–1200 ms) those of soft tissues being shorter (typically 50–200 ms) and fat shorter still (10–100 ms). All of these are shorter than their corresponding T1 values: for a given tissue, absolute T2 can never exceed T1. The elevation of T2 in disease processes leads to a very high

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sensitivity using a standard T2-weighted spin-echo imaging technique, which is often the ‘bread and butter’ sequence for detecting lesions. When exogenous contrast media are administered, T2 is shortened. This mechanism is commonly used in abdominal imaging. For the use of Gd-chelates in the central nervous system (CNS), this effect is generally less and rarely used by comparison to its corresponding T1 effect. However, monitoring the passage of rare earth metals such as Gd is routinely performed using its modulatory effect on a closely related parameter, T2*.

T2* and endogenous susceptibility The concept of T2* was introduced above. When an image is weighted by T2*, not only is it weighted by tissue T2, but also by another component that can be ascribed to the hastening of the intrinsic spin–spin interaction by perturbations in the local magnetic field. Such perturbations are caused by the presence or introduction of objects that have different magnetic susceptibilities (χ). Magnetic susceptibility defines how magnetized an object becomes when placed in a magnetic field. When adjacent structures inside the homogeneous MR magnet have different χ, a small magnetic field gradient will be present. This gradient is the perturbing agent. Most of the constituents of the body are diamagnetic, having weak susceptibility, and they lead to a subtle reduction in the field that passes through them. Exogenous contrast agents (e.g. Gd-chelates) and some endogenous agents (such as deoxyhaemoglobin) exhibit paramagnetic properties which enhance local magnetic flux. Ferromagnetic objects exhibit an extreme form of paramagnetism, experiencing strong forces when placed in a magnetic field. Increasing B0 leads to shortening in T2* and an increase in T2* contrast. Artefacts can result from local decreases in T2*. Signal dropout adjacent to nonferrous metallic implants can be dramatic, even on low- and mid-field strength systems

Figure 5.8 Typical appearance of a brain tumour, specifically a cerebellar medulloblastoma. (A) The tumour has a low signal on spinecho T1-weighted images owing to a prolonged T1. (B) After the injection of Gd-DTPA the tumour enhances avidly, depicting breakdown of the blood–brain barrier.

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(0.2–1T). At high field, signal dropout occurs at the edges of various intracranial structures, such as the base of the frontal lobes, due to differences between the χ of cortical parenchyma and air within the sinuses. Dropout can be minimized by the use of spatially localized high-order shimming and increasing sequence bandwidth (number of Hertz per pixel). The presence of endogenous susceptibility gradients can be put to good use, providing a valuable contrast mechanism. One such example is BOLD f MRI, used not just within clinical neuroradiology, but also within associated neuroscientific specialities such as psychiatry and psychology. It is able to detect regional haemodynamic responses to simple or complex stimulation tasks. Although still not totally understood, neuronal/synaptic activity results in a change in local energy consumption which gives rise to an alteration in the ratio of intravascular oxy- and deoxy-haemoglobin and blood flow: the result being a localized net increase in the amount of fresh oxyhaemoglobin and hence T2*-weighted signal.This contrast is very subtle: activity within the primary visual or motor areas leads to signal changes of the order of 2–3% at 1.5T which approximately doubles to 4–6% at 3T. Much data have to be collected, processed and compared using computer-intensive algorithms to obtain statistically significant contrast. Clinical applications include aiding pre-operative neurosurgical planning and intra-operative neurosurgical guidance (Fig. 5.9). There are numerous other important uses of endogenous susceptibility-related, T2*weighted contrast, such as the depiction and timing of blood breakdown products following haemorrhage (Fig. 5.10).

Exogenous contrast agents Several agents have been tested, approved and are commercially available. Two groups will be considered: Gd compounds (the most common) and super-paramagentic iron oxide particles (SPIOs). Being a rare earth metal, Gd is toxic in isolation. Its toxicity is negated by appropriate chelation: the initial product to be introduced uses diethylenetriamene penta-acetic acid for this purpose (Gd-DTPA, Magnevist, Schering AG). Predominantly administered by intravenous injection, Gd-DTPA is rapidly distributed

Figure 5.9 Blood oxygen level dependent functional MRI is being investigated for its use in aiding pre-operative neurosurgical planning and intra-operative neurosurgical guidance. These data were obtained from a patient with a glioma in the left parietal lobe. Areas of activation due to finger tapping are overlaid in orange/yellow. Two anatomical slices are shown for right-hand motion and left-hand motion. Activation that correlates with right-hand movement can be seen close to the top of the lesion (bottom right).

throughout the vasculature. It is excreted by the kidneys, having a biological half-life of approximately 90 min. The agent lowers localized T1,T2 and T2*, as outlined above. Decreased T1 leads to bright pixels on T1-weighted spin-echo images (the most commonly used contrast mechanism [see Fig 5.8]), and decreased T2 can lead to less intense pixels on heavily T2-weighted images, particularly at high Gd concentrations. The effect on T2* is dramatic: the decrease causes low signal on T2*-weighted images which, on a suitable dynamic dataset, depicts parenchymal perfusion in real-time (Fig. 5.11; see section on ‘perfusion’ below).

Figure 5.10 Haematoma. A patient presents with a history suggestive of subarachnoid haemorrhage but MRI shows an extensive left frontal haematoma. The haemoglobin in the haematoma is in different stages of breakdown as shown on (A) the spin-echo T1- and (B) fast spin-echo T2-weighted images. (C) Note the high signal rim on FLAIR imaging indicative of oedema. (D) Gradient-echo sequences are very sensitive for acute haemorrhage and show prominent ‘blooming’ of reduced signal due to susceptibility effects.

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A

INTENSITY v, TIME

B

INV. INTENSITY v, TIME

0,00 13,2 28,6 39,7 52,9 66,2 79,4 92 1

2

C

ROI AREA 1. 426 4 2. 363 9

PEAK 96.2 87.6

D

0,00 13,2 28,6 39,7 52,9 66,2 79,4 92,6sec 1

2

Figure 5.11 Exogenous perfusion data obtained from a time series of T2*-weighted echo planar images in a 70-year-old woman who presented with amaurosis fugax and was found to have a 95% stenosis of the right internal carotid artery. (A) A base image shows two regions of interest within the middle cerebral artery territories. (B) A drop in signal intensity can be seen due to the first pass of the Gd-chelate from which (C) a concentration–time curve is calculated and a gamma-variate fit is performed (solid lines). (D) The resultant time-to-peak (TTP) map shows prolonged TTP in the affected hemisphere shown as high signal.

Gd-chelates do not cross the intact blood–brain barrier, but accumulate where it has been compromised (e.g. intracranial tumours, abscesses and acute demyelination).This has been one of their primary clinical uses. They are particularly effective in the delineation of small tumours, such as acoustic neuromas. High-grade malignancies generally show more enhancement than tumours of lower grade. Areas of cystic necrosis may also show enhancement but the greatest clinical value of chelated Gd has been in distinguishing tumour from oedema. Care should be exercised as the integrity of the blood–brain barrier may be altered by the modulatory influences of corticosteroids. Applications outside the CNS benefit, for example, dynamic contrast uptake characteristics may aid breast lesion differentiation. Having Gd-chelates ‘on-board’ can increase overall vessel conspicuity when using standard TOF or phase-contrast angiography techniques, although the most common angiographic application is in contrast-enhanced MRA (CE-MRA)

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and MR digital subtraction angiography (MR-DSA), where blood T1-shortening effects are used to visualize the passage of a bolus of contrast medium. If a particularly ‘tight’ bolus is needed, higher concentrations are available (e.g. 1 M Gadovist, Schering AG). Oral preparations can be used to visualize the gastrointestinal tract. The other class of agents considered here, SPIOs, is primarily for use in liver (Fig. 5.12) or spleen imaging (Endorem, Guerbet; Resovist, Schering AG).These particles have also been used in oral form for labelling the gut. In clinical applications to date, relatively large particles have been used which, after intravenous injection, lodge in the reticulo-endothelial system (Kupfer cells). Once lodged, they cause strong perturbations to the main magnetic field, producing a loss of transverse coherence, shortening T2. Tumours or other lesions which do not have reticulo-endothelial cells do not take up the SPIO and retain their high MR signal on T2- or T2*-weighted imaging. Lesions down to a few millimetres in diameter can be delineated in the liver.These iron-based agents are metabolized into the iron pools of the body and are excreted over a period of weeks. A selection of other exogenous contrast agents is available or under development, including coated iron-oxide and Gdcomplex blood-pool agents/strong albumin binding agents, hepatocyte-specific Gd-chelates (MultiHance, Guerbet), manganese-containing agents (Teslascan, GE-Healthcare) for the liver, pancreas and cortex of the kidneys; Mn-DPDP may be useful for assessment of acute myocardial ischaemia. Natural compounds, such as blueberry juice, may act as negative contrast agent in upper abdominal MR investigations, such as MR cholangiopancreatography. Other targeted agents, which may be necrosis specific (bis-Gd-mesoporphyrin), provide lymphographic contrast, or are specific for inflammation detection. The exact role of these agents is currently unclear, but they could considerably alter the practice of radiology.

Figure 5.12 Liver contrast agents—super-paramagnetic iron oxide particles (SPIOs). (A) Pre and (B) post iron oxide single-shot fast spinecho images. Both areas of FNH take up the iron oxide. Notice the central scar which has high signal on T2 and low signal on T1. (Courtesy of Dr A Blakeborough, Royal Hallamshire Hospital, Sheffield, UK.)

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Chemical shift, spectroscopy and water/fat imaging The phenomenon of chemical shift (δ) has important consequences for imaging as well as MR spectroscopy (MRS). In addition to the provision of clinical information, an overview of MRS can aid the understanding of many aspects and underlying principles of MR. Analytical chemists have used bench-top spectrometers since the 1950s in their quest to identify, understand and model molecular structure. The technique relies on information provided by chemical shift. In proton MRS (H-MRS), a hydrogen nucleus attached to a particular molecule does not ‘see’ the exact field produced by the magnet. This is because it is not a free proton; rather it is a proton in a chemical bond attached to a molecule. Neighbouring atoms that form that molecule have associated electron clouds which shield the hydrogen nucleus from the main magnetic field. The shielding effects within different molecules will differ. Back to the Larmor equation, since the resonant frequency is proportional to the field, the hydrogen nucleus will resonate at a particular frequency that is characteristic of that molecular environment. A measurement of the frequency components that emanate from a sample (in the absence of a frequencyencoding imaging gradient) will yield a frequency spectrum. This usually contains a number of peaks, the position of which (or shift along the frequency axis) is given in units of parts per million (ppm) of B0. Each peak can be attributed to a chemical group. Thus, MRS provides direct biochemical information. This can be spatially localized using a number of methods: by the spatial sensitivity of a surface coil, by the intersection of three slice-select gradients (single-voxel selection [SVS]), or a 2D or 3D metabolite map can be created by phase encoding the spectroscopic signal (chemical shift imaging [CSI]). It has become feasible to assess clinically important chemi-

cals and metabolities which are present in tissues in fairly low concentrations (millimoles in proton spectroscopy of the CNS). Spectroscopy is demanding in terms of the signal-to-noise ratio of the system and B0 homogeneity. The homogeneity within the spectroscopic region of interest must be such that any changes in resonant frequency are dominated by the chemical shift and not any heterogeneity in the applied magnetic field itself. Spectroscopy packages (particularly proton) have developed over the last 25 years to a stage where complex high-order shimming (B0 homogeneity optimization), signal localization, and data sampling and post-processing can be performed by ‘one-press’ button automation. Since its implementation in whole-body medical imaging systems, MRS has sometimes struggled to find a true clinical role. In part, that may follow from being seen as a disparate, complicated technique compared to MRI. On the contrary, it is often simpler. The technique has become more robust, forming part of a clinical investigative brain examination in many centres. It is often sensitive to the presence of disease, but lacks specificity; its clinical use (as for many imaging techniques) relies on other contextual information. Just as with standard imaging, spectra can be metabolite concentration-, T1- or T2-weighted, or a mixture of the three, depending upon acquisition parameters such as TE and TR. The brain has been the most extensively studied organ to date by proton MRS (Figs 5.13 and 5.14). If left alone, the hydrogen nuclei from water will dominate the MR ‘visible’ cerebral metabolites. This large peak from water (at 4.77 ppm) needs to be suppressed, so that an appropriate dynamic range can be obtained for metabolite detection. The three main cerebral metabolites are attributed to choline-containing

Figure 5.13 Two examples of the applications of proton spectroscopy in neuroimaging. (A) The patient is a child with known mitochondrial abnormality who presents with seizures. MRI shows extensive areas of hypoxic damage and proton spectroscopy shows the doublet characteristic of lactate. Lactate is not normally seen. The other three major peaks (choline, creatine and N-acetyl aspartate [NAA]) are normal except for a mild reduction in the Na/Cr ratio. (B) In comparison, a child with a cerebellar tumour shows a massive increase of choline and complete loss of NAA relative to creatine. This is highly suggestive of tumour and characteristic of medulloblastoma, which was confirmed on histology.

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Figure 5.14 A ‘metabolite map’ or chemical shift image (CSI) where phase encoding is used in two dimensions to map the spectral metabolites. This example shows the distribution of N-acetyl aspartate in a patient with a periventricular space-occupying lesion. A colour overlay is used. (Courtesy of Dr P. Pattany, University of Miami, Florida, USA.)

compounds (Cho) centred at 3.2 ppm, the total creatine pool (creatine plus phosphocreatine) at 3.0 ppm, and N-acetyl (NA) groups at 2.0 ppm (such as N-acetylaspartate [NAA] and N-acetyl-aspartyl-glutamate [NAG]). The biochemical role of NA is not completely understood, but the peak serves as a putative marker of neuronal integrity/function, being predominantly confined within neuronal cell bodies and axons. In a variety of disorders the NA signal may be decreased when there is little or no change on MRI. These include diseases in

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which there is acute or chronic neuronal loss, such as some of the dementias, chronic head injury, temporal lobe epilepsy and infective encephalopathies. In the latter, in particular HIV-associated encephalopathy, spectroscopy has been shown to follow clinical neurological status more closely than imaging following the administration of antiretroviral medication. Proton MRS appears complementary to MRI, which is generally of most value in acute and subacute disease. At short TEs (where T2 and modulation effects are reduced) more detail on other biochemicals within the brain, such as glutamate, glutamine and myo-inositol can be obtained. Phase-encoded CSI yields metabolite images whose spatial resolution is sufficient to allow differentiation between normal tissues and pathology. Potential applications of proton MRS to other organ systems have been investigated. Most notably it has been investigated for the diagnosis and staging of prostate cancer where the level of citrate decreases, while the choline peak is high. This is the reverse of findings in the normal peripheral zone of the prostate, where citrate is high and choline low, and benign prostatic hypertrophy with intermediate citrate and choline levels. From an imaging point of view, the slightly different resonant frequencies of fat and water can lead to band artefacts at tissue boundaries (the component water and fat images are shifted with respect to each other).These can be minimized by increasing the range of resonance frequencies covered along the frequency-encode direction (acquisition bandwidth); as ever, there is a trade-off as more noise is sampled. Chemical shift can be used to provide images of just water or just fat, or their relative contributions can be altered. Fat- or water-only images can be produced by selective excitation, where the centre frequency of an rf excitation pulse (ChemSat) of narrow bandwidth is placed over either the water or fat peak (Fig. 5.15). Another method utilizes interference effects between fat and water signals. It is useful to consider the phase of the signal. Because of the difference in resonant frequency, their signals will alternatively be in and out of phase. The detected signals cancel out when they are 180 degrees out of phase and add together when they come

Figure 5.15 Saturation of orbital fat using a chemical shift selective pulse. (A) Axial fast spin-echo T2 images in a 2-year-old child showing proptosis of the right eye. (B) Axial images through the orbits show a mass intermingled with the orbital fat and conal musculation. (C) The anatomy is clarified using a post Gd-DTPA fat-saturation sequence.

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back into phase. The phenomenon is like the beating effect from two musical notes which are slightly out of tune. At 1.5T, the first water–fat cancellation point occurs at TE = 2.2 ms (Fig. 5.16). Such imaging can provide invaluable information in certain areas (e.g. adrenal imaging).

Flowing spins The given description of the spatial encoding process in the earlier section makes a bold assumption for the production of artefact-free images – that protons stay still while they are being excited and their position is encoded. This is often a tall order for the patient in a magnet with an itchy nose and, of course, impossible for humans to have totally still spins while they have a functioning circulatory system! The different MRI behaviour of fluids can be harnessed to yield information regarding fluid flow. There are various forms of in vivo flow or flow-like movement that that can be imaged to provide spin-movement related contrast.

Macrovascular flow (angiography) Flow within large vessels (arterial and venous) can lead to various appearances using standard imaging techniques: vessels can be void of signal (Fig. 5.17) or often they return hyperintense signal. An understanding of the principles underlying the appearance of flowing blood on MRI has led to the development of magnetic resonance angiography (MRA), where the protons in flowing blood produce a high signal against a background of little or no signal from stationary tissues. Such high contrast datasets can be manipulated and viewed, often using maximum intensity projection (MIP) algorithms, to reveal projected vascular anatomy. The common contrast mechanisms can be split into three groups: (A) TOF; (B) phase contrast; and (C) contrast enhanced. Time of flight effects utilize differences in magnetization when very short TR is used. Contrast is provided between stationary background spins in the imaging volume and inflowing, fresh

Figure 5.16 Colorectal metastasis in a fatty liver. (A) In-phase and (B) out-of-phase T1 gradient-echo axial images at same level. There is marked loss of signal from the liver parenchyma on the out-of-phase image indicating fatty infiltration. Notice the metastasis in the right lobe, and an artefact from aortic pulsation in the midline. (Courtesy of Dr A Blakeborough, Royal Hallamshire Hospital, Sheffield. UK.)

Figure 5.17 Flow effects. This patient presented with right-sided seizures. (A) Fast spin-echo T2-weighted images show a large area of signal void within the area of the left sensorimotor cortex, which was present on all other sequences. This is characteristic of a high-flow vascular malformation. (B,C) Time of flight angiograms before (B) and after Gd-DTPA (C) confirm the presence of a large pial arteriovenous malformation.

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blood.The stationary spins are repeatedly exposed to the excitation pulse and, due to the short TR, there is not enough time for their longitudinal magnetization to return to equilibrium: it becomes saturated and there is a lack of magnetization with which to form a signal. The inflowing blood, on the other hand, experiences its first excitation pulse and it returns a high signal. This phenomenon provides endogenous contrast. The imaging volume can be encoded as a set of 2D slices or a 3D dataset. High field strength systems (3T in particular) can provide excellent vascular depiction due to high signal-to-noise ratio and prolongation of both the T1 of blood and stationary background protons (Fig. 5.18). Gradient-echo sequences with high T1-weighting are often used as they can be acquired at very short TR, maximizing the TOF contrast. Phase contrast techniques utilize the basic phenomenon that phase changes are introduced to the transverse magnetization when spins are exposed to a magnetic field gradient.This is put to use in phase encoding where the phase difference in a single TR is used to encode the signal at one spatial frequency in the phase-encode direction. If, after a time delay, the phase-encode gradient were to be reversed, then the phase differences in the spins across the sample introduced by the initial gradient will be completely reversed or rewound. This is only true for stationary spins. If a spin has moved in the direction of the gradient between its initial application and its reversal, then the spin will either not have been rewound enough or it will have been rewound too much. It will have developed an overall phase change. Thus, phase-contrast encoding is performed by a pair of additional ‘bipolar gradients’, the magnitude, duration and time interval between which will determine the phase change experienced by a spin moving at a particular velocity. This information can be used to quantitate the velocity of the moving spins. In qualitative PC angiography, velocity encoding has to be applied in more than one direction. For a 3D implementation, separate flow encoding is applied in each direction. As with the TOF technique, PC is also an endogenous contrast mechanism.

Figure 5.18 3D Time of flight MR angiography projection of an intracranial, middle-cerebral artery berry aneurysm.

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Contrast-enhanced depiction of flow uses fast T1-weighted acquisitions to capture signal from a bolus injection of exogenous Gd-based contrast media. The addition of Gd into the vasculature causes a decrease in the T1 of blood which will appear bright on T1-weighted images. In order to delineate the arterial phase, the acquisition is required to be performed within one cardiac cycle. In practice, the low spatial frequency components are collected during the arterial phase as these form the major components of the image. Care is necessary in recognizing flow effects, for it is relatively easy to diagnose a solid lesion when all that is being seen is an unusual flow effect within a fluid-filled space.

Microvascular flow (perfusion) One of the key indicators of normal tissue function is that of normal arterial flow and tissue perfusion. Perfusion-weighted MRI has also been developed and can be performed with the aid of endogenous or exogenous contrast agents.The latter are by far the most common implementation. Techniques using endogenous contrast media rely on the rf labelling of proximal arterial blood, which can then be detected as it reaches an image plane selected through the region of interest. The noninvasive nature of this measurement makes it ideal in certain situations, e.g. in the assessment of placental perfusion in utero or when several repeat studies are needed. However, the contrast-to-noise ratios are less than those that can be obtained following the administration of exogenous contrast media. Gd-chelates are suitable exogenous agents for use in MR perfusion studies (see Fig. 5.11). The presence of the Gd–ion complex shortens both T1 and T2*. If a time series of T2*weighted images is acquired with high temporal resolution (approximately 1 frame s−1), the presence of Gd can be detected as a drop in signal as blood transporting the agent arrives at the image plane. A concentration–time curve can be obtained from which parameters such as bolus arrival time (BAT), mean transit time (MTT), time-to-peak (TTP) and relative blood volume (rBV) can be derived, and the application of the central volume theorem can yield information regarding relative cerebral blood flow (rCBF). Early MR perfusion studies performed using clinical systems were limited by image acquisition times. Fast gradientecho techniques (such as FLASH) could be used but usually on a single-slice basis. The introduction of EPI into the clinical setting has revolutionized MR perfusion imaging: enabling subsecond, multislice datasets to be acquired. As with diffusion-weighted imaging (DWI), most of the experience of perfusion-weighted imaging is in the brain, and particularly in stroke and other vascular abnormalities. Ischaemic stroke is usually due to occlusion of the cervicocranial vessels. The resulting reduced blood flow will have effects on the parameters measured by perfusion-weighted MR. In the acute setting the most commonly encountered changes are: increased time-to-peak; increased mean transit time; reduced cerebral blood volume and flow. It is hoped that a combination of DWI and perfusion-weighted imaging will permit delineation of the ischaemic penumbra in stroke, defining potentially

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salvageable tissue. Another area of interest is myocardial perfusion—used to provide information regarding the viability of the myocardium.

Very slow flow (molecular diffusion) The diffusion of water molecules is very slow random movement which can be thought of as slow directional flow when its randomness is restricted by a surrounding barrier (e.g. an axonal tract in brain parenchyma). Just as with arterial and venous intravascular blood flow and CSF flow, molecular DWI contrast can be introduced into MRI. The technique utilizes the same principles as outlined in the phase-contrast MRA section above: depending on the alteration in the phase of protons attached to water molecules as they travel along a magnetic field gradient. If a bi-lobed diffusion-encoding gradient pulse scheme is applied along one physical direction between the initial rf excitation pulse and data collection, any protons which are displaced along the direction of diffusion encoding will accumulate a relative phase change.Those that are stationary will not. The bipolar diffusion gradients are most commonly added to a single-shot EPI sequence, which enables a snap shot of the molecular diffusion to be obtained in one direction. This can be repeated along the three mutually orthogonal directions within the image plane. The degree of diffusion weighting can be changed by altering what is referred to as the b-value. The amplitude and duration of the bipolar gradients determine this b-value and images that have strong diffusion weighting require the application of very strong field gradients. Due to the inclusion of the time-consuming bipolar gradient scheme, data collection occurs at a relatively long effective TE and thus the diffusion-weighted images are also T2 weighted. This can lead to ‘T2 shinethrough’: high pixel values in areas of increased T2 as well as in areas of abnormal diffusion, which can lead to confusion! It is common practice to acquire a set of images with the bipolar gradients turned off, yielding a set of images with identical T2 but no diffusion weighting. Post-processing can then be performed to eliminate

the T2-dependent image contrast, yielding maps of apparent diffusion coefficients (ADCs). DWI is being assessed in many types of brain disease. Its major contribution appears to be in the distinction between cytotoxic oedema (which produces restricted diffusion) and vasogenic oedema (which does not restrict diffusion of water). The pathology that primarily produces cytotoxic oedema is ischaemia/infarction and DWI appears to be a sensitive and reasonably specific means of detecting ischaemic stroke. DWI is often used in conjunction with dynamic, Gd-enhanced perfusion imaging in the investigation of acute ischaemic stroke (Fig. 5.19).

PULSE SEQUENCES The most commonly used groups of pulse sequences are outlined below. Two main groupings are given: sequences where the echo results from the application of (A) an rf pulse and (B) a gradient.

Variations on a spin echo Basic two-dimensional spin-echo sequence In this pulse sequence; the digitized signal echo is produced by flipping the spins over in the x–y plane by a 180-degree rf pulse. This is applied at a time TE/2 after an initial 90-degree excitation pulse, producing a spin echo at time TE. Multiple slices are encoded by staggering each slice-selecting excitation pulse within each TR period and the Larmor frequency of each slice. Each of these slices experiences the application of one phase-encode step. Slice timing within each TR can be sequential (adjacent slices excited one after another: 1,2,3,4, 5…) or interleaved (1,3,5….2,4,6…): the latter is performed to reduce the effects of any overlap between slice edges that can occur at low TR (cross-talk). Parameters that alter image contrast are TE and TR. This is a very versatile sequence that can be PD, T2 or T1 weighted. PD-weighted images result if

Figure 5.19 Imaging of ischaemic stroke by multisequence MR. (A) An axial fast spin-echo T2-weighted image from a patient with an acute onset of left hemiparesis which shows a large area of T2 prolongation in the confines of the middle cerebral artery. The image is somewhat degraded by movement artefact as is often the case when using standard sequences in acutely unwell patients. (B) The single-shot fast spin-echo (imaging time < 1 s for one slice), which gives the same information. (C) A diffusion-weighted image acquired in 15 s shows high signal and (D) the apparent diffusion coefficient map shows a low signal, indicating an acute stroke.

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(A) TE is short (≤ 20 ms), thereby not allowing any differences in signal to evolve between tissues that may have different T2s, at the same time as (B) TR is long (≈ 3000 ms), enabling the spins to return to equilibrium between each rf excitation pulse. Differences in signal will be due to differences in the number of spins: a high PD will be represented by a bright pixel while a low PD will be represented by a dark pixel. If the TR is kept long, then as TE is increased (80–100 ms), different tissues with different T2 values will return different signals, and the T2 weighting of the resultant images will increase. In this case, tissues with long T2 values (e.g. CSF) will still have high signal at long TE and be represented by a bright pixel and vice versa. If on the other hand TE is short (to minimize T2 influences as in the PD-weighted case) but TR is decreased (≈500 ms), the T1 weighting of the sequence increases. The latter occurs due to different amounts of saturation experienced by tissues that have different T1 values. A tissue with a short T1 (e.g. fat) with respect to the specified TR, will relax back to equilibrium before the next excitation pulse: maximum magnetization will be available and so a bright pixel will ensue. A tissue with a long T1 (e.g. CSF) will not have time to relax back to its equilibrium state before the next excitation: only a small component of its longitudinal magnetization will and so the signal returned will be low and hence the corresponding pixels will be dark. Thus, pixel intensity resulting from a T1weighted spin-echo sequence (a partial saturation sequence) is inversely related to T1. A dataset can be obtained from the spin-echo technique in the order of several minutes.

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slices can produce motion artefact-free images, but care should be exercised as unwanted movement can occur between slices, altering the relative slice positions. Blurring can occur in the phase-encode direction. Every phase-encode step is acquired at a different TE, leading to a variation of T2-weighting across spatial frequency components. All resultant images appear heavily T2 weighted. Use of the single-shot FSE (SS-FSE) technique includes MR cholangiopancreatography, imaging of the diaphragm, bowel imaging and imaging of the fetus in utero (Fig. 5.20). It is also useful as a fast T2-weighted screening sequence in a moving patient!

Inversion recovery In this sequence type, the magnetization is ‘prepared’ before the initial 90-degree excitation pulse by the addition of an 180-degree ‘inversion’ pulse.The signal obtained will be influenced by the relative degree of recovery experienced by the spins along the z-axis.The inversion time (TI) is the time allotted for this recovery process to evolve between the 180-degree inversion and 90-degree excitation pulses. The inversion pulse introduces heavy T1 weighting into this sequence. Specific forms of the technique are fluid attenuated inversion recovery (FLAIR) where the TI is chosen so that the magnetization from fluids is nulled (≈ 2200 ms) in the detection (x–y) plane and TE is long (80–100 ms), introducing a lot of T2 as well as T1 weighting. The combination of fluid nulling with T2 weighting is particularly useful in assessing lesions with prolonged T2 adjacent to fluid structures (e.g. periventricular demyelination; see Fig. 5.7). In this same acquisition, T1 shortening brought

Multi-spin echo More than one echo can be recalled per 90-degree excitation using multiple 180-degree rf refocusing pulses which yield image datasets with different contrasts (as they are obtained at different TEs).The maximum number of slices per TR will reduce as the number of recalled echoes increases. The most common type used in clinical practice has been the dual spin-echo with short and long TE datasets (≈20 and 80 ms, respectively) at long TR, yielding PD- and T2-weighted datasets, respectively.

Fast-spin echo or turbo-spin echo or rapid acquisition with relaxation enhancement (RARE) As mentioned previously, the introduction of more than one phase-encode, refocusing pulse and frequency-encoded echo per excitation pulse (increasing the echo train length [ETL]), can speed imaging up by factors of between 2 and 32. During any one TR period, different spatial frequency components in the phase-encode direction will be acquired at different TEs, leading to a complex mixture of image contrasts. It is impossible to produce images that are as heavily PD weighted as can be achieved with the standard spin-echo technique above. Both T2- and T1-weighted images are commonly produced.

Single-shot fast-spin echo or half-Fourier acquired single-shot turbo-spin echo (HASTE) This is an extension of the FSE technique that enables all phase-encoding steps to be obtained following one initial excitation. One slice is acquired at a time, in approximately 1 s. Covering a volume prone to movement with multiple single

Figure 5.20 Imaging of the fetus in utero using single-shot fast spin-echo. Each set of 20 slices takes 20 s to acquire. This fetus has agenesis of the corpus callosum.

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about by the presence of exogenous Gd-based contrast agents will return high signal due to the sequence’s T1 weighting. In short-tau inversion recovery (STIR), T1 is kept short, and is typically used to null signal from fat. An example of its use in this context is in the delineation of breast lesions. There are several other methods of fat suppression; such sequences often demonstrate subtle lesions to best effect.

Spin-echo echo planar imaging In this variant of EPI, several or all lines of k-space are swept through at once during the evolution and decay of the main echo. The main echo is produced by an 180-degree rf pulse, i.e. it is a spin echo which is less influenced by field heterogeneities than the gradient-echo variety (below). This spin-echo EPI variant tends to be used for DWI as it is less prone to susceptibility-related artefacts than the gradient-echo EPI variant (see below).The sequence is actually a mix of gradient echoes, refocused by the EPI technique, that occur during the evolution of the spin echo that results from the refocusing rf pulse. Readers are referred elsewhere for further explanation and discussion of mixed gradient and spin echo (GRASE) sequences which have mixed spin-echo/gradient-echo contrast features.

Variations on a gradient echo/field echo Basic two-dimensional gradient-echo sequence This is as above for the 2D spin-echo sequences, except that the echo is produced by a gradient (rather than an rf pulse), causing the components of the spin magnetization to refocus in the x–y plane, producing an echo, without ‘flipping’ them over (i.e. without using an 180-degree pulse) (see Fig. 5.3). Unlike 2D spin-echo sequences, reduction in signal amplitude resulting from faster dephasing due to the presence of magnetic susceptibility differences/localized heterogeneity is not cancelled in this technique. Images can have mixed contrast consisting of PD, T1 and T2* weighting. When a different type of echo formation is present (the Hahn echo), gradient-echo sequences can also be T2 weighted. An understanding of the Hahn echo is needed to understand how different combinations of these four parameters can be made to dominate the image contrast. The TR used in a gradient-echo sequence is often shorter than the component tissue T2 values. In other words, the magnetization in the x–y plane will not have dephased completely before the next excitation pulse is applied (unlike the transverse magnetization in the spin-echo sequence which completely dephases, even when short TR is used to introduce saturation of the longitudinal component, i.e. to introduce T1 weighting). This net transverse coherence plus the addition of a further rf pulse produces the Hahn echo. So, two echoes can be present: the gradient echo and the Hahn echo. Each or both of these echoes can be used as follows. 1 Spoiled gradient-echo or spoiled gradient-recalled echo (SPGR) or RF spoiled Fourier acquired in the steady state (RF-FAST) or T1 fast field echo (T1 FFE). Any magnetization coherence in the x–y plane can be destroyed by the addition of a gradient pulse or rf ‘spoiler’, applied towards the end of the TR period. This sequence is

often termed a ‘spoiled gradient echo’. There is no Hahn echo, just the gradient echo. At short TE (< 8 ms) and short TR (≈ 50 ms), T1-weighting predominates (as with spin echo at short TR, due to differential saturation effects), but the weighting is not as heavy as the T1-weighted spin-echo variants. FLASH is a variant of the spoiled gradient echo. Instead of an initial 90-degree rf pulse, a low flip-angled pulse (α) is used. Very short repetition times can be used as saturation along the z-axis is minimized; enabling fast acquisition times and refresh rates for dynamic and angiographic studies. A relatively long TE (≈ 18 ms) increases the T2* weighting, with low α (≈ 25 degrees), decreasing the T1 weighting, allowing the T2* weighting to dominate. 2 Contrast-enhanced Fourier acquired in the steady state (CE-FAST) or PSIF (mirrored FISP) or T2 fast field echo (T2 FFE). T2-weighted images can be produced by imaging the steady-state coherence or Hahn echoes (that build up over a few repetitions) and not the gradient echo. The Hahn echoes are sampled towards the end of the TR period and the effective TE is approximately twice the TR. 3 Gradient recalled acquisition in the steady state (GRASS) or fast imaging with steady-state precession (FISP) or Fourier acquired in the steady state (FAST) or fast field echo (FFE). Residual phase coherence at the end of each TR is not destroyed and both the gradient and Hahn echoes contribute to the image. Complex, combined T1/T2 weighting results.

Three-dimensional gradient echo Secondary phase encoding is performed instead of slice selection. The penalty associated with this is an increase in acquisition time. However, as gradient-echo sequences can run with very short TR, this is manageable with typical standard 3D gradient-echo acquisition times in the order of 5–15 min. Acquisition times can be reduced substantially (with lower coverage and resolution), enabling breath-hold techniques (10–20 s). The spatial resolution in the second phase-encode direction is generally less than 2 mm (above this, 2D techniques tend to be used) and the signal-to-noise ratio at high resolution is superior to 2D techniques. Isotropic, submillimeter voxels facilitate true 3D visualization strategies.

Magnetization prepared rapid acquisition gradient echo (MP-RAGE) or turbo-FLASH or inversion recoveryprepped fast spoiled gradient-recalled echo As with the inversion recovery spin-echo sequence, an inversion pulse is applied before the excitation pulse, producing a T1-weighted sequence that is often used with rapid 3D encoding for high-resolution imaging of, for example, brain malformations. Coupled with its ability to depict exogenous contrast medium which has traversed the damaged blood–brain barrier, it is also useful for intra-operative neurosurgical guidance.

Gradient-echo echo planar imaging This is similar to spin-echo EPI but the main echo is produced by a gradient lobe. This sequence is heavily weighted to reflect differences in magnetic susceptibility. It is often used

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for BOLD fMRI studies and EPI-based exogenous perfusion assessment.

SAFETY CONSIDERATIONS Undergoing an MR investigation or working in a MR unit does not involve exposure to ionizing radiation and no clear long-term biological effects have been reported. However, the environment is quite unusual, presenting several potential risks to human safety that need to be fully addressed by those who work in it and for those who have occasion to visit it. Each unit should have a set of local rules based on advice outlined in documents from the relevant regulatory bodies (UK’s Medicines and Healthcare products Regulatory Agency (MHRA), European Union, etc.) and all MR unit staff should be familiar with these. Inner and outer ‘controlled areas’ that have restricted access should be detailed. Accountability to the hospital’s radiation safety committee is to be commended, ensuring that incidents are reported appropriately and that necessary safeguards/recommendations are acted upon. The invisible MR environment includes potential effects resulting from the following.

Magnet Ferromagnetic objects (mainly containing iron, nickel or cobalt), when near to a magnet, experience a force of attraction towards the magnet bore (magnetic isocentre). The force depends upon factors including magnetic field magnitude, proximity, object mass and composition.The danger associated with this hazard is real: fatalities have resulted. All patients, visitors, non-MR personnel and pieces of equipment should be screened appropriately before entry into the controlled area. Cardiac pacemakers contraindicate entry as do intracranial aneurysm clips of ferromagnetic/unknown composition. In very high fields (>> 1.5T) mild sensory activations (such as visual magnetophosphenes and balance alteration) have been reported. There is no evidence that these are harmful. If the magnet’s liquid helium/nitrogen Dewar is being replenished, the magnet room should be kept clear due to risk of cryogenic burns and suffocation. There may be occasion when the magnet needs to be shut down in an emergency, e.g. if a person becomes trapped between the magnet and a ferromagnetic object. Once the emergency run down unit (ERDU) button is depressed, liquid helium will vaporize and there is a valve/ pipe system to vent this gas to the outside. However, as a matter of caution, all personnel should exit the magnet room and the door should be kept closed.

Time-varying magnetic field gradients At high amplitudes and slew rates, these can cause unpleasant peripheral nerve stimulation. This is an acute effect and not harmful. Modern system software will alert the operator when there is risk of attaining such levels. The acoustic noise generated due to the fast switching of currents within the gradient coils while restrained in a high static magnetic field (an expensive loudspeaker!) may be considerable20, levels being up to

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108 dBA. Protective ear plugs/headphones should be worn by patients (and accompanying personnel), particularly in systems operating at 1.5T and above. Recent advances in gradient coil design and construction have led to a decrease in gradientassociated noise on some systems for given performance levels.

Radiofrequency field The transmitted rf field deposits energy within the body. Energy deposition is expressed as the specific absorption rate (SAR) in watts per kilogram. The levels given in MHRA guidelines (for SARs applied over a 15-min period) have been set to limit tissue heating to less than 1°C. Modern system software indicates the SAR to the operator for each acquisition. Care should be exercised when examining anaesthetized patients who require ECG monitoring. Burns can result from rf Eddy currents being induced under the skin electrodes (e.g. where clinical indications suggest SAR-intensive sequences such as FSE imaging of the lumbar spine). In these circumstances, pain sensation cannot be communicated while a burn is developing. Caution should also be made when the patient’s circulatory system is compromised. Clinical need should be noted in cases such as these. MR is not advised during the first trimester of pregnancy. This is precautionary as no deleterious effects to mother or child are known. Patients with various implants (from deep brain stimulators to stents) should be assessed for possible interactions with static field and rf heating: evidence from an up-to-date reference should be sought. At the time of writing, an EU Directive covering work exposure to electromagnetic radiation is due to become part of UK law in 2008. It will affect working practices in clinical MR units. The relevant exposure is likely to be related to the time-varying fields produced by the gradient subsystem. Staff will not be able to stand at the entrance to the magnet bore to comfort the patient, initiate examinations from the magnet fascia, perform close monitoring of anaesthetized patients or take part in MR-guided interventional procedures. Various professional bodies are presently attempting to address these issues and it is hoped that these restrictions will not be necessary.

CONCLUSION In the first 25 years of clinical practice, MRI has moved from being a curiosity to being the technique of first choice in a variety of diseases. The physics necessary for image interpretation is more complex than that for any other technique in radiology, yet the great diversity of the technique provides a wide range of possibilities, many of which are being developed or are yet to be explored. Clinical MR is truly 3D, and with the advent of modern workstations there is an opportunity to obtain radiographic views that have not been available previously.The recent development of fast imaging ciné studies, perfusion and diffusion techniques, hyperpolarized gas imaging (Fig. 5.21) and solid

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Figure 5.21 Image of a healthy lung obtained with a two-dimensional, rapid, steady-state free precession sequence with 300 ml. Hyperpolarized 3 He at 30% polarization. (Courtesy of Dr J.M. Wild, University of Sheffield, UK.)

state methods provide new possibilities. The development of new contrast agents, targeted at specific organs, diseases, cell or gene types is likely to result in a considerable expansion of the options now available. Parallel acquisition methods promise radically to increase the throughput of MR techniques and allow contrast mechanisms, which previously could only be acquired statically, to be acquired in dynamic mode. Specialized MR systems targeted at specific body regions or diseases may increase access to MR and provide options for monitoring and even performing minimally invasive therapy. The full potential of MR is yet to be realized.

REFERENCES 1. Bloch F, Hansen W W, Packard M E 1946 Nuclear induction. Phys Rev 69: 127. 2. Purcell E M, Torrey H C, Pound C V 1946 Resonance absorption by nuclear magnetic movements in a solid. Phys Rev 64: 37–38. 3. Lauterbur P C 1973 Image formation by induced local interactions: examples employing NMR. Nature 242: 190–191. 4. Mansfield P, Grannell P K 1973 NMR ‘diffraction’ in solids? J Phys C 6: 422–426. 5. Mansfield P, Maudsley A A 1977 Medical imaging by NMR. Br J Radiol 50: 188–194. 6. Damadian R, Goldsmith M, Minkoff L 1977 NMR in cancer: Fonar image of the live human body. Physiol Chem Phys 8: 97–108. 7. Hinshaw W S, Bottomley P A, Holland G N 1977 Radiographic thin section of the human wrist by nuclear magnetic resonance. Nature 270: 722–723. 8. Hawkes R C, Holland G N, Moore W S, Worthington B S 1980 NMR tomography of the brain: a preliminary clinical assessment with demonstration of pathology. J Comput Assist Tomogr 4: 577–586. 9. Edelstein W A, Hutchinson J M S, Johnson G, Redpath T 1980 Spin warp NMR imaging and application to human whole body imaging. Phys Med Biol 25: 751–756. 10. Thomas D L, Lythgoe M F, Pell G S, Calamante F, Ordidge R J 2000 The measurement of diffusion and perfusion in biological systems using magnetic resonance imaging. Phys Med Biol 45: R97–138.

11. Wilkinson I D, Griffiths P D, Hoggard N, et al 2003 Short-term changes in cerebral micro-hemodynamics following carotid stenting assessed by MR perfusion imaging. Am J Neuroradiol 24:1501–1507. 12. Neumann-Haefelin T, Moseley M E, Albers G W 2000 New magnetic resonance imaging methods for cerebrovascular disease: emerging clinical applications. Ann Neurol 47: 559–570. 13. Taylor A M, Keegan J, Jhooti P, Gatehouse P D, Firmin D N, Pennell D J 2000 A comparison between segmented k-space FLASH and interleaved spiral MR coronary angiography sequences. J Magn Reson Imaging 11: 394–400. 14. Wilkinson I D 2005 Perfusion and diffusion imaging in chronic carotid disease. In: Gillard J, Waldman A, Barker P (eds) Clinical MR neuroimaging: diffusion, perfusion and spectroscopy. Cambridge: Cambridge University Press. 15. Paley M 1996 Human brain proton spectroscopy. In: Bydder G M, Bradley W (eds) Advanced MR imaging techniques. London: Martin Dunitz. 16. Schaefer S, Balaban R S (eds). 1992. Cardiovascular magnetic resonance spectroscopy. New York: Springer. 17. Ogawa S, Tank D W, Menon R, et al 1992 Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc Natl Acad Sci USA 89: 5951–5955. 18. Rosen B R, Aronen H J, Kwong K K, Belliveau J W, Hamberg L M, Fordham J A 1993 Related articles advances in clinical neuroimaging: functional MR imaging techniques. RadioGraphics 13: 889–896. 19. Middleton H, Black R D, Saam B, et al 1995 MR imaging with hyperpolarized 3He gas. Magn Reson Med 33: 271–275. 20. Sodickson D K, Manning W J 1997 Simultaneous acquisition of spatial harmonics (SMASH): fast imaging with radiofrequency coil arrays. Magn Reson Med 38: 591–603. 21. Pruessmann K P, Weiger M, Scheidegger M B, Boesiger P 1999 SENSE: sensitivity encoding for fast MRI. Magn Reson Med 42: 952–962.

FURTHER READING Overviews Edelman R R, Hesselink R R 2005 Clinical magnetic resonance imaging. Philadelphia: WB Saunders. McRobbie D W, Moore E A, Graves M J, Prince M R 2003 MRI from picture to proton. Cambridge: Cambridge University Press. Reimer P, Parizel PM (rds) 2006 Clinical MR imaging: A practical approach. Berlin: Springer-Verlag.

Sequences design/spatial encoding/hardware Haacke E M, Brown R W, Thompson M R, Venkatesan R 1999 Magnetic resonance imaging: Physical principles and sequence design. Chichester: J Wiley & Sons. Holland G N, MacFall J R 1992 An overview of digital spectrometers for MR imaging. J Magn Reson Imaging 2: 241–246. Landini L, Positano V 2005 Advanced image processing in magnetic resonance imaging. CRC Press. Nassaivier M 1996 All you really need to know about MRI physics. Simply physics. www.simplyphysics.com. Robitaille P-M, Berliner L (eds) 2006 Ultra high field magnetic resonance imaging. Berlin: Springer-Verlag. Schmitt F, Stehling M K, Turner R 1998 Echo-planar imaging: theory, techniques and application. Berlin: Springer-Verlag. Schoenberg S O 2007 Parallel imaging in clinical MR applications. Berlin: Springer-Verlag. Tweig D B 1983 The k-trajectory formulation of the NMR imaging process with applications in analysis and synthesis of imaging methods. Med Phys 10: 610–623.

Diffusion, perfusion and spectroscopy Danielson E B, Ross B 1998 Magnetic resonance spectroscopy diagnosis of neurological diseases. New York: Marcel Dekker.

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Gillard J, Waldman A, Barker P (eds) 2005 Clinical MR neuroimaging: diffusion, perfusion and spectroscopy. Cambridge: Cambridge University Press. Warach S, Davis S 2003 Magnetic resonance imaging in stroke. Cambridge: Cambridge University Press. Young I R (ed) 2000 Methods in biomedical magnetic resonance imaging and spectroscopy. Chichester: J Wiley & Sons.

BOLD fMRI Buxton R B 2001 Introduction to functional magnetic resonance imaging: Principles and techniques. Cambridge: Cambridge University Press. Frackowiak R S J, Friston K J, Frith C D, Dolan R J, Mazziotta J C 1997 Human brain function. New York: Academic Press.

Exogenous contrast Jackson A 2005 Dynamic contrast-enhanced magnetic resonance imaging in oncology. Berlin: Springer-Verlag. Kauczor H-U (ed) 2000 Special issue: hyperpolarized gases in MRI. NMR Biomed 13: 173–264. Stark D D, Weissleder R, Elizando G, et al 1989 Superparamagnetic iron oxide: clinical application as a contrast agent for magnetic resonance imaging. Radiology 168: 297–301. Weinmann H-J, Brasch R C, Press W R, Wesbey G E 1984 Characteristics

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of gadolinium-DTPA complex: a potential NMR contrast agent. Am J Roentgenol 142: 619–624.

Angiography/cardiology/interventional Bogaert J, Dymarkowski S, Taylor A M (eds) 2005 Clinical cardiac MRI. Berlin: Springer-Verlag. Graves M J 1997 Magnetic resonance angiography. BJR 70: 6–28. Lee V 2006 Cardiovascular MRI: Physical principles to practical protocols. Philadelphia: Lippincott, Williams & Wilkins. Lufkin R B 1999 Interventional MRI. St Louis: Mosby. Morris E, Liberman L 2005 Breast MRI: Diagnosis and intervention. Berlin: Springer-Verlag.

Safety Medical Devices Agency 2002 Guidelines for magnetic equipment in clinical use with particular reference to safety. London: Medical Devices Agency. Moseley I F 1994 Safety of magnetic resonance imaging. Br Med J 308: 1181–1182. National Radiation Protection Board 1991 Principles for the protection of patients and volunteers during clinical MRI. NRPB 2 (no 1). Shellock S G 2006 Reference manual for magnetic resonance safety, implants, and devices: 2007 edition. BRPG. Shellock R, D Services Inc. www.mrisafety.com.

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Angiography: Principles, Techniques (Including CTA and MRA) and Complications

6

James E. Jackson, David J. Allison and James Meaney

Multidetector CT angiography • Clinical applications Magnetic resonance angiography • Background • Contrast mechanisms • Post-processing • MRA in clinical practice • ‘Supplemental’ imaging: when is imaging of the lumen not enough? • Future directions Catheter arteriography • Technique • Preparation of the patient

• Contraindications • Anaesthesia • Arterial puncture • Digital subtraction angiography • Intravenous digital subtraction angiography (IVDSA) • Aftercare • Complications Catheter venography • Techniques • Complications Embolization techniques • Embolic materials and techniques • Indications for therapeutic arterial embolization

The imaging of blood vessels has changed considerably since the first edition of this textbook and, indeed, there have been significant new developments in cross-sectional imaging techniques even since the 4th edition. These have made many of the diagnostic catheter angiographic techniques described in previous editions almost obsolete. On the whole this is clearly a welcome advance; the newer multidetector CT angiographic techniques are obviously less invasive and, therefore, safer. Furthermore, in many instances these techniques will give more diagnostic information than could be obtained by conventional catheter arteriography because of the concurrent visualization of surrounding tissues and the ability to reconstruct the data in any plane. One of the disadvantages of the decline in the number of diagnostic catheter

angiograms performed, however, is that it has become more difficult for radiologists to acquire suitable expertise in the catheter techniques that are still required for more complex therapeutic interventional procedures. As a good understanding of the basic principles and techniques of catheter angiography remains essential for those intending to become interventional radiologists (and it becomes less likely that they will be able to obtain sufficient practical experience during their training for the reasons given earlier) it perhaps becomes more important that this information is available in this textbook. The newer cross-sectional techniques for imaging blood vessels will, however, be discussed first as these will, quite rightly, be requested before (and often instead of ) conventional catheter angiography.

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MULTIDETECTOR CT ANGIOGRAPHY (MDCTA) The development of CT machines combining a fan-shaped x-ray source and multiple detector rows has led to the ability to acquire image data from a large tissue volume in a single breath hold. With IV contrast medium and appropriate timing, exquisite images can be obtained of blood vessels during any particular vascular phase. Optimal imaging of the vessels requires the relatively rapid IV injection of iodinated contrast medium (usually 3–5 mls-1) and the acquisition of data at the appropriate time of vascular enhancement. The latter can be estimated based upon the ‘normal’ time of arrival of the contrast medium within the organ being imaged or, more commonly nowadays, by the more accurate use of contrast bolus detection technology. ‘Tight’ boluses of contrast medium using a chaser of normal saline may be useful not only to improve vascular opacification but also to reduce the total volume of contrast medium required. Depending upon the region and volume of the body being imaged hundreds, if not thousands, of axial images will be acquired; whilst all the diagnostic information is available in this data-set, evaluation of the axial images alone can be extremely time-consuming and is helped considerably by reconstruction of the data in axial, coronal, and oblique planes without loss of resolution, so-called multiplanar reconstruction (MPR). Tortuous vessels can be ‘straightened’ by curved MPR to aid in the assessment of luminal narrowing due to, for example, atheromatous disease or encasement by tumour. Maximum intensity projection (MIP) and volume rendering (VR) techniques are additional tools that help greatly in the assessment of blood vessels. Each of these reconstruction techniques has its advantages and disadvantages: 1 MPR is very useful for the rapid review of blood vessels in any plane including the surrounding bone and soft tissues, and will allow the assessment of vessel walls that might be obscured in MIP and VR techniques by the presence of, for example, calcification or an endoluminal stent. Each image, however, gives

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only one ‘slice’ of information and multiple separate images are required to see the vessel in its entirety (Fig. 6.1). 2 MIP techniques produce a planar image from a volume of data within which the pixel values are determined by the highest voxel value in a ray projected along the data set in a specified direction.The images obtained are those most similar to a conventional arteriogram but one of the clear disadvantages of this technique is that any tissue of high density (such as bone or vascular calcification) lying within the ray through a vessel will determine the pixel intensity instead of the contrast medium itself within the blood vessel (Fig. 6.2).This is a common cause of overestimation of vascular stenoses. 3 Volume-rendering techniques assess the entire volume of data with an attenuation threshold for display and produce a three-dimensional image. Typically, tissues are assigned a

Figure 6.2 An MIP image from an MDCT of a renal transplant artery clearly demonstrating the vascular anatomy.

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Figure 6.1 MDCT images of a gastroduodenal artery pseudoaneurysm. (A) An axial image demonstrates an enhancing pseudoaneurysm cavity surrounded by a large haematoma in the region of the pancreatic head. (B) A sagittal MPR image demonstrates a pseudoaneurysm arising from the gastroduodenal artery. (C) A further sagittal MPR image demonstrates that the right hepatic artery, from which the gastroduodenal artery arises, originates from the superior mesenteric artery.

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• ANGIOGRAPHY: PRINCIPLES, TECHNIQUES (INCLUDING CTA AND MRA) AND COMPLICATIONS

colour that is dependent upon their attenuation values, facilitating the differentiation of structures of differing density (Figs 6.3, 6.5). The final images can be rotated in real time to find the best projection to display anatomy and pathology and this is the most important feature of this technique. Vascular stenoses can be overestimated, however, and small vessels may not be clearly visualized. It should be remembered that, whilst these post-processing techniques are very helpful for diagnostic assessment and for display in multidisciplinary team meetings, the axial source images are essential and often allow the operator to distinguish between artefact and disease when an abnormality is suggested on reformatted views.

CLINICAL APPLICATIONS MDCT angiography (MDCTA) is replacing conventional angiography in many, if not all, body areas and is indicated, therefore, in any disease process that requires the visualization

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of blood vessels to improve diagnosis and outcome. Within the thorax, for example, this would include the assessment of: pulmonary embolic disease1,2 (Fig. 6.4); thoracic aortic disease3–5; coronary artery graft patency6–10; and bronchial artery anatomy and pathology in massive haemoptysis11. In the abdomen common indications include the pre-operative planning and posttreatment assessment of abdominal aortic aneurysmal disease12,13 (Fig. 6.5); the assessment of native and transplant renal arteries14–16; the staging of hepato-pancreaticobiliary neoplasms17–20; and the assessment of vascular complications in patients suffering severe trauma21. It is also used increasingly in the assessment of peripheral arterial disease in the lower (and upper) limbs where it is less invasive, less expensive and exposes the individual to less radiation than conventional catheter angiography22–26. The scanning technique (positioning of the patient, rate of contrast medium administration, time of image acquisition), and the post-processing techniques most suited to the different indications listed earlier will clearly vary and lie outside the scope of this chapter; interested readers are referred to other chapters within this book and to other texts cited in the reference list.

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Figure 6.3 The value of MDCT MPR and VR images in the assessment of pulmonary sequestration. (A) The CXR demonstrates a mass projected through the left side of the cardiac silhouette. (B) An axial image from an MDCT examination demonstrates a left paraspinal soft-tissue mass. A feeding vessel arising from the thoracic aorta is visible. (C) MPR and (D) VR images show the full length of the oblique course of feeding artery.

Figure 6.4 MDCT demonstration of bilateral pulmonary emboli. (A) Axial and (B) coronal MPR images demonstrating extensive bilateral pulmonary emboli in central pulmonary arteries.

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Figure 6.5 MDCT images of abdominal aortic aneurysmal disease before and after stent insertion. A large infrarenal abdominal aortic aneurysm is seen on axial (A and D), coronal MPR (B and E) and VR (C and F) images before and after the insertion of an endoluminal bifurcated stent

MAGNETIC RESONANCE ANGIOGRAPHY BACKGROUND Magnetic resonance angiography (MRA) is a method for generating images of blood vessels with magnetic resonance imaging (MRI)27,28. With improved understanding of the nature of the signals emanating from blood vessels on MR images, it became evident that rather than simply contribut-

ing a source of artefacts on MR images, flow phenomena could be harnessed to generate diagnostic ‘angiograms’27–29. MRA has undergone a revolution over the last decade, replacing catheter angiography as the primary diagnostic tool for the evaluation of most vascular territories (apart from the coronary arteries); this change is due mainly to the success of contrast-enhanced techniques30.

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CONTRAST MECHANISMS Unenhanced (time-of-flight [TOF] and phase contrast [PC]) MRA With these techniques, the intravascular signal depends on inherent properties of flow, and the MR parameters must be carefully tailored to ensure a high intravascular signal27,28. In the case of TOF MRA, for example, data must be acquired perpendicular (and ideally orthogonal) to the direction of flow, and the time between successive radio frequency (RF) pulses (the repetition time [TR]), must be sufficiently long to allow an adequate ‘inflow’ of fully relaxed protons into the imaging slice27.The TR, therefore, is dictated by expected flow rates within the regionof-interest and, typically, should be 35 ms or greater. As the data acquisition time is directly proportional to the TR (acquisition time = TR × number of phase-encoding steps × number of slices × number of excitations), a TR substantially greater than the shortest possible for gradient-echo imaging (3–5 ms) must be used, with resultant prolongation of scan time. Additionally, owing the predominant head–foot orientation of the major arteries (e.g. the aorta, ilio-femoral and infra-popliteal vessels), the axial plane must be used, which also prolongs the data acquisition owing to the large number of slices required. Despite ‘faster’ techniques, therefore, acquisition times for TOF MRA are artificially prolonged, firstly as a result of physiological bloodflow rates that mandate the use of a relatively long TR and secondly by the requirement for axial imaging, which affords poor spatial coverage in comparison with sagittal or coronal imaging30. Selective arteriograms or venograms can be acquired by employing a (travelling) saturation pulse placed downstream of the imaging slice for MRA (to eliminate venous return from the opposite direction) or upstream of the imaging slice to generate MRV’s (venograms). If no saturation pulses are employed, both arteries and veins are identified on the same image.

Time-of-flight MRA methodology and limitations TOF angiography relies on the fact that the blood enters the volume under consideration with relatively high velocity and traverses it quickly, so that it receives very few RF pulses27,28. In order to maintain a highest possible inflow effect, all protons within the imaging volume must be replenished between successive TRs, though maximal inflow may not be necessary in clinical practice and some trade-offs can be accepted.An oblique course of the blood vessel being imaged in relation to the slice orientation and short TRs both adversely affect signal-to-noise ratios (SNR) as a result of protons under these circumstances experiencing more RF pulses whilst in the imaging slice. The severity and length of stenoses also tend to be overestimated on TOF MRA images because of intra-voxel dephasing secondary to turbulent, slow or pulsatile flow. As a result of these limitations,TOF MRA has failed to offer a viable non-invasive screening alternative to conventional arteriography, and has not had a major impact on clinical practice.

Phase-contrast MRA Phase-contrast angiography (PCA) is now seldom used in clinical MRA. The methodology underpinning the technique

is somewhat complex and, like TOF MRA, images are prone to artefacts and data acquisition is lengthy29. The term ‘phase’ refers to the angle that the transverse magnetization makes relative to a reference axis. When protons are moving, for example, in flowing blood, a change in phase proportional to the distance the proton moves (and, therefore to blood velocity) is induced by the imaging gradients, in particular the slice-selection gradient and the frequencyencoding gradient. As these gradients actually consist of a pair of gradient pulses applied in opposite directions (so-called bipolar gradients), the effect of each gradient on the phase of protons for stationary (i.e. background, motionless) tissues is equal and opposite, and the effect cancels out. For moving (flowing blood) protons, the position of each proton will change between consecutive pulses resulting in a phase change relative to stationary protons that is proportional to velocity. This observation of gradient-induced phase change provides the basis for phase-contrast angiography in which the gradient pulses are designed to produce phase changes for a given velocity range. In this way, the signals do not cancel, phase information is preserved during the image reconstruction. Pixel brightness is directly proportional to the phase-shift acquired by a moving proton in the magnetic field and, therefore, to velocity. In practice, as the method is only sensitive for the velocity component applied along the flow-encoding gradient, the acquisition must be repeated a total of four times in order to generate an ‘angiogram’: an initial flow-compensated sequence is followed by three flow-encoded acquisitions one for each direction of flow (head–foot, left–right, anteroposterior), followed by a complex subtraction to generate the final angiographic image. As the phase is unchanged for static protons, the subtraction completely suppresses the signal from the background tissue thus facilitating the generation of high-quality images29. One of the major challenges of PCA relates to the requirement of the operator to appropriately select the velocity-encoding gradient.As the signal intensity is proportional to velocity, the range of velocities present within the vessels of interest must be inferred or measured to allow the operator to set the velocity-encoding gradient (Venc) correctly.This assumes an a priori knowledge of the blood flow velocities within the relevant artery and, though this can be rapidly measured directly by acquiring a series of 2D PC images with different phase-encoding values, it is time-consuming and the presence of different flow velocities within the arteries enclosed within a single field of view may introduce artefacts29.

Limitations of unenhanced MRA and requirement for contrast agents At each stage of the evolution of MRA, high accuracy was reported for almost all techniques when compared with catheter angiography27–29 but TOF and PC MRA did not gain widespread acceptance in clinical practice because of long examination times, suboptimal resolution and frequent artefacts. TOF MRA was used to evaluate disease involving the carotid bulb and the femoro-popliteal and pedal arteries as these vascular territories were ideally suited to this technique due to the relatively straight course of their vessels, which

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meant that adequate ‘inflow’ could be ensured. MRA was also established as an accurate modality for portrayal of the proximal intra-cranial arteries (despite the fact that the arteries demonstrate marked tortuosity) because of the relatively small volume of tissue that needed to be covered, coupled with the fact that constant blood flow within the cerebral arteries over the cardiac cycle optimizes intravascular signal29,30.

Contrast-enhanced MRA (CEMRA) Because of their unmatched high contrast-to-noise ratios, high spatial resolution, rapid speed of acquisition and relative freedom from artefacts, contrast-enhanced techniques have almost universally replaced non-contrast techniques in clinical practice30. Unlike TOF and PCA techniques, where the intravascular signal is dependent on inherent properties of flow and is, therefore, at the mercy of alterations in flow rate secondary to vascular disease, intravascular signal for contrast-enhanced MRA (CEMRA) depends on a T1 shortening effect induced by the injection of a paramagnetic contrast agent (usually gadolinium based). Images can, therefore, be acquired in any plane including coronal, which affords the best anatomical coverage for virtually all vascular territories outside the brain (Fig. 6.6). In addition, the ability to exploit ultrafast 3D acquisitions (by using the shortest TRs possible), allows rapid image acquisition that can easily be accommodated within a single breath-hold, an important factor when imaging in the chest and abdomen. In order to generate ‘selective’ arteriograms, images are acquired during the first arterial passage of the contrast agent before its arrival within the veins.The synchronization of data acquisition with the peak arterial bolus is one of the major challenges of CEMRA as the rate of transit of contrast medium from the peripheral vein injection site to the vessel of interest is affected by a number of factors including heart rate, stroke volume and the presence or

Figure 6.6 A surgically created dialysis (arteriovenous) fistula in the left arm of patient with chronic renal failure.

absence of proximal steno-occlusive lesions. Although the circulation time can be measured using a test bolus, or can be inferred by making some assumptions about the patient’s cardiovascular status, the process is now automated by employing an MR fluoroscopic approach – a technique that demonstrates contrast medium arrival in real time on the display monitor, thus signalling the appropriate time for data acquisition31. The unique nature of k-space (the array of data from which the final image is generated) whereby the central lines determine image contrast and the peripheral lines determine image resolution, can be uniquely exploited to generate CEMRA images with unrivalled signal-to-noise ratios32. In situations where breath-holding is not required (e.g. peripheral MRA and carotid artery imaging) as long as collection of the contrast-defining central lines of k-space is completed during the arterial peak before contrast medium reaches the veins, the continued collection of resolution-defining peripheral lines of k-space during venous enhancement does not result in venous contamination of the images32. CEMRA is now the standard of reference for MRA against which all new techniques must be measured.

POST-PROCESSING Regardless of which method is employed to generate MR angiograms, the aim of all techniques is to make the arteries the brightest structures on the images, and to extract the vascular data by means of a maximum intensity projection (MIP) computer algorithm28 (Figs 6.7, 6.8). Other methods of post-processing include multi-planar reformatting, volume rendering and surface-shaded displays. For phase-contrast MRA, there is inherent complete background suppression because of the absence of bulk motion in background tissues.

Figure 6.7 Normal MRA. Note clear depiction of the abdominal aorta, iliac arteries and renal arteries on the frontal MIP.

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monary angiography; and the fact that catheter pulmonary angiography, the reference standard against which new and improved MRA techniques should be compared, has largely disappeared from clinical practice due to the success of CTA, thus depriving MRA of a valid arbiter for comparative studies. Improvements in spatial resolution bring the subsegmental arteries within the realm of MRA (Fig. 6.9) and further refinements including MR perfusion and ventilation (mirroring the ventilation and perfusion components of nuclear medicine studies albeit at much higher resolution) offer additional functionality to determine the location and distribution of small emboli36.

Abdominal aorta, renal and mesenteric arteries

Figure 6.8 Severe left renal artery stenosis and right common iliac artery occlusion.

For TOF MRA, the background is suppressed by virtue of the short TR in relation to the longish T1s of background tissues. Although fat remains bright, it can be eliminated by use of fat-saturation techniques, albeit with an additional time penalty. For CEMRA, there is the additional benefit that the background tissues can be completely eliminated by the subtraction of a mask acquired before the injection of contrast material.

CEMRA is the MR technique of choice for imaging the aorta in its entirety and for evaluating its large and medium-sized branches including the renal (Fig. 6.8) and proximal mesenteric arteries30,37–40. Because of the need for breath-holding the technique’s spatial resolution remains inferior to that of catheter angiography because of the inability to collect a highresolution data-set that matches that of DSA during a breathhold. Nonetheless, numerous studies and meta-analyses attest to the accuracy of MRA in clinical practice38. An additional benefit of MRA lies in its ability directly to measure the flow rate to each kidney using a two-dimensional (2D) cardiactriggered, phase-contrast approach, which facilitates both the assessment of both end-organ damage and the likelihood of success of transluminal angioplasty37. MRA is also highly accurate for depicting the mesenteric arteries in patients with suspected chronic mesenteric ischaemia39. In patients with abdominal aortic aneurysms, the external dimensions of the aneurysm can easily be delineated, should this be necessary, with targeted pre-contrast or post-contrast

MRA IN CLINICAL PRACTICE MRA is an excellent technique for imaging most vascular territories but is generally avoided in unstable and/or ventilated patients and those with severe trauma because of the hazards of the MR environment and the difficulties in monitoring patients within the MR room. Standard contra-indications to MRI (pacemakers, intracranial uneurysm clips) also preclude use of MRA.

Thoracic aorta and great arteries Because of the relatively large size of these vessels, they can be demonstrated with a wide variety of techniques but CEMRA is favoured in most instances owing to its rapid speed of acquisition and the quality of the images generated33,34.

Pulmonary arteries Although several studies have established high accuracy for MRA compared with pulmonary angiography for the evaluation of suspected pulmonary embolism, it is not widely used clinically35,36. Reasons for this include a reluctance to refer potentially unstable patients to MRI; the availability of CT pul-

Figure 6.9

Normal pulmonary MRA.

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images as only the lumen is demonstrated with CEMRA40. Calcium within the wall is not demonstrated, however, and aneurysm assessment for planning endovascular stenting is usually performed with CTA.

Carotid arteries Because of the requirement accurately to differentiate stenosis at a 70 per cent cut-off within a relatively small (internal carotid) artery, there are stringent spatial resolution requirements for carotid MRA41. As the carotid bifurcation does not move with respiration a relatively long data acquisition that generates images with sufficiently high (isotropic) spatial resolution is recommended. Despite the fact that the resultant data acquisition is substantially longer than the arterio-venous transit

A

D

G

B

E

H

time of 8–12 s (the blood–brain barrier prevents the parenchymal extraction of gadolinium and therefore facilitates rapid transit from artery to vein), this does not lead to unacceptable venous contamination of the images as there is sufficient time within this arterio-venous window for acquisition of the contrast-defining central lines of k-space. Clearly, acquisition of these central lines must be synchronized with the peak arterial bolus by combining some form of bolus detection as described previously with a ‘centric’ order of k-space filling. In comparison with cathether angiography CEMRA has demonstrated high accuracy in evaluating the carotid artery, e.g. for differentiating between significant and insignificant stenoses, differentiating between critical stenoses and occlusions, and for depicting carotid and vertebral dissections (Fig. 6.10).

C

F Figure 6.10 T2, FLAIR and diffusion-weighted images in a patient with right-sided weakness and aphasia. All the images were acquired in the axial plane at the same level. (A–D) Note the high signal on T2 (A), FLAIR (B), and Diffusion-weighted images (C) (arrowed) with a corresponding low-signal intensity on ADC map (D), ringed indicating an acute cerebral infarct. (E, F) Whole-volume MIP images from a TOF MRA in coronal (E) and axial (F) orientation demonstrate reduced signal intensity within the left internal carotid (short arrows) and left middle cerebral arteries. Targeted MIP images of the left-sided carotid and vertebral arteries demonstrate a severe stenosis of the internal carotid artery just beyond the bulb (not shown). Axial T1 (G) and T2w (H) images with fat-saturation reveal crescentic high-signal intensity within the left ICA (long arrows) at the site of the stenosis demonstrated on CEMRA, diagnostic of acute dissection.

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• ANGIOGRAPHY: PRINCIPLES, TECHNIQUES (INCLUDING CTA AND MRA) AND COMPLICATIONS

Peripheral arteries In the peripheral arteries, as in most other areas, TOF MRA has been superseded by CEMRA. Although the spatial coverage offered by single-field-of-view imaging is insufficient to address all of the relevant anatomy, the introduction of moving-table MRA has opened the way for routine noninvasive MRA of the entire run-off arteries in a short timeframe (<20-minute examination)42,43 (Fig. 6.11). The major limitation of moving-table MRA is venous contamination in the third location. Methods to eliminate this include the use of tourniquets inflated to sub-systolic pressures to delay onset of venous enhancement, careful attention to detail in setting up the examination (to avoid any redundancy in anatomical coverage), the use of high parallel-imaging factors and the exploitation of ultra-short TR imaging42,43.

Figure 6.11 Peripheral MRA performed using a threestation, moving-table approach. The study demonstrates excellent visualization of the entire run-off arteries from the mid-abdominal aorta to the level of the pedal arch. Note extensive vascular stenoses and occlusions and a bypass graft from the right popliteal artery to the right anterior tibial artery.

‘SUPPLEMENTAL’ IMAGING: WHEN IS IMAGING OF THE LUMEN NOT ENOUGH? Currently, virtually all clinical decision making is based on the appearance of the lumen, though clearly the relevant pathology (atheroma) lies within the wall. Efforts to delineate the various components of plaque, in particular the ‘unstable’ plaque, have met with mixed results. A particular situation exists in the imaging of carotid and vertebral artery dissections, where imaging of the lumen alone simply demonstrates narrowing indistinguishable from other causes, but where cross-sectional imaging of the lumen with spin-echo imaging is essential to demonstrate the typically bright appearance of the usually crescent-shaped intramural haematoma. Therefore, in all cases of suspected carotid or vertebral dissection pre-contrast T1 and T2w fat images saturated should be performed. Failure to do so results in the identification of a focal stenosis only, and robs the clinician of the opportunity to prescribe anticoagulation therapy, the treatment of choice for dissection. Other instances in which imaging additional to that provided by the ‘luminogram’ is helpful include arteritides (e.g Takayasu’s and Behçets disease), aneurysms and the assessment of vessels narrowed or invaded by tumour.

FUTURE DIRECTIONS Improvements in MRA are aimed at increasing both spatial and temporal resolution whilst minimizing contrast-to-noise loss.

Improved coil efficiency and new parallel imaging methods that increase acquisition speed and/or spatial resolution by a factor of 2–16 are becoming routine in clinical practice44,45 and 3T imaging opens new horizons due to its improved signalto-noise capability44,46. New contrast agents (1.0 M and bloodpool agents) and the potential for routine functional imaging of end-organ function offer exciting prospects for future improvements. Currently, new applications are being added constantly, and isotropic submillimetre resolution studies for all regions of interest combined in a single examination with functional evaluation are anticipated within the near future.

CATHETER ARTERIOGRAPHY TECHNIQUE The risks associated with modern arteriography are extremely small. Arteriography is still nevertheless an ‘invasive’ procedure and it should never be undertaken unless the radiologist is satisfied that the likely benefits justify the potential risks. An arteriogram should never be carried out simply because it has been scheduled or ‘routinely requested’ by a clinical team;

mistakes inevitably occur and the radiologist responsible for the procedure should be satisfied in every case that proper indications exist for the particular study requested. The arteriographer should also be quite clear before starting as to what information is required from the procedure; this ensures that the correct studies and projections are obtained and allows for rational decision making during the procedure if something unexpected is shown or a problem arises. Most of these

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comments are clearly applicable to any imaging technique but are arguably more important and perhaps easier to enforce than is the case for non-invasive studies.

PREPARATION OF THE PATIENT Informed consent should be obtained for arteriography. A doctor, preferably the responsible radiologist or a member of the radiology department, should see the patient before the procedure to explain what is to be done, check that no contraindications to the study exist, check the appropriate pulses and ensure that adequate premedication is arranged.The groin should be shaved if a femoral approach is to be used. It has been the usual practice for patients to be ‘nil by mouth’ for an appropriate period before the procedure to avoid the risk of aspiration during a possible reaction to contrast medium or other serious accident. It is now the policy in many departments, however, only to stop solid foods and to permit free oral fluids unless general anaesthesia or heavy premedication is being used. Whatever regimen is adopted, adequate measures should be taken to avoid dehydration during the procedure and the recovery period.

CONTRAINDICATIONS There are very few absolute contraindications to arteriography but there are many factors that considerably increase the hazards of the technique. Always check that a patient is not pregnant before arteriography, as the radiation dose may be considerable. If arteriography is essential in a pregnant patient, the dose to the fetus should be minimized by protection, field collimation and careful choice of filming sequences. Caution should be exercised in patients on anticoagulant therapy or with other bleeding diatheses.Arteriography should be avoided if possible in such cases; if it is essential then all possible steps should be taken to correct or improve the coagulation defect before and during the procedure if this is clinically acceptable. Other factors that increase the risk of bleeding from an arterial puncture site include systemic hypertension and disorders predisposing to increased fragility of the vessel wall such as Cushing’s syndrome, prolonged steroid treatment and rare connective tissue disorders such as certain types (especially type IV) of the Ehlers–Danlos syndrome. Arteriography may be necessary in a patient with a suspected or known previous adverse reaction to contrast medium and this problem is discussed in Chapter 2. Arteriography can require larger doses of contrast medium than any other radiological procedure and particular care must be exercised in infants and in dehydrated or shocked patients, patients with serious cardiac or respiratory disease, patients in hepatic or renal failure, and other patients with serious metabolic abnormalities.

ANAESTHESIA Most arteriography is performed under local anaesthesia, though general anaesthesia is necessary for babies and young

children, for confused, difficult or very nervous patients, and in some complex and interventional procedures. Although general anaesthesia can be more pleasant for the patient than local anaesthesia and reduces motion artefact on the radiographs, it nevertheless adds to the risks of arteriography. This is not only because of the (small) risks inherent in general anaesthesia but also because it masks the patient’s subjective symptoms and reactions.These may provide the radiologist with immediate warning of a mishap such as the subintimal injection of contrast medium or the inadvertent wedging of the catheter tip in a small artery: a warning that may well prevent more serious injury.

ARTERIAL PUNCTURE It is often said that the most important part of an angiographic procedure is the initial vessel puncture and there is no doubt that a good technique is likely to make the subsequent angiogram not only more comfortable for the patient but also easier for the angiographer. It should go without saying that the most suitable route of access in order to achieve the aims of the study should have been chosen before the patient enters the angiographic suite; this decision will often depend upon a number of factors including previous imaging studies, operation notes and clinical examination. For example, when performing a diagnostic arteriogram (or angioplasty) of the main artery supplying a renal transplant it is worthwhile reviewing the operative notes to see if the arterial anastomosis was made end-to-end with the internal iliac artery or end-to-side with the external iliac artery; the former is often easier to selectively catheterize from a contralateral femoral arterial approach, whilst the latter is best studied via an ipsilateral puncture. The most common vessel punctured for diagnostic and therapeutic angiography is the common femoral artery. Axillary, brachial or radial approaches can be used but these routes are usually reserved for those patients in whom a femoral approach is not possible due to iliac occlusive disease.There has, in recent years, been a trend towards the greater use of upper extremity access even in those individuals with patent femoral vessels.This is partly because DSA enables adequate studies to be obtained by injection through smaller calibre catheters (presumed to be associated with a lower morbidity than larger catheters) and partly because of the move towards the performance of angiography as an outpatient or day-case investigation. The latter trend, motivated by economic and logistic considerations as well as those related to the patient’s convenience, favours the upper extremity approach because of the rapidity with which a patient who has undergone an axillary, brachial, or radial procedure can be mobilized in comparison with one who has had a groin puncture and the greater ease with which the upper extremity puncture or arteriotomy site can be monitored and controlled during the hours following the investigation.A popliteal artery puncture may be useful in certain instances such as angioplasty of the superficial femoral artery when it is not possible to catheterize this vessel via an antegrade approach. The technique of arterial puncture and catheterization of those vessels most commonly used for arterial access will be described.

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• ANGIOGRAPHY: PRINCIPLES, TECHNIQUES (INCLUDING CTA AND MRA) AND COMPLICATIONS

Retrograde Femoral Artery Puncture (Fig. 6.12) The artery is palpated to select the site of puncture before local anaesthetic is injected. Various anatomical descriptions are given regarding the site at which to puncture but the aim should be to enter the common femoral artery a short distance below the inguinal ligament. This is best achieved by puncturing the vessel where it can be most easily palpated, irrespective of the relationship of this point to the inguinal skin crease. Since this is the point where the artery crosses the pubic bone it is also the easiest point at which to achieve haemostasis afterwards. It is important that the arterial puncture site should be adequately anaesthetized. After cleansing the skin with a suitable preparation, 5–10 ml of 0.5–1 per cent lignocaine is infiltrated around the artery. It is important to inject the local anaesthetic agent posterior to the artery as well as anterior to it, even if a single-wall puncture of the vessel is subsequently made, as it makes the arterial puncture and subsequent catheter manipulation much more comfortable for the patient. In addition, if the puncture site is inadequately anaesthetized arterial spasm is more likely, which may make selective catheterization very difficult because of the lack of free catheter movement. After local anaesthesia a small scalpel incision is made in the skin (large enough to accommodate the anticipated catheter), the skin being temporarily drawn laterally during the incision to avert the risk of a scalpel injury to the arterial wall. A pair of fine artery forceps is inserted into the incision and used to create a tunnel through the subcutaneous tissues down to the artery. This manoeuvre is particularly

Figure 6.12 Percutaneous catheterization. One of the commonly used techniques of percutaneous arterial catheterization. The artery (1) is transfixed (2). The needle is partially withdrawn and re-angled (3). A guidewire is passed into the needle during free backflow of blood (3, 4), the needle removed and a catheter or introducer inserted over the wire (5, 6). When the catheter is safely within the arterial lumen the wire is withdrawn (7).

important in large or obese patients, for it not only facilitates catheterization but it reduces the risk of a postoperative haematoma: any escaping blood emerges through the incision and is immediately apparent, instead of collecting subcutaneously. The technique employed for puncturing the artery is a matter of personal preference. A reliable way is to feel the artery with the middle and index fingers of the left hand and insert the needle (held in the right hand) between the two palpating fingers. Gentle pressure with the needle will alter the pulse as detected by the lower (index) finger, giving reassurance as to its correct alignment. The needle is held angled forwards and passed through the anterior wall alone or right through the artery depending upon the angiographer’s preference (see later). A single-wall puncture technique is most commonly performed with a one-part needle, in which case free pulsatile blood flow will occur as soon as the needle enters the vessel lumen. When a double-wall puncture technique is performed a two-part needle is used; after passing through the vessel, the central stylet is removed, the needle angled slightly more towards the horizontal and then withdrawn at an even rate, assisted by gentle rotatory movements to avoid any sudden jerking. When the tip of the needle is safely in the arterial lumen there will be a free, spurting backflow of blood from the hub. While the needle is held steady with one hand the soft tip of a guidewire is threaded through the needle into the artery. When a sufficient length of wire is inside, the needle is removed and firm manual pressure maintained on the puncture site until the needle has been exchanged for a catheter or dilator. The guidewire is removed when the tip of the catheter is in a satisfactory position and the catheter is then flushed free of blood with heparinized saline. At the end of a correctly conducted insertion procedure there should be no bleeding around the catheter, which will move freely and painlessly through the puncture site when manipulated. There are arguments in favour of both single- and doublewall arterial punctures; some radiologists prefer to puncture only the anterior wall of the artery to minimize the trauma to the vessel, although puncture to both vessel walls does not increase the risk of complications as these are usually caused by the subsequent manipulations with guidewires and catheters. Proponents of a double-wall puncture technique maintain that this method is safer, particularly when first learning angiography, with a lesser risk of intimal dissection when introducing the guidewire through the needle when compared with a single-wall technique. Whichever method is employed, if a guidewire does not pass freely into the arterial lumen it should not be forced; this technique is never successful and usually causes an intimal dissection. If there is good backflow of blood the reason for failure of the wire to pass freely may be either that the needle is angled sharply towards one wall of the blood vessel or that the wire is passing into a small branch vessel such as the deep circumflex iliac artery. A number of manoeuvres may help, including fluoroscopy, cautious repositioning of the angle of the needle or changing to a J-wire. A gentle injection of contrast medium is possible to help ascertain the nature

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of the problem but only if good backflow is present. If there is poor backflow then the needle may be positioned near an atheromatous plaque or a stenosis, may be only partially in the lumen, or may have caused an intimal dissection. In these circumstances discretion is advised and it is wise to start again with a fresh puncture. In difficult cases remember that there is usually a femoral artery in the opposite leg! Better two groin punctures than a dissection or a large haematoma. The catheter is flushed with a heparinized saline solution throughout the procedure to prevent clotting.Various concentrations of heparin are used in different centres; the authors use 2000 IU heparin L-1 normal saline. During an average procedure it would be unusual for a patient to receive much more than about 500–1000 IU in this way. It is almost always preferable to give a firm hand flush intermittently, rather than maintain a continuous slow flush infusion. This technique not only leaves the proximal end of the catheter free for manipulation but also is more effective, since a slow infusion may only clear the proximal holes of a catheter with multiple side-ports; clot forms in the end-port and the more distal side-ports, and is then blown out into the vascular system when a pressure contrast injection is performed.

Antegrade femoral artery puncture The most common indication for an antegrade puncture of the femoral artery is when performing ipsilateral superficial femoral, popliteal or infragenicular artery angioplasty. Once again, the aim should be to puncture the common femoral artery just below the inguinal ligament. The most common problem associated with this procedure is catheterization of the profunda femoris and many methods have been described in order to manipulate the catheter out of this vessel into the superficial femoral artery when this has happened. With a good technique, however, this complication should rarely occur. Preparation of the patient is important; obese patients may have an abdominal ‘apron’ that hangs over the groin and this should be lifted superiorly and strapped out of the way with heavy-duty tape. It is well worthwhile when performing an antegrade femoral puncture to screen over the femoral head to determine the correct site for vessel puncture, as this is often considerably higher than anticipated when using palpation alone. The fovea of the femoral head is a useful landmark for the correct site of arterial access and this can be marked on the skin before local anaesthetic is infiltrated in the same way as for a retrograde puncture. A skin incision is made with a scalpel blade and blunt dissection is again performed of the soft tissues over the femoral artery. The vessel is then punctured with the needle angled slightly towards the feet. The best wire to use is a wide-angled J-wire with a curvature of radius 7.5 mm. This should be introduced through the needle with the tip of the curve directed anteriorly so that, as it exits the needle tip within the vessel lumen, it is directed into the superficial femoral artery rather than the profunda femoris. A straight guidewire is much more likely to pass directly into the latter vessel because of the posterolateral orientation of this artery.

Popliteal artery puncture The patient is placed prone on the angiography table and US is used to visualize and puncture the popliteal artery, which lies deep and lateral to the popliteal vein in the popliteal fossa. Intra-arterial vasodilator agents are commonly employed routinely to reduce the risk of spasm.

Axillary artery puncture When performed correctly this is arguably the safest puncture to perform in the upper limb47–49. The term axillary puncture is in fact incorrect as the most proximal portion of the brachial artery is punctured rather than the axillary artery itself and the description of ‘high brachial’ is preferred by some. With the arm abducted (the left arm is preferred) to approximately 135 degrees and the hand placed under the patient’s head, the artery is palpated over the superior portion of the humerus, where it is punctured after local anaesthetic infiltration and skin puncture as previously described. Complications of haematoma and pseudoaneurysm formation are seen in less than 1 per cent of patients and the feared complication of brachial plexus injury is rare but if a haematoma should develop there should be low threshold for performing surgical decompression to prevent a neurological deficit. Arterial spasm is less common than when low brachial and radial artery punctures are performed and intra-arterial vasodilator agents are not administered routinely.

Brachial artery puncture The brachial artery may be punctured anywhere along its course but the most common site is the antecubital fossa above the elbow joint, where it lies medial to the biceps tendon50. Arterial spasm is more common than when an ‘axillary’ artery puncture is performed51,52 and intra-arterial vasodilators are administered routinely by some practitioners once the vessel has been catheterized. If a sheath of greater than 7 Fr in size is likely to be necessary then a formal surgical cut-down is preferred by some.

Radial artery puncture This vessel is cannulated using a micropuncture set. A 4 Fr sheath is then introduced through which a 120 cm diagnostic catheter is manipulated over a guidewire into the aorta. Intra-arterial vasodilator agents are routinely administered to reduce the risk of arterial spasm. Before employing this route it is important to confirm that there is a good collateral supply to the hand through the ulnar artery in case of subsequent radial artery occlusion.

Selective catheterization By manipulating a catheter under fluoroscopic control it is possible to insert the catheter selectively into various branches of the vascular system such as the renal artery, coeliac axis, axillary artery, etc. Different catheter shapes are available (Fig. 6.13), each of which is suitable for a particular manoeuvre or for catheterizing certain arterial branches. Superselective catheterization (also known as subselective embolization) is the term used for the catheterization of small subsidiary arteries that themselves arise from named branch arteries and is most frequently performed during embolization procedures. A co-axial

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are taken so as to embrace all the different phases of the cardiac cycle, then appropriate mask selection will subsequently permit virtually any contrast-filled image to be presented free of artefact.The same technique can be used in those individuals who are unable to hold their breath for any length of time. Such patients should be asked to breathe normally throughout the run and multiple images are obtained before the injection of contrast medium so that a suitable mask for subtraction is available for every phase of respiration. This technique is particularly suited to visceral angiography (Fig. 6.15).

INTRAVENOUS DIGITAL SUBTRACTION ANGIOGRAPHY (IVDSA) Figure 6.13 Some examples of catheters in common use. Some of the many different catheter shapes available are illustrated. From left to right: straight flush; pigtail; cobra; and sidewinder. Note the side-ports in some of the catheters.

catheter (one that passes through the lumen of a diagnostic or guiding catheter) is often used for the catheterization of these small vessels (Fig. 6.14).

DIGITAL SUBTRACTION ANGIOGRAPHY With any DSA examination particular attention must be paid to the elimination of movement artefact. Respiratory motion needs to be controlled (a nose-clip is often helpful) and in the case of abdominal and pelvic examinations the effects of bowel movement can be minimized by the use of paralytic agents. Multiple mask acquisition is a simple and muchneglected technique for counteracting the effect of inevitable movement such as, say, the artefacts produced in pulmonary arteriograms by cardiac motion. If several precontrast images

The introduction of IVDSA was hailed as a major breakthrough and enthusiasts initially predicted that it would eventually replace intra-arterial angiography. Experience, however, has proved that IVDSA often produces nondiagnostic images because of patient movement, poor cardiac output and the superimposition of vessels. It may also require the use of very large volumes of contrast medium, which not only restricts the number of studies that can be obtained during any one procedure but also makes the technique unsuitable for patients in whom a significant load of contrast medium would be particularly undesirable; the indications for its use are now limited.

AFTERCARE When an arteriographic study is completed the catheter is withdrawn and firm manual pressure applied to the puncture site for 5–10 min. The radiologist should be absolutely satisfied that bleeding has stopped before the patient leaves the angiography suite. The wound site is then checked at regular intervals by the nursing staff, who should also record pulse and

Figure 6.14 Co-axial catheterization. (A) A coeliac axis arteriogram performed through a 7 Fr catheter shows an aneurysm at the splenic hilum. This needs selective embolization but the long tortuous splenic artery presents a formidable technical obstacle to catheterization with a conventional catheter. (B) A co-axial (tracker) catheter has been passed to the site of the aneurysm, which was successfully occluded without compromising the splenic circulation.

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Figure 6.15 Example of use of breathing technique during visceral angiography. Arterial (A) and venous (B) images from a superior mesenteric arteriogram acquired during patient respiration. Intestinal peristalsis has been obliterated with hyoscine butylbromide. The arterial and venous images were acquired at different phases of respiration but the use of different masks (mask 2 for the arterial image and mask 10 for the venous image), acquired before the injection of contrast medium, has resulted in excellent quality images.

blood pressure observations for a reasonable period following the procedure and check that distal pulses remain palpable. Pressure pads, sand bags and other accoutrements are generally a waste of time. It is much better to be able to see the puncture site than to cover it up. If bleeding does not stop from a puncture site, press for longer! Almost all post-catheterization bleeding can ultimately be controlled by local pressure unless the artery has been torn or there is a coagulation abnormality. Several devices are now available that are used to seal the puncture point in the vessel wall at the time of catheter withdrawal in order to allow rapid mobilization and discharge of the patient, often within 1–2 h53–55. These have become popular in many centres following cardiac catheterization and are being utilized more commonly in peripheral angiography. Care should be exercised in their use, however, as a least one meta-analysis of published data has demonstrated little evidence that they are effective and concluded that they may be associated with an increased risk of haematoma and pseudoaneurysm formation56. An adequate record of the procedure should be entered in the patient’s case notes. This should include: • date • name of the operator • puncture site • catheter size • studies performed • names and doses of anaesthetic agents • volumes and concentrations of contrast medium and other drugs administered • preliminary findings • any complications during the procedure • integrity or otherwise of the pulses peripheral to the puncture site at the end of the procedure • post-procedural nursing instructions.

These notes are important not only for patient care but also as a medico-legal record and they should be comprehensive and accurate.

COMPLICATIONS The principal complications of arteriography are listed in Table 6.1.

Contrast medium reactions The many possible adverse effects of contrast media, together with details of their prevention and treatment, are discussed in Chapter 2.

Adverse drug reactions Apart from contrast medium reactions, local anaesthetic agents or other drugs given during the procedure may cause adverse or idiosyncratic effects.

Puncture site complications Haemorrhage Haemorrhage may occur from the puncture site and may cause external blood loss or a subcutaneous haematoma, which can result in extensive bruising (Fig. 6.16). Retroperitoneal bleeding is uncommon but may occur if the arterial puncture is performed above the inguinal ligament. Perhaps the commonest reason for this is the introduction of the needle during retrograde femoral artery catheterization at too acute an angle so that it passes through the back wall of the external iliac artery above the inguinal ligament. It is less well recognized, however, that this complication may also occur when the femoral artery is correctly punctured; this is probably due to a downward extension of the pelvic and abdominal wall fascial layers around the femoral artery and vein, the so-called femo-

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Table 6.1

• ANGIOGRAPHY: PRINCIPLES, TECHNIQUES (INCLUDING CTA AND MRA) AND COMPLICATIONS

COMPLICATIONS OF ARTERIOGRAPHY

Contrast medium-related complications Minor adverse reactions Major adverse reactions and death Local vascular changes (effects on blood cells, viscosity, vascular tone; results of extravasation, etc.) Systemic vascular changes (effects on blood volume, osmolality, etc.) Individual organ toxicity (heart, kidney, brain, etc.) Adverse reactions to local anaesthetic or other drugs Puncture site complications Haemorrhage (external bleeding or haematoma) Intramural or perivascular injection of contrast medium Vascular thrombosis (dissection, local trauma) Peripheral embolization from puncture site Vascular stenosis or occlusion Aneurysm or pseudoaneurysm formation AV fistula Local sepsis Damage to nerves Damage to other local structures Catheter-related and general complications Catheter thrombus embolism Air embolism Gauze embolism Dissection, perforation or rupture of vessels Organ ischaemia or infarction secondary to spasm, dissection or embolism Interventional accidents Fracture and loss of guidewire or catheter fragments Knot formation in catheters Inadvertent injection of toxic material (e.g. skin-cleansing lotion) Inadvertent overheparinization Vasovagal reaction

Figure 6.16 Extensive groin haematomas in a patient following bilateral femoral artery catheterization.

ral sheath. If this sheath is transgressed at the time of vessel puncture, and bleeding subsequently occurs from the puncture site after catheter or sheath removal for any reason, then blood may spread along the fascial planes continuous with the femoral sheath into the retroperitoneum or, indeed, into the anterior abdominal wall. Four types of haematoma may occur after femoral artery puncture: (A) abdominal wall, (B) retroperitoneal, (C) groin and thigh and (D) intraperitoneal. The first three may all result from puncture of the common femoral artery (i.e. below the inguinal ligament), with (A) and (B) resulting when there is bleeding into the femoral sheath and (C), the commonest, when there is spread into the femoral triangle. Intraperitoneal haemorrhage is even less frequent than retroperitoneal bleeding and generally requires transgression of the peritoneum itself, which is more likely to occur if vessel puncture is performed above the level of the inguinal ligament. Some intraperitoneal bleeding has also been described, however, when the arterial puncture is below the inguinal ligament; it has been postulated that this may be due to the presence of defects in the parietal peritoneum. Excessive bleeding is usually the result of bad technique. Particular caution is necessary in patients with a bleeding diathesis or hypertension and following the use of balloon catheters in transluminal angioplasty. If inexplicable bleeding continues, check that inadvertent over-heparinization has not occurred.This can be corrected if necessary by the administration of protamine sulphate (10 mg of which counteracts the effects of approximately 1000 IU heparin).

Intramural and perivascular contrast medium injection Contrast medium may be inadvertently injected into the wall of a vessel or outside the vessel (perivascular). In most cases little harm (apart from pain) results from a perivascular injection but it is possible to dissect and occlude an artery with a subintimal injection of contrast medium. Never inject into a needle or catheter that does not exhibit free backflow. Vascular thrombosis can result from severe trauma to the vessel at the puncture site or from a subintimal contrast injection. It is also possible that thrombus wiped off the outside of the arterial catheter during its extraction forms a nidus for thrombus at the puncture site.Vascular trauma at the puncture site can be minimized by good technique. Never use force to introduce a wire into a vessel; if it does not pass easily something is wrong! It is often better for the inexperienced operator to start again with a fresh needle puncture than to persist with one that is causing problems. A 10-minute delay with a successful outcome is always preferable to a dissection and/or a groin haematoma. Peripheral embolization from the puncture site probably occurs to a minor degree in many cases but clinically obvious embolization is rare. Local vascular complications such as false aneurysm (pseudo-aneurysm) or AV fistula formation and late stenosis or occlusion can all result from arterial procedures. Good technique is the best preventive measure. Femoral artery pseudoaneurysms are usually due to a combination of a low puncture

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– the superficial femoral or profunda femoris arteries have often been cannulated instead of the common femoral artery when this complication occurs – and inadequate compression of the vessel at the end of the procedure. Local sepsis may occur following an arterial puncture (although it is extremely rare) and this factor is particularly important if early surgery is contemplated. The utmost care should be taken to observe sterile precautions and when a study is performed in a patient with local skin contamination (e.g. open wound, ileostomy, etc.) a protective adhesive sheet helps to keep the operative field uncontaminated. Injury to local structures such as nerves, joints and bones is rarely of clinical significance. Occasionally damage to branches of the femoral nerve gives rise to areas of cutaneous anaesthesia or paraesthesia in the thigh57. These normally recover completely, although this may take several months in some instances.

Catheter-related and general complications 1 Thrombi can form in or on a catheter (Fig. 6.17) and be ejected into the vascular system. This is always undesirable and in areas such as the cerebral or coronary circulation is extremely dangerous. Catheters should be flushed assiduously during all arteriographic procedures to prevent thrombus formation. Other types of embolism that may occur are air embolism (sometimes from incorrectly loaded pressure injectors) and thread embolism from fragments of gauze swab (Fig. 6.17). 2 Vascular injuries distant from the puncture site may be produced by the catheter or guidewire, or by the intramural injection of contrast medium or saline. If there is ever any doubt about whether a needle or catheter tip is in a satisfactory position, contrast medium should always be injected in preference to saline. Under fluoroscopic control, it is then possible to stop the injection immediately if any extravasation or other mishap is apparent. The most common injury is dissection of the tunica intima from the tunica media and this complication is far more likely to occur in previously diseased vessels than in normal vessels. The intima forms a raised flap (Fig. 6.18) that may completely occlude the ves-

Figure 6.18 Dissection of the aorta and iliac vessels. A catheter has been passed subintimally from the right groin and created an extensive arterial dissection involving the aorta and both iliac systems. Note the suspiciously straight edge of the aortic opacification and the ‘twisted tape’ appearance of the left common iliac artery as the dissection spirals down the vessel (arrow).

sel. It is also possible to perforate vessels with a guidewire or to rupture them when a forced injection is made through a catheter wedged into a vessel of the same calibre. 3 Injuries to organs are normally caused by ischaemia during arteriographic procedures (other than those related to the effects of contrast medium. This may occur through wedging of the catheter so that the normal flow to an organ is obstructed; dissection of the feeding artery; spasm, thrombosis or rupture of the feeding artery; or embolism. The ischaemia resulting from one or more of the earlier mentioned events may have no observable clinical sequelae, may result

Figure 6.17 Catheter thrombus. During a renal arteriogram (A) a filling defect was noted at the catheter tip (arrow). On cautious withdrawal of the catheter a thrombus was found protruding from the side ports. (B) Note the fragment of gauze thread on the catheter tip; this was incorporated in the clot and presumably caused it. Care should always be taken when handling swabs in association with wires or catheters.

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• ANGIOGRAPHY: PRINCIPLES, TECHNIQUES (INCLUDING CTA AND MRA) AND COMPLICATIONS

in temporary or permanent functional abnormalities in the affected organ or system, or may cause infarction of the organ. The clinical importance of these accidents depends very much on the vascular territory in which they occur; complete occlusion of a carotid, coronary or renal artery is likely to have disastrous consequences whereas occlusion of, say, a hepatic artery may not necessarily produce any adverse effects. 4 Guidewire fracture. Occasionally fragments of guidewire or catheter may become detached within the vascular system. Catheters may also become knotted during overenthusiastic manipulation procedures.With good technique they should not occur in the first place. 5 Injection accidents. Tragedies have occurred when toxic substances have been inadvertently injected into blood vessels.

Skin-cleansing fluids should always be removed from the instrument trolley immediately after the puncture site has been prepared. Drugs should always be double-checked before injection through a catheter and particular care is necessary with heparin, which is available in solutions that differ considerably in their concentration. 6 Vasovagal reactions. Vagally mediated reactions may occur during arteriography in response either to the injection of contrast medium or to the discomfort and psychological effects of the procedure. Bradycardia is a prominent feature of such reactions, which must be distinguished from acute allergic responses to the contrast medium or local anaesthetic. The incidence of vasovagal reactions is considerably reduced if proper premedication is employed.

CATHETER VENOGRAPHY TECHNIQUE Direct venography This is the most common means of opacifying the venous system. A needle or catheter is placed directly into the vein to be imaged and contrast medium injected. This can be done using an antegrade approach, for example a needle inserted into an antecubital fossa vein to demonstrate the brachial, axillary, subclavian and brachiocephalic veins and superior vena cava, or a catheter placed in the iliac veins to demonstrate the inferior vena cava. Alternatively, a catheter may be directed retrogradely into the venous system, as in selective hepatic venography, which is now most commonly performed as part of a transjugular liver biopsy procedure or when performing a transjugular intrahepatic portosystemic stent shunt.

Indirect venography In this approach contrast medium is injected into the arterial system of the area being studied and delayed films are obtained to image the venous return. This technique is used to great advantage for examining the portal venous system, for while it is possible to gain direct access to the portal venous system, the latter approach is more invasive and requires greater technical expertise than the indirect approach. Other areas where indirect venography is used include the cerebral and renal veins.

COMPLICATIONS The complications that may occur following venography can be divided into three main groups: those occurring locally at the site of injection, those occurring within the vascular system, and systemic complications. Many of the complications of arteriography (Table 6.1) also apply to venography.

Local complications Pain may occur at the site of contrast injection. Hypertonic contrast agents in particular may cause local pain due to irritation of the vessel. Extravasation of contrast medium will also cause pain due to both the irritant nature and volume of the medium injected. Extravasation of contrast media into the skin may cause tissue necrosis and sloughing of skin, although this is less likely with low-osmolality agents. When injecting any substance careful attention should be paid to the patient’s comments. Severe pain at the injection site should never be ignored, as it does not occur if the needle is correctly positioned within the vein.

Vascular complications Dissection of the vein being cannulated/catheterized may occur at the puncture site or distally, due to catheter and/or guidewire manipulation.

Intraosseous venography

Systemic complications

This technique is now of historical interest only; it involves the injection of contrast medium into the bone marrow cavity at a site distal to the venous system that is to be imaged. Contrast medium is injected rapidly into the marrow cavity from which it drains via sinusoids and small veins into the deep venous system of the region. The technique was most widely used for leg venography with injections made into the malleoli or calcaneum for the calf, into the tibial tubercle or femoral condyle for the thigh, and into the greater trochanter to show the pelvic veins and inferior vena cava.

1 Pulmonary embolism. Ultrasound is now most commonly used to confirm or exclude lower limb deep vein thrombosis and ascending venography is performed infrequently. If venography is considered necessary it should be remembered that calf and femoral vein clots, if loose, can be dislodged by manipulation of the leg and the forceful injection of contrast medium. This complication is rare but when deep vein thrombosis is demonstrated, vigorous massage of the calf is inadvisable. Clots in the iliac vein, renal vein, hepatic vein and inferior vena cava can all be dislodged by the manipulation

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of catheters and guidewires, as well as by pressure injections of contrast medium. 2 Cardiac arrhythmias. The manipulation of catheters in the right side of the heart for any reason can cause arrhythmias. Injections of large volumes of contrast medium in the right heart, especially for pulmonary angiography, may also

cause dysrhythmias and continuous electrocardiographic monitoring is essential. 3 Air embolism. Because of the danger of air embolism in the venous system, care should be taken neither to inadvertently inject air into a vein, nor to leave the lumen of any large-bore cannula or catheter open to the atmosphere.

EMBOLIZATION TECHNIQUES The deliberate occlusion of arteries, veins or abnormal vascular spaces by embolic material injected through a selectively positioned catheter or needle is one of the major therapeutic applications of interventional radiology. Several of the indications for embolization are covered in other chapters in this book and for this reason only the important basic principles and techniques of the procedure will be discussed here.

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•

EMBOLIC MATERIALS AND TECHNIQUES Many different materials have been used to embolize blood vessels but those most commonly used are metallic coils, absorbable gelatin sponge, polyvinyl alcohol foam, sodium tetradechyl sulphate, absolute ethanol and N-butyl-2-cyanoacrylate. The choice of agent in any particular setting will depend upon the indication for embolization and the angiographic findings. Detailed descriptions of the radiological techniques employed in embolization are not included here but a few important points should be noted: • Embolization should always be preceded by high-quality angiography to define precisely the vascular territory under consideration and its anastomotic communications. • Embolizing catheters should be sited as selectively as possible to avoid the unintentional embolization of adjacent vascular territories. Coaxial catheters may be necessary to achieve the necessary degree of selectivity and failure to obtain a satisfactory catheter position will require the procedure to be abandoned. • The likely route of any ‘overspill’ of emboli should be noted during preliminary angiography. Reflux of emboli into other vessels occurs very easily as flow progressively diminishes in the embolized bed and this hazard is best avoided by injecting emboli in small quantities at a time, under constant fluoroscopic control, or by the use of a balloon catheter (see later). It is important to remember that a selective preliminary arteriogram may not reveal all routes of collateral flow, even if they communicate directly with the vessel into which contrast medium is being injected. This is because the blood flow in collateral vessels may be towards the lesion under investigation (especially if it is very vascular or is shunting into a vein) and therefore they may not necessarily be opacified when contrast medium is injected into a principal vessel feeding the lesion. When the flow haemodynamics are changed during the embolization procedure, flow may reverse along such collaterals

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and carry embolic material to an adjacent bed that was not visualized on the preliminary arteriograms and, therefore, fallaciously regarded as being unconnected with the lesion being embolized. Non-opaque emboli should always be injected as a suspension in contrast medium so that they are visible as filling defects during the injection sequence. Particular care is necessary in certain areas (e.g. CNS, lower GI tract, peripheral limb vessels); where there has been previous surgery (which may have reduced any potential collateral circulation to a region); and where there is preexisting vascular insufficiency (e.g. atheroma). It may be useful to employ a balloon catheter in some situations, either to reduce flow through the bed to be embolized or as a temporary obstruction to flow in nearby branches supplying normal structures when there seems a potential danger of emboli entering such vessels. It is prudent to cover some embolization procedures with antibiotic prophylaxis.

INDICATIONS FOR THERAPEUTIC ARTERIAL EMBOLIZATION There are numerous indications for arterial embolization but the most common are: • the control of severe bleeding (e.g. gastrointestinal or posttraumatic haemorrhage from the liver, kidney, or spleen) • the reduction of blood flow to certain tumours as a definitive treatment (e.g. uterine fibroids, certain aneurysmal bone cysts) • as a preoperative measure (e.g. juvenile nasal angiofibroma, meningioma) • as a palliative measure (e.g. hepatocellular carcinoma, neuroendocrine hepatic metastases) • in the management of vascular malformations. The most common indication for venous embolization is the treatment of male varicoceles. Interested readers are referred to other chapters in this book for more details of some of these techniques. The incidence of serious complications following embolization is low provided that the procedure is conducted with patience and scrupulous care and that only suitable patients are selected for treatment by the technique.

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• ANGIOGRAPHY: PRINCIPLES, TECHNIQUES (INCLUDING CTA AND MRA) AND COMPLICATIONS

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50.

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aorta and lower extremity arteries: preliminary experience. Radiology 211:59–67 van den Brink J S, Watanabe Y, Kuhl C K et al 2003 Implications of SENSE MR in routine clinical practice. Eur J Radiol 46:3–27 Herborn C U 2004 On the difference between 0.5-M and 1.0-M gadolinium chelates for 3D MR angiography. Eur Radiol 14(Suppl 5):M21–M22 Lin W, An H, Chen Y et al 2003 Practical consideration for 3T imaging. Magn Reson Imaging Clin N Am 11:615–639 McIvor J, Rhymer J C 1992 245 transaxillary arteriograms in arteriopathic patients: success rate and complications. Clin Radiol 45:390–394 Inglese L, Lupattelli T, Carbone G L et al 2004 Axillary artery access for interventional procedures. J Endovasc Ther 11:414–418 Ray C E, Kaufman J A1996 Complications of diagnostic angiography. In: Ansell G, Bettman M A, Kaufman J A, Wilkins R A (eds) Complications in Diagnostic Imaging and Interventional Radiology, 3rd edn. Blackwell Science, Cambridge, chapter 14, pp 303–316 Heenan S D, Grubnic S, Buckenham T M, Belli A M 1996 Transbrachial arteriography: indications and complications. Clin Radiol 51: 205–209 Hildick-Smith D J, Khan Z I, Shapiro L M, Petch M C 2002 Occasionaloperator percutaneous brachial coronary angiography: first, do no arm. Catheter Cardiovasc Interv 57:161–165

52. Chatziioannou A, Ladopoulos C, Mourikis D, Katsenis K, Spanomihos G, Vlachos L 2004 Complications of lower-extremity outpatient arteriography via low brachial artery. Cardiovasc Intervent Radiol 27:31–34 53. Boccalandro F, Assali A, Fujise K, Smalling R W, Sdringola S 2004 Vascular access site complications with the use of closure devices in patients treated with platelet glycoprotein IIb/IIIa inhibitors during rescue angioplasty. Catheter Cardiovasc Interv 63:284–289 54. Nikolsky E, Mehran R, Halkin A et al 2004 Vascular complications associated with arteriotomy closure devices in patients undergoing percutaneous coronary procedures: a meta-analysis. J Am Coll Cardiol 44:1200–1209 55. Applegate R J, Sacrinty M, Kutcher M A et al 2006 Vascular complications with newer generations of angioseal vascular closure devices. J Interv Cardiol 19:67–74 56. Koreny M, Riedmuller E, Nikfardjam M, Siostrzonek P, Mullner M 2004 Arterial puncture closing devices compared with standard manual compression after cardiac catheterization: systematic review and metaanalysis. JAMA 291:350–357 57. Hallett J W Jr, Wolk S W, Cherry K J Jr, Gloviczki P, Pairolero P C 1990 The femoral neuralgia syndrome after arterial catheter trauma. J Vasc Surg 11:702–706

CHAPTER

Radionuclide Imaging: General Principles

7

Djilda Segerman and Kenneth A. Miles

• • • • • • • • •

Introduction and general principles Basic physics The gamma camera Principles of positron emission tomography Hybrid systems: SPECT-CT and PET-CT Quantification and image processing Image interpretation Nonimaging applications Radiopharmaceuticals

INTRODUCTION AND GENERAL PRINCIPLES Frequently, the first impression of radionuclide images is one of poor anatomical definition compared with other imaging techniques. If the aim of diagnostic imaging were merely the demonstration of human anatomy, the lower spatial resolution of radionuclide imaging would indeed be a disadvantage. However, the intent of diagnostic imaging is not illustration of anatomy, rather the improvement of health outcomes for patients through more accurate diagnosis. The increasing incorporation of radionuclide imaging into national clinical management guidelines, for example the National Institute for Clinical Excellence (NICE) guidance on the use of myocardial perfusion scintigraphy in the UK, testifies to the ability of radionuclide imaging to impact positively on the care of patients. The aim of this chapter is to describe how the ‘fuzzy’ images produced using radionuclides achieve this clinical impact. Radionuclide images depict organ function rather than structure.The images are obtained by mapping the distribution of an administered radiopharmaceutical within the body.Thus, as for X-ray radiography and computed tomography, radionuclide imaging uses ionizing radiation. However, the radiation is emitted from within the patient and subsequently detected in the imaging device, rather than transmitted through the patient from an external X-ray source. The specific organ

function depicted is determined by the biological behaviour of the radiopharmaceutical. For example, a radiopharmaceutical excreted by the kidney will evaluate renal function whilst one excreted in the bile will depict the biliary tree. The biological behaviour of radiopharmaceuticals can be traced to particular cellular or molecular mechanisms. Thus, by using different radiopharmaceuticals, a range of cell types can be imaged within the same organ (Fig. 7.1), or different molecular mechanisms with the same cell type (Fig. 7.2). It is perhaps ironic that, despite limited spatial resolution, radionuclide images depict structures (i.e. cells and molecules) that are too small to be visualized by anatomical imaging techniques. Another advantage of radionuclide imaging is that quantification of the amount of radiopharmaceutical within a particular organ can be achieved through counting the amount of radiation emitted within a specific time. By obtaining repeated images, the change in concentration of radiopharmaceutical over time can be measured and displayed as time–activity curves, giving additional insights into the functional status of tissues (Fig. 7.3). With appropriate mathematical modelling, these changes in concentration can be used to quantify particular physiological processes, such as glomerular filtration rate (GFR) or left ventricular ejection fraction. As repeated images can be obtained after a single administration of radiopharmaceutical, these temporal data are obtained with no additional radiation exposure to the patient. It is the ability of radionuclide imaging to depict function that confers the ability to impact upon health outcomes. The magnitude of change in functional activity, rather than the size of an abnormality, determines whether a disease can be detected by radionuclide imaging. Radionuclide imaging devices are highly sensitive and can detect relatively small changes in functional activity. Thus, a change in tissue function is frequently detectable before any change in structure has occurred or can be detected confidently by anatomical imaging. For example, increased glucose metabolism of cancer cells within lymph nodes can be detected using positron emission tomography (PET) before the size of the lymph

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• IMAGING TECHNIQUES AND GENERAL ISSUES

Figure 7.1 Radionuclide images depicting three different cell types within the liver obtained using different radiopharmaceuticals. (A) 99mTc sulphur colloid taken up by Küpfer cells. (B) 99mTc HIDA taken up and excreted by hepatocytes. (C) Leucocytes labelled (ex-vivo) using 99mTc HMPAO. (The crosses mark the costal margins.)

node exceeds the threshold to be diagnosed as abnormal on computed tomography (CT) (Fig. 7.4). Similarly, successful treatment may return functional activity to normal before anatomical abnormalities have resolved and thus radionuclide imaging can be advantageous in monitoring treatment (e.g. for patients with cancer). In other circumstances, the functional status of an organ is more important for determining clinical management than its structural appearance. For instance, the anatomical finding of a dilated renal collecting system does not necessarily indicate renal tract obstruction. It is the presence of obstruction and its impact on renal function, as demonstrated by renal radionuclide imaging, that more accurately determines whether clinical intervention is required. More recently, the limited anatomical definition of radionuclide imaging has been addressed to some degree by the development of hybrid imaging in which radionuclide imaging devices are combined with computed tomography in a single imaging system. The resulting images display the functional data obtained from the radionuclide distribution (usually in colour), overlaid on the anatomical information from CT (usually in grey scale) (Fig. 7.5). Because the two image data sets are acquired using the same imaging system within a short time of each other, the two image data sets can be co-registered more accurately than when obtained on separate imaging systems. Not only do these hybrid systems allow abnormalities

Figure 7.2 Radionuclide images of breast cancer (arrows) demonstrating different uptake mechanisms in the same cell type (adenocarcinoma). Uptake of 18F-FDG on PET (A) is due to increased expression of glucose transporters and hexokinase. Uptake and retention of 99mTc methoxyisobutylisonitrile on gamma scintigraphy (B) are dependent on perfusion and expression of multidrug resistance pglycoprotein. (Note uptake in nodal metastases in the axilla in case B, as indicated by the arrowhead.) Figure 7.4 A mediastinal lymph node (arrow) is not sufficiently enlarged to confidently diagnose nodal metastasis on CT (A) but demonstrates uptake of 18F-FDG on PET (B), implying the presence of tumour cells. (* = primary tumour.) MAG3 Renogram (LASIX AHEAD) Right peak

4000 3600 3200

Left kidney Right kidney Right uptake region Left uptake region Aorta Bladder

2800 2400 2000 1600 1200

Left peak

Activity (counts)

130

800 400 0 0

4

8

12

16 20 Minutes

24

28

32

Figure 7.3 Time–activity curves from the kidneys, bladder and aorta following injection of a radiopharmaceutical (MAG-3) that is excreted by the kidney.

Figure 7.5 PET-CT images from a patient with active lymphoma. The 18 F-FDG uptake has been displayed in colour over grey scale CT images in (A) transaxial, (B) coronal and (C) sagittal formats.

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seen on radionuclide images to be assigned to precise anatomical structures, they also enable the morphological appearances of disease processes depicted by CT to be assimilated into the interpretation of the findings on radionuclide images. For example, such combined interpretation can aid the distinction of malignant and inflammatory causes of uptake of the positron emitting radiopharmaceutical 18F-fluorodeoxyglucose (FDG). Further advantages of hybrid systems include the use of the CT data to correct radionuclide images for artefacts resulting from attenuation of photons within the body and the ability to incorporate radionuclide image data into CT-based radiotherapy planning systems.

• RADIONUCLIDE IMAGING: GENERAL PRINCIPLES

In 1910 Rutherford established experimentally that each atom had to have a dense, positively charged nucleus which was surrounded by a cloud of negative electrons. Bohr’s model (1913) included electrons in discrete orbits circling about the dense nucleus. This is the model of the atom generally accepted today. Atoms are composed of three types of particle: protons, neutrons and electrons. The protons and neutrons form a central nucleus. Each proton has a positive electric charge (+); neutrons have no charge; electrons have a negative electric charge (−) and orbit around the nucleus, attracted by its positive charge. Protons and neutrons are nearly 2000 times heavier than electrons, so most of the mass of an atom is in the nucleus. A nucleus is described by its mass number, A, which is the sum of the number of neutrons (N) and protons. The atomic number, Z, is equal to the number of protons. The mass number is therefore given by:

it will emit radiation either as photons (X or gamma rays) or as high-velocity particles.The remaining protons and neutrons will form a daughter nucleus, which may itself be radioactive, or may be stable. The particular nature and energy of emissions are characteristic of each radionuclide. The radiation generally is ionizing, meaning that it is highly energetic and damaging to living tissue. The rate of radioactive decay is characteristic of each radionuclide. Decay is governed by probability, which means that it is impossible to predict when a particular nucleus will disintegrate. However, with large numbers of nuclei the overall rate of decay is entirely predictable. As the nuclei in a sample of radionuclide disintegrate, the number of radioactive nuclei left is reduced, and the rate of decay reduces in proportion. This effect is described mathematically by the equations of exponential decay. An important parameter is the half-life (T1/2) which is defined as the time period during which half the nuclei will decay. For example, the half-life of 131I is 8 d. In the course of 8 d, half the 131I nuclei in a sample will have decayed, and the rate of decay will have fallen to half its original value. The relationship is extremely accurate for large numbers of nuclei; with smaller numbers it is true but only on average. This can be observed in the erratic clicks of a Geiger counter that is picking up just a few counts per second. The rate of radioactive decay of a sample is called activity. The SI unit of activity is the becquerel (Bq), defined as one nuclear disintegration per second. Doses of radioisotopes given to patients for diagnostic purposes are usually measured in kBq or MBq. Originally the unit of activity was the curie (Ci) defined as 3.7 × 1010 disintegrations per second, thought to be the number of disintegrations found in 1 g of radium. Conversion factors are:

A=Z+N

1 mCi = 37 MBq; 1 microCi = 0.037 MBq.

BASIC PHYSICS Structure of the atom

The atomic number Z is constant for a given element. The same element can have varying numbers of neutrons; these different forms of an element are called isotopes. The chemical properties of the different isotopes of an element are the same. Isotopes with more neutrons will be heavier, so some physical properties may differ. To distinguish the isotopes of an element, the mass number A is normally written as a superscript. For example, the isotope of iodine with A = 131 is written 131I. Other conventions are: I131 and 53131I. In the latter example the subscript signifies Z, the atomic number of the element. A nuclide is the term to denote a type of atom characterized by both Z and N. A radionuclide is a nuclide that is radioactive.

Radioactivity A radioactive nucleus is one that is unstable and will spontaneously disintegrate or decay at some time. The reason for the instability is either that the nucleus is too large or because there is an imbalance between the protons and neutrons. Unstable nuclei have an excess of energy. When a nucleus disintegrates,

Table 7.1 lists some medically important radionuclides.

Alpha radiation Alpha decay occurs only when a heavy nucleus ejects an alpha particle. The alpha particle (α) consists of two neutrons and two protons and is identical to a helium nucleus. Alpha particles interact strongly with matter, so have a very short range, typically 1 mm or less in tissue.Within this range alpha particles repeatedly collide with atoms, disrupting their chemistry, which is extremely damaging in living tissue. Historically, radium and radon were the principal alpha emitters of medical interest.These are no longer used in medicine. Other alpha emitters are being researched for therapeutic approaches using radiopharmaceuticals that can target the delivery of short half-life alpha emitters into cancerous cells2. Due to their very short range, alpha particles have the potential to deliver a lethal radiation dose to small metastatic cell clusters, while mostly sparing the surrounding tissue. All work with alpha emitters must be conducted under very strictly controlled conditions. A significant health hazard would exist

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Table 7.1 PHYSICAL PROPERTIES OF SOME COMMONLY USED RADIONUCLIDES Main emissions (keV) Radionuclide

Half-life

Main use

Gamma or X

Beta (Emax)

Carbon-11

11

C

20 min

p

511

960

Carbon-14

14

C

5730 years

n

–

157

27.7 d

n

320

–

51

Cr

Chromium-51 Cobalt-57

57

270 d

n

122

–

Cobalt-58

58

Co

71 d

n

811

475

Fluorine-18

18

109 min

p

511

634

Gallium-67

67

Indium-111

111

Co F

Ga In

78 h

g

93, 185, 300

–

67 h

g

171, 245

–

Iodine-123

123

13.2 h

g

159

–

Iodine-125

125

60 d

n

27, 31

–

Iodine-131

131

8d

t (g)

365

606

I I I 81m

Kr

Krypton-81m Nitrogen-13 Oxygen-15 Selenium-75

13

N

15

O

75

Se

89

Strontium-89

Sr 99m

Tc

Technetium-99m 201

Tl

Thallium-201

13.5 s

g

191

–

10 min

p

511

1199

2 min

p

511

1732

120 d

g

136, 265, 401

–

50.7 d

t

–

1492 –

6h

g

140

3d

g

71

–

Xenon-133

133

5.2 d

g

31, 81

346

Yttrium-90

90

2.7 d

t

–

2284

Xe

Y

Main use: g = gamma camera, n = nonimaging diagnosis, p = PET, t = therapy. Beta (Emax): maximum energy of continuous spectrum; mean energy = approximately one-third of Emax. Main source of decay data1.

if these radionuclides were inadvertently ingested or inhaled, as cells lining the tracheobronchial tree or gastrointestinal tract would then receive high doses of radiation.

Beta radiation A beta particle (beta− or β−) is an electron emitted by a nucleus. Beta decay occurs in nuclei that contain an excess of neutrons. One of the neutrons (n) will convert to a proton (p+), an electron (e−) and a neutrino (ν). This can be visualized as: n → p+ + β− + ν + energy The proton remains in the nucleus, and the beta and neutrino are emitted with high velocity. The electron and the neutrino share a set quantity of energy in variable proportions, so the electrons will have a continuous spectrum of energies. An example of beta decay is that of 89Sr: 89 Sr 38

→ 3989 Y + β− + ν + energy

One of the neutrons has converted to a proton, increasing the atomic number from 38 to 39; strontium is converted to yttrium.The neutrino has an extremely small mass, no electric charge and interacts extremely weakly with matter. It will have no effect on the patient. Beta particles cause damage to tissue in a similar manner to alphas, but less severely. They follow a zig-zag path, undergoing many collisions with atoms. At each collision the beta gives up some of its energy, causing excitation and

ionization of the atoms. The range of betas depends on their initial energy and the electron density of the material.Typical ranges in tissue are a few millimetres; in air the range may be up to several metres. Beta emitters are routinely used to deliver therapeutic radiation doses to tumours.

Positron emission A positron (beta+, β+ or e+) is a particle similar to an electron except that it has a positive electric charge. The decay process is a type of beta decay, except in this case the nucleus has an excess of protons. p+ → n + β+ + ν + energy Positron emitters are used in PET imaging. An example is fluorine-18: 18 F 9

→ 818O + β+ + ν + energy

The behaviour of positrons in tissue is very similar to beta particles, with one important difference: once a positron has been slowed down by atomic collisions, it is annihilated by interaction with an electron from a nearby atom. The combined mass of the β+ and e− is converted into two annihilation photons, each with energy 511 keV, in accordance with Einstein’s famous equation, E = mc2: β+ + e− → γ + γ

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The two photons are emitted at 180 degrees to each other, a property exploited by PET.

X and gamma radiation Definitions Gamma rays and X-rays are both a form of electromagnetic radiation, and have the same properties. The two names arose historically. Roentgen discovered and named X-rays; these were produced by a beam of electrons striking a heavy object, the same mechanism as in a modern X-ray tube. A few years later, the names alpha, beta and gamma were given to the different rays emitted by radioactive uranium. It was only later realized that X-rays and gamma rays are essentially the same. The modern definitions are that gamma rays are emitted by an atomic nucleus in an excited state, whereas X-rays are the result of changes involving electrons. The properties exhibited are both wave-like and particle-like. The particles are called photons. Each photon has a definite energy and zero mass. Its wave-like properties are a frequency which is in proportion to its energy, and a wavelength which is in inverse proportion.

Reactions that produce X and gamma radiation Some beta emitters produce gamma photons in the course of beta decay.The decay is a two-stage process, with beta emission leaving the nucleus in an excited state. The excited nucleus then decays to its stable daughter, emitting the excess energy as a gamma photon. There may be several possible excited states, each with a particular probability of occurrence. The result will be a range of gamma photons, each with its specific energy and probability. An example is the beta emitter 131I, whose principal gamma ray is used in imaging. Certain excited nuclei do not decay immediately but remain in their excited state for some time. These nuclei are termed metastable.This type of decay is known as an isomeric transition (IT) because the parent and daughter nuclei are isomers, i.e. they contain the same number of protons and nuclei. An example is the metastable radionuclide of technetium, 99mTc, which emits a single gamma photon of energy 140 keV, and is the most commonly used radionuclide for imaging. In many decay schemes, nuclear energy is transferred to the atom’s orbital electrons. When the orbital electrons revert to their ground state they emit characteristic X-rays. In some cases, instead of producing an X-ray, the energy will eject an outer orbital electron as an Auger electron. In their properties, and in their interactions with matter, X-rays are the same as gamma rays, and Auger electrons are the same as beta particles. Electron capture (EC) is another radioactive decay process that can occur in a nucleus with excess protons. One of the orbital electrons is captured by a proton in the nucleus and changes the proton into a neutron. If the original nucleus has enough excess energy to produce two 511 keV photons, it may decay by either positron emission or electron capture. If the excess energy is less than 1022 keV, then positron emission cannot occur and electron capture is the only decay mode. Electron capture can be visualized as: p+ + e−→ n + ν + energy

• RADIONUCLIDE IMAGING: GENERAL PRINCIPLES

Some of the energy is carried off by the neutrino and some is transferred to the orbital electrons of the atom, resulting in characteristic X-rays and possibly Auger electrons. In some cases EC will leave the nucleus in an excited state, which will decay to its stable daughter by gamma emission. Beta particles and Auger electrons can give rise to another form of radiation called Bremsstrahlung (German for braking radiation).When a high-energy beta particle passes close to the nucleus of another atom, electrostatic attraction deflects and decelerates the beta particle, and its lost energy is converted to an X-ray photon (Fig. 7.6). This Bremsstrahlung radiation has a continuous spectrum. The energy tends to be higher when the betas have high energy and the material they are passing through has a high atomic number. For this reason radiation shields for high-energy beta emitters are made of plastic which has a low atomic number.

Interaction of X and gamma radiation with matter (Fig 7.7) Two types of interaction are important in nuclear medicine: • In a photoelectric absorption, an atom absorbs all the energy of an incident photon. The photon ceases to exist but the energy is transferred to a photoelectron which is ejected from the atom. • In a Compton scattering, the photon transfers only some of its energy to a recoil electron. As a result the photon is ‘scattered’ or deflected off in a new direction with a lower energy. In both interactions an orbital electron is ejected. It will lose its energy locally in the same way as a beta particle. The Compton-scattered photon will subsequently undergo either another Compton scattering or a photoelectric absorption. Unlike alphas and betas, gamma rays and X-rays do not have definite ranges, but are attenuated on passing through matter. A certain fraction of the photons will pass through, the fraction depending on the material, its thickness, and the energy of the photons.

Figure 7.6 A fast-moving beta particle is deflected by a nucleus, producing a Bremsstrahlung photon. (From Hart G, Armes F 1992 Medical physics for advanced level. Simon & Schuster Education, London.)

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Figure 7.7 (A) Photoelectric absorption. (B) Compton scattering. (From Hart G, Armes F 1992 Medical physics for advanced level. Simon & Schuster Education, London.)

THE GAMMA CAMERA A gamma camera (Fig. 7.8) is a system of one or more detectors, linked to an acquisition computer. In front of each detector is a collimator, which projects an image of the radioactive distribution onto the crystal. These images are ‘shadow pictures’, analogous to planar X-rays. The crystal converts the incoming gamma-ray signal to a light signal, which is detected by an array of photomultiplier tubes (PMTs).The PMT signals are processed to form the image which is stored on an acquisition computer. Images are downloaded to a processing computer. Depending on the clinical information required, this computer may, for example, track changes with time, or create a tomographic reconstruction similar to CT or MRI.

Detector and acquisition computer The crystal is a single crystal of sodium iodide. It is typically large and rectangular, perhaps 40 × 55 cm, and between 9.5 and 19 mm thick. (Older gamma cameras tended to have circular crystals.) When a gamma photon enters the crystal, electrons are ejected from their atomic orbits in photoelectric or

Compton interactions (see above). The ejected electrons collide with nearby atoms in the crystal and energize them (see above). The atoms of the crystal release their excess energy by scintillation, giving off a characteristic blue light. In most cases all the energy of the incoming gamma photon is converted to scintillation photons3. Attached to the back of the crystal is an array of perhaps 90 or so PMTs. These extremely sensitive light detectors are coupled to the crystal with special grease to give maximum transmission of light from the crystal. Each PMT consists of an evacuated glass envelope, containing a series of electrodes. A scintillation photon striking the first electrode causes emission of an electron. This electron is accelerated towards the next electrode, which emits two or three electrons for every one striking it. This amplification process is repeated at each electrode in the cascade, until at the last electrode the signal may be amplified by a factor of about 1 million. Image formation is accomplished by combining the signals from several PMTs. In the crystal, the scintillation photons resulting from one gamma photon are given off in all directions, and are picked up by the nearby PMTs. From the relative size of signals from all the PMTs, the detector determines the position of the gamma photon’s interaction in the crystal to within a few millimetres, even though each PMT is several centimetres across. It is important to exclude from the image radiation that has been scattered within the patient or gamma camera before interacting with the crystal. Only those gamma rays that trace back to the distribution of radioactive material in the patient are used for image formation. Exclusion of scattered photons is made possible because the scattered rays have reduced energy (see above, Compton scattering). Figure 7.9 shows a typical energy spectrum for 99mTc displaying the number of events detected by the gamma camera across a range of photon energies. The tall peak, known as the photopeak, represents the unscattered gammas. These have their original energy, which is 140 keV in the case of 99m Tc. The scattered gammas appear as the broad distribution to the left of the photopeak. The detector identifies the energy of each incoming gamma photon by summing the signals from all the PMTs. A suitable energy window is set at the photopeak as shown in Figure 7.9. Each gamma within the energy window will register one count, and is saved in the pixel corresponding to the X and Y coordinates that denote the position of the photon interaction within the crystal. As most of the scattered gammas have energies outside the window, they are excluded from the image.

Collimators Up to this point, only the physical steps involved in the detection of a gamma-ray interaction within the crystal have been discussed. To form a meaningful image of the distribution of radioactive material, a collimator is placed in front of the crystal to restrict the direction of gamma rays entering the crystal. Without a collimator, gamma rays arising from radioactivity in all parts of the body can strike all parts of the crystal and so no meaningful image is formed.

CHAPTER 7

HV supply

• RADIONUCLIDE IMAGING: GENERAL PRINCIPLES

Computer memory Digital circuitry A/D converters Amplifiers Photomultiplier tubes Crystal Collimator

B Figure 7.8 (A) A gamma camera. This model has two detectors mounted on the circular gantry ring to the left of the picture. (Image supplied by Siemens Medical Solutions.) (B) Components of a modern ‘digital’ gamma camera with one analogue-to-digital (A/D) converter for each photomultiplier tube.

The usual form of collimator is a block of lead with an array of holes orientated perpendicular to the face of the crystal. Gamma rays that originate directly in front of a hole can pass through to the crystal, but rays arriving at an angle are stopped by the lead septa between the holes. The performance of the collimator is determined by the number of holes, the diameter and length of each hole and the septal thickness. Collimators with differing performance can be chosen depending on the energy of the gamma rays being detected and whether high resolution or high sensitivity is needed. Because their septa need to be thicker, the resolution of collimators designed for high-energy isotopes is generally poorer than that of those used for low-energy isotopes. Several types of magnifying and minifying collimators have been used in the past.These have included converging, diverging and fan-beam collimators, all of which employ nonparallel arrangements of holes.The pinhole collimator is a hollow metal cone that fits over a circular detector face, and has a single hole at its point. As all of these collimators introduce distortions, the scale of an anatomical feature on the image would depend on its distance from the detector.These types of collimator have largely fallen into disuse.

Count rate

Energy window

In a modern gamma camera, magnification is controlled by choice of a zoom factor on the acquisition computer. Typically this may range from 1.1 to 8.0. The zoomed image is magnified by the zoom factor, but covers only a portion of the detector’s field of view. The images are easier to interpret because zoom magnification is not affected by distance from the detector.

Temporal resolution The speed at which a gamma camera can count incident photons is limited by the properties of the crystal and the electronics of the camera.The detector can only process one event at a time. After a photon is absorbed in the crystal it will scintillate for approximately 230 nanoseconds4. If a second photon hits the crystal during this ‘integration time’, the two photons will not be detected as separate events, but rather as one with excess energy and a misplaced position. The capacity of the camera to record many scintillations rapidly is also a function of the time for the electronics to process each event. The overall ‘dead time’ of a detector is that time during which the system cannot respond to a second incident photon. Most types of imaging camera operate in a mode with a dead time of 1–2 ms.The count rate performance is described by the count rate at which there is a 20% loss of recorded scintillations due to dead time, which may then typically be around 75 000 counts per second. Most imaging is performed at count rates considerably less than this. Sometimes cameras have a high count rate mode with a slightly reduced integration time and hence a reduced dead time which can be used for quantitative dynamic studies with high count rates (e.g. radionuclide angiocardiography).

Techniques of image acquisition and processing 0

140 Gamma energy keV

Figure 7.9

99m

Tc spectrum and energy window.

A major strength of nuclear medicine imaging is its ability to show and quantify physiological function.This capability is supported by a range of acquisition protocols and image processing software. This section introduces the main types of study.

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• IMAGING TECHNIQUES AND GENERAL ISSUES

Static image This is the basic image; other acquisitions consist of a series of such images. A matrix size is chosen, usually 64 × 64, 128 × 128, 256 × 256, or 512 × 512. This determines the number of pixels there will be in the image. Each gamma ray that is accepted by the camera is saved as a count in the pixel corresponding to its location. A typical image may contain between 100 000 and 1 million counts, and take up to several minutes to acquire. Dynamic imaging consists of a sequence of basic images or frames acquired over time. The frame rate is chosen according to the rate of change of the radiodistribution, and may be as rapid as 40 frames per second. The number of counts acquired in a short time can be increased by the use of a high-sensitivity collimator which has larger holes and therefore poorer resolution than a general purpose collimator. Processing can generate time–activity curves of selected organs (e.g. the kidneys in a renogram). Parametric or functional images display particular aspects of a physiological process in each individual pixel (picture element) making up the image; for example, in a renogram, the colour scale might show time-to-peak activity in different regions across the kidney. (For an introduction to parametric images, see Chandler & Thomson 2003, in Suggested Further Reading.) Whole body imaging Most modern cameras allow whole body imaging in which either the camera or the patient is moved slowly longitudinally during acquisition. The result is an extended image that can include the whole patient. With a dual-headed camera it is possible to acquire anterior and posterior whole body images simultaneously and to allow, for example, a whole body survey for bone metastases to be acquired in less than 20 min. For quantitative measurements, a series of static images is preferable. Gated imaging It is possible to use a physiological signal from a patient to ‘gate’ images as they are acquired on a gamma camera. The commonest application is to image the blood pool or the myocardium gated with an electrocardiogram (ECG) signal. The result is a series of images of the heart at points throughout the cardiac cycle that is built up over several hundred cardiac cycles. Dual isotope imaging involves two radionuclides which are imaged simultaneously by setting two different energy windows on a detector; for example, a lung study using 81mKr gas for imaging ventilation and 99mTc microspheres for perfusion. The 81mKr energy window at 190 keV is well separated from the 140 keV 99mTc window. The camera acquires two separate images. Care needs to be taken with technique to avoid artefacts due to activity from one or other isotope being erroneously detected in the wrong window. SPECT acquisition (single photon emission computed tomography) Most current gamma cameras can be used for both planar and tomographic imaging. Tomographic images are obtained by rotating the detectors around the patient.

A series of projection images is acquired from many angular views around the patient from which the tomographic slices are reconstructed using computer processing. The sensitivity of a SPECT system is proportional to the number of its detectors which typically range from one to three. Gated SPECT acquisition is commonly used in myocardial perfusion imaging. SPECT reconstruction produces a set of axial slices, perpendicular to the camera’s rotation axis (and the patient’s spine), and can be performed using either filtered back-projection (FBP) or iterative algorithms such as ‘OSEM’. Mathematical filters reduce noise and enhance the images. In essence, the counts in each pixel of a slice correspond to the radioactive concentration at that point within the patient, though this is not strictly true because of the various ‘camera limitations’ discussed in the next section. These data can also be rearranged into coronal and sagittal slices, with all three sets displayed simultaneously. New slices can be defined to align with anatomical axes (e.g. of the heart or brain). In reconstruction it is essential to use the same algorithm and filter parameters for a particular investigation, and not to alter these for individual patients5.

Gamma camera limitations The effects described here are not faults, but are inherent to the workings of gamma camera imaging. The resultant distortions of the image need to be understood and allowed for. • The spatial resolution of a gamma camera is limited primarily by the size of the collimator holes and statistical variations in the distribution of light photons detected by the PMTs. A small radioactive source will appear as a broad peak. Manufacturers generally specify resolution in terms of full width half maximum (FWHM). This parameter is a measure of the spread of the image of a very small source (Fig 7.10A). A typical value near the surface of a high-resolution collimator is 6–8 mm, and, for a high-sensitivity or a high-energy collimator, 10–12 mm. Resolution is degraded when the source is at a distance from the collimator (Fig 7.10B). • A consequence of limited resolution is the partial volume effect. When an object is smaller than the resolution of the camera, the measured signal is reduced in amplitude. For example, a tumour that is smaller than approximately 2 × FWHM will appear larger than its true size and fainter than its true uptake of radionuclide. • Attenuation is the reduction in intensity of a beam of gamma rays, due to absorption and scatter. Patient tissue between the radioactive material and the detector can very significantly reduce the radiation reaching the detector. For 99m Tc, a soft tissue thickness of approximately 4.5 cm will reduce the intensity to one half 6. To correct for attenuation in SPECT, some cameras offer attenuation correction. The correction algorithm needs, as input, a map of the distribution of scattering material within the patient. This information may be obtained from previously acquired CT or by using a hybrid SPECT-CT system. Several conventional gamma cameras use a radioactive line source, usually gadolinium

CHAPTER 7

• RADIONUCLIDE IMAGING: GENERAL PRINCIPLES

Crystal Collimator Hole Lead

Maximum height

Source A

Full width half maximum

A

B

Source B

Figure 7.10 (A) Full width half maximum is a measure of the width of a peak, taken at half its maximum height. (B) The effect of distance on resolution. Gamma rays from source B will pass through a larger number of holes in the collimator, and activate a larger area of the crystal. Resolution is therefore poorer for the more distant source B.

(153Gd), to obtain transmission data. As with all methods of attenuation correction, national guidelines emphasize the need for proper validation and quality control, and for comparison of the images with the noncorrected reconstruction5,7. • For distant sources, the number of counts acquired is not reduced, but image quality is compromised. This can be understood from Figure 7.10B. In both cases, the cone of rays that passes through the collimator has the same angle, which means that the same number of rays is transmitted. However, those from the more distant source are spread over a larger zone of the crystal. This reduces both the sharpness (spatial resolution) and the contrast of the image. • Scattered radiation (Compton scattering) contributes random noise that tends to obscure the signal. Most of the scattered radiation is eliminated by the energy window. • Count rate limitation. Because of the finite time the detector takes to process each gamma photon, acquisitions carried out at high count rates should not be used for quantitative estimations of absolute or relative organ uptake.

PRINCIPLES OF POSITRON EMISSION TOMOGRAPHY PET uses the coincidence detection of paired 511 keV annihilation photons from positron-emitting radionuclides such as 11 C, 13N, 15O and 18F. A PET camera (Fig. 7.11A) contains several rings of block detectors as shown in Figure 7.11B. The principle of PET is that an event is only registered if two detectors record a photon interaction at almost exactly the same time. Because the photons are emitted 180 degrees apart, it can be inferred that the annihilation occurred somewhere along a line of response (LOR) connecting the two detectors. This inherent spatial information makes it possible to acquire and reconstruct a tomographic image without the need for collimators. PET can therefore potentially offer much higher sensitivity and better spatial resolution than SPECT. Although sodium iodide detectors similar to those used in gamma cameras can be employed, the physical properties are less than ideal for the high-energy photons involved in PET. PET detectors typically use crystals such as bismuth germinate (BGO),

B Figure 7.11 (A) A combined PET/CT system. (Image supplied by Siemens Medical Solutions.) (B) Coincidence detection of paired photons in a PET imaging system. (From Sharp P F, Gemmell H G, Smith F W 1998 Practical nuclear medicine, 2nd edn. Oxford University Press, Oxford.)

137

138

SECTION 1

• IMAGING TECHNIQUES AND GENERAL ISSUES

lutetium orthosilicate (LSO) and gadolinium orthosilicate (GSO). PET detectors surround the patient and acquire data from all angles simultaneously, which allows dynamic acquisitions with frame times as short as 1 s 8. Gated acquisitions are also possible with PET. In 2D mode, each ring of detectors works independently, and only registers annihilations that occur within its own plane. Lead septa between the rings absorb any oblique photons and prevent them from registering. Using algorithms similar to SPECT, the data from each ring are reconstructed to form an axial image.The stack of axial images forms the complete tomographic map. To increase sensitivity, the septa may be designed so that each axial is formed from a set of adjacent detector rings; this causes some loss of spatial resolution in the axial direction. In 3D mode the septa are removed, and sensitivity is greatly increased by acquiring coincidence events from any pair of detectors. Special 3D algorithms are used for image reconstruction. PET images are degraded by scatter, attenuation, random coincidences, dead time and noise. Attenuation correction is particularly important for PET because absorption or scatter of either of the pair of photons will result in loss of detection of the annihilation event. Spatial resolution of PET is limited by the length of the positron path (a few millimetres), noncolinearity of annihilation photons (about quarter of a degree) and the size of the detector blocks. Gamma cameras have been developed that include coincident detection for use in PET imaging9. Their use is limited, partly because gamma cameras are not optimized for PET, so their performance is inferior. Another reason is that it is not economic for a department to conduct occasional PET studies, because the high radiation doses necessitate substantial expense and reorganization of a department. As well as the physical advantages, PET also benefits from the types of radiopharmaceutical that can be used. Most physiological molecules are made of carbon, nitrogen and oxygen, enabling them to be labelled with positron emitters 11C, 13N and 15O. Cellular uptake of the glucose analogue 18F-FDG reflects the rate of transmembranous exchange of glucose. PET provides the clinician and researcher with a unique tool to study and quantify physiological and pathological functions of human tissues and organs. Examples of how PET radiopharmaceuticals can be used to measure glucose and oxygen utilization in tumours, or to quantify cerebral or myocardial blood flow, are given in subsequent chapters.

The CT image can also be used for attenuation correction of the nuclear medicine image. By using a single gantry, errors due to movement of the patient between the CT and nuclear medicine acquisitions are significantly reduced. However, respiratory motion can lead to a mismatch of organs near the diaphragm, particularly if patients hold their breath for the CT acquisition, but breathe naturally during the nuclear medicine image (Fig. 7.12). Motion correction by respiratory gating of the nuclear medicine acquisition may lead to improvements10. PET-CT has now replaced dedicated PET for the systems currently in production. The early systems that used CT merely for attenuation correction and localization of abnormalities are now being replaced by diagnostic-quality CT. A greater throughput of patients is achievable with PET-CT due to the shorter acquisition time of the CT as compared to the transmission images performed using dedicated PET systems. This results in an increasing need for clinicians proficient in interpreting both nuclear medicine and CT11.

QUANTIFICATION AND IMAGE PROCESSING Processing computers provide a range of software to extract quantitative data reflecting clinically relevant physiological parameters from data acquired either with gamma cameras or PET. Dynamic and gated acquisitions generate particularly large quantities of data. Basic processing functions are as follows: • Measurement of activity within regions of interest (ROIs) outlining specific organs or areas. ROIs may be drawn manually or determined by various computer algorithms. • Background subtraction, to compensate for activity in overlying tissues, when estimating the activity within an

HYBRID SYSTEMS: SPECT-CT AND PET-CT The development of SPECT-CT and PET-CT systems allows the superimposition of nuclear medicine and CT images, a technique known as functional–anatomical mapping (Fig. 7.5). In a range of clinical scenarios, interpretation of images obtained using these hybrid devices has proved to be more diagnostically accurate than evaluation of the two sets of images separately. This combined imaging approach also allows functional data to be incorporated into the selection of radiation fields during radiotherapy planning.

Figure 7.12 PET-CT study in which the CT data (right) has been used for attenuation correction of the PET image (left). A crescent of lung just cranial to the left hemidiaphragm (arrow) demonstrates reduced activity—an artefact due to differences in position of the left hemidiaphragm between acquisition of CT and PET data.

CHAPTER 7

• • •

• •

organ. Various algorithms are available, or the background may be defined in terms of a background ROI. Consistency in the estimation of background can be extremely difficult to attain, and has led to significant differences in the numerical results from different centres. Generation of time–activity curves (TACs) for ROIs applied to dynamic image series. Smoothing and filtering, to reduce statistical noise, both spatial and temporal. Curve fitting, to reduce complex TACs to a few parameters that can be compared against normal values (e.g. gastric emptying half-times). Mathematical modelling to quantify discrete physiological processes. Statistical analysis to highlight image regions that vary significantly from a reference set of normal images.

For a discussion of these functions, and an introduction to more sophisticated methods, see Lawson (1999), in Suggested Further Reading. When the counts in an image are low, random variations become significant. These variations result in a grainy appearance that can be removed by smoothing algorithms, often automatically included in processing protocols. Low counts are a particular problem in applications involving subtraction of tissue background from counts within an organ. The background region chosen will be a compromise between a small ROI with a large percentage error and a larger ROI that includes areas less representative of background behind the organ. Measurements of activity within a ROI are often compared to activity within a reference region (e.g. target-to-background ratio). A more precise quantitative measure of uptake of radiotracer in tissue is the standard uptake value (SUV): SUV =

Activity per unit mass of tissue Injected activity per unit body mass

Estimation of SUVs may be affected by choice of ROI, time since injection of the radiopharmaceutical and by some of the camera limitations discussed above. (For a discussion of these factors, and of how uptake may be affected by clinical considerations, see Thie 2004, in Suggested Further Reading.) For tomographic images, accurate quantification is more readily achieved with PET than SPECT. SUV measurements are more commonly used in PET. Image registration is the geometric alignment of two images. There are two fundamentally different applications: • In dealing with images from one patient, registration may align different examinations (e.g. CT to nuclear medicine) or may be used to correct for patient motion. Software may operate automatically, or with shifts and rotations determined by the operator. • A patient’s images may also be compared against those of another individual by stereotactic normalization or warping. The images are deformed to make them the same size and shape. This technique has found application in brain

• RADIONUCLIDE IMAGING: GENERAL PRINCIPLES

imaging, where an individual’s image is compared to a ‘normal’ image, a composite formed by warping images obtained from several normal subjects. The technique is recommended in dopamine transporter SPET imaging, as outlined in the EANM guidelines12. Current research is assessing the usefulness of different methods13.

IMAGE INTERPRETATION The processes of acquiring radionuclide images, along with the focus on depiction on function rather than structure, result in the need for an approach to image interpretation that differs in some aspects from other imaging techniques. Image annotation is important for radionuclide images which may have few anatomical landmarks to help orientation. Unlike conventional radiography, planar images obtained with a gamma camera may differ considerably depending on whether they have been acquired from the anterior or posterior aspect of the patient (Fig. 7.13). This difference is due to attenuation and scatter of radiation emitted by structures further from the camera.The resulting images are displayed in the orientation in which they are acquired. Thus, a posterior view will be orientated with the patient’s right-hand side on the right side of the image. Tomographic views from SPECT and PET are displayed in accordance with the same conventions used for other cross-sectional imaging techniques. Image artefacts may be caused by the gamma camera being out of adjustment or by inappropriate selection of imaging conditions by the operator. Any geometrical or nonanatomical shape on an image is likely to be a camera artefact. The detection of artefacts is improved by: (A) being familiar with their typical appearance; (B) adjustment of the grey scale; and (C) varying one’s distance from the computer screen. The examples below are restricted to artefacts that occur in patient images, i.e. those that are of concern to clinicians. Technical staff will be concerned also with the artefacts of quality-control images. Busemann Sokole’s ‘Atlas’ (see Suggested Further Reading) illustrates and explains a comprehensive range of gamma camera artefacts. • A common artefact of older gamma cameras is a regular pattern of dark or light spots that mimic the arrangement of the PMTs behind the crystal.The example shown in Figure 7.14 is a faulty uniformity flood test, acquired using a uniform sheet of radioactive material known as a flood phantom. With a patient on the camera, the image would show the organs containing radioactivity, but with the pattern of spots superimposed. This pattern can have various causes, for instance a shift in the high voltage supply to the PMTs, a fault in one of the camera’s correction matrices, or selection of the wrong energy window for the radionuclide being scanned. • A single cold spot of similar size would indicate a single faulty PMT. • A straight line, or lines, across the field of view may indicate a fault in the circuits that determine the spatial coordinates.

139

140

SECTION 1

• IMAGING TECHNIQUES AND GENERAL ISSUES

Anterior

Posterior

Anterior

Tissue phase

A

Posterior Delay

B

C

D

Figure 7.13 Bone scintigram in a child with osteomyelitis of the distal left femur acquired using 99mTc methylene diphosphonate. The distribution of the radiopharmaceutical changes between the early tissue phase images (A, B) and the delayed images (C, D). The bones are visualized more clearly on later images. The epiphyseal plates show increased uptake, a normal finding in children. There are differences between corresponding anterior and posterior images and right–left (R–L) annotation on anterior and posterior images.

• Star-like rays emanating from hot spots can be produced by septal penetration if a low-energy collimator is used to image high-energy gamma rays. • Irregular lines or sharp-edged patches usually mean the crystal has cracked, or humidity may have leaked in. The

NaI crystal is hygroscopic and very delicate. Its front and sides are protected by thin aluminium sheeting, and the back is sealed to the PMTs with special light-transmitting grease. • If a SPECT reconstruction shows a circular ring or arc, this usually means that detector uniformity is at fault, and may need to be recalibrated. A ray-like artefact may be produced when a region of intense radioactivity lies within the reconstructed volume. The detection and understanding of artefacts is an essential aspect of quality assurance. Firstly, artefacts can distort images and therefore an understanding of them is essential to the interpretation of patients’ images. Secondly, certain artefacts indicate camera faults or poor working practice, and these will need to be corrected.

Figure 7.14 phantom.

Faulty uniformity flood test, acquired using a flood

Knowledge of the normal biodistribution of the injected radiopharmaceutical is essential for accurate interpretation, just as knowledge of normal anatomy is required for other imaging techniques. It is also important to be aware of how the distribution changes with time and with the age of the patient. For example, skeletal scintigraphy in a child will show normal epiphyseal activity related to growth, an appearance that is lost in the mature skeleton (Fig. 7.13). An unusual distribution of radioactivity may not necessarily indicate disease. Some normal tissues will show variable uptake of a radiopharmaceutical; for example, breast uptake of

CHAPTER 7

67

Ga-gallium citrate, or uptake of 18F-FDG in brown fat within the neck and superior mediastinum. The radiochemical purity may be poor; for example, an excess of unbound technetium, not combined in the intended form, would accumulate in the thyroid. The possibility that the patient may have been given the wrong radiopharmaceutical also needs to be considered. Radiodistribution is affected by patient preparation. Factors such as hydration, fasting and the patient’s medication are important in certain studies. Radioactive contamination will show up on images. Radiopharmaceuticals excreted in the urine may contaminate clothes or skin following micturition. Other examples include extravasation of radiopharmaceutical at a site of venous injection, a contaminated injection swab in a patient’s pocket and contamination transferred from the fingers to the patient’s skin or the camera. Motion of the patient during image acquisition will lead to loss of resolution and may produce other artefacts.

Abnormal biodistribution due to disease can comprise either increased or decreased uptake of radiopharmaceutical, depending on whether the pathological process concerned results in loss or upregulation of the mechanism of uptake. Some radiopharmaceuticals have highly specific uptake mechanisms and failure to demonstrate a site of disease may be due to absence of the uptake mechanism in that particular case. Such instances may not represent diagnostic failures because demonstrating the lack of uptake can have important implications for subsequent clinical management. For example, a tumour that fails to accumulate the somatostatin analogue 111In-octreotide will not be suitable for subsequent octreotide therapy. Abnormalities in nontarget organs can provide clinical information relevant to the disease under study or indicate a new concomitant diagnosis. For example, skeletal scintigraphy looking for metastatic cancer as a cause of back pain may reveal incidental renal obstruction or occasionally demonstrate uptake in additional hepatic metastases. Interpretation of images from hybrid devices requires skills that are additional to those involved in reporting each imaging investigation in isolation. Some image artefacts are specific to hybrid imaging devices (see above). Furthermore, the anatomical appearances of lesions can modify the interpretation of the radionuclide image data and vice-versa. The greater use of hybrid systems is likely to produce an increasing need for clinicians proficient in interpreting both nuclear medicine and CT11.

NONIMAGING APPLICATIONS Most nuclear medicine departments also use radionuclides for therapeutic administrations and nonimaging diagnostic tests. Beta-emitting radionuclides are most commonly used for therapy as they deliver most of the radiation dose locally. Examples are iodine-131 for thyrotoxicosis and thyroid cancer,

• RADIONUCLIDE IMAGING: GENERAL PRINCIPLES

phosphorus-32 for polycythaemia vera, yttrium-90 for arthritic conditions and strontium-89 for bone metastases. There is a range of nonimaging tests, most of which involve administering radiopharmaceuticals to patients and measuring the radioactive content of plasma, urine, faeces, or breath samples.There is a larger range of usable radionuclides for these purposes than there is for imaging, as in samples it is possible to detect lower energy photon emissions (e.g. from iodine-125) or even beta emissions (e.g. from carbon-14 and tritium (3H)). One of the commonest nonimaging tests is the measurement of glomerular filtration rate (GFR) with chromium-51 (51Cr) EDTA. Red blood cells labelled with 51Cr can be used to document splenic sequestration and decreased red cell survival in patients with suspected haemolysis, or increased red cell mass in patients with polycythaemia vera. The urinary excretion of cyanocobalamin labelled with cobalt-57 can be used to diagnose vitamin B12 malabsorption (Schilling’s test). An emerging application of radionuclides entails the use of a gamma probe during surgery to identify surgically relevant structures that have accumulated radioactivity following a preoperative administration. One example is sentinel node biopsy during surgery for breast cancer. The sentinel node is the first lymph node in a nodal bed to receive drainage from a tumour, and examination of this node will demonstrate metastasis if any lymphatic spread has occurred. A peritumoural injection of 99mTc nanocolloid is given preoperatively. During surgery a gamma probe is used to identify the sentinel node to allow its removal and histological examination. If no tumour is found, dissection and removal of the remaining nodes in that group can be safely avoided.

RADIOPHARMACEUTICALS Radiopharmaceuticals must be viewed in terms of their biological behaviour, their mode of radioactive decay and the radiation dose to the patient. The biological behaviour of a particular radiopharmaceutical is defined by its physical and chemical properties and determines its localization in a specific organ or compartment within the body at particular times following injection. The mode of radioactive decay determines the radiation dose to the patient, as well as the imaging properties needed by the detection system. Large numbers of emitted photons are needed for the accurate temporal and spatial localization of a radiopharmaceutical. Short-lived isotopes that can be given in large doses to yield high count rates over a relatively short period of time are desirable so that the count rates are high, yet with a low total body radiation.While it is desirable for an isotope to have the shortest practical half-life, this must be compatible with the duration of the physiological process being studied. Any isotope that decays away before completion of the biological process under study would obviously be of little clinical use. The energy of the emitted gamma ray is also important for its efficient detection by a gamma camera. For conventional collimated single-photon imaging, gamma rays in the energy range 75–300 keV are most suitable.

141

Salivary gland study

Dry mouth (connective tissue disease)

Bone scintigraphy + white cell or gallium scintigraphy Lymphoscintigraphy

Osteomyelitis

Lymphoedema

Painful prosthesis

Metabolic bone disease

Arthropathy

Avascular necrosis

Fracture

Tumour Bone scintigraphy

Parathyroid scintigraphy

Hyperparathyroidism (presurgical localization)

Musculoskeletal system

Thyroid scintigraphy

I sodium iodide Tc pertechnetate

Ga gallium citrate Tc nanocolloid

99m

67

Tc- or 111In-leucocytes

Tc polyphosphate 99m

99m

Tc polyphosphate compounds

99m

Tc pertechnetate

99m

Tc MIBI

99m

99m

123

F fluorodeoxyglucose

Tc HMPAO

18

Ictal SPECT Interictal PET

F fluorodeoxyglucose

99m

Thyrotoxicosis Thyroid nodule Ectopic thyroid

Neck

Epilepsy (presurgical localization)

18

Cerebral metabolism PET

Tc HMPAO

99m

Cerebral perfusion SPECT

Dementia

Tc HMPAO

99m

In DTPA (intrathecal)

111

Tc HMPAO

99m

Blood–brain barrier (BBB) study

Cerebrospinal fluid (CSF) study

Cerebral perfusion SPECT

Radiopharmaceutical

Encephalitis

CSF rhinorrhoea

Hydrocephalus

Cerebrovascular accident

Head

Imaging technique

RADIOPHARMACEUTICALS COMMONLY USED FOR A RANGE OF CLINICAL PROBLEMS

Clinical problem

Lymphatic uptake and trapping

Binds to transferrin and leaks into extravascular space

Leucocyte migration

Osteoblastic activity

Osteoblastic response (+ vascularity on early phases)

Secretion in saliva

Differential expression of p-glycoprotein between parathyroid adenoma and thyroid

Active uptake (123I and 99mTc) followed by organification (123I)

Marker of glucose metabolism

Uptake proportional to blood flow

Marker of glucose metabolism

Uptake proportional to blood flow

Passage across disrupted BBB

Marker of CSF flow.

Uptake proportional to blood flow

Biological behaviour

SECTION 1

Table 7.2

142 • IMAGING TECHNIQUES AND GENERAL ISSUES

Quantitative shunt study

Congenital heart disease

Alveolar permeability study

Occult lung disease (alveolitis)

Meckel’s diverticulum scintigraphy White cell scintigraphy

Ectopic gastric mucosa

Diarrhoea (inflammatory bowel disease)

Tc sulphur colloid

Heat damaged 99mTc labelled red blood cells

Splenic scintigraphy

Ga gallium citrate

Ectopic splenic tissue

Tc or 111In leucocytes

99m

Tc iminodiacetic acid derivatives

99m

Tc labelled red blood cells

99m

In DTPA in orange juice (liquid phase)

111

Tc sulphur colloid in egg (solid phase)

99m

Tc leucocytes

99m

Tc pertechnetate

99m

Tc labelled red cells

99m

Tc sulphur colloid

99m

99m

Tc DPTA aerosol

Pyrexia of unknown origin

White cell or gallium scintigraphy

Hepatobiliary study

Red blood cell study

F fluorodeoxyglucose

99m

18

Ventilation: 99mTc aerosols 133 Xe gas, 81mKr gas 99m Tc red blood cells

Macroaggregates

Perfusion: 99mTc albumin

I fatty acids

123

F fluorodeoxyglucose

Tc red blood cells

Tc phosphines

67

Abdominal sepsis

Bile leak (post-op)

Biliary atresia

Biliary dyskinesia

Cholecystitis

Focal liver lesion (haemangioma)

Dumping

Gastric emptying study

GI bleed study

Gastrointestinal haemorrhage

Vomiting (gastroparesis)

Oesophageal transit and reflux

Difficulty in swallowing

Gastrointestinal system

Tumour imaging

Solitary pulmonary nodule

Pulmonary system

Ventilation/perfusion (V/Q) scan

18

Myocardial viability study

Pulmonary embolism

99m

Cardiac ventriculography (gated study)

99m

Tc teboroxime

99m

Tc isonitriles

99m

Cardiac failure

Tl (thallous chloride)

Myocardial perfusion scan

201

Radiopharmaceutical

Chest pain

Cardiovascular system

Imaging technique

RADIOPHARMACEUTICALS COMMONLY USED FOR A RANGE OF CLINICAL PROBLEMS—Cont’d

Clinical problem

Table 7.2

Splenic trapping of damaged cells

(Continued)

Binds to transferrin and leaks into extravascular space

Leucocyte migration

Uptake by hepatocytes and excretion into bile

Red cell pooling

Compartmental localization of labelled material

Leucocyte migration

Active uptake by ectopic gastric mucosa

Blood pool label extravasating into bowel

Transit of labelled material

Passage across alveolar membrane into blood

Marker of glucose metabolism

Blood pool label

Distributes in lungs in proportion to gas regional ventilation

Pulmonary arteriole blockade

Demonstrates shift from metabolism of fatty acids to glucose

Blood pool label

Uptake proportional to blood flow

Lipophilic compound which accumulates by diffusion

Cationic complexes taken up by myocytes in proportion to blood flow

K+ analogue indicating perfusion (ischaemic heart disease) (delayed uptake reflects viability)

Biological behaviour

CHAPTER 7 • RADIONUCLIDE IMAGING: GENERAL PRINCIPLES 143

Diuresis renography Static renal scintigraphy Indirect micturating cystogram Adrenal study Adrenal study

Renal tract obstruction

Renal scarring

Vesicoureteric reflux

Adrenal medullary tumour

Adrenal cortical tumour

Soft tissue mass (sarcoma)

Hypoxia imaging Lymphoscintigraphy

Tumour hypoxia

Sentinel node detection

Based on EC Referral Guidelines for Imaging .

MIBG scintigram

Somatostatin receptor study

Neuroblastoma

Carcinoid tumour

Insulinoma

Tumour response assessment

Tumour recurrence

15

Bone scintigraphy Tumour imaging

Skeletal metastases

Tumour imaging

Whole body iodine scintigram

Thyroid cancer

Tumour staging

Tumour imaging

Space occupying lesion in brain (SOL)

Cancer

Captopril renography

Imaging technique

Hypertension (renovascular disease)

Urological, adrenal and genitourinary systems

Clinical problem

Tl (thallous chloride)

I MIBG Tc nanocolloid

99m

F fluoromisonidazole

18

123

In pentetreotide (Octreotide®)

111

F fluorodeoxyglucose

18

F fluorodeoxyglucose

18

Tc polyphosphate

Tl (thallous chloride)

201

99m

I sodium iodide

131

F fluorodeoxyglucose

18

201

I iodocholesterol

123

I MIBG

123

Tc MAG3

99m

Tc DMSA

99m

Tc MAG3

99m

Tc DTPA

99m

Tc MAG3

99m

Radiopharmaceutical

RADIOPHARMACEUTICALS COMMONLY USED FOR A RANGE OF CLINICAL PROBLEMS—Cont’d

Lymphatic uptake and trapping

Trapped in hypoxic cells

Uptake by noradrenaline transporter

Binds to somatostatin receptors

Tumour glucose metabolism

Marker of glucose metabolism

K+ analogue indicating perfusion

Osteoblastic response

Uptake by Na/I transporter

Marker of glucose metabolism

K+ analogue indicating perfusion

Incorporation into hormone metabolism

Uptake by noradrenaline transporter

Compartmental localization

Glomerular filtration and proximal tubular uptake

Proximal tubular secretion

Glomerular filtration

Captopril-induced change in renal transit time and/or function

Biological behaviour

SECTION 1

Table 7.2

144 • IMAGING TECHNIQUES AND GENERAL ISSUES

CHAPTER 7

Pure gamma emitters (e.g.99mTc) are preferred whenever possible because beta particles give patients very much higher doses of radiation without contributing to the image. As the higher-dose investigations carry a theoretical lifetime cancer risk in the region of 1 in 1000, it is important to avoid unnecessary administration. Practical considerations concerning the availability and storage of isotopes also ultimately determine the usefulness of the given radiopharmaceutical. Technetium-99m is the most frequently used radionuclide in nuclear medicine today. Its parent nuclide, molybdenum-99 (99Mo), can be produced in either a reactor or a cyclotron.99Mo has a half-life of 66 h and therefore 99Mo/99mTc generators can conveniently be supplied weekly to nuclear medicine departments, providing a fresh daily supply of the radionuclide. The 6-h half-life of 99m Tc is sufficiently long for most imaging applications and its 140 keV gamma radiation has reasonable tissue penetration but can still be easily collimated.99mTc can be administered in free form as the pertechnetate ion (TcO4); however, owing to its diverse chemistry, it can also be incorporated into various pharmaceuticals for visualization of different organ systems. PET imaging requires positron emitters, which are typically produced in a cyclotron by irradiating a target material with a beam of charged particles. The need for a dedicated on-site cyclotron for the production of short-lived radiopharmaceuticals restricts the widespread availability of 11C, 13N and 15O.18F has a longer half-life of 109 min, and can be distributed by commercially operated central pharmacies. Common adverse, nonspecific reactions such as vasovagal reactions with syncope, hypotension and diaphoresis can occur with the intravenous administration of any drug and are not specific for radiopharmaceuticals. Significant allergic reactions, which include urticaria (hives), bronchospasm and anaphylaxis, are extremely rare when administering radiopharmaceuticals. In a recent 5-year study of over 750 000 radiopharmaceutical injections, no adverse reactions were severe enough to require hospitalization14.The 95% confidence interval for the prevalence of either a ‘possible’ or ‘probable’ reaction was 0.001–0.0003%. This compares to 4–13% for X-ray contrast agents (ionic) and 0.7–15% for all drugs administered in a hospital setting. The commonest reaction was a rash. One of the few caveats for the administration of a radiopharmaceutical is the injection of macroaggregated albumin for lung perfusion in patients with severe pulmonary hypertension. In these patients, a sudden increase in vascular pulmonary resistance due to capillary blockade by the radiopharmaceutical could exacerbate right-heart failure. Albumin macroaggregates are also contraindicated in patients with a history of hypersensitivity reactions to albumin products. A list of important radiopharmaceuticals applicable to a range of clinical problems is given in Table 7.2. Basic scientific research in molecular nuclear medicine currently conducted in most laboratories is aimed at designing more specific molecules to detect cells and tissues with genomic abnormalities.

• RADIONUCLIDE IMAGING: GENERAL PRINCIPLES

REFERENCES 1. Delacroix D, Guerre J P, Leblanc P et al 2002 Radionuclide and radiation protection data handbook 2002. Radiation Protection Dosimetry 98: 1–168 2. Mulford D A, Scheinberg D A, Jurcic J G 2005 The promise of targeted α-particle therapy. J Nucl Med 46: 199S–204S 3. Bolster A 2003 Quality control of gamma camera systems. Report No. 86. Institute of Physics and Engineering in Medicine 4. Medcylopedia website: www.amershamhealth.com/medcyclopaedia/ medical/index.asp; search under ‘Scintillation’ 5. Anagnostopoulos C, Harbinson M, Kelion A et al 2003 Procedure guidelines for radionuclide myocardial perfusion imaging, adopted by the British Cardiac Society, the British Nuclear Cardiology Society, and the British Nuclear Medicine Society. British Nuclear Medicine Society website: www.bnms.org.uk/downloads/MPI%20guidelines%20final.pdf 6. Parker R P, Smith P H S, Taylor D M 1984 Basic science of nuclear medicine, 2nd edn. Churchill Livingstone, Edinburgh, p 65 7. ACC/ AHA/ ASNC 2003 Guidelines for the clinical use of cardiac radionuclide imaging. American College of Cardiology Foundation and the American Heart Association, Inc. website: www.americanheart.org/ downloadable/heart/1061222494555RNIFullTextFinal.pdf 8. Biomedical Imaging Research Laboratory 2004 University of California Electrical Engineering Department website: http://neuroimage.usc.edu/ ResearchPETDynamic.html. 9. Hillel P (ed.) 2004 Basics of gamma camera positron emission tomography. Institute of Physics and Engineering in Medicine, York 10. Visvikis D, Lamare F, Turzo A et al 2005 List mode data based respiratory motion correction in whole-body PET. Nucl Med Commun 26: 286 11. Fletcher J W 2005 Clinical PET/ CT: a win or a loss for nuclear medicine? J Nucl Med 46: 385 12. Tatsch K (coordinator) 2001 Guidelines for brain neurotransmission SPET using 123I-labelled dopamine transporter ligands. European Association of Nuclear Medicine website: www.eanm.org 13. Dickson J C, Hutton B F, Cullum I D et al 2005 Quantifying uptake in Datscan: is what you see what you get? Nucl Med Commun 26: 277 14. Silberstein E B, Ryan J 1996 Prevalence of adverse reactions in nuclear medicine. J Nucl Med 37: 185–192 15. Royal College of Radiologists 2003 Making best use of a department of clinical radiology: Guidelines for doctors, 5th edn. Royal College of Radiologists, London

SUGGESTED FURTHER READING Busemann Sokole E 2003 IAEA quality control atlas for scintillation camera systems. IAEA, Vienna. IAEA website: www-pub.iaea.org/ MTCD/ publications/PubDetails.asp?pubId=6337 Chandler S T, Thomson W H (eds) 2003 Mathematical techniques in nuclear medicine. Report No. 73. Institute of Physics and Engineering in Medicine and Biology, York, pp 119–133 Lawson R S 1999 Application of mathematical methods in dynamic nuclear medicine studies. Phys Med Biol 44: R57–R98 Sharp P F, Gemmell H G, Smith F W 1998 Practical nuclear medicine, 2nd edn. Oxford University Press, Oxford Taylor A, Schuster D M, Alaxraki N 2003 A clinician’s guide to nuclear medicine. Society of Nuclear Medicine, Reston Thie J A 2004 Understanding the standardized uptake value, its methods, and implications for usage. J Nucl Med 45: 1431–1434 Turkington T G 2001 Introduction to PET instrumentation. J Nucl Med Technol 29: 4–11 Wahl R L, Buchanan J W (eds) 2002 Principles and practice of positron emission tomography. Lippincott, Philadelphia

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Functional and Physiological Imaging

8

Kenneth A. Miles, Martin J.K. Blomley†, A. Michael Peters, Gustav K. von Schulthess and David O. Cosgrove

Physiological imaging with contrast media • Why use kinetic modelling? • Contrast agent pharmacokinetics • Measurement of tracer concentration • Modelling and mathematical approaches • Summary Principles of molecular imaging • Molecular imaging and hypoxia inducible factor-1 • Comparison of molecular imaging strategies • Molecular imaging and biotechnology • Applications of molecular imaging • Summary Appendices 1–5

Historically, radiological methods have been seen as tools for anatomical rather than functional imaging. The exception to this has been in nuclear medicine, where a huge array of radiopharmaceuticals with different pharmacokinetic and imaging properties is used to image many aspects of physiology and pathophysiology. Of late, however, the traditional division has become blurred in some areas, notably perfusion and blood volume imaging. The cross-sectional techniques, in particular, have increasingly come to be seen as important tools for functional and physiological imaging. Nuclear medicine has shown that functional and physiological imaging offers two advantages over a purely structural approach: (A) the potential for earlier diagnosis before anatomical changes have developed; and (B) a closer correlation between the functional status of disease and clinical outcome which translates to improved clinical decision making. Many of the methods developed for nuclear medicine can be applied to MR, CT and ultrasound to produce techniques that combine the benefits of functional imaging with the high spatial resolution achieved with modern scanners.

In recent years, research initiatives in the biological sciences, such as the ‘human genome project’, have focused the understanding of medicine to the level of molecular biology. Diagnostic imaging has by no means been immune to this change, and increasingly imaging is not only understood in terms of molecular processes but is also used to demonstrate these processes in vivo. Although the resolution of diagnostic imaging techniques is clearly insufficient to depict individual molecules, a range of functional and physiological imaging characteristics can act as correlates for the activity of particular molecular and genetic processes.This approach has been dubbed ‘molecular imaging’. It is important, however, to realize that functional imaging in its widest sense has always been an inextricable part of radiology. Many everyday imaging methods, such as Doppler ultrasound, intravenous urography, or an expiratory chest CT, are as much ‘functional’ as ‘anatomical’ techniques.To describe all such applications would require coverage of a significant part of the whole subject of radiology, and is beyond the scope of this chapter, which instead focuses on two areas: the first—Physiological imaging with contrast media—describes how tracer kinetic methods in general developed for nuclear medicine and in turn derived from classic physiological principles, can be applied to a variety of imaging applications; the second—Principles of molecular imaging—outlines, with examples, the general approaches by which imaging can be used to study molecular and genetic processes. Only limited coverage will be given to the hugely important subject of physiological and molecular imaging with nuclear medicine and positron emission tomography (PET), as this is discussed in more detail elsewhere. For simplicity also, many other extremely important applications of MR to functional imaging—including functional brain MR using intrinsic contrast methods, notably blood oxygenation level dependent (BOLD) studies, magnetic resonance spectroscopy and diffusion/perfusion-weighted sequences—are omitted as they are also described in detail elsewhere.

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PHYSIOLOGICAL IMAGING WITH CONTRAST MEDIA WHY USE KINETIC MODELLING? In diagnostic imaging, contrast agents are generally used to highlight anatomical structures or pathologies that are otherwise difficult or impossible to see (e.g. blood vessels, kidneys, liver metastases, etc.). Such structures are often said to ‘enhance’ following the administration of contrast agent. Frequently, basic information about the functional status of these structures can be inferred from visual inspection of contrastenhanced images. For example, a kidney that does not opacify after administration of standard X-ray contrast agent may be deduced to be nonfunctioning. Similarly, structures that are judged to opacify to a greater or lesser degree, or at an earlier or later time than normal, may be considered to exhibit altered function. The degree of functional change can be assessed by visual grading or measurement of the amount of enhancement. Although readily obtainable, these semiquantitative approaches have significant constraints, most notably a poor or indirect relationship between the amount of enhancement and the physiological process assessed. For instance, reduced enhancement in a kidney may be due to a general reduction in cardiac output rather than impaired renal function. To overcome such constraints, it is possible to create models that describe how enhancement changes over time, encompassing a range of physiological factors and weighting each factor appropriately. By representing these models as mathematical formulae, it is possible to derive more precise measurements of individual physiological processes. This mathematical analysis is known as ‘kinetic modelling’. Because the pattern of contrast enhancement is determined by particular physiological processes, contrast agent can be considered to be a ‘tracer’. In order to use tracer kinetic methods in a meaningful manner, several requirements need to be met. Firstly, it is important to be able to model the pharmacokinetics of the contrast agent, or tracer, being used. Secondly, it must be possible to measure contrast agent concentration, or at least to be able to compare it in different areas. Appropriate mathematical methods can then be used to calculate a variety of physiological indices of clinical value. These functional indices can then be calculated directly or displayed as a parametric ‘functional image’ co-registered with an anatomical image.

CONTRAST AGENT PHARMACOKINETICS Although all types of contrast agent can be used as tools for functional imaging, it is crucial to understand their different kinetics. For example, the conventional iodinated X-ray and gadolinium chelate MR contrast media are relatively small molecules (about 1000 Da), which pass rapidly from plasma into the interstitial fluid in most tissues of the body, with subsequent excretion into the urine. However, transfer into the extracellular space does not occur in the brain where the blood–brain barrier prevents these molecules leaving the intravascular space. Thus these agents can, in principle, be used

for measuring various indices of vascularity, such as fractional vascular volume (FVV) and perfusion (i.e. flow per unit volume or mass of tissue). They are also well suited for estimating the rate of efflux into interstitial compartments (loosely speaking, vascular ‘leakiness’). These applications are discussed in more detail below. Some types of contrast agent, such as microbubbles (ultrasound contrast agents) remain intravascular and therefore act as blood pool markers similar to technetium (99mTc)-labelled red blood cells. These agents are highly suitable for measuring indices of the blood volume and perfusion in all organs and show great promise as a tool for measuring transit times through the vessels of various organ beds. Some contrast agents are selectively taken up into the reticuloendothelial system of the liver and spleen. Colloidal agents have these properties and have long been available in nuclear medicine; similar kinetics apply to the superparamagnetic iron oxide (SPIO) contrast agents in MR and to some liver-specific microbubbles. Additional contrast agents are available with selectivity for other tissues such as the biliary system (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid, or Gd-EOB-DTPA; 99m Tc-dimethyl-iminodiacetic acid, or HIDA) or pancreas (manganese dipyridoxyl diphosphate, or Mn-DPDP). In principle, uptake rates into these different types of tissue can be measured. A number of freely diffusible gases can also be used for functional imaging studies, such as xenon for CT and MR, and hyperpolarized helium in MR. These gases potentially lend themselves to the measurement of blood flow indices.

MEASUREMENT OF TRACER CONCENTRATION In some aspects, the measurement of the in vivo concentration of contrast agents is simpler than measurement of signals from radionuclides. For example, there is less need to make corrections for factors such as tissue attenuation. The higher spatial resolution of CT, MR and US means that regions of interest can be placed more accurately over specific structures in which the tracer concentration is to be measured. Difficulty of obtaining data with a sufficiently high temporal resolution in a particular scan plane is another limitation of conventional nuclear medicine techniques. On the other hand, the sensitivity of radionuclide imaging means that lower concentrations of tracer are measurable using nuclear medicine techniques other than CT, MR, or US. The concentration of X-ray contrast agents can be measured with particular ease using CT. There is a linear relationship between the increase in attenuation and iodine concentration1 in the absence of artefacts such as significant beam hardening.The precise relationship depends upon X-ray tube voltage, the age of the X-ray tube and the design of the CT system; however, in general, an increase in iodine density of 1 mg/ml will increase attenuation in a voxel by 25–30 HU. For practical purposes, therefore, a baseline-subtracted time– attenuation curve on CT after a bolus injection of contrast

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agent can be treated as a scaled time–concentration curve. This linearity is a particular advantage of CT. Unfortunately, difficulties in evaluating a thickness of tissue greater than the width of the CT detector track in one acquisition, as well as the need to minimize patient radiation burden, have precluded its wider use for quantitative functional imaging. These limitations may, however, be partly overcome by the high detection efficiency of newer multidetector slice CT systems. MR systems are more sensitive to contrast agents than CT but measurement of the concentration of MR contrast agents is much more difficult. The interested reader is referred elsewhere for a fuller discussion, as there is a large literature on this subject2,3. In general, the alterations in T2* relaxation time by susceptibility effects (e.g. with SPIO agents imaged using gradient-echo sequences) can be quantified in the vascular system with good results4. However, most interest has focused on analysis of the T1 shortening effects of the gadolinium chelates5, typically using T1-weighted spin-echo sequences for which it is assumed that changes in T2* effects are small compared to T1 changes.The relative signal change in a region on a T1-weighted sequence can be considered approximately proportional to the local gadolinium concentration when the concentration is low. Unfortunately, this somewhat simplistic analysis often breaks down at higher concentrations when T2* shortening cannot be neglected. The T2* effects may start to counteract the positive contrast effects of the T1 shortening. In addition, flow effects may be important in vessels. For both these reasons, quantitative measurements of vascular as well as parenchymal signal concentration are rarely successful. In general, quantification is possible using this approach, but only within certain concentration ranges, and ‘input function’ data from vessels are hard to obtain. Quantification of the enhancement effects of microbubble contrast agents in ultrasound is both helped and hindered by the fragility of microbubbles. Microbubbles are unique amongst contrast agents in that they can be destroyed by the very act of imaging them, even at low acoustic power settings6. This consideration leads to two opposing approaches to quantification7. The first approach is to use ultrasound with low acoustic powers and passively observe the enhancement effects produced. A particularly promising method is to quantify the intensity changes in spectral Doppler or power Doppler signals. It has been shown that regional microbubble concentrations can indeed be measured by quantifying the intensity of these signals8. Grey-scale signals can also be quantified, although usually newer harmonic imaging modes are needed to observe useful changes. The second approach is actively to seek to destroy microbubbles with a single pulse of high acoustic power and then scan using very low power settings, observing microbubble refilling rates into an area of interest during an infusion9. One method is repeatedly to pulse ultrasound at varying triggering intervals, waiting for a steady state and to study the relationship between steady-state enhancement levels and triggering delay settings10. In principle, both methods can measure microcirculatory flow speeds and the FVV of a tissue. Quantification can be

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performed off-line from the external video and audio output signals produced by the machines, or in some cases using proprietary software provided by the manufacturers. In all cases, corrections need to be made for nonlinear machine processing, notably the log compression widely employed in the display of ultrasound data.

MODELLING AND MATHEMATICAL APPROACHES Using a variety of approaches, many functional indices of vascularity can be measured, including fractional vascular and extravascular volumes, perfusion, transit times and indices of permeability or contrast clearance. As elsewhere in this chapter, only an overview of this subject can be given, and the reader is referred to several more detailed texts on these subjects for a fuller account11–13.

Perfusion Probably the most important single index that can be measured is perfusion, which is defined as flow either per unit volume or per unit mass of tissue. (Since the specific gravity of body tissues is close to 1, there is little difference between these two.) It is generally simpler to calculate perfusion in units of flow per unit volume and this convention will be followed here. Although tissue perfusion can, in principle, be measured using MR without exogenous tracers, the most successful approaches involve the kinetics of external tracer wash-in, wash-out and bolus passage.

Wash-in studies In wash-in studies, an agent is given which does not pass through a tissue bed, and accumulates progressively in the organ of interest.The classic example of this is the intra-arterial administration of microspheres deliberately engineered to be too large to pass through capillaries and which therefore mechanically embolize in a tissue bed (in the absence of shunts). Although such use of microspheres is confined to invasive animal studies, other tracers available for use in patients behave in a similar fashion, including ultrasonic contrast agents based on specialized large microbubbles with a diameter greater than that of capillaries (i.e. ≥ 8 microns)14.The concept of a ‘chemical microsphere’ pertains to tracers, typically radiopharmaceuticals, that can be administered intravenously but are extracted by the tissue of interest with an efficiency approaching 100%, and therefore accumulate in the tissue in a manner comparable to intra-arterial microspheres. As with all such agents, perfusion can be calculated as the ratio of tissue concentration at equilibrium with the integral of arterial tracer concentration (although corrections need to be made for an incompletely extracted tracer). Arterial concentration is classically determined from arterial blood samples drawn at a known rate (Appendix 1), although less invasive methods can be used.

Wash-out studies In wash-out studies, the principle is to observe the time– concentration curve for an agent during its passage out of

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a tissue bed. With appropriate corrections, perfusion can be calculated from the slope of a semilogarithmic plot of the time–concentration curve (Appendix 2). Although one (invasive) way of performing such a study is to give a very short, fast arterial injection of a tracer, such as an intracarotid xenon injection for brain perfusion studies, it is far more practical to give a freely diffusible tracer for a relatively long period to achieve a steady state and then abruptly discontinue it. The tracer will then be eliminated by pulmonary passage very rapidly. Examples include inhaled inert xenon in CT.

Bolus passage The pharmacokinetics of many agents used for perfusion measurements (especially conventional CT and MR tracers) are rarely ideal for perfusion imaging. Problems such as the partial extraction of an agent into the extracellular space during vascular passage may confound calculations, and recirculation has to be accounted for. A number of approaches to deal with these difficulties have been developed, involving analyses of the effects of a bolus of contrast medium (Appendix 3).Two are particularly useful in measuring perfusion. One method is to calculate perfusion as the ratio of peak parenchymal enhancement to the area under the arterial time–enhancement curve. This method has been applied to functional CT of the myocardium, spleen and other organs.Whilst useful, errors will arise if significant venous outflow occurs before peak tissue enhancement takes place15–19. A more robust method, developed by Miles for functional CT, is less subject to this problem of error from venous wash-out because perfusion is calculated from the ratio of the peak gradient of the tissue time–concentration curve to the peak height of the arterial curve20–22. Another advantage of this ‘gradient’ method is that it can be extended to tissues with ‘portal’ circulations (i.e. more than one type of input vessel), such as the liver23,24.Various extensions of the gradient method have been applied to the measurement of liver blood flow: one approach uses a correction based on the spleen and gives values for both hepatic arterial and portal venous perfusion of the liver in line with expected values, with marked differences between normal subjects and patients with cirrhosis25–27. An alternative approach is based on measurements of mean transit time (MTT) for a tracer to pass from inflow to outflow28 (Appendix 4). Strictly speaking, MTT should be measured by calculating the MTT values for a feeding artery and a draining vein and taking the difference. However, the simultaneous determination of arterial and venous concentrations can be difficult in practice, and MTT values are often determined from tissue time–concentration curves or ‘residue functions’ which can be determined by mathematical analysis known as deconvolution29,30. Microbubbles may offer a particularly appealing and elegant method of measuring true vascular transit times through organ beds, for two main reasons: they generally behave as pure blood pool enhancers and it is often possible to study single vessels or groups of vessels. For example, a spectral Doppler gate can be placed over the pedicle of a kidney so that the signal from one stereo channel shows arterial flow (towards the transducer) and that from the other channel shows venous flow (away

from the transducer). Time–intensity profiles from each vessel can be analysed and the transit time through the kidney (about 4 s) easily calculated31. Other types of temporal index can be calculated using microbubbles: this is discussed below.

Fractional vascular volume The fraction of tissue occupied by blood is, in itself, an important physiological measurement of the microcirculation, corresponding to the ‘vascularity’ of the tissue. As can be seen above, it is also needed as part of some algorithms for calculating perfusion. In theory, this index should be obtainable directly using the widely available method of power Doppler ultrasound (PD). PD may be seen as a machineprocessed, log-compressed map of the number of moving red cells, principally detected as rouleaux. Compensation for nonlinear machine processing effects can be applied and estimates of FVV obtained32,33. Unfortunately, the detection of a vascular signal in smaller vessels (i.e. ≤ 100 microns) with Doppler without microbubble enhancement is difficult for both practical and theoretical reasons, and the measurements obtained can probably only be regarded as relative yardsticks. Tracer kinetics can be applied relatively simply to the measurement of blood volume. The simplest approach is to administer a blood pool tracer, wait until steady state, and then calculate the ratio between tissue and blood pool concentration. Alternatively, fractional volume can be calculated dynamically. For example, the ratio of the area under a tissue time–concentration curve to that of the arterial time– concentration curve will calculate FVV, although this simple relationship may be complicated by recirculation and passage of tracer into the extravascular space.

Direct and indirect indices of permeability Many agents, such as conventional X-ray and MR contrast agents, diffuse rapidly into the interstitial spaces outside the brain. Compartmental and other types of analysis can be applied to their kinetics (Appendix 5) and indices of these processes calculated34–36. Such indices can provide a useful tool for characterizing malignancy, as vascular hyperpermeability is known to be a feature of tumour neoangiogenesis. Changes in permeability can be used, for example, to demonstrate acute radiation injury37. When applied to CT data acquisition of the kidney, permeability measurements will reflect contrast clearance per unit volume of the kidney, which is closely related to the glomerular filtration rate (GFR) per unit volume of the kidney, an interesting and appropriately scaled index of nephron function38,39. Since GFR and renal volume can be measured using other methods, this provides an opportunity to validate these approaches. In a recent study, Tshushima et al showed that a good correlation could be seen between the Patlak method and conventionally determined GFR measurements40.

Other functional indices A large variety of other functional indices can be measured. These include global renal function (i.e. GFR), which can be

determined using serial assays of iodinated contrast agents which, being renally filtered, are analogous to Tc-DTPA41–43. Using CT, the concentration of iodinated agents can be conveniently measured without the need for blood sampling. It can be shown that the slope of a semilogarithmic plot of their concentration against time measures GFR per unit volume of extracellular space44,45. Another promising class of functional indices is the large number of temporal indices that can be measured using microbubble enhancement. For example, the time–intensity profile of the Doppler signal from a hepatic vein after bolus injection of a microbubble gives much useful information about transit through the liver. Patients with cirrhosis and liver malignancy, who have portovenous and other shunts, and arterialization of their liver blood supply, show much earlier transit, with enhancement beginning at 24 s or less after injection, whereas normal subjects enhance later, typically over 30 s. This phenomenon shows great promise as a tool in the assessment of diffuse liver disease and also in the detection of early metastatic disease46,47. The ease with which microbubbles can be destroyed, referred to earlier, opens up other functional imaging methods. For example, if a microbubble is infused and pulses of ultrasound are sent at varying trigger intervals, a steady state will be reached at each trigger setting in which the amount of microbubbles destroyed equals the amount flowing into the imaging plane. A plot of echogenicity against triggering interval will be asymptotic (Fig. 8.1): the initial upslope measures microcirculatory flow speed whilst the asymptote measure is proportional to FVV9. Alternatively, if all the microbubbles in an area are destroyed and then imaged while they refill a tissue, the initial upslope of the time–concentration curve should also estimate microcirculatory flow speed.

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Echogenicity

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Pulsing interval

Figure 8.1 A plot of echogenicity against triggering interval for microbubble infusion will be asymptotic: the initial upslope (thick) measures microcirculatory flow speed whilst the asymptote measure is proportional to fractional vascular volume. (After Wei K, Jayaweera A R, Firoozan S et al 1998 Quantification of myocardial blood flow with ultrasound induced destruction of microbubbles administered as a constant venous infusion. Circulation 97: 73–83.)

SUMMARY The vascular system plays a fundamental role in the pathogenesis of the two major causes of death in western societies, namely cardiovascular disease and cancer, and is an essential factor in inflammatory processes. Contrast agents used for MR, CT and US can provide physiological information about the status of the vascular system combined with anatomical data obtained at the same examination. The most promising parameters are perfusion, permeability, or clearance measures, and temporal or ‘transit’ time. Such measurements offer an insight into the functional status of the vascular system with an increasing number of clinical applications.

PRINCIPLES OF MOLECULAR IMAGING Molecular imaging is often thought to be a highly specialized technique that is more applicable to research than everyday clinical practice. Contrary to this perception, there are many imaging techniques in widespread use that have been shown to correlate with particular biomolecular events (Fig 8.2). For example, the degree of enhancement of lung nodules on computed tomography correlates with the expression of vascular endothelial growth factor (VEGF), a molecule that stimulates tumour angiogenesis. Uptake of radio-iodine in thyroid tumours, one of the oldest techniques in nuclear medicine, results from expression of the sodium-iodide symporter molecule on the tumour cell surface. Other examples from nuclear medicine are illustrated in Figure 8.2. The imaging strategies that are capable of assessing molecular and genetic processes can be classified as direct, surrogate, or indirect48: • Direct molecular imaging involves direct interaction between the imaging probe and the molecular target (e.g. a specific enzyme or receptor). • Surrogate molecular imaging reflects the downstream physiological effects of one or more molecular or genetic processes.

• Indirect molecular imaging strategies are more complex, typically involving reporter gene approaches in which cellular function is modified so that the target gene induces a molecular change that can be assessed with a complementary imaging probe. Reporter gene imaging is summarized in Figure 8.3. The reporter gene comprises a length of deoxyribonucleic acid (DNA) which is introduced into the target cells by transfection using, for example, a viral vector. The reporter gene can be designed so that it is activated by one of a range of genetic or molecular processes of interest. The activated reporter gene is transcribed into the corresponding messenger ribonucleic acid (mRNA) which is in turn translated to the reporter protein. Subsequent administration of a reporter substrate that interacts with the reporter protein produces an imaging signal. A frequently used reporter gene is the herpes simplex virus type 1 thymidine kinase (HSV1-TK) which has radiolabelled substrates (e.g. fluoro-deoxy-arabinofuranosyl-iodouracil, or FIAU) that can be labelled with iodine-123 for single photon emission tomography or iodine-124 for positron emission tomography48. MR-based reporter genes include those

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Contrast-enhanced CT

B

131I

Na+/ISymporter

VEGF

C

111I-octreotide

Somatostatin Receptor

D

18F-FDG

GLUT-1

Figure 8.2 Examples of ‘everyday’ molecular imaging. (A) Peak contrast enhancement of a lung nodule (arrow) on CT correlates with expression of vascular endothelial growth factor (VEGF). (B) Uptake of radioiodine (131I) in miliary lung metastases (arrowheads) of thyroid cancer reflecting expression of the sodium/iodide (Na+/I−) symporter. (C) Uptake of 111In-octreotide in a pelvic carcinoid tumour (arrow) indicates expression of somatostatin receptors. (D) Uptake of 18F-fluorodeoxyglucose (FDG) in multiple metastases due to expression of Glut-1 glucose transporters.

encoding for a modified human transferrin receptor that increases the signal on MR imaging due to binding of supraparamagnetic iron compounds49. Another MR reporter gene produces β-galactosidase for which a special gadolinium contrast agent (EgadMe) acts as substrate50. Access of water to the gadolinium is blocked unless the contrast molecule is cleaved by β-galactosidase, thereby producing contrast enhancement on MR.

MOLECULAR IMAGING AND HYPOXIA INDUCIBLE FACTOR-1 Each of the three molecular imaging strategies can be illustrated by considering the molecular biology related to hypoxia

Reporter Gene

Transfection

Reporter substrate

Nuclear DNA

Direct molecular imaging

Transcription

Reporter mRNA

Translation

inducible factor-1 (HIF-1) as summarized in Figure 8.4. HIF1 activity is increased in ischaemic tissue and tumour, and thus this molecule plays an important role in the pathogenesis of the two major causes of mortality in western societies: cardiovascular disease and cancer51. In the case of ischaemic tissue, hypoxia results in stabilization of HIF-1 and so increases the activity of this molecule. Hypoxia can also be a factor that increases HIF-1 activity in tumours; however, oncogene mutations, such as the von Hippel–Lindau (VHL) gene or mutations in the p53 suppressor gene, play an important additional role. HIF-1 is a transcription factor that increases the expression of a whole raft of genes.The resulting alterations in cellular function enable cells to respond and adapt to hypoxic conditions. For example, increased nitric oxide activity results in vasodilatation, thereby producing a compensatory increase in oxygen delivery (Fig. 8.5). In the case of tumours, many of the secondary effects of HIF-1 confer a survival advantage to the malignant cells (e.g. making the cells resistant to therapy). Several aspects of the molecular biology related to HIF-1 can be depicted using molecular imaging.

Reporter protein

Imaging signal

Figure 8.3 Summary of the imaging reporter gene concept. The reporter gene is incorporated into the nuclear DNA of the target cells by transfection (e.g. viral vector). If the reference gene is active, the cell translates the reporter gene to produce reporter messenger RNA (mRNA) which is translated to the reporter protein. The reporter substrate interacts with the reporter protein to produce an imaging signal (e.g. gamma ray, paramagnetic effect).

Examples of direct molecular imaging include fluorodeoxyglucose (FDG) PET and 99mTc methoxyisobutylisonitrile (MIBI) scintigraphy. FDG interacts directly with Glut-1 glucose transporters that become upregulated in response to increased HIF-1 activity, resulting in increased FDG uptake as commonly seen in a variety of tumours (Fig. 8.2D). Increased FDG uptake is also seen in hypoxic tissue, for instance the myocardium where FDG uptake in the presence of reduced perfusion can be used clinically to identify ischaemic yet viable heart muscle that would benefit from revascularization (i.e. hibernating myocardium).99mTc-MIBI interacts directly with a p-glycoprotein (pgp) that produces

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Up – regulated molecules

Nitric Oxide Tissue Hypoxia VEGF HIF– 1 Glut – 1 Oncogene Mutations e.g. p53

MDR p – Gp

Biological effects Vascular Dilatation and Permeability

Imaging techniques

Contrast enhanced CT and MR Doppler US

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Figure 8.4 Molecular imaging and hypoxia inducible factor-1 (HIF-1). HIF-1 activity is increased by tissue hypoxia and oncogene mutations. Increased HIF-1 activity upregulates several molecules with biological effects that are accessible to noninvasive imaging. FDG = fluorodeoxyglucose, MDR = multidrug resistance, MIBI = methoxyisobutylisonitrile, p-Gp = p-glycoprotein, VEGF = vascular endothelial growth factor.

Angiogenesis Increased Glucose Metabolism Multi – drug resistance

multidrug resistance in tumours. Many therapeutic agents and 99mTc-MIBI are substrates for the pgp molecule which confers drug resistance by eliminating these agents from the cell. The elimination of 99mTc-MIBI can be assessed by comparing tumour uptake on delayed images with initial uptake, with rapid elimination of MIBI implying drug resistance52. Although FDG-PET and 99mTc-MIBI scintigraphy can be considered direct molecular imaging techniques for Glut-1 and pgp on account of the direct interactions between the imaging probes and their target molecules, respectively, these imaging techniques can also provide surrogate imaging for HIF-1 activity, because increased expression of Glut-1 and pgp are secondary effects of HIF-1.

Surrogate molecular imaging Surrogate molecular imaging of HIF-1 can be performed using the physiological imaging techniques described above. Vascular dilatation, increased permeability and new vessel formation (angiogenesis) are secondary physiological effects of increased nitric oxide activity and VEGF expression respectively (Fig. 8.4). In tumours, these changes in vascular physiology are detectable as increased contrast enhancement on CT and MR (Fig. 8.2A), and can be quantified as measurements of perfusion, relative blood volume and permeability using the kinetic modelling described above. The increased Doppler signal frequently observed during ultrasound examination of tumours can also be attributed to these vascular effects. In the case of ischaemic tissue, perfusion is reduced secondary to vascular disease. However, the vasodilatory effects of increased nitric oxide activity can be depicted using functional CT techniques that measure perfusion and blood volume separately. When applied to the brain in the acute phase of stroke, perfusion and blood volume are both reduced in the infarct53. On the other hand, the surrounding penumbra demonstrates preserved blood volume in the presence of reduced perfusion (Fig. 8.5). By indicating on-going molecular activity, this finding implies the presence of viable brain tissue that is potentially recoverable with suitable therapy.

FDG – PET

Tc99m MIBI scintigraphy

Indirect molecular imaging Indirect molecular imaging has been used in experimental animals to image the activity of HIF-1 and the p53 tumour suppressor gene54,55 (Fig. 8.6). In both cases, the reporter protein was HSV1-TK imaged using radiolabelled substrates for PET. In separate experiments, the reporter gene DNA constructs were designed so that HSV1-TK was placed under the control of either a hypoxia-response element or a p53-specific enhancer. A retrovirus was then used to introduce the reporter genes into the genome of tumour cell lines which were subsequently grafted into rodents. Tumours expressing HIF-1 or p53 showed increased uptake on PET images whereas no uptake was seen in control tumours that did not express these molecules (Fig. 8.6). In the cases of HIF-1, greater uptake was seen in larger hypoxic tumours and following ischaemic injury.

Figure 8.5 Functional CT images of cerebral blood volume (CBV: left) and cerebral blood flow (CBF: right) in acute stroke. The infarct core (red outline) shows matched reductions in CBV and CBF. The surrounding penumbra (white outline) demonstrates preserved CBV despite reduced CBF reflecting upregulation of nitric oxide (NO) secondary to increased activity of HIF-1. (Adapted from Miles K A, Griffiths M 2003 CT perfusion: a worthwhile enhancement? Br J Radiol 76: 220–231.)

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Nontreated

Treated (BCNU 40 mg/kg i.p.)

%Dose/g

A

0.50

0.10 U87wt (neg. control)

0.05

U87p53TKGFP (test)

0.01

0.00

B

RG2TKGFP (pos. control)

C6 control

Sagittal

#4C6 Reporter

xenografts

images

xenografts

Axial images 1.5 1.2 1.0 0.6 0.2 0.1 0.05 0.02 0.01 0.00 18 F-FEAU % dosing

Figure 8.6 Indirect molecular imaging of the expression of p53 (A) and HIF-1 (B) in experimental animals. (A) Positive and negative control tumours were grafted onto the left shoulder and left thigh respectively. The test tumour on the right shoulder only accumulates radioactivity after activation of the p53 pathway in response to DNA damage produced by administration of N,N′-bis(2- chloroethyl)-N-nitrosourea (BCNU). (From Doubrovin M, Pnonmarev V, Beresten T et al 2001 Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc Natl Acad Sci USA 98: 9300–9305.) (B) Tumours grafted onto the animal’s left side accumulate radioactivity due to activation of HIF-1. Greater activity is seen in larger tumours, reflecting more severe hypoxia. Control tumours on the animal’s right side show no accumulation of radioactivity. (From Serganova I, Doubrovin M, Vider J et al 2004 Molecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice. Cancer Res 64: 6101–6108. With permission of the American Association for Cancer Research.)

COMPARISON OF MOLECULAR IMAGING STRATEGIES Each molecular imaging strategy is able to evaluate different stages of gene action from DNA transcription, through translation into a protein, to the ultimate functional and physiological effects of the expressed gene. Indirect molecular imaging with reporter genes can assess expression of an individual gene (e.g. p53) or protein (e.g. HIF-1). The activity of gene-specific proteins can also be assessed using direct molecular imaging whereas surrogate imaging evaluates the final physiological effects of the gene. Biological amplification occurs at each stage, such that

increased activity of a single gene will produce multiple copies of the corresponding protein. Similarly, the magnitude of secondary physiological effects of molecular genetic processes that form the basis of surrogate imaging often exceeds the magnitude of the primary molecular genetic event. The biological amplification at each stage increases the intensity of the corresponding image signal, making the molecular and genetic process easier to assess. However, as the imaging process moves further from the originating genetic event, the imaging signal becomes less specific to a particular gene.This loss of specificity is due to the fact that the activity of a particular protein can be controlled by more than one gene, and the downstream physiological effects can depend upon the activity of many different

CHAPTER 8

molecular genetic events. For example, tumour uptake of FDG has been shown to correlate not only with activity of HIF-1 and Glut-1, but also microvessel density and inflammatory cell infiltration. In the case of reporter gene systems, the reporter gene construct confers genetic/molecular specificity whilst the use of a reporter protein provides signal amplification. However, the benefits of this combination are at the expense of increased complexity and, to date, this molecular imaging strategy has largely been confined to experimental animals.

MOLECULAR IMAGING AND BIOTECHNOLOGY By reflecting the different stages of gene action, molecular imaging strategies have equivalent biotechnological techniques that assess molecular genetic events in tissue samples. Broadly speaking, indirect molecular imaging corresponds to genomics or proteomics, direct imaging to proteomics and surrogate imaging to physiomics or metabonomics. It should be noted that, unlike molecular imaging, some biotechnology approaches such as DNA microarrays assess many hundreds or thousands of molecular genetic events simultaneously. However, molecular imaging has some distinct advantages over tissue-sampling methods. Firstly, the need for invasive biopsy is avoided. In some cases, obtaining tissue for genetic analysis can be difficult and it is possible that tissue perturbation resulting from the biopsy process can alter gene expression. Secondly, spatial heterogeneity of gene expression, well recognized within tumours, may result in biological features being missed on biopsy due to sampling error whereas imaging can assess the whole tumour. Such heterogeneity has been shown to produce discrepancies in the apparent degree of expression of pgp-mediated multidrug resistance as assessed in vitro by immunohistochemistry and in vivo by MIBI imaging56. Differences in gene expression at different disease sites in the same patient and changing expression over time are also well-recognized phenomena that will be more readily appreciated through molecular imaging whereas multiple biopsies are likely to be undesirable or impracticable. Furthermore, molecular imaging can assess molecular and genetic processes in the target tissue and other organs simultaneously.

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molecular imaging can be used as an early marker of response. Levels of expression of specific genes before therapy may also determine the likelihood of subsequent response.Thus molecular imaging could be used in drug trials to identify subpopulations of patients enriched for response, increasing the probability of demonstrating drug efficacy. The use of molecular imaging as a response marker is gaining in interest in clinical practice, particularly in oncology where the limitations of a purely structural approach are becoming apparent. A slow tumour response, residual nonmalignant masses and measurement errors are significant constraints on using size criteria to assess tumour response to therapy. Molecular processes that can provide an early marker of tumour response are those associated with glucose metabolism, angiogenesis and apoptosis (programmed cell death). In lymphoma, for example, assessing the glucose metabolic response to therapy with FDG-PET has greater accuracy than CT, and can identify nonresponders earlier in the course of treatment. Angiogenesis imaging in lymphoma with contrastenhanced CT or MRI, or conventional scintigraphy with 210 Tl or 99mTc-MIBI, may emerge as less expensive and more widely available alternatives to FDG-PET that may be particularly appropriate in assessing response to anti-angiogenesis therapy. Preliminary work in follicular lymphoma suggests that the degree of apoptosis, imaged with 99mTc Annexin-V uptake 24 h after the last fraction of radiotherapy, can predict the ultimate clinical response58. The ability of molecular imaging to select patients for specific therapy and to assess therapeutic response is also gaining recognition in clinical practice. A clear illustration of the application of molecular imaging in selecting therapy is the use of 111Inoctreotide to confirm tumour expression of somatostatin receptors before somatostatin therapy. Potentially, such approaches can be highly cost-effective by enabling the cost and morbidity of treatment to be avoided in those patients with a low likelihood of response. For example, 99mTc-MIBI could be used to identify patients with non-small cell lung cancers that express pgpmediated multidrug resistance (MDR) and so fail to respond to chemotherapy. Using currently available data, it has been estimated that this approach could potentially save £964 per patient with no loss in life expectancy. If extrapolated to a national level, the total saving in the UK would be in excess of £1.5 million per year59.

APPLICATIONS OF MOLECULAR IMAGING Molecular imaging has both research and clinical applications. One clear research application has been in the development of gene therapies where molecular imaging can confirm the success of gene transfection, determine whether transfection is localized to the target organ, and assess whether the level of transgene expression is sufficient for therapeutic effect. Molecular imaging has also gained an important role in the development of drugs that have specific molecular targets (e.g. an anticancer drug that aims to block VEGF activity). In the early stages of drug development, molecular imaging can confirm the mechanism of action (i.e. proof-of-principle) and assess the duration and magnitude of effect for specific drug dosages57. In later phase trials,

SUMMARY By providing imaging correlates for molecular and genetic processes in vivo, molecular imaging has applications both in research and clinical practice. In research, molecular imaging aids in the development of gene therapy and drugs with specific molecular targets. In clinical practice, molecular imaging can characterize disease processes more precisely so that the optimum treatment and response markers can be selected for an individual patient. This potential for ‘personalized’ medicine suggests a role for molecular imaging comparable to that advocated for gene-based biotechnologies such as DNA microarrays.

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APPENDICES APPENDIX 1

it will be close to the FVV of the tissue being imaged, and this needs to be measured for the determination of f.

Perfusion can be calculated using a microsphere or completely extracted tracer as follows. Let c(t) be tissue concentration and a(t) be arterial concentration at time t. Then in time δt the change in c(t) or δc( (t) ) is f.a(t) where f is perfusion. Going to the limit and integrating c(t) = ƒ ∫0t a(t)dt

APPENDIX 3 Suppose arterial concentration is again a(t),venous concentration v(t) and c(t) again is tissue concentration. Then, for a volume V, δ(c(t) ) = f.a(t).dt–f.v.(t).δt. Hence ƒ =

As t→∞, a steady state is reached and all the tracer accumulates in the body tissues. Perfusion can then be calculated

dc(c) dt

a(t)-v(t)

ƒ=

c(∞) ∞∫0a(t)dt

(1)

The denominator term, i.e. the integral of arterial concentration, is conventionally calculated in a microsphere study by drawing arterial blood at a rate F. In time δ(t) additional activity equivalent to F.a(t).δt accumulates. Thus total activity at time t, or M(t), is given by M(t) = F t∫0 a(t)dt

(2)

Thus, as t→∞, the ratio M(t)/F tends to ∞∫0a(t)dt. In practice, it is only necessary to draw blood for a short while, after which the blood will be cleared of tracer. Let M be the activity in the drawn blood at this time. Then, from equation 2, ∞∫0a(t)dt = M F Hence

ƒ=

F.c(∞) M

More complex calculations or modelling of arterial concentration are necessary if a tracer is incompletely extracted, or arterial blood concentrations are not directly measured.

APPENDIX 2 Perfusion can be calculated from the time–concentration curve for an agent during wash-out from a tissue bed. Provided there is no significant arrival of additional (arterial) tracer in this time, the time–concentration curve declines monoexponentially. If c(t) is concentration at time t, c(t) = c(0)e−kt where k is the ‘wash-out constant’: the ratio between perfusion f and partition coefficient λ. The concept of the partition coefficient, λ, merits some discussion. λ is defined as the ratio between the relative concentration of the tracer in tissue and in venous blood at steady state. λ is thus a dimensionless index. For an intravascular tracer

Perfusion can thus be calculated as the peak gradient of the tissue time–concentration curve divided by peak arterial concentration, provided venous concentration is relatively small at the time at which this peak gradient is measured.That is, tissue transit time is long compared to bolus width. Alternatively, perfusion can be measured as peak tissue concentration divided by the area under the arterial time– concentration curve peak, again provided transit is long. For a more detailed discussion on the relative merits and extensions of these methods, see Blomley and Dawson12.

APPENDIX 4 The central volume theorem of classic indicator dilution theory states that perfusion equates to f = α/MTT where α is the fraction of tissue in which the tracer is distributed (central volume) and MTT is the mean transit time for the tracer to pass from inflow to outflow28. For many tracers, α can generally be equated with the FVV, which can be determined using various means as described above. MTT can be harder to determine. Strictly speaking, this should be measured by calculating the mean transit time values for a feeding artery and a draining vein and taking the difference. MTT is calculated as the centroid of the time–concentration curve, c(t), of a region, i.e. ∫t.c(t)dt/∫c(t)dt. Alternatively, MTT can be calculated from ‘residue functions’ determined by deconvolution. This approach involves making assumptions about the distribution of transit times through an organ bed and is subject to errors of up to 100%29. For a discussion on these complex issues, the reader is referred to Gobbel et al30.

APPENDIX 5 The simplest model for determination of an index of permeability comprises reversible (vascular) and irreversible (tissue interstitium) compartments, in which the rate of transfer from plasma to interstitium is governed by a rate constant, k1 (Fig. 8.7). Modelling is greatly aided by the presence of both parenchymal and vascular (‘input function’) data, but these data are not always possible to obtain, especially in MR, and other approaches—such as modelling the vascular time–concentration curve—are necessary.

CHAPTER 8

K1 Plasma

Interstitium

Figure 8.7 The simplest two-compartmental model in which exchange occurs from plasma to interstitium governed by a rate constant k1.

c(t)/a(t) Gradient measures /V: contrast clearance per unit volume of tissue

Intercept measures FVV: (fractional vascular volume)

∫a(t)dt/a(t)

Figure 8.8 Patlak graphical analysis. If a(t) is vascular concentration and c(t) is tissue concentration, a plot of c(t)/a(t) against ∫a(t)dt/a(t) will tend towards a straight line.

A number of such models have been developed and applied3–5. Where vascular and tissue data are available, a simple method of estimating k1 is the Patlak graphical analysis34–36. If a(t) is vascular concentration and c(t) is tissue concentration, a plot of c(t)/a(t) against ∫a(t)dt/a(t) will tend towards a straight line (Fig. 8.8) as long as no tracer leaves the system.The slope will measure k1 and the intercept will be an indirect measure of FVV. It is important to realize that this rate constant k1 is not the same as the classic Crone–Renkin index of ‘permeability’38. This index is the ratio between the flux of tracer into the interstitium and the capillary concentration, and is usually expressed as the product of capillary surface area (S) and a permeability coefficient for the tissue bed P (‘PS product’) expressed in relation to a particular tissue volume. It can be shown that, where fplasma is the rate of perfusion, expressed for mathematical convenience as plasma flow per unit volume, it follows that if PS is very small and PS << fplasma, then k1 ≈ PS. Conversely, where PS is large and fplasma << PS, then k1 ≈ fplasma. In other words, k1 and PS are equivalent for a poorly extracted tracer, whereas k1 is closely related to blood flow for a highly extracted tracer. Where a tracer is partially extracted, such as a conventional X-ray or MR contrast agent, the relationship becomes more complex and it is perhaps safest to consider k1 as an index of tracer clearance rather than confusing it with either permeability or flow, as it is related to both11.

REFERENCES 1. Dean P B, Plewes D B 1984 Contrast media in computed tomography. In: Sovak M (ed.) Handbook of experimental pharmacology, Vol 73. Springer Verlag, Berlin, pp 479–523

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2. Hennig J 1998 Radiowaves: magnetic resonance. In: von Schultess G K, Hennig J (eds) Functional imaging. Lippincott-Raven, Philadelphia, pp 261–390 3. Brix G, Kemp K, Gückel F, Hoffmann U, Semmler W, Lorenz W J 1994 Quantitative assessment of tissue microcirculation by dynamic contrast-enhanced MR imaging. Adv MR Contrast 2: 68–77 4. Uematsu H, Maeda M, Sadato N et al 2000 Vascular permeability: quantitative measurement with double-echo dynamic MR imaging— theory and clinical application. Radiology 214: 912–917 5. Roberts H C, Roberts T P, Brasch R C, Dillon W P 2000 Quantitative measurement of microvascular permeability in human brain tumors achieved using dynamic contrast-enhanced MR imaging: correlation with histologic grade. Am J Neuroradiol 21: 891–899 6. Walker K W, Pantely G A, Sahn D J 1997 Ultrasound mediated destruction of contrast agents: effects of ultrasound intensity, exposure and frequency. Invest Radiol 32: 728–734 7. Blomley M J K, Eckersley R J, Cosgrove D O 1999 Potential for quantitation. In: Thomsen H, Muller R N, Mattrey R F (eds) Trends in contrast media. Springer Verlag, Heidelberg, pp 343–353 8. Schwarz K Q, Bezante G P, Chen X et al 1993 Quantitative echocontrast concentration measurement by Doppler sonography. Ultrasound Med Biol 129: 289–297 9. Hope-Simpson D, Burns P N 1999 Pulse inversion Doppler: a new method for detecting non-linear echoes from microbubble contrast agents. IEEE Trans Ultrason Ferroelectr Freq Control 46: 372–382 10. Wei K, Jayaweera A R, Firoozan S, Linka A, Skyba D M, Kaul S 1998 Quantification of myocardial blood flow with ultrasound induced destruction of microbubbles administered as a constant venous infusion. Circulation 97: 73–83 11. von Schultess G K, Burger C, Buck A 1998 Principles of quantitative function analysis: physiologic modeling. In: von Schultess G K, Hennig J (eds) Functional imaging. Lippincott-Raven, Philadelphia, pp 61–114 12. Blomley M J K, Dawson P 1997 Theoretical aspects and physiological models. In: Miles K A, Dawson P, Blomley M J K (eds) Functional CT. ISIS Press, Oxford, pp 47–60 13. Peters A M 1998 Fundamentals of tracer kinetics for radiologists. Br J Radiol 71: 1116–1129 14. Kasprzak J D, Vletter W B, van Meegen J R et al 1998 Improved quantification of myocardial mass by three-dimensional echocardiography using a deposit contrast agent. Ultrasound Med Biol 24: 647–653 15. Rumberger J A, Feiring A J, Lipton M J, Higgins C B, Ell S R, Marcus ML 1987 Use of ultrafast computed tomography to quantitate myocardial perfusion: a preliminary report. J Am Coll Cardiol 9: 59–69 16. Wolfkiel C J, Ferguson J L, Chomka E V et al 1987 Measurement of myocardial blood flow by ultrafast computed tomography. Circulation 76: 1262–1273 17. Gould R G, Lipton M J, MacNamara M T, Sievers R E, Koshold S, Higgins C B 1988 Measurement of regional myocardial blood flow in dogs by ultrafast CT. Invest Radiol 23: 348–353 18. Wolfkiel C J, Brundage B H 1991 Measurement of myocardial blood flow by UF CT: towards clinical applicability. Int J Cardiac Imaging 7: 89–100 19. Blomley M J, Kormano M, Coulden R, Lim-Dunhan J, Dawson P, Lipton M J 1997 Splenic blood flow: evaluation with computed tomography. Acad Radiol 4: 13–20 20. Miles K A, Hayball M, Dixon A K 1991 Colour perfusion imaging: a new application of computed tomography. Lancet 337: 643–645 21. Miles K, Blomley M 1997 Perfusion CT: normal organs. In: Miles K, Dawson P, Blomley M (eds) Functional computed tomography. ISIS Medical Media, Oxford, pp 71–88 22. Blomley M J K, Coulden R, Bufkin C, Lipton M J, Dawson P 1993 Contrast bolus dynamic computed tomography for the measurement of solid organ perfusion. Invest Radiol 28: S72–S77 23. Miles K A, Hayball M P, Dixon A K 1993 Functional images of hepatic perfusion obtained with dynamic CT. Radiology 188: 405–411

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24. Leggett D A, Kelley B B, Bunce I H, Miles K A 1997 Colorectal cancer: diagnostic potential of CT measurements of hepatic perfusion and implications for contrast enhancement protocols. Radiology 205: 716–720 25. Blomley M J K, Coulden R, Dawson P et al 1995 Liver perfusion studied with ultrafast CT. J Comput Assist Tomogr 19: 424–433 26. Tsushima Y, Blomley J K, Kusano S, Endo K 1999 The portal component of hepatic perfusion measured by dynamic CT: an indicator of hepatic parenchymal damage. Dig Dis Sci 44: 1632–1638 27. Bader T R, Herneth A M, Blaicher W et al 1998 Hepatic perfusion after liver transplantation: noninvasive measurement with dynamic singlesection CT. Radiology 209: 129–134 28. Maier P, Zierler K L 1954 On the theory of indicator dilution method for the measurement of blood flow and volume. J Appl Physiol 4: 308–314 29. Axel L 1980 Brain blood flow determination by rapid sequence computed tomography. Radiology 137: 679–686 30. Gobbel G T, Cann C E, Fike J R 1991 Measurement of regional cerebral blood flow using ultrafast computed tomography: theoretical aspects. Stroke 22: 768–771 31. Blomley M J K, Albrecht T, Eckersley R J et al 1998 Renal arteriovenous transit time measured non-invasively using bolus injections of microbubble contrast. Radiology 209: 1444 32. Rubin J M, Adler R S, Fowlkes J B et al 1995 Fractional blood volume: estimation with power Doppler US. Radiology 197: 183–190 33. Rubin J M, Bude R O, Fowlkes J B, Spratt R S, Carson R L, Adler R S 1997 Normalizing fractional moving blood volume estimates with power Doppler US: defining a stable intravascular point with the cumulative power distribution. Radiology 205: 757–765 34. Patlak C S, Blasberg R G, Ferstenmacher J D 1983 Graphical evaluation of blood to brain barrier transfer contrasts from multiple time-uptake data. J Cereb Blood Flow Metab 3: 1–7 35. Dawson P, Peters A M 1993 Dynamic contrast bolus computed tomography for the assessment of renal function. Invest Radiol 28: 1039–1042 36. Crone C 1963 The permeability of capillaries in various organs as determined by the use of the indicator diffusion method. Acta Physiol Scand 58: 292–305 37. Harvey C, Dooher A, Morgan J, Blomley M, Dawson P 1999 Imaging of tumour therapy response by dynamic CT. Eur J Radiol 30: 221–226 38. Blomley M J K, Dawson P 1996 Quantifying renal function with computerised tomography. Br J Radiol 69: 989–995 39. Miles K A, Leggett D A, Bennett G A 1999 CT derived Patlak images of the human kidney. Br J Radiol 72: 153–158 40. Tshushima Y, Blomley M J K, Kusano S, Endo K 1999 Use of contrastenhanced computed tomography to measure clearance per unit renal volume: a novel measurement of renal function and fractional vascular volume. Am J Kidney Dis 33: 754–760 41. Gaspari F, Perico N, Remuzzi G 1998 Application of newer clearance techniques for the determination of glomerular filtration rate. Curr Opin Nephrol Hypertens 7: 675–680 42. O’Reilly P H, Brooman P J C, Martin P J, Pollard A J, Farah N B, Mason G C 1986 Accuracy and reproducibility of a new contrast clearance method for the determination of glomerular filtration rate. Br Med J 26: 234–236 43. Stake G, Monn E, Rootwelt K, Grönberg T, Monclair T 1990 Glomerular filtration rate estimated by X-ray fluorescence technique in children:

44. 45.

46.

47.

48. 49. 50.

51. 52. 53. 54.

55.

56.

57. 58.

59.

comparison between the plasma disappearance of Tc-99m-DTPA and iohexol after urography. Scand J Clin Invest 50: 161–167 Peters A M 1992 Expressing glomerular filtration rate in terms of extracellular fluid volume. Nephrol Dial Transplant 7: 205–210 Dawson P, Blomley M J K 1996 Contrast agents as extracellular fluid markers: adaptation of the central volume theorem. Br J Radiol 69: 717–722 Albrecht T, Blomley M J, Cosgrove D O et al 1999 Non-invasive diagnosis of hepatic cirrhosis by transit-time analysis of an ultrasound contrast agent. Lancet 353: 1579–1583 Blomley M J K, Albrecht T, Cosgrove D O et al 1998 Liver vascular transit analysed using bolus injections of ultrasound contrast: early experience in seven patients with metastases. Radiology 209: 862–866 Blasberg R G, Tjuvajev J G 2003 Molecular-genetic imaging: current and future perspectives. J Clin Invest 111: 1620–1629 Weissleder R, Moore A, Mahmood U et al 2000 In vivo magnetic resonance imaging of transgene expression. Nat Med 6: 351–355 Louie A Y, Huber M M, Ahrens E T et al 2000 In-vivo visualization of gene expression using magnetic resonance imaging. Nat Biotechnol 18: 321–325 Semenza G L 2001 Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology. Trends Mol Med 7: 345–350 Del Vecchio S, Ciarmiello A, Salvatore M 1999 Clinical imaging of multidrug resistance in cancer. Q J Nucl Med 43: 125–131 Miles K A, Griffiths M 2003 CT perfusion: a worthwhile enhancement? Br J Radiol 76: 220–231 Serganova I, Doubrovin M, Vider J et al 2004 Molecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice. Cancer Res 64: 6101–6108 Doubrovin M, Pnonmarev V, Beresten T et al 2001 Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc Natl Acad Sci 98: 9300–9305 Kostakoglu L, Ruacan S, Ergun E L et al 1998 Influence of the heterogeneity of P-glycoprotein expression on technetium-99m-MIBI uptake in breast cancer. J Nucl Med 39: 1021–1026 Collins J M 2003 Functional imaging in phase I studies: decorations or decision making? J Clin Oncol 21: 2807–2809 Haas R L, De Jong D, Valdes Olmos R A et al 2004 In vivo imaging of radiation-induced apoptosis in follicular lymphoma patients. Int J Radiat Oncol Biol Phys 59: 782–787 Miles K A 2004 Cancer imaging – is it cost-effective? Cancer Imaging 4: 97–103

SUGGESTED FURTHER READING Miles K A, Eastwood J D, Konig M 2007 Multidetector Computed Tomography in Cerebrovascular Disease: CT perfusion imaging. Informa, Oxford Peters A M P, Myers M J 1998 Physiological measurements with radionuclides in clinical practice. Oxford University Press, Oxford von Schultess G K, Hennig J 1998 Functional imaging. Lippincott-Raven, Philadelphia

CHAPTER

Radiation Issues Governing Radiation Protection and Patient Doses in Diagnostic Imaging

9

Karen Goldstone and Stuart J. Yates

• • • • •

Radiation risks Principles of radiation protection and legislation Patient doses in diagnostic imaging Areas for special attention Radiation protection of staff and public

It is assumed that the reader has a basic knowledge of the interaction processes between ionizing radiation and tissue and the quantities (absorbed dose, equivalent dose and effective dose) and units (mGy and mSv) relevant in radiation protection.

RADIATION RISKS The benefit of using ionizing radiation in medicine is widely acknowledged. Although alternative methods of imaging—for example, ultrasound (US) and magnetic resonance imaging (MRI)—have been developed, ionizing radiation will continue to be used for the foreseeable future. However, it is recognized that ionizing radiation can cause harm and it is therefore important that the users of radiation are aware not only of the clinical benefits, but also of the possible risks to their patients and themselves and the legislation that is in place to control the risks. Soon after the discovery of X-rays and radioactivity, it became evident that radiation could cause somatic damage to tissues (e.g. erythema), but it was not for some years that the long-term and genetic effects began to be appreciated. Current knowledge of the risks of ionizing radiation is based on a wide range of epidemiological evidence from plant, animal and cell biology. The most significant body of information comes from the on-going study of those who survived the atom bombs dropped on Hiroshima and Nagasaki in 1945.

Deterministic and stochastic effects The damaging effects of radiation can be divided into two categories: deterministic effects and stochastic effects. Deterministic effects occur at high dose levels, such as those given in radiotherapy treatments and are due to radiation-induced cell death. These effects are characterized by having a threshold dose below which the effect is not observed. The severity of the effect increases with dose and dose rate. This may result in the death of the individual, depending on the organs exposed and the dose received. Cataract formation and skin damage are examples of deterministic effects. Normally, in diagnostic procedures, doses are well below the threshold where deterministic effects are observed, but the increasing use of interventional techniques has made exceeding a threshold dose for skin damage a possibility that cannot be ignored1. Doses lower than about 1 Gy generally cause no noticeable acute effects other than slight cellular changes (e.g. measurable chromosome aberrations). There is, however, the small possibility that a cell with noncritically damaged DNA can continue to reproduce and, with the effect of other agents, result in an increased probability of induced cancer or leukaemia. The timing of the appearance of radiation-induced cancers varies, with a mean incidence for leukaemia at about 7 years postirradiation, about 5 years for thyroid and bone cancers and 20 or more years for most other cancers2. The time lag in the induction of cancers means that younger subjects are at greater risk. If damage is to the germ cells, genetic effects may occur in future offspring. To date, no hereditary effects have been demonstrated convincingly in humans; however, based on animal experiments, it is concluded that hereditary effects are a possibility. These long-term, low-dose stochastic effects are of a random statistical nature and the probability of occurrence (but not the severity of the effect) is related to dose.

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In stochastic effects, the probability of an effect occurring increases with dose up to a maximum, above which the curve flattens off 2. At low doses (< 100–200 mGy) effects cannot be easily measured because of the high incidence of cancer in the population and for practical purposes it is assumed that there is no ‘safe’ dose. It is this lack of evidence of a threshold dose that has resulted in the principle of keeping radiation doses as low as reasonably practicable (ALARP). There has, however, been some recent evidence to suggest that there may be some protective effect of radiation at very low doses, but this is a matter of current controversy3. Much of the epidemiological data on induced cancers relate to high radiation doses (2–5 Sv) received over a short period of time. For radiation protection purposes, these data need to be extrapolated to dose levels of a few mSv or less, such as encountered in diagnostic radiology and in the workplace. Such levels are comparable with annual doses received from background radiation of approximately 2.2 mSv per year4. In the absence of any definitive evidence to the contrary, a linear extrapolation is assumed. Epidemiological analysis gives a derived risk of radiationinduced fatal cancer of 5% per Sievert for the general population. For children and young people the risk is assumed to be two or three times this value, whereas for those over the age of 60 the risk is about a factor of five less, due to limited time for expression of the detriment. Risk factors (Table 9.1) have also been estimated for nonfatal cancers and hereditary effects in both the workforce and the general population5. Factors for the latter group are higher because children are included.

Fetal irradiation Cell killing and cancer induction may occur as a result of in utero radiation and it is recognized that the fetus is highly radiosensitive during prenatal development. There are radiation-related risks throughout pregnancy, associated with the stage of pregnancy at which irradiation occurs and the fetal absorbed dose. Risks are most significant during organogenesis and the early fetal period, less in the second trimester and least in the third. Irradiation of a fetus can result in a reduction in IQ (if irradiation takes place 8–25 weeks postconception when the central nervous system is developing), an increased risk of cancer in later life, an increased incidence of congenital abnormality, or a genetic risk to the next generation. However, a recent ICRP report6 on pregnancy and medical irradiation concludes that, for most well-conducted diagnostic procedures, there is no measurable increase in risk over the background Table 9.1

RADIATION RISK FACTORS5 Risk (10−2 Sv−1)

Effect

Adult workers

Whole population

Fatal cancer

4.0

5.0

Nonfatal cancer

0.8

1.0

Severe hereditary effects

0.8

1.3

Total

5.6

7.3

incidence of such effects. For a detailed description of the effects of radiation on the development of the fetus, ICRP 907 is recommended.

PRINCIPLES OF RADIATION PROTECTION AND LEGISLATION The aim of radiation protection practice is to restrict radiation dose so that, with the exception of radiotherapy treatments, doses to staff, patients and the public remain below the level at which deterministic effects occur and the probability of stochastic effects occurring is limited to an acceptably low level. To achieve this aim, the ICRP5 recommends the application of three principles: justification, optimization and limitation. • Justification implies that no practice resulting in exposure to ionizing radiation should be adopted unless it results in sufficient net benefit to exposed individuals or society to offset the detriment. The use of radiation in healthcare is a justified practice8. • Optimization requires that the individual dose, the number of people exposed and the likelihood of inadvertent exposure should be kept as low as reasonably achievable (ALARA), economic and social factors being taken into account. In UK legislation this is translated into as low as reasonably practicable (ALARP). • Limitation: The exposure of individuals should be subject to dose limits designed to ensure that no individual is exposed to an unacceptable radiation risk. It is possible in this chapter to give only a short summary of the major points of UK legislation covering the safety of patients, employees, the public and the environment. The legislation is based on ICRP recommendations and subsequent European directives.

Ionising Radiation (Medical Exposure) Regulations 20009 Ionising Radiation (Medical Exposure) Regulations (IRMER) encompass exposures given for health screening, occupational health and medico-legal and research purposes, as well as those for diagnosis or treatment. The main aim of the regulations is to ensure that all medical exposures are justified for the individual exposed and, having been justified, are optimized. To realize this objective, the employer must provide a framework so that individuals involved in the exposure know their roles and responsibilities and carry them out according to the written procedures. Under IRMER, a referrer refers a patient to a practitioner who justifies the use of radiation in the individual patient with regard to the need for the examination, in terms of both the information to be gained and the radiation detriment. Such a decision is made in the light of the information supplied and it is the responsibility of the referrer to supply sufficient clinical information to enable the practitioner to decide whether the examination is justified or whether some other procedure might be more appropriate. Guidance has been given by the Royal College of Radiologists10 on the value of

CHAPTER 9

• RADIATION ISSUES: RADIATION PROTECTION AND PATIENT DOSES IN DIAGNOSTIC IMAGING

certain radiological examinations. To indicate that the justification process has taken place, the referral must be authorized by the practitioner. For many radiological examinations, the decision as to whether to authorize the examination may be taken by a radiographer acting under a departmental protocol which has been drawn up and approved by the practitioner. IRMER also requires that clinical audit is undertaken. Such audits could consider the appropriateness of the examination and the use made of X-ray reports. Taken together, these two factors can provide evidence as to whether the examination was justified. The operator, defined under IRMER as a person carrying out any practical aspect of the exposure (including authorizing the exposure), has an important role in keeping the dose to the patient as low as reasonably practicable commensurate with the diagnostic purpose. The type of examination and imaging technique, including the number of views necessary, must be selected so as to minimize the dose to the patient. Optimization also implies that X-ray equipment is initially selected so as to be as dose-efficient as possible and is installed and correctly maintained thereafter. IRMER requires that special attention is given to high dose exposures (e.g. CT, interventional radiology) and to special patient groups (e.g. pregnant patients). Exposures undertaken as part of research studies must be submitted for ethics committee approval. Dose limits do not apply to patients since they are expected to obtain individual benefit from the radiation they receive. However, studies have shown that there is a wide range of doses delivered for the same investigation and therefore, although dose limits are not appropriate, IRMER requires that diagnostic reference levels (DRLs) must be established locally for all standard examinations and types of equipment in each institution. Patient doses should be audited regularly and action taken to reduce them where DRLs are exceeded. Those acting as practitioners or operators must receive appropriate theoretical and practical training as specified in the IRMER schedule. In the case of radiologists and radiographers, although their professional training is assumed to cover the required theoretical syllabus, practical training in both techniques and specific equipment is also required and should be updated as necessary. The employer must consult a medical physics expert (MPE) to advise on optimization, patient dosimetry, quality assurance and radiation protection in medical exposures.

Table 9.2

Medicines (Administration of Radioactive Substances) Regulations 197811 In the UK it is illegal for anyone to administer a radioactive medicinal product to patients or to volunteers involved in research projects unless they are a doctor or a dentist who holds a certificate issued by the Health Minister advised by the Administration of Radioactive Substances Advisory Committee (ARSAC) in respect of that product, or is a person acting in accordance with the written directions of an ARSAC certificate holder.Thus, for nuclear medicine, the IRMER practitioner is by definition the ARSAC certificate holder.

Ionising Radiations Regulations 199912 The Ionising Radiations Regulations (IRR) apply to health and safety of staff and the public. A patient, not at the time undergoing a radiological procedure, is considered to be a member of the public. The regulations set down the arrangements for the management of radiation in the workplace and control methods pertaining to areas, people and radiation sources. The employer must make a suitable and sufficient risk assessment before any new work involving ionizing radiation. This enables the employer to identify the measures to be taken to restrict exposures to staff and the public and to consider the possibility of radiation accidents occurring and the actions required to prevent them or minimize their consequences. Risk assessments need to be reviewed and revised regularly and as procedures change; for example, when new fluoroscopically guided interventional procedures are introduced. The employer has a responsibility to ensure that no employee is exposed to levels of ionizing radiation exceeding the dose limits (Table 9.2) and to keep radiation doses to employees and others who may be affected by the work as low as reasonably practicable. This must be done by a hierarchy of control methods: • engineering controls and design features, safety features and warning devices • systems of work • personal protective equipment. Management responsibility for compliance with the regulations lies with the employer but the employer cannot comply with the requirements without the cooperation of the employees. Employers must appoint a radiation protection adviser (RPA)—a suitably experienced and certificated physicist—to

SUMMARY OF ANNUAL DOSE LIMITS12 Effective whole body dose (mSv)

Employees aged 18 years and over

Individual organs or tissues (skina, hands, forearms, feet, ankles) (mSv)

Lens of eye limits (mSv)

20

500

Trainees aged under 18 years

6

150

45

Any other persons

1

50

15

a

Averaged over 1 cm2.

150

161

162

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• IMAGING TECHNIQUES AND GENERAL ISSUES

give advice on compliance with the legislation; for example, design of radiation facilities, monitoring of doses and safety checks on radiation equipment. Good practice recommends there should normally be a Radiation Protection Committee consisting of representatives from management and staff, who meet regularly to review implementation of the regulations, consider reports on staff doses and discuss any incidents. The employer must also ensure that employees and others who may be affected are given information and training appropriate to their role in the use of ionizing radiation. For female employees this includes informing them about possible risks to the fetus and, where unsealed sources are used, the nursing infant. Where special procedures are required in order to restrict significant exposure, or where three-tenths of any adult dose limit may be exceeded (bearing in mind both normal operation and potential accident situations), the employer must designate controlled areas. Controlled areas must be demarcated and suitable and sufficient warning signs displayed. For all controlled areas the employer must issue written local rules which give key working instructions for the area. Local rules must be brought to the attention of all persons who may be affected by them and compliance is supervised on the employer’s behalf by the Radiation Protection Supervisor. Staff who are likely to receive in excess of three-tenths of any dose limit in the course of their work must be designated by the employer as classified workers. They must receive annual medical examinations and have their radiation doses appropriately assessed. There are relatively few employees working in radiology and nuclear medicine departments who require classification. Only persons who are ‘classified’ or who are working under an agreed system of work may enter a controlled area. Where persons other than classified persons enter controlled areas, the employer must demonstrate by personal monitoring or other suitable means that radiation doses are limited to less than three-tenths of a dose limit.This is the main reason for personal dosimeters being worn in diagnostic imaging departments.

higher the dose, the better the image. Whether using X-rays or radioactive materials, the radiological technique or imaging investigation should be selected so that the image is of sufficiently high quality to give adequate diagnostic information.

Estimating patient doses The risk associated with a particular radiological examination depends on the organs irradiated, the dose received by each of them and the resultant effective dose. Although direct measurement of effective dose is not possible in diagnostic radiology, several indirect methods are in use which measure related parameters. For radiography and fluoroscopy, one method is the use of a dose–area product (DAP) meter.This is a large, flat plate ionization chamber fixed to the collimator on the X-ray tube and through which the whole X-ray beam passes. The DAP meter measures the product of the dose exiting the X-ray tube and the area at the X-ray tube which, due to the inverse square law, is the same as the product of the dose at the entrance surface of the patient and the area of tissue irradiated (Fig. 9.1). DAP is measured in µGy m2, Gy cm2, etc. New X-ray equipment should give an indication of patient dose and this is most frequently achieved by having a DAP meter installed. Another method, suitable for single-view radiography, is to measure the entrance surface dose (ESD), the absorbed dose in air with backscatter at the point where the X-ray beam enters the patient, using thermoluminescent dosimeters (TLDs) on

X ray tube

x DAP meter Dose D area L2 DAP = DL2

L

Radioactive Substances Act 199313 The Radioactive Substances Act (RSA) requires employers using radioactive materials to have a registration to keep and use radioactive materials and an authorization to accumulate and dispose of radioactive waste. The registration and authorization certificates impose strict limits on the activities to be used and disposed of and the disposal routes. Suitable facilities with appropriate levels of security must be used and comprehensive records kept. It is essential that anyone using radioactive materials familiarizes themselves with the terms of the certificates in order to avoid unwittingly breaking the law. This is especially important if a research project involving radioactive materials is being planned.

4x

D 42 area (4L2) DAP = DL2

Dose

4L

PATIENT DOSES IN DIAGNOSTIC IMAGING There is always a balance to be struck between radiation dose and image quality. In a correctly set-up system, generally the

Patient

Figure 9.1

Principle of operation of a dose area product meter.

CHAPTER 9

• RADIATION ISSUES: RADIATION PROTECTION AND PATIENT DOSES IN DIAGNOSTIC IMAGING

the surface of the patient. A third method is to calculate the ESD based on knowledge of X-ray output from quality assurance measurements and individual exposure factors. Regular assessment of patient dose must be carried out. In the UK, the Health Protection Agency (Radiation Protection Division) collates doses from throughout the country and publishes regular patient dose reviews14. These national data enable the establishment of national reference levels for particular examinations (Tables 9.3, 9.4). Local measurements can be used to establish local diagnostic reference levels15. To calculate effective dose from ESD or DAP requires knowledge of the incident X-ray spectrum and its absorption in tissues, as well as knowledge of the relative positions of the organs with respect to the primary and scattered X-ray beam. Conversion tables have been published enabling such calculations to be made16,17.

Table 9.3 RECOMMENDED NATIONAL REFERENCE DOSES FOR INDIVIDUAL RADIOGRAPHS ON ADULT PATIENTS14 Examination

ESD per exposure (mGy)

DAP per exposure (Gy cm2)

Lumbar spine: AP

6

Lumbar spine: Lat

14

Lumbar spine: LSJ

26

3

Abdomen: AP

6

3

Pelvis: AP

4

3

Chest: PA

0.2

0.12

Chest: Lat

1

*

Skull: AP/PA

3

*

Skull: Lat

1.5

*

Thoracic spine: AP

3.5

*

Thoracic spine: Lat

1.6 3

*

10

*

For these examinations there was insufficient DAP data collected nationally to recommend a national reference dose.

Table 9.4 RECOMMENDED NATIONAL REFERENCE DOSES FOR COMPLETE PROCEDURES ON ADULT PATIENTS14 Procedure

DAP per procedure (Gy cm2)

Fluoroscopy time per procedure (min)

Barium enema

31

Barium follow-through

14

2.2

Barium meal

13

2.3

Barium swallow

11

2.3

IVU

16

–

Venogram

5

2.7

2.3

Femoral angiogram

33

5

Coronary angiogram

36

5.6

Pacemaker

27

10.7

IVU = intravenous urogram.

Doses in CT are based on measurements made with a pencil ionization chamber in standard CT phantoms. Most commonly, a 16 cm diameter polymethyl methacrylate (PMMA) phantom is used for the head and a 32 cm diameter phantom for the body. Knowing the parameters (e.g. scan length) for any individual examination, patient dose can be estimated18. A similar principle is used for estimating radiation doses in mammography where measurements are made relating to a standard 4.5-cm thick Perspex phantom and the mean glandular breast dose computed19. In radionuclide imaging, the effective dose received by the patient depends on the radionuclide given, its activity and its chemical form, which determine where the radionuclide will locate in the body and its metabolic rate. The effective dose may also depend on individual patient physiology; for example, if kidney function is impaired, clearance may be slow. Patient doses received in various common radionuclide examinations and the means to calculate them have been published by a number of organizations20–22.

Typical patient doses A summary of recently published data on effective doses in a variety of typical radiological and radionuclide examinations is given in Table 9.5. The examinations that give rise to the highest dose are those involving multiple radiographs or fluoroscopy, or CT examinations of the abdomen or pelvis, since these examinations involve irradiation of the most radiosensitive organs. Table 9.5 compares the effective dose with multiples of that received from a standard chest X-ray (0.02 mSv) and the length of time in which a similar dose would be received from natural background radiation (2.2 mSv year−1).

Optimizing patient dose in conventional radiography and fluoroscopy Manufacturers are continually improving X-ray equipment and its associated ancillary devices in order to produce the best image for the lowest dose22–24. In recent years, features that have been introduced include: • use of carbon fibre and other low attenuation materials in table tops, grids and cassettes • use of high frequency generators to produce an improved energy spectrum • choice of additional filters to reduce entrance skin dose • use of last image hold and pulsed fluoroscopy • a selection of curves for automatic control of kV and mA in fluoroscopy • improved collimation and the use of virtual field indicators in fluoroscopy so that the irradiated area can be seen before undertaking clinical fluoroscopy • the use of lasers for beam centring in fluoroscopy • the use of digital fluoroscopy in which the video signal from a high-resolution camera is digitized and then processed before display. Such equipment may be used either in fluoroscopy mode or in image acquisition mode, during which the patient dose rate is a factor of 5–10 times higher. (Note that with digital fluoroscopy systems it is very easy to obtain images and there may be a tendency to obtain more images

163

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Table 9.5 EFFECTIVE DOSES FOR COMMON RADIOLOGICAL EXAMINATIONS EXPRESSED IN TERMS OF THE EQUIVALENT NUMBER OF CHEST X-RAYS AND LENGTH OF EXPOSURE TO BACKGROUND RADIATION THAT WOULD GIVE THE SAME DOSE10 Examination Limbs and joints (except hip)

Typical effective dose (mSv)

Equivalent number of chest X-rays

< 0.01

Equivalent length of background exposure

< 0.5

< 1.5 d

Chest PA

0.02

1

3d

Skull

0.06

3.0

9d

Thoracic spine

0.7

Lumbar spine

1

50

5 months

Hip

0.4

20

2 months

Pelvis

0.7

35

4 months

Abdomen

0.7

35

4 months

IVU (intravenous urogram)

2.4

120

14 months

Barium swallow

1.5

75

8 months

Barium meal

2.6

130

15 months

Barium follow-through

3

15

16 months

Barium enema

7.2

360

3.2 years

CT head

2.0

100

10 months

CT chest

8.8

400

3.6 years

CT abdomen or pelvis Lung ventilation 133Xe

10

35

4 months

500

4.5 years

15

7 weeks

0.3

Lung perfusion 99mTc

1

50

6 months

Kidney 99mTc

1

50

6 months

Thyroid 99mTc

1

50

6 months

99m

1.8 years

4

200

Dynamic cardiac 99mTc

6

300

2.7 years

PET head 18FDG

5

250

2.3 years

Bone

Tc

than necessary, thus irradiating the patient excessively. Nonuseful images should not be deleted so that audits can be done periodically to review whether all the images taken were essential.) Some of these features (e.g. carbon fibre) are inherent in the system and some are automatically selected (e.g. additional filtration), but many are under the control of the operator and should be used to full effect.

Optimizing patient dose in computed and digital radiography Digital technology is developing extremely rapidly and there are two distinct systems, commonly known as computed radiography (CR) and digital radiography (DR). CR is a cassette-based system and so can be used with existing X-ray equipment. Storage phosphor imaging plates are contained within cassettes similar to conventional screen/film cassettes. The image plate is exposed as normal and the image stored as a pattern of excited electrons. The plate is subsequently ‘read’ using a data acquisition laser beam to extract the stored image information and the light energy released is detected by a sensitive optical system. The output signal is then processed, displayed on a workstation and transferred to a PACS system.

DR systems use solid-state flat panel detectors. These are of two main types: direct and indirect. Indirect is more common and in this system the X-ray image is converted to light using caesium iodide which is deposited on an amorphous silicon plate.The plate forms an image matrix of an array of pixels and photodiodes convert the light from the caesium iodide into an electrical charge which is read out line by line. In the direct system, X-rays impinge on an amorphous selenium plate which converts the image directly into an electrical signal without the light conversion step. (Recently, similar flat panel detectors have been developed for use in fluoroscopy.) There are a number of advantages of digital systems, notably that the image can be manipulated to enhance image quality, thus reducing the need for repeat exposures and it can be transmitted electronically to locations throughout the hospital. The main disadvantage is that overexposure can occur without any detriment to image quality, unlike conventional screen/ film radiography where an overexposed film may be too black to be of clinical use. It is therefore very important that staff are aware of the doses actually being given by recording the DAP reading and systems and comparing with local diagnostic reference levels. For CR systems, a dose or exposure index is displayed on the final image which gives an indication of the system performance and sensitivity; acceptable ranges of the index should be displayed on a chart for standard views.

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• RADIATION ISSUES: RADIATION PROTECTION AND PATIENT DOSES IN DIAGNOSTIC IMAGING

The energy response of digital systems is not the same as that of screen/film systems and optimization of the system is essential and complex; for example, there has been much discussion about the best kV to use for chest radiography and whether a grid is necessary25. Because of the digital nature of the image, resolution is determined by the pixel size and, in the case of CR systems, the dimensions of the read-out laser beam. This means that spatial resolution is generally not as good as screen/film systems. However, image processing means that contrast resolution can generally be better and so potentially image quality overall is improved. Poorer spatial resolution has meant that in mammography, where, for screen/film systems, resolution is of the order of 20 line pairs per millimetre, digital technology has been slower to develop. However, digital systems are now in use, although the use of CR systems is not universally accepted because of their limited resolution. ICRP Publication 9326 gives an excellent review of the dose issues involved in digital radiology with much practical advice.

Optimizing patient dose in computed tomography In 2001–2002, CT in the UK contributed some 47% of the collective dose from X-ray examinations4, although CT examinations only comprised about 7% of the number of examinations carried out. As such, CT clearly constitutes a high dose technique and the justification and optimization of CT examinations are vital. CT has developed exceedingly rapidly in recent years. The majority of machines in clinical use are now multidetector systems, acquiring up to 64 slices in a single rotation. Multidector CT allows the user to acquire larger volumes and thinner slices in the same time, both of which will result in increased patient doses. The new technology also opens up additional possibilities for CT imaging, such as performing cardiac-gated studies. To optimize CT, it is essential that both the practitioner and operator have a good understanding of the new technology and in particular how multislice CT differs from single slice.

For example, in most multidetector CT, increasing the pitch no longer results in a dose reduction as the reconstruction technique means that the mAs must be increased to compensate. Modern CT systems are equipped with many dose-reducing features (e.g. automatic exposure controls) which modulate the tube current to account for variations in patient attenuation. To get the best from these systems it is essential that they are set up appropriately in the first instance, which again requires a good understanding of both the imaging task and the technology27. ICRP Publication 8728 provides further information on factors affecting dose in CT. Typical doses for a range of common CT examinations were established in the UK in 200329 (Table 9.6).

Optimizing patient dose in nuclear medicine In nuclear medicine patient dose is dependent on the activity administered. Standard operating procedures should specify the normal activity to be used in adult patients and the imaging protocol to be used (e.g. choice of collimator). Generally, dynamic and tomographic studies require more activity to be administered. If too little activity is administered the study may be inadequate and have to be repeated. Adequate patient preparation is essential for the procedure to be effective; taking of fluids should be encouraged to increase the clearance rate from the body and thus reduce the dose received. If a patient requires multiple procedures, some of which involve radioactive materials, the order in which the tests are done is important to avoid one test interfering with another. (To minimize staff radiation dose, the inactive tests should be done first.) Dual-headed cameras are now common and these are capable of automatically acquiring whole-body images in one pass, allowing the simultaneous collection of two or more images (e.g. anterior and posterior or lateral or oblique views). They have reduced the acquisition time for many studies when compared with the single-headed cameras, including SPECT sequences, thus reducing the chance of patient movement and so improving image quality. Positron emission tomography (PET) is becoming more common and its use, especially in oncology, is well recognized.

Table 9.6 TYPICAL DOSES FOR CT IN THE UK29 Procedure

Adult/child

DLP (mGy cm)

Effective dose (mSv)

Head (acute stroke)

Adult

690

1.5

Abdomen (liver metastases)

Adult

350

5.3

Chest, abdomen and pelvis (lymphoma staging or follow-up)

Adult

670

9.9

Chest (lung cancer)

Adult

400

5.8

Chest (high resolution)

Adult

88

1.2

Chest (detection of malignancy)

Child (0–1 year old)

160

6.3

Chest (detection of malignancy)

Child (5 years old)

200

3.6

Head (trauma)

Child (0–1 year old)

230

2.5

Head (trauma)

Child (5 years old)

380

1.5

DLP = dose–length product.

165

166

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Two technologies exist: the dedicated PET system and the specially adapted gamma camera that can detect positronemitting radionuclides. Hitherto many departments have chosen the latter option on grounds of cost but recently dedicated systems have become more common. For the patient, the radiation dose received using a dedicated PET system is slightly higher than conventional nuclear medicine procedures. The most recent development in PET imaging is to combine the PET with a CT in order to give precise anatomical location of the activity and an attenuation correction. The patient thus receives a dose for both procedures.

AREAS FOR SPECIAL ATTENTION IRMER highlights a number of areas for special attention. This is required because of the increased radiosensitivity of the subject (e.g. the fetus), the fact that there is no direct clinical indication for the exposure (e.g. health screening), or the dose is high (e.g. interventional procedures).

Pregnancy and potential pregnancy Exposure of the fetus to diagnostic levels of radiation would never, of itself, be a reason to terminate a pregnancy, but efforts should be made to minimize the irradiation of known pregnant or potentially pregnant women. In women of child-bearing age (say, 12–55 years), for any radiology examination where the fetus may be in the primary beam or very close to it and any nuclear medicine investigation, the possibility of pregnancy should be taken into account. If the patient is pregnant or is probably pregnant, justification for the procedure should be reviewed. If examinations may give doses to the uterus of some tens of mGy (e.g. barium enema, pelvic CT), they should, if possible, be scheduled within the first 10 d of the menstrual cycle when conception is unlikely to have occurred30. In order to implement this guidance, the referring clinician should indicate the last menstrual period (LMP) on the referral. In addition, the operator should check immediately before giving the exposure whether the patient may be pregnant and it is also helpful if advisory notices are posted at several places within the department requesting patients to notify staff if they think they may be pregnant.

Table 9.7

If, despite the patient being pregnant, the exposure cannot be delayed, special attention should be given to optimization of the exposure, taking into account the exposure of both the expectant mother and the unborn child. In nuclear medicine, for radionuclides that are rapidly eliminated by the bladder, frequent voiding should be encouraged to reduce fetal dose since the bladder acts as a reservoir of activity. ICRP Publication 8831 gives doses to the fetus from intakes of radionuclide by the mother. The commonest radionuclide procedure that may be required urgently during pregnancy is a lung ventilation– perfusion scintigram. There has been much discussion over whether it is preferable to do a high-resolution CT of the chest which gives a lower fetal dose but a higher maternal dose than the nuclear medicine procedure (Table 9.7)32. A summary of fetal doses from a range of common diagnostic procedures is given in Table 9.8.

Infants and children As children are more radiosensitive than adults and their longer life expectancy gives greater opportunity for the radiation detriment to be expressed, special care must be taken to ensure that any radiation doses to children are justified by the diagnostic information to be gained as a result of the procedure. In addition, very young children may be uncooperative and need some form of sedation or immobilization. The assistance of a parent will usually help to keep the child still, but the parent should be provided with protective clothing and the possibility of a mother being pregnant must also be considered. In X-ray procedures, fast imaging systems should be used so that exposure times are as short as possible; additional tube filtration will reduce skin dose (although excessive filtration will harden the beam and reduce image quality). The use of a grid is often unnecessary, particularly with smaller children and removing it can reduce the dose by as much as 50%. The X-ray beam should be well collimated and appropriately sized gonad shielding used to minimize the dose to organs outside the area of interest33. In nuclear medicine procedures, the biological distribution, uptake and retention of radiopharmaceuticals vary considerably throughout childhood. The activity administered should be the minimum consistent with obtaining a diagnostic result.

DOSE TO FETUS IN INVESTIGATION FOR PULMONARY EMBOLISM

Procedure

Radioactive material or technique

Lung ventilation

80 MBq 99mTc-DTPA aerosol inhalation

0.5

Lung ventilation

40 MBq 99mTc-technegas

0.07

Lung perfusion

100 MBq

99m

Tc-MAA

PA chest radiograph Chest CT:

Maximum dose to fetus (mGy)

0.4 < 0.01

120 kVp, 100 mA

first trimester

1 s rotation, pitch 1, collimation 2.5 mm

0.02

second trimester

Scan length 11 cm

0.08

third trimester

0.14

CHAPTER 9

Table 9.8

• RADIATION ISSUES: RADIATION PROTECTION AND PATIENT DOSES IN DIAGNOSTIC IMAGING

FETAL DOSES FROM A SELECTION OF COMMON DIAGNOSTIC PROCEDURES30

Procedure

Mean fetal dose (mGy)

AP abdomen

Maximum fetal dose (mGy)

1.4

Barium enema

6.8

PA chest

4.2 24

< 0.01

< 0.01

Pelvis

1.1

4

CT abdomen

8.0

49

Bone 99mTc

3.3

Dynamic cardiac

99m

Tc

GFR (EDTA) 51Cr

4.6

3.4

3.7

<0.01

<0.01

For a child, the adult-administered activity in simple proportion to body weight34 (as long as the activity is not too low) will give image quality and imaging time comparable with that expected for adults. Care needs to be taken to ensure that infants are not inadvertently irradiated if their breast-feeding mother receives a nuclear medicine procedure35. Breast-feeding may need to be suspended for some time after the administration of a radiopharmaceutical. Detailed recommendations for such cases are given in Section 7 of the ARSAC guidance notes21.

Research exposures All research involving exposure of individuals to ionizing radiation must be approved by an ethics committee. A practitioner must justify the use of radiation in the study and a medical physics expert or radiation protection adviser must estimate the radiation dose received, recommend a dose constraint and give an indication of the consequent risk. An ARSAC research certificate must be obtained for all research projects involving the use of radionuclides; the ARSAC certificate holder is then the practitioner under IRMER. The employer’s procedures must ensure that individuals participate voluntarily and that they are informed about the radiation risks. Children and pregnant women should not be included in research except where problems specific to them are under investigation. Whenever possible, women in research studies should be aged over 55 to minimize the risk of unintentional irradiation of a fetus.

Health screening programmes Screening programmes (e.g. breast screening) require the exposure of a well population.The object of the programme is to permit the earlier detection of breast cancers so as to give a significant improvement in prognosis. However, the radiation results in a slight possibility of a radiation-induced carcinoma, so that the benefits of screening must be weighed against this possible risk36. In general, the risk of induced cancer will be higher in younger women (since there is usually about a 10year time lapse before cancers begin to appear and there is more glandular tissue in the younger breast).Therefore screening is not currently recommended for women below about 50 years of age, though this lower age limit may be reduced as techniques improve and more experience and data accrue.

High dose techniques High dose techniques require special attention because of the increased risk they carry. In diagnostic radiology, CT data acquisition and interventional radiology can be considered as high dose techniques. Dose reduction in CT data acquisition has already been discussed. Interventional radiology is a special case of fluoroscopy and full use should be made of all the dose-reducing features. In some techniques, however, doses are high enough to produce deterministic effects, in particular skin erythema (if doses are ≥ 2 Gy) and epilation (permanent at doses >7 Gy). It is essential that interventional radiologists are aware of the risks, counsel their patients on the possible damage and are trained to use the information on skin dose that should be available on the equipment1.

RADIATION PROTECTION OF STAFF AND PUBLIC The ICRP principles of justification and optimization apply to staff and the public just as much as they apply to patients. In addition, limitation applies. The presence of staff in a radiation area is only justified if they are essential to the procedure or if they are being trained. The public should be excluded from radiation areas unless they are accompanying a patient (e.g. a child) and their presence is essential. In radiation areas designated as controlled areas (e.g. X-ray rooms), local rules are applicable and all those entering such areas must have the rules brought to their attention. With regard to optimization (keeping radiation doses as low as reasonably practicable), almost anything that will help to reduce patient doses will also tend to reduce staff dose (e.g. reducing irradiated field size reduces scattered radiation dose). However, staff should be aware of the three physical parameters of distance, time and shielding which, frequently when used in combination, can keep doses ALARP. For unsealed radionuclides, containment in addition to these factors must also be used to minimize the risk of contamination.

Distance The intensity of X-radiation decreases with the square of the distance from a point source and applies at distances greater than 1 m from an irradiated patient or a patient containing

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radionuclide. Application of the use of distance is seen in the following practices: • making as full a use as practicable of the length of the exposure cable in fluoroscopy or mobile radiography • ensuring adequate distance between patients when patients are radiographed on the ward • stepping back when carrying out image acquisition in a fluoroscopy procedure • using remote handling tools to maximize the distance of the hands from a radioactive source • having the room designed so that staff can be a reasonable distance from the patient and radiation source • arranging the nuclear medicine waiting area so that injected patients do not have to wait in close proximity to reception staff or visitors • ensuring nuclear medicine patients returning home are given instructions if they should avoid close contact with others for a period of time.

Time The amount of radiation received is directly proportional to the length of the exposure time and so may be minimized by conducting procedures as quickly as possible. Application of the use of time to minimize dose is seen in: • the use of as fast imaging systems as practicable (usually at least 400 speed) to reduce exposure times • the use of pulsed fluoroscopy • the use of image storage facilities and last image hold • the use of frame grabbing rather than a full acquisition image • training, including the use of simulators to practise technique, so that the procedure can be done as quickly as possible in the patient • practising radioactive manipulations with an inactive material • the use of butterfly needles or cannulas for administering radionuclide to patients.

protective apron should be moved to the lower edge of the carriage and the operator should move to the front of the patient to make maximum use of the shielding. Staff working close to the patient during fluoroscopic procedures should wear personal protection consisting of lead-equivalent aprons. Aprons of 0.25–0.35 mm lead equivalent attenuate the radiation by a factor of about 10, depending on thickness and the kVp (Table 9.9) and provide a reasonable compromise between weight and attenuation. Lead gloves should be worn if the hands are near the X-ray beam. In overcouch fluoroscopy the position of the X-ray tube and intensifier is reversed, allowing a greater versatility in positioning without moving the patient and enables much routine fluoroscopy work to be conducted by remote control, with the radiologist seated behind the protective screen. However, if the radiologist has to remain close by the table, accessible dose rates are higher than in the undercouch tube case (Fig. 9.2) and thyroid and eye shielding should be worn in addition to the lead apron. The development of interventional radiological techniques has led to development of U-arm or C-arm units for cardiological or operating theatre applications. When using such equipment for interventional techniques, it is most important that they are used with the X-ray tube beneath the patient so that hands are unlikely ever to enter the primary X-ray beam. Unfortunately, it is much more difficult to give adequate shielding if the operator needs to remain close to the patient37. Table-side lead rubber curtains to reduce scattered radiation to the lower legs and ceiling-suspended shields to reduce eye dose are essential. Mobile barriers may be used during fluoroscopic procedures where a member of staff needs to remain near the patient (e.g. ECG technicians). Dose rates can be high (e.g. 10 mSv h−1 at 1 m) during image acquisition procedures. It is therefore important that as many staff as possible move behind the protective screen (and maximize

Shielding Positioning of a barrier between the source of radiation and the recipient will reduce the dose by an amount dependent on the energy of the radiation source and the nature and thickness of the barrier. It is most effective to place barriers as close to the radiation source as practicable. The use of shielding is seen at all levels—from the design of an X-ray room and provision of protective clothing, down to syringe shields used in nuclear medicine. In undercouch fluoroscopy, the X-ray tube is located beneath the table, while the intensifier is mounted above. Most of the scattered radiation is in the downward direction (with the table horizontal) and is absorbed in the floor or the sidepanels of the table (Fig. 9.2). The intensifier carriage normally has a lead-equivalent apron approximately 450 mm square attached to its edge; this absorbs much of the scattered radiation emerging from the upper side of the patient and gives very effective shielding to the radiologist and other staff in the room. When the table is tilted to the vertical position, this

200

Height above floor in cm

168

150

X ray tube overcouch X ray tube undercouch

100

50

0 0

0.5

1.5 1.0 Dose rate mGy/ h−1

2.0

2.5

Figure 9.2 Dose distribution during fluoroscopy at the operator’s position 80 cm from a water phantom placed on the table for under- and overcouch X-ray tube configurations. Operating conditions: 125 kVp, 1 mA.

CHAPTER 9

• RADIATION ISSUES: RADIATION PROTECTION AND PATIENT DOSES IN DIAGNOSTIC IMAGING

Table 9.9 PERCENTAGE PRIMARY X-RAY BEAM TRANSMISSION THROUGH LEAD FOR VARIOUS KILOVOLTAGES FROM A CONSTANT POTENTIAL GENERATOR (THREE-PHASE OR MID-FREQUENCY) Percentage transmission Lead thickness (mm)

75 kVp

0.22

5.7

0.44

1.4

100 kVp 13 4.8

125 kVp 16.1 6.1

0.5

1.1

3.9

4.9

0.72

0.7

1.9

2.3

< 0.5

0.6

0.8

1

their distance from the patient) for the few seconds of high exposure. In an operating theatre or similar situation, the problem may be complicated by oblique views, the need for sterility and by the presence of staff unfamiliar with radiation hazards. Radiation-resistant gloves of similar flexibility to ordinary disposable rubber gloves are available and claim to reduce doses to the hands by up to 30% at 60 kVp. However, the attenuation will be less at higher kVp and may tend to give staff a false sense of security: it is better to develop techniques so that the hands are well away from the beam. CT data acquisition equipment generally poses few protection problems for staff who are normally outside the examination room. Occasionally anaesthetic or nursing staff may need to remain near the patient during image acquisition, or a radiologist may need to give a contrast medium injection. Modern CT systems produce a very finely collimated, fan-shaped X-ray beam that is always completely intercepted by the detector assembly. The maximum intensity of scattered radiation will be close to the entrance of the patient ‘tunnel’—normally higher at the front than at the back of the gantry.

Personal protection in nuclear medicine There are two principal hazards when handling unsealed radioactive materials: external radiation and contamination. Of the two, contamination is generally the more serious as it can result in a higher overall radiation dose. Because of the higher energy radiation used in nuclear medicine, the use of lead aprons to reduce external radiation exposure is impractical. Instead, staff rely on efficient handling techniques and keeping close contact with the radioactive patient to the minimum. Syringe shields should be used to reduce finger dose, with doses for injection being drawn up behind a lead–glass barrier to reduce external exposure to the body. Disposable gloves must be worn when preparing and administering radionuclide injections to prevent skin contamination and the hands must be thoroughly washed and monitored for radioactive contamination after the injection.

Accidents can happen—a syringe may detach from the needle or may be dropped on the floor—and prompt action must be taken to control the spread of contamination. All users of radioactive materials must be familiar with decontamination procedures.

Radiation hazards from nuclear medicine patients It may be helpful for the patient if nuclear medicine and ultrasound, or any other procedures, can be carried out on the same day. Ideally, the nonradioactive procedures should be undertaken first; however, if this is not possible, a risk assessment should be carried out to estimate the dose that staff may receive and apply appropriate control methods. A sample of blood or urine taken from a person to whom an unsealed radioactive substance has been administered may need to be treated itself as a further radionuclide source. Pathology samples should be appropriately labelled with a warning notice. Both inpatients and outpatients may be allowed to leave hospital to return home or elsewhere, provided they are unlikely to create a hazard to other persons with whom they may come into contact. If a patient is returned or transferred to another hospital or a nursing home immediately after a diagnostic test, appropriate advice should be provided to the receiving establishment.

Dose monitoring There is a legal requirement for radiation doses to be monitored. This is normally done by film or TLD badges to assess whole body dose. The badge should be positioned at waist level under the lead apron if one is worn. In addition, if there is potential for the eyes, hands, feet and ankles to be irradiated significantly, additional dosimeters should be worn to assess these doses. Electronic dosimeters with solid-state detectors which give an instantaneous readout dose are useful when investigating the dose received in specific procedures. Doses for staff involved in PET imaging may be significantly higher than for conventional nuclear medicine because of the high energy of the annihilation radiation, which, during

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Table 9.10 OCCUPATIONAL WHOLE BODY EXPOSURES IN MEDICAL IMAGING DEPARTMENTS IN 20014 Average effective dose (mSv)

Group

Work area

Diagnostic radiologists

Diagnostic radiology

0.15

Interventional radiologists

Diagnostic radiology

0.35

Cardiologists

Diagnostic radiology

0.20

Other clinicians

Diagnostic radiology

0.08

Radiographers

Diagnostic radiology

0.06

Nurses

Diagnostic radiology

0.07

Clinicians

Nuclear medicine

0.28

Pharmacists

Nuclear medicine

0.42

Radiographers and technologists

Nuclear medicine

0.71

Nurses

Nuclear medicine

0.7

Table 9.11

OCCUPATIONAL EXTREMITY EXPOSURES IN MEDICAL IMAGING DEPARTMENTS IN 20014 Average equivalent dose (mSv)

Maximum equivalent dose range (mSv)

Location

Work area

Left hand/finger

Diagnostic radiology

6.15

> 50

Right hand/finger

Diagnostic radiology

4.70

> 50

Hand

Diagnostic radiology

2.50

20–30

Eye/forehead

Diagnostic radiology

2.16

30–40

Lower leg

Diagnostic radiology

5.11

30–40

Left hand/finger

Nuclear medicine

10.08

> 50

Right hand/finger

Nuclear medicine

10.00

> 50

Eye/forehead

Nuclear medicine

2.04

5–10

injection and positioning of the patient on the couch, is difficult to shield. Typical doses received by staff in diagnostic imaging departments are shown in Tables 9.10 and 9.11.

Pregnant staff The dose to the fetus during the declared term of pregnancy (i.e. after the employer has been informed in writing) should be less than 1 mSv. For those receiving exposure to diagnostic X-rays this is equivalent to about 2 mSv to the surface of the abdomen. An individual risk assessment must be carried out for the pregnant employee but, as can be seen from Table 9.10, it is unlikely that a member of staff will exceed this dose.The evidence available indicates that there should be no need for a change in work patterns except perhaps for staff who are involved in a heavy interventional radiology workload or working with high activity unsealed sources (e.g. in the radiopharmacy). In these cases it may be advisable to change work schedules or to limit the number of procedures performed and to offer additional monitoring. However, it should be stressed that such measures are often mainly to give peace of mind to the staff concerned.

REFERENCES 1. ICRP 2000 Avoidance of radiation injuries from medical interventional procedures. ICRP Publication 85. Ann ICRP 30. Pergamon, Oxford. ICRP website: www.icrp.org/docs/ ICRP_85_Interventional_s.pps 2. ICRP 2001 Supporting Guidance 2. Radiation and your patient: a guide for medical practitioners. Ann ICRP 31. Pergamon, Oxford. ICRP website: www.icrp.org/docs/ ICRP_85_Interventional_s.pps 3. Dendy P P 2005 Low dose radiation risk: UKRC 2004 debate. Br J Radiol 78: 1–2 4. Watson S J, Jones A L, Oatway W B et al 2005 Ionising radiation exposure of the UK population: 2005 review. Health Protection Agency, Chilton 5. ICRP 1991 The 1990 recommendations of the International Commission on Radiological Protection. ICRP Publication 60. Ann ICRP 21. Pergamon, Oxford 6. ICRP 2000 Pregnancy and medical radiation. ICRP Publication 84. Ann ICRP 30. Pergamon, Oxford. ICRP website: www.icrp.org/docs/ICRP_84_ Pregnancy_s.pps 7. ICRP 2003 Biological effects after prenatal irradiation (embryo and fetus). ICRP Publication 90. Ann ICRP 33. Pergamon, Oxford. 8. The Justification of Practices Involving Ionising Radiation Regulations 2004 Statutory Instrument 2004 No. 1769. The Stationery Office, London 9. The Ionising Radiation (Medical Exposure) Regulations 2000 Statutory Instrument 2000 No. 1059. The Stationery Office, London

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• RADIATION ISSUES: RADIATION PROTECTION AND PATIENT DOSES IN DIAGNOSTIC IMAGING

10. Royal College of Radiologists 2003 Making the best use of a department of clinical radiology: guidelines for doctors, 5th edn. Royal College of Radiologists, London 11. The Medicines (Administration of Radioactive Substances) Regulations 1978 SI 1006/1978. HMSO, London. And Amendment Regulations 1995 (SI 2147/1995) 12. Health and Safety Commission 2000 Work with ionising radiation. The Ionising Radiation Regulations 1999: approved code of practice and guidance. The Stationery Office, Norwich 13. Radioactive Substances Act 1993 (Chapter 12). HMSO, London 14. Hart D, Hillier M C, Wall B F 2002 Doses to patients from medical X-ray examinations in the UK: 2000 Review. NRPB W14. NRPB, Chilton 15. Institute of Physics and Engineering in Medicine 2004 Guidance on the establishment and use of diagnostic reference levels for medical X-ray examinations. Report 88. IPEM, York 16. Hart D, Jones D G, Wall B F 1994 Estimation of effective dose in diagnostic radiology from entrance surface dose and dose–area product measurements. NRPB-R262. NRPB, Chilton 17. Hart D, Jones D G, Wall B F 1996 Coefficients for estimating effective doses from paediatric X-ray examinations. NRPB-R279. NRPB, Chilton 18. Keat N 2002 ImPACT CT patient dosimetry calculator (version 0.99m). ImPACT, London. ImPACT website: www.impactscan.org/ctdosimetry.htm 19. Institute of Physics and Engineering in Medicine 2005 The commissioning and routine testing of mammographic X-ray systems. Report 89: 1987–1997. IPEM, York 20. ICRP 1998 Radiation doses to patients from radiopharmaceuticals. ICRP Publication 80. Ann ICRP 28. Pergamon, Oxford 21. Administration of Radioactive Substances Advisory Committee 1998 Notes for guidance on the clinical administration of radiopharmaceuticals and use of sealed radioactive sources. The Stationery Office, London 22. RADAR—The internal dose assessment system. RADAR website: www. doseinfo-radar.com/RADARIntSys.html 23. Institute of Physics and Engineering in Medicine 1998 Cost-effective methods of patient dose reduction in diagnostic radiology. Report 82. IPEM, York 24. Rawlings D 2005 Options for radiation protection of the patient. Br J Radiol 78: 877–879 25. Honey I D, MacKenzie A, Evens D S 2005 Investigation of optimum energies for chest imaging using film-screen and computed radiography. Br J Radiol 78: 422–427

26. ICRP 2004 Managing patient dose in digital radiology. ICRP Publication 93. Ann ICRP 34. Elsevier, Oxford. ICRP website: www.icrp.org/docs/ ICRP_93_digital_educational_version_20April04.pdf 27. Lewis M A, Edyvean S 2005 Patient dose reduction in CT. Br J Radiol 78: 880–883 28. ICRP 2000 Managing patient dose in computed tomography (CT). ICRP Publication 87. Ann ICRP 30. Pergamon, Oxford. ICRP website: www.icrp. org/docs/ICRP_87_CT_s.pps 29. Shrimpton P C, Hillier M C, Lewis M A et al 2005 Doses from computed tomography (CT) examinations in the UK: 2003 Review. NRPB-W67. NRPB, Chilton 30. National Radiation Protection Board 1998 Diagnostic medical exposures. Advice on exposure to ionizing radiation during pregnancy. NRPB, Chilton 31. ICRP 2002 Doses to the embryo and fetus from intakes of radionuclides by the mother. ICRP Publication 88. Ann ICRP 31, corrected version. Elsevier, Oxford 32. Winer-Muram H T, Boone J M, Brown H L et al 2002 Pulmonary embolism in pregnant patients: fetal radiation dose with helical CT. Radiology 224: 487–492 33. Cook J V, Shah K, Pablot S et al 1998 Guidelines on best practice in the X-ray imaging of children. St George’s Hospital, London 34. Paediatric Task Group of the European Association of Nuclear Medicine 1990 A radiopharmaceuticals schedule for imaging in paediatrics. Eur J Med 17: 127–129 35. ICRP 2004 Doses to infants from ingestion of radionuclides in mothers’ milk. ICRP Publication 95. Ann ICRP 34. Elsevier, Oxford 36. Becket J R, Kotre C J, Michaelson J S 2003 Analysis of benefit:risk ratio and mortality reduction for the UK breast screening programme. Br J Radiol 76: 309–320 37. Whitby M, Martin C J 2003 Radiation doses to the legs of radiologists performing interventional procedures: are they a cause for concern? Br J Radiol 76: 321–327

SUGGESTED FURTHER READING Institute of Physics and Engineering in Medicine 2002 Medical and dental guidance notes. A good practice guide on all aspects of ionising radiation protection in the clinical environment. IPEM, York

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CHAPTER

Clinical Governance and Audit in Radiology

10

Richard A. Nakielny, Adrian Manhire and Raymond J. Godwin

Clinical governance in radiology • Definition of clinical governance • Setting standards for clinical audit • Risk management • Revalidation

Clinical audit—‘reality rather than belief’ • Clinical audit’s history and the wider perspective • The audit cycle/spiral • Achieving successful organization of audit • The re-launch of audit

CLINICAL GOVERNANCE IN RADIOLOGY Richard A. Nakielny In the mid/late 1990s a series of perceived major failures of the UK Medical Health System received intense media publicity. It was felt that the professional accountability of doctors to the public needed reinforcing.The government response culminated in two White Papers, The New NHS: Modern, Dependable1 and A First Class Service: Quality in the New NHS2, in which the concept of clinical governance was introduced and defined. These two White Papers signalled a culture change from an emphasis on numbers treated to an emphasis on quality of care, cooperation and patient involvement3. The new system is a multiprofessional approach which includes all the healthcare professionals within a clinical team. One of the objectives of this change was to reduce the substantial variations in medical practice and outcome across the country. It was recognized that this change would not happen overnight and the stated target was a 10-year programme of modernization of the NHS.

responsibility for the maintenance and development of service quality as well as the financial affairs of the Trust. Most NHS Trusts have set up committees in the following areas to satisfy external reviews of compliance with clinical governance: • Clinical audit (critical analysis of clinical care set against known standards) • Risk management • Clinical effectiveness (extent to which processes do what they are intended to do, i.e. greatest health gain from available resources) • Quality assurance • Staff development • Research and development.

DEFINITION OF CLINICAL GOVERNANCE

Local self-regulation, particularly through personal audit, is a cornerstone of clinical governance. All hospital doctors will be required to participate in a national audit programme appropriate to their specialty or subspecialty2. Within radiology, written standards related to equipment, process and appropriate clinical outcome need to be in place to comply with this aspect of clinical governance. Most radiology departments already have a substantial number of standards in place, particularly with regard to equipment and process. In addition, there are Royal College of

Clinical governance was defined as ‘a framework through which NHS organisations are accountable for continuously improving quality of their services and safeguarding high standards of care by creating an environment in which excellence in clinical care will flourish’. The essence of clinical governance is local accountability for the continuous monitoring and improvement of clinical quality.The Trust Chief Executive has statutory

SETTING STANDARDS FOR CLINICAL AUDIT

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Radiologists’ publications containing suggested standards4. These can be categorized under the following headings: 1 Equipment standards 2 Process standards: • Referral guidelines—there is national advice on referral guidelines5 • Requests for examination—legible, sufficient clinical detail, signed, dated, etc. • Procedure—target times for waiting lists, satisfactory patient identification, systems, informed consent, radiation, protection protocols, etc. • Patient care—written information about examination, acceptable environment, user satisfaction questionnaire, defined system for dealing with patient complaints, etc. • Reporting times • Critical incident reporting • Continuing professional development (CPD) for staff— induction programmes, fire regulations, radiation protection, cardiopulmonary resuscitation training, etc. • Staffing levels—national advice is available6. 3 Outcome standards These are much more difficult to set than process standards. There are few nationally accepted figures for minimum diagnostic accuracy in an everyday work situation.The accuracies of various imaging methods are published in the literature but these levels are often obtained by specialists who are working under optimal conditions. It is essential that any standards set under the auspices of clinical governance are practicable and achievable in the working situation. • Mammography screening—this was set up with process and outcome standards in position from the outset. However, mammography screening has the advantage of dealing with a single anatomical area and, in effect, a single pathological entity. This enables outcome standards to be more readily set and monitored than in the more complex everyday work situation where a wide number of investigations and pathologies are encountered. • Interventional radiology—The Society of Cardiovascular Interventional Radiology (SCVIR) in the USA has developed and published extensive standards relating to the success and complication rates of interventional procedures.The British Society of Interventional Radiology (BSIR) is developing a comparable set of practical and achievable standards. • Radiology—setting outcomes standards in other subspecialty areas of radiology is difficult and complex. National advice has been issued on possible audit projects7 but the majority are process rather than outcome audits. This illustrates the practical difficulties of identifying viable outcome audit projects. How, for example, does one assess the accuracy of a chest X-ray report other than on the most simplistic criteria? As the issue of standards in radiology is so problematical, it may be necessary to await central directives on standards in radiology from the National Institute for Health and Clinical Excellence (NICE) (NHS, UK) after appropriate consultation with national bodies and subsequently to set up audits

in these particular areas to ensure conformance with the standards set by NICE. In the interim it will be essential to develop an involvement with audit, not only to demonstrate departmental conformance with clinical governance, but also because individual revalidation by the General Medical Council (GMC) will require proof of audit activity.

RISK MANAGEMENT Clinical governance and risk management are inextricably linked. There are two main components of risk management: • the identification of potential problems which could compromise the safety of patients, visitors and staff • the installation of procedures and protocols to minimize these. There are already many areas of well-established risk management regulations including health and safety regulations, equipment maintenance and safety, radiation safety, infection control, cardiopulmonary resuscitation, IT security, etc. The introduction of clinical governance has raised the profile of several other important aspects in the practice of radiology.

Staffing levels/workload Clinical governance emphasizes quality of care, and adequate staffing levels are a prerequisite for this. Stress caused by understaffing will affect performance.There is at present a significant undersupply of radiologists in the UK to accommodate the increasing number of referrals and the complexity of modern radiology. The Royal College of Radiologists has attempted to define a reasonable workload for a radiologist, and also to assess the impact of new clinical appointments in other clinical specialties on radiology staffing6.

Skill mix Team-working is emphasized by clinical governance. There is national support from the Royal College of Radiologists for a responsible introduction of skill mix8 so that appropriately trained, supervised and audited (usually nonmedical graduate) staff can help to offset the radiological workload. An important prerequisite for this is that both the delegator and the person to whom the task has been delegated agree to the delegation which must conform to GMC guidelines9. In particular, it must be established that the person to whom the work is delegated is competent to carry out the task.This person then assumes a clinical and medico-legal responsibility for their actions but overall medical responsibility can only be transferred, by referral, to another medically qualified practitioner. It is essential that improved quality of patient care, rather than a reduction in costs, is the main aim of skill mix. Improved quality of care may be achieved with skill mix by releasing highly trained medical practitioners from time-consuming yet relatively straightforward tasks to allow them to concentrate on tasks that require a level of expertise commensurate with their ability and training.

CHAPTER 10

Continuing professional development The concept of lifelong learning is a firmly established component of clinical governance. It is not sufficient to view a qualification examination certificate, no matter how advanced, as being the final stage of medical education. Most radiologists have been voluntarily pursuing further learning throughout their careers and the formalization of this process does not pose any major conceptual difficulty. The public require reassurance that doctors, and indeed all staff, are keeping up to date with advances in medical knowledge. Documentation of this is a vital component of risk management and is also required for revalidation. Continuing medical education (CME) forms the backbone of continuing professional development (CPD) but CPD also includes the development of managerial, appraisal, teaching and other skills where appropriate.

Quality of reporting The quality and timeliness of reporting are central to the input into patient care by a radiology department. However, the setting of standards for quality of reports is problematical. In diagnosis, errors in perception are much more common than errors of interpretation. Overload of work, fatigue, repeated distractions and environmental conditions all have an important bearing on the incidence of these errors and it is important to minimize these adverse factors. Attendance at clinicoradiological and multidisciplinary team meetings is important to enable feedback on the accuracy of reporting to occur. Good communication between team members involved in clinical care is emphasized repeatedly in clinical governance. Formal records of attendance at these meetings would be useful documentary evidence for revalidation. Formal medical discrepancy meetings (see later) to discuss (anonymously) cases where possible errors have occurred are an essential development of clinical governance.

Working beyond competence All clinicians are becoming more specialized and radiology is no exception. Subspecialization is, however, a two-edged sword. It can produce a high-quality service during normal working hours but it also leads to a situation in which oncall work may be in an area outside the expertise of the consultant on-call. Consultant staff should together define who within the department has adequate expertise to perform and/or interpret the specialized procedures that may occur in an on-call setting. Arrangements should then be put in place, possibly involving other NHS Trusts, for on-call cover for these procedures. If such cover cannot be made available on an on-call basis owing to the local situation, risk managers must be made aware of this. National advice for on-call radiological practice10 includes the following: • Only those examinations that will affect immediate patient management during the out-of-hours period should be

• CLINICAL GOVERNANCE AND AUDIT IN RADIOLOGY

performed, and each department should have a portfolio of examinations that it believes can be offered safely and reliably out of hours. This list should be agreed with the Trust. • Out of hours, a radiologist should only carry out those procedures that they are competent to perform in normal working hours. • Appropriate staff and equipment must be available for outof-hours work that would normally be available for in-hours work. Another aspect of working beyond competence is the introduction of new radiological procedures. New procedures need to be evidence-based. Careful consideration should be given to organizing adequate study leave to acquire the skills for new procedures. The cost of complications incurred while performing a new procedure for which the radiologist is not adequately trained may be considerably more than the cost of obtaining training in that procedure.

Informed consent Clinical governance stresses greater patient involvement in decision making. The attitude of the general public to the amount and quality of the information they require before consenting to medical procedures has changed radically. The ease of access to information through the media and internet, together with an irreversible move away from the presumed infallibility of doctors, has resulted in a climate in which it is no longer acceptable to give inadequate information about medical procedures. In an excellent review of informed consent11, the differences in attitude in the UK and America were highlighted. In America the law requires that the patient is given all the relevant information. This contrasts with the UK where the law allows, to some extent, clinical judgement to determine what information is given to the patient. There must still be ‘sufficient disclosure’ to allow the patient to make an informed choice. The legal meaning of ‘sufficient disclosure’ is that patients must be informed of any serious risk, even if it is of low frequency. They must also be told of less serious risks which occur more commonly. Details/risks of a procedure may only be withheld if it is felt that they are likely to cause ‘serious harm to the mental or physical health of a patient’. If a patient asks a direct question about risks, this must be answered truthfully and as fully as the patient demands, i.e. information cannot be withheld if a direct question is asked. The GMC has issued advice on informed consent12. Aspects of this advice relevant to radiological practice in the UK have been incorporated into a guidance document issued by the Royal College of Radiologists13. Careful explanation and oral consent will be sufficient for the majority of radiological investigations. High-risk procedures require a full and careful explanation, and adequate time must be allowed for the patient to assimilate this information. This should occur prior to any pre-medication. Written aids and

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patient-focused literature have a positive role in this process. The person explaining the procedure must have sufficient knowledge and experience to answer any relevant questions fully and truthfully. Written consent is then required, but it is not a legal safeguard if complications arise that were not explained to the patient. If any information is withheld on the grounds that it may cause serious harm to the patient, this must be recorded before the procedure in the clinical notes together with the reason for doing so, as this may need to be justified in law. Examinations involving high radiation doses (e.g. CT, extended fluoroscopy) should have the risks/benefits of the procedure explained in terms that can be clearly understood. Again, pre-prepared information sheets may well be helpful. Research procedures must not be contrary to the interests of the patient, and a full explanation and written consent are mandatory.

Professional registration Policies must be in place for checking the professional registration of staff within the department. If the employment of certain groups of staff is subcontracted then the responsibility for confirming appropriate staff registration must be clearly defined.

Patient record security The confidentiality of patient records, both written and held on computer, is an important part of risk management. Clear policies must be in place for the maintenance of this security. Safeguards governing the access to, and storage of, confidential patient information must be in place.

Major accident response Clear policies defining the departmental response in the face of a major accident must be in place.

Critical incident reporting Clear policies for recording, openly discussing and disseminating any lessons learned from critical incidents must be in place. Any lessons learned must be applied promptly. The Royal College of Radiologists has produced an overview of the impact of risk management on clinical radiology14.

REVALIDATION Clinical governance incorporates both departmental and individual performance. The GMC have stated their view of the components of good medical practice for individual doctors9 and in future will require all UK doctors to undergo a revalidation process to maintain their licence to practise15. There is national guidance about how good medical practice impacts on radiologists16. However, the Shipman Inquiry findings17 (where a general practitioner was found guilty of the murder of more than 200 of his patients)

have criticized the proposed GMC revalidation procedure for failing to incorporate a robust assessment of a doctor’s fitness to practise. A leading article in the British Medical Journal18 succinctly discusses the rationale that underpins this criticism. The implementation of the GMC version of revalidation had been planned for April 2005, but this has now been postponed to allow for the incorporation of any future recommendations resulting from the Shipman Inquiry. The following is a summary of the principles of the GMC revalidation so far; however, it should be borne in mind that there will be additions to this when further recommendations are published, taking into account the findings of the Shipman Inquiry. • Individual clinical performance meets any national professional standards. • The basis will be appraisal and assessment of local performance in the workplace in relation to any appropriate national standards (i.e. an examination system is not thought to be appropriate). • It is seen to be fair to doctors and open and clear to the public and employers. • It is capable of appraising and assessing all doctors whatever the circumstances of their practice. • It is simple, unobtrusive, economical in time and effort, and is as inexpensive as is consistent with effectiveness (i.e. detailed performance assessment will only be invoked in cases in which there is local evidence of serious dysfunction in performance). It has been proposed that revalidation should be primarily based on the outcome of the local annual appraisal process for those employed within a managed setting, and will occur on a 5-yearly cycle. It will be essential for doctors to collect and maintain appropriate documentary evidence for revalidation. The GMC has stated that there will need to be evidence available in the following categories in order to obtain revalidation.

Suggested documentary evidence for radiologists 1 Good medical practice: • Audit results and record of attendance at audit meetings • Medical discrepancy personal records • Record of attendance at medical discrepancy meetings. 2 Maintaining good medical practice: • CME/CPD records • Personal development plan • Record of attendance at clinicoradiological and/or multidisciplinary team meetings. 3 Working with colleagues: • 360-degree appraisal documentation (see later) • Record of attendance at any radiology team meetings. 4 Relationships with patients: • 360-degree appraisal documentation (see later) • Record of complaints/plaudits.

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5 Research 6 Teaching/training: • Feedback documentation (anonymous). 7 Health/probity:

• Sickness record • Self-signed statement that ‘health (of the doctor) has never endangered patients or colleagues’ • Self-signed statement that ‘conduct work to highest ethical and moral standards’ • 360-degree appraisal documentation (see later). Most of the above documentary evidence can be collected relatively easily. However, documentary evidence for two of the cornerstones of clinical governance—namely medical discrepancy meetings (quality improvement by learning from errors) and 360-degree appraisals (team working)—requires more active organization. The following is a précis of suggested methods for setting up these two processes with the emphasis on simplicity.

Medical discrepancy meetings • Empathic lead person: involves everyone in the process, encouraging a constructive, nonconfrontational atmosphere. • Case collection: lockable collection boxes placed in easyto-reach sites with standardized forms adjacent (and replenished regularly!). • Meetings at regular intervals (e.g. monthly). • Cases presented by a lead person: the radiologist involved should remain anonymous. It is impossible to re-create the original reporting conditions but it is important to present the same clinical information that the reporting radiologist had available. • Discussion focused on learning, not blame. • Consensus vote on whether error actually has occurred. • Simple consensus scoring system for degree of error (grade and significance). • Lead person gives confidential feedback if an error has occurred. • Annual analysis by lead person of cases discussed to see if there are any patterns that may require a more structured solution. • Attendance recorded formally (documentary evidence for revalidation).

360-degree appraisal Satisfactory team working and a willingness to listen and act on constructive comments about performance from patients and colleagues (medical and nonmedical) are essential in clinical governance.Three hundred and sixty degree appraisal is a process where the views of patients and colleagues are

• CLINICAL GOVERNANCE AND AUDIT IN RADIOLOGY

gathered together and fed back to the individual at predetermined time intervals (approximately 3 years if there are no significant problems). Although 360-degree appraisal is viewed as an essential part of the overall appraisal process (and hence for revalidation), it must be stressed that 360degree appraisal is only one part of this overall appraisal, and is not a pass/fail process. The tasks and interactions of radiologists are different from those of physicians and surgeons. Consequently, the following suggested method for 360-degree appraisal has been adapted to conform to the requirements of radiologists, and has been issued as guidance by the Royal College of Radiologists on their website, www.rcr.ac.uk. The essence of the 360-degree appraisal questionnaire is as follows: • Five sections, the first three to be completed only by the relevant professional group (medical colleagues, radiographers/nurses and clerical/secretarial staff) and the final two sections to be completed by all staff groups. • Each section has about 10 simple questions relevant to that professional group in appraising the radiologist. There is a simple numerical scoring system ranging from 1 (poor) to 10 (excellent). • Within the radiographer/nurse section there are questions relating to patient interactions. This element allows radiologists with infrequent patient contact to obtain some documentary evidence for the ‘relationships with patients’ section for revalidation. • The penultimate section contains a simple question on the health and probity of the radiologist undergoing the 360degree appraisal. • The final section is for free text comments. • A pilot study has shown that the average time taken to complete the questionnaire is 7 min. • A minimum of 10–12 questionnaires (e.g. four from each of the three professional groups chosen) must be completed to give a reasonable overview and also to maintain anonymity of the staff completing the questionnaires. • A system for collecting the questionnaires anonymously and analysing them for feedback at the overall appraisal process needs to be in place. • A reasonable time interval between 360-degree appraisals, assuming there are no particular problems, would be 3 years to allow documentary evidence to be available for the 5yearly revalidation process. In an age where form filling is in danger of proliferating out of control, it is important that the 360-degree appraisal questionnaire is kept as simple as possible. If any significant problem areas are identified, these can then have in-depth assessment at the annual appraisal.

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CLINICAL AUDIT—‘REALITY RATHER THAN BELIEF’ Adrian Manhire and Raymond J. Godwin You will almost certainly have been referring to other chapters in this publication, using it as a reliable source of current opinion in diagnostic radiology, searching for best practice and the latest knowledge, and for research evidence in support of it. Having gathered such knowledge, are you able to show that you are practising to these new standards of care? Clinical audit is the tool that should enable you to produce evidence to show that you have achieved these standards in your own practice and you need to be able to do this. Audit is an integral part of clinical governance. In the foreword to Principles for Best Practice in Clinical Audit, Hine (Chair of Commission for Health Improvement) and Rawlins (Chairman, National Institute for Clinical Excellence) state19: Public and professional belief in the essential quality of clinical care has been hit hard in recent years, not least by a number of highly public failures. Clinical governance is the organizational approach for quality that integrates the perspectives of staff, patients and their carers and those charged with managing our health service. Clinical audit is at the heart of clinical governance.

One of the most prominent of the public failures was investigated in the Shipman report20. How well doctors carry out their professional activities has also been brought to the centre of public debate, along with the process of audit as a method of enquiry21. In this section, we review the origins of clinical audit, consider what audit is, how it can be carried out, how it can help underpin clinical governance, and how it might be built into departmental practices, creating the environment in which clinical audit can flourish.

The definition of audit The systematic, critical analysis of the quality of medical or clinical care, including the procedures used for diagnosis and treatment, the use of resources, and the resulting outcome and quality of life for the patient. Secretaries of State for Health, Wales, Northern Ireland and Scotland (1989)22

CLINICAL AUDIT’S HISTORY AND THE WIDER PERSPECTIVE Audit of medical care is not new. As early as the Crimean War (1854–1856), Florence Nightingale used a form of audit as an aid to her management of the injured and sick in her care, using standardized methods for the collection of information on death and infection23. She used this audit evidence to assist her argument for resources and changes in practice. In the United States, in 1917, the American College of Surgeons introduced a process of reviewing clinical notes against a set of minimum explicit standards, questioning their quality and adequacy of facilities (including radiology)24. These processes developed into criterion-based patient outcome audit

by 1975 under the overview of a national body, the Joint Commission on Accreditation of Healthcare Organisations25. At the same time, mainly as an aid to keeping public healthcare spending under control, the US Congress created Professional Standards Review Organisations. These were instituted to review the appropriateness of medical services and their quality through medical audit. There is a marked similarity to the development of the Commission for Health Improvement (CHI) and the UK National Institute for Health and Clinical Excellence (NICE).

Audit in the UK In the United Kingdom, prior to the late 1980s, there was no requirement within the NHS for clinicians to demonstrate any evidence of the quality of their clinical practice. In 1989, the UK government introduced medical audit as a requirement within all doctors’ job plans22, extended this in 1997 to include all healthcare professionals as clinical audit1,2,26, and integrated it into clinical governance. Together with the logical requirement to practise evidence-based medicine, the infrastructure for clinical governance was now in place, awaiting its formal introduction2. Not only is there now a mandatory requirement for all doctors to participate in clinical audit, the GMC9 advises all doctors that they: …must take part in regular and systematic medical and clinical audit, recording data honestly. Where necessary, you must respond to the results to improve your practice, for example by undertaking further training.

Although most doctors routinely practise audit informally by comparing their work to published data, there is now a clear obligation to record this and have it available to validate their personal practice and that of their clinical team, department and hospital.

Making it possible There are two factors that are important for successful audit: • creating a local environment that is supportive of audit (including providing adequate resources in terms of time and assistance, and ensuring that the resulting change occurs) • using audit methods that are most likely to lead to audit projects that result in real improvement.

Difficulties in audit Many of those involved in audit have unfortunately lost enthusiasm because of the difficulties that they have encountered. • Poor project design has led to data of poor quality. Information has been collected because it is available rather than being a relevant measure of clinical quality. • Many projects are poorly managed. Demonstrating inadequate care is not sufficient unless it can be carried through into changes that improve practice. Change is

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often the most difficult part of audit but it is often left to inexperienced junior staff without appropriate support, influence and resources. As much attention needs to be devoted to change for improvement as to the collection and analysis of data. It is the perception of improvements in care that drives the individual on to further audit.

What does audit really mean? Many clinicians find the term ‘audit’, with its financial undertones and rather formal definition (above), confusing and difficult to remember. Fowkes27 has given a more pragmatic definition: ‘Comparison of actual practice to a standard of practice and as a result of the comparison, any deficiencies in actual practice may be identified and change undertaken to rectify the deficiencies.’

The words ‘actual practice’, ‘standard of practice’, ‘comparison’, ‘deficiencies’ and ‘change undertaken to rectify’ clearly describe the audit cycle and emphasize the essential need for change for the better if standards are not achieved. Donabedian28 has subdivided audit into three types: structure, process and patient health outcome. Structure—What you need The availability and organization of resources (material as well as human) required for the delivery of a service. An example of this is the availability of adequate resuscitation equipment within a department of radiology. Process—What you do How well has a required procedure been followed? Have all radiology reports been checked and validated by the reporting radiologist prior to circulation? Patient health outcome—What you expect This describes the alteration in healthcare status of an individual which is directly attributable to clinical intervention. Outcome audits in radiology are often related to interventional radiology procedures, where the clinical improvement achievable with such techniques is more readily measured; however, it is not unreasonable to include accuracy of imaging diagnosis as an outcome audit, as it can also aid in the patient’s clinical improvement or cure29.

Audit is not research Research and audit are often confused.There are clear differences, the awareness of which enables differentiation. Donabedian30 distinguished between the assessment of medical technology Table 10.1

• CLINICAL GOVERNANCE AND AUDIT IN RADIOLOGY

(research) and the assessment of the quality of medical care (audit) (Table 10.1). The most important illustration of these differences is that an audit can be carried out on a relatively small number of cases and does not always require the time and expense of a research programme. Research sets the standards and audit determines whether clinical practice meets them.

What not to audit There is a tendency for new users of audit methodology to use it as a tool to demonstrate the inadequacies of other clinicians’ practice. It is tempting to audit how others use imaging services and the use of the published guidance on how best to use imaging encourages this31,32. Audit of third parties is unlikely to achieve the essential elements of change and improvement, which are the key features of a successful audit33. All involved should be committed to the audit or it will generate ill-feeling and the results are likely to be dismissed or ignored. Using such standards as part of an inclusive multidisciplinary audit process alongside nonradiological colleagues is much more likely to achieve change and reinforce, not strain, local professional relationships. Audit of personal practice should take the prime place. A standard is the keystone to the process and unless a clear standard is identified at the beginning of an audit, it is unlikely to succeed. It helps to ensure that a project is audit and not research. Audit activity must be relevant to current local activity and needs, and must reflect the problems encountered in everyday work.The likely required change should be achievable, otherwise effort used in trying to implement it is likely to be wasted. It is also better not to attempt audits with a high level of complexity, as these are more likely to fail to complete their second cycle34.

THE AUDIT CYCLE/SPIRAL The main aims of audit are to demonstrate either: • compliance with an agreed standard of care, or • to use the results of the initial audit to identify possible change(s) which, following implementation of those changes, may enable the standard to be achieved. The original concept was the audit cycle (or loop) (Fig. 10.1). Firstly, a topic is chosen for audit and a standard is identified. By identifying a suitable indicator (see later) and collection of related data, the reality of practice is identified and compared with a previously agreed target. • If the set target is achieved, the audit, on this occasion, is completed, reassurance has been achieved, and the audit result is available as governance evidence.

DIFFERENCES BETWEEN RESEARCH AND AUDIT

Research

Audit

Identifies what is best practice

Determines if this has been put into practice

Is concerned with techniques, instruments or materials

Is concerned with the performance of individuals or teams

Uses statistical models and usually requires statistical compliance

Does not have to reach statistical significance

Usually requires a long time scale for completion

May be carried out in a very short time (sometimes a matter of a few hours)

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Select a topic

Accept a standard of practice (e.g. from Research)

Observe your practice (i.e. Audit)

Implement change

Compare your practice with the standard

Figure 10.1 The audit cycle.

• If the target is not achieved, the need for some form of change is indicated to enable the required improvement in performance. After the introduction of the agreed change(s), the process of data collection is repeated. The second cycle will show if the changes have improved practice and whether the target has been achieved. The concept of the audit spiral (Fig. 10.2) adds a third dimension of continued improvement, recognizing that standards and targets can change with time and new developments. The more important audits are likely to be continuous processes, with multiple cycles year on year, rather than closed loops.

a successful audit such as the success and complication rates of angioplasty. Audit is a tool for showing how a practitioner measures up to local and national standards which are now becoming more readily available. In the UK, nationwide audits are now organized by the Royal College of Radiologists (RCR) or one of the affiliated clinical interest bodies, such as the audit of nephrostomy practice (RCR and British Society of Interventional Radiology).This enables comparison of local practice and its outcomes with similar institutions across the country. At the individual level, the collected evidence may assist in revalidation, and take its place in a personal folder for discussion at annual appraisal. However, with clinical governance, there is a need to demonstrate corporate accountability for clinical performance2 through a process of ‘regular and systematic formal Clinical Review’ (or clinical audit). Quality monitoring within the specific areas described earlier will be essential to provide this evidence. Some of these areas may require the creation of running audits as a monitoring process (e.g. waiting times for radiological examinations). Suggestions for what these areas of audit could be are available in a publication from the RCR35 which contains illustrative recipes. Topics and standards for governance issues are frequently incorporated into NICE guidance and Department of Health publications. An illustration of likely audit activity related to governance is shown in Figure 10.3. It is also possible to prioritize the choice of subjects for audit using the list below36, recognizing that not all areas can be audited at once. As an aid to prioritization, consider audit topics of activities which involve: • high risk • high volume • high cost • wide variation in clinical practice • local clinical anxiety (e.g. untoward events or questionable clinical performance).

Choosing topics to audit

What standard should be used?

Areas of concern in clinical practice that arouse the interest of an individual are more likely to produce enthusiasm for

When designing an audit, it is essential to identify an appropriate standard at the beginning of the process.

Figure 10.2 The audit spiral. (From Godwin R J, DeLacey G, Manhire A (eds) 1996 Clinical audit in radiology: 100+ recipes. Royal College of Radiologists, London, with permission.)

5 Re-audit 1 Select a standard 4 Implement change 2 Assess local practice

3 Compare with standard

Improvement or reassurance

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• CLINICAL GOVERNANCE AND AUDIT IN RADIOLOGY

Adverse events detected. Investigated. Lessons learnt and translated into change in practice.

Poor clinical performance identified early. Then dealt with skilfully, speedily and sensitively, in order to avoid harm to patients.

Quality of data necessary for monitoring clinical care to be of a consistently high standard.

Leadership skills developed at the clinical team level.

Systematic learning from clinical complaints. Translated into change in practice.

Where is your evidence

?

Continuing professional development programmes in place.

Quality improvement processes (clinical audit) to be integrated into an organizational quality programme.

Clinical risk reduction programme in place and of high quality.

Evidence-based practice and infrastructure in place and utilized.

Clinical audit will provide: • the evidence • indication of where changes need to be made • the help needed in order to meet the Trust’s statutory obligation1,2

Figure 10.3 Acquiring the evidence on effective governance. (Courtesy of Dr G DeLacey.)

Standards may be based upon research evidence, but this is frequently not available. A guideline may also be used as a standard, derived either nationally (e.g. from a specialty group or the National Institute for Health and Clinical Excellence) or locally agreed, based upon the best available information, respected opinion and local circumstances. Each standard has three components: A recommendation + an indicator + a target A Recommendation: a statement about the structure, process or outcome against which the quality of performance is to be judged. B Indicator: the variable (or item of information) that needs to be measured in order to determine whether the recommendation is being met.This is also known as the criterion. It may be represented as a percentage of compliance with a standard. C Target: the expected level of achievement or the minimum score that is considered locally to be acceptable in

good practice. It may be that when auditing for the second or third time, the target can be gradually raised. In this way, early failure, disappointment and disillusion might be avoided33.

The measurable indicator There may be more than one indicator within a single audit, each representing a step along a multilevel standard. This situation arises within audits of care pathways, where a number of criteria for completeness are required for the standard to be achieved. As an example of an indicator within an audit of double reading of breast screening mammograms, the recommendation might be that ‘all screening mammograms will be read by two radiologists’. The indicator here would be the actual percentage of mammograms reported by two radiologists.The target would be the minimum percentage conformity such as 90%. Similarly, the recommendation may be that pneumothoraces after lung biopsy should not exceed 15% at 1 h post-procedure.

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The indicator would be the number of patients with a pneumothorax on a chest film taken at 1 h post-procedure, and the initial target might be 20%. The standard will indicate ideal expectation, the indicator signifies reality, and the target gives the required minimum achievable result locally, perhaps during the development period of the biopsy service.

Numbers for audit As mentioned in the section on audit and research, large numbers are not necessary for a successful audit and may indeed lead to failure of completion of the audit cycle. The choice of sample size can be difficult and should be decided for each individual circumstance.The number of cases or episodes audited should reflect the number seen locally in practice. There is no need for controls. In audits where a high percentage compliance is required (e.g. 100%) a relatively small sample might show failure of compliance early on (even after review of the first case). It may be that in an audit of a high risk, low frequency activity (e.g. percutaneous nephrolithotomy), the preference may be to include all cases for audit prospectively, running the audit as a continuous process, reviewing results on a month-by-month, or year-by-year basis, in order to show trends. For a higher frequency clinical activity, it may be decided to review only a randomly chosen 5% sample of cases or reports within the audit (e.g. double reporting of CT staging scans in cases of lung cancer). The error rate in reporting can be a useful audit process to improve the quality of report content and structure37. Audit of even a low number of cases may indicate that there is a cause for concern and that further work is required. It is important not to draw premature conclusions without considering all the factors influencing the initial audit outcome. An excellent analysis of numbers in audit is available in a RCR governance publication (see Suggested Further Reading).

Implementing change and re-audit The most difficult, but also the most satisfying aspect of audit, is the successful implementation of any required or recommended change. The change required will depend upon local circumstances, available resources, and a willingness to adopt change in practice. The most important aid to introducing change is the acceptance by those involved in the audit of the need for change, should the audit show a failure to reach target. It is also essential to involve and inform those with the authority to introduce (and fund) change, and identify and empower those who will implement the changes. It has been shown that when the real cost of carrying out an audit is known to managers and clinicians, the recommended changes are more likely to be implemented38. Clinical audit can be a powerful force in the process of introducing new techniques, managing staff development and creating improved services and circumstances for staff and patients. As a business tool, it can be a two-edged sword, not only identifying poor performance but also supplying the evidence of need where resource inadequa-

cies exist39,40. The date by which any changes should have been introduced must be made clear and also the date by which any second audit will be carried out. Re-audit is an essential part of the process in order to demonstrate that the changes have really produced the expected improvements. To these ends, it is essential to create written reports of any audits carried out, with the associated recommendations for change clearly stated. Circulate these effectively and use them in the clinical governance report to the directorate and Trust. These actions will make the results and the process for change explicit and available as part of the governance process, and available for review. Here we come to the important matter of confidentiality.

Confidentiality In the collection of data during the audit process, details about patients and clinicians will be identified. If this information is available within the public domain, clinicians will inevitably become less willing to give further information and to cooperate. Although the results of audit need to be available to those with a legitimate interest in generating high clinical standards (Trusts, Royal Colleges, managers, purchasers and patients), such results should be of a general nature rather than person specific. Such person-specific audit information needs to be protected. There is, of course, a requirement that a responsible individual within each Trust (usually the Medical Director) has access to information relating to any one individual or group. This is particularly important where matters of clinical performance are brought into question. The GMC recommends that patient data should be kept anonymous for the protection of individuals41.

ACHIEVING SUCCESSFUL ORGANIZATION OF AUDIT The essential requirements for successful departmental audit are time, facilities, clarity of organization and responsibility, multidisciplinary involvement and a readiness to accept change. An absence of any of these, particularly time42, makes the achievement of successful audit much more difficult. Time allocation for audit work and meetings to receive and discuss results is essential. It is part of the agreed job plan for doctors under the new NHS contract introduced in 2003 and should be achievable and acceptable to the directorate. Advice and help with data collection and IT support are present within all Trusts, funding having been allocated for audit staff. Each department requires a clearly identifiable leader for audit with the responsibility to organize meetings, coordinate appropriate audits and create an annual audit report to the Trust43. The audit leader is also supported by the RCR audit subcommittee. Opportunities should be sought for cross-specialty audit and the creation of multidisciplinary care pathways with agreed standards.

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All staff groups should ideally be included within the audit processes and consideration must also be given to inclusion of patients in the audit process44.

THE RE-LAUNCH OF AUDIT It is well recognized that since its launch in the UK, the expected improvements in clinical practice from clinical audit have not materialized, despite major investment and work by many to facilitate its acceptance. One reason for this is the tendency for medical staff to see audit as a time-consuming process separate from the rest of their clinical activities, rather than as an integrating tool to show what they are achieving and what resources they need. The bulk of the work is often left to junior medical staff or radiographers who do have a role to play as team members. Furthermore, there may well be different agendas and priorities held by clinicians and managers. With the requirement to develop real clinical governance, and the responsibility for quality of care now clearly lying with chief executives, we may now see the tool of audit being used more coherently with less divergence of opinion and priority45. The development of multidisciplinary working and clear standards of care and process in recent years should make it easier to identify effective and reproducible audit processes that can be shared nationally and allow comparison of outcomes and methods over the whole National Health Service.

REFERENCES 1. Department of Health 1997 The new NHS: modern, dependable. The Stationery Office, London 2. Dobson F 1998 A first class service: quality in the new NHS. Government White Paper 35. The Stationery Office, London 3. Scally G, Donaldson L J 1998 Clinical governance and the drive for quality improvement in the new NHS in England. Br Med J 317: 61–65 4. Royal College of Radiologists 1999 Good practice guide for clinical radiologists. RCR, London 5. Royal College of Radiologists 2003 Making the best use of a department of clinical radiology: guidelines for doctors, 5th edn. RCR, London 6. Royal College of Radiologists 1999 Workload and manpower in clinical radiology. RCR, London 7. Royal College of Radiologists 2000 Clinical governance and revalidation: a practical guide for radiologists. RCR, London 8. Royal College of Radiologists 1999 Skills mix in clinical radiology. RCR, London 9. General Medical Council 2001 Good medical practice. GMC, London 10. Royal College of Radiologists 1996 Advice to clinical radiology members and fellows with regard to out of hours working. RCR, London 11. Panting G 1999 Where do we stand on informed consent? Continuing Medical Education Journal: Radiology Update 1: 29–31 12. General Medical Council 1999 Seeking patients’ consent: the ethical considerations. GMC, London 13. Royal College of Radiologists 1999 Guidance on consent by patients to examination or treatment in a Department of Clinical Radiology. RCR, London 14. Royal College of Radiologists 2002 Risk management in clinical radiology. RCR, London

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15. General Medical Council 2003 A licence to practise and revalidation. GMC, London 16. Royal College of Radiologists 2004 Individual responsibilities—a guide to good medical practice for clinical radiologists. RCR, London 17. Shipman Inquiry 2004 Fifth report—Safeguarding patients: lessons from the past, proposals for the future. HMSO website: www.theshipman- inquiry.org.uk/fifthreport.asp 18. Smith R 2005 The GMC: expediency before principle. Br Med J 330: 1–2 19. National Institute for Clinical Excellence (NICE) 2002 Principles for best practice in clinical audit. Radcliffe Medical Press, Oxford 20. Department of Health 2000 Harold Shipman’s clinical practice 1974–1998: a review commissioned by the Chief Medical Officer. The Stationery Office, London 21. Lanier D C, Roland M, Burstin H, Knottnerus J A 2003 Doctor performance and public accountability. Lancet 362: 1404–1408 22. Secretaries of State for Health, Wales, Northern Ireland and Scotland 1989 Working for patients. Working Paper 6: Medical audit. HMSO, London 23. Nightingale F 1863 Notes on hospitals, 3rd edn. Longman Green/ Longman, Roberts and Green, London, p 63 24. American College of Surgeons 1924 The minimum standard of the American College of Surgeons’ hospital standardisation program. Bull Am Coll Surgeons 8: 4 25. Joint Commission on Accreditation of Hospitals 1975 Supplement to the accreditation manual for hospitals. JCAH, Chicago 26. Department of Health 2000 The NHS plan: a plan for investment, a plan for reform. The Stationery Office, London 27. Fowkes F R G 1982 Medical audit cycle. A review of methods and research in clinical practice. Med Educ 16: 228–238 28. Donabedian A 1966 Evaluating the quality of medical care. Milbank Mem Fund Q 44: 166–206 29. Godwin R J, DeLacey G, Manhire A (eds) 1996 Clinical audit in radiology: 100+ recipes. RCR, London 30. Donabedian A 1988 The assessment of technology and quality. A comparative study of certainties and ambiguities. Int J Technol Assess Health Care 4: 487–496 31. Royal College of Radiologists Working Party 2003 Making the best use of a Department of Clinical Radiology: guidelines for doctors, 5th edn. RCR, London 32. McCreath G T, O’Neill K F, Kincaid W C, Hay L A 1999 Audit of chest X-rays in general practice: a case for local guidelines? Health Bull 57: 180–185 33. Godwin R 1995 Nothing succeeds like success—some do’s and don’ts in clinical audit. Clin Radiol 50: 818–820 34. Jackson G 1997 Clinical audit—KISS is better. Int J Clin Pract 51: 83 35. DeLacey G, Godwin R J, Manhire A R (eds) 2000 Clinical governance and revalidation. RCR, London 36. Shaw C 1989 Medical audit: a hospital handbook. King’s Fund Centre, London 37. Peters M A, Bomanji J, Costa D C et al 2004 Clinical audit in nuclear medicine. Nucl Med Commun 25: 97–103 38. Tomalin D, Renshaw M 1999 Clinical audit. Count the cost. Health Serv J 109: 28–29 39. DeLacey G 1995 Don’t look a gift horse in the mouth. Clin Radiol 87: 815–817 40. Jackson S 1999 Achieving a culture of continuous improvement by adopting the principles of self assessment and business excellence. Int J Health Care Qual Assur Inc Leadersh Health Serv 12: 59–64 41. General Medical Council 2004 Confidentiality: protecting and providing information. GMC, London 42. Manhire A, Cook A, Adam J et al 1998 Audit in radiology: a survey of hospital departments in the UK. Health Trends 30: 72–77 43. Renshaw M, Ireland A 2003 Specialty audit leads: has this concept been effective in implementing clinical audit in an acute hospital? Int J Health Care Qual Assur Inc Leadersh Health Serv 16: 136–142 44. Avis M 1997 Incorporating patients’ voices in the audit process. Qual Health Care 6: 86–91 45. Berger A 1998 Why doesn’t audit work? Br Med J 316: 875–876

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SUGGESTED FURTHER READING: CLINICAL AUDIT DeLacey G, Godwin R J, Manhire A R (eds) 2000 Clinical governance and revalidation. RCR, London Dixon N 1996 Good practice in clinical audit—a summary of selected literature to support criteria for clinical audit. National Centre for Clinical Audit, London

Godwin R J, DeLacey G, Manhire A (eds) 1996 Clinical audit in radiology: 100+ recipes. RCR, London National Institute for Clinical Excellence 2002 Principles for best practice in clinical audit. Radcliffe Medical Press, Oxford

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Techniques in Thoracic Imaging

11

Zelena A. Aziz and David M. Hansell

• • • • • • • •

Chest radiography Computed tomography High-resolution computed tomography Ultrasound Magnetic resonance imaging Ventilation–perfusion scintigraphy Positron emission tomography Positron emission tomography–computed tomography

Chest radiography and computed tomography (CT) are the two most important imaging tests used to evaluate respiratory disease. The basic technique of chest radiography has changed little over the past 100 years but recent developments in image receptor technology have resulted in the more efficient acquisition of chest radiographs with the benefit of a lower radiation dose. These images are produced in digital format, so facilitating their incorporation into picture archiving and communications systems (PACS). Advancing CT technology has meant that multidetector row CT (MDCT) systems have largely replaced single-detector CT. The resultant increase in data acquisition speed and z-axis spatial resolution has meant that volumetric high-resolution acquisitions are increasingly becoming the norm. Protocols for MDCT continue to be developed and refined, and currently, particular attention is being directed at dose-reducing strategies. The recent development of fused CT–positron emission tomography (PET) images has revolutionized the investigation of patients with suspected neoplastic disease, enabling the simultaneous assessment of both metabolic function and anatomical location.The role of other imaging techniques such as magnetic resonance imaging (MRI) and ultrasound (US) is limited to specific clinical situations and this is likely to remain the case given the obvious capabilities of MDCT.

CHEST RADIOGRAPHY Many chest radiographs are still acquired with conventional film–screen radiography systems that provide, at low cost,

good image quality and high spatial resolution1,2. However, the disadvantages of film–screen radiography are a limited exposure range, a relatively high retake rate and inflexibility of image display and manipulation1. As computer technology and storage capacities have developed over recent years, the considerable advantages of digital imaging systems and of PACS have become increasingly evident. As a result, digital imaging systems are now commonplace in radiology departments. Early digital imaging systems used a photostimulable phosphor image receptor plate (generally termed ‘computed radiography’ [CR]); these CR systems continue to be widely used because of their compatibility with existing radiography equipment. The phosphor plate stores some of the energy of the incident X-ray as a latent image. On scanning the plate with a laser beam, the stored energy is emitted as light that is detected by a photomultiplier and converted to a digital signal. The digital information is then manipulated, displayed and stored in whatever format is desired. More recently, full-field digital amorphous silicon flat-panel X-ray detector radiography systems based on caesium iodide and amorphous silicon have become commercially available. These thin film transistor (TFT) flat-panel detector systems (also referred to as DR [direct radiography]) are now widely available.The advantages of this technology include high detection efficiency and rapid image display.These systems have excellent image quality3,4 and allow a significant reduction in effective dose compared with either conventional film–screen or storage phosphor based CR systems5. Digital radiography systems have many advantages over conventional radiography: the photostimulable phosphor plate is reusable, user controlled post-processing is automatically performed to generate the display features desired for the anatomical part selected, and there is more efficient image archiving, retrieving and transmission. One of the most important advantages over conventional radiography is the wide dynamic range or latitude of the image plate—consequently, exposure errors are reduced and the need for repeat examinations is lessened.

Additional radiographic views Frontal and lateral projections are adequate for most purposes. Other radiographic views are less frequently performed

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because of the ready availability of cross-sectional imaging. One projection that is occasionally used is the lateral decubitus view, taken as a frontal projection with a horizontal beam and the patient lying on his/her side. Its main purpose is to identify an effusion that is not visible on an erect chest radiograph, or to demonstrate the movement of fluid in the pleural space.The lateral decubitus view is recommended by American Thoracic Society (ATS) guidelines for all patients presenting with community-acquired pneumonia; the rationale being that if the thickness of the effusion on the lateral decubitus view is < 1 cm, the effusion is small enough not to require further intervention6 (in practice this guideline is studiously ignored).The contrary view is that a parapneumonic effusion large enough to be potentially clinically significant can usually be defined by postero-anterior (PA) and lateral radiographs, and that if loculations are suspected, then CT will define the pleural space more accurately than a lateral decubitus radiograph7. Occasionally the lateral decubitus radiograph can confirm the presence of small amounts of fluid if there is a subpulmonic effusion or if the costophrenic angles are obscured by a pulmonary infiltrate. Radiographs exposed in expiration are valuable in the investigation of air trapping, particularly in paediatric practice in the context of a suspected inhaled foreign body. An expiratory radiograph may also enhance the demonstration of a small pneumothorax.

Portable chest radiography The imaging problems associated with portable chest radiography are (A) scattered radiation; (B) the inability of the radiograph to capture all relevant information; and (C) the lack of control over the overall optical density of the resulting image when there is slight over- or under-exposure. Additionally, the shorter focus–film distance results in undesirable, and sometines misleading, magnification of structures. High kilovoltage techniques cannot be used because portable machines are unable to deliver a sufficiently high kilovoltage, and as the maximum current is limited, long exposure times are needed, increasing movement artefact.The development of CR systems has provided solutions to some of the limitations of portable chest radiography by controlling optical density and contrast, but it does not eliminate the problem of scatter. Though their instant readout capabilities would be a great advantage at the bedside, DR detectors are not applicable to portable work, largely due to cost considerations. Therefore, it is expected that storage phosphors will continue to be the media of choice for portable radiography for some time to come.

COMPUTED TOMOGRAPHY The introduction of spiral (helical) CT in the early 1990s constituted a fundamental evolutionary step in the ongoing refinement of CT imaging, replacing the discontinuous acquisition of data in conventional CT with volumetric data acquisition. In 1998 several CT manufacturers introduced MDCT systems, which provided considerable improvement in data acquisition speed and longitudinal resolution, and more efficient use of X-rays8–10. These systems typically offered simultaneous

acquisition of four sections with a gantry rotation time of 0.5 s. Since then, there has been further rapid improvement in scanner performance with increased numbers of detector rows and faster tube rotation; currently, systems with 16-, 32-, 40- and 64-active detector rows are available. Rotation times of the X-ray tubes have decreased from 0.5 s to 0.33 s per rotation. The faster data acquisition enables not only better coverage in a single breath-hold, but also results in a significant reduction in patient movement artefacts. In paediatric practice this has meant less frequent need for sedation11. The introduction of MDCT has expanded the clinical indications for CT; these are summarized in Table 11.1. With MDCT systems, different section widths are achieved by collimating and adding together the signals of neighbouring detector rows. The Somatom Sensation 4 system (Siemens, Forchheim), for example, uses the adaptive array detector design and has eight detector rows. Their widths in the longitudinal direction range from 1 to 5 mm at the isocentre and this arrangement allows the following collimated section widths: two sections at 0.5 mm, four at 1 mm, four at 2.5 mm, four at 5 mm, two at 8 mm and two at 10 mm. Currently, there is a trend amongst thoracic radiologists towards acquiring high-resolution (1–1.25-mm thickness) volumetric images which can then be reconstructed at 1.25–5-mm intervals for interpretation depending on the clinical question. Hence, from the same dataset, both narrow sections for high spatial resolution detail or three-dimensional (3D) post-processing, and wide sections for better contrast resolution or quick review, can be derived.The convenience of a single protocol is particularly useful for patients with suspected focal and interstitial lung disease. Thin section reconstructions are recommended for volumetric assessment12 and characterization13 of pulmonary nodules, the evalution of interstitial lung disease and the evaluation of pulmonary embolism14, whereas 3–5-mm reconstructions are usually adequate for the initial assessment of mediastinal masses and for lung cancer staging studies. In younger patients, however, a more critical approach

Table 11.1

INDICATIONS FOR CT OF THE CHEST

In the acute setting Chest trauma Evaluation of acute aortic syndromes (dissection, transection) Demonstration of pulmonary embolism Identification of complications post thoracic surgery (mediastinal haematomas, complex pleural collections) In the nonacute setting Further evaluation of nodules, hilar or mediastinal masses identified on a chest radiograph Lung cancer diagnosis and staging Assessment of congenital anomalies of the thoracic great vessels Characterization of interstitial lung disease Identification of bronchiectasis/small airways disease Detection of pulmonary metastases from known extrathoracic malignancy

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should be adopted with the CT examination being tailored to the specific clinical question being asked, to avoid unnecessary radiation dose. The introduction of 16- and 64-detector MDCT systems has allowed the goal of truly isotropic imaging to be realized. Here, each image data element (voxel) is of equal dimensions in all three spatial axes, and forms the basis for image display in any arbitrarily chosen imaging plane. The acquisition of volumetric high-resolution data has particularly revolutionized the noninvasive assessment of vascular disease in the chest, and also paved the way for the further development of more sophisticated 3D image processing techniques. Many anatomical features of the chest do not conform to a single two-dimensional (2D) axial plane and full exploitation of isotropic MDCT data requires 2D and 3D post-processing techniques to harness the added advantage of improved z-axis resolution and coverage. Table 11.2 summarizes the main post-processing techniques used in evaluating chest disease.

Definition of spiral pitch An important parameter for characterizing helical CT is the pitch, which according to International Electrotechnical Commission specifications is defined as p = TF/W, where TF is the table feed per rotation and W is the total width of the

Table 11.2

• TECHNIQUES IN THORACIC IMAGING

collimated beam.15 With four sections at 1-mm collimation and a table feed of 6 mm per rotation, the pitch is p = 6/(4 × 1) = 1.5. This definition holds true for both single- and multidetector row CT systems. In the early days of four-detector CT, the term detector pitch was introduced, which accounted for the width of a single section in the denominator. For the sake of uniformity, the term detector pitch should no longer be used16.

Dose considerations Despite the undisputed clinical benefits of MDCT, there is the issue of increased radiation compared to single-detector CT to consider. In a CT X-ray tube, a small area on the anode plate emits X-rays that penetrate the patient and are registered by the detector. A collimator between the X-ray tube and the patient, the pre-patient collimator, is used to shape the beam and establish the dose profile. In general, the collimated dose profile is a trapezoid in the longitudinal direction. In the umbral region, X-rays emitted from the entire area of the focal spot fall on the detector; however, in the penumbral regions, only a part of the focal spot illuminates the detector—the pre-patient collimator blocking off other parts. With single-detector CT, the entire trapezoidal dose profile can contribute to the detector

POST-PROCESSING TECHNIQUES THAT MAY BE APPLIED IN EVALUATING CHEST PATHOLOGY

Post-processing technique

Technical considerations

Clinical applications

Multiplanar and curved multiplanar reconstructions (MPR and CMPR)

2D techniques that provide alternate viewing perspectives, usually with conventional window settings. Images are obtained by a reordering of the voxels into 1 voxel-thick tomographic sections, excluding those voxels outside the imaging plane

Evaluation of the large airways and pulmonary emboli, particularly for interpretative difficulties on axial sections either due to partial volume averaging or the inability to differentiate periarterial from endoluminal abnormalities

Maximum intensity projection (MIP)

A ray is cast through the CT data and only data that are above an assigned value are displayed, thus reducing all data in the line of the ray to a single plane. Sliding slabs of 5–10 mm are commonly used

Main use is in vascular imaging (Fig. 11.1) and in the evaluation of micronodular disease (more accurate identification of nodules versus vessels, and more precise characterization of nodule distribution)

Mininum intensity projection (MinIP)

Similar to MIP, but only data below an assigned value are displayed and thus it is best suited for showing areas of low density

May improve conspicuity of subtle density differences of lung parenchyma and therefore highlight regions of emphysema or air trapping

Shaded surface display (SSD)

This technique reformats data around a threshold that defines the interface of tissues. SSD does not reveal any internal detail

Evaluation of airway abnormalities

Volume rendering

Volume rendering is a unique form of 3D visualization. In this process a ray is projected through the dataset and a weighted representation of all the Hounsfield units encountered is displayed depending on their representation within the tissues. Voxels that are only partially filled with a density of interest are also included. The resultant images contain depth information whilst maintaining 3D spatial relationships

Used in angiographic examinations and also to evaluate large airway abnormalities (Fig. 11.2)

‘Virtual bronchoscopy’

Surface rendering and volume rendering are used to produce endoscopic simulations of the airway (Fig. 11.3)

Virtual endoscopic or perspective volume rendering images are not widely applied as they seldom give information that cannot be obtained by MPR. However, virtual CT bronchoscopy used in association with 3D techniques providing extraluminal information can provide additional information such as safe routes for tracheobronchial biopsy. Monitoring the position of airway stents is another potential application of this technique

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Figure 11.1 Maximum intensity projection (MIP) in vascular imaging. MIP reconstructed using 5-mm slabs demonstrates a markedly tortuous thoracic aorta. The descending thoracic aorta is aneurysmal with extensive mural thrombus.

signal, and thus the relative dose utilization of a single-detector CT system can be close to 100%. With MDCT, only the plateau region of the dose profile is used to ensure an equal signal level for all detector elements. The penumbral region is then discarded, either by a post-patient collimator or by the intrinsic self-collimation of the MDCT, and represents ‘wasted’ dose. The relative contribution of the penumbral region decreases with increasing section width and with an increasing number of simultaneously acquired images (Fig. 11.4). Thus, the relative

dose utilization with four-section 1-mm collimation CT is 70% or less depending on the scanner type, whereas with 16-section CT systems, dose efficiency can be improved to 84%. The CT parameters that affect radiation dose include gantry geometry, tube current and voltage, acquisition modes, collimation, pitch and gantry rotation time. Reduction in tube current is the most practical means of reducing CT radiation dose. A 50% reduction in tube current can halve effective radiation dose17. Authors of several studies using MDCT have suggested that it is possible to reduce tube current markedly (to between 40 and 70 mAs) in chest examinations without affecting image quality18,19. On a 64-detector MDCT, the dose for a volumetric high-resolution (1-mm sections) acquisition of the thorax in a 70 kg adult can be as low as 3.6 mSv if parameters of 120 kVp and 90 mAs (pitch of 1) are used (E. Castellano-Smith, personal communication). In lung cancer screening examinations, tube current can be remarkably low and yet yield images of diagnostic quality. Itoh et al have shown that images obtained at an effective tube current of 20 mAs are of equal diagnostic utility to those obtained at 50 mAs for the detection of 6-mm simulated nodules20. Another recommendation comprises acquisition of the entire chest using a 1-mm collimation (MDCT) at 120 kVp and 10–40 mAs depending on the body habitus of the individual21. At a tube current of 10 mAs, the effective radiation dose is 0.27 mSv; equivalent to just five conventional PA chest radiographs. In the paediatric population, some institutions favour the use of 1 mAs kg−1 for imaging the thorax; an approach that significantly reduces radiation dose. Tube potential (peak voltage) determines the incident X-ray mean energy, and variation in tube potential causes a substantial change in CT radiation dose. The effect of tube voltage on image quality is complex, since it affects both image noise and

Figure 11.2 Volume rendering to evaluate large airway abnormalities. (A) The axial image of a patient with recurrent adenoid cystic carcinoma shows narrowing of the right main bronchus with abnormal soft tissue surrounding the right upper lobe bronchus. (B) The volume rendered 3D image enables the entire extent of the stenosis to be visualized on a single image.

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• TECHNIQUES IN THORACIC IMAGING

Figure 11.3 ‘Virtual bronchoscopy’ of the airway. (A) Axial CT and (B) virtual bronchoscopic rendition demonstrating a carcinoid tumour protruding into the lumen of the distal trachea just above the level of the carina.

tissue contrast.Thus, the image quality ramifications of a decrease in tube voltage to reduce radiation exposure must be carefully examined before being implemented. For chest examinations, 120 kVp is commonly used. In thin patients (< 50 kg) and in the paediatric population, 100 kVp is recommended; the use of 80 kVp has been found to be associated with unacceptable beam hardening even in the smallest of patients (Fig. 11.5)22. With helical CT systems, beam collimation, table speed and pitch are interlinked parameters that affect diagnostic image quality. Faster table speed for a given collimation, resulting in a higher pitch, is associated with a reduced radiation dose (if other data acquisition parameters, including tube current, are held constant) because of a shorter exposure time. However, this is not true for some multidetector systems that use an effective milliampere–second setting (defined as milliampere seconds divided by pitch). Here, the effective milliampere–second level is held constant (by automatic tube current adjustment) irrespective of pitch value, so that radiation dose does not vary as pitch is changed23. Caution should be exercised when extrapolating dose reduction strategies from single- to multi-detector CT systems.

4–slice collimator

CT

detector

16 – slice collimator

CT

Automatic tube current modulation is a technical innovation that can substantially reduce patient dose.There are two methods used currently with CT systems: z-axis modulation and angular (x- and y-axis) modulation. In z-axis modulation, tube current is adjusted to maintain a user-selected quantum noise level in the image data. z-axis modulation attempts to render all images with similar noise, independent of patient size and anatomy. In angular modulation, the tube current is adjusted to minimize X-rays in projections (angles) that have less importance for the reduction of overall image noise content. With this technique, the tube output is adapted to the patient geometry during each rotation to compensate for strongly varying X-ray attenuation in asymmetric body regions such as the shoulders. A recent investigation of CT imaging studies in children in whom angular modulation was used demonstrated a mean reduction of 22% in dose without loss of image quality24. Ultimately, the complexity of the interrelationships between the different CT parameters and dose requires a close collaboration between radiologists and medical physicists to ensure that the radiation burden to patients is as low as possible without diagnostic accuracy being compromised.

Figure 11.4 Dose profiles for 4- and 16detector MDCT. The relative contribution of the penumbral region (P), representing wasted dose, decreases with increasing number of simultaneously acquired sections.

detector

Umbra

P

Detectors

P

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sibly a reduced volume. Typical injection parameters for fourdetector MDCT are 100–150 ml of 240–320 mg ml−1 of iodine injected at a rate of 3–4 ml s−1. For 64-detector MDCT, some institutions have experimented with 90–120 ml of 320–370 mg ml−1 of iodine injected at 3.5–5 ml s−1. A recent study using a four-detector system evaluated the influence of iodine flow concentration on vessel attenuation29. There was significantly better visualization of fourth-, fifth- and sixth-order pulmonary arteries using a protocol based on 90 ml of 400 mg ml−1 of iodine when compared with 120 ml of 300 mg ml−1. An injection rate of 4 ml s−1 was used in both groups. A specific application of contrast enhancement is in the differentiation between benign and malignant pulmonary nodules and the reader is referred to two papers for details of this protocol30,31.

Window settings

Figure 11.5 Image obtained at 80 kVp on a 64-detector MDCT in a 1-year old with cough. Right lower lobe collapse is identified but the image is unacceptably noisy, making evaluation of the lung parenchyma difficult.

Intravenous contrast medium enhancement The following section will cover the basic principles of intravenous enhancement as applied to the evaluation of pulmonary disease. Intravenous enhancement is used routinely for CT angiography of the thorax; the most common indications being the evaluation of the pulmonary arterial tree in suspected pulmonary embolism, the aorta and lung cancer staging studies. Intravenous enhancement is influenced by several factors: body size and cardiac output of the patient, the concentration and volume of contrast material, the rate and duration of the injection, the delay between the injection and the initiation of data acquisition, the duration of data acquisition and whether bolus tracking or a set delay is used. With single-detector CT, protocols are relatively straightforward. A volume of 100 ml of 150 mg ml−1 of iodine injected at a rate of 2.5 ml s−1 after a 25-s delay is recommended for general thoracic work25. Suggested protocols for evaluating the pulmonary arterial tree using single-detector CT use between 120 and 140 ml of 240–300 mg ml−1 of iodine injected at a rate of 3–4 ml s−1 26,27 with either a fixed delay of 20 s28 or the use of automated triggering mechanisms. With advances in CT technology, however, the way contrast medium is delivered has had to be rethought. A CT study acquired using a 16-detector system in < 10 s leaves little room for error, and imaging at peak enhancement requires not only precise timing but careful tailoring of the volume and rate of delivery of contrast medium. One dilemma for fast CT is the chance of contrast medium still being injected when data acquisition is complete. Protocols for CT angiography of the chest using MDCT are still being refined, but it is generally accepted that the faster acquisition times of MDCT require a faster rate of injection, a higher concentration of contrast medium and pos-

The density within each voxel is represented by a Hounsfield unit (HU) value. In the thorax these units encompass a wide range, from aerated lung (approximately −800 HU) to ribs (+700 HU). No single-window setting can depict this wide range of densities on a single image. For this reason, a thoracic CT examination requires viewing in at least two settings in order to demonstrate the lung parenchyma and the soft tissues of the mediastinum. Furthermore, it may be necessary to adjust the window settings to improve the demonstration of a particular structure or abnormality. Preferred window settings for thoracic CT vary between institutions, but some generalizations can be made. For the soft tissues of the mediastinum and chest wall a window width of 300– 500 HU and a centre of +40 HU are appropriate. For the lungs a wide window of approximately 1500 HU or more at a centre of approximately −600 HU is usually satisfactory. The window settings have a profound influence on the visibility and apparent size of normal and abnormal structures. The most accurate representation of an object appears to be achieved if the value of the window level is halfway between the density of the structure to be measured and the density of the surrounding tissue. For example, the diameter of a pulmonary nodule, measured on soft tissue settings appropriate for the mediastinum, will be grossly underestimated31. It is also important to remember that when inappropriate window settings are used, smaller structures (e.g. peripheral pulmonary vessels) are proportionately much more affected than larger structures.

HIGH-RESOLUTION COMPUTED TOMOGRAPHY For the majority of patients being investigated exclusively for suspected interstitial lung disease, interspaced (as opposed to volumetric) high-resolution CT (HRCT) remains an adequate examination and should be used for younger patients. This is because the dose of interspaced HRCT is considerably lower than a volumetric high-resolution acquisition. Even when techniques are optimized for dose, volumetric HRCT of the chest incurs a dose that is at least three times higher than interspaced HRCT, and in certain cases the dose

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increase can be up to 10-fold, particularly if a relatively high milliampere–second setting (170 mAs) is used32.The fundamental components of an HRCT technique include thin collimation, usually 1–2 mm, coupled with a high spatial frequency algorithm reconstruction. Thin collimation improves spatial resolution and consequently enhances the detection of key morphologic features in HRCT interpretation: thickened interlobular septa, ground-glass opacification, small nodules and abnormally thickened or dilated airways. Reducing the section thickness below 1 mm will not yield any significant further improvement in spatial resolution and at the same time will reduce the signal-to-noise ratio of the image. A sharp reconstruction algorithm reduces image smoothing and makes structures visibly sharper, although image noise becomes more obvious33. Images are usually obtained in the supine position from the apices to the lung bases at full inspiration and at 10- or 20-mm intervals. When early interstitial fibrosis is suspected, HRCT is often performed in the prone position to prevent confusion with the increased opacification often seen in the dependent posterobasal segments in the usual supine position (Fig. 11.6). However, there is no advantage in prone CT if there is obvious diffuse lung disease on a contemporary chest radiograph34. Prone CT is mandatory in the evaluation of asbestosis in which subtle parenchymal abnormalities are most frequently seen in the caudal parts of the posterobasal segments (Fig. 11.7)35. The necessity of expiratory CT sections is somewhat controversial. In most patients with clinically significant small airways disease, the mosaic attenuation pattern attributable to small airways disease is apparent on inspiratory images. However, images obtained at end-expiration can certainly accentuate the regional heterogeneity of lung density, thus revealing small or subtle areas of air trapping (Fig. 11.8)36,37.

• TECHNIQUES IN THORACIC IMAGING

ULTRASOUND The main advantages of chest ultrasonography are its bedside availability, absence of radiation and the ease of guided aspiration of pleural fluid and some solid tumours. Visualization of the chest wall requires a high frequency linear probe (5– 7.5 MHz), whereas pleural and pulmonary pathology is better detected with a sector or phased-array probe with a lower frequency (3.5 MHz). Most pleural fluid collections of clinical significance are readily identified on standard chest radiographs, but in the intensive care setting even small effusions may cause respiratory compromise and ultrasound (US) is an effective way of detecting and subsequently guiding aspiration. US is also valuable for identifying septations within loculated collections which may influence the choice of treatment38. With real-time US, the movement of the diaphragm may be observed and the reduced motion of paralysis may be of diagnostic value. US is also a quick and effective way of guiding percutaneous needle biopsy of peripheral lung, pleural or chest wall lesions39, but cannot be used if there is any aerated lung between the ultrasound probe and the lesion. An early study reported a potential use of US in diagnosing chest wall invasion in lung cancer staging (disruption of the pleural line which is normally seen as an echogenic interface), but this technique has not become widely used40.

Endoscopic ultrasonography Endoscopic ultrasonography (EUS) is a unique investigation in which a high-frequency US transducer is incorporated into the tip of an endoscope to provide high-resolution images of the gastrointestinal wall and structures in close proximity to the gastrointestinal tract. Linear echoendoscopes that can image parallel to the long axis of the instrument allow visualization

Figure 11.6 HRCT for suspected interstitial fibrosis. (A) Supine HRCT image of a patient being investigated for suspected interstitial lung disease reveals increased opacification in the posterior aspects of both lower lobes, which completely resolve with the patient prone (B).

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Figure 11.7 HRCT for suspected asbestosis. (A) HRCT image in the supine position demonstrates fine reticulation and increased subpleural density (arrows). (B) These changes (arrows) persist on the prone image and may represent early asbestosis in this patient who had an appropriate asbestos exposure.

Figure 11.8 (A) Inspiratory and (B) end-expiratory HRCT images in a patient with known hypersensitivity pneumonitis. There is evidence of a subtle mosaic attenuation on the inspiratory image but this is made much more conspicuous on the end-expiratory image revealing spared secondary pulmonary lobules.

of a projecting needle, relative to adjacent tissue, making EUSguided aspiration or intervention possible. Transoesophageal EUS-guided real-time fine-needle aspiration (FNA) of mediastinal lymph nodes has become a useful, minimally invasive and safe method for staging the mediastinum41–43. In patients with non-small cell lung cancer (NSCLC) who have enlarged mediastinal nodes on CT, the accuracy of EUS-guided FNA is approximately 96%43. EUS-guided FNA is particularly suited for posterior mediastinal staging, with enlarged lymph nodes in the subcarina, aortopulmonary window, para-oesophageal area and para-aortic area. EUS can also play a significant role in identifying patients with unresectable (N3) NSCLC when adenopathy was not present on CT44. The importance of histological confirmation by EUS–FNA is emphasized as echo characteristics alone are not adequately sensitive to predict malignancy.

MAGNETIC RESONANCE IMAGING General technical considerations of magnetic resonance imaging (MRI) are outlined elsewhere and its specific applications in the chest are described where appropriate in the succeeding chapters. Accumulated evidence has demonstrated that MRI is no substitute for CT in the investigation of most thoracic conditions that require cross-sectional imaging; this is largely due to the relatively poor spatial resolution of MRI, the extremely low proton density of normal lung, the further decrease of signal by strong susceptibility artefacts induced by the multiple air–soft tissue interfaces within the lung, and the consequences of cardiac and respiratory movement. The advent of MDCT has allowed the acquisition of high-resolution thin sections and with this, the ability to produce multiplanar reconstructions. Consequently, MDCT is used for most aspects of thoracic

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imaging, including areas thought previously to be the domain of ‘problem-solving’ MRI. The main indications for MRI in the chest include the evaluation of the heart and great vessels, characterization of mediastinal lesions that are equivocal on CT, evaluation of superior sulcus tumours, particularly if brachial plexus involvement is suspected, and in demonstrating pulmonary embolism if radiation and intravenous contrast medium need to be avoided. This section will summarize the spectrum of MRI techniques that are used in thoracic imaging. Traditional imaging sequences have included T1-weighted spin echo (SE) with or without the use of gadolinium chelates (for the initial detection of abnormalities or the demonstration of anatomy) and T2-weighted fast spin echo (FSE) (for further characterization of abnormalities). Occasionally, a fatsaturation MRI technique (phase-shift gradient-echo imaging or proton-selective fat-saturation imaging) can be useful to detect fat and distinguish it from haemorrhage in the evaluation of mediastinal masses45. MRI is useful in confirming the cystic nature of mediastinal lesions that appear solid on CT (cysts containing nonserous fluid can have high attenuation on CT) as these cysts will have characteristically high signal intensity when imaged with T2-weighted sequences regardless of the nature of the cyst contents. To overcome the problem of respiratory motion, other sequences (fast low-angle shot [FLASH] and half Fourier turbo-spin echo [HASTE]) have been developed that can be acquired in one breath-hold with acquisition times well below 30 s. Additional techniques to compensate for respiratory motion in non-breath-hold MRI have also been evaluated. These include navigator techniques with registration of the diaphragm, reordering of phase encoding (ROPE) and phase encoding and reordering (PEAR). Recently developed 3D gradient-recalled echo (GRE) sequences for volumetric interpolated breath-hold imaging of the lung may introduce new capabilities for MRI of lung morphology with high spatial resolution46. Early studies indicate that images obtained with this technique provide good visualization of lung anatomy with a low prevalence of artefacts47. The introduction of new lymph node-specific contrast agents used in conjunction with MRI is an interesting development. Ultrasmall superparamagnetic iron oxide nanoparticles traverse the vascular endothelium and are phagocytosed by macrophages in normally functioning lymph nodes. This results in a uniform signal loss in T2- and T2*-weighted images, a feature that was first demonstrated in animal models48. Preliminary data in patients with bronchogenic carcinoma have shown a good sensitivity, but a relatively low specificity for the diagnosis of metastatic normal sized lymph nodes49. Currently, the most important clinical application of MRI is in the imaging of the heart and great vessels, and the specific techniques required for this are dealt with in detail in Chapter 22. In summary, pulse sequences used for cardiac and great vessel imaging can generally be divided into dark or black blood, and bright or white blood imaging techniques. In black blood imaging techniques, rapidly flowing blood is black or of low signal intensity. Examples of this technique include conven-

• TECHNIQUES IN THORACIC IMAGING

tional spin-echo, breath-hold FSE or turbo spin-echo (TSE) variants with double inversion recovery pulses to suppress blood signal (HASTE, double IR TSE–FSE).These techniques are typically used for anatomical delineation of the heart, pericardium, mediastinum and great vessels. In bright blood techniques flowing blood is white or of high signal intensity.These are usually GRE sequences (Fig. 11.9). Cine GRE sequences that produce a motion picture loop throughout the cardiac cycle are used for assessment of cardiac function (and can be used to assess relative motion of adjacent structures in the context of masses abutting vessels or the heart). A single slice multiphase or multislice single-phase acquisition can be performed in a short breath-hold period. Examples of this technique include fast low angle shot (TurboFLASH), fast spoiled

Figure 11.9 (A) Black blood T1 spin-echo image and (B) white blood GRE cine image of the heart. Spin-echo imaging is particularly useful for high-definition anatomical imaging of the heart and vessels, whereas the acquisition of cine loops during a GRE sequence is useful for the assessment of valves and regional contractile function of the myocardium. (Courtesy of Dr Sanjay K. Prasad.)

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GRE, turbo field echo and fast field echo. More recently, faster short TE–GRE sequences with completely refocused gradients have been used to provide excellent contrast between myocardium and blood pool (true FISP, balanced fast field echo, FIESTA). For imaging the intrathoracic vessels, contrast-enhanced MR angiography (MRA) is performed using short, breathhold, 3D T1-weighted GRE sequences (Fig. 11.10). Using the T1-shortening effects of gadolinium-based contrast agents, blood appears bright regardless of flow patterns or velocity. Synchronization of image acquisition and arrival of the contrast bolus is crucial to obtain high image quality. Newer sequences that allow near real-time assessment of a gadolinium contrast bolus are now available, and may be useful for assessment of shunts and fistulas. There is also continued interest in the role of MRA for the diagnosis of pulmonary embolism, either by direct demonstration of the intravascular thrombus50,51 or by decreased signal areas representing underperfused lung on gadolinium-enhanced MRI52. Although still largely a research tool, the introduction of hyperpolarized noble gas imaging using either 3He or 129Xe has been used to demonstrate ventilated parts of the lung53 and

Figure 11.10 3D Gadolinium-enhanced MRA of a patient with aortic dissection. The intimal flap (arrows) is clearly delineated. (Courtesy of Dr Sanjay K. Prasad.)

thus enabled the evaluation of structure–function relationships in lung disease54. Diffusion-sensitive MRI techniques allow mapping of the ‘apparent diffusion coefficient’ (ADC) of 3He within lung spaces, where ADC is physically related to local bronchoalveolar dimensions55. ADC values are increased in fibrosis and emphysema, and show good agreement with predicted lung function56; however, these sophisticated techniques are not widely available.

VENTILATION–PERFUSION SCINTIGRAPHY Ventilation–perfusion (V/Q) scintigraphy is a noninvasive technique for the assessment of the distribution of pulmonary blood flow and alveolar ventilation and has primarily been used for the diagnosis of pulmonary embolism. Perfusion scintigraphy is performed following the intravenous injection of 99m Tc-labelled protein microparticles which, because of their size, undergo micro-embolization in the pulmonary vascular bed. The number of particles injected may range from a minimum of 60 000 to a maximum of 700 000, with the recommended average being 200 000. Because of the theoretical possibility of embolization of a medium-sized systemic vessel, microspheres should be used rather than larger macroaggregates in the presence of a known right-to-left shunt. Krypton-81m is in many ways the ideal agent of choice for ventilation imaging but it has a very short half-life and is expensive to produce. Unlike longer-lived radioactive gases, such as 133Xe, 81mKr does not accumulate progressively in regions of lung with a low ventilatory turnover. The lung can be imaged in multiple projections and in each projection, perfusion and ventilation images can be acquired sequentially, or, with the newer digital cameras, simultaneously. Another commonly used agent for ventilation imaging is 133Xe (half-life of 5.3 d). 133Xe has three advantages over 81mKr: it is cheaper, is readily available in comparison to 81mKr which is available from its generator for 1 d only, and it can be used to detect air trapping. Since the energy of 133Xe is less than that of 99mTc, the ventilation images must be acquired before the 99mTc injection. Furthermore, only one projection is available and, with the lower energy of xenon, the images are of poorer resolution. Other agents include 99mTc-diethylenetriaminepentaacetic or 99mTc-technegas. Technegas is an ultrafine aerosol that is considered to behave truly like a gas due to the mean aerodynamic diameter of the particles being between 30 and 90 nm. The small particle size results in efficiency values of up to 20% (efficiency being defined as the ratio between the amount of applied activity and its actual pulmonary deposition) compared to conventional aerosols which show a degree of efficiency between 1 and 3%. Lung scintigraphy remains part of the diagnostic algorithm in the investigation of patients with pulmonary embolism, and guidelines suggest that it may be considered, subject to its availability, as the initial imaging investigation provided the chest radiograph is normal and there is no significant symptomatic concurrent cardiopulmonary disease57. A recent study evaluating ventilation–perfusion lung scintigraphy performed using SPECT technique (as opposed to

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merely using planar acquisitions) has shown that diagnostic accuracy is comparable with MDCT (four-detector system with 1.25-mm effective slice thickness)58. Analogous to developments in the fields of neurology and cardiology, it can be expected that SPECT will replace planar lung scintigraphy in the near future, but lack of availability will mean that this technique is unlikely to be frequently used for patients with suspected pulmonary embolism.

POSITRON EMISSION TOMOGRAPHY Positron emission tomography (PET) was initially used as a research tool for functional studies of the brain and the assessment of cardiac metabolism, but in the past 8 years most of its indications have been in the ambit of assessment of patients with suspected malignancy, particularly those being considered for surgery59. The different applications relevant to lung cancer are listed in Table 11.3, but a discussion of the advantages of PET in the staging of lung cancer is given in Chapter 18. The use of [F-18]fluoro-2-deoxy-glucose (FDG)-PET in oncology is based on its ability to identify the differences between glucose metabolism in various tissues. Neoplastic cells have a much higher rate of glycolysis that non-neoplastic cells. [F 18]FDG, a glucose analogue in which the oxygen molecule in position 2 is replaced by the positron-emitting 18 F, undergoes the same uptake as glucose, but is metabolically trapped and accumulates in neoplastic cells after phosphorylation by hexokinase. To gain a quantitative measure of FDG uptake, attenuationcorrected images are required; this is because the intensity of the photon emission of a lesion is position dependent, and therefore the intensity seen on the nonattenuation corrected whole-body images does not truly reflect the actual FDG uptake. If the images are corrected for photo-attenuation by a ‘transmission’ study which estimates the attenuating characteristics of the patient, quantification of FDG metabolism becomes possible. The use of a transmission study allows the

Table 11.3 INDICATIONS FOR [F-18]FLUORO-2DEOXYGLUCOSE PET IN RESPIRATORY ONCOLOGY Common clinical indications Evaluation of nodules and masses

• TECHNIQUES IN THORACIC IMAGING

Standardized Uptake Value (SUV) to be reported.The SUV of a lesion is a semiquantitative index of glucose utilization that is obtained by normalizing the accumulation of FDG in the lesion to the injected dose and patient body weight60.The criterion for a positive result is either greater uptake in the lesion than in the background mediastinum or a SUV of > 2.561. The most important role of FDG–PET is in the clarification of the nature of an incidental nodule or mass identified on an ‘anatomical’ study62. Based on several prospective studies, FDG–PET has proven to be accurate in differentiating benign from malignant lesions as small as 1 cm with an overall sensitivity of 96% (range 83–100%) and specificity of 79% (range 52–100%). Potential pitfalls in sensitivity are due to the fact that a critical mass of metabolically active malignant cells is required for PET diagnosis; false-negative findings can occur in lesions < 1 cm63 and in lesions with low metabolic activity, e.g. carcinoid tumours64 and bronchioloalveolar cell carcinomas65. Errors in specificity are due to FDG uptake in inflammatory conditions, such as bacterial pneumonia66 and particularly granulomatous diseases such as sarcoidosis67, tuberculosis, or Wegener’s granulomatosis. A further emerging use of PET is in the staging of nodal metastases with studies consistently showing significantly greater accuracy of PET compared with CT for the detection or exclusion of mediastinal nodal disease68. The use of PET will undoubtedly increase as the technique becomes more available and a routine part of the investigative algorithm of patients with suspected lung cancer. Table 11.4 summarizes the indications for PET in the diagnosis and staging of patients with lung cancer. PET may well have a role in the evaluation of other intrathoracic malignancies, particularly in the assessment of response to chemotherapy that may occur before there is any discernible morphological change in the tumour on conventional imaging. Finally, a whole new field—applying PET to molecular biology using new radiopharmaceutical probes—is under investigation. These techniques may allow the evaluation of molecular-targeted lung cancer therapies or even gene therapy.

POSITRON EMISSION TOMOGRAPHY– COMPUTED TOMOGRAPHY PET/CT imaging was introduced in 1998.The concept of combined PET/CT imaging is to supplement metabolic information

Locoregional staging Extrathoracic staging Applications under investigation Radiotherapy planning Evaluation of response post radiotherapy Evaluation of response post (induction) chemotherapy Follow-up and diagnosis of recurrence Molecular applications Early assessment of chemotherapy Assessment of molecular targeted therapy

Table 11.4 INDICATIONS FOR PET IN THE STAGING OF LUNG CANCER All patients who are staged on CT as candidates for surgery: to identify involved intrathoracic lymph nodes and distant metastases Patients who are otherwise surgical candidates but have, on CT, limited (one to two stations) N2/N3 disease of uncertain pathological significance All patients who are candidates for radical radiotherapy To investigate solitary pulmonary nodules in cases in which biopsy is not possible or has failed, depending on nodule size

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from a whole-body PET study with more detailed anatomical information, thereby improving diagnostic accuracy.

Image acquisition Conventional PET employs transmission images for photon attenuation correction using an external radiation source and consequently, a conventional whole-body PET study covering six to eight bed positions requires about 1 h for completion. PET/CT imaging differs in that it utilizes whole-body CT data for attenuation correction. Depending on the number of CT detectors used, attenuation correction is achieved within seconds to slightly over 1 min and thus whole-body imaging times are reduced by 50%. The incremental value of PET/CT over PET alone for staging and restaging of cancer has not been fully established, but preliminary data suggest significant increments in diagnostic and staging accuracy of NSCLC69,70. The latter study demonstrated that tumour staging and nodal staging were significantly more accurate with integrated PET/CT than with PET alone. Moreover, PET/CT provided additional information in 41% of patients, including localization of lymph nodes (n = 9), precise identification of chest wall infiltration (n = 3), correct differentiation between tumour and inflammation (n = 7) and localization of distant metastases (n = 2)70. However, it is important to note that this study did not examine prospectively whether the ‘additional information’ led to significant changes in patient management. More clinical trials with greater patient numbers will be required to firmly establish possible advantages of PET/CT over PET or CT alone for each type of cancer.

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9. Hu H, He H D, Foley W D, et al 2000 Four multidetector-row helical CT: image quality and volume coverage speed. Radiology 215: 55–62 10. McCollough C H, Zink F E 1999 Performance evaluation of a multi-slice CT system. Med Phys 26: 2223–2230 11. Pappas J N, Donnelly L F, Frush DP 2000 Reduced frequency of sedation of young children with multisection helical CT. Radiology 215: 897–899 12. Wormanns D, Kohl G, Klotz E et al 2004 Volumetric measurements of pulmonary nodules at multi-row detector CT: in vivo reproducibility. Eur Radiol 14: 86–92 13. Yi C A, Lee K S, Kim E A et al 2004 Solitary pulmonary nodules: dynamic enhanced multi-detector row CT study and comparison with vascular endothelial growth factor and microvessel density. Radiology 233: 191–199 14. Revel M P, Petrover D, Hernigou A et al 2005 Diagnosing pulmonary embolism with four-detector row helical CT: prospective evaluation of 216 outpatients and inpatients. Radiology 234: 265–273 15. International Electrotechnical Commission 2002 60601-2-44 Amendment 1. Medical Electrical Equipment, part 2-44: Particular requirements for the safety of x-ray equipment for computed tomography. International Electrotechnical Commission, Geneva 16. Flohr T G, Schaller S, Stierstorfer K et al 2005 Multi-detector row CT systems and image-reconstruction techniques. Radiology 235: 756–773 17. Kalra K K, Maher M M, Toth T L et al 2004 Strategies for CT radiation dose optimization. Radiology 230: 619–628 18. Jung K J, Lee K S, Kim S Y et al 2000 Low-dose, volumetric helical CT: image quality, radiation dose, and usefulness for evaluation of bronchiectasis. Invest Radiol 35: 557–563 19. Yi C A, Lee K S, Kim T S et al 2003 Multidetector CT of bronchiectasis: effect of radiation dose on image quality. Am J Roentgenol 181: 501–505 20. Itoh S, Ikeda M, Arahata S et al 2000 Lung cancer screening: minimum tube current required for helical CT. Radiology 215: 175–183 21. Schoepf U J, Becker C R, Obuchowski N A et al 2001 Multi-slice computed tomography as a screening tool for colon cancer, lung cancer and coronary artery disease. Eur Radiol 11: 1975–1985 22. Cody D D, Moxley D M, Krugh K T et al 2004 Strategies for formulating appropriate MDCT techniques when imaging the chest, abdomen, and pelvis in pediatric patients. Am J Roentgenol 182: 849–859 23. Mahesh M, Scatarige J C, Cooper J et al 2001 Dose and pitch relationship for a particular multislice CT scanner. Am J Roentgenol 177: 1273–1275 24. Greess H, Nomayr A, Wolf H et al 2002 Dose reduction in CT examination of children by an attenuation-based on-line modulation of tube current (CARE Dose). Eur Radiol 12: 1571–1576 25. Leung A N 1997 Spiral CT of the thorax in daily practice: optimization of technique. J Thorac Imag 12: 2–10 26. Remy-Jardin M, Remy J, Artaud D et al 1997 Peripheral pulmonary arteries: optimization of the spiral CT acquisition protocol. Radiology 204: 157–163 27. Kuzo R S, Goodman L R 1997 CT evaluation of pulmonary embolism: technique and interpretation. Am J Roentgenol 169: 959–965 28. Hartmann I J, Lo R T, Bakker J et al 2002 Optimal scan delay in spiral CT for the diagnosis of acute pulmonary embolism. J Comput Assist Tomogr 26: 21–25 29. Schoellnast H, Deutschmann H A, Fritz G A et al 2005 MDCT angiography of the pulmonary arteries: Influence of iodine flow concentration on vessel attenuation and visualization. Am J Roentgenol 184: 1935–1939 30. Swensen S J, Viggiano R W, Midthun D E et al 2000 Lung nodule enhancement at CT: multicenter study. Radiology 214: 73–80 31. Harris K M, Adams H, Lloyd D C F et al 1993 The effect on apparent size of simulated pulmonary nodules of using three standard CT window settings. Clin Radiol 47: 241–244 32. Kelly D M, Hasegawa I, Borders R et al 2004 High-resolution CT using MDCT: Comparison of degree of motion artefact between volumetric and axial methods. Am J Roentgenol 182: 757–759 33. Murata K, Khan A, Rojas K A et al 1988 Optimization of computed tomography technique to demonstrate the fine structure of the lung. Invest Radiol 23: 170–175

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34. Volpe J, Storto M L, Lee K et al 1997 High-resolution CT of the lung: determination of the usefulness of CT scans obtained with the patient prone based on plain radiographic findings. Am J Roentgenol 169: 369–374 35. Aberle D R, Gamsu G, Ray C S 1988 High-resolution CT of benign asbestos-related diseases: Clinical and radiographic correlation. Am J Roentgenol 151: 883–891 36. Arakawa H, Webb W R, McCowin M et al 1998 Inhomogeneous lung attenuation at thin-section CT: diagnostic value of expiratory scans. Radiology 206: 89–94 37. Lucidarme O, Coche E, Cluzel P et al 1998 Expiratory CT scans for chronic airway disease: correlation with pulmonary function test results. Am J Roentgenol 170: 301–307 38. Lomas D J, Padley S P G, Flower C D R 1993 The sonographic appearances of pleural fluid. Br J Radiol 66: 619–624 39. Yang P C 1997 Ultrasound-guided transthoracic biopsy of peripheral lung, pleural, and chest-wall lesions. J Thorac Imag 12: 272–284 40. Suzuki N, Saitoh T, Kitamura S 1993 Tumour invasion of the chest wall in lung cancer: diagnosis with US. Radiology 187: 39–42 41. Fritscher-Ravens A, Soehendra N, Schirrow L et al 2000 Role of transesophageal endosonography-guided fine-needle aspiration in the diagnosis of lung cancer. Chest 117: 339–345 42. Bhutani M S, Hawes R H, Hoffman B J 1997 A comparison of the accuracy of echo features during endoscopic ultrasound (EUS) and EUSguided fine-needle aspiration for diagnosis of malignant lymph node invasion. Gastrointest Endosc 45: 474–479 43. Gress F G, Savides T J, Sandler A et al 1997 Endoscopic ultrasonography, fine-needle aspiration biopsy guided by endoscopic ultrasonography, and computed tomography in the preoperative staging of non-smallcell lung cancer: a comparison study. Ann Intern Med 127: 604–612 44. LeBlanc J, Devereaux B M, Imperiale T F et al 2005 Endoscopic ultrasound in non-small cell lung cancer and negative mediastinum on computed tomography. Am J Respir Crit Care Med 171: 177–182 45. Outwater E K, Siegelman E S, Hunt J L 2001 Ovarian teratomas: tumor types and imaging characteristics. RadioGraphics 21: 475–490 46. Semelka R C, Cem B N, Wilber K P et al 2000 Breath-hold 3D gradientecho MR imaging of the lung parenchyma: evaluation of reproducibility of image quality in normals and preliminary observations in patients with disease. J Magn Reson Imaging 11: 195–200 47. Biederer J, Both M, Graessner J et al 2003 Lung morphology: fast MR imaging assessment with a volumetric interpolated breath-hold technique: initial experience with patients. Radiology 226: 242–249 48. Vassallo P, Matei C, Heston W D et al 1994 AMI-227-enhanced MR lymphography: usefulness for differentiating reactive from tumorbearing lymph nodes. Radiology 193: 501–506 49. Pannu H K, Wang K P, Borman T L et al 2000 MR imaging of mediastinal lymph nodes: evaluation using a superparamagnetic contrast agent. J Magn Reson Imag 12: 899–904 50. Meaney J F M, Weg J G, Chenevert T L et al 1997 Diagnosis of pulmonary embolism with magnetic resonance angiography. N Engl J Med 336: 1422–1427 51. Gupta A, Frazer C K, Ferguson J M et al 1999 Acute pulmonary embolism: diagnosis with MR angiography. Radiology 210: 353–359 52. Amundsen T, Kvaerness J, Jones R A et al 1997 Pulmonary embolism: detection with MR perfusion imaging of lung—a feasibility study. Radiology 203: 181–185 53. Kauczor H U, Hofmann D, Kreitner K F et al 1996 Normal and abnormal pulmonary ventilation: visualization at hyperpolarized He-3 MR imaging. Radiology 201: 564–568 54. Eberle B, Markstaller K, Schreiber W G et al 2001 Hyperpolarised gases in magnetic resonance: a new tool for functional imaging of the lung. Swiss Med Wkly 131: 503–599 55. Hanisch G, Schreiber W, Diergarten T et al 2000 Investigation of intrapulmonary diffusion by 3He MRI. Eur Radiol 10 (suppl 1): S345

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56. Kauczor H 2003 Hyperpolarized helium-3 gas magnetic resonance imaging of the lung. Top Magn Reson Imaging 14: 223–230 57. British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax 58: 470–483 58. Reinartz P, Wildberger J E, Schaefer W et al 2004 Tomographic imaging in the diagnosis of pulmonary embolism: a comparison between V/Q lung scintigraphy in SPECT technique and multislice spiral CT. J Nucl Med 45: 1501–1508 59. Vansteenkiste J F 2002 Imaging in lung cancer: positron emission tomography scan. Eur Respir J 19 (suppl 35): 49s–60s 60. Meikle S R, Bailey D L, Hooper P K et al 1995 Simultaneous emission and transmission measurements for attenuation correction in wholebody PET. J Nucl Med 36: 1680–1688 61. Patz E F, Lowe V J, Hoffman J M et al 1993 Focal pulmonary abnormalities: evaluation with F-18 fluorodeoxyglucose PET scanning. Radiology 188: 487–490 62. Vansteenkiste J F, Stroobants S G, De Leyn P R et al 1997 Mediastinal lymph node staging with FDG-PET scan in patients with potentially operable non-small cell lung cancer: a prospective analysis of 50 cases. Leuven Lung Cancer Group. Chest 112: 1480–1486 63. Dewan N A, Gupta N C, Redepenning L S et al 1993 Diagnositc efficacy of PET-FDG imaging in solitary pulmonary nodules. Potential role in evaluation and management. Chest 104: 997–1002 64. Erasmus J J, McAdams H P, Patz E F Jr et al 1998 Evaluation of primary pulmonary carcinoid tumors using FDG PET. Am J Roentgenol 170: 1369–1373 65. Kim B T, Kim Y, Lee K S et al 1998 Localized form of bronchioloalveolar carcinoma. FDG PET findings. Am J Roentgenol 170: 935–939 66. Kapucu L O, Meltzer C C, Townsend D W et al 1998 Fluorine-18fluorodeoxyglucose uptake in pneumonia. J Nucl Med 39: 1267–1269 67. Brudin L H, Valind S O, Rhodes C G et al 1994 Fluorine-18 deoxyglucose uptake in sarcoidosis measured with positron emission tomography. Eur J Nucl Med 21: 297–305 68. Steinert H C, Hauser M, Allemann F et al 1997 Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node mapping and sampling. Radiology 202: 441–446 69. Cerfolio R J, Ojha B, Bryant A S et al 2004 The accuracy of integrated PET-CT compared with dedicated PET alone for the staging of patients with nonsmall cell lung cancer. Ann Thorac Surg 78: 1017–1023 70. Lardinois D, Weder W, Hany T F et al 2003 Staging of non-smallcell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 348: 2500–2507

SUGGESTED FURTHER READING Flohr T G, Schaller S, Stierstorfer K et al 2005 Multi-detector row CT systems and image-reconstruction techniques. Radiology 235: 756–773 Kalra M K, Maher M M, Toth T L et al 2004 Strategies for CT radiation dose optimization. Radiology 230: 619–628 Kauczor H U, Chen X J, Beek E R J et al 2001 Pulmonary ventilation imaged by magnetic resonance: at the doorstep of clinical application. Eur Respir J 17: 1008–1023 Müller N L 2002 Computed tomography and magnetic resonance imaging: past, present and future. Eur Respir J 19 (suppl 35): 3s–12s Remy-Jardin M, Remy J, Mayo J R et al 2001 CT angiography of the chest. Lippincott, Williams and Wilkins, Philadelphia Schoepf U J (ed) 2004 Multidetector-row CT of the thorax. Springer Verlag, Berlin Schrevens L, Lorent N, Dooms C et al 2004 The role of PET scan in diagnosis, staging and management of non-small cell lung cancer. Oncologist 9: 633–643

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The Normal Chest

12

Simon Padley and Sharyn L. S. MacDonald

• • • • • •

The lungs The central airways The lungs beyond the hila The hila The mediastinum The diaphragm

THE LUNGS Each lung is divided into lobes surrounded by pleura. There are two lobes on the left: the upper and lower, separated by the major (oblique) fissure; and three on the right: the upper, middle and lower lobes separated by the major (oblique) and minor (horizontal) fissures. The fissures are frequently incomplete, particularly medially, containing localized defects which form an alveolar pathway for collateral air drift and the spread of disease. For a fissure to be visualized on conventional radiographs, the X-ray beam has to be tangential to the fissure. In most people, some or all of the minor fissure is seen in the frontal projection, but neither major fissure can be identified. In the lateral view, both the major and minor fissures are often identified, but usually only part of any fissure is seen; in fact, it is very unusual to see both left and right major fissures in their entirety. The major fissures have similar anatomy on the two sides. They run obliquely anteriorly and inferiorly from approximately the fifth thoracic vertebra to pass through the hilum and contact the diaphragm 0–3 cm behind the anterior costophrenic angle. Each major fissure follows a gently curving plane somewhat similar to a propeller blade (Fig. 12.1), with the upper portion facing anteriorly and laterally, and the lower portion facing forward and medially. Owing to the undulating course of the major fissure, either fissure may be seen as two lines on the lateral view. Consequently it may appear to the unwary that a fissure is displaced when it is in fact in its normal position, or both fissures may appear to be in their normal positions when in reality one of them is so displaced that it is no longer visible.

The inferior few centimetres of either or both major fissures may be widened owing to the presence of fat or pleural thickening between the leaves of the pleura. In these circumstances the contact with the diaphragm will often be broadened and lead to a localized loss of silhouette, an appearance referred to as the juxtaphrenic peak. With modern multislice computed tomography (CT), the normal major fissures are frequently visible, but if not clearly defined the position can be inferred from the presence of a relatively avascular zone that forms the outer cortex of the lobe. With high-resolution CT (HRCT), a normal major fissure is seen as a thin line traversing the avascular zone1, although it may be represented as two parallel lines on at least one level in approximately one-third of the population because of an artefact related to cardiac and respiratory motion2. The minor fissure fans out anteriorly and laterally from the right hilum in a horizontal direction to reach the chest wall. On a standard chest radiograph, the minor fissure contacts the chest wall at the axillary portion of the right sixth rib. The fissure curves gently, with its anterior and lateral portion usually curving downwards. Because of the curvature of the major fissure described above, part of the minor fissure may be projected posterior to the right major fissure on the lateral view. On CT the minor fissure position is represented by an oval area of reduced vascularity at the level of the bronchus intermedius (Fig. 12.2). The normal minor fissure is not seen as a line on axial CT imaging but is apparent on multiplanar reformats. In 1% of the population an accessory fissure3 called the ‘azygos lobe fissure’ (Fig. 12.3) is seen. This fissure contains the azygos vein at its lower end and results from failure of normal migration of the azygos vein from the chest wall to its usual position in the tracheobronchial angle and persistence of the invaginated visceral and parietal pleurae.There is no corresponding alteration in the segmental architecture of the lung, so the term ‘lobe’ is a misnomer. The ‘azygos lobe’ may, however, be smaller and therefore less transradiant than corresponding normal lung4. On CT the altered course of the azygos vein can be seen traversing the lung (Fig.12.3B).

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Figure 12.1 The different position and shape of the major fissures (arrows) in the lower and the upper zones is well shown by CT. Note that (A) below the hila, the major fissures bow forward, whereas (B) above the hila, the major fissures bow backward. (The images are high-resolution thin-section [1.5 mm] CT scans.) Sagittal reformats from the (C) right and (D) left lungs demonstrate the detail of fissure anatomy available on this 16-channel CT study.

Figure 12.2 Minor fissure on CT. (A) The minor fissure is apparent as an area of avascularity anterior to the major fissure. In this example the slightly bowed horizontal fissure undulates through the plane of the slice. (B) The position of the minor fissure, in another patient, is indicated by the oval deficiency of vessels in the right mid zone (arrows).

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• THE NORMAL CHEST

Figure 12.3 (A) Azygos lobe fissure (curved arrows) and aortic nipple (horizontal straight arrow). The azygos vein in the lower end of the fissure is well seen (lower curved arrow). Note its absence from its usual location in the right tracheobronchial angle (open arrow). The aortic nipple, due to the left superior intercostal vein, is particularly large in this example. (B) CT of the azygos lobe fissure.

Other accessory fissures are occasionally identified3. A minor fissure may separate the lingular segments from the remainder of the upper lobe, similar to the right minor fissure. A horizontally orientated fissure, a superior accessory fissure, may separate the apical segment from the basal segments of either lower lobe. An inferior accessory fissure is sometimes seen in one or other lower lobe, usually the right, separating the medial and anterior basal segments. This fissure runs obliquely upward and medially towards the hilum from the diaphragm. The inferior pulmonary ligaments5 are pleural reflections from the mediastinum which hang down from the hila and are analogous in shape to the peritoneal reflections forming the broad ligament of the uterus. These two layers of pleura may extend down to the diaphragm or may have a free inferior edge. The intersegmental septum of the lower lobe, a septum within the lung immediately beneath the inferior pulmonary ligament, is often visible on CT (Fig. 12.4)6.When the inferior pulmonary ligament reaches the diaphragm it may contain a small amount of fat. This may efface the diaphragm, resulting in a juxtaphrenic peak. Otherwise neither the intersegmental septum nor the inferior pulmonary ligament is visible on plain radiographs.

THE CENTRAL AIRWAYS The trachea is a straight tube that, in children and young adults, passes inferiorly and posteriorly in the midline. In subjects

Figure 12.4 Intersegmental septum deep to the inferior pulmonary ligament shown by CT (arrows).

with unfolding and ectasia of the aorta the trachea may deviate to the right and may also bow forward. In cross-section the trachea is usually round, oval, or oval with a flattened posterior margin. Maximum coronal and sagittal diameters in adults on plain chest radiography are 21 and 23 mm, respectively, for women, and 25 and 27 mm for men7. On CT, which allows precise assessment of diameters and cross-sectional areas without magnification, the mean transverse diameter is 15.2 mm (sd 1.4) for women and 18.2 mm (sd 1.2) for men,

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the lower limit of normal being 12.3 mm for women, and 15.9 mm for men8. The diameters in growing children and young adults have been documented9. Calcification of the cartilage rings of the trachea is a common normal finding after the age of 40 years, increasing in frequency with age. The trachea divides into the two mainstem bronchi at the carina. In children the angles are symmetrical, but in adults the right mainstem bronchus has a steeper angle than the left. The range of angles is wide, and alterations in angle can be diagnosed only by right–left comparisons, not by absolute measurement. The left main bronchus extends up to twice as far as the right main bronchus before giving off its upper lobe division. The lobar and segmental branching pattern is shown in Figure 12.5. There are many variations of the segmental and subsegmental branches10,11. Airways to subsegmental level can be routinely identified on volumetric thin-collimation CT.

THE LUNGS BEYOND THE HILA The usual method of deciding normal lung density in the frontal view is by comparison with equivalent areas on the opposite side. Since this is not possible on the lateral chest radiograph, the detection of subtle densities is more difficult, but the density over the spine should decrease gradually as the eye travels down the spine until the diaphragm is reached. Certain other comparisons can be made, but are less reliable: the density of the high retrosternal areas is approximately equal to that of the area immediately posterior to the left ventricle; the density over the heart is usually similar to that over the shoulders; and, apart from the cardiac fat pads and overlying ribs, there should be no abrupt change in density over the heart shadow. The segmental bronchi divide into smaller and smaller divisions until after 6–20 divisions they become bronchioles and

Figure 12.5 Diagram illustrating the anatomy of the main bronchi and segmental divisions. The nomenclature is that approved by the Thoracic Society. (Courtesy of the Editors of Thorax.)

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no longer contain cartilage in their walls. The bronchioles divide and the last of the purely conducting airways are known as the terminal bronchioles, beyond which lie the alveoli. The walls of the segmental bronchi are invisible on the chest radiograph unless seen end-on, when they may cause ring shadows (Fig.12.6). The acinus, which is 5–6 mm in diameter, comprises respiratory bronchioles, alveolar ducts and alveoli. The acini are grouped together in lobules of three to five acini which, in the lung periphery, are separated by septa and together comprise

the secondary pulmonary lobule.These peripheral interlobular septa, when thickened by disease, are the so-called septal or Kerley B lines. The bronchopulmonary segments are based on the divisions of the bronchi.The boundaries between segments are complex in shape and have been likened to the pieces of a three-dimensional (3D) jigsaw puzzle; there is no septation between them (except in the rare instance of a patient with accessory fissures). Atelectasis or pneumonia may predominate in one or other segment, but rarely conforms precisely to the whole of just one segment, since collateral air drift occurs across the segmental boundary. The position of the segments as seen on standard radiographs is illustrated in Figure 12.7. The pulmonary blood vessels (Fig. 12.8) are responsible for branching linear markings within the lungs both on conventional radiographs and CT. It is not possible to distinguish arteries from veins in the outer two-thirds of the lungs on plain radiographs. Centrally, the orientations of the arteries and veins differ: the lower lobe veins run more horizontally and the lower lobe arteries more vertically. In the upper lobes, the arteries and veins show a similar gently curving vertical orientation, but the upper lobe veins (when not superimposed on the arteries) lie lateral to the arteries and can sometimes be traced to the main venous trunk, the superior pulmonary vein. The diameter of the blood vessels beyond the hilum varies with the position of the patient and with various haemodynamic factors. On plain chest radiographs taken in the upright position, there is a gradual increase in the relative diameter of vessels equivalent in distance from the hilum as the eye travels from apex to base.The differences are abolished when the patient lies supine. These observations correlate

Figure 12.6 Ring shadows (arrows) due to end-on bronchi as a normal finding on chest radiography. The patient has a dual chamber pacing system.

1

6 10

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4 9

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17

• THE NORMAL CHEST

16

Figure 12.7 Diagrams of position of segments seen on plain frontal and lateral chest radiographs. There is substantial overlap of the projected images of the segments in both views; this overlap is worse in the frontal than the lateral projection. (A) Shows only the segments in the upper lobes and the middle lobe; (B) shows only the segments in the lower lobes; (C,D) show all the segments in the right and left lung, respectively, in the lateral view. H = hila, 1 = apical segment of right upper lobe (RUL), 2 = posterior segment of RUL, 3 = anterior segment of RUL, 4 = lateral segment of right middle lobe (RML), 5 = medial segment of RML, 6 = apical posterior segment of left upper lobe (LUL), 7 = anterior segment of LUL, 8 = superior segment of lingula, 9 = inferior segment of lingula, 10 = apical (superior) segment of right lower lobe (RLL), 11 = medial basal segment of RLL, 12 = anterior basal segment of RLL, 13 = lateral basal segment of RLL, 14 = posterior basal segment of RLL, 15 = apical (superior) segment of left lower lobe (LLL), 16 = anterior basal segment of LLL, 17 = lateral basal segment of LLL, 18 = posterior basal segment of LLL.

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Figure 12.8 Pulmonary angiogram shows appearances in (A) arterial phase and (B) venous phase. Note the difference in arrangement of the central arteries and veins. The peripheral arteries show similar anatomy to the peripheral veins. (C) Coronal maximum intensity projection slab image from a CT pulmonary angiogram demonstrating the combined arterial and venous phase image in a patient with normal circulation.

with physiological studies of perfusion which show that in the erect position there is a gradation of blood flow (the lower zones showing greater blood flow than the upper zones) from apex to base, a difference that is less obvious in the supine patient. While a general statement regarding these differences in zonal blood vessel size can be made, it is difficult to draw conclusions from the size of any particular peripheral pulmonary vessel. Certain measurements have, however, been suggested for upright chest radiographs: 1 The artery and bronchus of the anterior segment of either or both upper lobes are frequently seen end-on.The diameter of the artery is usually much the same as the diameter of the bronchus (4–5 mm). In the authors’ experience, an endon vessel with a diameter of over 1.5 times the diameter of the adjacent bronchus indicates that the vessel is increased in size. 2 Vessels in the first anterior interspace should not exceed 3 mm in diameter. A rich network of lymphatic vessels drains the lung and pleura to the hilar lymph nodes. The sub-pleural lymphatics are found beneath the pleura at the junction of the interlobular septa with the pleura. These vessels connect with each other and with the lymphatic vessels accompanying the veins in the interlobular septa. Lymph then flows to the hilum via deep lymphatic channels that run peribronchially and in the deep septa of the lungs. Under normal circumstances the lymphatic network is invisible radiographically but when thickened the septa are seen as line shadows known as septal or Kerley lines. Thickened interlobular septa correspond to Kerley B lines and thickened deep septa correspond to Kerley A lines. There are a few intrapulmonary lymph nodes, but they are small and cannot be identified on a chest radiograph but may be seen as small, peripherally located ellipsoid nodules on CT12,13.

THE HILA Understanding the normal hilum on plain radiography, CT and magnetic resonance imaging (MRI) requires an appreciation of the anatomy of the major blood vessels (Figs 12.9–12.13). On plain radiograph and CT the densities of the normal hilum are due mainly to blood vessels (Figs 12.10–12.12). Normal lymph nodes cannot be recognized as discrete structures, and the bronchial walls contribute little to the bulk of the hila, being thin and easily recognized for what they are. On MRI (Fig. 12.13), the lack of signal from fast-flowing blood within the vessels or from air in the bronchi means that there is relatively little signal generated from normal hilar structures on standard spin-echo sequences. The only signal will be from slow-flowing blood in the vessels, from the bronchial walls, and from the fat and hilar nodes. Normal lymph nodes of just a few millimeters in size are often evident as discrete structures on submillimeter collimation multislice CT. The major points to remember when viewing the hila are: 1 The transverse diameter of the lower lobe arteries before their segmental divisions can be determined with reasonable accuracy: they measure 9–16 mm on the normal postero-anterior (PA) chest radiograph (Fig. 12.11). 2 The posterior walls of the right main bronchus and its division into the right upper lobe bronchus and bronchus intermedius are outlined by air and appear as a thin stripe on lateral plain radiographs (Fig. 12.14) and on CT (Fig. 12.12).The posterior walls of the equivalent bronchi on the left are rarely visible on the plain radiograph because the left lower lobe artery intervenes between the lung and the bronchial tree. The lung does, in fact, frequently invaginate between the left lower lobe artery and the descending aorta to contact the posterior wall of the left lower lobe bronchus, but this is usually only visible on CT or MRI. 3 The right pulmonary artery passes anterior to the major bronchi, whereas the left pulmonary artery arches superior to the left main bronchus. The central portion of the right

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• THE NORMAL CHEST

Figure 12.9 Diagrams of the relationships between the hilar blood vessels and bronchi. (A) Frontal view. (B) Right posterior oblique view of right hilum. (C) Left posterior oblique view of left hilum. (D) Lateral chest radiograph with major blood vessels drawn in. IPV = inferior pulmonary vein—only one has been drawn in since they are superimposed, LPA = left pulmonary artery, LSPV = left superior pulmonary vein, RPA = right pulmonary artery; RSPV = right superior pulmonary vein. (Diagrams drawn by Ron Ervin and reproduced with permission from Armstrong P (ed) 1983 Critical problems in diagnostic radiology. Lippincott, Philadelphia.)

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Figure 12.10 Normal digital PA chest radiograph demonstrating position and density of the hilar structures. Arrows indicate the hilar points, where the superior pulmonary vein crosses the descending lower lobe artery, the left normally being level with or slightly higher than the right.

Figure 12.11 Frontal view of hila in plain chest radiograph. The measurement points for the diameter of the right lower lobe artery are indicated.

Figure 12.12 CT of normal hila. Two-millimetre collimation images have been obtained through the hilar structures during contrast medium enhancement and displayed on lung windows (L-500, W 1500). (A) Section just below the tracheal carina at the origin of the right upper lobe bronchus, immediately posterior to the upper lobe vein (v). (B) Section through level of right main pulmonary artery (RPA) and bronchus intermedius (curved arrow). Note the tongue of lung that contacts the left main bronchus between the aorta (A) and the left lower lobe artery (straight arrow). Note also that the right lung contacts the posterior wall of the bronchus intermedius as it extends into the azygo-oesophageal recess. (C) Section through the level of the middle lobe bronchus (long arrow) at the point of origin of the bronchus to the superior segment of the right lower lobe (arrow). Note that the middle lobe bronchus separates the right lower lobe artery from the right superior pulmonary vein as it enters the left atrium (LA). The lung contacts the posterior wall of the right lower lobe bronchus as it extends into the azygo-oesophageal recess. (D) Section through the level of the inferior pulmonary veins (arrows). At this level the lower lobe arteries have bilaterally divided into basal segmental divisions and are therefore narrower than 1 cm in diameter.

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5 The pulmonary veins are similar on the two sides.The superior pulmonary vein is the anterior structure in the upper and mid hilum on both sides. Since, however, the central portions of the pulmonary arteries are so differently organized on the two sides, the relationships of the major veins to the arteries differ. On the right the superior pulmonary vein is separated from the central bronchi by the lower division of the right pulmonary artery, whereas on the left the superior pulmonary vein is separated from the pulmonary artery by the bronchial tree.

Figure 12.13 MRI of normal hilum. Note that there is relatively little signal from the hila because there is no signal either from air in the bronchial tree or from fast-flowing blood in the pulmonary artery or vein branches.

Both inferior pulmonary veins travel obliquely anteriorly and superiorly, inferior to the branches of the left lower lobe artery, to enter the left atrium. They are slightly posterior to the plane of the left lower lobe bronchi. They may be seen either end-on or in oblique cross-section in PA, lateral and oblique projections and may, therefore, simulate a mass.

THE MEDIASTINUM The radiographic anatomy of the mediastinum can be described from many points of view, depending on the technique that is under discussion. In this chapter only plain radiographs, CT and MRI will be considered in any detail, CT and MRI being illustrated first because an appreciation of the cross-sectional anatomy of the mediastinum helps in understanding the appearances on plain chest radiographs. The mediastinum is conventionally divided into superior, anterior, middle and posterior compartments. The exact anatomical boundaries of these divisions are unimportant to the radiologist (indeed they vary according to different authors), since they do not provide a clear-cut guide to disease and nor do their boundaries form any barriers to the spread of the disease.

Computed tomography and magnetic resonance imaging

Figure 12.14 Lateral view of the hila showing normal thickness of the posterior wall of the bronchus intermedius (arrow).

hilum consists of a combination of the right pulmonary artery and the superior pulmonary vein. Since these two vessels are immediately adjacent to one another (on the left, the left main bronchus lies between them), they may be responsible for a density that is sufficiently great to be confused with a mass on lateral plain radiographs and even, on occasion, on CT. 4 On lateral chest radiographs the angles between the middle and right lower lobe bronchi on the right, and the upper and lower lobe bronchi on the left, do not contain any large end-on vessels; a rounded shadow of greater than 1 cm in these angles is therefore unlikely to be a normal vessel14.

The blood vessels, trachea and main bronchi make up the bulk of the mediastinum, and the CT/MRI anatomy of these structures is illustrated in Figures 12.12–12.16. The thymus is situated anterior to the aorta and right ventricular outflow tract or pulmonary artery; it is often best appreciated on a section through the aortic arch or great vessels (Fig. 12.17). Before puberty15 the thymus fills in most of the mediastinum in front of the great vessels. During this period of life the gland varies so greatly in size that measurement is of little value in deciding normality. Approximate symmetry is the rule. Also, the thymus fills in the spaces between the great vessels and the anterior chest wall as if moulded by these structures. In adults the thymus is bilobed or triangular in shape. The maximum width and thickness of each lobe decreases with advancing age. Between the ages of 20 and 50, the average thickness as measured by CT decreases from 8–9 mm to 5–6 mm, the maximum thickness of each lobe being up to 15 mm. These diameters are greater on MRI, presumably because MRI demonstrates the thymic tissue even when it is partially replaced by fat. On MRI, sagittal images demonstrate the gland to be 5–7 cm long in its craniocaudad dimension.

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Figure 12.15 CT of normal mediastinum. (A–E) Five 1-cm thick sections have been selected to show the important anatomical features. The level of each section is illustrated in the diagram. A. Ao = ascending aorta, Ao arch = aortic arch, AV = azygos vein, D. Ao = descending aorta, IA = innominate artery, LA = left atrium, LCA = left carotid artery, LIV = left innominate vein, LPA = left pulmonary artery, LSA = left subclavian artery, MPA = main pulmonary artery, N = normal lymph node, OES = oesophagus, RA = right atrium, RIV = right innominate vein, RPA = right pulmonary artery, RVO = right ventricular outflow tract, SPV = superior pulmonary vein, SVC = superior vena cava, T = trachea.

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• THE NORMAL CHEST

Figure 12.16 MRI of normal mediastinum and hila. Four sections have been chosen to show the important anatomical features: (A) is just below the tracheal carina; (B) is 1 cm below A; (C) is at the level of the right main pulmonary artery; (D) is at the level of the mid left atrium. A.Ao = ascending aorta, AV = azygos vein, BI = bronchus intermedius, D.Ao = descending aorta, LA = left atrium, LMBr = left main bronchus, LPA = left pulmonary artery; LV = left ventricle, MPA = main pulmonary artery, Oes = oesophagus, RA = right atrium, RMBr = right main bronchus, RSPV = right superior pulmonary vein, SPR = superior pericardial recess, SVC = superior vena cava, Th = thymus.

Figure 12.17 CT of normal thymus (arrows) in a young adult man.

In younger patients, the CT density of the thymus is homogeneous and close to that of other soft tissues, but after puberty the density gradually decreases owing to fatty replacement, so that above 40 years of age the thymus usually has an attenuation value identical to that of fat and is often indistinguishable from the adjacent mediastinal fat, apart from some residual thymic parenchyma which may be visible as streaky or nodular densities within the fat (Fig. 12.18)16,17. On MRI the intensity of the thymus in T1weighted images is similar to that of muscle and appreciably lower than that of mediastinal fat, although, as would be expected, this difference decreases with age. On T2weighted images, the intensity differences are slight and do not vary with age.

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Figure 12.18 Thymic residues (arrows) shown by CT.

Figure 12.19 Diagram showing AJCC–UICC classification of regional lymph nodes.

Lymph nodes are widely distributed in the mediastinum. Ninety-five per cent of normal mediastinal lymph nodes are less than 10 mm in diameter, and the remainder, with few exceptions, are less than 15 mm in diameter18–22. Lymph nodes in the paraspinal areas, in the region of the brachiocephalic veins and in the space behind the diaphragmatic crura are generally smaller, 6 mm or less, whereas nodes in the aortopulmonary window, pretracheal and lower paratracheal spaces, and subcarinal compartment are often 6–10 mm in diameter. Lymph nodes encircle the trachea and main bronchi except where the aorta, pulmonary artery, or oesophagus are in direct contact with the airway.There is no clear division between the various nodes, but they can be categorized according to site.

The nomenclature of mediastinal lymph nodes should accord with the terms agreed by the American Joint Committee on Cancer and the Union International Contre le Cancer (AJCC– UICC) designed for staging carcinoma of the bronchus (Fig. 12.19; Table 12.1)23,24. These terms replaced the previous American Thoracic Society (ATS) classification. The AJCC–UICC classification is based on cross-sectional imaging in that it is directly referable to axial cross-sectional anatomy. The plane tangential to the upper margin of the aortic arch is an important dividing plane with nodes above this level being designated as: ‘highest mediastinal nodes’ (station 1 if they are above the upper rim of the left brachiocephalic vein); ‘right, left and posterior upper paratracheal’ (stations 2R,

Table 12.1 AJCC–UICC CLASSIFICATIONS OF REGIONAL LYMPH NODES 1. Highest mediastinal nodes lie above a horizontal line at the upper rim of the bracheocephalic (left innominate) vein 2. Upper paratracheal nodes lie above a horizontal line drawn tangential to the upper margin of the aortic arch and below the inferior boundary of No1 nodes 3. Prevascular and retrotracheal nodes may be designated 3A and 3P: midline nodes are considered to be ipsilateral 4. Lower paratracheal nodes lie to the right or left of the midline of the trachea between a horizontal line drawn tangential to the upper margin of the aortic arch and a line extending across the right or left main bronchus at the upper margin of the ipsilateral upper lobe bronchus. They are contained within the mediastinal pleural envelope. NB: The left lower paratracheal nodes lie medial to the ligamentum arteriosum 5. Subaortic (aortopulmonary window) nodes lie lateral to the ligamentum arteriosum or the aorta or left pulmonary artery and proximal to the first branch of the left pulmonary artery and lie within the mediastinal pleural envelope 6. Para-aortic nodes (ascending aorta or phrenic) lie anterior and lateral to the ascending aorta and the aortic arch or the innominate artery, beneath a line tangential to the upper margin of the aortic arch 7. Subcarinal nodes lie caudal to the carina of the trachea, but not associated with the lower lobe bronchi or arteries within the lung 8. Para-oesophageal nodes (below carina) lie adjacent to the right or left of the midline, excluding subcarinal nodes 9. Pulmonary ligament nodes lie within the pulmonary ligament, including those against the posterior wall and lower part of the inferior pulmonary vein 10. Hilar nodes lie distal to the mediastinal pleura reflection and the nodes adjacent to the bronchus intermedius on the right 11. Interlobar nodes lie between the lobar bronchi 12. Lobar nodes lie adjacent to the distal lobar bronchi 13. Segmental nodes lie adjacent to the segmental bronchi 14. Subsegmental nodes lie around the subsegmental bronchi NB. Station 1 through 9 nodes lie within the mediastinal pleural envelope, whereas station 10 through 14 nodes lie outside the mediastinal pleura within the visceral pleura.

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2L and 3P, respectively); and ‘prevascular’ if they lie anterior to the arteries to the head and neck (station 3A). The nodes below the plane tangential to the upper margin of the aortic arch include the following: right and left lower paratracheal (stations 4R and 4L); subaortic (aortopulmonary window) nodes (station 5); para-aortic nodes which lie anterior and lateral to the ascending aorta, the aortic arch, or the proximal brachiocephalic artery (station 6); and subcarinal nodes, which lie beneath the main bronchi within the mediastinal pleura (station 7). Low down in the mediastinum are the para-oesophageal (station 8) and pulmonary ligament nodes (station 9). Nodes are also present in the retrocrural areas and cardiophrenic angles. The nodes outside the mediastinal pleura are hilar (station 10), interlobar (station 11), lobar, segmental and subsegmental (stations 12–14); all these nodes are removed at pneumonectomy. The oesophagus is visible on all axial CT and MRI sections from the root of the neck down to the diaphragm. It may contain a small amount of air in approximately 80% of normal people. If there is sufficient mediastinal fat, the entire circumference of the oesophagus can be identified, and if air is present in the lumen, the uniform thickness of the wall can be appreciated. Without air, the collapsed oesophagus appears circular or oval in shape and measures approximately 1 cm in its narrowest diameter. On MRI the signal intensity on T1-weighted images is similar to muscle but on T2-weighted images the oesophagus often shows much higher signal intensity than muscle.

• THE NORMAL CHEST

Ant. junction line IA LCA Paratracheal stripe

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Radiographic appearances Plain chest radiographs provide limited information regarding mediastinal anatomy, since only the interfaces between the lung and the mediastinum are visualized (Fig. 12.20).

Junction lines25,26 When there is only a small amount of fat anterior to the ascending aorta and its major branches, the two lungs may be separated anteriorly by little more than the four intervening layers of pleura. In such patients an anterior junction line is visible on frontal chest radiographs (Fig. 12.21).The line diverges and fades out superiorly and cannot be identified above the level of the clavicles. It descends for a variable distance, usually deviating to the left, but never extending lower than the point where the two lungs separate to envelop the right ventricular outflow tract. The lungs may also come close together behind the oesophagus, forming the posterior junction line (Fig. 12.21). This line, unlike the anterior junction line, separates to envelop the aortic arch. It may reform below the aortic arch where the two lungs occasionally abut behind the oesophagus. Superiorly, the posterior junction line extends to the level of the lung apices where it diverges and disappears, a level appreciably higher than the medial ends of the clavicles. The differences in the superior extent of the anterior and posterior junction lines are related to the sloping boundary between the root of the neck and the thorax.

Oesophagus Azygo-oesophageal line Right paraspinal line

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Ao Azygos vein Left paraspinal line

Figure 12.20 Diagrams illustrating the mediastinal boundaries and junction lines. The visualization of the junction lines on a plain chest radiograph is variable, depending on how much fat is present in the mediastinum and on how closely the two lungs approximate to one another. (A) Section just above the level of the aortic arch; (B) section through the aortic arch; (C) section through the heart.

The major value of being able to identify the anterior and posterior junction lines is that a mass, or other space-occupying process, in the junctional areas can be excluded if these lines are visible. Since both junction lines are inconsistently seen, however, the lack of visualization of one or both is not a reliable sign of disease.

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Figure 12.22 Right tracheal stripe (straight arrows) and pleurooesophageal line (curved arrows) demonstrated on (A) plain radiograph and (B) unenhanced CT.

Figure 12.21 Anterior junction line (curved arrows) and the supraaortic posterior junction line (straight arrows). Note that the supraaortic posterior junction line goes well above the level of the clavicles and extends down to the top of the aortic arch but then stops, whereas the anterior junction line starts below the clavicles and continues well below the aortic arch.

Right mediastinum above the azygos vein The right superior mediastinal border is formed by the right brachiocephalic (innominate) vein and the superior vena cava. With aortic or brachiocephalic (innominate) artery ectasia or unfolding, either of these veins may be pushed laterally or the mediastinal border may be formed by the aorta or the right brachiocephalic artery. The right paratracheal region can be seen through the right brachiocephalic vein and superior vena cava because the lung contacts the right tracheal wall from the level of the clavicles down to the azygos vein, producing a visible stripe of uniform thickness known as the right paratracheal stripe (Fig.12.22), between the tracheal air column and the lung.This stripe, which should be no more than 5 mm wide, is visible in approximately two-thirds of normal people. It consists of the wall of the trachea and the adjacent mediastinal fat, but no focal bulges due to individual paratracheal lymph nodes can be seen. As with the junction lines, the diagnostic value of this stripe is that its presence excludes a spaceoccupying process in the area where the stripe is visible. The azygos vein is outlined by air in the lung at the lower end of the right paratracheal stripe. The diameter of the azygos vein in the tracheobronchial angle is variable: it may be considered normal when its diameter is 10 mm or less. The nodes immediately beneath the azygos vein are known as azygos nodes and are not recognizable on the normal chest radiograph. The lung posterior to the trachea contacts the right wall of the oesophagus so that a recognizable border may be seen in

the frontal projection. If the oesophagus at this level contains air, then the right wall of the oesophagus is seen as a stripe, the so-called oesophageal–pleural stripe27, curving superiorly and laterally behind the tracheal air column (Fig. 12.22). In summary, on a frontal radiograph three interfaces are potentially recognizable in the right mediastinum above the azygos vein: the superior vena cava border, the right wall of the trachea, and the right wall of the oesophagus.

Left mediastinum above the aortic arch The mediastinal shadow to the left of the trachea above the aortic arch is of low density and is caused by the left carotid and left subclavian arteries together with the left brachiocephalic (innominate) and jugular veins. The usual appearance on the frontal projection is a gently curving border formed by the left subclavian artery, which fades out where the artery enters the neck. A separate interface may occasionally be discernible for the left carotid artery or left brachiocephalic vein. The outer margin of the left tracheal wall is virtually never outlined, because the lung is separated from the trachea by the aorta and other vessels listed above.

Trachea and retrotracheal area in the lateral view The air column in the trachea can be seen throughout its length as it descends obliquely inferiorly and posteriorly. The course of the trachea on a normal lateral view is straight, or bowed anteriorly in patients with aortic unfolding, with no visible indentation from adjacent vessels. Small indentations into the air column of the trachea from tracheal cartilage rings may be apparent on the lateral view. The carina cannot be identified on the lateral view (though the right main bronchus is often mistaken for it). Its anterior wall is visible in a minority of patients, but the posterior wall is usually seen because lung often passes behind the trachea, thereby permitting visualization of the posterior tracheal (stripe) band28.The thickness of this stripe is 2–3 mm, provided it is formed solely by the tracheal wall and pleura (Fig. 12.23). If a large amount

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Figure 12.23 Lateral view of trachea and major bronchi. (A) In this example, the posterior wall of the trachea is outlined by lung posterior to it (arrow). (B) In this example, the collapsed oesophagus is between the lung and the trachea (arrow).

of air is present in the oesophagus, the posterior tracheal band may be much thicker, since it then comprises the combined thicknesses of the posterior tracheal wall and the anterior oesophageal wall. Alternatively, the lung may be separated from the trachea by the full width of a collapsed oesophagus, leading to a band of density measuring 10 mm or more (Fig. 12.23).

Supra-aortic mediastinum on the lateral view A variable proportion of the aortic arch and its major branches is visible on the lateral view, depending largely on the degree of aortic unfolding. The brachiocephalic (innominate) artery is the only branch vessel that is recognizable with any frequency. It arises anterior to the tracheal air column; usually the origin is unclear but, after a variable length, the posterior wall can be seen as a gently S-shaped interface as it crosses the tracheal air column. The left and right brachiocephalic (innominate) veins are also sometimes visible on the lateral view. The left brachiocephalic vein is seen as an extrapleural bulge behind the manubrium in a small proportion of normal people (Fig. 12.24).

Figure 12.24 Bulge behind manubrium representing normal left innominate (brachiocephalic) vein (arrow).

Right middle mediastinal border below the azygos arch Below the azygos arch, the right lower lobe makes contact with the right wall of the oesophagus and the azygos vein as it ascends next to the oesophagus. This portion of the lung is known as the azygo-oesophageal recess, and the interface is known as the azygo-oesophageal line (Fig. 12.25). The shape of the azygos arch varies considerably in different subjects and therefore the shape of the upper portion of the azygo-oesophageal line varies accordingly. The upper few centimetres of the azygo-oesophageal line are, however, always straight or concave toward the lung, so that a convex shape suggests the

presence of a subcarinal mass or left atrial enlargement. The azygo-oesophageal line can be traced down to the posterior costophrenic angle in normal subjects.

Left cardiac border below the aortic arch This left cardiac border is formed by the main pulmonary artery and heart. The pleura smoothing the angle between the mid-portion of the aortic arch and the main and left pulmonary artery, the so-called aortic–pulmonary mediastinal stripe29, is the lateral extent of the aortopulmonary

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Figure 12.25 Azygo-oesophageal line (arrows).

window. Because the aortopulmonary window is a sensitive place to look for lymph node enlargement, Blank and Castellino30 investigated the variable shape of this pleural reflection, as illustrated in Figure 12.26. A small ‘nipple’ may occasionally be seen projecting laterally from the aortic knuckle owing to the presence of the left superior intercostal vein31,32 (see Fig. 12.3A). The vein, which is formed by the junction of the left first to fourth intercostal veins, arches forward around the aorta just below the origin of the left subclavian artery to enter the left brachiocephalic vein. This normal nipple should not be misinterpreted as adenopathy projecting from the aortopulmonary window. The interface between the lung and the left wall of the aorta can almost invariably be followed down to the level of the diaphragm, though contact with the proximal portion of the left pulmonary artery may silhouette a small portion of the interface.The shape varies with the degree of aortic unfolding. Though the lung invaginates between the heart and aorta to contact the left wall of the oesophagus, the interface with the oesophagus may be seen as a line if air is present within the lumen of the oesophagus.

Paraspinal lines Although lymph nodes and intercostal veins occupy the space between the spine and the lung, they cannot normally be recognized individually. In individuals with little fat, the interfaces, known as the paraspinal lines, may closely reflect the

Figure 12.26 Patterns of pleural reflection along the left border of the great vessels and heart. The heavy line indicates the visible pleural interface. (Adapted from Blank N, Castellino R A 1972 Patterns of pleural reflections of the left superior mediastinum: normal anatomy and distortions produced by adenopathy. Radiology 102: 585–589, with permission from the Radiological Society of North America).

undulations of the lateral spinal ligaments, but the more fat there is, the more these undulations are smoothed out. The thickness of the left paravertebral space is usually greater than that of the right and can be more than 10 mm in obese subjects. Aortic unfolding contributes to the thickness of the left paraspinal line; as the aorta moves posteriorly and laterally, it strips the pleura from its otherwise close contact with the profiled portions of the spine.

Retrosternal line The band-like opacity simulating pleural or extrapleural disease is often seen along the lower third of the anterior chest wall on a lateral chest radiograph (Fig. 12.27)33. This density is due to mediastinal fat and to the differing anterior extent of the left and right lungs. The left lung does not contact the most anterior portion of the left thoracic cavity at these levels because the heart occupies the space. The band-like opacity is therefore accounted for by the normal heart and mediastinum, rather than by disease.

THE DIAPHRAGM The diaphragm consists of a large dome-shaped central tendon surrounded by a sheet of striated muscle which is attached to ribs 7 to 12 and to the xiphisternum. The two diaphragmatic crura, which arise from the upper three lumbar vertebrae, arch superiorly and anteriorly to form the margins of the aortic

CHAPTER 12

• THE NORMAL CHEST

Figure 12.28 Right phrenic nerve as it passes over the surface of the right hemidiaphragm (arrows).

Figure 12.27 Retrosternal stripe (arrowheads) and inferior vena cava in lateral projection (arrow).

and oesophageal hiatuses. The median arcuate ligament connecting the two crura forms the anterior margin of the aortic hiatus, and the crura themselves form its lateral boundary. The oesophageal hiatus lies anterior to the aortic hiatus, and anterior to that lies the hiatus for the inferior vena cava, which is situated within the central tendon immediately beneath the right atrium. In most individuals, the diaphragm has a smooth domed shape, but a scalloped outline is also common. The angle of contact with the chest wall is acute and sharp, but blunting of this angle can be normal in athletes, because they can depress their diaphragm to a remarkable degree on deep inspiration. The normal right hemidiaphragm is found at about the level of the anterior portion of the sixth rib, with a range of approximately one interspace above or below this level34. In most people, the right hemidiaphragm is 1.5–2.5 cm higher than the left, but the two hemidiaphragms are at the same level in some 9% of the population. In a few normal individuals the left hemidiaphragm is up to 1 cm higher than the right. The normal excursion of the diaphragm is usually between 1.5 and 2.5 cm, though greater degrees of movement are not uncommon. Transabdominal ultrasound, which is capable of providing accurate real-time measurement of movement, shows a considerable normal range of between 2.0 and 8.6 cm, the mean excursion of the right hemidiaphragm on deep inspiration being 53 mm (sd 16.4) and that of the left being 46 mm (sd 12.4)35. Incomplete muscularization, known as eventration, is also common. An eventration is composed of a thin membranous sheet replacing what should be muscle. Usually it is partial, involving one-half to one-third of the hemidiaphragm. The lack of muscle manifests itself radiographically as elevation of the affected portion of the diaphragm, and the usual appear-

ance is one of a smooth hump on the contour of the diaphragm.Total eventration of a hemidiaphragm, which is much more common on the left than the right, results in elevation of the whole hemidiaphragm; on fluoroscopy hemidiaphragm movement is poor, absent, or paradoxical, and severe cases of congenital eventration cannot be distinguished from acquired paralysis of the phrenic nerve. A linear density arising from the lateral wall of the inferior vena cava (Fig. 12.28) is often seen coursing over the surface of the right hemidiaphragm.This line represents pleura and an envelope of fat investing the phrenic nerve, according to Berkman et al36, or the inferior phrenic artery and vein, according to Ujita et al37.

REFERENCES 1. Glazer H S, Anderson D J, DiCroce J J et al 1991 Anatomy of the major fissure: evaluation with standard and thin-section CT. Radiology 180: 839–844 2. Mayo J R, Muller N L, Henkelman R M 1987 The double-fissure sign: a motion artifact on thin-section CT scans. Radiology 165: 580–581 3. Ariyurek O M, Gulsun M, Demirkazik F B 2001 Accessory fissures of the lung: evaluation by high-resolution computed tomography. Eur Radiol 11: 2449–2453. Epub 2001 May 19 4. Caceres J, Mata J H, Alegnet X 1993 Increased density of the azygos lobe on frontal radiographs simulating disease: CT findings in seven patients. Am J Roentgenol 160: 245–248 5. Rabinowitz J G, Cohen B A, Mendleson D S 1984 The pulmonary ligament. Radiol Clin North Am 22: 659–672 6. Berkman Y M, Drossman S R, Marboe C C 1993 Intersegmental (intersublobar) septum of the lower lobe in relation to the pulmonary ligament: anatomic, histologic, and CT correlations. Radiology 185: 389–393 7. Breatnach E, Abbott G C, Fraser R E 1984 Dimensions of the normal human trachea. Am J Roentgenol 142: 903–906 8. Vock P, Spiegel T, Fram E K et al 1984 CT assessment of the adult intra-thoracic cross section of the trachea. J Comput Assist Tomogr 8: 1076–1082 9. Griscom N T, Wohl M E 1986 Dimensions of the growing trachea related to age and gender. Am J Roentgenol 146: 233–237

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10. Jardin M, Remy J 1986 Segmental bronchovascular anatomy of the lower lobes: CT analysis. Am J Roentgenol 147: 457–468 11. Lee K S, Bae W K, Lee B H et al 1991 Bronchovascular anatomy of the upper lobes: evaluation with thin section CT. Radiology 181: 765–772 12. Oshiro Y, Kusumoto M, Moriyama N et al 2002 Intrapulmonary lymph nodes: thin-section CT features of 19 nodules. J Comput Assist Tomogr 26: 553–557 13. Hyodo T, Kanazawa S, Dendo S et al 2004 Intrapulmonary lymph nodes: thin-section CT findings, pathological findings, and CT differential diagnosis from pulmonary metastatic nodules. Acta Med Okayama 58: 235–240 14. Park C-K, Webb W R, Klein J S 1991 Inferior hilar window. Radiology 178: 163–168 15. Mendelson D S 2001 Imaging of the thymus. Chest Surg Clin North Am 11: 269–293 16. Dixon A K, Hilton C J, Williams C T 1981 Computed tomography and histological correlation of the thymic remnant. Clin Radiol 32: 255–257 17. Moore A V, Korobkin M, Olanow W et al 1983 Age-related changes in the thymus gland: CT-pathologic correlation. Am J Roentgenol 141: 241–246 18. Genereux G P, Howie J L 1984 Normal mediastinal lymph node size and number: CT and anatomic study. Am J Roentgenol 142: 1095–1100 19. Glazer G M, Gross B H, Quint L E et al 1985 Normal mediastinal lymph nodes: number and size according to American Thoracic Society mapping. Am J Roentgenol 144: 261–265 20. Schynder P A, Gamsu G 1982 CT of the pretracheal retrocaval space. Am J Roentgenol 136: 303–308 21. Ingram C E, Belli A M, Lewards M D et al 1989 Normal lymph node size in the mediastinum: a retrospective study in two patient groups. Clin Radiol 40: 355–339 22. Murray J G, O’Driscoll M, Curtin J J 1995 Mediastinal lymph node size in an Asian population. Br J Radiol 68: 348–350 23. Mountain C F, Dresler C M 1997 Regional lymph node classification for lung cancer staging. Chest 111: 1718–1723

24. Cymbalista M, Waysberg A, Zacharias C et al 1999 CT demonstration of the 1996 AJCC–UICC regional lymph node classification of lung cancer staging. Radiographics 19: 900 25. Proto A V, Simmons J D, Zylak C J 1983 The anterior junction anatomy. CRC Crit Rev Diagn Imaging 19: 111–173 26. Proto A V, Simmons J D, Zylak C J 1983 The posterior junction anatomy. CRC Crit Rev Diagn Imaging 20: 121–173 27. Cimmino C V 1981 The oesophageal–pleural stripe: an update. Radiology 140: 607–613 28. Bachman A L, Teixidor H S 1975 The posterior tracheal band: a reflection of local mediastinal abnormality. Br J Radiol 48: 352–359 29. Keats T E 1975 The aortic–pulmonary mediastinal stripe. Am J Roentgenol 116: 107–109 30. Blank N, Castellino R A 1972 Patterns of pleural reflections of the left superior mediastinum: normal anatomy and distortions produced by adenopathy. Radiology 102: 585–589 31. Lane E J, Heitzman E R, Dinn W M 1976 The radiology of the superior intercostal veins. Radiology 120: 263–267 32. Abiru H, Ashizawa K, Hashmi R et al 2005 Normal radiographic anatomy of thoracic structures: analysis of 1000 chest radiographs in Japanese population. Br J Radiol 78: 398–404 33. Whalen J P, Meyers M A, Oliphant M et al 1973 The retrosternal line. Am J Roentgenol 117: 861–872 34. Lennon E A, Simon G 1965 The height of the diaphragm in the chest radiograph of normal adults. Br J Radiol 38: 937–943 35. Houston J G, Morris A D, Howie C A et al 1992 Quantitative assessment of diaphragmatic movement: a reproducible method using ultrasound. Clin Radiol 46: 405–407 36. Berkman Y M, Davis S D, Kazam E 1989 Right phrenic nerve: anatomy, CT appearance, and differentiation from the pulmonary ligament. Radiology 173: 43–46 37. Ujita M, Ojiri H, Arizumi M et al 1993 Appearance of the inferior phrenic artery and vein on CT scans of the chest: a CT and cadaveric study. Am J Roentgenol 160: 745–747

CHAPTER

The Chest Wall, Pleura, Diaphragm and Intervention

13

John A. Verschakelen

The chest wall • Soft tissues • Bony structures The pleura • Pleural effusion

• Pneumothorax • Pleural thickening and fibrothorax • Pleural calcification • Pleural tumours The diaphragm

THE CHEST WALL Although there is a wide variety of tissues and structures that make up the chest wall, based on their radiographic presentation, its components can be grouped into two major parts: the soft tissues and the bony structures.

SOFT TISSUES On the chest radiograph the soft tissues present as areas of increased density that in part project next to the bony chest wall and in part overlay the different components of the chest. Abnormalities of the soft tissues will present as an abnormal increase or decrease in density often combined with the appearance of an abnormal contour or the disappearance of a normal contour. Because of better density resolution and multiplanar reformatting, computed tomography (CT) can better demonstrate the different tissues of the chest wall. CT has the advantage over magnetic resonance imaging (MRI) of higher spatial resolution and the ability to better identify bony structures. MRI, however, yields greater soft tissue contrast which can be important1,2. Multiplanar imaging and three-dimensional (3D) reformation can be performed with both techniques.

Ultrasound may also be used to examine the chest wall. In general it provides less detailed and comprehensive information but it usually enables the lesion to be localized, allows a distinction to be made between cystic and solid lesions, and enables guided aspiration/biopsy to be performed under imaging control.

Breasts On the female chest radiograph it is mandatory to check that both breasts are present. Unilateral radical mastectomy is usually easy to detect because it generates a unilateral mid/lower zone transradiancy and an abnormally straight anterior axillary fold that passes upwards and inwards towards the mid clavicle (Fig. 13.1). Bilateral radical mastectomy is more difficult to identify, but an overall increase in basal transradiancy and axillary fold abnormalities should provide adequate clues. Surgical interventions short of radical mastectomy may be impossible to detect, but close attention to the relative transradiancy of the breast regions and to the breast contours may provide suggestive findings. Nipple shadows can mimic intrapulmonary nodules. A putative nipple should be checked for compatible size (5– 15 mm), shape and location—its relation to the breast outline in a woman or the pectoralis opacity in a man.

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Figure 13.1 Left mastectomy. The left hemithorax is more transradiant than the right.

Muscles On the chest radiograph the pectoralis major produces a broad, band-like opacity extending downwards and medially from the axilla. Unilateral absence or hypoplasia of the pectoralis major results in a unilateral transradiancy and an abnormal anterior axillary fold as seen with mastectomy. In Poland’s syndrome these changes are accompanied by ipsilateral hand and arm anomalies (particularly syndactyly) with or without absence of pectoralis minor, rib anomalies, and hypoplasia of breast and nipple.

Soft tissue calcification Soft tissue calcification may occur in the chest wall, and clues to its site and nature are provided by its morphology distribution and the clinical history. Possible causes to consider include granulomatous lymph nodes, parasites (Taenia solium and Dracunculus medinensis), calcinosis universalis, childhood dermatomyositis, tuberculosis (spine, ribs, or soft tissues) and bone neoplasms. Ossification is rare and most commonly seen in fibrodysplasia ossificans progressiva.

Subcutaneous emphysema Subcutaneous emphysema of the chest wall is not uncommon following surgery, pleural drain placement, trauma, or in cases of spontaneous or acquired pneumomediastinum. Air dissects along tissue planes and between muscle bundles, giving an overall pattern of linear transradiancies which can significantly interfere with the interpretation of the underlying structures. In this way diagnosis of pneumothorax can become very difficult. In case of doubt CT can be performed.

Soft tissue tumours A soft tissue tumour of the chest wall gives rise to an opacity. Malignant and inflammatory lesions cause bony destruction and

benign ones result in rib separation and notch-like remodelling from pressure erosion. The most common benign chest wall tumour is a lipoma, but a variety of other mesenchymal tumours occur, including neurofibromas (focal or plexiform), neurilemmomas, haemangiomas and lymphangiomas (cystic hygromas). On CT, lipomas are well-demarcated homogeneous masses of low density (−90 to −150 HU).They contain few, if any, other soft tissue components; the presence of the latter in a fatty tumour suggests a liposarcoma. MRI features are also characteristic, with high signal on T1-weighted images, intermediate signal on T2-weighted images, and low signal with fat suppression1,2. Neurofibromas on CT characteristically have a lower density than muscle both before and after intravenous contrast medium. On MRI, neurofibromas give low to intermediate signal on T1-weighted images but high signal on T2-weighted images and marked contrast enhancement after gadolinium, which allows clear delineation of their extent. Haemangiomas are uncommon lesions that occasionally show phlebolithic calcification on plain radiography. Findings on CT include phleboliths, bone remodeling, and an enhancing mass. MRI is the best investigation for delineating their extent. Lesions give an intermediate signal on T1-weighted images and a high signal on T2-weighted images, accompanied by inhomogeneities generated by vessels, soft tissue, and elements derived from haemorrhage1,2. Lymphangiomas on CT have the features of a fluid-filled cyst with or without septation. On MRI they have the features of a cyst with low protein content. Malignant primary tumours arising in the soft tissues of the chest wall are unusual, the most common being lipo- or fibrosarcomas. Secondary tumours of the chest wall are common, particularly when due to local spread (carcinoma of the breast and lung, lymphoma) (Fig. 13.2); see bronchial carcinoma and Pancoast’s tumour, below.

BONY STRUCTURES Although depicting bone abnormalities is not the primary goal of a chest radiograph, the bony structures that are, as a result of the technique, often only partially visible should be carefully examined. CT, when indicated, is better at demonstrating congenital or acquired remodelling or complicated fractures; multidetector 2D or 3D reformations can be helpful.

Ribs There are normally 12 pairs of ribs. Cervical ribs occur in 1–2% of the population and are commonly bilateral, though often asymmetrical. Congenital abnormalities of modelling may be confined to one or two ribs or be generalized. One or a few upper ribs are commonly bifid, splayed, fused, or hypoplastic. Usually occurring in isolation, these anomalies are occasionally part of a syndrome (e.g. basal cell naevus syndrome) or associated with other anomalies (e.g. Sprengel’s deformity). With acquired remodelling, abnormalities tend to be focal, affecting one or many ribs. Such acquired changes may follow

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• THE CHEST WALL, PLEURA, DIAPHRAGM AND INTERVENTION

Figure 13.2 Invasive malignant T-cell lymphoma. (A) High-resolution chest wall ultrasound image through the intercostal space showing echoic cortical rib and consecutive echo void behind. Within the intercostal space hypo-echoic tumour tissue (arrowheads) is seen invading the posterior chest wall. (B) Same patient, transverse contrast-enhanced CT. Enhancing peripheral tumour tissue is widely invading the posterior chest wall. Exact definition of invasive tissue is impaired owing to low soft tissue contrast resolution in CT. (C) Same patient, sagittal T1-weighted MRI pre- (left) and post- (right) contrast medium nicely display the widespread invasion of the posterior chest wall by enhancing tumour tissue. There is already invasion of two ribs, including cortical rib destruction (arrowheads). The central nonenhancement of the tumour is due to necrosis. (Courtesy of Dr R. Bittner.)

fracture, surgery, osteomyelitis and empyema drainage, or result from external pressure (rib notching). The two main causes of rib notching are coarctation of the aorta and neurofibromatosis Type I. Ribs may fracture and the callus formed can sometimes mimic an intrapulmonary opacity. Destructive rib lesions occur most commonly in osteomyelitis or neoplastic disease. The former is uncommon and may be haematogenous (e.g. staphylococcal or tuberculous) or caused by direct spread from lung and pleural space (e.g. in actinomycosis). Bronchial carcinoma, including Pancoast’s tumour, commonly spreads from lung to rib. In this latter condition MRI can be performed to study the extent of the disease, especially the relationship between the tumour and the plexus brachialis in case of a Pancoast’s tumour3 (Fig. 13.3). Multidetector CT (MDCT) can also play an important role especially because it can better evaluate the invasion in the bony cortex of the ribs4 (Fig. 13.3D). Also, 3D image reconstruction methods can be used in selected cases to clarify a complex relationship between the tumour invading the chest wall and vascular structures of the thoracic inlet. Various primary and secondary tumours can affect ribs, causing localized lesions. Benign primary tumours are infrequent, and of these, the cartilaginous tumours (chondromas, osteochondromas) are the most common. They are predominantly anterior and may show characteristic cartilaginous calcification. Other lesions that broadly fall into this category include fibrous dysplasia, histiocytosis X, haemangioma and aneurysmal bone cyst1 (Fig. 13.4). The most common malignant rib tumours are metastatic deposits and myeloma. Primary malignant tumours are rare, chondrosarcomas being the least uncommon. Other malignancies that occur occasionally include lymphoma, osteosarcoma and round-cell tumours.

Sternum This is well displayed in a lateral chest radiograph but is inconspicuous in the frontal projection, in which only the manubrial margins are sometimes visible, giving rise to confusing shadows that may mimic mediastinal widening. Various sternal deformities are described, and the most important radiologically is the depressed sternum (funnel chest, pectus excavatum) in which there is approximation of the lower half of the sternum and the spine (Fig. 13.5). This may be an isolated abnormality or it may be associated with other disorders such as Marfan’s syndrome or congenital heart disease (particularly atrial septal defect [ASD]). The radiological signs on a postero-anterior (PA) chest radiograph consist of a shift of the heart to the left, straightening of the left heart border with prominence of the main pulmonary artery segment, loss of the descending aortic interface, and an increased opacity in the right cardiophrenic angle, often accompanied by a loss of clarity of the right heart border which simulates right middle lobe disease. The diagnosis can be suspected on a PA radiograph from the steep inferior slope of the anterior ribs and undue clarity of the lower dorsal spine seen through the heart. Pigeon chest (pectus carinatum) represents the reverse deformity and may be congenital or acquired. Neoplasms of the sternum are usually malignant (myeloma, chondrosarcoma, lymphoma or metastatic carcinoma), the most common benign tumour being a chondroma. Non-neoplastic processes that may affect the sternum include osteomyelitis, histiocytosis X, Paget’s disease, fibrous dysplasia, osteitis fibrosa cystica and intersternocostoclavicular hyperostosis. CT is the best investigation for imaging the sternum because it eliminates overlapping structures, detects bony destruction, allows imaging of adjacent soft tissues (the parasternal–internal mammary zone), and has good contrast resolution superior to that of conventional radiography or tomography.

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Figure 13.3 Pancoast’s tumour. (A,B) MRI. (A) Coronal and (B) sagittal image. Large tumour in the left upper lobe invading the soft tissues and displacing the vascular structures anteriorly (arrows). The brachial plexus has also been invaded (arrowheads). (C,D) CT (different patient). (C) Coronal and (D) sagittal image bone window setting. Large tumour in the left upper lobe invading the soft tissues, displacing and invading the left subclavian artery and invading a rib (arrow).

Clavicles The medial clavicular ends are important landmarks used together with the spine in assessing rotation on a radiograph. The joints at both ends are synovial but only the acromioclavicular joint can be assessed with confidence on a chest radiograph. It may be eroded in any synovitis, particularly rheumatoid arthritis, and is also commonly fuzzy and illdefined in hyperparathyroidism and rickets. Neoplasms of the clavicle are usually malignant (myeloma or metastatic). Other

primary tumours and tumour-like lesions include osteosarcoma, Ewing’s sarcoma, post-radiation sarcoma, aneurysmal bone cyst, histiocytosis X and intersternocostoclavicular hyperostosis. Either CT or MRI is required to provide a full evaluation of the medial clavicular ends.

Spine Kyphoscoliosis makes assessment of the chest radiograph difficult and CT is often necessary to evaluate possible thoracic disease.

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• THE CHEST WALL, PLEURA, DIAPHRAGM AND INTERVENTION

Figure 13.4 Fibrous dysplasia in a rib; chest radiograph detail of the left lung. Compared with the other ribs the ninth rib shows an increase in density and is slightly broadened.

Figure 13.5 Depressed sternum. (A) PA chest radiograph. The depressed sternum displaces the heart to the left and rotates it so that the left heart border adopts a straight configuration. The right heart border becomes ill-defined and is bounded by a hazy opacity, simulating collapse of the right middle lobe. The ribs show their characteristic configuration—horizontal posteriorly and steeply oblique anteriorly. The posterior displacement of the sternum is better demonstrated on (B) the lateral chest radiograph and (C) the axial CT.

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THE PLEURA The chest radiograph is still the most important and widely used means of demonstrating and following the progress of pleural disease, though ultrasound, CT and MRI can play a significant role in a number of specific situations. Pleural disease is manifest by the accumulation of fluid or air in the pleural space, by pleural thickening (with or without calcification), or by the presence of a pleural mass.

and left effusions with pancreatitis, pericarditis, oesophageal rupture and aortic dissection. Massive effusions are most commonly due to malignant disease, particularly metastases (lung or breast), but may also occur in heart failure, cirrhosis, tuberculosis, empyema and trauma.

PLEURAL EFFUSION

Free pleural fluid A small amount of free fluid may be undetectable on an erect PA chest radiograph as it tends initially to collect under the lower lobes. Such small subpulmonary effusions can be demonstrated by ultrasound or CT. An alternative technique, the lateral decubitus chest radiograph has largely been replaced by these newer techniques6. As the amount of effusion increases, the posterior and then the lateral costophrenic angles become blunted, by which time a 200–500 ml effusion is present. Following this the classical signs develop, viz homogeneous opacification of the lower chest with obliteration of the costophrenic angle and the hemidiaphragm. The superior margin of the opacity is concave to the lung and is higher laterally than medially. Above and medial to the meniscus there is a hazy increase in opacity owing to the presence of fluid posterior and anterior to the lungs (Fig. 13.6). Massive effusions cause dense opacification of the hemithorax with contralateral mediastinal shift (Fig. 13.7). Absence of mediastinal shift with a large effusion raises the strong possibility of obstructive collapse of the ipsilateral lung or extensive pleural

A number of different types of fluid may accumulate in the pleural space, the most common being transudate, exudate (thin or thick), blood and chyle. Occasionally effusions are highly specific, not falling into any of the above categories and containing, for example, bile, cerebrospinal fluid, or iatrogenic fluids. All types of pleural effusion are radiographically identical, though historical, clinical and other radiological features may help limit the diagnostic possibilities. Sometimes, also CT and MRI can help to specify the diagnosis. Bilateral pleural effusions tend to be transudates because they develop secondary to generalized changes that affect both pleural cavities equally—a rise in capillary pressure or a fall in blood proteins, etc. Some bilateral effusions are exudates, however, and this is seen with metastatic disease, lymphoma, pulmonary embolism, rheumatoid disease, systemic lupus erythematosus (SLE), post-cardiac injury syndrome, myxoedema and some ascites-related effusions. Right-sided effusions are typically associated with ascites, heart failure and liver abscess,

Imaging pleural effusion5 Chest radiograph

Figure 13.6 Bilateral pleural effusion. (A) Erect and (B) supine chest radiograph. The pleural effusion obscures the diaphragm and both costophrenic angles. It has a curvilinear upper margin concave to lung and is higher laterally than medially. This is opposite to the findings on the supine chest radiograph where the pleural effusion is hardly visible as a hazy opacity affecting the lower part of the thorax. Note also that the costophrenic angles are not obscured and that the vascular opacities are preserved in the overlying lung.

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• THE CHEST WALL, PLEURA, DIAPHRAGM AND INTERVENTION

Figure 13.7 Massive pleural effusion with mediastinal shift to the left. (A) Chest radiograph and (B) CT coronal reconstruction. A massive effusion displaces the mediastinum to the left. CT shows the important pleural effusion together with the enhanced atelectatic left lung. Note also the depression of the right hemidiaphragm (arrows).

malignancy, such as may be seen with mesothelioma or metastatic carcinoma (Table 13.1). Large effusions sometimes cause diaphragmatic inversion, particularly on the left where the diaphragm lacks the support of the liver7. Although pleural fluid collects initially under the lung, it is unusual for it to remain localized in this site once its volume exceeds 200–300 ml.This does happen occasionally, however, and may be suspected from an erect PA and lateral radiograph. On a PA radiograph this subpulmonary effusion7 presents as a ‘high hemidiaphragm’ with an unusual contour that peaks more laterally than usual, has a straight medial segment and falls away rapidly to the costophrenic angle laterally, which may or may not be blunted. Ultrasound or CT will confirm the diagnosis (see Fig. 13.20). Loculated (encysted, encapsulated) pleural fluid Fluid can loculate between visceral pleural layers in fissures or between visceral and parietal layers, usually against the chest wall. It is unusual for this to happen without some additional radiographic clue to the presence of pleural disease (Fig. 13.8). Both ultrasound and CT can be used to distinguish loculated fluid from solid lesions.

Table 13.1

CAUSES OF OPACIFICATION OF A HEMITHORAX

Pleural effusion Consolidation Collapse Massive tumour Fibrothorax Combination of above lesions Pneumonectomy Lung agenesis

Pleural effusion in the supine patient In the supine patient, pleural fluid layers out posteriorly and the meniscus effect, present from front to back, is not appreciated because of the projection. The main radiographic finding is a hazy opacity like a veil affecting the whole or the lower part of the hemithorax, with preserved vascular opacities in the overlying lung (see Fig. 13.6B). Additional signs include haziness of the diaphragmatic margin, blunting of the costophrenic angle, a pleural cap to the lung apex, thickening of the minor fissure and widening of the paraspinal interface.

Ultrasound6,8 Pleural fluid, especially when it is a transudate, is commonly echo-free and marginated on its deep aspect by a highly echogenic line at the fluid–lung interface. Exudative and haemorrhagic effusions may be echogenic and are often accompanied by pleural thickening. The pattern of echoes may be homogeneous, complex or septated. Features that help distinguish a fluid from a solid echogenic lesion include changes in shape with breathing, the presence of septa and fibrous strands, and movement of components induced by breathing (Fig. 13.9). Occasionally, in the absence of such features, some echogenic fluid pleural effusions are indistinguishable from solid ones.6 Ultrasound has a number of important roles in the evaluation and management of pleural fluid. It can be used to distinguish between pleural fluid, solid pleural (or extrapleural) lesions, and peripheral lung lesions. In peripheral lung lesions, the presence of fluid bronchograms and vessels on Doppler examination will positively identify consolidation. In addition, pleural lesions characteristically make an obtuse angle with the chest wall, whereas with intrapulmonary lesions the angle is often acute.This ability of ultrasound to distinguish pulmonary lesions (collapse, consolidation, abscess) from pleural effusion

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Figure 13.8 Encapsulated fluid on (A) PA and (B) lateral chest radiographs. Pleural fluid is encapsulated in the major fissure and against the anterior chest wall. These encysted fluid collections can mimic a lung tumour.

extent and location of the latter. Accurate localization of such loculated effusions is useful before drainage. CT distinguishes between parenchymal lung disease and pleural disease, a distinction that is often facilitated by a bolus of intravenous contrast medium. CT can characterize the morphology of pleural thickening that often accompanies a pleural effusion, distinguishing between malignant thickening (nodular, with focal masses) and benign thickening, which is typically uniform. CT can also identify any underlying lung disease that might have provoked an effusion and it facilitates percutaneous aspiration and biopsy (Fig. 13.10).

Figure 13.9 Ultrasound of an empyema. The pleural fluid is separated by septa (arrows). Although the pleural fluid is echo-free in part, some areas return echoes owing to the turbid nature of the empyema fluid.

is particularly useful when it comes to the evaluation of the opaque hemithorax. Ultrasound can also be used to identify small amounts of pleural fluid, or pleural fluid in unusual locations, as with a subpulmonary effusion (see Fig. 13.20). Ultrasound is widely used to localize pleural fluid for aspiration and identify any solid components to allow guided biopsy. Furthermore, ultrasound may identify the cause of an effusion when it lies inside or even outside the chest (e.g. subphrenic abscess, metastasis).

Computed tomography6,9 CT is very sensitive in detecting pleural fluid and can distinguish between free and loculated fluid, identifying the

Figure 13.10 CT of malignant pleural disease. In this right pleural effusion CT identifies the extensive and irregular pleural thickening characteristic of a malignant process (pleural metastases). Note also the primary tumour in the right breast.

CHAPTER 13

A pleural effusion appears on CT as a dependent sickleshaped opacity with a lower CT number than that of any adjacent pleural thickening or mass. CT numbers do not allow a distinction between transudate and exudate. However, parietal pleural thickening at contrast-enhanced CT almost always indicates the presence of pleural exudates. The higher density of clotted blood in a haemothorax is sometimes apparent.The fat-containing chylothorax does not have a lower CT number than normal, because of its protein content. Loculated effusions have a lenticular configuration with smooth margins and they displace the adjacent parenchyma.

Magnetic resonance imaging6 MRI has a limited role in the evaluation of pleural effusion. Pleural fluid has a low signal on T1-weighted sequences and a high signal on T2-weighted images, with a tendency for exudates to give a higher signal than transudates on T2-weighted sequences. In addition, complex exudates have greater signal intensity than simple exudates. It may also be possible to differentiate transudates from exudates using triple echo-pulse sequence, and benign from malignant changes using high-resolution MRI.10 Chylous effusion can cause high signal intensity on T1-weighted images similar to subcutaneous fat. In the subacute and chronic stage, haematomas show bright signal intensity on T1-weighted images, surrounded by a dark rim caused by haemosiderin.

Some specific pleural effusions Exudates and transudates Pleural effusion is common in heart failure and tends to be more frequent and larger on the right. All types of pericardial disease may be associated with pleural effusion which is predominantly left sided. Pleural effusion is a characteristic finding in the post-cardiac injury syndrome, seen in about 80% of patients. It may be bilateral or unilateral and is commonly accompanied by consolidation and pericardial effusion. Pulmonary embolism is commonly associated with pleural effusion which is seen in 25–50% of cases. A number of drugs have been described as causing pleural effusions. The most common agents are cytotoxics (methotrexate, procarbazine, mitomycin, busulphan, bleomycin and interleukin-2), nitrofurantoin, antimigraine drugs (ergotamine, methysergide), amiodarone, propylthiouracil, bromocriptine and gonadotropins. With a number of these agents pleural thickening is more common than a pleural effusion. Pleural effusion is also a recognized complication of hepatic cirrhosis. The principal mechanism of its production is the transdiaphragmatic passage of ascites, though other factors such as hypoalbuminaemia may contribute in a small number of cases. Both acute and chronic pancreatitis are associated with pleural effusions which have high amylase levels. In acute pancreatitis, exudative and often blood-stained effusions form in 15% of patients, particularly on the left side where the diaphragm is closely related to the pancreatic tail. Associated elevation of the hemidiaphragm and basal lung consolidation are common. In chronic pancreatitis, effusions tend to be large and recurrent and patients present with dyspnoea, unlike effusions in acute

• THE CHEST WALL, PLEURA, DIAPHRAGM AND INTERVENTION

pancreatitis in which abdominal symptoms predominate. The pathogenesis of pleural effusion in chronic pancreatitis is fistula formation following ductal rupture. Pleural effusion is common with subphrenic abscess and occurs in about 80% of patients. The effusion is often accompanied by basal lung collapse and consolidation, an elevated hemidiaphragm and a subdiaphragmatic air–fluid level. Pleural effusion may occur in a number of renal conditions. Exudative effusions may be seen in uraemia and are often accompanied by pericarditis. Effusions can be large or small and are often unilateral, behaving in a rather indolent fashion. In common with other hypoproteinaemic states, bilateral effusions develop in about 20% of patients with nephrotic syndrome. Peritoneal dialysis can produce pleural effusions by the direct transdiaphragmatic passage of fluid, as occurs with cirrhotic ascites. In common with other ascites-related effusions they are predominantly right sided, but these effusions have a diagnostically high level of glucose. Patients with acquired immune deficiency syndrome are at risk for a variety of pleural infections and neoplasms that can be associated with pleural effusion. These effusions are most frequently caused by pneumonic infections but can also be the result of non-Hodgkin’s lymphoma. Empyema is a suppurative exudate usually parapneumonic. Less commonly it is caused by transdiaphragmatic extension of a liver abscess or by bronchopleural fistula (Fig. 13.11).

Bronchopleural fistula Bronchopleural fistula differs from a pneumothorax in that the communication with the pleural space is via airways rather than distal air spaces. It occurs in two main settings, following partial or complete lung resection and in association with necrotizing infections.

Figure 13.11 Empyema. An enhanced CT shows a fluid collection in the right pleural space. The pleura is thickened but smooth and enhancing. The empyema followed pneumonia. Soft tissue medially is collapsed and consolidated lung. Note the oedema of the extrapleural fat.

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Chylothorax Chylous effusions are commonly milky because they contain triglycerides in the form of chylomicrons. Chylous and non-chylous pleural effusions are indistinguishable on the chest radiograph. In addition, despite its high fat content, the increased protein level of a chylothorax gives it an attenuation on CT similar to that of other pleural effusions. Chylous effusion can cause high signal intensity on T1-weighted images similar to subcutaneous fat. Chyle collects in the pleural space following rupture of the thoracic duct or seepage from collaterals. Rarely, it crosses the diaphragm from the abdomen in the presence of chylous ascites.

Haemothorax On the plain chest radiograph an acute haemothorax is indistinguishable from other pleural fluid collections. Once the blood clots there is a tendency for loculation and occasionally a fibrin body will form. Pleural thickening and calcification are recognized sequelae. On CT a haemothorax may show areas of hyperdensity, and in the subacute or chronic stage it will appear on MRI as a high signal on T1- and T2-weighted images, possibly with a low signal rim caused by haemosiderin. The most common cause of haemothorax is trauma, but it is seen in a number of other conditions, including ruptured aortic aneurysm, pneumothorax, extramedullary haemopoiesis and coagulopathies.

Table 13.2

CAUSES OF ADULT PNEUMOTHORAX

Spontaneous, primary Spontaneous, secondary Airflow obstruction

Asthma Chronic obstructive pulmonary disease Cystic fibrosis

Pulmonary infection

Cavitary pneumonia Tuberculosis Fungal disease AIDS Pneumatocoele

Pulmonary infarction Neoplasm Diffuse lung disease

Metastatic sarcoma Histiocytosis X Lymphangioleiomyomatosis Fibrosing alveolitis Other diffuse fibroses

Hereditable disorders of fibrous connective tissue

Marfan’s syndrome

Endometriosis (catamenial pneumothorax)

Traumatic, noniatrogenic Ruptured oesophagus/trachea Closed chest trauma (± rib fracture) Penetrating chest trauma

PNEUMOTHORAX

Traumatic, iatrogenic Thoracotomy/thoracocentesis

Air in the pleural space is a pneumothorax. When air and liquid are present the nomenclature depends on their relative volumes and the type of liquid. Small amounts of liquid are disregarded and the condition is still called a pneumothorax; otherwise the prefix hydro-, haemo-, pyo- or chylo- is added, depending on the nature of the liquid.

Primary spontaneous pneumothorax Iatrogenic causes apart, the most common type of pneumothorax in the adult is the so-called primary spontaneous pneumothorax (PSP). A pneumothorax occurring without an obvious precipitating event is spontaneous, and if the patient has essentially normal lungs it is in addition primary. PSP occurs predominantly in young adults (65% are between 20 and 40 years of age) and it is five times more common in men than women. Untreated, at least one-third of patients will have a recurrence, most commonly within a few years and on the ipsilateral side. PSP is nearly always caused by the rupture of an apical pleural bleb. Although not detectable on interval chest radiographs, one taken at the time of the pneumothorax will show one or more blebs projecting from the apical lung margin in 20% of patients; such abnormal apical airspaces are much more commonly shown by interval CT.11

Secondary spontaneous pneumothorax A large number of conditions predispose to pneumothorax (Table 13.2). In a number of these disorders pneumothorax occurs frequently.

Percutaneous biopsy Tracheostomy Central venous catheterization

Diagnosis The diagnosis of pneumothorax is made with the chest radiograph, which also detects complications and predisposing conditions and helps in management5 (Fig. 13.12).

Typical signs These are seen on erect radiographs in which the pleural air rises to the lung apex. Under these conditions the visceral pleural line at the apex becomes separated from the chest wall by a transradiant zone devoid of vessels. Though this sounds a straightforward sign to assess, difficulties of interpretation can arise with avascular lung apices, as in bullous disease and when linear shadows are created by clothing or dressing artefacts, tubes and skin folds. Skin folds cause problems particularly in neonates and in old people radiographed slumped against a cassette in the AP projection (Fig. 13.13) Features that help identify artefacts and skin folds include extension of the ‘pneumothorax’ line beyond the margin of the chest cavity, laterally located vessels, and an orientation of a line that is inconsistent with the edge of a slightly collapsed lung. In addition, the margin of skin folds tends to be much wider than the normally thin visceral pleural line. In indeterminate circumstances a repeat

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• THE CHEST WALL, PLEURA, DIAPHRAGM AND INTERVENTION

Figure 13.13 Skin folds mimicking a right pneumothorax (arrows). The laterally located blood vessels, the wide margin of the lines, and the orientation of the lines that is inconsistent with the edge of a slightly collapsed lung help to differentiate them from a real pneumothorax.

chest wall at the apex or laterally. Signs that suggest a pneumothorax under these conditions are12,13 (Fig. 13.14): • ipsilateral transradiancy, either generalized or hypochondrial • a deep, finger-like costophrenic sulcus laterally • a visible anterior costophrenic recess seen as an oblique line or interface in the hypochondrium; when the recess is manifest as an interface it mimics the adjacent diaphragm (‘double diaphragm sign’) • a transradiant band parallel to the diaphragm and/or mediastinum with undue clarity of the mediastinal border • visualization of the undersurface of the heart, and of the cardiac fat pads as rounded opacities suggesting masses • diaphragm depression.

Figure 13.12 Left primary spontaneous pneumothorax. Chest radiograph (A) at deep inspiration and (B) at deep expiration. The left lung has partially collapsed and an area of extreme low density without vascular markings becomes visible. The pneumothorax is accentuated on the chest radiograph at suspended deep expiration (B).

chest radiograph, an expiratory radiograph (see Fig. 13.12B) or one taken with the patient decubitus may clarify the situation. Should doubt still remain, then CT is particularly helpful in distinguishing between bullae and a pneumothorax.

In a patient who cannot stand, the presence of a pneumothorax can be confirmed with a lateral decubitus view or a supine decubitus projection with the cassette placed dorsolaterally at 45 degrees and the X-ray tube angled perpendicular to the cassette. When the pleural space is partly obliterated a pneumothorax may be loculated, and must be differentiated from other localized transradiancies. These include cysts, bullae, pneumatocoeles, pneumomediastinum and local emphysema. These cannot always be differentiated by plain radiographs, but can be by CT.

Atypical signs

Complications Haemopneumothorax

These arise when the patient is supine or the pleural space partly obliterated. In the supine position, pleural air rises and collects anteriorly, particularly medially and basally, and may not extend far enough posteriorly to separate lung from the

This is a common complication of traumatic pneumothorax. Small amounts of serous or bloody fluid may also occur with a spontaneous pneumothorax but only 2% of individuals develop a clinically significant haemothorax in these circumstances.

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Figure 13.14 Supine pneumothorax. Portable chest radiograph (A) before and (B) immediately after development of a pneumothorax. There is an increase of transradiancy at the left lung base, the costophrenic sulcus laterally is more pronounced, and the diaphragm is slightly depressed.

Blood may clot in the pleural space, producing a mass which can mimic a pleural tumour.

Tension pneumothorax This life-threatening complication is present when intrapleural pressure becomes positive relative to atmospheric pressure for a significant part of the respiratory cycle. Tension has an adverse effect on gas exchange and cardiovascular performance, causing a rapid deterioration in the patient’s clinical condition. The diagnosis is usually made clinically and treatment instituted without a radiograph. Should a chest radiograph be taken, it will show contralateral mediastinal shift and ipsilateral diaphragm depression. Mild degrees of contralateral mediastinal shift are not unusual with a nontension pneumothorax because of the negative pressure in the normal pleural space. Moderate or gross mediastinal shift, however, should be taken as indicating tension, particularly if the ipsilateral hemidiaphragm is depressed.This latter sign is the more reliable and is almost invariably present with significant tension.

Pyopneumothorax This unusual complication is seen most commonly following necrotizing pneumonia or oesophageal perforation.

Adhesions These generate straight band shadows extending from the lung margin to the chest wall. They limit collapse but at the same time may account for continued air leakage from the lung surface, and if they tear they may bleed. They can be identified with CT.

Re-expansion oedema This unusual complication is sometimes seen following the rapid therapeutic re-expansion of a lung that has been markedly collapsed for several days or more. Oedema comes on within hours of drainage, may progress for a day or two and clears within a week. It usually causes only mild morbidity.

PLEURAL THICKENING AND FIBROTHORAX5 Pleural thickening is common and usually represents the organized end stage of various active processes such as infective and noninfective inflammation (including asbestos exposure and pneumothorax) and haemothorax. When generalized and gross, it is termed a fibrothorax and may cause significant ventilatory impairment. Radiologically, pleural thickening gives fixed shadowing of water density, most commonly located in the dependent parts of the pleural cavity. Viewed en profile, it appears as a band of soft tissue density up to approximately 10-mm thick, more or less parallel to the chest wall and with a sharp lung interface. En face, it causes ill-defined, veil-like shadowing. Blunting of the costophrenic angle, often with tenting of the diaphragm, is a common finding. On ultrasound, benign pleural thickening produces an homogeneous echogenic layer just inside the chest wall. It is not reliably detected unless it is 1 cm or more thick. CT on the other hand is very sensitive at detecting pleural thickening, which is most easily assessed on the inside of the ribs, where there should normally be no

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soft tissue opacity. In chronic conditions pleural thickening is commonly accompanied by thickening of the normally inconspicuous fatty layer that lies immediately outside the parietal pleura, a feature that can be appreciated on CT. Fibrous pleural thickening is common in the apical pleural cupola. This may be secondary to tuberculosis or represent apical cap. Caps are age-related changes of unknown aetiology. Sometimes they have a scalloped contour or are associated with a tenting towards the lung. They are as commonly unilateral as bilateral. Caps should be distinguished from the companion shadows of the upper ribs, from extrapleural linear fat deposition and most importantly from a Pancoast’s tumour. Companion shadows of the ribs are usually smoothly bordered towards the lung apex while extrapleural fat is usually bilateral, symmetrical, and also located along the lateral chest wall. Caps may be indistinguishable from Pancoast’s tumour on the chest radiograph. In case of doubt CT or MR should be performed. Fibrous pleural thickening can be induced by asbestos exposure14 (Fig. 13.15). This thickening can be diffuse or is more often multifocal. These pleural plaques can undergo

• THE CHEST WALL, PLEURA, DIAPHRAGM AND INTERVENTION

hyaline transformation, calcify, or ossify. They are most commonly found along the lower thorax and on the diaphragmatic pleura. On CT, they appear as circumscribed areas of pleural thickening separated from the underlying rib and extrapleural soft tissues by a thin layer of fat. Because of their higher density they can easily be differentiated from circumscribed increase of extrapleural fat, as sometimes seen in obese patients. Diffuse pleural thickening is also a manifestation of asbestos exposure. The radiographic definition of diffuse pleural thickening or fibrothorax is somewhat arbitrary. It has been suggested to consider as fibrothorax a smooth uninterrupted pleural density that extends over at least one-quarter of the chest wall. On CT fibrothorax has been defined as a pleural thickening which extends more than 8 cm in the craniocaudal direction, 5 cm laterally and with a thickness of more than 3 mm. Common causes of fibrothorax are empyema, tuberculosis and haemorrhagic effusion. Asbestos exposure-related fibrothorax is less common than pleural plaques and is usually the sequel of a benign exudative effusion. CT may be helpful

Figure 13.15 (A–D) Pleural plaques caused by asbestos exposure. Pleural plaques are most commonly found along the lower thorax, on the diaphragmatic pleura and, when involvement is extensive, also along the lateral and anterior thorax (arrows). They can partially or completely calcify or ossify.

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to find the aetiology of the fibrothorax. Extensive calcification favours previous tuberculosis or empyema5 (Fig. 13.16). Asbestos exposure-related fibrothorax is usually bilateral and rarely calcified. Generalized, postinflammatory pleural thickening must be distinguished from diffuse pleural malignancy caused by mesothelioma, metastatic disease (particularly adenocarcinoma), lymphoma and leukaemia. Mesothelioma and adenocarcinoma cause diffuse pleural thickening which is often lobulated, and may surround the whole lung and extend into and along fissures. These features are frequently obscured by an effusion. The most useful signs on CT that indicate malignant as opposed to benign pleural thickening are circumferential thickening, nodularity, parietal thickening of more than 1 cm, and involvement of the mediastinal pleura5 (see Figs 13.18, 13.19). MRI signal intensity seems to be a valuable additional feature for differentiating benign from malignant disease, especially since MRI is often able to demonstrate the tumour extension into the chest wall. Signal hypointensity with long TR sequences is a reliable predictive sign of benign pleural disease15.

PLEURAL CALCIFICATION Pleural calcification is most commonly seen following asbestos exposure, empyema (usually tuberculous) and haemothorax (Fig. 13.16). In the last two conditions, calcification is irregular, resembles a plaque or sheet, and is contained within thickened pleura. It may occur anywhere but is most common in the lower posterior half of the chest and is usually unilateral, unlike that found in silicosis, particularly of the asbestos-related type, where calcification occurs as more discrete collections within plaques and is usually bilateral.

PLEURAL TUMOURS Localized pleural tumours16 These are relatively uncommon, the most common being a localized fibrous tumour (localized mesothelioma) (Fig.

13.17). These lesions most commonly present in middle age, about half the patients being asymptomatic. Hypertropic osteoarthropathy is a well-recognized complication (10–30% of patients) and uncommonly the tumour produces hypoglycaemia. Microscopically two-thirds are benign and one-third is malignant.The plain radiographic findings are of a pleurallybased, well-demarcated, rounded and often slightly lobulated mass (2–20-cm diameter) which may, because of pedunculation, show marked positional variation with changes in posture and respiration. Pleural fibromas usually make an obtuse angle with the chest wall and may reach enormous sizes. Occasionally they may arise in a fissure. CT findings are similar to those observed on plain radiography: a mobile mass, often heterogeneous because of necrosis, haemorrhage, frequently enhancing after contrast medium administration, and rarely calcified. Malignant types are usually larger than 10 cm and may invade the chest wall. Typically these tumours show low signal intensity on both T1- and T2-weighted images, although tumours with intermediate to high signal intensity have been described.17 Lipomas are asymptomatic benign tumours that are usually discovered incidentally on chest radiographs as sharply defined pleural masses. Diagnosis is easy with CT because this examination can delineate the pleural origin and the fatty composition. This fatty density is homogeneous. When heterogeneous and when also soft tissue attenuation components are found, a liposarcoma should be suspected. Pleural lipomas have high signal intensity on T1-weighted images. On T2-weighted images signal is moderately bright. Diagnosis of pleural extension of bronchogenic carcinoma on a chest radiograph is very difficult.The only reliable indicator is rib destruction.With CT and MRI also diagnosis can be difficult. Features such as a large contact (> 3 cm) between the mass and the pleura, an obtuse angle between the tumour and the chest wall, an associated pleural thickening and the presence of pleural tags usually considered as signs of chest wall invasion also occur in benign lesions. The accuracy of CT can be increased by performing 2D and 3D reconstructions.

Figure 13.16 Pleural calcification. (A,B) On the chest radiograph an extensive sheet-like calcification of the right pleura with additional pleural thickening (old tuberculous empyema) is seen. (C) CT demonstrates the extent and thickness of the pleural calcification (arrow).

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Figure 13.17 Benign pleural fibroma. (A) Frontal and (B) lateral radiographs show a small well-demarcated, homogeneous, slightly lobulated mass (arrows). (C) CT shows that the mass is pleural based, sharply defined, and slightly enhancing.

In cases where tumour invasion is obvious, 2D sagittal or coronal reconstructions can be helpful in ascertaining the extent of the mass. MRI has a slight advantage over CT in the evaluation of chest wall and pleura invasion. Before spiral CT, MRI was considered better for studying superior sulcus tumours and their extension to the chest wall (see Fig. 13.3). However, studies have shown that spiral CT and MRI showed comparable sensitivity but that spiral CT had higher specificity. CT is superior in the detection of pleural calcifications and osseous destruction (see Fig. 13.3D). MDCT can also be used in selected cases to clarify a complex relationship between tumour invading the chest wall and vascular structures of the thoracic inlet. Pleural metastases are the most common pleural neoplasms. They are usually an adenocarcinoma with sites of origin including the ovary, stomach, breast and lung. Pleural metastatic disease can present as a solitary mass but more often multiple pleural locations are seen (Fig. 13.18). Pleural metastases are very often accompanied by pleural effusion, which can be the only finding on a chest radiograph. CT, MRI and ultrasound are more sensitive to demonstrate pleural metastasis as the cause of the pleural effusion.9

On CT malignant mesothelioma presents as a nodular soft tissue mass sometimes with hypodense areas corresponding with necrosis. Metastatic enlargement of hilar and mediastinal nodes is seen in up to 50% of patients. Malignant mesothelioma has a minimally increased signal on T1 and a moderately increased signal on T2. MRI may be superior to CT in determining extent of disease because it allows better evaluation of the relationship of the tumour to the structures of the chest wall, mediastinum and diaphragm. However,

Diffuse pleural tumours Diffuse tumoural thickening of the pleura can be caused by malignant mesothelioma or by pleural metastasis. Both entities are usually indistinguishable with imaging. Diffuse malignant mesothelioma is a rare primary neoplasm and its development is strongly related to asbestos exposure. It presents on a chest radiograph as an irregular and nodular pleural thickening with or without associated pleural effusion. Tumour extension into the interlobular fissures, accompanying pleural effusion, and invasion into the chest wall are better appreciated with CT (Fig. 13.19).

Figure 13.18 Malignant pleural thickening caused by metastatic disease. Malignant pleural thickening was caused by pleural metastases. Note the compression on the right hemidiaphragm and the extension of the tumour into the liver (arrows).

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lesion is adjacent to major cardiovascular structures, such as the aorta.21

Ultrasound Ultrasound is well suited for interventional procedures in the pleura. Because of the development of high-resolution, highfrequency probes with special biopsy ports, ultrasound guided biopsy of small pleural lesions has become possible22. Ultrasound is particularly indicated to guide percutaneous aspiration and catheter drainage of a pleural fluid or air collection, even in small amounts. Advantages of this technique include real-time visualization during needle placement, absence of ionizing radiation, and in the case of biopsy of a mass, the ability to target non-necrotic portions for sampling20. In addition, ultrasound is a safe and convenient method of guiding interventional procedures at the bedside of the patient and obviates the need to transport patients on life support devices to the radiology department. A disadvantage is that ultrasound is limited by attenuation of the beam as it transverses air-filled lung or pleura.

Computed tomography

Figure 13.19 Malignant mesothelioma. (A, B: axial and coronal CT) Diffuse lobulated and nodular thickening of the pleura with tumour extension into the lobar fissure (arrows). Note the metastatic enlargement of some hilar and mediastinal lymph nodes.

in most cases CT and MRI provide similar information. Ultrasound may be a supplementary method for biopsy and surgery planning.18,19

Pleural interventions Fluoroscopy Uni- or bi-planar fluoroscopy was the first imaging technique used to guide percutaneous pleural interventions. The technique is widely available, allows real-time control of the procedure, and gives an overview of the thorax. In addition, the technique is familiar to most investigators.20 However, fluoroscopy is not suitable for every lesion. Small lesions may be difficult or impossible to identify. Some lesions may be superimposed on or not separable from normal thoracic structures. Another important limitation is that biopsy or drainage using fluoroscopic guidance may not be advisable if the

Major advantages of CT over fluoroscopy are its multiplanar capabilities and its exquisite anatomical detail. CT is particularly useful for sampling lesions visible in only a single radiographic projection or when great imaging detail is required for the interventional procedure. The administration of intravenous contrast medium is mandatory for the identification of tissue necrosis, fluid content, and identification of normal and abnormal vascular structures. CT allows for determination of an optimal cutaneous entry point for the biopsy needle or for tube placement. Disadvantages of CT guided interventional procedures include greater patient discomfort lying on the CT table and greater expense than with fluoroscopically guided biopsies. A disadvantage compared to ultrasound is the fact that this technique also requires ionizing radiation. However, the introduction of CT continuous imaging, also called CT fluoroscopy, has improved the ease of performing interventional thoracic procedures because it allows real-time visualization of the lesion and of the progression of the needle or tube23. Compared with conventional spiral CT, there is also a markedly decreased patient radiation dose because the procedure can be shortened.

Magnetic resonance imaging Although MRI is often used for guidance of interventional procedures, little experience has been gained in thoracic or pleural interventions24. This technique combines the absence of ionizing radiation with good anatomical detail and has become possible with the introduction of non-ferromagnetic MRI compatible biopsy needles. Major disadvantages, however, include high cost, limited availability, the length of the procedure and the lack of real-time control.

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THE DIAPHRAGM The diaphragm is only seen because there is air-containing lung adjacent to it superiorly. It is 2–3-mm thick, but this will only be appreciated if there is air immediately beneath it, as with a pneumoperitoneum. Localized loss of clarity occurs when the diaphragm is not tangential to the X-ray beam, but usually indicates adjacent pulmonary or pleural disease, e.g. the costophrenic or costovertebral angles are obliterated by pleural fluid, and much of the diaphragmatic outline may be obliterated by basal pneumonia. Each hemidiaphragm is normally represented on the PA radiograph by a smooth, curved line which is convex upwards. The lateral attachment of the diaphragm to the ribs is represented by the lateral costophrenic recess, a sharply-defined acute angle. When the diaphragm is flat, as in emphysema, the most lateral muscle slips extend slightly upwards and may be seen as digitations. The costophrenic angle then becomes less acute, or even obtuse, and the appearance may simulate a small pleural effusion. Medially, the diaphragm meets the heart at the cardiophrenic angle. This is higher than the costophrenic angle and unlike the latter is often ill-defined owing to the presence of fat. On the right, this may simulate disease in the middle lobe, and on the left, disease in the lower lobe or lingula. Prominent fat pads at the cardiophrenic angles are an occasional cause of overestimation of the transverse cardiac diameter, particularly if the film is underexposed. On correctly exposed radiographs, the relatively low radio-opacity of the fat pad enables it to be distinguished from the cardiac apex. On the lateral radiograph each dome makes an acute angle with the ribs posteriorly to form the posterior costophrenic recesses. The latter lie considerably lower than the highest part of each leaf—a point of great importance, as localized pulmonary or pleural disease adjacent to the posterior aspect of the diaphragm will often not be recognized on the PA radiograph, on which only the highest anterior portion of the diaphragmatic dome is represented. The right hemidiaphragm makes an upward curve as it extends anteriorly to the sternum. This part of its attachment is often poorly defined because of adjacent fat. Localization of disease requires the correct identification of each leaf on the lateral radiographs. The left diaphragm is obscured anteriorly by the heart and usually has an air-distended gastric fundus beneath it; whichever leaf is nearer the film is related to the ribs least magnified by the diverging beam.

Height In most people the diaphragm in the mid lung field lies at the level of the fifth or sixth anterior rib interspace. It may lie at a lower level in normal young individuals, particularly those of an asthenic build and at a slightly higher level in the obese, the elderly and young infants. In over 90% of normal people the right hemidiaphragm is higher than the left. This difference in height on the PA film is usually about 15 mm, but may be as much as 30 mm. Depression of the diaphragm occurs in emphysema and in acute severe asthma, but flattening only occurs in emphysema.

Inversion of the diaphragm is sometimes seen with a tension pneumothorax and with large basal bullae. It is also a common accompaniment of pleural effusions.Table 13.3 shows the most common causes of bilateral symmetrical elevation of the diaphragm. Elevation of a single hemidiaphragm is usually secondary to adjacent pleural, pulmonary or subphrenic disease, or to phrenic nerve palsy (Table 13.4). A minor degree of diaphragmatic elevation is a common accompaniment of pleurisy, lower lobe pneumonia and pulmonary thromboembolism. In the latter there may be no visible change in the affected lung. Upper abdominal inflammatory processes and rib fractures may also cause a high diaphragm. A high hemidiaphragm may be mimicked by a subpulmonary pleural effusion (Fig. 13.20), a large well-defined tumour adjacent to the dome, or by combined middle and lower lobe collapse.

Eventration In eventration a part of the normal diaphragmatic muscle is replaced by a thin layer of connective tissue and a few scattered muscle fibres25. The unbroken continuity differentiates it

Table 13.3 CAUSES OF BILATERAL SYMMETRICAL ELEVATION OF THE DIAPHRAGM Supine position Poor inspiration Obesity Pregnancy Abdominal distension (ascites, intestinal obstruction, abdominal mass) Diffuse pulmonary fibrosis Lymphangitis carcinomatosa Disseminated lupus erythematosus Bilateral basal pulmonary emboli Painful conditions (after abdominal surgery) Bilateral diaphragmatic paralysis

Table 13.4 CAUSES OF UNILATERAL ELEVATION OF THE DIAPHRAGM Posture—lateral decubitus position (dependent side) Gaseous distension of stomach or colon Dorsal scoliosis Pulmonary hypoplasia Pulmonary collapse Phrenic nerve palsy Eventration Pneumonia or pleurisy Pulmonary thromboembolism Rib fracture and other painful conditions Subphrenic infection Subphrenic mass

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Figure 13.20 Subpulmonary pleural effusion. On the (A) erect PA and (B) lateral radiograph the effusion simulates a high hemidiaphragm. (C) Ultrasound and (D) CT clearly show that the effusion is located above the diaphragm. Arrows = diaphragmatic area.

from diaphragmatic hernia. Some authors consider eventration to be a congenital anomaly resulting from failure of muscularization of part or all of the diaphragmatic leaf. Most authors, however, also include within the definition elevation occurring as a result of acquired paralysis with atrophy of the diaphragmatic muscle; an inclusion justified by the fact that many adults with surgically proven eventration have previously had normal chest radiographs. Total eventration shows a marked left-sided predominance, for which there is no acceptable explanation. Although eventration is a recognized cause of respiratory distress in the newborn, it is not usually associated with symptoms in the adult. Localized forms of the condition are relatively common, particularly in the elderly, and predominantly affect the right hemidiaphragm at its anteromedial aspect (Fig. 13.21). The distinction between a localized eventration and a small diaphragmatic hernia or a mass arising from the lung,

pleura, or diaphragm is best made using CT or MRI. The various causes of focal elevation or bulging of a diaphragm are given in Table 13.5.

Movement and paralysis Unequal excursion of the two hemidiaphragms occurs in approximately 80% of normal people. However, this inequality of diaphragmatic excursion is less than 10 mm in most people. While normal young adults can move the diaphragm over at least 30 mm, this range is greatly reduced in the elderly. As the chest radiograph is exposed at the end of a full inspiration, any severe unilateral limitation of diaphragmatic movement will be apparent on this static examination. Diaphragmatic movement is, however, better assessed by fluoroscopy, which should, ideally, be performed in both the AP and lateral projections with the patient erect and supine. The

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Figure 13.21 Focal eventration. (A) PA chest radiograph reveals a soft tissue opacity arising from the diaphragm. (B) CT shows the presence of fat and liver under the elevated part of the diaphragm.

latter position is useful as the range of movement is usually greater than it is in the erect position. With the patient in the lateral position, any inequality of movement of the two leaves is readily assessed and localized restriction of movement identified better26. Restriction of diaphragmatic movement occurs secondary to disease of the phrenic nerve and secondary to inflammatory and painful conditions adjacent to the diaphragm, such as lower lobe pneumonia and subphrenic infection. Phrenic palsy is most commonly secondary to involvement of the phrenic nerve by tumour—usually a bronchial carcinoma. Phrenic nerve paresis may be caused by trauma (road accidents, birth injury, brachial plexus block and phrenic crush), irradiation and a variety of neurological conditions such as poliomyelitis, herpes zoster, and cervical disc degeneration. The recognition of phrenic paresis depends upon finding a high hemidiaphragm which exhibits absent, restricted, or paradoxical movement.The latter is particularly well demonstrated by sniffing. Diaphragmatic motion can also be examined with ultrasound26. Especially in patients who cannot come to the fluoroscopy room, bedside ultrasound is very useful. This technique has also a high accuracy to discover absent and paradoxical diaphragmatic

Table 13.5 CAUSES OF FOCAL ELEVATION (BULGE) OF THE DIAPHRAGM Partial eventration Diaphragmatic hernia Diaphragmatic tumour Pleural tumour Pulmonary tumour Focal diaphragmatic dysfunction Focal diaphragmatic adhesions

motion. In addition measurement of diaphragmatic thickness can be helpful to confirm diaphragmatic paralysis, since a paralysed diaphragm does not thicken during inspiration. An important mimic of phrenic paresis is eventration (usually left sided, see above). In a significant small number of patients in whom there is little doubt that a phrenic paresis exists, no cause can be discovered. In this ‘idiopathic’ group the right leaf is more commonly affected than the left and it has been suggested that the palsy may be a legacy of previous viral neuritis. Weakness or paralysis of both hemidiaphragms is most commonly seen in association with chronic neuromuscular disease and causes severe clinical disability. Bilateral paralysis may not be recognized by fluoroscopic examination, for passive descent of the diaphragm may occur with inspiration.

Diaphragmatic hernias Intrathoracic herniation of abdominal contents occurs through congenital defects in the muscle, through traumatic tears or, most commonly, through acquired areas of weakness at the central oesophageal hiatus. Congenital hernias presenting in childhood are discussed elsewhere. When the defect is small it may not come to attention until adulthood, when it usually presents as an incidental abnormality on the chest radiograph. Bochdalek defects through the pleuroperitoneal canal occur along the posterior aspect of the diaphragm and the hernia usually contains retroperitoneal fat or a portion of kidney or spleen27 (Fig. 13.22). The majority occur on the left. A well-defined, dome-shaped, soft tissue opacity is seen midway between the spine and lateral chest wall on the frontal view and above the posterior costophrenic recess on the lateral view. It may appear to ‘come and go’ on serial PA radiographs because of varying degrees of inspiration and differences in transdiaphragmatic pressure. It has been shown that asymptomatic small Bochdalek hernias are present in 6% of otherwise

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Figure 13.22 Bochdalek hernia. (A) Lateral chest radiograph shows a focal bulge on the diaphragmatic contour just above the posterior costophrenic recess (arrows). (B) CT shows a fatty mass abutting the defect in the posteromedial aspect of the left hemidiaphragm (arrowheads).

normal adults.These hernias appear on a lateral radiograph as a focal bulge centred approximately 4–5 cm anterior to the posterior diaphragmatic insertion. On CT and MRI the diagnosis can be made when a soft tissue or fatty mass is seen protruding through a small defect in the posteromedial aspect of either hemidiaphragm. A Morgagni hernia presents in adulthood as an anterior opacity at the right cardiophrenic angle. It frequently contains omentum and may contain gut. Its smooth, welldefined margin and soft tissue radiodensity usually allow its differentiation from the much more common fat pad collection at this site. It is more difficult to differentiate from a low-lying pericardial cyst. Morgagni hernias containing gut can be diagnosed using barium but the diagnosis is more simply established by means of CT or MRI. Hernias through the oesophageal hiatus are extremely common, particularly in the elderly in whom they may be an incidental finding on CT.

Diaphragmatic trauma Because diaphragmatic rupture is often associated with thoracic or abdominal injuries that require surgical treatment, many cases are diagnosed during surgery28. If surgery is not indicated, diaphragmatic tear can be missed, especially when it is small and when there is no herniation of abdominal structures to the chest. That is why suspicion is needed in all cases of trauma to the lower chest, but also in patients with severe pelvic trauma. The chest X-ray should be evaluated carefully. Special attention has to be given to small changes in the diaphragm or to basal lung atelectasis or consolidation. If possible, the post-traumatic thorax should always be compared with previous chest X-rays. The diagnostic tools are different in the acute and latent phase. In the acute phase surgical procedures are often necessary and if the patient has severe injuries bedside examinations, such as chest X-ray and ultrasound, should be relied upon (Fig. 13.23). In the latent phase barium studies, spiral CT and MRI can give additional diagnostic information.

Figure 13.23 Traumatic diaphragmatic rupture. (A) Ultrasound and (B) CT show traumatic laceration of the liver and herniation of liver tissue into the fluid-filled pleural space.

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In the acute phase the chest X-ray is normal in about onequarter of cases. In some cases gas and fluid shadows are seen in the thorax. Sometimes there is only a localized density in close relationship to the diaphragm, or an alteration in the diaphragmatic shape. The position of a nasogastric tube can help to localize the gastric fundus, but does not tell anything about the position of the diaphragm, which is essential in the diagnosis of a diaphragmatic tear. A follow-up X-ray of an acutely injured patient showing progressive opacification of one thorax side by a gas-filled structure is strongly suggestive for diaphragmatic rupture (Fig. 13.24). Barium studies can be very helpful in making the correct diagnosis, when an extrinsic narrowing occurs on the border of the stomach or bowel at the point where they pass the

• THE CHEST WALL, PLEURA, DIAPHRAGM AND INTERVENTION

diaphragmatic tear. However, since barium studies cannot be used in emergency situations, they are predominantly indicated in the latent phase and eventually in the obstructive phase. Pneumoperitoneum can be established by bringing a small amount of air into the abdominal cavity. If air shifts through the diaphragmatic tear and a pneumothorax occurs, the test is diagnostic for diaphragmatic rupture. However, no shift of air will occur when the tear is closed by adhesions or by the herniated organs themselves. In this case the exact position of the diaphragm can be visualized since it is delineated by the subdiaphragmatic air. Ultrasound can be diagnostic if both the diaphragm and the herniated organs can be visualized. Examination of the right hemidiaphragm is facilitated by the presence of the liver,

Figure 13.24 Traumatic rupture of the diaphragm diagnosed 2 months after the trauma. (A) Detail of the left hemithorax. The supine chest radiograph immediately after the trauma shows multiple rib fractures, a pleural effusion and a poorly-defined opacity at the left lung base. (B) One month after the trauma the chest radiograph is normal but (C) 2 months later a large gas-filled structure corresponding with the air-containing stomach is seen in the left hemithorax suggesting rupture and herniation. (D) CT confirmed the diagnosis of diaphragmatic rupture and shows the herniated stomach (S).

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Figure 13.25 Primary malignant tumour of the diaphragm. (A) PA chest radiograph shows a small focal bulge of the diaphragm in combination with a small pleural effusion. (B) CT and (C) MRI show an irregular mass with central necrosis in continuity with the right hemidiaphragm (arrows).

acting as an acoustic window. However, this technique is limited by the often minimal visualization of the diaphragm itself, the tenderness over the upper abdomen and the presence of gas in herniated bowel. The MDCT diagnosis of diaphragmatic rupture is largely based on the fact that abdominal organs are seen in the pleural space outside the diaphragm. However, the identification of the diaphragm on standard CT images can be very difficult; multiplanar CT reconstructions can help to show the defect directly. The more usual CT signs of diaphragmatic rupture include29,30: discontinuity of the diaphragm with direct visualization of the diaphragmatic injury; herniation of abdominal organs with liver, bowel or stomach in contact with the posterior ribs (‘dependent viscera sign’); thickening of the crus (‘thick crus sign’); constriction of the stomach or bowel (‘collar sign’); active arterial extravasation of contrast material near the diaphragm; and, in the case of a penetrating diaphragmatic injury, depiction of a missile or puncturing instrument trajectory. Because it is in most cases difficult to perform an MRI examination during the acute phase, this technique is more valuable in the latent phase. It allows both a static and a dynamic view of the diaphragm. However, as in CT, the parts of the diaphragm in contact with the liver and spleen are not visible.

Neoplasms of the diaphragm Primary tumours of the diaphragm are rare (Fig. 13.25). Both benign and malignant varieties are mostly derived from muscle, fibrous tissue, blood vessels, or fat. They are usually well defined and on the right may mimic an elevated diaphragm or local eventration. Calcification has been described in lipomas. Malignant tumours may present as a pleural effusion. Secondary invasion of the diaphragm by malignant tumours of the lung, pleura, stomach, or pancreas may occur. Imaging with CT or MRI is particularly helpful in such patients.

REFERENCES 1. Kuhlman J E, Bouchardy L, Fishman E K et al 1994 CT and MR imaging evaluation of chest wall disorders. RadioGraphics 14: 571–595 2. Fortier M, Mayo J R, Swensen S J et al 1994 MR imaging of the chest wall lesions. Radiographics 14: 597–606

3. Takasugi J E, Rapoport S, Shaw C 1989 Superior sulcus tumors: the role of imaging. J Thorac Imaging 4: 41–48 4. Deschildre F, Petyt L, Remy-Jardin M et al 1994 Evaluation de la TDM par balayage spirale volumique (BSV) vs IRM dans le bilan d’extension pariétal des masses thoraciques. Rev Im Med 6(S): 188 5. Müller N L 1993 Imaging the pleura. Radiology 186: 297 6. McLoud T C, Flower C D R 1991 Imaging the pleura: sonography CT, and MR imaging. Am J Roentgenol 156: 1145–1153. 7. Fleischner F G 1963 Atypical arrangement of free pleural effusion. Radiol Clin North Am 1: 347–362 8. Lomas D J, Padley S G, Flower C D R 1993 The sonographic appearances of pleural fluid. Br J Radiol 66: 619–624 9. McLoud T C 1998 CT and MR in pleural disease. Clin Chest Med 19: 261–276 10. Bittner R C, Schnoy N, Schonfeld N et al 1995 High-resolution magnetic resonance tomography (HR-MRT) of the pleura and thoracic wall: normal findings and pathological changes. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 162: 296–303 11. Lesur O, Delorme N, Fromaget J M et al 1990 Computed tomography in the etiologic assessment of idiopathic spontaneous pneumothorax. Chest 98: 341–347 12. Gordon R 1980 The deep sulcus sign. Radiology 136: 25–27 13. Rhea J T, vanSonnenberg E, McLoud T C 1979 Basilar pneumothorax in the supine adult. Radiology 133: 593–595 14. Aberle D R, Gamsu G, Ray C S 1988 High resolution CT of benign asbestos-related diseases: clinical and radiographic correlation. Am J Roentgenol 151: 883 15. Falaschi F, Battolla L, Maschalchi M et al 1996 Usefulness of MR signal intensity in distinguishing benign from malignant pleural disease. Am J Roentgenol 166: 963–968 16. England D M, Hochholzer L, McCarthy M J 1989 Localized benign and malignant fibrous tumors of the pleura. A clinicopathologic review of 223 cases. Am J Surg Pathol 13: 640–658 17. Kinoshita T, Ishii K, Miyasato S 1997 Localized pleural mesothelioma: CT and MR findings. Magn Reson Imaging 15: 377–379 18. Layer G, Schmitteckert H, Steudel A et al 1999 MRT, CT and sonography in the preoperative assessment of the primary tumor spread in malignant pleural mesothelioma. RoFo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 170: 365–370 19. Rusch V W, Godwin J D, Shuman W P 1988 The role of computed tomography scanning in the initial assessment and the follow-up of malignant pleural mesothelioma. J Thorac Cardiovasc Surg 96: 171 20. Klein J S, Zarka M 1997 Transthoracic needle biopsy: an overview. J Thorac Imaging 12: 232–249 21. vanSonnenberg E, Casola G, Ho M et al 1988 Difficult thoracic lesions: CT-guided biopsy experience in 150 cases. Radiology 167: 457–461 22. Ikezoe J, Morimoto S, Kozuka T 1991 Sonographically guided needle biopsy of thoracic lesions. Semin Intervent Radiol 8: 15–22

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23. White C S, Meyer C A, Templeton P A 2000 CT fluoroscopy for thoracic interventional procedures. Radiol Clin North Am 38: 303–322 24. Buecker A, Adam G, Neuerburg J M et al 1998 MR-guided biopsy using a T2-weighted single-shot zoom imaging sequence (local look technique). J Magn Reson Imaging 8: 955–959 25. Deslauriers J 1988 Eventration of the diaphragm. Chest Surg Clin North Am 8: 315–330 26. Houston J G, Fleet M, Cowan M D et al 1995 Comparison of ultrasound with fluoroscopy in the assessment of suspected hemidiaphragmatic movement abnormality. Clin Radiol 50: 95–98

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27. Demartini W J, House A J S 1980 Partial Bochdalek herniation: computerized tomographic evaluation. Chest 77: 702–704 28. Shah R, Sabanathan S, Mearns J A et al 1995 Traumatic rupture of diaphragm. Ann Thorac Surg 60: 1444–1449 29. Bergin D, Ennis R, Keogh C et al 2001 The “dependent viscera” sign in CT diagnosis of blunt traumatic diaphragmatic rupture. Am J Roentgenol 177: 1137–1140 30. Leung J C, Nance M L, Schwab C W et al 1999 Thickening of the diaphragm: a new computed tomography sign of diaphragm injury. J Thorac Imaging 14: 126–129

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CHAPTER

The Mediastinum, Including the Pericardium*

14

Sharyn L. S. MacDonald and Simon Padley

Mediastinal diseases • Mediastinal masses • Other mediastinal lesions The pericardium • Normal anatomy

• Imaging pericardial disease • Developmental anomalies • Acquired pericardial disease

MEDIASTINAL DISEASES MEDIASTINAL MASSES Incidence The true incidence of mediastinal masses is difficult to ascertain because most surgical series are biased towards patients requiring surgery and therefore do not include all aneurysms, intrathoracic goitres, or lymph node masses in patients with established diagnoses such as lymphoma or sarcoidosis. In adult surgical series1–3, the most frequent tumours are of neurogenic (17–23%) or thymic (20–25%) origin, or are neoplastic disorders of lymph nodes (10–20%). Developmental cysts, thyroid masses, and germ-cell tumours constitute the next most frequent group (approximately 10% each). In children, neuroblastoma/ganglioneuroma, foregut cysts and germ-cell tumours account for over three-quarters of cases, whereas thymoma and thyroid masses are rare. Mediastinal masses are conventionally divided by location into anterior, middle, or posterior mediastinal compartments. This division into compartments is for descriptive convenience only, since it is not based on anatomical boundaries that limit spread; nor do radiologists in general use these terms in the way they are defined by anatomists. Localization of a mass to one of these compartments is a useful step towards reaching the most appropriate diagnosis or differential diagnosis; the age of the patient and such characteristics as the presence of calcification, fat, fluid, or soft tissue within the mass, invasion of the mediastinal fat (indicating malignant rather that

benign disease) and contrast enhancement characteristics on computed tomography (CT) and magnetic resonance imaging (MRI) are important in narrowing the differential diagnosis, which is considered later in this chapter.

Imaging techniques Mediastinal masses are often incidentally detected on chest radiograph. Despite diagnostic limitations the chest radiograph is also important for detecting and localizing mediastinal masses when suspected clinically.

Computed tomography Computed tomography is the most useful investigation for localizing, characterizing and demonstrating the extent of a mediastinal mass and its relationship to adjacent structures. Multidetector CT (MDCT) following intravenous contrast medium with multiplanar reformats provides an excellent assessment of mediastinal structures, including vessels, and has largely obviated the need to proceed to MRI for imaging in the coronal and sagittal planes. CT may also be used to guide biopsy, plan resection and follow response to therapy.

Magnetic resonance imaging Magnetic resonance imaging remains useful for imaging suspected neurogenic tumours, for demonstrating intraspinal extension of a mediastinal mass and for further evaluating the relationship of a mass to the heart, pericardium and larger intrathoracic vessels. MRI may have advantages over

*The section on the pericardium is adapted from Chapter 42 by Anna Rozenshtein, Lawrence M. Boxt, Kathleen Reagan and Robert M. Steiner from the fourth edition of this textbook.

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contrast-enhanced CT for distinguishing between solid tissue and adjacent vessels (fast flowing blood in vessels results in a signal void on spin-echo sequences) and may be useful for confirming that a mass is cystic. Unlike CT, MRI is not sensitive to the presence of calcification.

Ultrasound Ultrasound of the mediastinum, including echocardiography and endoscopic ultrasound, may be of use in selected patients, in particular for distinguishing cystic from solid mediastinal masses and for distinguishing cardiac from paracardiac masses. Ultrasound may also be used to guide mediastinal biopsy.

Radionuclide examinations Radionuclide examinations have a limited role in the assessment of mediastinal masses. Positron emission tomography (PET) and PET–CT using [F-18]2-deoxy-d-glucose (18F-FDG) has proven useful in the evaluation of mediastinal lymph node involvement in lung cancer and lymphoma4,5. Radionuclide examinations may also be useful in the imaging of thyroid masses, neuroendocrine tumours and phaechromocytomas.

Thyroid masses Most thyroid masses (Fig. 14.1) in the mediastinum represent downward extensions of either a multinodular colloid goitre or, occasionally, an adenoma or carcinoma. Intrathoracic thyroid masses usually have a well-defined outline, which may be spherical or lobular. Rounded or irregular, well-defined areas of calcification may be seen in benign areas, whereas amorphous cloud-like calcification is occasionally seen within carcinomas. Almost all intrathoracic thyroid masses displace the trachea, which may also be substantially narrowed. The direction of displacement depends on the location of the mass. Thyroid

masses are most commonly anterior and lateral to the trachea. Posteriorly placed masses often separate the trachea and the oesophagus, and such separation by a localized mass rising into the neck is virtually diagnostic of a thyroid mass. Radionuclide imaging with 123I or 131I demonstrates the presence of thyroid tissue within the mediastinum in almost all intrathoracic goitres. Although radionuclide imaging is a sensitive and specific method of determining the thyroid nature of an intrathoracic mass, CT is more useful as the initial investigation because it provides more information should the mass prove to be something other than a thyroid lesion and is almost as specific as nuclear medicine in diagnosing a thyroid origin. CT optimally demonstrates the shape, size and position of the mass (Fig. 14.2)6,7. It is usually possible to diagnose a thyroid origin by noting a well-defined mass in the paratracheal or retrotracheal region, almost invariably being continuous with the thyroid gland in the neck. Another useful sign is that normal thyroid tissue within the mass shows a higher attenuation value than muscle on images obtained both before and after contrast medium. Focal areas of calcification are frequently identified and rounded, focal, nonenhancing low density areas are common. It is not possible to distinguish between a benign and malignant mass on CT unless the tumour has clearly spread beyond the thyroid gland. It should, however, be noted that multiple masses are a feature of benign multinodular goitre, though carcinoma can develop in multinodular goitre. MRI of intrathoracic goitre, like CT, can identify cystic and solid components, and can show haemorrhage to advantage, but will not reliably demonstrate calcification.

Parathyroid masses The parathyroid glands may migrate into the chest during fetal development. Mediastinal parathyroid tumours causing hyperparathyroidism are most commonly located in or around

Figure 14.1 Intrathoracic thyroid mass on (A) AP and (B) lateral radiographs. This benign multinodular goitre is predominantly posterior to the trachea with components to either side, resulting in forward displacement and narrowing of the trachea.

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otherwise normal gland, may lie within a thymoma, or may follow thymic irradiation for Hodgkin’s disease10.

Thymomas

Figure 14.2 Intrathoracic extension of thyroid on coronal image from multidetector CT. Contrast medium has been administered. The thyroid demonstrates heterogeneous contrast enhancement, and is mainly of greater attenuation than skeletal muscle. There are flecks of calcification in the gland.

the thymus. They are small and almost never visible on plain radiographs. They are probably best detected using ultrasound (Fig. 14.3) and if not readily apparent, by subsequent 99m Tc-sestamibi imaging with CT or MRI only in selected cases8,9.

Thymic tumours Tumours that arise within the thymus include thymoma, lymphoma, thymic carcinoid, germ-cell tumour/teratoma and thymolipoma. Thymic cysts are another cause of a thymic mass (Fig. 14.4). They may be simple cysts and occur in an

Figure 14.3 High-resolution ultrasound of the left lobe of the thyroid (LLT) anterior to a parathyroid adenoma (white arrows). There is a small area of cystic degeneration within the posterior aspect of the adenoma. Black arrows indicate the common carotid artery.

Thymomas are the most common tumour of the thymus in adults, and the most common primary tumour of the anterior mediastinum in adults. The average age at diagnosis is approximately 50 years, earlier in those who present with myasthenia gravis. Thymomas are rare under 20 years of age and extremely unusual below the age of 15. Up to 50% of patients with thymoma have myasthenia gravis, and approximately 10–20% of patients with myasthenia gravis have a thymoma. A variety of other syndromes are seen in patients with thymoma, including hypogammaglobulinaemia and red cell aplasia11,12. Most thymomas (90%) arise in the upper anterior mediastinum. The mass is usually anterior to the ascending aorta, lying above the right ventricular outflow tract and pulmonary artery (Fig. 14.5). A few are situated more inferiorly, projecting from the left or right heart border, or lying close to the cardiophrenic angles. They are usually spherical or oval in shape and may show lobulated borders. They may contain one or more cysts and a few are predominantly cystic (Fig. 14.6). Calcification, punctate or curvilinear, may be seen (Fig. 14.7). All of these features are best demonstrated using CT13,14, which is the most sensitive technique for the detection of thymoma in patients with myasthenia gravis15. The diagnosis depends on identifying a focal swelling rather than applying a specific measurement. Thymomas as small as 1.5– 2.0 cm in diameter are readily identified over the age of 40, largely because the rest of the thymus is atropic. Before age 40, and particularly before 30, diagnosing a small thymoma can be difficult, because the normal gland is variable in size and in myasthenia gravis the associated hyperplasia may cause a bulky gland. In these circumstances a useful rule is that thymoma usually gives rise to an asymmetrical focal swelling. Fortunately, thymoma is so infrequent in children that the potentially difficult problem of finding a thymoma in a child with myasthenia gravis rarely arises. Thymomas usually show homogeneous density and uniform enhancement after contrast medium and may occasionally be cystic. Invasion of the mediastinal fat and adjacent pleura may be identified with invasive thymomas (Fig. 14.8), and while CT shows such invasion to advantage it cannot reliably diagnose invasive thymoma if the tumour is still confined to the thymus16. Remote pleural metastases resulting from transpleural spread are a feature of invasive thymomas, and therefore the whole of the pleural cavity should be carefully examined16 (Fig. 14.8). MRI, in general, provides similar information to CT, though it can be useful to show mediastinal spread when there is doubt on the latter. On T1-weighted images, thymomas have a signal intensity similar to that of muscle and the adjacent normal thymic tissue. On T2-weighted images, the signal intensity increases and may make it difficult to distinguish a thymoma from adjacent mediastinal fat. Heterogeneity of signal intensity caused by septation, cystic change and haemorrhage is common16.

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Figure 14.4 Thymic cyst producing an anterior mediastinal mass on (A) AP and (B) lateral chest radiographs, filling in the normal retrosternal window and widening the mediastinum. (C) The cystic nature is best demonstrated by CT.

Figure 14.5 Thymic enlargement on (A) PA and (B) lateral radiographs of a patient with a malignant thymic mass. The lateral view demonstrates pleural metastases posteriorly (arrows). (C) CT confirms the anterior position of the primary tumour suspected from the filling of the retrosternal window apparent on the lateral radiograph (B).

Thymic carcinomas Thymic carcinomas are aggressive locally invasive malignancies that have frequently metastasized to regional lymph nodes and distant sites at presentation. They are typically large, heterogeneous masses, containing areas of necrosis and calcification and demonstrating evidence of invasion of adjacent structures, in particular the mediastinum, pericardium and pleura17,18.

Thymic lymphoma Thymic lymphoma is usually part of generalized disease, but isolated involvement is very occasionally encountered. It is most commonly associated with Hodgkin’s disease. The imaging features are the same as those of thymoma. Figure 14.6 Cyst formation in a thymoma demonstrated on CT in a patient with myasthenia gravis. The wall is irregular and enhances following administration of intravenous contrast medium.

Thymic carcinoid Thymic carcinoid is histologically distinct from thymoma. A noteworthy feature is that these tumours may secrete

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Figure 14.7 Thymoma presenting on a chest radiograph obtained before orthopaedic surgery in an otherwise asymptomatic elderly female patient. There is a large anterior mediastinal mass (A) with coarse calcification visible on (B) the lateral view and (C) contrast-enhanced CT.

Figure 14.8 Invasive thymoma in a young man. (A) Shows a lobular anterior mediastinal mass associated with a pleural effusion. (B) Image obtained through the lower chest demonstrates mixed soft tissue (arrows) and fluid attenuation owing to transpleural spread of tumour.

adrenocorticotropic hormones in sufficient quantities for the patient to present with Cushing’s syndrome. The plain radiograph and CT features of thymic carcinoid are indistinguishable from those of thymoma.

Thymolipomas Thymolipomas are rare tumours composed of a mixture of mature fat and normal-looking or involuted thymic tissue.The age range is 3–60 years. Individual cases have been reported in association with a variety of conditions, including myasthenia gravis, aplastic anaemia, Graves’ disease and hypogammaglobulinaemia. Thymolipomas can grow to a very large size before discovery and, being soft, mould themselves to the adjacent mediastinum and diaphragm, and may mimic cardiomegaly or lobar collapse19. CT/MRI show the fatty nature of the mass, with islands of thymus and fibrous septa running through the lesion19,20.

Thymic hyperplasia The most common association of thymic hyperplasia is myasthenia gravis, but thymic hyperplasia is also seen in other conditions, notably thyrotoxicosis. Thymic hyperplasia is rarely severe enough to cause visible enlargement of the thymus, but when it does, both lobes are enlarged, usually uniformly, though on occasion thymic hyperplasia may mimic a thymic mass. The thymus may atrophy due to stress or as a consequence of steroid or antineoplastic drug therapy21,22.The gland usually returns to its original size on recovery or cessation of treatment, but it may become larger than its previous normal size in the phenomenon known as rebound thymic hyperplasia. It may then be difficult to distinguish between thymic rebound and thymic involvement by neoplasm. The diagnosis depends on a known reason for thymic rebound, the absence of clinical

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features to indicate tumour recurrence and the presence of an enlarged, normally-shaped thymus22,23.

Germ-cell tumours of the mediastinum Germ-cell tumours of the mediastinum are believed to be derived from primitive germ-cell elements left behind after embryonal cell migration. The mediastinum is the most common extragonadal site for these tumours, almost all of which arise in the anterior mediastinum, within, or in intimate contact with, the thymus. Mediastinal germ-cell tumours include mature teratoma (benign) and a number of malignant forms, chiefly seminoma, malignant teratoma, embryonal carcinoma, choriocarcinoma, endodermal sinus tumour and tumours with mixtures of these cell types24. Malignant germ-cell tumours secrete human chorionic gonadotrophin and α-fetoprotein, which can be used as markers to diagnose and monitor the tumour.

Mature teratomas Mature teratomas are the most common mediastinal germcell tumour2; most are cystic. Mature teratomas are found at all ages, particularly in adolescents and young adults, with women slightly outnumbering men25,26. They are usually asymptomatic and diagnosed incidentally on chest radiography or CT, but may give rise to cough, dyspnoea, or chest pain if they compress the bronchial tree or superior vena cava, or if they rupture into the mediastinum or lung. They are frequently large and may be huge, occupying much of one hemithorax. The lesions are usually stable, but haemorrhage or infection may lead to a rapid increase in size. On chest radiograph or CT most mature teratomas present as a well-defined, rounded or lobulated mass, localized to the anterior mediastinum. Fat and calcification may occasionally be identified on chest radiograph. CT appearances are variable, combinations of fat, fluid, soft tissue components and calcification may be seen25 (Fig. 14.9). The presence of fat, either as focal collections or fluid fat, is a very helpful diagnostic feature

favouring mature (benign) cystic teratoma over the other causes of anterior mediastinal mass. MRI provides similar information to CT, although it may not detect calcification.

Malignant germ-cell tumours Malignant germ-cell tumours are usually seen in young adults and are much more common in men (>90%) than women. Seminoma is the most common form27. They are more commonly more symptomatic than mature teratoma, usually due to mass effect or invasion of adjacent structures. The plain radiographic findings are similar except that the malignant tumours are more often lobular in outline, fat density is not seen and visible calcification is rare. Because they are malignant tumours, they grow rapidly and metastasize readily to the lungs, bones, or pleura. CT shows a lobular, asymmetrical mass.The adjacent mediastinal fat planes may be obliterated, and the tumours are either of homogeneous soft tissue density or show multiple areas of contrast enhancement interspersed with rounded areas of decreased attenuation due to necrosis and haemorrhage28,29. MRI provides similar information to CT (Fig. 14.10).

Mediastinal lymphadenopathy Lymph node calcification Extensive lymph node calcification is common following tuberculosis and fungal infection, and is occasionally seen with other infections. It may also be encountered in a variety of other conditions, notably sarcoidosis, silicosis and amyloidosis. Although it may be seen in lymph node metastases from calcifying primary malignancies, such as osteosarcoma, chondrosarcoma and mucinous colorectal and ovarian tumours, lymph node calcification is rare in metastatic neoplasm. It is virtually unknown in untreated lymphoma though it is occasionally seen in nodes involved by Hodgkin’s disease following therapy. CT demonstrates more calcification than plain radiographic techniques. Calcification is not usually visible on MRI. Two

Figure 14.9 Teratoma in a young man undergoing an immigration chest radiograph. (A) There are no specific features on the plain radiograph to indicate the nature of the mass. (B) CT demonstrates that the opacity visible on the chest radiograph is well defined and contains soft tissue and fat densities.

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with inflammatory disorders, particularly tuberculosis, fungal disease32, sarcoidosis and neoplasm. When striking, it points particularly to the diagnosis of metastatic neoplasm from a highly vascular primary tumour, such as melanoma, renal and thyroid carcinoma, carcinoid tumour, or leiomyoma/sarcoma. A rare cause of strikingly uniform contrast enhancement is Castleman’s disease. A low-density centre with rim enhancement of the enlarged node is a useful pointer towards the diagnosis of tuberculous infection31 (Fig. 14.12).

Lymph node enlargement Figure 14.10 Malignant germ-cell tumour in a 25 year old man presenting with chest pain, dyspnoea, malaise and features of pericardial tamponade. The CT shows a lobular asymmetrical mass with low attenuation areas corresponding to necrotic tumour intersected by neoplastic septation.

common patterns of calcification are coarse, irregularly-distributed clumps within the node and homogeneous calcification of the whole node. A strikingly foamy appearance is seen with Pneumocystis jiroveci (previously P. carinii) infection in acquired deficiency syndrome (AIDS) patients30 and in some cases of metastatic mucinous neoplasms. Sometimes there is a ring of calcification at the periphery of the node—so-called ‘eggshell calcification’, which is a particular feature of sarcoidosis and of prolonged dust exposure in coal and metal mines.

Low attenuation nodes On CT, areas of low attenuation within enlarged nodes, corresponding to necrosis (Fig. 14.11), may be seen in a variety of conditions, particularly tuberculosis31 and occasionally in fungal disease32, infections in immunocompromised patients, metastatic neoplasm (notably from testicular tumours33) and lymphoma34. Attenuation values below that of water are seen in fatty replacement of inflammatory nodes and have also been described in Whipple’s disease35.

When mediastinal or hilar nodes are greater than 2 cm in their short axis diameter, the enlargement is likely to be due to metastatic carcinoma, malignant lymphoma, sarcoidosis, tuberculosis, or fungal infection. With lesser degrees of enlargement the differential diagnosis broadens to include lymph node hyperplasia and pneumoconiosis. Widespread moderate mediastinal lymph node enlargement is a frequent accompaniment of chronic diffuse lung disease and bronchiectasis. Normal sized nodes are demonstrable at CT/MRI, but are not visible on plain chest radiographs or on conventional tomography. The ease with which enlarged nodes can be recognized using plain radiography varies according to their location. Nodes in the right paratracheal group are readily identified: they show uniform or lobular widening of the right paratracheal stripe. Enlarged azygos nodes displace the azygos vein laterally and enlarge the shadow that normally represents just the azygos vein to over 10 mm in its short axis diameter. If the lymph nodes beneath the aortic arch become large enough to project beyond the aortopulmonary window they cause a local bulge in the angle between the aortic arch and the main pulmonary artery. Hilar lymph node enlargement causes enlargement and/or lobulation of the outline of the hilar shadows (Fig. 14.13).The diagnosis of lymph node enlargement on

Contrast-enhanced CT Contrast enhancement of enlarged nodes, when moderate in degree, is non-specific, being seen

Figure 14.11 Low attenuation lymph node enlargement. There is necrosis within malignant right hilar and subcarinal nodes which have arisen from the primary tumour in the right lung.

Figure 14.12 Tuberculous lymphadenopathy. Following contrast enhancement there is rim enhancement and central low attenuation due to caseation (arrows).

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normally concave toward the lung, flattens or becomes convex towards the lung, an appearance that may be confused with left atrial enlargement. Posterior mediastinal lymph node enlargement causes localized displacement of the paraspinal and paraoesophageal lines. Lymph nodes elsewhere in the mediastinum are only recognizable on plain radiographs when substantially enlarged (Fig.14.14). CT is an excellent method for detecting mediastinal lymph node enlargement (Figs 14.15–14.17). It is usually easy to distinguish between the normal vascular structures and enlarged lymph nodes using contrast-enhanced CT, although without excellent opacification of the left atrium it may, on occasion, be difficult to distinguish enlarged subcarinal lymph nodes from a normal or enlarged left atrium. The short axis measurement provides the most representative guide to true size, since long axis measurements vary to a significant degree according to the orientation of the lymph node within the CT section. In the assessment of lymph node enlargement, MRI provides essentially the same information as CT, although its use is limited to selected cases due to longer acquisition times and relatively limited spatial resolution (which may make measurement of individual nodes difficult). Figure 14.13 Sarcoidosis producing symmetrical bilateral hilar lymph node enlargement.

plain radiography depends on the recognition of the edge of a round or oval hilar mass, an analysis that requires a detailed understanding of the normal anatomy of the hilar blood vessels. Subcarinal lymph node enlargement widens the carinal angle and displaces the azygo-oesophageal line, so that the subcarinal portion of the azygo-oesophageal line, which is

Sarcoidosis Sarcoidosis is the most common cause of intrathoracic lymph node enlargement, the hilar nodes being enlarged in almost all cases36. Additionally, tracheobronchial, aortopulmonary and subcarinal nodes are enlarged in over half the patients37. Anterior mediastinal nodes occasionally increase in size, but posterior mediastinal node enlargement is very unusual and it is seldom that either is seen in isolation. The important diagnostic feature of lymphadenopathy in sarcoidosis is its symmetry (Fig. 14.13).

Figure 14.14 Massively enlarged lymph nodes. (A,B) Massive anterior mediastinal lymphadenopathy due to malignant lymphoma. There are huge lobulated swellings in the upper anterior mediastinum which are easily seen in both projections. (C) Massive anterior mediastinal nodal enlargement secondary to Hodgkin’s disease demonstrated by CT. There is marked compression and distortion of the mediastinal structures and bilateral small pleural fluid reactions.

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Malignant lymphoma and leukaemia

Figure 14.15 Right paratracheal lymph node enlargement (arrows) due to sarcoidosis.

Malignant lymphoma often involves mediastinal and hilar lymph nodes, multiple nodal groups usually being involved, particularly in Hodgkin’s disease. Lymph node enlargement is seen in a higher proportion of patients with Hodgkin’s than non-Hodgkin’s lymphoma. Any intrathoracic nodal group may be enlarged and the possible combinations are legion, but the following generalizations regarding plain radiograph, CT and MRI findings can be made38,39. 1 The anterior mediastinal and paratracheal nodes are the groups most frequently involved, the tracheobronchial and subcarinal nodes also being enlarged in many cases. In most cases, the lymphadenopathy is bilateral but asymmetrical. Hodgkin’s disease, particularly the nodular sclerosing form, has a propensity to involve the anterior mediastinal and paratracheal nodes (Fig. 14.14). 2 Hilar node enlargement is rare without accompanying mediastinal node enlargement, particularly in Hodgkin’s disease. 3 The posterior mediastinal nodes are infrequently involved— the enlarged nodes are often low down in the mediastinum and contiguous retroperitoneal disease is likely. 4 The paracardiac nodes are rarely involved but become important as sites of recurrent disease because they may not be included in the initial radiation therapy fields40.

Lymph node enlargement is also seen occasionally with leukaemia, the pattern being the same as with lymphoma. The lymph node enlargement in both lymphoma and leukaemia may resolve remarkably rapidly with therapy (Fig. 14.18).

Figure 14.16 Malignant mediastinal lymph node enlargement due to metastases from a small cell carcinoma of the lung.

Tuberculosis and histoplasmosis Lymph node enlargement due to tuberculous or fungal infection may affect any of the nodal groups in the hila or mediastinum. One or more lymph nodes may be visibly enlarged and an associated area of pulmonary consolidation may or may not be present. Occasionally, widespread massive mediastinal and hilar node enlargement is seen. With healing, the nodes usually become smaller, often returning to normal size. Dense calcification is frequent both in nodes that stay enlarged and in those that shrink. The enlarged nodes, together with surrounding fibrosis, may compress the superior vena cava or pulmonary veins and cause obstruction. Rim enhancement with a low density centre may be seen with tuberculosis on contrast-enhanced CT examination31 (see Fig. 14.12). Metastatic carcinoma Mediastinal lymph node metastases from bronchial carcinoma are discussed in Chapter 18. Metastases may also occur from extrathoracic primary carcinomas. In one large series, half the cases of mediastinal lymph node enlargement from extrathoracic primary carcinomas arose from tumours of the genitourinary tract, particularly the kidney and testis41. Other major sources are head and neck tumours and breast carcinomas.

Figure 14.17 Metastatic malignant teratoma involving mediastinal nodes and directly invading the lumen of the superior vena cava (arrow), where it is outlined by intravenous contrast medium.

Reactive hyperplasia in nodes draining infection or neoplasm may cause mild nodal enlargement that is recognizable on CT but rarely so with plain radiograph techniques. Castleman’s disease is a specific type of lymph node hyperplasia of uncertain aetiology which can cause substantial lymph node enlargement

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Figure 14.18 (A,B) Acute lymphocytic leukaemia in a 9-year-old boy showing rapid resolution of massive mediastinal adenopathy following chemotherapy. The two radiographs were taken 7 d apart.

in many sites in the body. When seen within the thorax, the enlarged nodes are usually situated in the middle or posterior mediastinum. The lymph node mass is often localized to one area, can be huge, and may be very vascular. The nodes may calcify and may show striking contrast enhancement on both CT and MRI42,43.

Foregut duplication cysts ‘Foregut duplication cyst’ is a useful term that covers various congenital cysts derived from the embryological foregut, including bronchogenic, enteric and neurenteric cysts.

Bronchogenic cysts Bronchogenic cysts are usually solitary asymptomatic mediastinal masses which may present at any age. Typically they have

a thin fibrous capsule, are lined with respiratory epithelium and contain cartilage.The cyst contents usually consist of thick mucoid material. Most are located adjacent to the trachea or main bronchi44. The cysts can grow very large without causing symptoms, but they may compress surrounding structures, particularly the airways and give rise to symptoms. In rare cases they become infected or haemorrhage occurs into the cyst; these complications may be life-threatening, particularly in infants and young children. On chest radiography nonmalignant mediastinal cysts present as spherical or oval masses with smooth outlines projecting from either side of the mediastinum (Fig. 14.19). Most are unilocular and do not have a lobulated outline, though lobulation may be seen. They usually contact the carina or

Figure 14.19 Oesophageal duplication cyst on (A) chest radiography and (B) CT. This case shows the typical features of a well-defined spherical mass projecting from the mediastinum.

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main bronchi, but may be seen anywhere along the course of the trachea and larger airways, and frequently project into the middle and/or posterior mediastinum. Calcification of the wall or of the cyst contents is rare. When located in the subcarinal area, these cysts may closely resemble an enlarged left atrium. Foregut duplication cysts frequently push the carina forward and the oesophagus backward—displacements that are almost never seen with other masses (the exceptions being thyroid masses and an aberrant left pulmonary artery). CT is an excellent method of demonstrating the size, shape and position of a bronchogenic cyst (Fig. 14.20). In some cases, it may demonstrate a thin-walled mass, with contents of uniform CT attenuation close to that of water (0 HU), thereby effectively making the diagnosis of a fluid-filled cyst45. In other cases, the CT attenuation is similar to soft tissue and therefore to tumour, in which case the differential diagnosis becomes wider (Fig. 14.20). Rarely, the cyst may show uniformly high density, probably due to a high protein content, or very high density indicating a very high calcium content (milk of calcium) within the fluid46. MRI shows the expected features of a fluid-filled cyst.

Oesophageal duplication cysts Oesophageal duplication cysts are uncommon44. They usually present first in childhood, but may not present until adulthood: initial presentation up to the age of 61 has been reported. They are distinguished from bronchogenic cysts pathologically by the presence of smooth muscle in the walls and contain mucosa resembling that of the oesophagus, stomach, or small intestine. Many are clinically silent and are first discovered as an asymptomatic mass on an imaging examination of the chest, but they may cause dysphagia, pain, or other symptoms due to the compression of adjacent structures. A duplication cyst may become infected or ectopic gastric mucosa within the cyst may cause haemorrhage or perforation. The imaging features of oesophageal duplication cysts

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(see Fig. 14.19) on CT and MRI are identical to those of bronchogenic cysts (see Fig. 14.20) except that in the former the wall of the lesion may be thicker, the mass may assume a more tubular shape, and it may be in more intimate contact with the oesophagus44. Due to their close proximity to the oesophageal wall, barium swallow will show the features of extrinsic or intramural compression.

Neurenteric cysts Neurenteric cysts result from incomplete separation of the foregut from the notochord in early embryonic life. The cyst wall contains both gastrointestinal and neural elements with an enteric epithelial lining. There is usually a fibrous connection to the spine or an intraspinal component. Communication with the subarachnoid space or the gastrointestinal tract may be present, but communication with the oesophageal lumen is rare. There are typically associated vertebral body anomalies such as butterfly or hemivertebra. These cysts frequently produce pain and are often found early in life. Radiologically44, a neurenteric cyst is a well-defined, round, oval or lobulated mass in the posterior mediastinum between the oesophagus (which is usually displaced) and the spine. Appearances on CT and MRI are similar to those of other foregut duplication cysts, with MRI being the investigation of choice for demonstrating the extent of intraspinal involvement44.

Mediastinal pancreatic pseudocyst On rare occasions, a pancreatic pseudocyst extends into the mediastinum. Most patients are adults and have the clinical features of chronic pancreatitis; in children, the usual cause of the pseudocyst is trauma. On imaging examinations, most patients have left-sided or bilateral pleural effusions. The mediastinal component of the pseudocyst is almost always in the posterior mediastinum adjacent to the oesophagus, having gained access to the chest via the oesophageal or aortic hiatus47. CT is the optimal method of demonstrating these

Figure 14.20 Bronchogenic cyst. (A) Bronchogenic cyst in right paratracheal area in a young asymptomatic man. (B) In this instance the CT attenuation was almost the same as that of the other soft tissue structures and it was not possible to predict the cystic nature of the mass. The cyst was surgically removed.

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thin-walled cysts, which show continuity with the pancreas and any peripancreatic fluid collections.

Neurogenic tumours Neurogenic tumours are the most common tumours to arise in the posterior mediastinum, and most neurogenic tumours occur in this location44. Most neurogenic tumours in adults are benign and are discovered as asymptomatic masses on chest radiography, though some, particularly the malignant lesions, cause chest pain.They can be classified as tumours arising from peripheral nerves, including neurofibroma, neurilemmoma (schwannoma) and malignant tumours of nerve sheath origin (neurogenic sarcomas), or as tumours arising from sympathetic ganglia. MRI is the best investigation for these tumours48.

Peripheral nerve tumours Peripheral nerve tumours typically originate in an intercostal nerve in the paravertebral region. Radiologically, the benign tumours (neurofibromas and schwannomas) present as welldefined round or oval posterior mediastinal masses. Pressure deformity causing a smooth, scalloped indentation on the adjacent ribs, vertebral bodies, pedicles, or transverse processes is common, particularly with the larger lesions44,49 (Fig. 14.21). The scalloped cortex is usually preserved and is often thickened.These bone changes are diagnostic of a neurogenic lesion, the only differential diagnosis being that of a lateral thoracic meningocele. The rib spaces and the intervertebral foramina may be widened by the tumour44,49. On CT the tumours may be homogeneous or heterogeneous, usually enhancing heterogeneously after intravenous contrast medium50. Punctate foci of calcification may be seen. On MRI neurofibroma and neurilemmoma have variable T1-weighted signal intensity that may be similar to spinal cord (Fig. 14.22). They may have

Figure 14.22 Neurofibroma in left paravertebral region. This coronal T1-weighted, spin-echo image demonstrates the tumour well and shows that it does not enter the spinal canal or encroach significantly on the adjacent foramina.

characteristic high signal intensity peripherally and low signal intensity centrally (target sign) on T2-weighted images51, and enhance uniformly after gadolinium. Ten per cent of paravertebral neurofibroma and neurilemmoma extend into the spinal canal and appear as dumb-bell-shaped masses with widening of the affected neural foramen52. Malignant tumours of nerve sheath origin are rare neoplasms, typically occurring in the third to fifth decades, although they may occur earlier in patients with neurofibromatosis Type 1. Radiologically the masses are usually larger than 5 cm in diameter44. Although MRI cannot reliably differentiate benign from malignant neurogenic tumours, sudden change in size of a pre-existing mass, the development of heterogeneous signal intensity (caused by haemorrhage and necrosis), or infiltration of adjacent mediastinum or chest wall are cause for concern48.

Sympathetic ganglion tumours

Figure 14.21 Neurofibrosarcoma showing widening and pressure deformity of adjacent ribs. It was not possible to predict the malignant nature of this tumour from the plain radiographs. A benign neurofibroma would have had identical features.

Sympathetic ganglion tumours are rare neoplasms forming a continuum ranging from benign ganglioneuroma to malignant neuroblastoma, with ganglioneuroblastoma being an intermediate form44. Ganglioneuromas are benign neoplasms usually occurring in children and young adults. Ganglioneuroblastomas exhibit variable degrees of malignancy and usually occur in children53. Neuroblastomas are highly malignant tumours that typically occur in children younger than 5 years of age53. The posterior mediastinum is the most common extra-abdominal location of a neuroblastoma. Ganglioneuromas and ganglioneuroblastomas usually arise from the sympathetic ganglia in the posterior mediastinum and therefore usually present radiologically as well-defined elliptical masses, with a vertical orientation, extending over the anterolateral aspect of three to five vertebral bodies44,54. Calcification occurs in approximately 25%. CT appearance is variable44. On MRI ganglioneuromas and ganglioneuroblastomas

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are usually of homogeneous intermediate signal intensity on T1- and T2-weighted images. Neuroblastomas are typically more heterogeneous due to areas of haemorrhage, necrosis, cystic degeneration and calcium. They may be locally invasive and have a tendency to cross the midline48.

Mediastinal paragangliomas Intrathoracic paragangliomas are of two types: chemodectomas or phaeochromocytomas (functioning paragangliomas), either of which may be benign or malignant. Almost all intrathoracic chemodectomas are in a location close to the aortic arch and are classified as aortic body tumours. Other mediastinal chemodectomas are very rare55.They are usually single, but multicentric cases are reported. Fewer than 2% of phaeochromocytomas occur in the chest. Most intrathoracic phaeochromocytomas are found in the posterior mediastinum or closely related to the heart, particularly in the wall of the left atrium or the interatrial septum. Approximately one-third of mediastinal phaeochromocytomas are nonfunctioning and asymptomatic, the remainder presenting with the symptoms, signs and laboratory findings of overproduction of catecholamines. The various paragangliomas have similar appearances on chest radiography, CT and MRI. They form rounded, soft tissue masses, which are usually very vascular and therefore enhance intensely on CT56. On MRI, phaeochromocytomas usually show a signal intensity similar to muscle on T1-weighted images and very high signal intensity on T2weighted images57. MRI is particularly useful for demonstrating intracardiac phaeochromocytomas. Radio-iodine MIBG (meta-iodobenzylguanidine) and somatostatin receptor scintigraphy both show increased activity in paragangliomas, and are useful techniques for identifying extra-adrenal phaeochromocytomas57,58.

Lateral thoracic meningocele Lateral thoracic meningoceles are protrusions of the spinal meninges through an intervertebral foramen. Like neurofibromas, they are commonly associated with neurofibromatosis59. They are rare lesions that present as an asymptomatic mass, often with pressure deformity of the adjacent bone, indistinguishable on plain radiographs from neurofibromas. CT and MRI can both indicate the correct diagnosis by showing the mass to be fluid filled rather than solid44. If necessary, the diagnosis can be established by CT with intrathecal contrast medium demonstrating flow into the lesion.

Extramedullary haematopoiesis Extramedullary haematopoiesis is a rare phenomenon caused by compensatory expansion of bone marrow in various anaemias, particularly congenital haemolytic anaemias. The mass itself almost never causes symptoms. Radiographically, extramedullary haematopoietic tissue typically produces one or more smooth, lobular or spherical masses in the paravertebral gutter, usually in the lower thorax (Fig. 14.23).The bones may be normal or may show an altered lacelike trabecular pattern due to marrow expansion. The masses are usually of homogeneous soft tissue attenuation on CT, although occasionally,

Figure 14.23 Extramedullary haematopoiesis showing smooth pleurally-based masses and altered bone texture in this patient with thalassaemia. There is also a small right pleural effusion.

a fatty component may be visible60. Usually the masses are bilateral and reasonably symmetrical.

Mesenchymal tumours and tumour-like conditions Lymphangiomas (cystic hygromas) Lymphangiomas (cystic hygromas) are focal mass-like congenital malformations of the lymphatic system comprising complex lymph channels or cystic spaces containing clear or strawcoloured fluid. Lymphangiomas can occur in any part of the mediastinum, but are most common in the anterior or superior mediastinum. Mediastinal lymphangiomas may on occasion be wholly confined to the mediastinum but they are more frequently an extension from a lymphangioma in the neck. Most cervicomediastinal lymphangiomas present in early life as a neck mass, whereas the purely mediastinal lymphangiomas usually present in older children and adults as an asymptomatic mediastinal mass. Typically they appear as cystic masses, with the attenuation of the contents close to that of water on CT61.

Fatty tumours of the mediastinum Fatty tumours of the mediastinum are rare. On chest radiography, regardless of whether they are benign or malignant, fatty tumours are seen as well-defined round or oval mediastinal masses. Benign lipomas are soft and do not, therefore, compress surrounding structures unless they are very large. On CT they show uniform fat attenuation apart from a few strands of soft tissue62. Mediastinal liposarcomas are malignant fat-containing tumours.They often occur in the anterior mediastinum where the fat appears heterogeneous on CT. In contradistinction to benign lipomas, they usually contain large areas of soft tissue density material. Lipoblastoma, a benign tumour of childhood, contains fat and soft tissue63,64. Occasionally, the amount of fat attenuation is relatively small. Angiolipoma and myelolipoma are both benign tumours which may show a combination of soft tissue and fat attenuation on CT and therefore can be indistinguishable from liposarcoma65,66. Other mesenchymal tumours, such as benign and malignant fibrous tumours and haemangiomas, may occur anywhere in the mediastinum.

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Herniation of abdominal fat Herniation of omental and perigastric fat is a common cause of a localized fatty mass in the mediastinum.The fat may herniate through the oesophageal hiatus, the foramen of Morgagni, or the foramen of Bochdalek. Such herniations are usually readily diagnosed because of their characteristic locations. On CT or MRI, appearances consistent with fat eliminate confusion with other mediastinal masses64.

Mediastinal lipomatosis Relatively large collections of fat are often present in the cardiophrenic angles, particularly in obese subjects. These cardiophrenic fat pads may resemble a mass. Massive collections of fat throughout the mediastinum may be seen in so-called ‘mediastinal lipomatosis’, a phenomenon seen particularly in Cushing’s disease, in patients on steroid therapy and in obese subjects. When the fat deposits are extensive and symmetrical, the diagnosis is usually obvious. Localized masses may also be seen and CT is helpful in these cases since it can clearly demonstrate fat attenuation throughout the mass.

Sternal and spinal disease Disorders of the stern um and spine may give rise to anterior and posterior mediastinal masses, respectively. The conditions that are particularly likely to do so are paravertebral abscess, myeloma, metastasis, traumatic haematoma, lymphoma, and primary tumours (Figs 14.24–14.26).

Aortic aneurysms and aortic arch anomalies

Figure 14.25 Sternal destruction due to a radiation-induced sarcoma following treatment for breast carcinoma many years previously. Note the thickening of the overlying skin (arrows), the radical mastectomy and pleural effusion.

Prevascular masses Almost all masses anterior to the ascending aorta and the head and neck vessels are: 1 thyroid masses 2 thymic masses 3 germ-cell tumours/cystic teratomas 4 lymphadenopathy.

The differential diagnosis of a mediastinal mass depends on the age of the patient, the location, shape, size and characteristics of the lesion, and on the number of masses present. Location in particular is important in the differential diagnosis. This is best assessed with cross-sectional imaging, in particular CT.

Thyroid masses can usually be specifically diagnosed or excluded because of their contiguity with the thyroid gland in the neck and their high CT attenuation. In addition, many show cystic areas of attenuation close to water, as well as one or more areas of discrete calcification. Almost all masses located superiorly in the anterior mediastinum which cause focal deviation of the trachea are likely to be thyroid in origin. Thymic masses and germ-cell tumours/cystic teratomas can be thought of together, as most arise within the thymus. Clinical and laboratory features may help distinguish between

Figure 14.24 Sternal metastatic deposit. CT demonstration of bone destruction by a soft tissue mass in a patient with an adenocarcinoma of unknown primary.

Figure 14.26 Sternal destruction due to direct extension from mediastinal lymphoma. Note the soft tissue swelling and obliteration of fat planes in the right-sided pectoral muscles owing to soft tissue involvement.

These important causes of mediastinal masses are discussed in Chapter 27.

Differential diagnosis of mediastinal masses

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the two, e.g. myasthenia gravis is associated with thymoma, whereas elevated human chorionic gonadotrophin levels are seen with malignant germ-cell tumours. Fat, fluid, or teeth within an anterior mediastinal mass are pathognomonic of cystic teratoma. Rarer causes of prevascular masses are parathyroid adenoma, lymphangioma (cystic hygroma), pericardial cyst, aortic body chemodectoma, lipoma/liposarcoma or other mesenchymal tumours, or aneurysms. Many of these masses have features that permit a specific diagnosis to be made: parathyroid adenomas are usually associated with hyperparathyroidism; lymphangiomas almost always have broad contact with the root of the neck and show numerous areas of nonenhancing, water or near-water attenuation on CT; lipomas show uniform fat attenuation, apart from a few soft tissue strands; liposarcomas show an unusual mixture of fat interspersed by irregular strands or masses of soft tissue attenuation; aneurysms should be recognized by luminal enhancement; pericardial cysts are, in general, of uniform water attenuation with a thin wall of uniform thickness, and need only be considered when the mass in question is in contact with the pericardium. Mesenchymal tumours such as fibrosarcomas or haemangiomas have no distinguishing features.

Paracardiac masses The likely diagnoses for paracardiac masses in direct contact with the diaphragm are pericardial cyst, diaphragmatic hernia, fat pad or lymphadenopathy. If the mass is separated from the diaphragm, the likely differential diagnosis widens to include germ-cell, mesenchymal and pericardial tumours, cystic teratomas and thymic masses. Approximately 20% of thymomas are found in a paracardiac location, though contact with the diaphragm is very unusual. Lack of connection with the diaphragm eliminates the possibility of a diaphragmatic hernia.

Masses in the paratracheal, subcarinal and paraoesophageal regions These three regions are contained within a common fascial sheath which continues into the neck. The likely possibilities for a mass in these locations are lymphadenopathy, intrathoracic thyroid mass, developmental foregut cyst, oesophageal tumour, hiatus hernia, paraspinal mass encroaching on the middle mediastinum and aortic aneurysm. Aneurysms are readily diagnosed on CT by observing contrast enhancement of the lumen.The nature of other masses can often be predicted with reasonable certainty: nonvascular masses in the aortopulmonary window or deep to the azygos vein are almost invariably enlarged lymph nodes; bronchogenic cysts can be diagnosed with confidence if the criteria of a thin wall and contents exhibiting uniform water attenuation are met; and splitting of the trachea from the oesophagus is a characteristic shared only by thyroid masses, bronchogenic cysts, oesophageal tumours and an aberrant origin of the left pulmonary artery. Patients with oesophageal carcinoma (the most common oesophageal tumour) nearly always present with dysphagia when the tumour mass is still relatively small, whereas a leiomyoma or other mesenchymal tumour of the oesophagus may occasionally present first as an asymptomatic mediastinal mass. The intimate

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relationship with the oesophagus usually leads to a barium swallow examination. Hiatus hernia is an exceedingly common cause of enlargement of the mediastinum in the region of the lower oesophagus and plain radiography is so characteristic that a barium swallow is rarely required for diagnosis.

Paravertebral masses Neurogenic lesions and neoplastic lymphadenopathy dominate the differential diagnosis for paravertebral masses. The less common causes of paravertebral masses include: extramedullary haematopoiesis; pancreatic pseudocyst; mesenchymal tumours such as lipoma, fibroma and haemangioma; and lesions arising from the oesophagus, pharynx, spine, or aorta. The oesophageal or pharyngeal lesions that may project posteriorly include leiomyoma, foregut duplication cyst, and congenital or acquired diverticula of the oesophagus. The spinal origin of masses such as paraspinal abscess, primary or metastatic tumours of the vertebral body, or haematoma from trauma to the spine, are usually readily diagnosed by observing corresponding changes in the spine.Aneurysms of the descending aorta that truly mimic a mediastinal mass are uncommon, as the majority of large aneurysms in this location are obvious dilatations of the descending aorta and have curvilinear calcification in their wall. An aneurysm is readily diagnosed on CT when opacification of its lumen can be demonstrated.

OTHER MEDIASTINAL LESIONS Acute mediastinitis Acute infection of the mediastinum is rare. Oesophageal perforation, either iatrogenic or from swallowed objects, is the most frequent cause. Forceful vomiting may tear the oesophageal wall (Boerhaave’s syndrome) and if the tear is deep enough, air, alimentary juices and food may leak into the mediastinum causing acute mediastinitis. Such tears are almost invariably just above the gastro-oesophageal junction. Other causes of acute mediastinal infection are leakage from the oesophagus into the mediastinum through a necrotic neoplasm, and extension of infection from the neck, retroperitoneum, or adjacent intrathoracic or chest wall structures into the mediastinum. Clinically, the patients are often very ill with an abrupt onset of high fever, tachycardia and chest pain. The chest radiograph may show widening and lack of clarity of the mediastinal outline adjacent to the oesophagus. Streaks or round collections of air may be seen within the mediastinum, and there may even be one or more mediastinal air–fluid levels. Pleural effusions are frequent and are usually confined to, or greatest on, the left. Lower lobe pneumonia or atelectasis often complicate the radiographic picture. A swallow using nonionic contrast medium may show the site of perforation, with extravasation into the mediastinum. CT shows obliteration of the normal mediastinal fat planes and gas bubbles may be identified within the mediastinum (Fig. 14.27). In advanced cases there may be walledoff discrete fluid or air–fluid collections indicating abscess formation. There may be an associated empyema, subphrenic or pericardial collection. When acute mediastinitis

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Figure 14.27 Abscess formation. (A) Abscess in anterior mediastinum demonstrated on CT. (B) This coronal reformat of an axial CT dataset demonstrates a tuberculous mediastinal abscess and associated lung changes in a different patient.

is suspected following sternotomy, CT shows the extent of inflammation and any drainable mediastinal or pericardial fluid collections67. Distinguishing a retrosternal haematoma from reactive granulation tissue or cellulitis is difficult, as is distinguishing osteomyelitis from the direct effects of the surgical incision68. It should be remembered that substernal fluid collections and dots of air are normal in the first 20 d following sternotomy. Therefore, before gas-forming infections can be diagnosed, the air collections must appear de novo or must progressively increase in the absence of any other explanation69.

Fibrosing mediastinitis Fibrosing mediastinitis (sclerosing mediastinitis or mediastinal fibrosis) is a disorder that results in proliferation of fibrous tissue and collagen within the mediastinum. It is usually due to

previous infection from histoplasmosis or tuberculosis70. The fibrosis is usually maximal in the upper mediastinum but may extend to the lung roots. The most common clinical consequences are obstruction to the superior vena cava and, occasionally, obstruction to the central pulmonary arteries or veins. Other causes of fibrosing mediastinitis include idiopathic (similar to retoperitoneal fibrosis/peri-aortitis), autoimmune disease, radiation therapy and drugs (in particular methysergide). The chest radiograph is non-specific and often underestimates the extent of mediastinal disease. In fibrosing mediastinitis due to previous tuberculous or fungal infection, the chest radiograph may show calcification of mediastinal or hilar lymph nodes. CT typically shows an infiltrative, often extensively calcified, hilar or mediastinal process (Fig. 14.28), which may be relatively focal when disease is due to previous histoplasmosis or tuberculosis, and more diffuse in the idiopathic form71. Airway

Figure 14.28 Mediastinitis. (A) Fibrosing mediastinitis. There is confluent soft tissue infiltration throughout the mediastinum without evidence of a discrete mass. Note the marked narrowing of the superior vena cava (SVC). The patient had clinical evidence of SVC compression and a history of previous radiotherapy for lymphoma, diagnosed by surgical biopsy through a median sternotomy. This original biopsy, 30 years previously, had been complicated by post-operative infection. (B) Tracheal narrowing from mediastinal fibrosis of unknown cause in a different patient. The trachea (arrow) is markedly narrowed and distorted and lies within the fibrotic scarring. The more posterior oesophagus is relatively dilated and gas filled.

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narrowing (Fig. 14.28), vascular encasement and obstruction may also be seen. MRI provides similar information to CT, with the fibrosis appearing as heterogeneous signal intensity on T1and T2-weighted imaging72, but lacks sensitivity for detection of calcification, which is an important feature for differentiating fibrosing mediastinitis from other infiltrative disorders of the mediastinum, such as lymphoma and metastatic carcinoma.

Mediastinal haemorrhage Mediastinal haemorrhage is most commonly due to trauma to the arteries and veins within the mediastinum, with other causes including rupture of an aneurysm, aortic dissection and complications of central venous catheterization. Radiologically haemorrhage produces an increase in the mediastinal diameter which is maximal at the point of bleeding73. Blood may track through the mediastinum, frequently running over the apex of the left lung to produce a smooth and well-defined apical cap. When haemorrhage is severe blood may rupture into the pleural cavity or dissect into lung along peribronchovascular sheaths, resulting in a radiographic pattern resembling interstitial oedema. On unenhanced CT, acute haemorrhage may appear of relative high attenuation. The appearance of mediastinal haematoma on MRI varies with the age of the haemorrhage.

Mediastinal emphysema Air may enter the mediastinum from a perforation of the pharynx, oesophagus, or major airways. In many instances, however, a pneumomediastinum is the result of an air leak from a tear in a small intrapulmonary airway, the air dissecting through the lung via the hilum into the mediastinum. Asthma is the most common precipitating cause. In other cases the leak is probably related to abrupt changes in intrathoracic pressure such as those associated with vomiting. Occasionally, air tracks into the mediastinum from retroperitoneal air collections. The presence of a pneumomediastinum is, in itself, of little significance (though it may be responsible for substernal chest pain), but the condition causing the air leak (particularly bronchial, oesophageal, or pharyngeal perforation) may be of great significance to the patient. On imaging the condition is recognized as streaky translucencies within the mediastinum that are usually most obvious adjacent to the left heart border, aortic knuckle, main pulmonary artery and adjacent left hilum (Fig. 14.29). The air dissects through

Figure 14.29 Mediastinal emphysema in a patient with Pneumocystis jiroveci (formerly carinii) pneumonia. The air has tracked through the mediastinum into the neck and chest wall.

the perivascular areolar tissues and may track up into the neck, supraclavicular areas and axillae, as well as down into the retroperitoneum. It may also track extraserosally on either side of the diaphragm, which will occasionally be seen as a continuous line of transradiancy known as the ‘continuous diaphragm sign’74. The differential diagnosis of a pneumomediastinum on chest radiograph includes a medially placed pneumothorax and a ‘Mach effect’ due to the abrupt change in density between the lung and the adjacent heart and mediastinum. It is easy to appreciate why a medial pneumothorax can be mistaken for a pneumomediastinum, since in both instances there is a linear collection of air bounded on its lateral side by a thin line of pleura. Deciding whether the line is mediastinal parietal pleura or visceral pleura can be difficult; the distinction often depends on recognizing the full extent of the air and looking carefully for a pneumothorax lying against the chest wall, or looking for evidence of air elsewhere in the mediastinum. Pneumomediastinum is easy to diagnose on CT as streaks or rounded collections of air surrounding the vessels and other structures within the mediastinum.

THE PERICARDIUM NORMAL ANATOMY The pericardium is a fibrous bag consisting of the (inner) visceral pericardium, the (outer) parietal pericardium, and the 20–60-ml cavity between them (Fig. 14.30). Beneath the visceral pericardium is either myocardium or epicardial fat. The visceral pericardium extends for short distances along the pulmonary veins, the superior vena cava below the azygos vein, the inferior vena cava, and the ascending aorta to

a point 20–30 mm above the aortic root and the main pulmonary artery as far as its bifurcation. It then reflects upon itself to become the parietal pericardium. The reflection of the two pericardial layers around the great arteries and veins forms the two ‘appendages’ or diverticula of the pericardium. The arterial mesocardium is an anterior extension of all layers of the pericardium around the ascending aorta and pulmonary trunk. It lies obliquely in the coronal plane and is higher on the right, over the ascending aorta, than on the

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Superior vena cava

Transverse pericardial sinus

Ascending aorta Pulmonary trunk

Left pulmonary veins Right pulmonary veins Oblique pericardial sinus Inferior vena cava

Diaphragm

Pericardium (cut edge)

Diaphragmatic part of pericardium

A Figure 14.30 The normal pericardium. (A) Drawing of the reflections of the normal pericardial sac. (B) The normal pericardium on narrow-section CT is demonstrated as a thin (1–2 mm) soft tissue density line separated from the cardiac muscle by the epicardial fat (arrows).

left, over the pulmonary trunk. The arterial mesocardium is divided into an anterior compartment (the pre-aortic recess), lying between the ascending aorta and pulmonary trunk, and another compartment behind the ascending aorta immediately above the right pulmonary artery (the retroaortic recess) (Fig. 14.31). Posterior and lateral to the heart, the extraparenchymal pulmonary veins and the superior and inferior venae cavae are enveloped by the venous mesocardium, which has the shape of an inverted U. Beneath the apex of the U is the space between the pulmonary veins and the left atrium—the oblique sinus. The arterial and venous

mesocardia are connected by the transverse sinus. This space is limited anteriorly by the aorta and pulmonary arteries, and posteriorly by the superior vena cava and left atrium. It forms a communication, at the base of the heart, between the right and left sides of the pericardial cavity. The pericardium is considered to support the heart and cardiac function in three major ways: it contains the heart and limits its motion within the middle mediastinum; it acts as a protective membrane to shield the heart from local inflammatory disease; and it limits excessive acute dilatation of the cardiac chambers in response to increased preload75.

Figure 14.31 Contrast-enhanced CT demonstrating normal pericardial recesses. (A) The retro-aortic recess appears as a crescentic structure closely apposed to the posterior wall of the aorta (arrows). It is characteristically of slightly lower attenuation than the unenhanced blood pool. In this example of a patient in mild cardiac failure there is slightly more fluid than is usually seen. (B) Pericardial fluid in the anterior compartment (pre-aortic recess) (arrows).

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On the lateral chest radiograph the normal pericardium may be seen as a 1–2-mm thick curved stripe anterior to the heart, set between more radiolucent mediastinal fat anteriorly and epicardial fat posteriorly. The visceral pericardium is normally very thin and is therefore not visualized separately by any imaging modality. The combination of the visceral pericardium and the small layer of physiological pericardial fluid constitutes the normal pericardium routinely visualized on CT and MRI as a 1–2-mm thick layer76,77 (Fig. 14.30B), which can appear focally thicker at the sites of its major attachments. Although the pericardium is readily visualized overlying the right atrium and right ventricle in most individuals, it is often not visible over the lateral and inferior walls of the left ventricle. It is essential to appreciate the anatomical extent and location of the pericardial recesses78 since they are frequently seen on both CT79,80 and MRI and may be confused with aortic dissection, adenopathy, a mediastinal mass, or thymus.

• THE MEDIASTINUM, INCLUDING THE PERICARDIUM

collections and masses. Limitations of MRI include its inability to reliably depict calcification, relatively longer data acquisition times, and greater demands on the patient with regard to cooperation with breath-holding. Additionally, arrhythmias, which commonly occur in association with pericardial disease, may detrimentally affect image acquisition and quality.

DEVELOPMENTAL ANOMALIES Congenital absence of the pericardium

Computed tomography is the best investigation for localizing, characterizing and demonstrating the extent of a collection or mass in the acute setting. Multidetector CT (MDCT) with multiplanar reformats, particularly if ECG gated, provides excellent motion-free assessment of the pericardium. MDCT has the advantage of speed and generally greater availability and accessibility. It is highly sensitive for the detection of pericardial calcification, an important finding in constrictive pericarditis. Pericardial assessment with CT may be limited by motion artefact if not ECG gated; additionally, differentiating pericardial fluid from thickening may occasionally be difficult on CT.

Compromise of the vascular supply to the pleuropericardial membrane during embryological development is associated with congenital defects in the pericardium. Pericardial deficiency is associated with congenital anomalies of the heart and lungs, including atrial septal defect, tetralogy of Fallot, patent ductus arteriosus, bronchogenic cysts and pulmonary sequestration81. The defects vary in size from small communications between the pleural and pericardial cavities to complete (bilateral) absence of the pericardium. The most common form is complete absence of the left pericardium, with preservation of the pericardium on the right. Bilateral and isolated right-sided lesions are very rare. Pericardial defects are frequently associated with large defects in the parietal pleura, through which the left lung can herniate and surround the intrapericardial vascular structures82,83. Complete absence of the pericardium is usually asymptomatic, whereas partial or localized absence of the pericardium may be complicated by herniation and entrapment of a cardiac chamber, in particular the left atrial appendage in left-sided defects. Chest radiograph findings are frequently subtle and nonspecific82,83. When present, chest radiograph findings in complete absence of the left pericardium include displacement of the heart into the left chest and interposition of lung between the aorta and pulmonary artery, as well as between the left hemidiaphragm and cardiac silhouette. Both the medial and lateral borders of the main pulmonary artery may be visualized more clearly due to absence of the anterior pericardial reflection between the aorta and the pulmonary artery. Due to leftward displacement and rotation, the right cardiac border may not be seen. In partial pericardial defects, varying degrees of prominence of the pulmonary artery and/or left atrial appendage may be seen, while the heart retains its normal position in the thorax82 (Figs 14.32, 14.33). A definitive diagnosis of absence of the pericardium can be obtained with either CT or MRI.

Magnetic resonance imaging

Pericardial cysts and diverticula

Magnetic resonance imaging can provide a comprehensive assessment of the pericardium. When T1- and T2-weighted imaging sequences (a number of which can be performed using ECG-gated breath-hold techniques), are combined with gradient-echo cine-based functional cardiac imaging, both pericardial disease and its impact on cardiac function can be assessed. MRI has some advantages over echocardiography and CT in the detection and characterization of pericardial

Pericardial cysts and diverticula are thought to be the result of persistence of blind-ending ventral parietal pericardial recesses. Those cysts that communicate with the pericardial space are termed pericardial diverticula. They almost invariably appear as a well-defined, oval or occasionally lobulated mass attached to the pericardium84 (Fig.14.34). Most occur in the right cardiophrenic angle, with a proportion being situated in the left cardiophrenic angle and some higher in the

IMAGING PERICARDIAL DISEASE Chest radiography Chest radiography is of limited use in the detailed assessment of pericardial disease although pericardial effusions, calcification and secondary signs and complications of pericardial disease may be evident.

Ultrasound Ultrasound is the most commonly used investigation in the initial evaluation of pericardial disease. Restricted acoustic windows limit its evaluation of the entire pericardium. Loculated collections, intrapericardial blood clot and pericardial thickening in particular may be difficult to assess or may be overlooked.

Computed tomography

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Figure 14.32 Complete absence of the pericardium. (A) PA radiograph. The heart is displaced into the left chest, obscuring the right heart border by the spine. The cardiac apex (arrow) is elevated, and air-filled lung is seen beneath it. (B) On lateral barium swallow, the increased density of the left ventricle surrounded by the air-filled lung (arrows) is apparent.

Figure 14.33 Partial absence of the pericardium. Axial spin-echo MRI. (A) Image through the aortic valve and proximal ascending aorta (Ao). The heart is displaced into the left chest and rotated in a clockwise manner. (B) Image 1-cm cephalad through the pulmonary valve (PV). A sliver of lung (arrow) invaginates to come into contact with the ascending aorta. (C) Image 1-cm cephalad to the main (MP) and transverse right (RP) pulmonary arteries. The MP protrudes to the left and is in contact with the lung.

Figure 14.34 Pericardial cyst. Axial spin-echo MRI at the base of the heart. (A) An intermediate signal intensity smooth mass extrinsic to the heart is identified (arrow). Ao = ascending aorta, LA = left atrium, PA = main pulmonary artery, S = superior vena cava. (B) Chest radiograph, lateral view. The smooth lobulated density superimposed on the cardiac silhouette (arrows) is a pericardial cyst.

PA Ao S LA

A

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mediastinum. They contain clear fluid and can be recognized as fluid-filled cysts surrounded by normal pericardium on echocardiography, CT, or MRI85, the cyst contents showing characteristics similar to water.

Intrapericardial bronchogenic cysts Intrapericardial bronchogenic cysts are rare. They may cause symptoms secondary to mass effect on adjacent cardiac structures. Appearances are similar to bronchogenic cysts occurring elsewhere in the mediastinum.

ACQUIRED PERICARDIAL DISEASE Pericarditis including pericardial effusion Inflammation of the pericardium (pericarditis) may occur in response to a variety of insults. It typically results in cellular proliferation, or the production of fluid (pericardial effusion) or fibrin, either alone or in combination. Causes include myocardial infarction (acute or post-myocardial infarction [Dressler] syndrome), pericardiotomy, mediastinal irradiation, infection (viral or bacterial), connective tissue disease (rheumatoid arthritis, systemic lupus erythematosus), metabolic disorders (uraemia, hypothyroidism), neoplasia and AIDS. The most common imaging manifestation of acute pericarditis is a pericardial effusion, the nature of the fluid varying with the underlying cause (Fig. 14.35). Transudative pericardial effusions may develop after cardiac surgery or in congestive heart failure, uraemia, post-pericardiectomy syndrome, myxoedema and collagen–vascular diseases. Haemopericardium may be due to trauma, aortic dissection, aortic rupture, or neoplasm (especially primary pericardial mesothelioma) (Fig. 14.35). Chylopericardium resulting from injury or obstruction of the thoracic duct is rare. On chest radiograph sudden increase in the size of the cardiac silhouette without specific chamber enlargement suggests the diagnosis of pericardial effusion. Filling in of the retrosternal space, effacement of the normal cardiac borders, development of a ‘flask’ or ‘water bottle’ cardiac conFiguration, and bilateral hilar overlay are features of pericardial

• THE MEDIASTINUM, INCLUDING THE PERICARDIUM

effusion (Fig. 14.36). The epicardial fat pad ‘sign’ is positive when, visualized in the lateral projection, an anterior pericardial stripe (bordered by epicardial fat posteriorly and mediastinal fat anteriorly) is thicker than 2 mm. This sign is diagnostic of pericardial thickening or fluid86,87. Echocardiography is the most commonly used method for diagnosing pericardial effusion. It is highly sensitive and specific although visualization may be limited in patients with marked obesity or emphysema, and loculated collections and intrapericardial clot in postoperative patients may be difficult to detect88. CT and MRI are indicated when a loculated or haemorrhagic effusion or pericardial thickening is suspected. Increased attenuation in a pericardial effusion on CT suggests haemorrhage89 (see Fig. 14.35), although occasionally the attenuation values of a haemorrhagic effusion may overlap with the pericardial fluid found in patients with hypothyroidism. On spin-echo MRI, the signal characteristics of pericardial collections vary depending on the composition of the fluid. In the absence of haemorrhage, effusions are typically of predominantly low signal intensity, although intermediate signal intensity may be seen in inflammatory conditions such as uraemia, tuberculosis, or trauma, possibly reflecting high protein content and when more focal, the presence of adhesions limiting normal flow of pericardial fluid in the pericardial space77,85. In haemorrhagic effusions, signal intensity varies depending on the age of blood products. Thickened inflamed pericardium can appear of moderate to high signal intensity on spin-echo MRI, and pericardial enhancement may be seen on both MRI or CT performed after intravenous contrast medium administration.

Constrictive pericarditis Any insult to the pericardium can progress from an acute pericarditis with pericardial effusion to a subacute stage of resorption of the effusion with organization, and then to a chronic phase of fibrous scarring, pericardial thickening and obliteration of the pericardial cavity. Constrictive pericarditis is the condition in which a thickened, fibrotic and often calcified pericardium restricts diastolic filling of the heart (Fig. 14.37).

Figure 14.35 Pericardial effusion. (A) Small pericardial effusion is present in the anterior pericardial sac in a patient with advanced pulmonary artery hypertension. Note the dilated right-sided cardiac chambers. (B) Large haemopericardium complicating a type A aortic dissection. This is an unenhanced image and the haemopericardium is the same density as soft tissue structures (compare to A). (C) The dissection flap can be seen on this enhanced CT within the transverse arch.

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Figure 14.36 Large pericardial effusion. (A) The heart had become rapidly enlarged in this patient who had previously undergone aortic valve replacement. (B) Lateral view demonstrates the pleural fluid lying posteriorly. (C) Unenhanced CT through the level of the valve replacement demonstrates the large pericardial effusion.

Figure 14.37 Dense pericardial calcification demonstrated on (A,B) chest radiograph (arrows) and (C) CT. There are bilateral pleural effusions in this patient with constrictive calcific pericarditis due to previous tuberculosis.

Constrictive pericarditis is usually the result of a chronic pericardial insult. The aetiology is unknown in many cases, presumed to be secondary to an occult viral pericarditis and other causes of pericarditis90. Outside the USA, the most common cause is probably tuberculosis or fungal aetiology. Constriction due to neoplastic infiltration of the pericardium is most commonly secondary to carcinoma of the lung or breast, lymphoproliferative malignancies and melanoma. Pericardial constriction after mediastinal irradiation, usually performed to treat breast carcinoma or Hodgkin’s disease, may occur months to years after treatment91. Pericardial thickening is seen in up to 88% of confirmed cases of constrictive pericarditis92. In the majority of cases, constrictive pericarditis involves the entire pericardium, restricting filling of all cardiac chambers. Occasionally, in particular anterior to the right ventricle in postoperative patients, the pericardial thickening is more localized78. Patients with constrictive pericarditis frequently present with symptoms of heart failure such as dyspnoea, orthopnoea and fatigability; they may occasionally present with hepatomegaly and ascites. The clinical findings of constriction overlap with those of restrictive cardiomyopathy, a primary disorder of the myocardium. The differential diagnosis is important since the patients with pericardial constriction may benefit from

pericardiectomy, while restrictive cardiomyopathy is managed medically or by cardiac transplantation. The hallmarks of pericardial constriction are pericardial thickening, pericardial calcification and abnormal diastolic ventricular function. On chest radiograph the heart size may be normal or appear increased due to the presence of pericardial fluid. The superior vena cava and azygos vein may be of increased size due to raised right heart pressures. Although echocardiography is routinely performed and provides an excellent assessment of haemodynamic function, it is not highly accurate at depicting pericardial thickening. CT and MRI are significantly more sensitive, with CT having the added advantage over MRI of being able to demonstrate the presence of calcification, which is associated with pericardial constriction (see Fig. 14.37C). Pericardial thickening of 4 mm or more is abnormal and, when accompanied by clinical features of constriction, is highly suggestive of constrictive pericarditis85,92. Both CT and MRI may show the secondary effects of constriction on the central cardiovascular structures. The right ventricle tends to be of reduced volume and has a narrow tubular configuration. A sigmoid-shaped interventricular septum or prominent leftward convexity of the septum may be seen78. The right atrium,

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• THE MEDIASTINUM, INCLUDING THE PERICARDIUM

superior and in particular inferior venae cavae, and hepatic veins may be dilated. Hepatomegaly and ascites may be seen. Cardiac MRI can also be used to provide a more detailed assessment of cardiac function and myocardial wall thickness, which has prognostic implications for outcome after pericardiectomy.

Cardiac tamponade Gradual accumulation of pericardial fluid may fail to produce clinical signs or symptoms for an extended period of time. However, rapid accumulation of as little as 100–200 ml of fluid can cause a haemodynamically significant compression of the heart, which severely impedes diastolic filling, the condition known as pericardial tamponade. Even in the face of preserved ejection fraction, diminished ventricular end-diastolic volume leads to reduced stroke volume. In addition to other clinical signs of pericardial effusion, those of cardiac tamponade include pulsus paradoxus, which is exaggeration of the normal inspiratory drop in systolic blood pressure. Since acute tamponade may occur with small effusions, clinically important pericardial enlargement may be difficult to detect on plain radiographs. Subtle changes in cardiac contour may only be detectable by comparison with previous studies. If there is decreased pulmonary vascularity in spite of the cardiac enlargement or if the superior vena cava and azygos veins are dilated, tamponade should be suspected. Echocardiographic demonstration of pericardial effusion and the clinical findings are usually sufficient to make the diagnosis of tamponade. CT and MRI are frequently instrumental in suggesting the cause of the effusion (i.e. haemorrhage, neoplastic involvement, inflammation due to tuberculosis, or other infectious processes, etc).

Pericardial neoplasms Primary pericardial neoplasms are rare, with approximately equal incidence of benign versus malignant pericardial neoplasms. Benign tumours include teratomas, fibromas, neurofibromas, lipomas, haemangiomas, lymphangiomas and hamartomas. Although these patients are usually symptom free, pericardial effusion or constriction, particularly in the case of childhood teratomas, may occur.

Figure 14.38 Phaeochromocytoma of the heart. There is abnormal soft tissue in the right atrioventricular groove (arrows) that proved to be a primary cardiac phaeochromocytoma on histological examination following resection.

in approximately 10% of all patients with malignancy94. The most common malignancies encountered are lung, lymphoma, breast, leukaemia, stomach, melanoma, liver and colon94 (Fig. 14.39). A pericardial effusion is the most common finding in pericardial malignancy, whether primary pericardial or metastatic. Intrapericardial neoplasms tend to compress and deform normal intrapericardial structures, whereas extrapericardial masses tend to displace the intrapericardial structures without compression or distortion. Chest radiographs are often abnormal, but are non-specific. Alteration of fat-pad contours, cardiac enlargement, mediastinal widening, hilar adenopathy, or a hilar mass may be seen. Echocardiography is usually the initial technique for evaluation of a suspected pericardial neoplasm, with MRI and CT being useful for further evaluation. Both MRI and CT are excellent at providing information regarding the size, location and extent of pericardial neoplasms, but are not tissue specific. Fatty tumours (lipomas, fat-containing teratomas) are the exception, due to their typically low attenuation on CT and increased signal intensity on spin-echo T1-weighted MRI. Fatty tumours must be differentiated from the focal

Malignant mesothelioma Malignant mesothelioma is the most common primary pericardial malignancy. A causal relationship between it and asbestosis is uncertain because of the low prevalence of this neoplasm. Mesothelioma may present as a well-defined single mass, multiple nodules, or diffuse plaques involving the visceral and parietal pericardium and wrapping around the cardiac chambers and great vessels. Clinically it presents with haemorrhagic effusion and tamponade, congestive heart failure, arrhythmia and occasionally pericardial constriction93. Other malignant primary tumours include lymphoma, sarcoma, phaeochromocytoma and liposarcoma (Fig. 14.38).Teratomas of the pericardium may also be malignant and are most commonly seen in children.

Pericardial metastases Pericardial metastases are much more common than primary pericardial neoplasms. They are identified at autopsy

Figure 14.39 Metastatic melanoma. There is a mass within the right atrial cavity that demonstrates high signal intensity on this T1-weighted image in keeping with the known diagnosis of metastatic malignant melanoma (arrows). Note the enlarged left axillary lymph nodes.

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deposits of subepicardial fat and non-neoplastic lesions that can simulate fatty tumours, such as mesenteric fat in a hiatal hernia. Metastatic melanoma may have high signal intensity on T1- and T2-weighted images (see Fig. 14.40)95, a feature that may be useful in differentiating it from other metastatic neoplasms, which are frequently of low signal intensity on T1and high signal intensity on T2-weighted images96. In addition to discrete masses and effusions, metastatic involvement of the pericardium may cause focal or diffuse pericardial thickening, which may be irregular and usually enhances. Primary lipoma, liposarcoma and lymphoma of the pericardium typically appear as large heterogeneous masses frequently associated with a serosanguinous pericardial effusion93.

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21. Choyke P L, Zeman R K, Gootenberg J E, Greenberg J N, Hoffer F, Frank J A 1987 Thymic atrophy and regrowth in response to chemotherapy: CT evaluation. Am J Roentgenol 149: 269–272 22. Kissin C M, Husband J E, Nicholas D, Eversman W 1987 Benign thymic enlargement in adults after chemotherapy: CT demonstration. Radiology 163: 67–70 23. Cohen M, Hill C A, Cangir A, Sullivan M P 1980 Thymic rebound after treatment of childhood tumors. Am J Roentgenol 135: 151–156 24. Moran C A, Suster S 1997 Primary germ cell tumors of the mediastinum: I. Analysis of 322 cases with special emphasis on teratomatous lesions and a proposal for histopathologic classification and clinical staging. Cancer 80: 681–690 25. Moeller K H, Rosado-de-Christenson M L, Templeton P A 1997 Mediastinal mature teratoma: imaging features. Am J Roentgenol 169: 985–990 26. Strollo D C, Rosado de Christenson M L, Jett J R 1997 Primary mediastinal tumors. Part 1: tumors of the anterior mediastinum. Chest 112: 511–522 27. Knapp R H, Hurt R D, Payne W S et al 1985 Malignant germ cell tumors of the mediastinum. J Thorac Cardiovasc Surg 89: 82–89 28. Lee K, Im J, Han M, Kim C, Kim W 1989 Malignant primary germ cell tumors of the mediastinum: CT features. Am J Roentgenol 153: 947–951 29. Rosado-de-Christenson M L, Templeton P A, Moran C A 1992 From the archives of the AFIP. Mediastinal germ cell tumors: radiologic and pathologic correlation. RadioGraphics 12: 1013–1030 30. Radin D R, Baker E L, Klatt E C et al 1990 Visceral and nodal calcification in patients with AIDS-related Pneumocystis carinii infection. Am J Roentgenol 154: 27–31 31. Pombo F, Rodriguez E, Mato J, Perez-Fontan J, Rivera E, Valvuena L 1992 Patterns of contrast enhancement of tuberculous lymph nodes demonstrated by computed tomography. Clin Radiol 46: 13–17 32. Landay M J, Rollins N K 1989 Mediastinal histoplasmosis granuloma: evaluation with CT. Radiology 172: 657–659 33. Yousem D M, Scatarige J C, Fishman E K, Siegelman S S 1986 Lowattenuation thoracic metastases in testicular malignancy. Am J Roentgenol 146: 291–293 34. Hopper K D, Diehl L F, Cole B A, Lynch J C, Meilstrup J W, McCauslin M A 1990 The significance of necrotic mediastinal lymph nodes on CT in patients with newly diagnosed Hodgkin disease. Am J Roentgenol 155: 267–270 35. Samuels T, Hamilton P, Shaw P 1990 Whipple disease of the mediastinum Am J Roentgenol 154: 1187–1188 36. Miller B H, Rosado-de-Christenson M L, McAdams H P, Fishback N F 1995 Thoracic sarcoidosis: radiologic–pathologic correlation. RadioGraphics 15: 421–437 37. Bein M E, Putman C E, McLoud T C, Mink J H 1978 A reevaluation of intrathoracic lymphadenopathy in sarcoidosis. Am J Roentgenol 131: 409–415 38. Castellino R A, Hilton S, O’Brien J P, Portlock C S 1996 Non-Hodgkin lymphoma: contribution of chest CT in the initial staging evaluation. Radiology 199: 129–132 39. Castellino R A, Blank N, Hoppe R T, Cho C 1986 Hodgkin disease: contributions of chest CT in the initial staging evaluation. Radiology 160: 603–605 40. Jochelson M S, Balikian J P, Mauch P, Liebman H 1983 Peri- and paracardial involvement in lymphoma: a radiographic study of 11 cases. Am J Roentgenol 140: 483–488 41. McLoud T C, Kalisher L, Stark P, Greene R 1978 Intrathoracic lymph node metastases from extrathoracic neoplasms. Am J Roentgenol 131: 403–407 42. McAdams H P, Rosado-de-Christenson M, Fishback N F, Templeton P A 1998 Castleman disease of the thorax: radiologic features with clinical and histopathologic correlation. Radiology 209: 221–228 43. Yamashita Y, Hirai T, Matsukawa T, Ogata I, Takahashi M 1993 Radiological presentations of Castleman’s disease. Comput Med Imaging Graph 17: 107–117

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44. Strollo D C, Rosado-de-Christenson M L, Jett J R 1997 Primary mediastinal tumors: part II. Tumors of the middle and posterior mediastinum. Chest 112: 1344–1357 45. Nakata H, Nakayama C, Kimoto T et al 1982 Computed tomography of mediastinal bronchogenic cysts. J Comput Assist Tomogr 6: 733–738 46. Mendelson D S, Rose J S, Efremidis S C, Kirschner P A, Cohen B A 1983 Bronchogenic cysts with high CT numbers. Am J Roentgenol 140: 463–465 47. Kawashima A, Fishman E K, Kuhlman J E, Nixon M S 1991 CT of posterior mediastinal masses. RadioGraphics 11: 1045–1067 48. Erasmus J J, McAdams H P, Donnelly L F, Spritzer C E 2000 MR imaging of mediastinal masses. Magn Reson Imaging Clin North Am 8: 59–89 49. Reed J C, Hallet K K, Feigin D S 1978 Neural tumors of the thorax: subject review from the AFIP. Radiology 126: 9–17 50. Kumar A J, Kuhajda F P, Martinez C R, Fishman E K, Jezic D V, Siegelman S S 1983 Computed tomography of extracranial nerve sheath tumors with pathological correlation. J Comput Assist Tomogr 7: 857–865 51. Bhargava R, Parham D M, Lasater O E, Chari R S, Chen G, Fletcher B D 1997 MR imaging differentiation of benign and malignant peripheral nerve sheath tumors: use of the target sign. Pediatr Radiol 27: 124–129 52. Aughenbaugh GL 1984 Thoracic manifestations of neurocutaneous diseases. Radiol Clin North Am 22: 741–756 53. Adam A, Hochholzer L 1981 Ganglioneuroblastoma of the posterior mediastinum: a clinicopathologic review of 80 cases. Cancer 47: 373–381 54. Bar-Ziv J, Nogrady M B 1975 Mediastinal neuroblastoma and ganglioneuroma. The differentiation between primary and secondary involvement on the chest roentgenogram. Am J Roentgenol Radium Ther Nucl Med 125: 380–390 55. Olson J L, Salyer W R 1978 Mediastinal paragangliomas (aortic body tumor): a report of four cases and a review of the literature. Cancer 41: 2405–2412 56. Spizarny D L, Rebner M, Gross B H 1987 CT evaluation of enhancing mediastinal masses. J Comput Assist Tomogr 11: 990–993 57. van Gils A P, Falke T H, van Erkel A R et al 1991 MR imaging and MIBG scintigraphy of pheochromocytomas and extraadrenal functioning paragangliomas. RadioGraphics 11: 37–57 58. Krenning E P, Kwekkeboom D J, Bakker W H et al 1993 Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med 20: 716–731 59. Miles J, Pennybacker J, Sheldon P 1969 Intrathoracic meningocele. Its development and association with neurofibromatosis. J Neurol Neurosurg Psychiatry 32: 99–110 60. Long J A Jr, Doppman J L, Nienhuis A W 1980 Computed tomographic studies of thoracic extramedullary hematopoiesis. J Comput Assist Tomogr 4: 67–70 61. Shaffer K, Rosado-de-Christenson M L, Patz E F Jr, Young S, Farver C F 1994 Thoracic lymphangioma in adults: CT and MR imaging features. Am J Roentgenol 162: 283–289 62. Glazer H S, Wick M R, Anderson D J et al 1992 CT of fatty thoracic masses. Am J Roentgenol 159: 1181–1187 63. Whyte A M, Powell N 1990 Mediastinal lipoblastoma of infancy. Clin Radiol 42: 205–206 64. Gaerte S C, Meyer C A, Winer-Muram H T, Tarver R D, Conces D J Jr 2002 Fat-containing lesions of the chest. RadioGraphics 22: 615–678 65. Kline M E, Patel B U, Agosti S J 1990 Noninfiltrating angiolipoma of the mediastinum. Radiology 175: 737–738 66. Kim K, Koo B C, Davis J T, Franco-Saenz R 1984 Primary myelolipoma of mediastinum. J Comput Tomogr 8: 119–123 67. Jolles H, Henry D A, Roberson J P, Cole T J, Spratt J A 1996 Mediastinitis following median sternotomy: CT findings. Radiology 201: 463–466 68. Bitkover C Y, Cederlund K, Aberg B, Vaage J 1999 Computed tomography of the sternum and mediastinum after median sternotomy. Ann Thorac Surg 68: 858–863 69. Carter A R, Sostman H D, Curtis A M, Swett H A 1983 Thoracic alterations after cardiac surgery. Am J Roentgenol 140: 475–481

• THE MEDIASTINUM, INCLUDING THE PERICARDIUM

70. Goodwin R A, Nickell J A, Des Prez R M 1972 Mediastinal fibrosis complicating healed primary histoplasmosis and tuberculosis. Medicine Balt 51: 227–246 71. Sherrick A D, Brown L R, Harms G F, Myers J L 1994 The radiographic findings of fibrosing mediastinitis. Chest 106: 484–489 72. Rossi S E, McAdams H P, Rosado-de-Christenson M L, Franks T J, Galvin J R 2001 Fibrosing mediastinitis. RadioGraphics 21: 737–757 73. Woodring J H, Loh F K, Kryscio R J 1984 Mediastinal hemorrhage: an evaluation of radiographic manifestations. Radiology 151: 15–21 74. Bejvan S M, Godwin J D 1996 Pneumomediastinum: old signs and new signs. Am J Roentgenol 166: 1041–1048 75. Holt JP 1970 The normal pericardium. Am J Cardiol 26: 455–465 76. Bull R K, Edwards P D, Dixon A K 1998 CT dimensions of the normal pericardium. Br J Radiol 71: 923–925 77. Sechtem U, Tscholakoff D, Higgins C B 1986 MRI of the normal pericardium. Am J Roentgenol 147: 239–244 78. Rienmuller R, Groll R, Lipton M J 2004 CT and MR imaging of pericardial disease. Radiol Clin North Am 42: 587–601, vi 79. Groell R, Schaffler G J, Rienmueller R 1999 Pericardial sinuses and recesses: findings at electrocardiographically triggered electron-beam CT. Radiology 212: 69–73 80. Budoff M J, Lu B, Mao S et al 2000 Evaluation of fluid collection in the pericardial sinuses and recesses: noncontrast-enhanced electron beam tomography. Invest Radiol 35: 359–365 81. Spodick D H 2001 Pericardial disease. In: Braunwald E (ed) Heart disease: a textbook of cardiovascular medicine. WB Saunders, Philadelphia, pp 1823–1876 82. Nasser W K, Helmen C, Tavel M E, Feigenbaum H, Fisch C 1970 Congenital absence of the left pericardium. Clinical, electrocardiographic, radiographic, hemodynamic, and angiographic findings in six cases. Circulation 41: 469–478 83. Van Son J A, Danielson G K, Schaff H V, Mullany C J, Julsrud P R, Breen J F 1993 Congenital partial and complete absence of the pericardium. Mayo Clin Proc 68: 743–747 84. Feigin D S, Fenoglio J J, McAllister H A, Madewell J E 1977 Pericardial cysts. A radiologic-pathologic correlation and review. Radiology 125: 15–20 85. Sechtem U, Tscholakoff D, Higgins C B 1986 MRI of the abnormal pericardium. Am J Roentgenol 147: 245–252 86. Lane E J Jr, Carsky E W 1968 Epicardial fat: Lateral plain film analysis in normals and in pericardial effusion. Radiology 91: 1–5 87. Carsky E W, Mauceri R A, Azimi F 1980 The epicardial fat pad sign: analysis of frontal and lateral chest radiographs in patients with pericardial effusion. Radiology 137: 303–308 88. Yousem D, Traill T T, Wheeler P S, Fishman E K 1987 Illustrative cases in pericardial effusion misdetection: correlation of echocardiography and CT. Cardiovasc Intervent Radiol 10: 162–167 89. Tomoda H, Hoshiai M, Furuya H et al 1980 Evaluation of pericardial effusion with computed tomography. Am Heart J 99: 701–706 90. Cameron J, Oesterle S N, Baldwin J C, Hancock E W 1987 The etiologic spectrum of constrictive pericarditis. Am Heart J 113: 354–360 91. Ling L H, Oh J K, Schaff H V et al 1999 Constrictive pericarditis in the modern era: evolving clinical spectrum and impact on outcome after pericardiectomy. Circulation 100: 1380–1386 92. Masui T, Finck S, Higgins C B 1992 Constrictive pericarditis and restrictive cardiomyopathy: evaluation with MR imaging. Radiology 182: 369–373 93. Grebenc M L, Rosado de Christenson M L, Burke A P, Green C E, Galvin J R 2000 Primary cardiac and pericardial neoplasms: Radiologic– pathologic correlation. RadioGraphics 20: 1073–1103 94. Abraham K P, Reddy V, Gattuso P 1990 Neoplasms metastatic to the heart: review of 3314 consecutive autopsies. Am J Cardiovasc Pathol 3: 195–198 95. Mousseaux E, Meunier P, Azancott S, Dubayle P, Gaux J C 1998 Cardiac metastatic melanoma investigated by magnetic resonance imaging. Magn Reson Imaging 16: 91–95 96. Fujita N, Caputo G R, Higgins C B 1994 Diagnosis and characterization of intracardiac masses by magnetic resonance imaging. Am J Card Imaging 8: 69–80

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SUGGESTIONS FOR FURTHER READING Choe Y H, Im J G, Park J H, Kim C W 1987 The anatomy of the pericardial space: a study in cadavers and patients. Am J Roentgenol 149: 693–697 Schoepf U J (ed) 2004 CT of the heart: Principles and applications. Humana Press, New Jersey Sharma A, Fidias P, Hayman L A, Loomis S L, Taber K H, Aquino S L 2004 Patterns of lymphadenopathy in thoracic malignancies. RadioGraphics 24: 419–434

Spindola-Franco H, Fish B G 1985 Radiology of the heart. Springer Verlag, New York Strollo D C, Rosado de Christenson M L, Jett J R 1997 Primary mediastinal tumors. Part 1: tumors of the anterior mediastinum. Chest 112: 511–522 Strollo D C, Rosado-de-Christenson M L, Jett J R 1997 Primary mediastinal tumors: part II. Tumors of the middle and posterior mediastinum. Chest 112: 1344–1357

CHAPTER

Pulmonary Infection in Adults

15

Philip C. Goodman

Specific pneumonias • Lobar pneumonias • Bronchopneumonia • Anaerobic pneumonias • Atypical pneumonia • Pulmonary tuberculosis • Nontuberculous mycobacterial disease • Fungal infections • Protozoal and metazoal diseases Pulmonary complications of HIV infection and AIDS Infections • Malignancies

The variety of infectious agents that produce pneumonia in humans is vast, encompassing bacteria, viruses, fungi, protozoa and parasites.The chest radiograph is invariably abnormal with pneumonia and when on occasion it is normal, CT of the chest may reveal underlying lung involvement. From a diagnostic standpoint radiographic findings should be combined with clinical and laboratory information to suggest the cause of infection. Differentiation of aetiologies based solely on the radiograph is not reliable, yet the pattern of abnormalities should be very useful in formulating a differential diagnosis of the nature of disease1.

SPECIFIC PNEUMONIAS Specific pneumonias are caused by organisms drawn from virtually all forms of microbial life. In the following sections the type of infections are classified in a variety of ways: their predominant appearance, by the situations in which they are acquired, and taxonomically. Some organisms cross over pattern and situational boundaries and will only be addressed briefly when that occurs. First an explanation of some terms is presented. Lobar pneumonia is usually unifocal, develops in the distal airspaces adjacent to the visceral pleura, and then spreads via collateral air drift routes to produce uniform homogeneous opacification of partial or complete segments of lung and occasionally an entire lobe. As the airways are not primarily involved and remain patent, there is little to no volume loss and air bronchograms are common. On the other hand, bronchopneumonia, frequently caused by aspiration of secretions from a colonized trachea, is usually multifocal and centred in distal airways. The process is initially heterogeneous and distributed along the course of the airways. Thus, radiologically a bronchopneumonia is characterized by large heterogeneous, scattered opacities which only later, with worsening of disease, become more homogeneous. An air bronchogram is usually absent.

The term atypical pneumonia was initially applied to the clinical and radiographic appearance of lung infection not behaving or looking like that caused by Streptococcus pneumoniae. Radiographically focal or diffuse small heterogeneous opacities are seen uniformly distributed in the involved lung. Frequently these opacities are described as reticular or reticulonodular. Community-acquired pneumonias are caused by a variety of typical and atypical organisms with a myriad of radiographic abnormalities. However, many community-acquired pneumonias are still commonly caused by Strep. pneumoniae and are lobar in appearance. Nosocomial pneumonias occur during hospitalization. They frequently appear as bronchopneumonia caused by Staphylococcus aureus and Gram-negative organisms. They may look like atypical infections, similar to those caused by Mycoplasma, viruses and Chlamydia. In practice, however, remember that radiological patterns can be indeterminate and that one infectious agent can produce many patterns2.

LOBAR PNEUMONIAS Streptococcus pneumoniae Strep. pneumoniae pneumonia (pneumococcal pneumonia) is the most common community-acquired bacterial pneumonia

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in adults. Predisposing factors include chronic illness, alcoholism, sickle-cell disease and splenectomy. Chest radiographs generally reveal a peripheral, homogeneous opacity with or without air bronchograms (Fig. 15.1).Though commonly basal and solitary, this pneumonia can occur in any lobe and may be multifocal. Round-shaped pneumonias may simulate lung masses (Fig. 15.2). Lobar volume usually remains unchanged but rarely it increases. Cavitation is very unlikely. Parapneumonic effusion is fairly common; empyema is less frequent. Atypical patterns of heterogeneous opacification have been described but are unusual. Radiographic resolution is fairly rapid with some improvement commonly seen within 1 week and total resolution within 2–6 weeks (Fig. 15.3). Failure to improve may be due to drug resistance, incorrect or inadequate antimicrobial treatment, an obstructing lesion, development

Figure 15.2 Pneumococcal pneumonia—simulates mass. A 56 year old man with fever and productive cough. (A) PA and (B) lateral chest radiographs demonstrate a discrete fairly well marginated opacity in the right lower lobe. The abnormality resolved following appropriate antibiotic therapy and Gram stains of sputum demonstrated Strep. pneumoniae. Figure 15.1 Pneumococcal pneumonia. A 38 year old man with Strep. pneumoniae pneumonia. A close-up of the PA chest radiograph demonstrates a homogeneous lingular opacity with central air bronchograms.

Figure 15.3 Pneumococcal pneumonia—resolution time. A 48 year old man with productive cough and fever. (A) AP chest radiograph demonstrates peripheral homogeneous poorly marginated opacity. (B) AP image demonstrates significant improvement 5 d after institution of therapy.

CHAPTER 15

of lung abscess or empyema, or noninfectious cause of the opacity, e.g. broncho-alveolar carcinoma3.

Klebsiella Klebsiella pneumoniae pneumonia may arise in the community or in hospital. The chest radiograph frequently demonstrates homogeneous opacity similar to Strep. pneumoniae or may reveal scattered focal heterogeneous opacities, a bronchopneumonia, as produced by other Gram-negative bacteria. Early series reported rapid cavitation of lobar consolidation often accompanied by bulging fissures signifying a very exudative response.

Legionella Legionella pneumophila causes a pneumonia (Legionnaires’ disease) which when severe has a 10–30% mortality rate. Legionnaires’ disease may be acquired in a community, nosocomial, or epidemic fashion associated with contaminated water sources. Predisposing factors include post-transplantation, chronic obstructive pulmonary disease (COPD) and heart failure. The typical radiographic patterns include solitary or multifocal, lobar pneumonia-like, homogeneous opacities, simulating Strep. pneumoniae infection4, but with a tendency to round and mass-like appearance (Fig. 15.4). Rapid progression is common, with confluence and/or spread of the initial frequently unilateral consolidation to other lobes. Cavitation has been described in immunocompromised and post renaltransplant patients. An effusion occurs in 10–35% of cases. Resolution may be quick when treated appropriately but in some instances may take weeks.

Actinomycosis Actinomycosis is caused by Actinomyces israeli, an anaerobic, Gram-positive bacterium.The organisms reside as commensals in the mouth and oropharynx and cause infection when access occurs to devitalized or previously infected tissues, particularly

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PULMONARY INFECTION IN ADULTS

in the cervicofacial region and abdomen. A chronic inflammatory reaction spreads across fascial planes and causes abscesses and fistulas containing tiny sulphur granules. In fewer than one-quarter of cases the lungs are involved from aspiration or spread from abdominal or cervicofacial foci. The chest radiograph usually reveals homogeneous opacification as a lobar type pneumonia or mass5. Cavitation is common and the appearance mimics bronchogenic carcinoma. Focal fibrosis and contraction may be severe.Widespread small nodules have been reported. Pleural effusion, pleural thickening or empyema formation, and extension of disease to the contiguous soft tissue or bones (as a periostitis) set this pneumonia apart from the usual bacterial types. (Tuberculosis and nocardiosis may have a similar appearance.) At CT, scattered peripheral areas of homogeneous consolidation with central low attenuation and adjacent pleural thickening are suggestive of actinomycosis6.

Nocardiosis Nocardia asteroides is an aerobic, Gram-positive, weakly acid-fast bacillus, related to, and sometimes confused with, A. israeli and the Mycobacteria. Infections by these organisms occur worldwide, but most reported cases are from North America. The majority of affected patients are immunocompromised, including patients with acquired immune deficiency syndrome (AIDS). Nocardiosis usually begins with a focus of pulmonary infection and may disseminate to other organs, notably the brain. The chest radiographic findings vary7. Pulmonary consolidation, either unifocal or multifocal, is the usual feature and cavitation is frequent. However, many chest radiographs reveal single or multiple pulmonary nodules resembling primary lung cancer or metastatic disease (Fig. 15.5). Cavitation is common as is pleural effusion. Lymphadenopathy or chest wall involvement may be evident, especially on CT 8.

Moraxella (Branhamella) catarrhalis Moraxella catarrhalis is a Gram-negative coccus that commonly causes otitis media and sinusitis in children, and acute tracheobronchitis or a relatively mild pneumonia in older patients with COPD. Many patients have additional serious underlying disease, including bronchial carcinoma, or are taking steroids. Presentation is most common during the winter and early spring, and the most frequent radiological pattern is lobar or segmental homogeneous opacification9. Bibasal and heterogeneous or mixed heterogeneous/homogeneous opacities are also reported. Small effusions occur in one-third of patients.

Chlamydial pneumonia

Figure 15.4 Legionnaires’ disease. A 35 year old man with high fevers. The AP radiograph demonstrates homogeneous opacities in the right upper lobe. The medial one resembles a mass. Subsequent images demonstrated bilateral spread of disease determined to be caused by Legionella pneumophila.

Chlamydiae are bacteria implicated in community-acquired pneumonias. C. psittaci and C. pneumoniae (strain TWAR) cause infections in adults, and C. trachomatis largely, but not entirely, in neonates. C. psittaci causes psittacosis (ornithosis), which is usually seen following direct bird contact but occasionally after outdoor activity, e.g. mowing lawns. The clinical manifestations may be indistinguishable from an acute bacterial pneumonia. Chest radiography reveals small to large homogeneous opacities and/ or perihilar or basal reticular opacities10. Hilar nodes are occasionally enlarged and small effusions are sometimes present.

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acquired by inhalation from farm livestock or their products, and occasionally from domestic animals. Radiographic abnormalities usually consist of unilateral, but occasionally bilateral, segmental, or lobar opacities14. In 20% of patients reticular opacities are observed15. Pleural effusion occurs but is not common. Radiographic resolution occurs within 6 weeks of starting treatment. Other rickettsial infections such as Rocky Mountain spotted fever are usually tick-borne and occasionally demonstrate diffuse heterogeneous or homogeneous opacities on chest radiographs, perhaps representing vasculitis or cardiogenic pulmonary oedema16.

Francisella tularensis Francisella tularensis is a Gram-negative coccobacillus that causes tularaemia. It is endemic in parts of Europe, Asia and North America. The disease is acquired from handling infected animals, bites of insect vectors and inhalation. In patients with pleuropulmonary tularaemia the most common radiographic findings in the chest are scattered airspace consolidation, hilar adenopathy and pleural effusion17.Various other, less common, changes are seen, including cavitation.

Yersinia (Pasturella) pestis

Figure 15.5 Nocardia infection. A young immune suppressed patient presented with fever and cough. (A) PA chest radiograph demonstrates large mass with possible cavitation in the right upper lobe. (B) Single CT section demonstrates well defined large mass with central necrosis.

Yersinia pestis is a Gram-negative coccobacillus that causes plague, a disease that is endemic in parts of South America Africa and Asia. It is also found in the southwestern USA, about 20 cases being reported annually, of which 10% have respiratory involvement18. Plague exists in three forms—primary septicaemic, bubonic and pneumonic. The latter two forms are the most common and both are associated with chest radiographic changes. The principal radiographic findings are basally predominant, bilateral, multifocal areas of consolidation that rapidly progress to become confluent. Pleural effusion is common and there may be mediastinal adenopathy, the latter sometimes being the sole manifestation in the chest of the bubonic form of the disease19.

Leptospirosis The radiographic opacity characteristically clears slowly and persistent changes at 3 months are not uncommon11. C. pneumoniae (strain TWAR) causes respiratory infections in adults that are often asymptomatic or mild. It is one of the most common causes of community-acquired pneumonia. The illness may be biphasic, with initial sore throat and hoarseness followed a few weeks later by lower respiratory tract symptoms. The most common radiographic pattern in primary infection is usually unifocal and occasionally multifocal homogeneous opacity. With recurrent infection, changes are more commonly bilateral and equally homogeneous and heterogeneous. Up to one-half of patients have pleural fluid, either small or moderate in size. In one series it was not possible reliably to differentiate between pneumonia caused by C. pneumoniae and S. pneumoniae12,13.

The Leptospira interrogans complex is a group of spirochaetes pathogenic for almost all mammals, including man.The disease in humans is usually acquired from contact with contaminated water (sewage workers, water-sport participants) or directly from infected animals. Leptospirosis is a biphasic illness characterized initially by fever, headache and myalgia, followed by skin rash and renal, neurological and hepatic disorder. Pulmonary involvement, reported in 11–67% of cases, is characterized by a haemorrhagic pneumonitis. The initial radiographic pattern is often nodular (1–7-mm diameter) evolving into confluent airspace or ground-glass opacities. Changes are bilateral, commonly peripherally predominant, and resolve in about 2 weeks20. Small pleural effusions and discoid atelectasis are also described.

Rickettsial pneumonia

Other pneumonias that need to be included in a differential list of lobar type infections include primary tuberculosis (see section on mycobacterial disease), coccidioidomycosis and blastomycosis (see section on fungal disease).

The most common rickettsial lung infection is sporadic or epidemic Q-fever pneumonia caused by Coxiella burnetii, an intracellular, Gram-negative bacterium. Infection is mainly

Miscellaneous infections

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PULMONARY INFECTION IN ADULTS

BRONCHOPNEUMONIA Staphylococcus aureus Staph. aureus pneumonia occurs in debilitated hospitalized or institutionalized patients, and less frequently as a community-acquired infection. It is usually acquired by aspiration from the upper respiratory tract. Chest radiographs typically demonstrate heterogeneous opacities in a scattered multifocal and bilateral distribution21 (Fig. 15.6). Pleural effusion or empyema, and cavitation are common; air bronchograms are unusual. Pneumatoceles may form, particularly in children. Septicaemic infections, as opposed to those acquired by aspiration, cause disseminated, poorly marginated, peripheral, multifocal, nodules which can cavitate.These septic emboli are seen in drug addicts, immunocompromised patients and patients with infective endocarditis or indwelling catheters.

Gram-negative pneumonias Gram-negative pneumonias are chiefly caused by enterobacteria (Enterobacter sp., Serratia marcescens, Proteus sp, Escherichia coli, Pseudomonas aeruginosa and Haemophilus influenzae) in a hospital setting. Patients affected are invariably debilitated by a chronic medical or pulmonary disease. These bacteria are generally aspirated from a colonized upper respiratory tract or may be inhaled or spread hematogenously. The lower lobes predominantly tend to be affected and the radiographic pattern is similar to that seen with Staph. aureus infections in adults (Fig. 15.7). A CT study of Ps. aeruginosa pneumonias revealed multifocal, predominantly upper lobe, airspace consolidation, random large nodules, tree-in-bud opacities, ground-glass opacity, necrosis and pleural effusion22.

Figure 15.6 Bronchopneumonia—staphylococcus. A 24 year old man with fever and cough developed within the hospital. The AP chest radiograph demonstrates bilateral scattered homogeneous and heterogeneous opacities, some almost nodular.

Figure 15.7 Gram-negative pneumonia—septic emboli. A 52 year old man with high fevers that developed during hospitalization. AP chest radiograph demonstrates scattered peripheral discrete and rounded opacities. Right upper lobe nodule is cavitated with thin walls. Left lower lobe nodule has thick-wall cavitation. Escherichia coli was cultured from blood.

ANAEROBIC PNEUMONIAS Most anaerobic pneumonias result from aspiration of bacteria, including Bacteroides, Peptostreptococcus, microaerophilic streptococcus, and Fusobacterium following a bout of altered consciousness, or mechanical ventilation23. Immediately following aspiration the chest radiograph is frequently normal although scattered opacities representing partial atelectasis caused by aspirated food may be seen. The appearance of pneumonia is usually delayed 24–72 h, at which time heterogeneous opacities are seen in dependent lung segments (posterior upper lobe, superior, or posterobasal lower lobe.) Involvement may be uni- or bi-lateral. Empyema is a common complication, may be large, and may occur with or without radiographic evidence of pneumonia. Multiple cavities reflecting severe lung necrosis may be seen 1–3 weeks following aspiration (Fig. 15.8). Patients who delay seeking medical help for 3–4 weeks may present with a discrete lung abscess24. Nearly two-thirds of these lesions occur in the apicoposterior segments of upper lobes and the superior segments of lower lobes. These may be large, ranging in size from 2 to 12 cm. Characteristically the wall is thick and irregular. Mediastinal nodal enlargement, though not common, may be observed. The above radiological features, coupled with an indolent course and systemic symptoms, closely resemble the findings of post primary tuberculosis or bronchogenic carcinoma.

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Figure 15.8 Anaerobic pneumonia. A 51 year old man with chronic fevers and productive cough. (A) PA and (B) lateral chest radiographs demonstrate left lower lobe opacity with multiple air–fluid levels. The patient was treated for an anaerobic pneumonia and improved rapidly. Incidentally noted are right paratracheal calcified lymph nodes from prior tuberculosis or histoplasmosis.

ATYPICAL PNEUMONIA Mycoplasma pneumonia Mycoplasma pneumoniae is a major nonbacterial cause of community-acquired pneumonia in patients between the ages of 20 and 40 years. Spread is from person to person by droplets during close contact, particularly in some communities (e.g. military barracks). Symptoms resemble a viral infection with progression from the upper to the lower respiratory tract. Pneumonia occurs in less than one-tenth of those infected, is accompanied by a minimally productive cough, and usually runs a self-limiting course. Extrapulmonary complications are well described. The radiological findings are variable and may be striking in the face of minor clinical signs. The most common pattern is unilateral lower lobe involvement beginning as heterogeneous, reticular, segmental, peribronchial opacifications that may become lobar and homogeneous. Bilateral or multilobar involvement is a frequently observed variation (Fig. 15.9). Pleural effusions are uncommon. Nodal enlargement is an unusual finding in adults, occurring in about one-fifth of patients in some series11. Radiological clearing is variable and may occasionally take as long as 6 weeks. CT demonstrates ground-glass and homogeneous opacities, a bronchiolitis with centrilobular nodules, and bronchovascular thickening in approximately 80% of patients25.

Influenza A and B Influenza A and B are common causes of pneumonia in adults, particularly the elderly. Radiographic findings within a few days after symptoms begin include scattered homogeneous opacities that rapidly become bilateral, extensive and confluent. Pleural effusion is uncommon or rare. Clinical

Viral pneumonias Viral pneumonia is common in infants and children but unusual in adults. Studies of community-acquired pneumonia suggest that about 8% are viral. The pneumonia may be solely a manifestation of respiratory tract involvement (e.g. influenza) or part of a more generalized viral illness (e.g. varicella). Viral infections predispose to secondary bacterial pneumonia.

Figure 15.9 Mycoplasma pneumonia. A 35 year old man presents with nonproductive cough and fever. The PA chest radiograph demonstrates bilateral perihilar and lower lobe heterogeneous reticular opacities as well as a more focal left upper lobe homogeneous opacity. Findings are characteristic of atypical community-acquired infections.

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relapse about 2 weeks after the onset of influenza may be due to secondary bacterial pneumonia (often Strep. pneumoniae or Staph. aureus). In patients with underlying haematological malignancies, chest radiographs demonstrate scattered bilateral consolidation and ill-defined nodules, and CT reveals groundglass opacities nodules and a tree-in-bud appearance26.

Herpes simplex virus (HSV)

Adenovirus

Hantavirus

Adenovirus, a common upper respiratory tract pathogen, rarely results in respiratory failure and a radiographic appearance of acute respiratory distress syndrome (ARDS)27,28. Initial radiographs show homogeneous lobar pneumonia that progresses to diffuse bilateral heterogeneous and homogeneous opacities. A similar appearance has been described in paediatric patients29.

Hantavirus is transmitted by human contact with infected deer mice and produces a pulmonary syndrome most frequently reported in the southwestern USA. Bilateral homogeneous opacities resembling ARDS are seen33 and nearly all patients have pleural fluid. The mortality rate of treated patients can approach 35%.

Infectious mononucleosis

Cytomegalovirus (CMV) pneumonia has been seen in increasing numbers with the proliferation of bone marrow and solid organ transplantation. Chest radiographs demonstrate focal and diffuse hazy opacification and multiple small (less than 5 mm) nodules, and less commonly focal consolidation34. CT reveals small centrilobar nodules and ground-glass or homogeneous consolidation generally in a symmetric and bilateral distribution35. Solitary or multiple large nodules are frequently identified at CT.

This is caused by the Ebstein–Barr virus. Radiological manifestations in the chest are uncommon and include hilar lymphadenopathy, heterogeneous opacities, small pleural effusions and lobar homogeneous consolidation30.

Varicella Varicella is unlike other viruses in that it causes pneumonia more frequently in adults than in children. Typically, young adults are affected, some predisposed to the infection by lymphoma, pregnancy, or steroid therapy. Pulmonary involvement follows the skin rash by 1–6 d. The radiological findings are characteristic, consisting of widespread 5–10 mm in diameter poorly marginated nodules or acinar opacities, which may become confluent (Fig. 15.10). The nodules usually resolve in a week or two but can persist for months (simulating metastases). CT findings are similar, including nodules and coalescing opacities; ground-glass opacities are also observed31. In resolution, numerous small irregular calcified nodules can develop; these can be evident on plain radiographs.

Figure 15.10 Varicella pneumonia. A 30 year old man with lymphoma and new development of fever and skin rash. The PA chest radiograph demonstrates bilateral poorly marginated 5–10 mm in diameter nodular opacities.

Herpes simplex virus (HSV) may also cause pneumonia characterized by hazy and homogeneous opacities seen in a segmental or subsegmental distribution, and pleural effusion in approximately 50% of patients. At CT similar findings are noted32.

Cytomegalovirus (CMV)

PULMONARY TUBERCULOSIS Mycobacterium tuberculosis accounts for more than 95% of pulmonary mycobacterial infections. Other mycobacterial species, mainly M. kansasii and the M. avium–intracellulare complex (MAC) account for the remainder. Infections are acquired via droplet inhalation from other infected individuals. In people who are previously unexposed, hypersensitivity to tuberculoprotein is absent and primary tuberculosis develops. This form is commonly seen in infants and children. With improved control of tuberculosis in western societies, however, more people reach adulthood without exposure, and primary patterns of disease are being seen with increasing frequency in adulthood. If a patient already possesses hypersensitivity to tuberculoprotein by virtue of a previous infection or BCG vaccination, then post-primary tuberculosis is seen. Should the primary disease pass into the post-primary form without a break, the term progressive primary tuberculosis is used. Factors that contribute to the large number of cases seen worldwide are human immunodeficiency virus (HIV) infection, inner city poverty, homelessness and immigration from areas with high rates of infection. Other predisposing conditions are diabetes mellitus, alcoholism, silicosis, malignancy, immune compromise from a variety of causes and living in closed institutions. Symptoms include loss of weight and appetite, malaise, fever, night sweats and cough, which may or may not be productive and accompanied by haemoptysis. Treatment is by chemotherapy and, given cooperation by the patient and a sensitive organism, it is very successful. Recourse to surgery is rare.The radiographs of patients with tuberculosis take many forms36,37, and are best discussed as primary and post-primary disease.

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Primary tuberculosis Pathologically, primary tuberculosis is characterized by macrophages, other monocytes and inflammatory fluid in an area of peripheral pneumonia. Spread of the bacilli to regional nodes and throughout the body follows within 2–6 weeks. Immunological changes in the host at this stage lead to the ability to kill the organism and healing by fibrosis, with or without subsequent calcification. Repeated episodes of arrest and progression may lead to a growing nodule, a tuberculoma. Radiographically, primary tuberculosis causes a pneumonia that is homogeneous and mimics community-acquired pneumonias, such as Strep. pneumoniae (Fig. 15.11). Any lobe may be involved; size varies from subsegmental to an entire lobe. Multifocal involvement is unusual and cavitation rare, the occurrence of the latter suggesting progressive primary disease. Compared with community-acquired pneumonia, primary tuberculosis may exhibit nodal enlargement, usually ipsilateral, hilar and/or mediastinal. In fact, lymphadenopathy is the most common manifestation of primary tuberculosis in children and occurs with or without pneumonia. In the former case, the pneumonia may sometimes obscure hilar enlargement. In adults hilar or mediastinal lymphadenopathy is less common declining to about 50% of cases in the older population. Asymmetrical bilateral hilar involvement is less commonly described38. Nodal pressure and bronchial erosion may cause segmental or lobar collapse; commonly in the anterior segment of the right upper lobe and the middle lobe. Bronchial perforation may permit endobronchial spread of disease giving rise to scattered, heterogeneous opacities mimicking a bronchopneumonia. Pleural effusion as a manifestation of primary tuberculosis occurs in children, who usually have parenchymal or nodal disease, or in teenagers and young adults, when it is frequently isolated. The effusions are often large and unilateral. Residual pleural change is unusual, pleural thickening and calcification

Figure 15.11 Primary tuberculosis. A 39 year old man with cough and fever. Homogeneous lingular opacity is noted. No definite lymphadenopathy is identified but this would not necessarily be expected in an adult.

being much more commonly due to a tuberculous empyema seen with post-primary disease. Although classically a manifestation of primary disease, miliary tuberculosis is now more commonly seen as a post-primary process in older patients. Multiple small (1–2 mm) discrete nodules are scattered evenly throughout both lungs (Fig. 15.12). Other features of primary tuberculosis may or may not be present. With therapy, the nodules clear, often rather slowly over months, leaving no residual changes. Calcification within miliary nodules is rare or nonexistent. Usually the primary pneumonia resolves completely. In one-third of patients a residual well defined rounded or irregular (linear) opacity, with or without calcification remains. This is a Ghon lesion or focus. Nodal calcification may occur in the ipsilateral hilum or mediastinum and is heterogeneous and irregular. When a Ghon lesion or focus and ipsilateral lymph node calcification are seen together the combination is termed a Ranke complex. This appearance reflects prior primary tuberculosis (Fig. 15.13). (Remember that this picture is evidence of an old infection but does not imply activity of disease. For that the clinical findings must be incorporated.)

Post-primary tuberculosis This term is used to describe tuberculosis in patients who by reason of previous infection or BCG vaccination have acquired tuberculoprotein hypersensitivity. Most cases are due to reactivation of quiescent lesions, but occasionally a new infection from an exogenous source occurs. Pathologically, the ability of the host to respond immunologically results in a greater inflammatory reaction and caseous necrosis. Radiographically, in 95% of patients the initial lesions are poorly marginated, nodular and linear opacities approximately 5–10 mm in diameter, which arise in the apicoposterior segments of an upper lobe and/or the superior segment of a lower lobe (Fig. 15.14). Isolated involvement of the anterior segment of an upper lobe with few exceptions virtually excludes the diagnosis of tuberculosis, although the anterior segment may become involved from contiguous segmental disease. Changes may be unilateral or bilateral. With progression the opacities clump together and coalesce.

Figure 15.12 Miliary tuberculosis. A 26 year old man with fevers, shortness of breath. The close-up of a PA chest radiograph demonstrates multiple, discrete 1–2 mm in diameter nodular opacities.

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Figure 15.13 Primary tuberculosis—Ghon focus, Ranke complex. A 70 year old man with a prior history of tuberculosis. The close-up of the PA chest radiograph demonstrates a right mid lung calcified nodule with ipsilateral right hilar lymph node calcification. The solitary calcified nodule is termed a Ghon focus. The combination of this with ipsilateral calcified lymph nodes is termed a Ranke complex.

Cavitation is seen in the region of abnormality in 40–80% of cases. Cavities may be single or multiple, large or small. Wall thickness varies from thin to thick. Air-fluid levels are unusual but have been recorded in up to 20% of cases (Fig. 15.15). A Rasmussen aneurysm is a rare life-threatening complication of cavitary tuberculosis caused by granulomatous weakening of a pulmonary arterial wall.

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Figure 15.15 Post-primary tuberculosis. A 53 year old man presents with night sweats and fever. A close-up of a PA chest radiograph demonstrates coalescence of poorly marginated reticular and nodular opacities in the right upper lobe with an irregularly margined moderately thick-walled cavity and small air–fluid level.

Some of the opacities calcify, though this occurs less commonly than with primary tuberculosis (Fig. 15.16). Bronchiectasis and the formation of cysts and bullae may be created by the lung distortion coupled with secondary bacterial infections. Endobronchial spread can occur with or without cavitary disease and is similar to that seen with primary tuberculosis.

Healing results in scar formation. Cavities are usually obliterated but rarely a sterile cavity remains. The fibrosis produces well defined, upper lobe nodular and linear opacities, often with evidence of severe volume loss and pleural thickening.

Pleural effusion accompanying post-primary tuberculosis is more likely an empyema which may lead to pleural thickening or calcification.

Figure 15.14 Post-primary tuberculosis. A 40 year old man presents with night sweats, nonproductive cough and fever. The chest radiograph demonstrates clumped nodular opacities, particularly in the superior segment of left lower lobe, but also in the peripheral right lung, probably in the posterior segment of the right upper lobe.

Figure 15.16 Post-primary tuberculosis. A 62 year old man with a history of tuberculosis. The chest radiograph demonstrates right upper lobe well marginated and perhaps calcified nodular opacities, as well as significant volume loss in the left upper lobe with upward retraction of the left hilum and left apical pleural thickening.

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Miliary tuberculosis now occurs more commonly as a manifestation of post-primary than of primary disease and has the same radiographic appearance as described above. If the patient goes untreated the miliary nodules get bigger but rarely more than 5 mm in diameter before death occurs. A tuberculoma may occur in the setting of primary or postprimary tuberculosis and probably represents localized parenchymal disease that alternately activates and heals.These 10–15 mm in diameter nodules are commonly single but may be multiple. The margins of the nodule are usually well defined and there may be satellite lesions nearby, though this is not a specific finding. Calcification is common. Tuberculomas frequently remain stable for years, but always carry the potential risk of activation and dissemination. Chest wall involvement may be due to haematogenous seeding or direct spread from the lung and may affect soft tissue, rib, or costal cartilage. Surgery for tuberculosis is rarely performed now but patients may still be seen and exhibit the results of phrenic nerve ablation, plombage (lucite balls or oil, inserted extrapleurally), and thoracoplasty. Several studies have looked at the value of CT in diagnosing both primary and post-primary tuberculosis39. CT can identify lymphadenopathy and parenchymal lesions not appreciated on plain radiography. Over 80% of patients have lymph nodes with low attenuation centres when contrast medium is administered. Complications or spread of tuberculosis may be better revealed by CT. However, routine use of CT would probably not be cost-effective; it is recommended when normal or equivocal radiographs are seen in association with the clinical suspicion of tuberculosis, or when complications are suspected. There is no simple answer to the frequently posed question as to whether a radiographically detected tuberculous lesion is active or not. Ill-defined coalesced nodules, poorly marginated linear opacities, and especially cavitary disease in the appropriate segments are suspicious for active disease, whereas well defined opacities are not. Exceptions occur, however, and clinical findings are necessary for the diagnosis. Stability of the radiographic appearance is comforting but it should be remembered that all tuberculous lesions, even those that strongly suggest a healed lesion, even calcified, are capable of reactivation. Resolution of abnormal opacities, decrease in cavity size, and volume loss from fibrosis all suggest a satisfactory response to treatment, with a time course in the order of weeks and months rather than days. Occasionally, during the first month of treatment, opacities will extend despite appropriate therapy. Extension of opacities or incomplete resolution on treatment should also raise the question of drug-resistant tuberculosis, failure to take the medication, or an associated bronchial neoplasm. Chest radiography may be used to screen populations for pulmonary tuberculosis and to aid in the management of known cases. Nonselective radiographic screening is still employed in some countries but has been abandoned in others

because the falling prevalence of tuberculosis has resulted in low detection rates, particularly of smear-positive cases, which, from an epidemiological point of view, are the important ones to detect. Screening is still used in some selected groups such as the military, prisons and in socio-economically disadvantaged communities. Follow-up chest radiography for known cases of tuberculosis is usually sufficient after 1, 6 and 9 months, or at the end of therapy. Long-term surveillance is no longer considered necessary in straightforward cases. This regimen may be modified if complications arise, and follow-up may be extended if there is doubt about patient compliance, if risk factors are present, or if there is severe lung damage.

NONTUBERCULOUS MYCOBACTERIAL DISEASE As mentioned above, 1−3% of pulmonary mycobacterial infections are caused by agents other than M. tuberculosis: usually M. avium–intracellulare complex (MAC ) and less commonly M. kansasii. These are free-living saprophytes, and infections are not acquired from human contacts but from the environment by inhalation or ingestion. Patients are often predisposed by reason of underlying debilitating disease, immune compromise, chronic airflow obstruction, previous pulmonary tuberculosis, or silicosis and following lung transplantation. MAC, in particular, is also seen in otherwise healthy, older women. Clinically, MAC may be an indolent process with symptoms of cough, with or without sputum production. The radiological pattern of M. kansasii is generally indistinguishable from post-primary tuberculosis40,41 and changes equivalent to primary tuberculosis are rarely described. More commonly, MAC presents with a radiological pattern that does not resemble that of post-primary tuberculosis. It consists of multiple nodules, with or without small ring opacities, showing no specific lobar predilection and bronchiectasis particularly in the lingula and right middle lobe. CT has identified a similar pattern with easier detection of bronchiectasis42,43. High-resolution CT (HRCT) demonstrates small centrilobular nodules, small airway or bronchiolar ectasia and tree-in-bud opacities (Fig. 15.17). Pleural effusion is uncommon and nodal enlargement and haematogenous spread are rare except in patients with AIDS.

FUNGAL INFECTIONS Cryptococcosis (torulosis) Cryptococcosis, also known as torulosis and European blastomycosis, is caused by inhaling spores of Cryptococcus neoformans, a fungus of worldwide distribution which is found in soil and in bird droppings. Most reports of the disease are from North America. Many patients have no symptoms and the pulmonary lesions heal spontaneously but in some the disease may spread to

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Figure 15.17 Mycobacterium avium complex (MAC). An elderly woman with a long history of emphysema and chronic cough. (A) PA chest radiograph demonstrates several poorly marginated nodular opacities in the right perihilar region as well as overlying the right costophrenic angle. More coarse linear opacities emanating from the right hilum suggest the possibility of scarring or bronchiectasis. (B) Lateral radiograph demonstrates bronchiectasis in the lateral segment of the right middle lobe. (C) CT section demonstrates right middle lobe tree-in-bud opacities as well as right lower lobe mucus-filled dilated bronchi. On the lateral view a pectus excavatum is also demonstrated on lateral projection. This finding has been associated with MAC.

many organs, meningoencephalitis being the most serious consequence. Approximately half the cases of symptomatic infection are associated with immunodeficiency. The chest radiograph44,45 shows three patterns: pulmonary masses, which are usually single, but may be multiple; homogeneous segmental or lobar opacifications with or without air bronchograms, cavitation and lymphadenopathy; and diffuse nodular, occasionally military, or reticulonodular opacities. The masses usually have an ill-defined edge and may cavitate and range from approximately 5 mm to very large (Fig. 15.18). CT reveals similar findings: some ‘acinar’ nodules but no tree-in-bud abnormalities46.

Histoplasmosis Histoplasma capsulatum is a fungus found in moist soil and in bird or bat excreta in many parts of the world, but human infection is only seen with any frequency in North America, particularly in the major river valley regions of the mid and eastern USA and Canada47. Occasional epidemics of symptomatic infection (similar to the flu) are reported in areas where construction is occurring or following exposure from entering bat caves or cleaning out chicken pens; however, most cases are asymptomatic. If detected while symptomatic the chest radiograph may reveal multiple poorly-defined nodules approximately 5–10 mm in diameter (Fig. 15.19).

Figure 15.18 Cryptococcus—asymptomatic. This young man presented for routine physical examination. (A) PA chest radiograph demonstrates poorly marginated left mid lung nodular opacity. (B) Single CT section demonstrates solid left lower lobe nodule with minimal surrounding halo. Surgical resection revealed Cryptococcus infection.

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Figure 15.19 Primary histoplasmosis. A 27 year old woman with flu-like illness 2 weeks after cave exploration in Mexico. A PA chest radiograph demonstrates three or four poorly marginated nodular opacities overlying the left lower lobe. Her husband, who was suffering from similar symptoms, had identical nodules.

Less commonly a segmental or lobar pneumonia is seen. Chronic pulmonary histoplasmosis radiologically resembles post-primary tuberculosis, with upper lobe contraction, calcification and cavitation. There may be substantial adjacent pleural thickening. Hilar and mediastinal lymph nodes are frequently enlarged48. If unsuspected the disease may be diagnosed in retrospect years later by the appearance on chest radiograph of multiple calcified 3–4 mm in diameter sharplymarginated, round nodules and calcified lymph nodes in the hila and mediastinum (Fig. 15.20). Occasionally a solitary, well defined nodule may form and is then termed a histoplasmoma. When the centre of this lesion calcifies it forms a ‘target’ lesion which is very specific for this entity (Fig. 15.21). In some cases of histoplasmosis fibrosing mediastinitis may develop and can lead to constriction of mediastinal structures, including the airways, superior vena cava, pulmonary arteries and pulmonary veins. CT is helpful in demonstrating this complication.

Figure 15.20 Chronic histoplasmosis. A 55 year old man undergoing routine pre-employment physical examination. A PA chest radiograph demonstrates several well defined uniform-sized calcified nodules in both lungs with bilateral hilar and mediastinal lymph node calcification. The patient was a long-time resident of the central USA, an area endemic for histoplasmosis.

The chest radiographic manifestations are variable49. In primary coccidioidomycosis unifocal or multifocal homogeneous opacities resembling community-acquired bacterial pneumonia may be seen. Cavitation and hilar/mediastinal adenopathy may be seen with approximately 20% of these lesions (Fig. 15.22). Often the pneumonias are round and produce thin-walled cavities that can lead to a pneumothorax. Primary disease almost invariably resolves spontaneously or reveals only small residual linear or nodular scars. Chronic fibronodular cavitary disease resembling post-primary tuberculosis may also be encountered. CT demonstrates expected findings of soft tissue solitary nodule, sometimes with a low attenuation centre, cavitation, or calcification. Ground-glass halos may be seen around these nodules50. Disseminated coccidioidomycosis may cause miliary nodules.

Coccidioidomycosis Coccidioidomycosis is caused by Coccidioides immitis, a fungus which is found in soil in arid regions of the southwestern USA and northern Mexico47. Infection is acquired by inhaling dust containing the fungus. Almost half the patients develop a febrile illness; the rest are asymptomatic. The illness usually resembles a non-specific viral infection but may present with erythema nodosum, erythema multiforme and arthritis. In most instances, the disease is self-limiting, but it may progress and can even result in fatal disseminated disease, particularly in the immunocompromised patient.

Figure 15.21 Histoplasmoma. The chest radiograph obtained for left lower lobe pneumonia in a 68 year old man. The right upper lobe demonstrates central target calcification with surrounding soft tissue opacity very suggestive of histoplasmoma.

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Figure 15.22 Coccidioidomycosis. An 18 year old man with flu-like symptoms. The PA chest radiograph demonstrates homogeneous left upper lobe opacity with cavitation as well as ipsilateral hilar adenopathy.

North American blastomycosis North American blastomycosis is due to Blastomyces dermatiditis47. Pulmonary infection may be accompanied by infection of the skin, bones and genitourinary tract. Pulmonary blastomycosis is often asymptomatic.When symptoms do occur, they may be non-specific or may be those of an acute pneumonia. The chest radiograph reveals homogeneous unifocal or multifocal segmental or lobar opacification indistinguishable from acute pneumonia. Cavitation occurs in approximately 15% of cases. Sometimes, the pneumonia is spherical in shape, closely resembling bronchial carcinoma.51 Pleural thickening or pleural effusion may accompany the pneumonia in 10–15% of cases. Lymph node enlargement is infrequent. Blastomycosis may cause miliary nodules particularly in immunocompromised patients. A chronic fibrocavitary form of the disease, which resembles post-primary tuberculosis, is also seen. CT reveals pulmonary masses, consolidation, effusions and cavitation as seen on chest radiographs.

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of bronchial carcinoma. When considering this differential diagnosis, it should always be borne in mind that mycetomas may be difficult to see in portions of the lung that have been severely distorted by previous cavitary disease. On occasion, bleeding may be severe enough to warrant surgical resection of the lung containing the mycetoma, and bronchial artery embolization may sometimes be helpful in management. The radiological diagnosis depends on recognizing a mass within a cavity and formation of an air crescent (Fig. 15.23). Calcification within the mass is extremely rare and fluid levels are infrequent. The cavity wall and the adjacent pleura may thicken. A freely-moving fungus ball can be demonstrated on decubitus images (Fig. 15.24). The differential diagnosis of mycetoma includes blood clot or lung debris in a cavity, echinococcal disease and cavitary neoplasm. Allergic bronchopulmonary aspergillosis (ABPA) describes a hypersensitivity reaction which occurs in the major airways. It is associated with elevated serum IgE, positive serum precipitins and skin reactivity to aspergillus, and it is the most common cause of pulmonary eosinophilia in the UK. The radiographic appearances consist of: nonsegmental areas of opacity most common in the upper lobes, lobar collapse, branching thick tubular opacities due to bronchi distended with mucus and fungus, and occasionally pulmonary cavitation. Bronchial wall thickening with tramlines and ring formation indicates bronchiectasis. The lungs are often overinflated, while late in the disease there may be volume loss due to fibrosis. In chronic necrotizing (formerly semi-invasive) aspergillosis, local invasion of lung parenchyma takes place, usually in the upper lobes.This form is seen in debilitated patients and in patients with pre-existing lung damage or chronic lung disease. Thus there is some decrease in host response to the fungus. Radiographically heterogeneous opacities resembling tuberculosis are followed by an enlarging, thick-walled cavity which develops over a period of weeks. Adjacent pleural thickening

Aspergillus infection Aspergillus infections of the lung are usually caused by Aspergillus fumigatus and can take different forms depending on an individual’s immune response to the organism52. Aspergillus mycetomas are saprophytic growths which colonize a pre-existing cavity in the lung. There is relatively little invasion of the cavity wall or surrounding lung. Most cavities (e.g. from sarcoidosis or tuberculosis) and thus mycetomas are in the upper lobes or superior segments of the lower lobes. The great majority of aspergillomas are asymptomatic. Haemoptysis is the important complication. When it occurs, there may be difficulty in distinguishing between mycetoma formation, reactivation of tuberculosis and the development

Figure 15.23 Aspergilloma. A 30 year old man with a right upper lobe cavity of uncertain etiology. Within the cavity there is a rounded soft tissue opacity and superior air crescent indicative of mycetoma.

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Figure 15.24 Aspergilloma. A 60 year old man with chronic lung disease of indeterminate aetiology. Patient presents with mild haemoptysis. (A) Supine and (B) prone CT of the upper lobe demonstrate a fungus ball moving within the left upper lobe cavity.

and involvement of the chest wall may occur. Occasionally a mycetoma is observed. Bilateral involvement may occur and multiple nodules have been reported. Invasive aspergillosis is virtually confined to immunocompromised hosts. Radiologically, the appearances are variable, but a common pattern is of one or more rounded poorly marginated areas of homogeneous opacification with or without air bronchograms (Fig. 15.25). With time the margins may become more discreet and the lesions resemble masses. They may cavitate with the formation of an air crescent (Fig. 15.26). Wedge-shaped peripheral opacities, believed to be pulmonary infarcts may also be seen. Rarely, miliary nodules are observed.

Figure 15.25 Invasive aspergillosis. A 65 year old man with immunosuppression and neutropenia presents with fever. A PA chest radiograph demonstrates multiple bilateral poorly marginated nodular opacities with some coalescence of nodules in the right lower lobe.

Figure 15.26 Invasive aspergillosis. A 46 year old man on steroids and methotrexate for asthma. The patient developed cough and fever. (A) Initial chest radiograph demonstrates peripheral homogeneous opacities in both upper lobes and heterogeneous opacities in the left lower lobe. (B) A subsequent PA chest radiograph demonstrates cavitation within the peripheral left opacity following appropriate antifungal therapy and reconstitution of neutrophils 6 d into course.

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CT reveals findings as expected from chest radiography but is more sensitive and may be abnormal when radiography is normal. CT may reveal ground-glass haloes around the nodules, as may be seen in other diseases (Fig. 15.27). Optimized HRCT may permit more specific diagnoses of angio-invasive infection by actually demonstrating occlusion of the vessel supplying the focal pulmonary lesion53.

PROTOZOAL AND METAZOAL DISEASES Protozoal infections Pleuropulmonary amoebiasis caused by Entamoeba histolytica is usually secondary to liver involvement and develops in about one-fifth of such patients. It is characteristically a disease of young adults and shows a distinct male preference. Lung involvement usually occurs in the right lung base and consists of hemidiaphragmatic elevation, pleural effusion and/or thickening and plate-like atelectasis. With erosion of a liver abscess through the diaphragm, basal homogeneous opacification develops and frequently cavitates. Occasionally haematogenous spread gives rise to similar disease in other lung locations. Amoebiasis should always be considered in the appropriate clinical setting with isolated right basal radiological changes that abut the hemidiaphragm54.

Metazoal infestations With the exception of Armillifer armillatus, metazoal pulmonary disease is due to either roundworms or flatworms (tapeworms and flukes). Roundworms generally cause pulmonary consolidation with eosinophilia (acute eosinophilic pneumonia) and very occasionally an isolated pulmonary nodule (Dirofilaria immitis)55.The manifestations of flatworm infestations are more varied, and paragonimiasis and echinococcosis are considered here in detail. Two others, Taenia solium and Schistosoma sp.,

Figure 15.27 Invasive aspergillosis. A 30 year old man with neutropenia presents with fever. A chest radiograph demonstrated multiple lung nodules. This thin CT slice demonstrates heterogeneous and ground-glass opacity in the azygo-oesophageal lung recess as well as a lingular nodule consisting of an opaque centre and ground-glass halo very suggestive of invasive aspergillosis.

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can also cause radiological changes on the chest radiograph. T. solium gives rise to multiple calcified cysticerci in the chest wall muscles which appear as calcified oval opacities of 3–10 mm in diameter. Schistosoma infestation manifests as pulmonary consolidation with eosinophilia, pulmonary arterial hypertension with or without miliary nodulation or reticulonodular opacities, and slightly larger individual nodules.

Paragonimiasis Paragonimiasis is caused by a fluke (Paragonimus westermani) that develops from a larval form in the lung, where it lives, often for years, producing ova. Water snails and crustaceans are intermediate hosts and infestations are acquired from eating raw or incompletely cooked fresh water crabs and crayfish. The disease mainly occurs in the Far East, southeast Asia and Africa, and the usual presentation is with chronic cough and sputum production with haemoptysis. Radiological changes tend to be bilateral and affect any lobe (particularly the mid lung). Various abnormalities are observed including a mixture of consolidation, nodules and band, tubular and ring opacities56. Ring opacities range in size from 5 to 30 mm and may or may not be accompanied by adjacent consolidation. In some series about half the patients have had a pleural effusion. In the lower lobes parenchymal changes mimic bronchiectasis, and in the upper lobes, tuberculosis. CT may reveal peripheral linear opacities thought to be worm migration tracks56. The diagnosis is established by detecting ova in the sputum or by identifying anti-Paragonimus antibody in the blood.

Hydatid disease Hydatid disease (echinococcosis) is caused by a tapeworm, usually Echinococcus granulosus. Humans are accidental hosts and acquire infection by ingesting ova from fomites or contaminated water and by direct contact with dogs. Cysts develop in the lung, or less commonly in the mediastinum and rarely in the heart and pulmonary arteries. They are usually solitary but in one series approximately 10% of cases were multiple and/or bilateral57. CT series have demonstrated a higher percentage of multiple cysts. They may be ruptured (two-thirds) or unruptured (one-third) at the time of presentation. The radiological findings with unruptured pulmonary cysts are one or more homogeneous, roughly spherical or oval, sharply demarcated mass lesions. They range in size from 1 to 10 cm and occur particularly in the mid and lower lobes. The intrapulmonary masses are of soft tissue density and almost never calcify, unlike mediastinal lesions. Cysts are easily deformed and this leads to: lobulation or eccentricity of contour, where they come up against major bronchovascular structures; flattening of peripheral aspects in contact with the chest wall or mediastinum, in such a way that in the latter case a mediastinal mass is simulated; and changes in shape with breathing. Cyst rupture is usually associated with secondary infection and may occur into the airways or pleural space. Acute symptoms often develop and frequently precipitate presentation. There are three layers to the wall, two in the cyst itself (endo- and ecto-cyst) and a third derived from the surrounding lung (pericyst). If the two inner layers remain intact, airway

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communication results in a ring opacity containing a rounded, homogeneous density. The radiographic appearance resembles the air crescent of a mycetoma. Should there be disruption of the inner layers, a complex cavitary lesion results with one or more of the following radiographic features: an air–fluid level, a floating membrane (water lily sign, camalote sign), a double wall, an essentially dry cyst with crumpled membranes lying at its bottom (rising sun sign, serpent sign), a cyst with all its contents expectorated (empty cyst sign). Secondary infection of a

hydatid cyst may produce a lung abscess with or without surrounding lung opacity. CT can demonstrate a number of these characteristic features to better advantage than the chest radiograph58. High specificity of CT for the diagnosis of perforated pulmonary hydatid cyst (‘air bubble’ sign) has been reported59. Rupture into the pleural space causes an effusion or, if there is additional airway communication, a hydropneumothorax.The diagnosis may be established by serological testing, or examination of the sputum if there is rupture into airways.

PULMONARY COMPLICATIONS OF HIV INFECTION AND AIDS INFECTIONS The great majority of the pulmonary complications of HIV infection are infectious in origin. Of these, the three most important are Pneumocystis jiroveci (carinii) pneumonia, which is still a common disease leading to the diagnosis of AIDS; tuberculosis, which is extremely common in developing countries and is thus by far the most important (worldwide) pulmonary complication of HIV infection; and communityacquired pneumonias and airways disease. The prevalence of HIV-associated pulmonary infections varies greatly between different countries, so that it is difficult to identify them in order of importance; the clinical and radiographic features of each of the most common causative agents are considered below.

Pneumatoceles are seen in 10% of patients with Pneumocystis pneumonia and AIDS. They generally appear within a few days of the initial pneumonia, are thin walled, may rapidly increase or decrease in size, and over the course of 2–3 months

Pneumocystis jiroveci (formerly carinii) P. jiroveci, formerly carinii, was for a long time considered a parasite but has been shown to be a fungus. The widespread use of the abbreviation PCP to refer to pneumonia caused by this organism continues and will be used here. P. jiroveci is ubiquitous and is believed to infect the majority of humans early in life. It only manifests as pneumonia when immunosuppressive disorders, including AIDS, cause a profound depression of cellular immunity. The majority of HlV-infected patients who develop PCP present with fever, dyspnoea, non-productive cough, weakness and weight loss. Elevation of the serum lactase dehydrogenase (LDH) has been used as a sensitive but non-specific indicator of PCP and may have some prognostic value. The definitive diagnosis of PCP is made by demonstrating typical organisms in secretions obtained from the lungs or in lung tissue itself. The chest radiograph in most patients with Pneumocystis pneumonia demonstrates bilateral, diffuse, symmetrical, fine to medium reticular opacities. The same pattern confined to one or two lobes or segments of lung may be seen (Fig. 15.28). In some cases upper lobe predominance of infiltrates has simulated reactivation tuberculosis. Unusual radiographic presentations include diffuse or focal miliary nodules, homogeneous opacities, solitary or multiple well formed nodules and moderate to thick-walled cavitary nodules60. Approximately 5–10% of patients will have normal chest radiographs at presentation, perhaps even more frequently in less severe disease. Pleural fluid and lymphadenopathy are rare or do not occur unless extrapulmonary involvement has been observed, usually in patients who have received prophylactic aerosolized pentamidine.

Figure 15.28 Pneumocystis jiroveci pneumonia (PCP). (A) PA chest radiograph demonstrates the typical bilateral distribution of fine to medium reticular opacities. (B) A close-up of the right upper lobe of the same patient reveals the nature of this typical pattern which occasionally is confined to one lobe.

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gradually resolve61. In some cases they persist as chronic, thinwalled, air-filled cavities (Fig. 15.29). Spontaneous pneumothorax, has been observed in approximately 5% of patients with PCP (Fig. 15.30). Management is notoriously difficult, because bronchopleural fistulas are common.

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Significant radiographic improvement is usually seen within 10 d of beginning treatment.The radiographic appearance may get worse during the first 3 d of therapy, especially with intravenous trimethoprim–sulphamethoxazole, possibly related to overhydration pulmonary oedema and possibly to an inflammatory reaction to dead and dying parasites (Fig. 15.31). Eventually, in most patients, the pneumonia resolves completely and the chest radiograph becomes normal, though in some, pulmonary fibrosis develops. The value of CT in PCP diagnosis is questionable given the cost of imaging but it has been used to differentiate between pneumonias and to exclude the diagnosis62. CT demonstrates unilateral or bilateral ground-glass or homogeneous opacities in geographical distribution. The possibility of recurrence of PCP due to immune reconstitution following retroviral therapy has been reported63.

Mycobacterium tuberculosis In the USA tuberculosis has occurred in approximately 4% of all patients with AIDS, but in sub-Saharan Africa, where millions of people are co-infected with HIV and tubercle bacilli,

Figure 15.29 Pneumocystis jiroveci pneumonia (PCP). (A) A close-up of the right upper lobe demonstrates medium reticular opacities. (B) This close-up of the right upper lobe was obtained 3 weeks after (A). The lung disease has resolved but a thin-walled pneumatocele 30 mm in diameter is now demonstrated (arrows).

Figure 15.30 Pneumocystis jiroveci pneumonia (PCP). An AP chest radiograph demonstrates a large right tension pneumothorax. Severe underlying bilateral pneumocystis pneumonia was diagnosed. What probably represents a large left upper lobe pneumatocele is also noted.

Figure 15.31 Pneumocystis jiroveci pneumonia (PCP). (A) AP chest radiograph demonstrates a mild, diffuse reticular pattern typical of P. jiroveci infection. (B) On the fourth day of trimethoprim– sulphamethoxazole therapy the chest radiograph demonstrates a worse, coarse, bilateral reticular pattern. Following diuretic therapy the radiographic appearance quickly returned to baseline.

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tuberculosis has become the most common and most important manifestation of AIDS. Worldwide, tuberculosis is the most common cause of death among AIDS patients. Clinical features depend on the stage of HIV-induced immunosuppression at the time that tuberculosis is encountered. Tuberculosis may be indistinguishable from ‘ordinary’ disease in patients whose HIV infection is at an early stage and whose cellular immunity is better preserved. Cutaneous reactivity to tuberculin is present, the chest radiograph is typical, and extrapulmonary disease occurs with the same frequency (15–20%) as it does in patients not infected with HIV. However, when tuberculosis develops in the late stages of HIV disease, patients often have a negative tuberculin skin test reaction; more than half will have extrapulmonary (especially lymph node) involvement; and the chest radiographs are usually atypical. The diagnosis of tuberculosis rests on isolation and identification of M. tuberculosis. Antituberculous chemotherapy is usually started with three or four drugs, including isoniazid, rifampicin and pyrazinamide, with ethambutol and or other drugs added when there is a possibility of drug resistance. Longer courses of treatment than usual have been recommended. In patients with early HIV disease and limited immunosuppression the chest radiograph is similar to that seen in the general population. Homogeneous segmental or lobar opacification mimicking Strep. pneumoniae is observed with or without ipsilateral hilar and/or mediastinal adenopathy. Alternatively the post-primary type of disease with upper lobe clumped nodular or coalesced coarse reticulonodular opacities with or without cavitation may be noted. However, with advanced HIV-induced immunosuppression, diffuse bilateral coarse reticulonodular opacities are typically demonstrated. The pattern is commonly distinctive enough to suggest that an infection other than Pneumocystis pneumonia is present. Hilar and/or mediastinal adenopathy is well documented, as is a mid or lower lobe predominance of lesions (Fig. 15.32). Cavitation is not expected in this setting64. A high prevalence of pleural effusion was observed in some HIV-infected patients with tuberculosis, but this has not been universally observed.With effective antituberculosis therapy, the majority of patients will demonstrate both clinical and radiographic improvement within 1–2 weeks. In comparison, if the radiographic appearances deteriorate, a second disease process or possibly infection with a drug-resistant strain of M. tuberculosis warrants consideration65. The use of highly active antiretroviral therapy (HAART) may lead to increasing mediastinal adenopathy and worsening or new lung opacities due to a systemic inflammatory response resulting from immune reconstitution66.

Mycobacterium avium complex Mycobacterium avium complex (MAC), a ubiquitous microorganism that is found in house dust, soil and water, may cause complications for patients with end-stage HIV infection but has decreased in incidence as antiretroviral regimens have been administered. The role of MAC in causing pulmonary abnormalities should be taken seriously since disseminated MAC infection decreases life expectancy. There are no distinctive chest radiographic abnormalities in patients with MAC infection and AIDS;67 moreover, other

Figure 15.32 Tuberculosis. A PA chest radiograph demonstrates a diffuse, bilateral coarse nodular pattern associated with right hilar adenopathy. This combination of findings should suggest the presence of fungal or mycobacterial disease.

associated opportunistic diseases are common. Among patients with MAC, diffuse bilateral opacities, focal consolidation, pleural fluid, adenopathy and normal radiographs have been reported. Cavitation is rare. Considerable overlap has been found in the CT findings of nontuberculous mycobacterial infection and tuberculosis. Both demonstrate centrilobular nodules, some ground-glass attenuation and lymphadenopathy68.

Other nontuberculous mycobacteria Virtually all nontuberculous mycobacterial disease in AIDS patients is caused by MAC, but M. kansasii, M. gordonae, M. fortuitum and M. chelonei have also been implicated. The radiographic features of these agents in AIDS patients are variable and include diffuse infiltrates, focal infiltrates, cavitation, heterogeneous and homogeneous opacities predominantly in the upper lobes, lymphadenopathy and pleural effusions69,70.

Pyogenic organisms Community-acquired pneumonias, especially Strep. pneumoniae and Haemophilus influenzae, are common in HIV-infected patients. Patients with HIV infection also develop pneumonias related to their cell-mediated immune deficiencies from organisms such as Nocardia asteroides, Salmonella sp. and Legionella sp. Infections with Staph. aureus, Moraxella, Branhamella catarrhalis, Rhodococcus equi and M. pneumoniae are also reported. The clinical presentation of HIV-related Strep. pneumoniae or H. influenzae pneumonia is indistinguishable from that seen in the normal host, and is characterized by the sudden onset of high fever and a productive cough71. The radiographic features of pyogenic bacterial pneumonia in patients with AIDS are similar to those seen in non-immunosuppressed individuals. Chest radiographs demonstrate focal or multiple areas of lobar homogeneous opacification72 and, occasionally, pleural effusion (Fig. 15.33). Bronchitis and bron-

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empyema are also seen. This aetiology should be considered when cavitary pneumonias are observed in HIV patients with low CD4 lymphocyte counts. CT reveals mediastinal lymph node enlargement simulating lymphoma74.

Cytomegalovirus

Figure 15.33 Streptococcal pneumoniae pneumonia. An AP radiograph demonstrates homogeneous opacification of the right lower lobe. This pattern of pyogenic bacterial pneumonia in AIDS patients is no different from that seen in nonimmunosuppressed individuals.

chiectasis may develop acutely or may be a sequel of recurrent pyogenic pneumonias in patients with AIDS. The abnormalities on plain radiographs include peribronchial thickening and ‘tram tracking’. On CT, dilated bronchi and peribronchial thickening with or without mucous plugs are observed73. Airways disease may also result from other infectious or noninfectious aetiologies including lymphocytic interstitial pneumonia (LIP), PCP and tuberculosis. Pulmonary nocardiosis presents with cavitation, abscesses, mixed heterogeneous and homogeneous patterns and pleural fluid. Rhodococcus equi may cause necrotizing pneumonia. Patients present with chest pain, fever, productive cough and haemoptysis. Chest radiographs demonstrate homogeneous opacity frequently with cavitation (Fig. 15.34). Pleural effusions and

Cytomegalovirus pneumonia is well documented in immunocompromised patients, especially after bone marrow, kidney, lung, or heart transplantation. However, its role in respect to pneumonia in patients with AIDS is problematical due to superimposed infections and difficulty in establishing the diagnosis. Cytomegalovirus can be isolated from respiratory secretions or lung tissue in one-quarter to one-third of patients with AIDS-related lung diseases, especially PCP. In this setting it is impossible to identify what contribution, if any, the virus is making to the clinical and radiographic features of the patient’s pulmonary disorder. The principal chest radiographic abnormality of suspected cytomegalovirus pneumonia in patients with AIDS is a bilateral fine reticular pattern, similar to that seen with PCP. An analysis of 21 patients with AIDS and cytopathological evidence of cytomegalovirus infection revealed chest CT abnormalities, including ground-glass opacities and dense consolidation, bronchial wall thickening, heterogeneous densities and discrete nodules75.

Cryptococcus neoformans The usual disease caused by Cryptococcus neoformans in patients with HIV infection is meningitis, but about one-third of these patients have simultaneous pulmonary involvement and present with respiratory symptoms. Patients with cryptococcal pneumonia typically present with weight loss, fever, productive cough and breathlessness. The definitive diagnosis is usually made by cytology and culture of induced sputum or broncho-alveolar lavage fluid. When cryptococcal lung disease is found, the patient should be evaluated for meningeal involvement. The most common chest radiographic manifestation is diffuse reticular opacification. However involvement may be limited to one lung or lobe and focal homogeneous opacity, pleural effusion, hilar adenopathy, and cavitation have all been described (Fig. 15.35). CT may provide additional information76.

Histoplasma capsulatum

Figure 15.34 Rhodococcus equi. A 22 year old man with fever and cough. A PA chest radiograph demonstrates a thick-walled cavity adjacent to heterogeneous opacities in the right upper lobe. Necrotizing pneumonias are typical with this organism.

Cases of AIDS-related progressive disseminated histoplasmosis have been recognized in endemic regions of the USA. The same phenomenon may occur in endemic areas of Central and South America and elsewhere. Progressive systemic disease produces prominent weight loss and prolonged fever. Cough and dyspnoea are common in patients with chest radiographic abnormalities.The diagnosis is usually made by the biopsy and culture of bone marrow or blood. The radiographic features of histoplasmosis in patients with AIDS include normal chest radiographs in 50% of AIDS patients with extrapulmonary histoplasmosis, nodular or linear opacities in 50%, nearly 20% with pleural effusions, and approximately 10% with lymphadenopathy77 (Fig. 15.36).The lung abnormalities may be coarse and nodular, thus distinguishable from the

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Figure 15.35 Cryptococcus. An AP chest radiograph demonstrates a fine reticular pattern, right paratracheal and hilar adenopathy, and left pleural fluid. Although the pattern may simulate that seen with PCP, the presence of adenopathy and pleural fluid should direct attention towards another diagnosis.

fine reticular pattern seen with PCP. The presence of lymphadenopathy would also distinguish histoplasmosis from PCP.

Figure 15.37 Coccidioidomycosis. A close-up of a PA chest radiograph demonstrates coarse reticulonodular opacities typical of disseminated fungal or mycobacterial disease in AIDS patients. The possibility of left hilar adenopathy is raised.

Coccidioides immitis

Aspergillosis

Coccidioidomycosis, in AIDS patients may be seen in the endemic areas of the southwestern USA. Fever, weight loss, cough and fatigue are usually present in patients with AIDS-related disseminated coccidioidomycosis. Spherules can usually be identified in sputum and fungal cultures from broncho-alveolar lavage, or transbronchial biopsy are likely to be positive. Diffuse, medium to coarse nodular opacities similar to those seen with histoplasmosis and with disseminated tuberculosis were seen in 55% of patients; 36% had focal abnormalities, including single or multiple nodules, cavities and hilar and mediastinal adenopathy78 (Fig. 15.37).

Despite its importance as a complication of other immunosuppressive disorders, especially leukaemia and organ transplantation, aspergillosis is relatively infrequent in patients with HIV-induced immune deficiency. Two types of HIV-associated aspergillosis have been observed: invasive pulmonary aspergillosis, which is characterized by prolonged cough and fever; and obstructing bronchial aspergillosis, which is characterized by breathlessness, cough and chest pain. The radiographic features of aspergillosis in patients with AIDS include focal and occasionally persistent homogeneous opacities. These may remain stable for several months but are indicative of invasive aspergillosis. Approximately one-third of patients demonstrate cavitation, chiefly in upper lobe homogeneous opacities. Disseminated heterogeneous and homogeneous patterns are observed with widespread disease. CT may reveal nodules with surrounding ground-glass halos, or airway disease manifest by centrilobular nodules and peribronchial opacities79.

Protozoal diseases Toxoplasma gondii

Figure 15.36 Histoplasmosis. A PA chest radiograph demonstrates the typical findings of histoplasmosis in AIDS patients. A pattern composed of small nodules 2–4 mm in diameter is seen in both lungs.

Judging from serological studies, Toxoplasma gondii is a prevalent infection (40–60%) in the general population. Reactivation of central nervous system (CNS) toxoplasmosis is a common cause of seizures, focal neurological deficits and/or encephalopathy in patients with AIDS. In view of the frequency of CNS toxoplasmosis, pulmonary involvement is surprisingly unusual, though it may occur and progress to respiratory failure. Chest radiographs in the few reported patients demonstrate bilateral lower lobe homogeneous opacities, a solitary nodule and bilateral diffuse heterogeneous opacities. In our series, bilateral coarse nodular opacities were the most common

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Kaposi’s sarcoma

Kerley B lines are occasionally present. The lung abnormalities tend to coalesce together unlike the nodules seen with lymphoma82. Unilateral or bilateral pleural fluid is reported in 33–50% of patients and lymphadenopathy has been observed in 10–30% (Fig. 15.39). Rapid progression from a poorlydefined nodular pattern to one of airspace consolidation has usually been seen in patients with haemoptysis, and probably represents haemorrhage into the lung (Fig. 15.40). Unusual radiographic features of KS include pericardial fluid accumulation due to pericardial KS and the plain chest

At the beginning of the AIDS epidemic, Kaposi’s sarcoma (KS) was the indicator disease in 20–25% of all cases but its incidence has fallen considerably81. KS is caused by the human herpes virus 8 (HHV8). Most patients with KS present with one or more typical violaceous plaques on their skin or mucous membranes. Primary involvement of visceral organs may also occur, particularly in the gastrointestinal tract; other sites include lymph nodes, liver, spleen, heart and pericardium. Primary pulmonary KS is unusual. Most cases of pulmonary KS occur in the presence of obvious disease in the skin or elsewhere. The manifestations of pulmonary KS are fever, cough and breathlessness, and thus are indistinguishable from those of many pneumonias. Haemoptysis and upper airway obstruction rarely occur. Dyspnoea from effusions may require treatment. Compared with the non-specific radiographic abnormalities observed with the opportunistic pulmonary infections discussed above, the findings of KS are more specific and the diagnosis may sometimes be suggested on the basis of the chest radiograph and CT abnormalities.The usual pattern is a poorly defined peribronchovascular nodular opacity which typically measures 10–20 mm in diameter. Although solitary nodular KS may occur, bilateral multiple lesions are typically present. Coarse linear opacities are also commonly scattered throughout the lungs, particularly in the perihilar and lower lungs and

Figure 15.39 Kaposi’s sarcoma. A PA chest radiograph demonstrates coarse linear opacities in the perihilar regions. Some nodular opacities are noted in the right upper lobe. Left pleural fluid is present. This constellation of findings is highly suggestive of Kaposi’s sarcoma.

Figure 15.38 Toxoplasmosis. A close-up of a portable AP chest radiograph demonstrates a coarse nodular pattern which was present in the perihilar and lower lobe regions of the lung.

Figure 15.40 Kaposi’s sarcoma. Fairly large, coarse nodules are noted in the right upper lobe and left lung. An area of homogeneous opacification in the right middle lobe appeared at the same time as this patient developed haemoptysis. This radiographic abnormality probably represents haemorrhage in the lung.

pattern; lymphadenopathy was not observed and pleural effusion was uncommon80 (Fig. 15.38).

MALIGNANCIES Some malignancies have close association with infectious agents, and as they may mimic infection they are included here.

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diffuse parenchymal opacities, pleural fluid and rapidlygrowing well defined parenchymal nodules (Fig. 15.41). These nodules range in size from 10 to 60 mm, may be solitary or multiple and only rarely cavitate. CT may reveal similar findings and would be expected to be more sensitive than chest radiography.

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Figure 15.41 Non-Hodgkin’s lymphoma. (A) A close-up of a PA chest radiograph demonstrates a fairly well defined nodule, 15 mm in diameter, in the left upper lobe. (B) A close-up of the chest radiograph obtained 10 d later demonstrates considerable enlargement of the nodule which, on open lung biopsy, was shown to represent non-Hodgkin’s lymphoma.

radiographic demonstration of a large intratracheal Kaposi’s lesion. Endobronchial lesions may cause complete occlusion of airways. Occasionally septic emboli in intravenous drug abusers with AIDS may simulate KS. In this situation cavitation would be expected, whereas cavitation in KS is rare or not observed.

Non-Hodgkin’s lymphoma Although intrathoracic involvement by non-Hodgkin’s lymphoma in patients with AIDS is not common, when lesions occur they include: hilar and/or mediastinal adenopathy,

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77. Conces D J Jr, Stockberger S M, Tarver R D et al 1993 Disseminated histoplasmosis in AIDS: Findings on chest radiographs. Am J Roentgenol 160: 15–19 78. Fish D, Ampel N, Galgiani J et al 1990 Coccidioidomycosis during human immunodeficiency virus infection: a review of 77 patients. Medicine 69: 384–391 79. Pompili G G, Alineri S, Arbori G et al 1998 Invasive aspergillosis in AIDS: findings with high-resolution computerized tomography. Radiol Medica 96: 325–330

80. Goodman P C, Schnapp L M 1992 Pulmonary toxoplasmosis in AIDS. Radiology 814: 791–793 81. Engels E A, Goedert J 2005 Human immunodeficiency virus/acquired immunodeficiency syndrome and cancer: past, present, and future. J Natl Cancer Inst 97: 407–409 82. Goodman P 1992 Kaposi’s sarcoma. J Thorac Imaging 6: 43–48

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Large Airway Disease and Chronic Airway Obstruction

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Philippe Grenier

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Tracheal disorders Bronchiectasis Broncholithiasis Emphysema Chronic bronchitis Asthma Obliterative (constrictive) bronchiolitis

This chapter reviews lesions involving the trachea and proximal bronchi, describes the radiological signs of bronchiectasis, and discusses the role of imaging in obstructive lung disease, a group of diffuse lung diseases associated with chronic airflow obstruction that includes chronic obstructive pulmonary disease (COPD), asthma and obliterative bronchiolitis. In obstructive lung disease, decreased expiratory flow may be related to loss of lung recoil or small airway obstruction or a combination of both. The pathological lesion that best correlates with loss of recoil is emphysema. The process that causes the small airway obstruction is inflammatory in nature and is characterized by thickening of all the layers of the bronchiolar walls, as well as an accumulation of mucus in the airway lumen (COPD and asthma) and/or an irreversible fibrosis (obliterative bronchiolitis).

TRACHEAL DISORDERS1–4 The trachea may be affected by a variety of extrinsic or intrinsic processes. Extrinsic processes, particularly masses, displace and distort the trachea, while intrinsic ones cause narrowing, widening, or a mass effect.Tracheal narrowing may affect a short or a long segment, and may extend to the mainstem bronchi. Tracheal disease initially missed on the chest radiograph is usually evident on careful evaluation of the frontal and lateral radiograph5. Computed tomography (CT) allows precise delineation of the intratracheal and extratracheal extent of the abnormality. Multidetector CT (MDCT), by combining helical volumetric CT acquisition and thin collimation during a single breath-

hold, provides an accurate assessment of the proximal airways, allowing multiplanar reformations and three-dimensional (3D) rendering of very high quality. Complementary CT acquisition at suspended or continuous expiration allows tracheal collapsibility to be assessed.

Post-traumatic strictures Strictures of the trachea are usually secondary to damage from a cuffed endotracheal or tracheostomy tube, or to external neck trauma.The lesions consist of granulation tissue followed by the development of dense mucosal and submucosal fibrosis associated with distortion of cartilage plates. The two principal sites of stenosis following intubation or the insertion of a tracheostomy tube are at the stoma or at the level of the endotracheal or tracheostomy tube balloon. On radiographs, the stenosis may be seen as a focus of circumferential or eccentric narrowing associated with a segment of increased soft tissue. The size of narrowing is usually clearly seen on CT.The narrowing is often concentric. Postintubation stenosis extends for several centimetres and typically involves the trachea above the level of the thoracic inlet. Post-tracheostomy stenosis typically begins 1–1.5 cm distal of the inferior margin of the tracheostomy stoma and involves 1.5–2.5 cm of tracheal wall. Multiplanar reformations are particularly helpful in defining accurately the site, length and degree of the stenosis. In selected cases, the degree of stenosis may also be defined by use of virtual bronchoscopy.

Infectious tracheobronchitis A number of infections, both acute and chronic, may affect the trachea and proximal bronchi, resulting in both focal and diffuse airway disease. Subsequent fibrosis may result in localized airway narrowing. The most common causes of infectious tracheobronchitis are bacterial tracheitis in immunocompromised patients, tuberculosis, rhinoscleroma (Klebsiella rhinoscleromatis) and necrotizing invasive aspergillosis. On CT, the extent of irregular and circumferential tracheobronchial narrowing is clearly demonstrated, and in some patients an accompanying mediastinitis (opacification of the mediastinal fat) is evident.

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In active disease, the narrowed trachea and frequently one or other main bronchus have an irregularly thickened wall. In the fibrotic or healed phase, the trachea is narrowed but has a smooth wall of normal thickness.

Primary malignant neoplasms These are uncommon, accounting for less than 1% of all thoracic malignancies. The vast majority are squamous cell carcinoma and adenoid cystic carcinoma. Other neoplasms, such as mucoepidermoid carcinoma, carcinoid tumour, lymphoma, plasmacytoma and adenocarcinoma are rare. On CT, they appear as a soft tissue mass, most often in the posterior and lateral wall (Fig. 16.1A). Often sessile and eccentric, resulting in asymmetrical luminal narrowing, rarely they may appear circumferential. They can be polypoid and are mostly intraluminal with mediastinal extension in 30–40%. The surface of the tumour is often irregular in squamous cell carcinoma, whereas it is smooth in adenoid cystic carcinoma. Multiplanar reformation and volumetric rendering images are recommended for a precise pre-therapeutic assessment of tumour extent (Fig. 16.1B). The tumours are best treated surgically, especially with primary resection and re-anastomosis followed by radiation.

Secondary malignant neoplasms The large airways may be involved secondarily by malignant neoplasms as a result of either haematogeneous metastasis or direct invasion from the oesophagus, thyroid, mediastinum, or lung. Neoplasms that have a propensity to metastasize to the trachea and major bronchi include renal cell carcinoma and melanoma. On CT the abnormalities are usually focal and include intraluminal soft tissue nodules and wall thickening.

Benign neoplasms The most common benign neoplasms are hamartoma, leiomyoma, neurogenic tumour and lipoma. They are usually well demarcated, round and less than 2 cm in diameter. The radiological appearance typically consists of a smoothly marginated intraluminal polyp. Hamartomas and lipomas may demonstrate fat attenuation on CT. Tracheobronchial papillomatosis is a particular entity caused by human papillomavirus infection usually acquired at birth from an infected mother. The larynx is affected most commonly; extension into the trachea and proximal bronchi occurs occasionally. Exceptionally the infection spreads into the lung parenchyma. The typical radiological findings consist of multiple small nodules projecting into the airway lumen or diffuse nodular thickening of the airway wall. Although benign, papilloma may undergo transformation to squamous cell carcinoma.

Wegener’s granulomatosis Involvement of the large airways is a common manifestation of Wegener’s granulomatosis. Inflammatory lesions may be present with or without subglottic or bronchial stenosis, ulcerations and pseudotumours. Radiological manifestations include thickening of the subglottic region and proximal trachea with a smooth symmetrical or asymmetrical narrowing over a vari-

Figure 16.1 Adenoid cystic carcinoma of the trachea. (A) Axial CT at the level of the supra-aortic part of the mediastinum. Irregular stenosis of the tracheal lumen due to a soft tissue mass developing from the posterior and left lateral wall of the trachea. (B) 3D external volume rendering of the airways in a coronal view. The level of the tracheal lumen involvement (arrow) is accurately assessed with respect to the larynx and carina. The length and the degree of the stenosis are also clearly seen.

able length. Stenosis may also be seen on any main lobar or segmental bronchus. Nodular or polypoid lesions may also be seen on the inner contour of the airway lumen.

Relapsing polychondritis This is a rare systemic disease of autoimmune pathogenesis that affects cartilage at various sites, including the ears, nose, joints and tracheobronchial tree. Histologically, the acute inflammatory infiltrate present in the cartilage and perichondrial tissue induces progressive dissolution and fragmentation of the cartilage followed by fibrosis. Symmetrical subglottic stenosis is the most frequent manifestation in the chest (Fig. 16.2A). As the disease progresses, the distal trachea and bronchi may be involved. CT shows smooth thickening of the airway wall associated with more or less diffuse narrowing (Fig. 16.2B). In the early stage, the posterior wall of the trachea is spared

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Figure 16.2 Relapsing polychondritis. (A) PA chest radiograph targeted on the upper and mid parts of the mediastinum. The upper part of the tracheal lumen is narrowed (black arrows). The right paratracheal band is abnormally thickened (white arrows). (B) Axial CT at the level of the aortic arch showing abnormal thickening of the anterior and lateral walls of the trachea associated with calcium deposits (arrow). The posterior membranous wall of the trachea is unaffected.

but in advanced disease circumferential wall thickening occurs. The trachea may become flaccid with considerable collapse at expiration. Gross destruction of the cartilaginous rings with fibrosis may cause stenosis.

Amyloidosis Deposition of amyloid in the trachea and bronchi may be seen in association with systemic amyloidosis or as an isolated manifestation. As a result, the amyloid forms either multifocal or diffuse submucosal plaques or masses.The overlying mucosa is usually intact. Dystrophic calcification or ossification is frequently present. CT shows focal or, more commonly, diffuse thickening of the airway wall and narrowing of the lumen. Calcification may be seen. Narrowing of the proximal bronchi can lead to distal atelectasis, bronchiectasis, or obstructive pneumonia.

Tracheobronchopathia osteochondroplastica This rare disorder is characterized by the presence of multiple cartilaginous nodules and bony submucosal nodules on the inner surface of the trachea and proximal airways. Men are more frequently affected than women and most patients are older than 50. Histologically, the nodules contain heterotopic bone, cartilage and calcified acellular protein matrix. The overlying bronchial mucosa is normal and because it contains no cartilage, the posterior wall of the trachea is spared. The chest radiograph may be normal or may demonstrate lobar collapse or infective consolidation. If the tracheal air column is clearly seen, multiple sessile nodules that project into the tracheal lumen extending over a long segment of the trachea can be appreciated. On CT tracheal cartilage rings are thickened and shows irregular calcifications. The

nodules may protrude from the anterior and lateral walls into the lumen; they usually show foci of calcification.

Sabre-sheath trachea6 Characterized by a diffuse narrowing involving the intrathoracic trachea, this entity is almost always associated with COPD.The pathogenesis of the lesion is obscure, but probably it is an acquired deformity related to the abnormal pattern and magnitude of intrathoracic pressure changes in COPD. On radiographs and CT, the condition is easily recognized by noting that the internal side-to-side diameter of the trachea is halved or less than the corresponding sagittal diameter (Fig. 16.3A). On the postero-anterior (PA) radiograph and CT multiplanar reformations (Fig. 16.3B), the narrowing usually affects the whole intrathoracic trachea, with an abrupt return to normal calibre at the thoracic inlet. The trachea usually shows a smooth inner margin but occasionally has a nodular contour. Calcification of the tracheal cartilage rings is frequently evident.

Tracheobronchomegaly (Mounier–Kuhn disease) Tracheobronchomegaly refers to patients who have marked dilatation of the trachea and mainstem bronchi. It is often associated with tracheal diverticulosis, recurrent lower respiratory tract infection and bronchiectasis. Atrophy affects the elastic and muscular elements of both the cartilaginous and membranous parts of the trachea. The diagnosis is based on radiological findings. The immediately subglottic trachea has a normal diameter, but it expands as it passes to the carina and this dilatation often continues into the major bronchi. Atrophic mucosa prolapses between cartilage rings and gives the trachea a characteristically corrugated outline on a plain

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Figure 16.3 Sabre-sheath trachea in a patient with chronic obstructive pulmonary disease. (A) Axial CT at the level of the upper lobes shows a significant reduction of the coronal diameter of the trachea. Bilateral centrilobular and paraseptal emphysematous areas are also present in the upper lobes. (B) Coronal oblique reformation along the long axis of the trachea. Reduction of the coronal diameter of the tracheal lumen (arrows). The upper part of the trachea above the thoracic inlet has a normal appearance.

radiograph. Corrugations may become exaggerated to form sacculations or diverticula. On CT a tracheal diameter of greater than 3 cm (measured 2 cm above the aortic arch) and diameters of 2.4 and 2.3 cm for the right and left bronchi, respectively, are diagnostic criteria (Fig. 16.4A). Additional findings include tracheal scalloping (Fig. 16.4B) and diverticula (especially along the posterior membranous tracheal wall).

Tracheobronchomalacia6 This abnormality results from weakened tracheal cartilage rings and is seen in association with a number of disorders, including tracheobronchomegaly, COPD, diffuse tracheal inflammation such as relapsing polychondritis, as well as following trauma. On radiographs, an almost 300% reduction in the sagittal diameter at expiration is an excellent

Figure 16.4 Tracheobronchomegaly in a patient with bilateral bronchiectasis and recurrent pulmonary infections. (A) Axial CT at the level of the upper part of the chest shows the dilated irregular lumen of the trachea. There is bilateral cylindrical and varicose bronchiectasis in the upper lobes. (B) 3D external volume rendering of the airways showing irregular dilatation of both trachea and main bronchi. Dilatation is also present in the lobar bronchi. In addition, the trachea is irregular in contour with multiple corrugations. (Reprinted from “Imagerie Thoracique de l’ Adulte” 3rd. ed., 2006, Flammarion, with permission).

diagnostic indicator. On CT, diagnosis is based on a narrowing of the diameter of the lumen by more than 50% on expiration compared with that on inspiration. The increase in compliance is due to the loss of integrity of the wall’s structural components and is particularly associated with damaged or destroyed cartilage. The coronal diameter of the trachea becomes significantly larger than the sagittal one, producing a lunate configuration. The flaccidity of the trachea or bronchi is usually most apparent during coughing or forced expiration. In patients with COPD with high downstream resistance particularly high dynamic pressure gradients can be generated across the tracheal wall, and it is likely that calibre changes of more than 50% can occur at expiration with normal tracheal compliance. As a result only a decrease in the cross-sectional area of the tracheal

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lumen of greater than 70% at expiration indicates tracheomalacia. Dynamic expiratory MDCT may offer a feasible alternative to bronchoscopy in patients with suspected tracheobronchomalacia7. Dynamic expiratory CT may show collapse of the more than 75% of the airway lumen; indeed, complete collapse may be seen (Fig. 16.5). Involvement of the central tracheobronchial tree may be diffuse or focal. The reduction of the airway may have an oval or crescentic shape.The crescentic form is due to the bowing of posterior membranous trachea.

Tracheobronchial fistula and dehiscence8 MDCT with thin collimation is the most accurate technique to identify peripheral bronchopleural fistulas, which are most commonly caused by necrotizing pneumonia or secondary to traumatic lesions. Nodobronchial and nodobronchoesophageal fistulas, which are most commonly caused by Mycobacterium tuberculosis infection, are characterized by the presence of gas in cavitated hila or mediastinal lymphadenopathy adjacent to the airways. Tracheal diverticula and tracheobronchoesophageal fistulas may also be diagnosed, even in adults. Malignant neoplasia, particularly oesophageal, are the most common cause of tracheo-oesophageal fistulas in adults. Occasionally congenital fistulas first manifest in adults. Infection and trauma are the most frequent nonmalignant causes. MDCT has a high degree of sensitivity and specificity for depicting bronchial dehiscence occurring after lung transplantation. Bronchial dehiscence is seen as a bronchial wall defect associated with extraluminal air collections.

BRONCHIECTASIS1,3,4 Bronchiectasis is a chronic condition characterized by local, irreversible dilatation of bronchi, usually associated with inflammation. In spite of its decreased prevalence in developed countries, bronchiectasis remains an important cause of haemoptysis and chronic sputum production. Although the causes of bronchiectasis are numerous, there are three mechanisms by which the dilatation can develop: bronchial obstruction, bronchial wall

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damage, and parenchymal fibrosis (Table 16.1). In the first two mechanisms, the common factor is the combination of mucus plugging and bacterial colonization. Cytokines and enzymes released by inflammatory cells plus toxins from the bacteria result in a vicious cycle of increasing airway wall damage, mucous retention and bacterial proliferation. In parenchymal fibrosis, the dilatation of bronchi is caused by maturation and retraction of fibrous tissue located in the parenchyma adjacent to an airway (traction bronchiectasis). Pathologically, bronchiectasis has been classified into three subtypes, reflecting increasing severity of disease: cylindrical, characterized by relatively uniform airway dilatation; varicose, characterized by nonuniform and somewhat serpiginous dilatation; and cystic. As the extent and degree of airway dilatation increase, the lung parenchyma distal to the affected airway shows increasing collapse from fibrosis.

Radiographic findings Chest radiography reveals abnormalities in the majority of cases (Figs 16.6 and 16.7). Thickened bronchial walls are visible either as single thin lines or as parallel line opacities (tramlines). When seen end-on, bronchiectatic airways appear as poorly defined ring or curvilinear opacities (Fig. 16.6B). Dilated bronchi filled with mucous or pus result in tubular or ovoid opacities of variable size. Cystic bronchiectasis manifests as multiple thin-walled ring shadows often containing air–fluid levels (Fig. 16.7). Pulmonary vessels may appear increased in size and may be indistinct because of adjacent peribronchial inflammation fibrosis. In generalized bronchiectasis, such as that associated with cystic fibrosis, overinflation is often present (Fig. 16.7). Localized forms Table 16.1

MECHANISMS AND CAUSES OF BRONCHIECTASIS

• Bronchial obstruction Carcinoma Fibrous stricture (e.g. tuberculosis) Broncholithiasis Extensive compression (lymphadenopathy, neoplasm) • Parenchymal fibrosis (traction bronchiectasis) Tuberculosis Sarcoidosis Idiopathic pulmonary fibrosis • Bronchial wall injury Cystic fibrosis Childhood viral and bacterial infection Immunodeficiency disorders Dyskinetic cilia syndrome Allergic bronchopulmonary aspergillosis Lung and bone marrow transplantation Panbronchiolitis Systemic disorders (rheumatoid arthritis, Sjögren’s syndrome, inflammatory bowel disease, yellow nail syndrome)

Figure 16.5 Tracheobronchomalacia. Axial CT acquired during dynamic expiratory manœuvre. The collapse of the tracheal lumen is almost complete. The tracheal lumen is crescentic in shape because of the bowing of the posterior membranous trachea.

α1-Antitrypsin syndrome Congenital Williams Campbell syndrome

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cardinal sign of bronchiectasis) (Fig. 16.8), internal bronchial diameter greater than that of the adjacent pulmonary artery (signet ring sign) (Fig. 16.9), visualization of bronchi within 1 cm of the costal pleura or abutting the mediastinal pleura, and mucus-filled dilated bronchi (see Fig. 16.4A). In varicose bronchiectasis, the bronchial lumen assumes a beaded configuration (Fig. 16.8). Cystic bronchiectasis is seen as a string of cysts caused by sectioning irregular dilated bronchi along their

Figure 16.7 Cystic fibrosis. The PA radiograph shows slight overinflation and the presence of multiple thin-walled ring shadows in the right lung and the upper part of the left lung, reflecting cystic bronchiectasis. Some ring shadows contain air–fluid levels.

Figure 16.6 Bronchiectasis and obliterative bronchiolitis. (A) PA chest radiograph shows oligaemia in the lung bases with pulmonary blood flow redistribution in the upper parts of the lungs and slight overinflation of the lungs, more marked on the right side. (B) Targeted image of the right lung base in the same patient shows tramlines and ring opacities reflecting the presence of dilated and thick-walled bronchi.

are frequently accompanied by atelectasis which may be mild and detected only because of vascular crowding, fissure displacement, or obscuration of part of the diaphragm.

Computed tomography findings The major sign of bronchiectasis on thin-collimation CT (highresolution CT [HRCT]) is dilatation of the bronchi, with or without bronchial wall thickening. Bronchial dilatation on CT is often manifested by lack of tapering of bronchial lumina (the

Figure 16.8 Allergic bronchopulmonary aspergillosis. HRCT shows cylindrical and varicose bronchiectasis in the right upper lobe and the apicoposterior segment of the left upper lobe. Small centrilobular nodules representing infectious or inflammatory bronchiolitis are seen in the anterior segment of the right upper lobe. An area of parenchymal consolidation surrounded by a halo of ground-glass opacity is present within the superior segment of the left upper lobe (arrow). (Reprinted from “Imagerie Thoracique de l’ Adulte, 3rd. ed., 2006, Flammarion, with permission).

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Figure 16.9 Cystic fibrosis. HRCT image in the upper lobes shows bilateral bronchiectasis and thickening of the bronchial walls.

lengths, or a cluster of cysts, caused by multiple dilated bronchi lying adjacent to each other (Fig. 16.10). Clusters of cysts are most frequently seen in atelectatic lobes. Air–fluid levels, caused by retained secretions, may be present in the dependent portion of the dilated bronchi. Secretion accumulation within bronchiectatic airways is generally easily recognizable as lobulated gloved finger, V- or Y-shaped densities (Figs 16.11 and 16.12). When oriented perpendicular to the data acquisition plane the filled dilated bronchi are visualized as nodular opacities and recognized by observation of the homologous pulmonary arteries, whose diameters are smaller than those of the dilated filled bronchi. CT may show a completely collapsed lobe containing bronchiectatic airways. Subtle degrees of volume loss may be seen in lobes in relatively early disease.This is most evident in the lower lobes on the basis of crowding of the mildly dilated bronchi and posterior displacement of the oblique fissure. Associated CT findings of bronchiolitis are seen in about 70% of patients with bronchiectasis. Small centrilobular nodu-

Figure 16.10 Post-infectious cystic bronchiectasis. Presence of the clusters of cysts abutting the mediastinum and located within the left lower lobe and the inferior segment of the lingula. There is volume loss of the left lower lobe.

Figure 16.11 Allergic bronchopulmonary aspergillosis. HRCT of the upper lobes. Mucoid impactions are present within segmental and subsegmental dilated bronchi in the upper lobes. Small centrilobular linear branching opacities are seen in the periphery of the right upper lobe.

lar and linear branching opacities (tree-in-bud sign) express inflammatory and infectious bronchiolitis (Fig. 16.12). Areas of decreased attenuation and vascularity, mosaic perfusion pattern and expiratory air trapping reflect the extent of obliterative bronchiolitis (Fig. 16.13). These abnormalities are very common in patients with severe bronchiectasis and can even precede the development of bronchiectasis. The obstructive defect found at pulmonary tests in patients with bronchiectasis seems not to be related to the degree of collapse of large airways on expiratory CT or the extent of mucous plugging

Figure 16.12 Bronchiectasis with mucoid impactions and infectious bronchiolitis. Oblique reformat (4-mm thick slab) of the right lung with maximum intensity projection. Presence of mucoid impactions (arrows) in the dilated bronchi located within the anterior segment of the right upper lobe. Presence of multiple small centrilobular nodular and linear branching opacities (tree-in-bud sign).

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Cystic fibrosis1,4

Figure 16.13 Bronchiectasis and obliterative bronchiolitis. HRCT performed at full expiration shows air trapping in the right middle lobe, the superior segment of the left lower lobe, and some lobules of the left upper and right lower lobes. There is a cluster of cysts (cystic bronchiectasis) in the right middle lobe.

of the airway, but the consequence of an obstructive involvement of the peripheral airways (obliterative bronchiolitis)9. The extent of small airway disease commonly evident on CT (decreased lung attenuation, expiratory air trapping) in patients with bronchiectasis has proven to be the major determinant of airflow obstruction.

Accuracy of CT HRCT has replaced bronchography in the diagnosis and assessment of the extent of bronchiectasis10. By combining helical volumetric CT acquisition and thin collimation, CT has gained greater advantages by circumventing the limitations of HRCT, particularly the risk of missing bronchiectasis strictly localized within the intervals between slices11. Currently, MDCT with thin collimation is the technique of choice for the detection and the assessment of the extent of bronchiectasis. Multiplanar reformations increase the detection rate and the reader’s confidence as to the distribution of bronchiectasis, and improves agreement between observers as to the diagnosis12. In addition, maximum intensity projections improve the detection and display of both mucoid impactions and small centrilobular and linear branching opacities (tree-in-bud sign), characteristic of infectious bronchiolitis. The reliability of CT for determining the causes of bronchiectasis is somewhat controversial. An underlying cause for bronchiectasis is found in fewer than half of patients and CT features alone do not usually allow a confident distinction between idiopathic bronchiectasis and bronchiectasis with a specific cause4. Bilateral upper lobe distribution is most common in patients with cystic fibrosis and allergic bronchopulmonary aspergillosis; unilateral upper lobe distribution is most common in patients with tuberculosis; and a lower lobe distribution is most often seen after childhood viral infections. However, CT remains of little value in diagnosing specific aetiologies of bronchiectasis.

Cystic fibrosis results from an autosomal recessive genetic defect in the structure of the cystic fibrosis transmembrane regulation protein which leads to abnormal chloride transport across epithelial membranes. Although the mechanisms by which this defect leads to lung disease are not entirely understood, an abnormally low water content of airway mucus is at least partially responsible for decreased mucus clearance, mucous plugging of airways and an increased incidence of bacterial airway infection. Bronchial wall inflammation progressing to secondary bronchiectasis is always present in patients with long-standing disease. In patients with early or mild disease, the findings on chest radiography may be subtle. Hyperinflation reflects the presence of obstruction of the small airways (see Fig. 16.7). Thickening of the wall of the upper lobar bronchi can also be seen on the lateral radiograph. In more advanced disease, the radiographs can be diagnostic, showing increased lung volume, accentuated linear opacities in the upper lung areas, resulting from bronchial wall thickening or bronchiectasis, proximal bronchiectasis and mucoid impaction. Additional findings include cystic regions of the upper lobes (see Fig. 16.7), representing cystic bronchiectasis, healed abscess, cavities, or bullae; and atelectasis, findings of pulmonary hypertension or cor pulmonale, pneumothorax or pleural effusion. The chest radiographs are sufficient for clinical management, but it is important to know that usually there is a little visible radiographic change associated with clinical exacerbation. Several studies have shown that CT can offer an alternative to routine radiographic and clinical methods for monitoring disease status and progression as well as for assessing response to treatment. These studies consistently document close correlation between HRCT findings and both clinical and pulmonary functional evaluation of these patients. On CT, peripheral and/or central bronchiectasis is present in all patients with advanced cystic fibrosis (see Fig. 16.9). All lobes are typically involved, although early in the disease abnormalities are often predominantly distributed in the upper lobes, and sometimes with a right upper lobe predominance. Bronchial wall and/or peribronchial interstitial thickening is also commonly present. It is generally more evident than bronchial dilatation in patients with early disease. Mucous plugging is present in 25–50% of patients, and may be seen in all lobes. Collapse or consolidation is visible in up to 80% of patients. Lobar volume loss is often present in patients with advanced disease. Bullae may be difficult to distinguish from cystic bronchiectasis, particularly in fibrotic upper lobes. Abscesses may be difficult to distinguish from cystic bronchiectasis, particularly as both may contain air–fluid levels. Pleural thickening, which is often apparent on chest radiographs, is demonstrated to advantage by CT. Small centrilobular nodular and branching linear opacities (tree-in-bud sign) can be an early sign of disease.They reflect the presence of mucous impactions in dilated bronchioles associated with peribronchiolar inflammation. Focal areas of decreased lung attenuation are frequently present, representing air trapping and mosaic perfusion due to obstruction of the small airways. These areas often correspond to lobules and subsegments where mucous plugging in dilated airways is present.

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At an early stage of the disease, HRCT can demonstrate airway abnormalities in patients who are asymptomatic and have normal pulmonary function and a normal chest radiograph. In patients with more advanced disease, HRCT is superior to chest radiography in detecting bronchiectasis and mucous plugging.

dilection. Despite this upper lobar shrinkage, the lung volume is frequently increased, reflecting overinflation in the lower lobes due to obstruction of the small airways and the presence of bullae in cavitation in the upper lobes.

Allergic bronchopulmonary aspergillosis1, 4

The dyskinetic cilia syndrome results from an autosomal recessive genetic abnormality and is characterized by abnormal ciliary structure and function, leading to a reduced mucociliary clearance and chronic airway infection. Bronchiectasis and sinusitis are common manifestations. About half of patients have also situs inversus. The combination of bronchiectasis, sinusitis and situs inversus is termed Kartagener’s syndrome. Men and women are equally affected, but in men the syndrome may be associated with immotile spermatozoa and infertility. Respiratory symptoms can generally be traced back to childhood. Bronchiectasis develops in childhood and adolescence and is associated with recurrent pneumonia. Both plain radiographs and CT typically show bilateral bronchiectasis with a basal (lower or middle lobe) predominance, similar to that seen in patients with other causes of postinfectious bronchiolitis. Cylindrical bronchiectasis is the most common type and a diffuse bronchiolitis may be present.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to aspergillus and is characterized by asthma, blood, eosinophilia, radiographic pulmonary opacities and evidence of allergy to antigens of aspergillus species. It may also occur in patients with cystic fibrosis. Recurrent acute episodes cause progressive lung damage that can be controlled with steroids. The radiological features can be classified as acute and transient, or chronic and permanent. The most common acute changes are transient consolidation, mucoid impaction and atelectasis. Consolidation ranges from massive and homogeneous to lobar or segmental in configuration, or to subsegmental or smaller. When consolidation clears, it often leaves residual bronchiectasis, which creates a favourable environment for fungal recolonization, a finding that accounts for the fact consolidation often recurs in the same area. Mucoid impaction obstructs the airway lumen which becomes distended by retained secretions. At the same time, lung parenchyma remains aerated by collateral drift, permitting the visualization of the impacted airway. Bronchoceles appear as opacities of a variety of shapes (linear, branching or non-branching, band-like opacities that point to the hilum, toothpaste opacities, V- and Y-shaped opacities, gloved finger opacities). These opacities disappear once their airway contents have been coughed up, leaving ring or parallel linear opacities. Atelectasis is subsegmental, segmental or lobar and has a tendency to recur in the same area. Permanent changes indicate irreversible lung damage and are the clue that an asthmatic patient has ABPA when he/ she is in remission. Bronchiectasis is responsible for most of the permanent radiological changes. It affects lobar bronchi and the first- and second-order segmental bronchi. Beyond the proximal bronchi, more distal airways remain normal and patent, though small airway abnormalities are present on HRCT. These abnormalities include the tree-in-bud appearance reflecting mucoid impaction in dilated bronchioles, focal areas of decreased lung attenuation, and air trapping reflecting obstruction of the small airways. Compared with other bronchiectatic diseases, bronchiectasis in ABPA is more commonly widespread in central location, and more likely to contain cystic or varicose components. Mucus plugs within the ectatic airways are frequently seen on HRCT (see Fig. 16.11). High attenuation within the plugs is also relatively frequent, reflecting the presence of calcium concentration by the fungus. Hyperattenuated mucous plugs may be depicted within the areas of consolidation. Parenchymal scarring represents the fibrotic stage of the disease. It commonly follows bronchiectasis, and manifests as linear opacities and lobar shrinkage. Mirroring the distribution of bronchiectasis, these features have a strong upper zone pre-

Dyskinetic cilia syndrome1,4

BRONCHOLITHIASIS3,8 Broncholithiasis is a condition in which peribronchial calcified nodal disease erodes into or distorts an adjacent bronchus. The underlying abnormality is usually granulomatous lymphadenitis caused by Mycobacterium tuberculosis or fungi such as Histoplasma capsulatum. A few cases have been reported with silicosis. Calcified material in a bronchial lumen or bronchial distortion by peribronchial disease results in airway obstruction. This leads to collapse, obstructive pneumonitis, mucoid impaction, or bronchiectasis. Symptoms include cough, haemoptysis, recurrent episodes of fever and purulent sputum. Broncholithiasis is more common on the right, and obstructive changes particularly affect the right middle lobe. On chest radiographs, three major types of changes may be seen: • disappearance of a previously identified calcified nidus • change in position of a calcified nidus • evidence of airway obstruction, including segmental or lobar atelectasis, mucoid impaction, obstructive pneumonitis, obstructive oligaemia with air trapping. Calcified hilar or mediastinal nodes are a key feature. CT and fibre-optic bronchoscopy complement each other in this condition. Broncholithiasis is recognized on CT by the presence of a calcified endobronchial or peribronchial lymph node, associated with a bronchopulmonary complication caused by obstruction (including atelectasis, pneumonia, bronchiectasis and air trapping), in the absence of an associated soft tissue mass.

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EMPHYSEMA1,3,6,13 Emphysema is defined as a condition of the lung characterized by permanent, abnormal enlargement of airspaces distal to the terminal bronchioles, accompanied by the destruction of their walls without obvious fibrosis. The most important aetiological factor by far is cigarette smoking. Other inhaled pollutants have also been implicated, including gases such as nitrogen oxides and phosphogenes, as well as particulate smoke. There is also a causal relationship between HIV infection and the development of early emphysema. Various genetic disorders associated with emphysema include α1-antitrypsin deficiency, heritable diseases of connective tissue such as cutix laxa, Marfan syndrome and familial emphysema. Emphysema is thought to result from the destruction of elastic fibres caused by an imbalance between proteases and protease inhibitors in the lung and from the mechanical stresses of ventilation and coughing. Proteases are normally released in low concentration by phagocytes in the lung. Protease inhibitors, mainly α1-protease inhibitor (α1-antitrypsin), prevent them from causing structural damage to the lung. Imbalance in the protease–antiprotease activity may result from antiprotease deficiency (α1-antitrypsin deficiency) from excess release of protease stimulated by environmental agents, or from the defective repair of protease-induced damage. Tobacco smoke increases the number of pulmonary macrophages and neutrophils, reduces antiprotease activity, and may impair the synthesis of elastin. As emphysema develops lung destruction progresses, airspaces enlarge and elastic recoil declines, reducing radial traction on bronchial walls and on blood vessels, allowing airways and vessels to collapse.

Pathological classification Classification of emphysema is traditionally based on the microscopic localization of disease within the secondary pulmonary lobule. The principal types are centrilobular, panlobular, paraseptal and irregular emphysema. Centrilobular (centriacinar) emphysema affects mainly the proximal respiratory bronchioles and alveoli in the central part of the acinus. The process tends to be most developed in upper parts of the lungs. It is strongly associated with cigarette smoking. Inflammatory changes in the small airways are common with plugging, mural infiltration and fibrosis, leading to stenosis, distortion and destruction. Paraseptal emphysema selectively involves the alveoli adjacent to the connective tissues of septa and bronchovascular bundles, particularly at the margins of the acinus and lobule but also subpleurally and adjacent to the bronchovascular bundles. Airspaces in paraseptal emphysema may become confluent and develop into bullae, which may be large. Airway obstruction and physiological disturbance may be minor. Panlobular (panacinar) emphysema is characterized by a dilatation of the airspaces of the entire acinus and lobule. With progressive destruction, all that eventually remains are thin strands of deranged tissue surrounding blood vessels. It is the most widespread and severe type of emphysema. Pathological changes are distributed throughout the lungs, but they

are often basely predominant. Panlobular emphysema is the type of emphysema that occurs in α1-antitrypsin deficiency and in familial cases. Irregular (or paracicatricial) emphysema refers to irregular airspace enlargement, and occurs in patients with pulmonary fibrosis. It is commonly seen adjacent to localized parenchymal scars, in diffuse pulmonary fibrosis, and in pneumoconiosis, particularly progressive massive fibrosis.

Radiographic findings The main radiographic manifestations of emphysema are overinflation and alterations in the lung vessels. Signs of overinflation are the best predictors of the presence and severity of emphysema. Signs of overinflation include the height of the right lung being greater than 29.9 cm, location of the right hemidiaphragm at or below the anterior aspect of the seventh rib, flattening of the hemidiaphragm, enlargement of the retrosternal space, widening of the sternodiaphragmatic angle and narrowing of the transverse cardiac diameter (Fig. 16.14). Alterations in lung vessels include arterial depletion, whereas vessels of normal, or occasionally increased, calibre are present in unaffected areas of the lung, absence or displacement of vessels caused by bullae, widened branching angles with loss of side branches and vascular redistribution. With the development of cor pulmonale, or left heart failure, the radiographic appearance will alter and may become less obviously abnormal. The heart may then appear to be normal in size, or sometimes enlarged, the diaphragm becomes less flat and the pulmonary vessels less attenuated. Bullae may be as small 1 cm in diameter or may occupy the whole hemithorax causing marked relaxation collapse of the adjacent lung. Bullae caused by paraseptal emphysema are much more common in the upper zones, but when they are associated with widespread panlobular emphysema, the distribution is much more even. Occasionally the wall is completely absent and in such cases bullae can be difficult to detect. Plain radiographs markedly underestimate the number of bullae. The presence of emphysema associated with large bullae is referred to as bullous emphysema. An entity mainly seen in young men, characterized by the presence of large progressive upper lobe bullae which occupy a significant volume of a hemithorax and are often asymmetrical, is referred to as giant bullous emphysema, vanishing lung syndrome or primary bullous disease of the lung. Large bullae may be seen as avascular transradiant areas usually separated from the remaining lung parenchyma by a thin curvilinear wall (Fig. 16.15). They can cause marked relaxation collapse of the adjacent lung and can even extend into the opposite hemithorax, particularly by way of the anterior junctional area. Spontaneous pneumothorax commonly occurs in association with localized areas of emphysema or bullae affecting the lung apices. Bullae may enlarge progressively over months or years; a period of stability may be followed by a sudden expansion. Bullae may also disappear, either spontaneously or following infection or haemorrhage. The main complications of bullae include pneumothorax, infection and haemorrhage. In case of

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Figure 16.15 Giant bullous emphysema. The PA chest radiograph shows large avascular transradiant areas in the upper and lower parts of the right lung. The bullae are marginated with thin curvilinear opacities.

Computed tomography findings CT, particularly HRCT, is the most accurate means of detecting emphysema and determining its type and extent in vivo. On HRCT, emphysema is characterized by the presence of areas of abnormally low attenuation which can be easily contrasted with surrounding normal lung parenchyma if sufficiently low window values (−800 to −1000 HU) are used. Focal areas of emphysema usually lack distinct walls as opposed to lung cysts. In many patients, it is possible to classify the type of emphysema on the basis of its HRCT appearance, although the different types, as well as bullae, may be present in association in the same patient.

Centrilobular emphysema Figure 16.14 Severe diffuse emphysema. (A) PA and (B) lateral chest radiographs. The diaphragm is displaced downwards and appears flattened. On the PA radiograph (A) the transverse cardiac diameter is reduced. The diaphragm appears irregular in contour due to an abnormal visibility of diaphragmatic insertions on the ribs. Note the depression of vessels in the periphery of the lungs. On the lateral radiograph (B) there is a widening of the sternodiaphragm angle and an increase of dimensions of the retrosternal transradiant area.

infection or haemorrhage, bullae contain fluid and develop an air–fluid level.When a bulla becomes infected the hairline wall becomes thickened and may mimic a lung abscess. Carcinoma arising in or adjacent to bullae should be suspected in case of mural nodule, mural thickening, a change in diameter of the bulla, pneumothorax and the accumulation of fluid within the bulla.

Centrilobular emphysema predominantly affects the central portion of the lobule. On HRCT it is characterized by the presence of multiple, small round areas of abnormally low attenuation, distributed throughout the lungs but commonly having an upper lobe predominance (Fig. 16.16)14.The emphysematous spaces often appear to be grouped near the centre of secondary lobules surrounding the centrilobular arteries. Even when the centrilobular location of low attenuation areas is not recognized on HRCT, the presence of multiple, small areas of emphysema scattered throughout the lung is diagnostic of centrilobular emphysema. As the emphysema becomes more severe the areas of low attenuation become confluent and the centrilobular distribution becomes less apparent. In most cases, the areas of low attenuation have no visible walls. However, sometimes very thin walls may be seen when the areas of emphysema are extensive. These apparent walls probably represent atelectasis or interlobular septa adjacent to the emphysematous spaces.

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Occasionally the remaining interlobular septa may appear particularly prominent on the chest radiograph and in this way mimic lymphangitic carcinomatosis. HRCT of course will readily identify the true cause.

Panlobular emphysema Panlobular emphysema is characterized by widespread areas

of abnormally low attenuation, representing the uniform destruction of the pulmonary lobule. Pulmonary vessels in the affected lung appear fewer and smaller than normal (Fig. 16.18). Panlobular emphysema is almost always most severe in the lower lobes, where long lines may be present reflecting the presence of fibrosis within the remaining interlobular septa (Fig. 16.18). The characteristic appearances of extensive lung destruction and the associated paucity of vascular markings are easily recognized. On the other hand, mild and even moderately severe panlobular emphysema can be very subtle and difficult to detect radiologically15. Panlobular emphysema, secondary to α1-antitrypsin deficiency, is frequently associated with bronchiectasis. Figure 16.16 Centrilobular emphysema. HRCT of the right lung shows multiple small round areas of low attenuation that are distributed through the lungs, mainly around the centrilobular arteries (arrows).

Irregular emphysema

Paraseptal emphysema

mally low attenuation associated with features of fibrosis. It may be associated with diffuse pulmonary fibrosis or progressive massive fibrosis.

Paraseptal emphysema is characterized on HRCT by areas of low attenuation visible in the subpleural areas, along the peripheral or mediastinal pleura, mainly in the upper lobe and along the fissures (Fig. 16.17). The emphysematous spaces often have very thin but visible walls, mostly corresponding to interlobular septa thickened by associated fibrosis. Subpleural bullae are a frequently associated finding. They are commonly found in the azygoesophageal recess, adjacent to the superior mediastinal border and along the anterior junctional region. Because of its location adjacent to structures with soft-tissue attenuation, even mild paraseptal emphysema is easily detected on HRCT.

Figure 16.17 Paraseptal emphysema. HRCT of the right upper lobe shows multiple small areas of low attenuation distributed along the peripheral and mediastinal pleura (arrows).

Irregular emphysema is recognized on HRCT as areas of abnor-

Bullae Bullae are seen as avascular, low-attenuation areas that are larger than 1 cm in diameter and that can have a thin but perceptible wall. In most patients the parenchymal abnormalities are not visible on the chest radiograph. CT is more sensitive than the chest radiograph in demonstrating bullae and allows accurate assessment of their number, size, and position. CT is particularly useful when there is difficulty in distinguishing bullous disease from pneumothorax (Fig. 16.19A)16. Inspiratory and expiratory CT images indicate the extent to which a bulla is ventilated and the appearance of the rest of the lung helps in assessing the extent and degree of diffuse lung disease. This

Figure 16.18 Panlobular emphysema in a patient with α1-antitrypsin deficiency. HRCT of the lung bases showing the presence of large areas of decreased lung attenuation with a paucity of pulmonary vessels, more marked in the lower lobes. Long lines are visible within the remaining parenchyma of lung bases.

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can be highlighted on a CT image (density mask technique) and expressed as a percentage of the total pixels included in the lung section (Fig. 16.19B)18. Gevenois et al have shown that a threshold of −950 HU provides an accurate estimate of both macroscopic and, to a slightly lesser degree, microscopic emphysema19,20. However, this technique is very sensitive to technical factors. In particular, reducing the milliamperage may affect the measured extent of low attenuated lung. With MDCT, it has become feasible to apply density thresholding technique to volumetric data. Lung volume and volume of emphysema are quantified and displayed at a regional level, for a better preoperative assessment of lung disease in patients with severe emphysema who are candidates for bullectomy, lung volume reduction surgery, or lung transplantation. The use of the density mask method on both expiratory and inspiratory images has been used as a means of distinguishing areas of simple hyperinflation without tissue destruction from areas of emphysema. Expiratory CT does not correlate as well as inspiratory HRCT with the morphological extent of emphysema, but the expiratory HRCT is superior to inspiratory HRCT in reflecting functional air trapping. This technique has shown good correlations with indices of airflow obstruction and air trapping, particularly when a threshold of −900 HU is used.

CHRONIC BRONCHITIS1,6,13

Figure 16.19 Giant bullous emphysema. (A) Coronal reformation after MDCT thin collimation acquisition. Presence of large confluent bullae within the right lung associated with destruction of the right upper lobe. Presence of paraseptal emphysematous bullae within the left upper lobe along the mediastinum. (B) The same coronal reformation as in (A) after applying the density mask technique (−950 HU), making it possible to segment automatically the areas of emphysema before quantitative assessment.

ability makes CT useful for identifying patients suitable for treatment with bullectomy.

Assessment of extent of emphysema with computed tomography The distribution and severity of emphysema may be quantitated by CT. CT can be assessed by subjective visual methods, density measurements or by post-processing and texture analysis. Studies using various CT section thicknesses have shown good correlation between macroscopic pathological scores and visually assessed CT scores. However, intraand inter-observer variation in such subjective approaches is low to moderate. Objective methods using CT densitometry provides better correlation with a morphological reference17. The density of emphysematous areas is abnormally low. If a histogram plot is made of frequency against pixel density (HU), the emphysematous curve is shifted to the left compared with normal. Pixels with values below a certain number

Chronic bronchitis is defined as a clinical disorder characterized by excessive mucus secretion by the bronchial tree, manifested by chronic or recurring productive cough on most days in more than 3 months of each of 2 successive years. The pathogenesis of chronic bronchitis is related to cigarette smoking, air pollution and infection. The histological abnormalities present in chronic bronchitis include bronchial submucosal hyperplasia, smooth muscle hypertrophy, chronic inflammation and the obstruction of small airways. On pulmonary function tests, a patient with pure chronic bronchitis has normal total lung capacity and normal elastic recoil, but reduced expiratory flow and elevated residual volume. Airflow obstruction, which is concentrated in the small bronchioles, has both reversible (mucous plugging, inflammation, smooth muscle hypertrophy) and irreversible components (fibrosis and stenosis).

Radiographic findings The majority of patients with symptoms of chronic bronchitis have a normal chest radiograph. When radiographic abnormalities are present, they can include hyperinflation, oligaemia, bronchial wall thickening and accentuation of linear lung markings. Hyperinflation and oligaemia (sparse and attenuated lung vessels) can occur in patients with chronic bronchitis in the absence of emphysema, as a result of obstruction of the small airways (Fig. 16.20). Thickening of the bronchial walls leads to tubular and ring shadows. Increased lung markings cause the appearance of a ‘dirty chest’, a term widely used for describing a loss in clarity of the lung vessels (Fig. 16.20). In spite of these findings, it is

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Figure 16.20 Chronic bronchitis and obstructive lung disease. PA chest radiograph shows mild overinflation. A ring shadow is visible above the left hilum (arrow) reflecting bronchial wall thickening. There is also accentuation of linear markings in the right lung base.

widely admitted that the chest radiograph has little to offer in the detection or exclusion of chronic bronchitis. Sabre-sheath trachea may be present. Cor pulmonale is a recognized complication which is seen almost exclusively in hypoxic patients. With the onset of heart failure the heart and hilar and intermediate lung vessels become enlarged. Enlargement of vessels is present in all zones and affects particularly segmental vessels and a few divisions beyond.

Computed tomography findings On CT, bronchial wall thickening is present. Using thin-collimation MDCT acquisition and multiplanar reformations associated with minimum intensity projections, air-filled outpouchings or diverticula are seen in addition to the lumen of the main lobar or segmental bronchi. These abnormalities reflect the enlargement of mucous glands and are related to low or subepithelial connective tissue and herniation of airway mucosa between small muscle bundles. Because of the deficit of bronchial cartilage in patients with COPD, prominent collapse of airway lumen may occur with maximum force expiratory manœuvre. On expiratory CT, the lumen of segmental and subsegmental bronchi (mainly in the lower lobes) may collapse excessively, particularly in the lower lobes where the cartilage deficiency is most apparent. Airway remodelling occurs in COPD patients, but this abnormality involves essentially the small airways. As there is a significant association between the dimension of the small and large airways in COPD patients, measuring airway dimension in the larger bronchi can provide an estimate of small airway remodelling. It is likely that the same pathophysiological process that causes small airway obstruction also

takes place in larger airways where its functional effects are smaller. By using CT to assess the extent of emphysema and measure airway wall area in a cohort of COPD patients and asymptomatic smokers, some investigators have shown that individual COPD patients may have emphysema or airway wall remodelling as their predominant phenotypes21.The ability to separate airway-predominant from parenchymal-predominant pathology in COPD may prove useful in applying specific therapies designed to prevent or ameliorate the airway remodelling or parenchymal destruction. In the lung parenchyma, thin-section CT has proven its ability in demonstrating the presence of small airway abnormalities and centrilobular emphysema in asymptomatic smokers, before the development of an obstructive lung disease (Fig. 16.21). In a study of healthy adult volunteers, 20–25% of the smokers showed multiple areas of ground-glass attenuation and small nodules (Fig. 16.21)22. In another CT–pathology correlation study in heavy smokers, the areas of ground-glass attenuation corresponded to histological findings of respiratory bronchiolitis and the small centrilobular nodules corresponded to bronchiolectasis with peribronchiolar fibrosis23. The introduction of expiratory thin-section CT has demonstrated that air trapping observed in healthy volunteers is related to smoking and can be observed before pulmonary function deteriorates. In patients with COPD, the extent of lung hypoattenuation at expiration probably reflects air trapping more than reduction of the alveolar wall surface. However, expiratory air trapping in these patients may be the result of either airway obstruction caused by a loss of alveolar attachment to the airways, directly related to emphysema, or of intrinsic bronchial or bronchial abnormalities associated with cigarette smoking.

ASTHMA1,8 Asthma is a chronic inflammatory condition involving the airways. This inflammation causes a generalized increase in existing bronchial hypersensitivity to a variety of stimuli. This is commonly used in practice to confirm the clinical diagnosis of asthma. In susceptible individuals, this inflammation induces recurrent episodes of wheezing, chest tightness, breathlessness

Figure 16.21 Respiratory bronchiolitis and centrilobular emphysema in a heavy smoker. HRCT of the upper lobes shows patches of groundglass opacity associated with areas of centrilobular emphysema.

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and coughing, usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The chronic inflammation process leads to structure changes, such as new vessel formation, airway smooth muscle thickening and fibrosis, which may result in irreversible airway narrowing.

Radiographic findings Chest radiography is usually recommended in all asthmatic patients who are ill enough to justify admission to a hospital. Hyperinflation may be seen in both relapse and remission.The prevalence of hyperinflation is generally higher in children and in patients needing hospital admission. While hyperinflation is often transient, it may be a permanent change. Bronchial wall thickening is more frequent in children, but in adults when it becomes visible it is usually an irreversible phenomenon. The walls of end-on segmental airways become thickened and the normally invasive airways parallel to the radiographs appear as parallel or single line opacities. It may be present in up twothirds of patients. Chest radiography may depict complications including consolidation, atelectasis, mucoid impaction, pneumothorax and pneumomediastinum. Consolidation is commonly infective but in some cases it is due to eosinophilic consolidation probably associated with allergic aspergillosis. Collapse ranges from subsegmental to lobar and occasionally involves the whole lung. Collapse is due to mucoid impaction in large airways or more commonly mucous plugging in many small airways.

Computed tomography findings The clinical indications for CT in patients with asthma include the detection of bronchiectasis in patients with suspected ABPA, the documentation of the presence and extent of emphysema in smokers with asthma, and the identification of conditions that may be confused with asthma, such as hypersensitivity pneumonitis. In uncomplicated asthma, HRCT may show bronchial dilatation, bronchial wall thickening, mucoid impaction, decreased lung attenuation, air trapping and small centrilobular opacities24,25. These abnormalities may or may not be reversible with steroid treatment. The prevalence of these thin-section CT abnormalities increases with increasing severity of symptoms. Considerable variation exists, however, in the reported frequency of abnormalities. This variation is related to differences in diagnostic criteria and patient selection. Bronchial wall thickness measured on CT is prominent in patients with more severe asthma26. It correlates with the duration and severity of disease and the degree of airflow obstruction. Peribronchial inflammation may be partly responsible for the bronchial wall thickening, but if this feature is not reversible with steroid treatment, it reflects the development of hyperplasia and hypertrophy of smooth muscle on the bronchial wall reflecting airway wall remodelling. This observation supports the concept that quantitative assessment of bronchial wall area on CT could be used to assess airway wall remodelling in asthmatic patients in longitudinal studies to evaluate the effects of new therapies.

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Focal and diffuse areas of decreased lung attenuation seen in 20–30% of asthmatic patients are likely the results of a combination of air trapping and pulmonary oligaemia owing to alveolar hypoventilation. The areas of decreased attenuation in acute asthma almost always reflect hypoxic vasoconstriction in parts of the lung that are underventilated as a result of bronchospasm, and such areas of air trapping are more conspicuous and extensive on expiratory CT. In chronic asthma, morphological features of emphysema on CT are almost invariably related to cigarette smoking, rather than the asthma per se, in which the decreased attenuation areas represent small airway obstruction. Expiratory CT can show abnormal air trapping even in patients who have normal inspiratory images. The extent of such air trapping correlates with the severity of the asthma. Abnormal expiratory air trapping has been observed in 50% of asthmatic patients.This reflects the luminal obstruction of the airways and is potentially, but not always, reversible. CT may depict air trapping before lung function deteriorates. The mosaic perfusion pattern is frequent in patients with moderate persistent asthma27. In severe persistent asthma, diffuse decreased lung attenuation and expiratory air trapping make the pattern difficult to distinguish from that of obliterative bronchiolitis. In patients with persistent asthma, no change in air trapping scores after inhalation of a bronchodilator suggest that the air trapping may reflect permanent changes resulting from small airway remodelling27. Airway remodelling caused by smooth muscle hypertrophy and hyperplasia accounts for the faster and greater decrease in forced expiratory volume per second with age in asthmatics compared with controls.

OBLITERATIVE (CONSTRICTIVE) BRONCHIOLITIS1,3,4,6,13 Inflammation of the bronchioles (bronchiolitis) is a very common lesion in the lungs. However, the extent of such lesions is rarely extensive enough to cause clinical symptoms. Pathological studies have repeatedly emphasized the frequent involvement of the bronchioles in diverse diffuse disease. Inflammation of the bronchioles may be reversible under specific or antiinflammatory treatment or lead to subsequent scaring and obliteration. Obliterative bronchiolitis is a condition characterized by bronchiolar and peribronchiolar inflammation and fibrosis that ultimately leads to luminal obliteration affecting the membranous and respiratory bronchioles. Obliterative bronchiolitis is the result of a variety of causes but in rare cases it is idiopathic (Table 16.2). When a large proportion of the airways is affected, patients usually present with progressive shortness of breath and functional evidence of airflow obstruction.

Pathological features The pattern of obliterative bronchiolitis is characterized by the development of an irreversible circumferential submucosal fibrosis, resulting in bronchiolar narrowing or obliteration of bronchioles in the absence of intraluminal granulation tissue polyps or surrounding parenchymal inflammation. Proliferation of fibrosis extends predominantly between the epithelium

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Table 16.2 CAUSES OF AND ASSOCIATION WITH OBLITERATIVE (CONSTRICTIVE) BRONCHIOLITIS • Postinfection Childhood viral infection (adenovirus, respiratory syncytial virus, influenza, parainfluenza) Adulthood and childhood (Mycoplasma pneumoniae, Pneumocystis carinii in AIDS patients, endobronchial spread of tuberculosis, bacterial bronchiolar infection) • Postinhalation (toxic fume and gases) Nitrogen dioxide (silo filler’s disease), sulphur dioxide, ammonia, chlorine, phosgene Hot gases • Gastric aspiration Diffuse aspiration bronchiolitis (chronic occult aspiration in the elderly, patients with dysphagia) • Connective tissue disorders Rheumatoid arthritis Sjögren’s syndrome • Allograft recipients Bone marrow transplant Heart–lung or lung transplant • Drugs Penicillamine Lomustine • Ulcerative colitis • Other conditions Bronchiectasis Chronic bronchitis Cystic fibrosis Hypersensitivity pneumonitis Sarcoidosis Microcarcinoid tumorlets (neuroendocrine cell hyperplasia) Sauropus androgynus ingestion • Idiopathic

and the muscular mucosa and along the long axis of the airway, impairing collateral ventilation and leading to airflow obstruction. The epithelium overlying the abnormal fibrosis tissue may be flattened or metaplastic and is usually intact without any ulceration. In some instances, the accompanying artery is also obliterated by the same fibrotic process.

Radiographic findings The chest radiograph is often normal. In a small number of patients, mild hyperinflation, subtle peripheral attenuation of the vascular markings, widespread and conspicuous abnormalities in lung attenuation, and central bronchiectasis may be seen (see Fig. 16.6). Thin-section CT is superior to radiography in demonstrating the presence and extent of abnormalities. The main thin-section CT findings usually consist of areas of decreased lung attenuation associated with vessels of decreased calibre on inspiratory images and air trapping on expiratory images. Because the lesions of bronchiolar narrowing or obstruc-

tion are heterogeneously distributed throughout the lungs, redistribution of blood flow to areas of normal lung or less diseased areas give a pattern of mosaic perfusion. Bronchial wall thickening and bronchiectasis, both central and peripheral, are also commonly present. Although the vessels within areas of decreased attenuation on thin-section CT may be of markedly reduced calibre, they are not distorted as in emphysema. The lung areas of decreased attenuation related to decreased perfusion can be patchy or widespread. They are poorly defined or sharply demarcated, giving a geographical outline, and represent a collection of affected secondary pulmonary lobules. Redistribution of blood flow to the normally ventilated areas causes increased attenuation of lung parenchyma in these areas. The patchwork of abnormal areas of low attenuation and normal lung or less diseased areas, appearing normal in attenuation or hyperattenuated, gives the appearance of mosaic attenuation. The vessels in the abnormal hypoattenuated areas are reduced in calibre, whereas the vessels in normal areas are increased in size; the resulting pattern is called mosaic perfusion. The difference in vessel size between low and high attenuation areas allows the mosaic perfusion pattern to be distinguished from mosaic attenuation due to an infiltrative lung disease with patchy distribution, in which the vessels have the same calibre in both high and normal attenuation areas.The areas of decreased lung attenuation and perfusion may be confined to or predominant in one lung, particularly in Swyer–James or MacLeod syndrome, which is a variant form of postinfectious obliterative bronchiolitis in which the obliterative bronchiolar lesions affect predominantly one lung. Usually the regional inhomogeneity of the lung density seen at end-inspiration on thin-section CT is accentuated on sections obtained at end, or during, expiration because the high attenuation areas increase in density and the low attenuation areas remain unchanged. In the case of more global involvement of the small airways, the lack of regional homogeneity of the lung attenuation is difficult to perceive on inspiratory CT, and as a result mosaic perfusion becomes visible only on expiratory images (Fig. 16.22). In patients with particularly severe and widespread involvement of the small airways, the patchy distribution of hypoattenuation and mosaic pattern is lost. On inspiratory CT there is uniformly decreased attenuation in the lungs, and images taken at end-expiration may appear unremarkable. In these patients, the most striking features are a paucity of pulmonary vessels and no difference in the cross-sectional areas of the lung at comparable levels on inspiratory and expiratory images. In such a situation, there is a risk of misdiagnosis between obliterative bronchiolitis and panlobular emphysema. Both conditions are characterized by bronchial wall thickening and generalized decreased attenuation of the lung parenchyma and bronchial dilatation. However, patients with panlobular emphysema demonstrate parenchymal destruction with higher frequency and greater extent than those with obliterative bronchiolitis. Long lines reflecting limited thickened interlobular septa were significantly more frequent in patients with panlobular emphysema28.

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Figure 16.22 Obliterative bronchiolitis. HRCT acquired at (A) full inspiration and (B) full expiration. The mosaic perfusion appearance is very difficult to perceive on the inspiration image (A). The contrast in attenuation between normal and abnormal areas is accentuated at expiration. The areas that did not change in attenuation between inspiration and expiration represent areas of lung parenchyma containing obliterative lesions on the bronchioles.

Assessment of air trapping with computed tomography The most commonly used CT technique for the assessment of air trapping is based on postexpiratory thin-section images obtained during suspended respiration following a forced exhalation. Each of the postexpiratory images is compared with the inspiratory image that most closely duplicates its level to detect air trapping. More recently, dynamic expiratory manœuvre performed during helical CT acquisition has been described29. Motion artefacts, which increase as temporal resolution decreases, represent the major limitation of continuous expiratory CT. However, motion artefacts are at a maximum during the early phase of expiration and at a minimum during its late phase, which allows good visualization of lobular air trapping with helical CT. The extent of air trapping and the relative contrast scores are significantly higher with continuous expiratory CT than those obtained with suspended end-

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expiratory CT. This improvement can be explained by a small increase in the degree of expiration, which leads to a better detection of air trapping29. This technique is recommended when patients have difficulty performing the suspended endexpiration manœuvre adequately. MDCT with thin collimation over the lungs and low dose has become routine in many institutions to improve the conspicuity and apparent extent of air trapping. The technique of multiplanar volume rendering slab associated with the technique of minimum intensity projection increases the contrast between areas of normal lung attenuation and areas of lung hypoattenuation. This helps depict the mosaic perfusion pattern. Its application in expiratory CT can also facilitate the detection of air trapping and the assessment of its extent. The texture analysis technique has been developed to discriminate between patterns of obstructive lung disease on the basis of parenchymal texture alone on HRCT. The extent of air trapping present on expiratory CT can be measured using a semiquantitative scoring system that estimates the percentage of lung that appears abnormal in each study. In the scoring system proposed by Stern et al, estimates of air trapping were made at each level and for each lung on a four-point scale: 0: no air trapping; 1: 1–25%; 2: 26–50%; 3: 51–75%; and 4: 76–100% of the cross-sectional area of the lung affected. The air trapping score is the summation of these numbers for the level studied.This scoring system allows good inter- and intra-observer agreement. The extent of expiratory air trapping at CT has proved to correlate with the degree of airflow obstruction at pulmonary function tests in patients with obliterative bronchiolitis30. Objective measurement of air trapping can be done using CT densitometry. The assessment of extent can be expressed as a mean density of the voxels included in a chosen region of interest; as a histogram that shows the distribution of attenuation values within the lung; and as a density mask that highlights, or as a calculation that summarizes, the pixels with a density below a certain critical value. In the density mask technique, all the pixels included in areas of air trapping are segmented by thresholding at −910 HU and are highlighted and automatically counted. This permits calculation of the pixel index, which is defined as the percentage of pixels in both lungs on a single study that show an attenuation lower than a predetermined threshold value. Expressing lung density on a histogram has the advantage that changes in the distribution of attenuation values are detectable when mean attenuation is unchanged. Density changes between full inspiration and full expiration can be compared, and expiratory:inspiratory ratios can be calculated. The density mask has the advantage that it combines density measurement with the visual assessment of pathology. Using MDCT with thin collimation over the lungs performed at full expiration, an exhaustive assessment of the volume of air trapping may be provided, as well as a 3D visualization of the distribution of air trapping. Sophisticated image processing techniques can be used to compensate for the nondependent–dependent lung attenuation gradient.

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REFERENCES 1. Hansell D M, Armstrong P, Lynch D A et al 2005 Imaging of diseases of the chest, 4th edn. Elsevier Mosby, Philadelphia 2. Kwong J S, Muller N L, Miller R R 1992 Diseases of the trachea and main-stem bronchi: correlation of CT with pathologic findings. RadioGraphics 12: 645–657 3. Muller N L, Fraser R G, Lee K S et al 2003 Diseases of the lung. Lippincott Williams & Wilkins, Philadelphia 4. Naidich D P, Webb W R, Grenier P A et al 2005 Imaging of the airways. Lippincott Williams & Wilkins, Philadelphia 5. Berkmen Y M 1984 The trachea: the blind spot in the chest. Radiol Clin North Am 22, 539–562 6. Takasugi J E, Godwin J D 1998 Radiology of chronic obstructive pulmonary disease. Radiol Clin North Am 36: 29–55 7. Baroni R H, Feller-Kopman D, Nishino M et al 2005 Tracheobronchomalacia: comparison between end-expiratory and dynamic expiratory CT for evaluation of central airway collapse. Radiology 235: 635–641 8. Grenier P A, Beigelman-Aubry C, Fetita C et al 2002 New frontiers in CT imaging of airway disease. Eur Radiol 12: 1022–1044 9. Roberts H R, Wells A U, Milne D G et al 2000 Airflow obstruction in bronchiectasis: correlation between computed tomography features and pulmonary function tests. Thorax 55: 198–204 10. Grenier P, Maurice F, Musset D et al 1986 Bronchiectasis: assessment by thin-section CT. Radiology 161: 95–99 11. Lucidarme O, Grenier P, Coche E et al 1996 Bronchiectasis: comparative assessment with thin-section CT and helical CT. Radiology 200: 673–679 12. Remy-Jardin M, Amara A, Campistron P et al 2003 Diagnosis of bronchiectasis with multislice spiral CT: accuracy of 3-mm-thick structured sections. Eur Radiol 13: 1165–1171 13. Webb W R 1994 High-resolution computed tomography of obstructive lung disease. Radiol Clin North Am 32: 745–757 14. Foster W L Jr, Pratt P C, Roggli V L et al 1986 Centrilobular emphysema: CT–pathologic correlation. Radiology 159: 27–32 15. Spouge D, Mayo J R, Cardoso W et al 1993 Panacinar emphysema: CT and pathologic findings. J Comput Assist Tomogr 17: 710–713 16. Stern E J, Webb W R, Weinacker A et al 1994 Idiopathic giant bullous emphysema (vanishing lung syndrome): imaging findings in nine patients. Am J Roentgenol 162: 279-282 17. Bankier A A, De Maertelaer V, Keyzer C et al 1999 Pulmonary emphysema: subjective visual grading versus objective quantification with macroscopic morphometry and thin-section CT densitometry. Radiology 211: 851–858

18. Muller N L, Staples C A, Miller R R et al 1988 “Density mask.” An objective method to quantitate emphysema using computed tomography. Chest 94: 782–787 19. Gevenois P A, de Maertelaer V, De Vuyst P et al 1995 Comparison of computed density and macroscopic morphometry in pulmonary emphysema. Am J Respir Crit Care Med 152: 653–657 20. Gevenois P A, De Vuyst P, de Maertelaer V et al 1996 Comparison of computed density and microscopic morphometry in pulmonary emphysema. Am J Respir Crit Care Med 154: 187–192 21. Nakano Y, Muro S, Sakai H et al 2000 Computed tomographic measurements of airway dimensions and emphysema in smokers. Correlation with lung function. Am J Respir Crit Care Med 162: 1102–1108 22. Remy-Jardin M, Remy J, Boulenguez C et al 1993 Morphologic effects of cigarette smoking on airways and pulmonary parenchyma in healthy adult volunteers: CT evaluation and correlation with pulmonary function tests. Radiology 186: 107–115 23. Remy-Jardin M, Remy J, Gosselin B et al 1993 Lung parenchymal changes secondary to cigarette smoking: pathologic–CT correlations. Radiology 186: 643–651 24. Grenier P, Mourey-Gerosa I, Benali K et al 1996 Abnormalities of the airways and lung parenchyma in asthmatics: CT observations in 50 patients and inter- and intraobserver variability. Eur Radiol 6: 199–206 25. Park C S, Muller N L, Worthy S A et al 1997 Airway obstruction in asthmatic and healthy individuals: inspiratory and expiratory thinsection CT findings. Radiology 203: 361–367 26. Niimi A, Matsumoto H, Amitani R et al 2000 Airway wall thickness in asthma assessed by computed tomography. Relation to clinical indices. Am J Respir Crit Care Med 162: 1518–1523 27. Laurent F, Latrabe V, Raherison C et al 2000 Functional significance of air trapping detected in moderate asthma. Eur Radiol 10: 1404–1410 28. Copley S J, Wells A U, Muller N L et al 2002 Thin-section CT in obstructive pulmonary disease: discriminatory value. Radiology 223: 812–819 29. Lucidarme O, Grenier P A, Cadi M et al 2000 Evaluation of air trapping at CT: comparison of continuous versus suspended-expiration CT techniques. Radiology 216: 768–772 30. Hansell D M, Rubens M B, Padley S P et al 1997 Obliterative bronchiolitis: individual CT signs of small airways disease and functional correlation. Radiology 203: 721–726

CHAPTER

Pulmonary Lobar Collapse: Essential Considerations

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Susan J. Copley

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Mechanisms and causes of lobar collapse Radiographic considerations Computed tomography of lobar collapse Other imaging techniques in lobar collapse Patterns of lobar collapse

Collapse and atelectasis are terms which are often used synonymously and refer to loss of volume within the lung. In North America, the term collapse is often reserved to denote complete loss of volume within an entire lobe or lung1.

MECHANISMS AND CAUSES OF LOBAR COLLAPSE Broadly, lobar collapse can be divided into those due to endobronchial obstruction (either intrinsic or extrinsic) and those without obstruction2,3.The causes of lobar collapse are summarized in Table 17.1.The common causes differ slightly between adults and children. In adults the frequent causes of intrinsic obstruction are tumours and mucus plugs. In the clinical context of a middleaged or elderly smoker, lobar collapse should always be suspected to be due to a bronchogenic carcinoma until proved otherwise. All cell types of bronchogenic carcinoma can potentially cause intrinsic large airway obstruction and produce segmental, lobar or whole lung collapse (Fig. 17.1)2. More rarely, foreign bodies, broncholiths and focal bronchostenosis due to inflammation or trauma may be encountered. In children, causes such as inhaled foreign bodies or mucus plugs are common (Fig. 17.2), with tumours being very rare.

RADIOGRAPHIC CONSIDERATIONS The cardinal radiographic features of lobar collapse are increased opacity of the affected lobe and volume loss. The latter can be inferred by direct and indirect signs. Direct signs of volume loss refer to displacement of interlobar fissures, pulmonary vessels and bronchi, whereas indirect signs include

compensatory shifts of adjacent structures such as hyperinflation of other lobes. The effects of a lobar collapse are often maximal on immediately adjacent structures, e.g. an upper lobe collapse often results in a shift of the superior mediastinum, whereas a lower lobe collapse often demonstrates elevation of the posterior part of the diaphragm in particular. However, the general principles and fundamental radiographic signs are similar for all lobes. A collapsed lobe appears radiographically dense due to a combination of retained secretions or fluid within the lobe and reduction in aeration of the lobe4. However, retained fluid is the dominant process resulting in increased opacity of a partially collapsed lobe, as virtually complete collapse is required to displace sufficient air for the normally radiographically hyperlucent lung to appear dense.

Direct signs of volume loss Displacement of fissures is a reliable feature of lobar collapse, and is generally characteristic depending on the affected lobe5. The pulmonary vessels and bronchi become crowded together in the affected lobe as the lung loses volume. The sign may be one of the earliest seen in lobar collapse and can often be readily appreciated by comparison with previous radiographs. Hilar elevation on the PA chest radiograph is a wellknown sign of upper lobe collapse: the ipsilateral interlobar and lower lobe arteries remain visible as these structures are still outlined by aerated lung. It would seem logical to consider ‘hilar depression’ to be a sign of lower lobe collapse, but some authorities believe the small hilum to be a more accurate description5. This is due to the fact that when a lower lobe collapses, the opaque, collapsed lobe obscures the lower lobe artery that lies within it, and the interlobar artery is usually rotated so the margin is no longer in profile to the frontal X-ray beam. Consequently, it is difficult to recognize the hilum as being depressed and instead, smaller vascular structures are noted at the expected position of the hilum. Occasionally, confusion with a central hilar mass/ adenopathy can arise if the convex margin of an interlobar artery remains visible due to minimal rotation6.

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Table 17.1 CAUSES OF LOBAR COLLAPSE 2,3 Lobar collapse due to endobronchial obstruction • Intrinsic Bronchogenic carcinoma Bronchial carcinoid Adenoid cystic carcinoma Metastases (e.g. breast, renal cell and colonic carcinoma, melanoma, sarcoma) Lymphoma Benign tumours (e.g. lipoma, hamartoma, papillomas, endometriomas) Granulomatous diseases (e.g. sarcoidosis and tuberculosis) Miscellaneous conditions (e.g. aspirated foreign bodies, mucus plugs, gastric contents, malpositioned endotracheal tubes, bronchial torsion or rupture, amyloidosis, Wegener’s granulomatosis) • Extrinsic Hilar or mediastinal lymphadenopathy (commonly due to bronchogenic or breast carcinoma) Mediastinal masses Fibrosing mediastinitis Aortic aneurysms and congenital vascular anomalies Cardiac enlargement

Lobar collapse without endobronchial obstruction • Miscellaneous conditions (e.g. passive collapse due to pleural fluid or pneumothorax, radiation-induced collapse, tumour replacement [bronchiolo-alveolar cell carcinoma])

Figure 17.1 Total left lung collapse. (A) Frontal and (B) lateral chest radiographs. The cause of the collapse is a bronchogenic carcinoma; the endobronchial component is visible as an abrupt cut-off of the left main bronchus. Note the marked displacement of the right lung anteriorly and posteriorly across the midline (arrows). Note the marked anterior hyperlucency of the thorax on the lateral view (B).

As well as vascular reorientation, hilar bronchial alterations also occur. The central large bronchi undergo characteristic changes in position with collapse of either the upper or lower lobe. When either upper lobe collapses significantly, the ipsilateral main bronchus becomes more horizontally orientated than usual, hence the bronchus intermedius and the left lower lobe bronchus swing laterally. Conversely, when either lower lobe collapses, each main bronchus is more vertically orien-

tated than usual, with a medial swing of the bronchus intermedius on the right and the lower lobe bronchus on the left.

Indirect signs of volume loss Compensatory hyperinflation of adjacent lobes occurs with lobar collapse, resulting in fewer vessels per unit volume of lung. It is often easier to detect a paucity of vessels, which are more widely spaced than on the unaffected side, than

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Figure 17.2 Total right lung collapse in a neonate. The patient was ventilated for respiratory distress syndrome and the cause of the total lung collapse was a mucus plug.

subtle increased radiolucency. In isolation, the sign may be due to causes other than lobar collapse and other confirmatory features should be sought before making the diagnosis. The normal lung parenchyma should expand proportionally to compensate for the degree of collapse and often the greater the degree of lobar collapse, the greater the compensatory overinflation. Therefore when small lung volumes are involved, the hyperinflation usually only involves the remainder of the ipsilateral lung, whereas with larger volumes, the contralateral lung may expand across the midline. On a frontal radiograph the lung may expand across the midline superiorly, thus displacing the anterior junctional line to the contralateral side (see Fig. 17.1A). On a lateral view, the anterior medias-

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PULMONARY LOBAR COLLAPSE: ESSENTIAL CONSIDERATIONS

tinum appears hyperlucent (see Fig. 17.1B). Displacement of the azygo-oesophageal line and posterior junctional line on the PA radiograph, which denote protrusion of contralateral lung through other weak areas between the oesophagus and vertebral column and the retrocardiac space respectively, may be more difficult to recognize. Although the term ‘mediastinal herniation’ is sometimes used, some authorities emphasize that there is no actual mediastinal defect or hiatus and the sign more accurately denotes displacement of mediastinal structures7. A divergent or parallel pattern of vascular reorientation seen near the hilum has been described in marked upper lobe collapse8.The pattern is seen more commonly on the left than on the right, as a result of the different degree of compensatory overinflation in the superior segment of the ipsilateral lower lobe on each side8. The right middle lobe can also overinflate in compensation, which further explains the lesser degree of overinflation of the superior segment of the right lower lobe. The sign of vascular reorientation can be helpful when unusual patterns of upper lobe collapse are present. Hyperexpansion may also result in a change in position of lung lesions, such as granulomas resulting in the so-called shifting granuloma sign (Fig.17.3). Of particular note, the Luftsichel sign (from German, meaning air crescent) is due to the overinflated superior segment of the ipsilateral lower lobe occupying the space between the mediastinum and the medial aspect of the collapsed upper lobe, resulting in a paramediastinal translucency (Fig. 17.4)9. The sign is more common on the left than the right and is regarded as a typical appearance of left upper lobe collapse9. CT demonstrates the increased paramediastinal lucency to be due to a wedge shape of the collapsed upper lobe, with the apex of the V resulting from tethering of the major fissure by hilar structures (Fig. 17.4B).

Figure 17.3 Shifting granuloma sign. (A) Pre and (B) post right lower lobe collapse.

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Figure 17.4 Luftsichel sign. (A) A left upper lobe collapse demonstrating paramediastinal lucency (arrow). (B) CT shows interposition of aerated lung between the collapse and the mediastinum (arrow). There is also a large right paratracheal node causing some distortion of the SVC.

Mediastinal shift is another indirect sign of volume loss and the degree varies according to the position of the affected lobe. Usually the least mediastinal shift occurs in right middle lobe collapse, whilst the greatest shift, particularly of the inferior mediastinum, is seen with lower lobe collapse. The amount of mediastinal shift due to upper lobe collapse is often dependent on the chronicity: in acute upper lobe collapse there is often little shift, whereas in chronic upper lobe volume loss with fibrosis, the shift may be greater. The position of the trachea may be a useful indicator of superior mediastinal shift as it should be central in the superior mediastinum between the anterior ends of the clavicles or slightly deviated to the right by the aortic arch. Inferiorly within the mediastinum, anywhere between one-half and one-fifth of the cardiac outline normally lies to the right of the midline and greater or lesser variations indicate mediastinal shift. However, because of the wide variation in normal subjects, displacement of the cardiac outline may be more difficult to assess than changes in position of the trachea. The hemidiaphragms may be elevated in lobar collapse, particularly involving the left upper lobe and to a lesser extent the right upper and both lower lobes. However, the sign is of limited value because the position of the right hemidiaphragm is highly variable (0–3 cm higher than the left on the frontal chest radiograph). A useful ancillary sign of upper lobe collapse (or a combination of right upper and middle lobe collapse) is a juxtaphrenic peak of the diaphragm (Fig. 17.5)10. The sign refers to a small triangular density at the highest point of the dome of the hemidiaphragm, due to the anterior volume loss of the affected upper lobe resulting in traction and reorientation of an inferior accessory fissure11,12. Reduction in the volume of a hemithorax may result in relative reduction of the spaces between the ribs by comparison to the unaffected side. Rib crowding or approximation may be recognizable on the frontal radiograph in cases of chronic lobar collapse, but in acute collapse it may be more difficult to appreciate. Furthermore, the sign is considered to be unreli-

Figure 17.5 Juxtaphrenic peak sign. A small triangular density (arrow) is seen in a left upper lobe collapse. The sign is due to reorientation of an inferior accessory fissure.

able as patient rotation and minor degrees of scoliosis may result in apparent rib crowding.

Ancillary features of lobar collapse Occasionally the cause of a lobar collapse may be apparent and an endobronchial lesion may be clearly demonstrated radiographically (Fig. 17.1A). However, although the actual endobronchial component is often not directly visualized, lobar collapse due to a central obstructing bronchogenic carcinoma is most likely when Golden’s S sign is seen (Fig. 17.6). The sign refers to the S shape (or more accurately, reverse S on the right) of the fissure due to the combination of collapse and mass centrally resulting in a focal convexity with a concave outline peripherally. Although the sign was originally described in the right upper lobe, it can be seen in any lobe5,13. The CT equivalent is discussed later. Generally, absence of air

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PULMONARY LOBAR COLLAPSE: ESSENTIAL CONSIDERATIONS

Figure 17.6 Golden’s S sign. A right upper lobe collapse demonstrating peripheral concavity and central convexity (arrows) due to an underlying bronchogenic carcinoma resulting in a reverse S shape.

bronchograms within the affected lobe should also raise the suspicion of a central obstructing lesion as there is absorption of air from both the lung parenchyma and airways. The sign may be useful to distinguish a central obstructing mass from a consolidative process such as bacterial pneumonia (Fig. 17.7). The rare important caveats are when a mass results in only partial obstruction of the airways or in cases of acute bronchopneumonia where the airways are filled with an inflammatory exudate. However, the sign is not as reliable on CT, and often distal air bronchograms are visible in part of a collapsed lobe due to a central neoplasm (Fig. 17.8).

Figure 17.8 CT of a collapsed right upper lobe due to a squamous cell carcinoma. Note the peripheral air bronchograms (arrow) in (A) despite a central obstructing mass with amorphous calcification (B). There is a convex border of the collapsed lobe (arrows) (B) which is the CT equivalent of Golden’s S sign.

COMPUTED TOMOGRAPHY OF LOBAR COLLAPSE CT has become an invaluable method for the investigation of patients with lobar collapse. The obvious benefits are a lack of superimposition of overlying structures with the added advantage of demonstration of anatomical structures in the axial and, with computer reformatting, coronal and sagittal planes. Not only does CT aid the understanding of the radiographic appearances of lobar collapse, it also provides invaluable information about the cause which may not be apparent on chest radiography. The most common indication for CT in adults with lobar collapse is to identify an endobronchial or compressing lesion.

Technique

Figure 17.7 Air bronchograms in a collapsed and consolidated right lower lobe. The sign can be helpful in excluding a central obstructing mass and in this case the cause was a bacterial pneumonia.

Careful attention to CT technique is sometimes required to accurately demonstrate an obstructing lesion resulting in lobar collapse. The old recommendations using single slice CT14 have been superseded by techniques using helical and now multidetector CT (MDCT). Such systems can often provide high resolution images from the same data acquisition as used for other purposes with a saving in radiation dose. The facility to reconstruct and reformat volumetric data has resulted

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in advancements in the display of tracheobronchial anatomy. Three-dimensional (3D) and multiplanar (2D) images provide an extremely useful adjunct to axial images15.

Utility In some cases, the aetiology of lobar collapse can be determined from the patient’s clinical history, examination, and chest radiographic features. Using fibre-optic bronchoscopy as the reference standard, CT is clearly more sensitive than chest radiography for the detection of an obstructing carcinoma16. Reported sensitivities for detection by CT range from 83 to 100%17–20 but generally, when an endobronchial lesion is sufficiently large to cause lobar collapse, CT is a reliable method for detection2,16. False-positive diagnoses may be due to bronchial strictures, plugs of mucus or secretions and compression by large pleural effusions2,3,16. CT is not histologically specific, however, as bronchogenic carcinoma, endobronchial metastases, bronchial adenomas and lymphoma may all have similar appearances2. The accuracy of CT is, to some extent, dependent on technique and it may be more difficult to demonstrate endobronchial lesions in the right middle lobe and lingular bronchi owing to their oblique orientation relative to the axial plane. This is much less of a problem with MDCT. Accurate delineation of a tumour mass from a surrounding collapsed lobe may be problematical, but collapsed lung usually enhances to a greater degree than tumour with dynamically contrast-enhanced CT (Fig. 17.9)21. The difference in attenuation value is maximal between 40 s and 2 min after a bolus injection of contrast medium21. In practice, the distinction between tumour and collapsed lung may not be important and the technique is reserved for cases where more accurate delineation is necessary for treatment purposes, e.g. radiotherapy planning. Golden’s S sign on chest radiography has a CT equivalent that may be helpful in identifying an obstructing tumour22,23. Usually, a collapsed lobe is associated with concavity of the

Figure 17.9 CT of right upper lobe collapse due to bronchogenic carcinoma. Note how the attenuation of the necrotic tumour is lower than the adjacent collapsed lung which enhances with intravenous contrast medium.

adjacent fissure and a localized convexity is highly suggestive of an underlying mass (see Fig. 17.8). The sign is not entirely specific, but it is strongly indicative of a bronchogenic carcinoma. Unlike the frontal chest radiograph, in which the S sign is only helpful in the right upper lobe and to a lesser extent the right and left lower lobes, the S sign can be applied to all lobes on CT. Another CT sign that is highly suggestive of an obstructing lesion causing lobar collapse is the CT mucous bronchogram sign24. Histopathologically, the lobar and segmental bronchi are filled with inspissated secretions and are usually dilated. The airways are optimally demonstrated as tubular, low attenuation branching structures within the enhancing collapsed lobe following intravenous contrast enhancement (Fig. 17.10).

Figure 17.10 Left lung collapse. (A, B) Contrast-enhanced CT sections of whole lung collapse due to a squamous cell carcinoma in the left main bronchus (arrow in A). There is also a left pleural effusion and a small pericardial effusion. Note the low-attenuation areas relative to the densely enhancing left lower lobe parenchyma (B) which represent mucus-filled airways—the CT mucous bronchogram sign.

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Obstructing lesions such as bronchogenic carcinoma or benign causes, including tuberculous bronchostenosis, should be considered. The sign may also result from excessive mucus production combined with decreased mucociliary function in conditions such as allergic bronchopulmonary aspergillosis, asthma and cystic fibrosis25. CT also has a role in complicated or atypical lobar collapse as their appearances may be confusing on chest radiography. In particular, combined right middle lobe and right upper lobe collapse may be difficult to diagnose on chest radiography when the collapse is nearly complete26. CT is useful for demonstrating mediastinal anatomy and provides information about mediastinal lymph nodes and the staging of a tumour causing lobar collapse.Additional signs of lobar collapse, such as compensatory overinflation and the Luftsichel sign (described above), are also well demonstrated, providing explanations for the radiographic appearances of lobar collapse27,28.

Potential pitfalls The increased sensitivity of CT by comparison with radiography means that the presence of an air bronchogram within a lobar collapse does not necessarily exclude a central obstructing lesion (see Fig. 17.8.)24. In this context, an air bronchogram may be seen in the peripheral part of a collapsed lobe due to collateral air drift or tumour necrosis16. Similarly, a proximal obstructing lesion may not cause complete lobar collapse when a fissure is incomplete allowing ventilation by collateral air drift29. Occasionally the parenchyma and airways become filled with fluid owing to the presence of a central obstructing lesion with little or no associated volume loss, and the lobe may even be expanded giving rise to the appearance termed ‘drowned lobe’. The CT equivalent of the Golden’s S sign is particularly well demonstrated with right-sided lobar collapse and, on the left, care should be taken in interpretation owing to the fact that normal mediastinal structures may mimic a mass (e.g. thoracic aorta)22 (Fig. 17.11).

Figure 17.11 Left lower lobe collapse. Contrast-enhanced CT showing a tight left lower lobe collapse. Normal mediastinal structures (particularly left-sided) may cause a focal bulge in the contour of a lobar collapse (in this case by the well opacified descending thoracic aorta) and should not be confused with a Golden’s S sign due to tumour.

The accurate determination of the reversibility and chronicity of a lobar collapse may be problematical. Relatively acute collapses may show apparent bronchiectatic dilatation of the airways and may mimic a long-standing irreversible event (Fig. 17.12); a meaningful evaluation of the airways in the context of a lobar collapse is therefore often difficult.

OTHER IMAGING TECHNIQUES IN LOBAR COLLAPSE Magnetic resonance imaging (MRI) has been largely surpassed by CT in the investigation of lobar collapse owing to

Figure 17.12 Resolution of left lower lobe collapse. (A) An initial high-resolution CT of a young female patient with symptoms of recurrent respiratory tract infections shows a collapsed left lower lobe with possible bronchiectatic airways, raising the possibility of chronicity. (B) Follow-up conventional CT at the same level several months later shows complete resolution of the left lower lobe collapse and normal airways. This case illustrates the difficulty in making an accurate assessment of the airways in patients with lobar collapse.

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the superior spatial resolution of the latter. In particular, endobronchial tumours and smaller bronchi are less well demonstrated by MRI than CT30. Studies have investigated the ability of MRI to differentiate a tumour mass from postobstructive collapse by utilizing differences in signal characteristics31–33. Sometimes the distinction can be made on T1-weighted images, but it is generally accepted that T2-weighted images are superior as the tumour is of lower signal intensity than the obstructed lung which has a higher water content. On ultrasound of a large pleural effusion, the underlying collapsed lung is often visible as a hyperechoic wedge-shaped area within hypo-echoic or anechoic fluid. In practice, the main utility of ultrasound is to readily distinguish pleural effusion from a collapsed and consolidated lung when radiographic appearances are equivocal. On positron emission tomography (PET), a collapsed lobe often demonstrates less uptake of [18F]fluorodeoxyglucose than tumour. By comparison with CT, PET may therefore provide more accurate delineation of tumour from postobstructive collapsed lung, which may be useful in treatment with radiotherapy34.

Figure 17.13 Right upper lobe collapse. Typical example of a collapsed right upper lobe demonstrating the slightly concave inferior border of the opacified lung due to the horizontal fissure.

PATTERNS OF LOBAR COLLAPSE Right upper lobe collapse On the frontal radiographic view of a right upper lobe collapse, the collapsed lobe forms increased density at the apex of the hemithorax adjacent to the right side of the mediastinum, with the elevated horizontal fissure resulting in a concave inferior outline depending on the degree of collapse (Fig. 17.13). Even in cases where there is no obstructing lesion, there is often a small convexity at the hilum due to the pulmonary veins and artery where the apex of the lobe is attached to the hilum. On the lateral view, the horizontal and oblique fissure approximate and are both displaced superiorly and medially with the collapsed lobe forming a superior ill-defined wedgeshaped density. In cases where the collapse is very severe, the horizontal fissure parallels the mediastinum and appearances may simulate an apical cap of pleural fluid (Fig. 17.14) or mediastinal widening on the frontal radiograph (Fig. 17.15). There is also usually compensatory hyperinflation of the right middle and lower lobes, resulting in elevation and a more horizontal course of the lower lobe pulmonary artery and right main bronchus. The vascular reorientation can be recognized on the frontal view, but the right main and lower lobe bronchial displacement can be difficult to appreciate on both the frontal and lateral view. On CT the right upper lobe forms a triangular density with the base anteriorly against the chest wall and the apex at the hilum (Fig. 17.16). A focal bulge of the lateral border usually indicates an underlying mass. Compensatory hyperinflation of not only the right middle and right lower lobes but also the left upper lobe is often more easily appreciated on CT.

Left upper lobe collapse The cardinal features of left upper lobe collapse are fundamentally different from right upper lobe collapse as there is very rarely a horizontal fissure on the left. Consequently, the main

Figure 17.14 Right upper lobe collapse. An example of right upper lobe collapse mimicking an apical cap of fluid (arrow).

direction of volume loss is anteriorly and medially rather than superiorly, and the entire oblique fissure is displaced in that direction parallel to the chest wall on the lateral view. On the frontal view the signs may be variable depending on the degree of collapse, but there is a ‘veil-like’ increased density of the whole of the affected hemithorax in most cases. The increased density is often greatest at the hilum and it gradually fades out laterally, superiorly, and inferiorly without the clear inferior demarcation of the horizontal fissure as seen in right upper lobe collapse.The difference in transradiancy may be relatively subtle and therefore overlooked by the unwary. The other features that aid diagnosis on the frontal view are loss of the normal silhouette of structures

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Figure 17.15 Tight right upper lobe collapse. Note how the collapsed lobe (due to a central bronchogenic carcinoma) results in increased right paramediastinal density.

Figure 17.16 CT of right upper lobe collapse. The collapsed lobe forms a triangular wedge of soft tissue anteriorly in the right hemithorax.

adjacent to the collapse, such as the left heart border, mediastinum, and aortic arch, as these structures are no longer adjacent to aerated lung. There is some variability in which outlines are obscured depending on the degree of collapse. In cases of relatively less severe collapse, the left heart border, left mediastinal outline and aortic knuckle are obscured (see Fig. 17.5), whereas in more severe cases the apical segment of the left lower lobe is hyperexpanded superiorly adjacent to the aortic arch and somewhat paradoxically the aortic knuckle outline is therefore visible in more severe cases as it is adjacent to aerated lung (Fig. 17.17A). The Luftsichel sign (described above; see Fig. 17.4) is a particular manifestation of the hyperexpansion, and literally describes an ‘air crescent’ which may be seen between the aortic arch and the medial border of the collapse. On the lateral view the anterior outline of the ascending thoracic aorta can be seen with unusual clarity and this is due to compensatory hyperinflation of the right upper lobe across the midline and rotation of the medi-

Figure 17.17 Left upper lobe collapse. (A) A typical example of left upper lobe collapse demonstrating increased angulation between the left main bronchus and the lower lobe bronchus (arrow) on the frontal view. The aortic knuckle is visible in this example due to compensatory hyperinflation of the left lower lobe. (B) The lateral view demonstrates anterior displacement of the oblique fissure. Note the increased retrosternal lucency (see Fig. 17.18).

astinum so the anterior aspect of the aorta is outlined by aerated lung tangential to the X-ray beam (Fig. 17.17B). This feature is often readily appreciated on CT (Fig. 17.18). On the frontal radiograph the left main bronchus is reorientated and has a more horizontal course than usual. The superior displacement of this structure results in angulation between the left main bronchus and the left lower lobe bronchus (Fig. 17.17A). The CT appearances of left upper lobe collapse are similar to that of the right upper lobe with a triangular soft tissue density, the apex at the origin of the upper lobe bronchus and the base against the anterior chest wall, adjacent to the left border of the mediastinum. However, in the left upper lobe the lingular segment is seen as a density closely opposed to the left heart border. Rarely, left upper lobe collapse may mimic right upper lobe collapse (Fig. 17.19). The appearance is due to collapse of the apicoposterior and anterior segments of the left upper lobe with sparing of the lingular portion resulting in a concavity to the inferior border of the collapse, even in the absence of a left

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Figure 17.18 Left upper lobe collapse. Intravenous contrastenhanced CT of left upper lobe collapse shows increased wedge-shaped density of the left upper lobe adjacent to the mediastinum. Note the displacement of the right lung across the midline anteriorly, resulting in retrosternal hyperlucency and increased clarity of the anterior ascending thoracic aorta on the lateral view (see Fig. 17.17B).

collapsed lobe lies obliquely in the chest, more parallel with the major fissure, the only sign on the frontal radiograph may be indistinctness of a portion of the right atrial border (Fig. 17.21). By comparison, the triangular density of the collapsed right middle lobe is relatively easy to identify on the lateral view, with approximation of the minor and inferior portion of the major fissure, the apex of the triangle being at the hilum (Fig. 17.21B). In increasingly severe collapse the triangular shape is less marked as the fissures become almost parallel with only a thin wedge of density separating them. The CT appearances are characteristically of a triangularshaped density of varying size adjacent to the heart border. Depending on the orientation of the collapse, only a small portion may be identified on each section as the collapse represents a relatively flat sheet of tissue. The so-called middle lobe syndrome refers to a collapsed right middle lobe with bronchiectasis due to a focal bronchostenosis secondary to pulmonary tuberculosis. Although in theory any lobe may be affected, the middle lobe is the most common, resulting in characteristic CT features (Fig. 17.23).

Right and left lower lobe collapse minor fissure5. Apart from being on the left, isolated collapse of the lingula has a very similar appearance to right middle lobe collapse (Fig. 17.20).

Right middle lobe collapse The features of right middle lobe collapse may be extremely subtle on the frontal view and consequently easy to overlook. The collapsed lobe lies adjacent to the right heart border and there is loss of the silhouette of this structure to a variable degree (Fig. 17.21). There may or may not be a recognizable increase in density depending on the orientation of the collapse relative to the X-ray beam. When the collapse is orientated roughly parallel to the beam or if the patient is in a lordotic position, a triangular, sail-shaped density may be seen adjacent to the heart border (Fig. 17.22). However, if the

The features of right and left lower lobe collapse are very similar and will be considered together. In collapse of the lower lobes, the oblique fissure is displaced posteriorly and medially, and the collapsed lobe lies in the posteromedial portion of the chest, a feature readily appreciated on CT (see Fig. 17.11). On the frontal radiograph, the collapsed lower lobes usually form a triangular density behind the heart (Fig. 17.24). The medial portion of the hemidiaphragm may be obscured as it is no longer outlined by aerated lung (Fig. 17.25), but if the inferior pulmonary ligament is incomplete and does not attach to the diaphragm, the medial contour of the diaphragm may still be visualized. On the lateral radiograph, a posterior portion of the hemidiaphragm may not be seen (Fig. 17.24B), but in more severe collapse the contour may reappear as it becomes outlined by aerated lung from the

Figure. 17.19 Atypical left upper lobe collapse. (A) The frontal radiograph demonstrates the inferior concave border of the collapsed lobe and resembles a right upper lobe collapse. (B, C) CT images show increased triangular density to the left of the mediastinum (B), which does not extend along the left heart border (C), a feature usually seen in left upper lobe collapse. The appearance is due to sparing of the lingular segments.

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Figure 17.20 Lingular collapse. (A) Frontal view of isolated collapse of the lingular segments of the left upper lobe showing loss of clarity of the left heart border and a raised hemidiaphragm. (B) The similarity to a right middle lobe collapse can be appreciated on the lateral view.

Figure 17.21 Right middle lobe collapse. (A) Frontal view of a typical example showing loss of clarity of the right heart border. (B) The lateral view shows the wedge-shaped density extending anteriorly from the hilum.

Figure 17.22 Right middle lobe collapse. An example showing a triangular-shaped density adjacent to the right heart border.

Figure 17.23 Middle lobe syndrome. High-resolution CT showing right middle lobe collapse and bronchiectasis due to previous tuberculous infection.

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Figure 17.25 Left lower lobe collapse. A typical appearance of left lower lobe collapse resulting in a triangular density behind the heart (arrowheads). The contour of the medial left hemidiaphragm is lost.

Figure 17.24 Right lower lobe collapse. (A) Frontal view of an example of right lower lobe collapse demonstrating a triangular density which does not obscure the right hemidiaphragm silhouette. (B) The lateral radiograph shows the typical features of increased density of the posterior costophrenic angle and loss of the silhouette of the right diaphragm posteriorly.

hyperexpanded upper lobe. In addition, the vertebral column appears progressively denser inferiorly in lower lobe collapse (Fig. 17.24B), whereas normally the converse is true. On the frontal radiograph the lower lobe pulmonary artery is usually not seen in lower lobe collapse as it is no longer outlined by aerated lung (Fig. 17.26). The major airways, including the right and left main bronchi, are also displaced more vertically in lower lobe collapse and often the relevant aircontaining bronchus can be identified as leading directly into the triangular density of the collapsed lobe. There are several features involving the upper mediastinum which are sometimes helpful in diagnosing lower lobe collapse35. The first of these is the ‘superior triangle sign’ and refers to a triangular density to the right of the mediastinum seen in right lower lobe collapse due to displacement of anterior junctional structures36 (Fig. 17.26). The appearance should not be confused with right upper lobe collapse. The ‘flat waist sign’ is seen in extensive

collapse of the left lower lobe and describes flattening of the contours of the aortic knuckle and main pulmonary artery due to cardiac rotation and displacement to the left37. Third, the outline of the superior aortic knuckle may be lost in severe left lower lobe collapse35. On CT, the collapsed lower lobes form a triangle of soft tissue density posteriomedially in the thorax, adjacent to the spine. On the left, the collapsed lower lobe is seen to drape over the descending aorta, giving a focal convexity to the lateral border, a feature which potentially can cause confusion with an underlying mass on an unenhanced CT (Fig. 17.11).

Whole lung collapse Collapse of an entire lung results in complete opacification or ‘white-out’ of the affected hemithorax. In adults, the cause is often an obstructing neoplasm in the right or left main bronchi (see Fig. 17.1). There is marked volume loss with compensatory hyperinflation of the contralateral lung across the midline. The cardinal feature of volume loss can help discriminate between collapsed lung and a large pleural effusion, the latter usually resulting in mediastinal shift to the contralateral side. The lateral radiograph shows accentuation of the retrosternal space as the displacement of the contralateral lung is greatest anteriorly (see Fig. 17.1). By comparison, the opacity of the hemithorax is more uniform on the lateral view in large pleural effusion and may be a useful discriminating feature in equivocal cases.

Combinations of lobar collapse Occasionally various combinations of lobar collapse occur. Collapse of the right middle and right lower lobes is often due to an obstructing lesion in the bronchus intermedius (Fig. 17.27). The features are similar to right lower lobe collapse with the exception that the opacity extends laterally to the costophrenic

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Figure 17.26 Superior triangle sign. (A) An initial image shows the normal appearances (note the lower lobe artery is clearly visible). (B) The subsequent image shows a right lower lobe collapse demonstrating the superior triangle sign (arrow) (which should not be confused with a right upper lobe collapse). The lower lobe artery can no longer be seen.

Figure 17.27 Combined right middle and right lower lobe collapse. (A) On the frontal view the increased density extends to the right costophrenic angle. (B) On the lateral view the increased density also extends from the anterior to the posterior chest wall. The cause in this case was a bronchogenic carcinoma obstructing the bronchus intermedius.

angle on the frontal view and from the front to the back of the hemithorax on the lateral view5 (Fig. 17.27B). Collapse of the right upper and right middle lobes is more unusual as these lobes do not have a common bronchial origin which spares the lower lobe. In adults the cause is often a carcinoma which obstructs one bronchus and causes extrinsic compression of the other due to mass

effect. Combined collapse of the right upper and right middle lobes results in an appearance very similar to left upper lobe collapse on both frontal and lateral radiographs and CT38. Both bilateral lower lobe and upper lobe collapse are exceedingly rare and may occur as a result of metachronous bronchial neoplasms or mucous plugging (Fig. 17.28).

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Figure 17.28 Bilateral lower lobe collapse. Bilateral triangular densities are seen with obscuration of the medial portions of the hemidiaphragms. The cause was mucous plugging.

REFERENCES 1. Tuddenham W J 1984 Glossary of terms for thoracic radiology: recommendations of the Nomenclature Committee of the Fleischner Society. Am J Roentgenol 143: 509–517 2. Naidich D P, McCauley D I, Khouri N F, Leitman B S, Hulnick D H, Siegelman S S 1983 Computed tomography of lobar collapse: 1. Endobronchial obstruction. J Comput Assist Tomogr 7: 745–757 3. Naidich D P, McCauley D I, Khouri N F, Leitman B S, Hulnick D H, Siegelman S S 1983 Computed tomography of lobar collapse: 2. Collapse in the absence of endobronchial obstruction. J Comput Assist Tomogr 7: 758–767 4. Stein L A, Vidal J J, Hogg J C, Fraser R G 1976 Acute lobar collapse in canine lungs. Invest Radiol 11: 518–527 5. Proto A V, Tocino I 1980 Radiographic manifestations of lobar collapse. Semin Roentgenol 15: 117–173 6. Proto AV 1984 The chest radiograph: anatomic considerations. Clin Chest Med 5: 213–246 7. Lodin H 1957 Mediastinal herniation and displacement studied by transversal radiography. Acta Radiol 48: 337–350 8. Proto A V, Moser E S Jr 1987 Upper lobe volume loss: Divergent and parallel patterns of vascular reorientation. RadioGraphics 7: 875–887 9. Webber M, Davies P 1981 The Luftsichel: an old sign in upper lobe collapse. Clin Radiol 32: 271–275 10. Kattan K R, Eyler W R, Felson B 1980 The juxtaphrenic peak in upper lobe collapse. Semin Roentgenol 15: 187–193 11. Cameron D C 1993 Juxtaphrenic peak (Katten’s sign) is produced by rotation of an inferior accessory fissure. Australas Radiol 37: 332–335 12. Davis S D, Yankelevitz D F, Wand A, Chiarella D A 1996 Juxtaphrenic peak in upper and middle lobe volume loss: assessment with CT. Radiology 198: 143–149 13. Golden R 1925 The affect of bronchostenosis upon the roentgen-ray shadows in carcinoma of the bronchus. Am J Roentgenol Radiat Ther 13: 21–30 14. Naidich D P, Webb W R, Müller N L, Krinsky G A, Zerhouni E A, Siegelman S S 1999 Computed tomography and magnetic resonance of the thorax, 3rd edn. Lippincott–Raven, Philadelphia

15. LoCicero J, Costello P, Campos C T et al 1996 Spiral CT with multiplanar and three-dimensional reconstructions accurately predicts tracheobronchial pathology. Ann Thorac Surg 62: 818–822 16. Woodring J H 1988 Determining the cause of pulmonary atelectasis: a comparison of plain radiography and CT. Am J Roentgenol 150: 757–763 17. Henschke C I, Davis S D, Auh Y et al 1987 Detection of bronchial abnormalities: comparison of CT and bronchoscopy. J Comput Assist Tomogr 11: 432–435 18. Webb W R, Gamsu G, Speckman J M 1983 Computed tomography of the pulmonary hilum in patients with bronchogenic carcinoma. J Comput Assist Tomogr 1983;7:219–225. 19. Naidich D P, Lee J-J, Garay S M, McCauley D I, Aranda C P, Boyd A D 1987 Comparison of CT and fibreoptic bronchoscopy in the evaluation of bronchial disease. Am J Roentgenol 148: 1–7. 20. Mayr B, Ingrisch H, Häussinger K, Huber R M, Sunder-Plassmann L 1989 Tumours of the bronchi: role of evaluation with CT. Radiology 172: 647–652 21. Onitsuka H, Tsukuda M, Araki A, Murakami J, Torii Y, Masuda K 1991 Differentiation of central lung tumor from postobstructive lobar collapse by rapid sequence computed tomography. J Thorac Imaging 6: 28–31 22. Reinig J W, Ross P 1984 Computed tomography appearance of Golden’s “S” sign. J Comput Assist Tomogr 8: 219–223 23. Khoury M B, Godwin J D, Halvorsen R A, Putman C E 1985 CT of obstructive lobar collapse. Invest Radiol 20: 708–716 24. Woodring J H 1988 The computed tomography mucous bronchogram sign. J Comput Assist Tomogr 12: 165–168 25. Glazer H S, Anderson D J, Sagel S S 1989 Bronchial impaction in lobar collapse: CT demonstration and pathologic correlation. Am J Roentgenol 153: 485–488 26. Saida Y, Itai Y, Kujiraoka Y, Tohno E, Shimizu H T 1997 Bronchoarterial inversion: radiographic–CT correlation in combined right middle and lower lobe collapse. J Thorac Imaging 12: 59–63 27. Flanagan J J, Flower C D, Dixon A K 1982 Compensatory emphysema shown by computed tomography. Clin Radiol 33: 553–554 28. Blankenbaker D G 1998 The Luftsichel sign. Radiology 208: 319–320 29. Woodring J H, Reed J C 1996 Radiographic manifestations of lobar atelectasis. J Thorac Imaging 11: 109–144 30. Mayr B, Heywang S H, Ingrisch H, Huber R M, Häussinger K, Lissner J 1987 Comparison of CT with MR imaging of endobronchial tumors. J Comput Assist Tomogr 11: 43–48 31. Shioya S, Haida M, Ono Y, Fukuzaki M, Yamabayashi H 1988 Lung cancer: differentiation of tumor, necrosis, and atelectasis by means of T1 and T2 values measured in vitro. Radiology 167: 105–109 32. Herold C J, Kuhlman J E, Zerhouni E A 1991 Pulmonary atelectasis: signal patterns with MR imaging. Radiology 178: 715–720 33. Bourgouin P M, McLoud T C, Fitzgibbon J F et al 1991 Differentiation of bronchogenic carcinoma from postobstructive pneumonitis by magnetic resonance imaging: histopathologic correlation. J Thorac Imaging 6: 22–27 34. Nestle U, Walter K, Schmidt S et al 1999 18F-deoxyglucose positron emission tomography (FDG-PET) for the planning of radiotherapy in lung cancer: high impact in patients with atelectasis. Int J Radiat Oncol Biol Phys 44: 593–597 35. Kattan K R 1980 Upper mediastinal changes in lower lobe collapse. Semin Roentgenol 15: 183–186 36. Kattan K R, Felson B, Holder L E, Eyler W R 1975 Superior mediastinal shift in right lower lobe collapse: the “upper triangle sign.” Radiology 116: 305–309 37. Kattan K R, Wiot J F 1976 Cardiac rotation in left lower lobe collapse: “the flat waist sign.” Radiology 118: 275–279 38. Saterfiel J L, Virapongse C, Clore F C 1988 Computed tomography of combined right upper and middle lobe collapse. J Comput Assist Tomogr 12: 383–387

CHAPTER

Pulmonary Neoplasms

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Simon Padley and Sharyn L. S. MacDonald

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Bronchial carcinoma Pulmonary sarcoma and other primary malignant neoplasms Benign pulmonary tumours Benign lymphoproliferative disorders Malignant lymphoproliferative disorders Metastases Evaluation of the solitary pulmonary nodule

such as the inappropriate secretion of antidiuretic hormone or a peripheral neuropathy, are the cardinal symptoms at a stage when lobectomy or pneumonectomy may be curative; whereas hoarseness, chest pain, brachial plexus neuropathy and Horner’s syndrome (Pancoast’s tumour), superior vena caval obstruction, dysphagia and the problems of pericardial tamponade indicate invasion of the mediastinum or chest wall, and a poorer prognosis.

Early diagnosis

BRONCHIAL CARCINOMA Lung cancer is the most common cause of cancer-related death in both men and women1,2.Tobacco smoke is the most important causative agent imparting a 20–30-fold increased risk in smokers compared to non-smokers. Other risk factors include passive smoking3, exposure to inorganic substances such as asbestos, nickel and arsenic, interstitial pulmonary fibrosis and radiotherapy.

Pathology The World Health Organization (WHO) classification1 divides bronchial carcinoma into several histological subtypes. Four major cell types: adenocarcinoma, squamous cell carcinoma, large cell carcinoma and small cell carcinoma account for 95% of cases. Of the non-small cell carcinomas, adenocarcinoma accounts for 30–35% of cases. Its relative incidence is rising; it is now the predominant histological subtype in many countries4. The relative incidence of bronchiolo-alveolar carcinoma, which is a subtype of adenocarcinoma, is also increasing as smoking declines. In comparison, the relative incidence of squamous cell carcinoma (30–35% of cases) is decreasing. Large cell carcinoma accounts for 10–15% of cases. Small cell carcinoma accounts for 20–30% of cases.

Clinical presentation Clinical features vary with cell type5 and extent of disease. Approximately 25% of patients are asymptomatic at the time of diagnosis, following the discovery of an abnormality on chest radiograph or computed tomography (CT). Pneumonia is the other common presentation. Cough, wheeze, haemoptysis, symptoms of pneumonia and paraneoplastic syndromes,

Late presentation is one of the factors that have contributed to the lack of significant improvement in survival rates over the past 30 years, despite advances in detection methods and treatments. Median survival from diagnosis has remained at 6–12 months and overall 5-year survival is poor, approximately 5–15%6,7. No study has described definite benefit from screening for lung cancer. Recent large CT studies have demonstrated increased lung cancer detection in at-risk populations but many questions remain unanswered. Most importantly, there is no current evidence that screening confers a disease-specific survival benefit. In an effort to provide definitive evidence, a large-scale trial (National Lung Cancer Screening Trial [USA]) began in 2002 and is due to continue until 2009, after which the findings will be reported. This is a study of overall and comparative utility of chest radiography and spiral CT for lung cancer screening and has recruited 50 000 patients.

Imaging techniques Although lung cancers are frequently detected on chest radiograph, the chest radiograph is of limited use in the evaluation and staging of lung cancer. CT is a more sensitive test for the detection of lung cancer, and is the imaging investigation most widely used to evaluate the primary tumour and the extent of intrathoracic and regional extrathoracic disease. Magnetic resonance imaging (MRI) may provide additional information in selected cases when mediastinal or chest wall invasion is suspected8. Positron-emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) has become a very useful tool in lung cancer staging. It has been found to increase the accuracy of preoperative staging, particularly when used in conjunction with CT (PET–CT)9.

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Imaging features The thoracic imaging features of bronchial carcinoma are discussed under three headings: peripheral tumours; central tumours (arising in a large bronchus at or close to the hilum); and staging intrathoracic spread of bronchial carcinoma.

Peripheral tumours Approximately 40% of bronchial carcinomas arise beyond the segmental bronchi, and in 30% a peripheral mass is the sole radiographic finding10 (Fig. 18.1). Tumour shape and margins Tumours at the lung apex (Pancoast’s tumours, superior sulcus tumours) may resemble apical pleural thickening; however, the majority of peripheral lung cancers are approximately spherical or oval in shape. Lobulation, a sign that indicates uneven growth rates in different parts of the tumour, is common. Occasionally, a dumb-bell shape is encountered or two nodules are seen next to one another. The term corona radiata is used to describe numerous fine strands radiating into the lung from a central mass, sometimes with transradiant lung parenchyma between these strands11. While not specific, this sign is highly suggestive of bronchial carcinoma (Fig. 18.2). Absolutely spherical, sharply defined, smooth-edged nodules due to carcinoma of the lung are rare. A peripheral line shadow or ‘tail’ may be seen between a peripherally located mass lesion and the pleura12, a phenomenon that occurs in both benign and malignant lesions. When associated with carcinoma of the lung, the ‘tail’ probably represents either plate-like atelectasis secondary to bronchial obstruction beyond the mass, or septal oedema due to lymphatic obstruction. Although the edges of a tumour are frequently well defined, some peripheral cancers, notably adenocarcinoma and bronchiolo-alveolar carcinoma, have ill-defined edges similar to pneumonia (Fig. 18.3). Cavitation may be identified in tumours of any size (Fig. 18.4) and is best demonstrated by CT (Fig. 18.5). Squamous cell

Figure 18.1 Bronchial carcinoma in the left lower lobe showing typical rounded, slightly lobular configuration. The mass shows a notch posteriorly.

carcinoma is the most likely cell type to show cavitation. The walls of the cavity are of irregular thickness and may contain tumour nodules, but sometimes the wall has smooth inner and outer margins. The cavity wall is usually 8-mm thick or greater. Fluid levels are common. Calcification within bronchogenic carcinomas is rarely seen on chest radiograph but is identified on CT in 6–10% of cases13,14. Some foci of calcification represent pre-existing calcified granulomatous disease engulfed by tumour (Fig. 18.6). However, amorphous or cloudlike calcification consistent with dystrophic tumour calcification is seen in a significant proportion (Fig. 18.7). Most calcified tumours are large with a diameter of 5 cm or more, but calcification can also be seen in small peripheral tumours. Other findings Air bronchograms and bubble-like lucencies or pseudocavitation may be seen within lung cancers, in particular with bronchiolo-alveolar carcinoma and adenocarcinoma15. Occasionally, dilated mucus-filled bronchi (bronchocele, mucocele, mucoid impaction) are seen distal to a carcinoma obstructing a segmental or subsegmental bronchus16. Ground-glass attenuation may be seen as a component of nodules and is associated with a greater risk of malignancy than that of purely solid nodules. It is more commonly associated with bronchiolo-alveolar carcinoma17, which may present as a purely ground-glass opacity.

Central tumours The cardinal imaging signs of a central tumour are collapse/ consolidation of the lung beyond the tumour and the presence of hilar enlargement, signs that may be seen in isolation or in conjunction with one another. Collapse/consolidation in association with central tumours Obstruction of a major bronchus often leads to a combination of atelectasis and retention of secretions with consequent

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Figure 18.2 CT demonstrating a second primary bronchogenic carcinoma in the right lung in a patient who had undergone a previous left pneumonectomy 7 years earlier. The new tumour has spiculated edges infiltrating into the adjacent lung (corona radiata).

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pulmonary opacity18, but collateral air drift may partially or completely prevent these postobstructive changes. Secondary infection may occur beyond the obstruction. The following features suggest that pneumonia is secondary to an obstructing neoplasm: 1 The shape of the collapsed or consolidated lobe may be altered because of the bulk of the underlying tumour. In cases with lobar collapse due to a central tumour mass, the fissure in the region of the mass is unable to move in the usual manner and, therefore, the fissure may show a bulge (the Golden S sign) (Fig. 18.8). 2 The presence of pneumonia in an at-risk patient, confined to one lobe (or more lobes if there is a common bronchus supplying these lobes) that persists unchanged for longer than 2–3 weeks, or a pneumonia that recurs in the same lobe, particularly if the lobe shows loss of volume and no air bronchograms. Simple pneumonia often clears or spreads to other segments within a few weeks. In practice,

Figure 18.3 (A) Squamous cell carcinoma resembling pneumonia. The entire opacity seen on this radiograph is due to the carcinoma itself. (B) Apical bronchiolo-alveolar cell carcinoma of the left upper lobe with ground-glass attenuation margins.

Figure 18.4 Examples of neoplastic cavitation on chest radiography. (A) The cavity is eccentric (large cell undifferentiated carcinoma). (B) The inner wall of the cavity is irregular and an air–fluid level is present (squamous cell carcinoma). (C) The cavity wall is very thin (squamous cell carcinoma).

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Figure 18.5 CT showing cavitating squamous cell carcinoma. The wall of the cavity is variable in thickness.

complete resolution of pneumonia virtually excludes an obstructing neoplasm as a cause of infection. Although consolidation may improve partially on appropriate antibiotic therapy, it almost never resolves completely if secondary to an underlying carcinoma. Occasionally, the opacified lobe will appear larger than normal because of the build-up of infected secretions beyond the obstructing carcinoma, an appearance that has been labeled the ‘drowned lobe’. 3 The presence of a visible mass or irregular stenosis in a mainstem or lobar bronchus. Careful analysis of CT images will demonstrate the presence of an obstructing tumour in virtually every case of postobstructive atelectasis due to a lung carcinoma19. 4 Simple pneumonia rarely causes radiographically visible hilar adenopathy, though enlarged central nodes may be seen on

Figure 18.6 Calcified infectious granuloma engulfed by lung cancer. CT shows a cluster of densely calcified small nodules almost at the centre of a small carcinoma.

Figure 18.7 Tumour calcification. Large bronchial carcinoma in left lower lobe showing extensive amorphous and cloud-like calcification. Initial examination; no treatment had been given.

CT or MRI. Lung abscess can occasionally be confused with bronchial carcinoma because it may result in hilar or mediastinal adenopathy20. 5 Mucus-filled dilated bronchi may be visible within collapsed lobes on a CT examination as branching, tubular low-density structures, and when seen should prompt a search for a centrally obstructing tumour (Fig. 18.9). Hilar enlargement is a common presenting feature in patients with bronchial carcinoma. It may reflect a proximal tumour, lymphadenopathy, consolidated lung, or a combination of these phenomena21–24. In general, the more lobular the shape, the more likely that metastatic lymphadenopathy is present. A mass superimposed on the hilum may lead to increased density of the hilum owing to summation of the opacity of the mass and that of the normal hilar shadows (Fig. 18.10).This sign may be the only indication of lung cancer on a frontal chest radiograph; when suspected, it is essential to inspect a lateral radiograph with care. Radiographic patterns based on cell type The radiographic pattern of bronchial carcinoma varies to a degree with the cell type, which may aid in the differential diagnosis prior to obtaining histological confirmation25. Early, often massive, hilar or mediastinal lymphadenopathy (Fig. 18.11) and direct mediastinal invasion are well-recognized phenomena in both small cell carcinoma and large cell carcinoma. Adenocarcinoma frequently shows hilar and mediastinal adenopathy26, though the nodal enlargement is not as massive as it is with small cell and large cell undifferentiated tumours. A mass in, or adjacent to, the hilum is a particular characteristic of small cell carcinoma, seen in 78% of cases. A peripheral nodule is very common in adenocarcinoma (72% of cases) and large cell tumours (63% of cases); it occurs approximately twice as often as with squamous or small cell carcinomas. The largest peripheral masses are seen with squamous and large cell tumours, whereas most adenocarcinomas and small cell carcinomas are less than 4 cm in diameter.

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Figure 18.8 Lobe collapse. (A) Collapse of a lobe around a central mass. (B) The middle lobe has undergone collapse, but there is a central mass causing the central portion of both the oblique and horizontal fissures to bulge outwards (arrows).

Squamous cell cancers may attain great size and they cavitate more frequently than the other cell types; in one series cavitation was seen in 12% of squamous cell carcinomas presenting as a peripheral mass, compared with only 4–6% of peripheral large cell and peripheral adenocarcinomas27. Collapse/consolidation of the lung beyond the tumour is the most frequent feature seen with squamous cell carcinoma, in keeping with the predominantly central origin of this form of neoplasm. Pleural effusion (with dyspnoea) is a feature of adenocarcinoma.

Figure 18.9 Fluid-filled dilated bronchi beyond a central obstructing carcinoma are visible in this collapsed and consolidated left lower lobe.

Bronchiolo-alveolar carcinomas arise from the alveoli and the immediately adjacent small airways. They therefore present as peripheral pulmonary opacities rather than with the effects of large airway obstruction. The most common radiographic finding28 is a solitary lobulated or spiculated pulmonary mass indistinguishable from other types of carcinoma. Bubble-like lucencies corresponding to patent small bronchi, air-containing cystic lucencies, or air bronchograms and cavitation may be seen29,30. Bronchiolo-alveolar carcinomas

Figure 18.10 Dense hilum. The right hilum is dense owing to a mass superimposed directly over it. The mass proved to be a squamous cell carcinoma.

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Figure 18.11 Massive mediastinal adenopathy in a patient with small (oat) cell carcinoma of the bronchus. The primary carcinoma is not visible because it lies centrally in the bronchial tree.

may also appear as an ill-defined opacity resembling a patch of pneumonia; homogeneous consolidation of one lobe (which may be expansile); patchy consolidation; atelectasis; or multiple ill-defined nodules spread widely through multiple lobes in one or both lungs (Figs 18.12–18.14). Less commonly, a lepidic (scale-like) growth pattern or focal ground-glass opacity is seen31.

Figure 18.13 Bronchiolo-alveolar carcinoma. (A) Bronchiolo-alveolar carcinoma with widespread lung involvement. The appearance closely resembles bronchopneumonia or pulmonary oedema. (B) CT of a similar case showing the typical airspace filling with an obvious air bronchogram.

Staging intrathoracic spread of tumour

Figure 18.12 Bronchiolo-alveolar carcinoma occupying the right lower lobe. The appearance is identical to consolidation with partial collapse. Air bronchograms are present.

Lung cancer staging provides information about the anatomical extent and histological nature of disease, which allows the most appropriate treatment to be planned and gives an indication of prognosis. In those in whom surgery is not deemed appropriate, assessment of disease burden aids the oncologist to plan radiotherapy and chemotherapeutic regimens, and assists in the assessment of response to therapy. Small cell lung cancer is usually disseminated at the time of diagnosis. It is almost always treated medically, with the role

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Figure 18.14 Bronchiolo-alveolar carcinoma. (A) Bronchiolo-alveolar carcinoma demonstrating lepidote growth in the left upper lobe. CT obtained during fine needle aspiration biopsy. (B,C) Biopsy-proven bronchiolo-alveolar cell carcinoma presenting as diffuse consolidation and ground-glass shadowing on chest radiography (B) and CT (C).

of imaging largely being to determine the extent of intrathoracic (limited versus extensive) and extrathoracic disease for the purposes of treatment planning. The International Staging System for Lung Cancer7 uses the TNM system to describe the findings (Table 18.1), and the stage is derived from the TNM description (Table 18.2) (T

signifies the primary tumour, N the regional lymph nodes and M distant metastases.) The system is used for non-small cell lung cancers. In essence: • Following the 1997 revision of the International Staging System for Lung Cancer7 Stage I has been divided into IA and IB based on demonstrable survival differences between

Table 18.1 TNM DEFINITIONS FOR THE INTERNATIONAL STAGING SYSTEM FOR LUNG CANCER7 Primary tumour (T) TX

Tumour proved by the presence of malignant cells in bronchopulmonary secretions but not visualized radiographically or bronchoscopically, or any tumour that cannot be assessed as in a retreatment staging

T0

No evidence of primary tumour

T1S

Carcinoma in situ

T1

A tumour that is 3 cm or less in its greatest dimension, surrounded by lung or visceral pleura and without evidence of invasion proximal to a lobar bronchus at bronchoscopy* (i.e. not in the main bronchus)

T2

A tumour more than 3 cm in its greatest dimension, or a tumour of any size that either invades the visceral pleura or has associated atelectasis or obstructive pneumonitis extending to the hilar region. At bronchoscopy the proximal extent of demonstrable tumour must be within a lobar bronchus or at least 2 cm distal to the carina. Any associated atelectasis or obstructive pneumonitis must involve less than an entire lung

T3

A tumour of any size with direct extension into the chest wall (including superior sulcus tumours), diaphragm, or the mediastinal pleura or pericardium without involving the heart, great vessels, trachea, oesophagus, or vertebral body; or a tumour in the main bronchus within 2 cm of the carina without involving the carina

T4

A tumour of any size with invasion of the mediastinum or involving the heart, great vessels, trachea, oesophagus, vertebral body, or carina, or presence of malignant pleural effusion**, or with satellite tumour nodule(s) within the ipsilateral primary tumour lobe of the lung

Nodal involvement (N) NX

Regional lymph nodes cannot be assessed

N0

No demonstrable metastasis to regional lymph nodes

N1

Metastasis to lymph nodes in the peribronchial or the ipsilateral hilar region, or both, including direct extension

N2

Metastasis to ipsilateral mediastinal lymph nodes and subcarinal lymph nodes

N3

Metastasis to contralateral mediastinal lymph nodes, contralateral hilar lymph nodes, ipsilateral or contralateral scalene, or supraclavicular lymph nodes

Distant metastasis (M) MX

Presence of distant metastases cannot be assessed

M0

No (known) distant metastasis

M1

Distant metastasis present—specify sites

*The uncommon superficial tumour of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified T1. **Most pleural effusions associated with lung cancer are due to tumour. However, there are a few patients in whom multiple cytopathological examinations of the fluid reveal no tumour. In these cases the fluid is non-bloody and is not an exudate. When these elements and clinical judgement dictate that the effusion is not related to the tumour, the effusion should be excluded as a staging element and the patient’s disease should be staged T1, T2, or T3. Pericardial effusion is classified according to the same rules.

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Table 18.2

• THE CHEST AND CARDIOVASCULAR SYSTEM

STAGING GROUPING. TNM SUBSETS7

Stage

TNM subset

0

Carcinoma in situ

IA

T1N0M0

IB

T2N0M0

IIA

T1N1M0

IIB

T2N1M0

of collapsed lung relative to tumour on contrast-enhanced CT may assist; collapsed lung tends to enhance to a greater extent than the adjacent tumour32, although this is not always the case32–34.T1 and T2 tumours are the most amenable to surgical resection using standard techniques. T3 tumours that involve the chest wall or mediastinum to a limited extent may also be candidates for surgical resection, albeit with more complex techniques. T4 tumours are irresectable.

T3N0M0 IIIA

T3N1M0 T1N2M0 T2N2M0 T3N2M0

IIIB

T4N0M0 T4N1M0 T4N2M0 T1N3M0 T2N3M0 T3N3M0 T4N3M0

IV

Any T Any N M1

*Staging is not relevant for occult carcinoma, designated TXM0N0. For each stage, the prognoses, or estimated 5-year survival rates, in Europe are as follows:

• Stage IA—60% • Stage IB—38% • Stage IIA—34% • Stage IIB—24% • Stage IIIA—13% • Stage IIIB—5% (Stage IIIB and IV lesions are non-resectable.) • Stage IV—< 1%

patients with T1N0M0 lesions at presentation compared with T2N0M0 lesions. Both these lesions are resectable with a reasonable hope of cure. • For similar reasons, Stage II has also been subdivided into IIA and IIB. These lesions are the same T lesions as stage I but with hilar node involvement or resectable mediastinal/ chest wall invasion. They are resectable for potential cure but with less good prognosis than stage I lesions. • Stage III is divided into IIIA, in which there is locally extensive intrathoracic disease and/or hilar and ipsilateral lymph node involvement which may be surgically resectable, and IIIB where the intrathoracic disease is beyond the limits of conventional surgical resection. IIIB tumours may be considered localized in terms of planning radiotherapy. • Stage IV includes all patients with distant metastatic disease. Staging the primary tumour CT is the most commonly used tool in evaluation of the primary tumour. Defining the primary tumour in terms of T staging enables prediction of resectability.Tumour size, location, margins and relationship to adjacent structures should be described. Assessment of tumour size may not be straightforward as distinction from adjacent collapsed lung may be impossible. Differential enhancement

Mediastinal invasion Plain radiograph evidence of mediastinal invasion relies on demonstrating phrenic nerve paralysis. Caution is needed, however, before deciding that a high hemidiaphragm is caused by phrenic nerve invasion, because lobar collapse can also lead to elevation of a hemidiaphragm, a subpulmonary effusion may mimic it, and diaphragmatic eventration is common. The major CT and MRI signs of mediastinal invasion include the demonstration of visible tumour deep within the mediastinal fat, particularly if tumour surrounds the mediastinal vessels, oesophagus, or proximal mainstem bronchi (Figs 18.15, 18.16). Associated pneumonia or atelectasis may make it very difficult to determine whether or not mediastinal contact is present. Even clear-cut contact with the mediastinum is not enough for the diagnosis of invasion, and the apparent interdigitation of tumour with mediastinal fat can be a misleading sign on both CT and MRI. Glazer et al35 showed that the presence of (A) less than 3 cm of contact with the mediastinum; (B) less than 90 degrees of circumferential contact with the aorta; or (C) a visible mediastinal fat plane between the mass and any vital mediastinal structures indicated a very high likelihood of technical resectability, even if the tumour had crossed into the mediastinum, and that most tumours in their series conforming to this description had no mediastinal invasion at surgery. When the question is turned round to enquire as to the criteria for irresectability, however, the answer is less certain36–39. Tumours that obliterate fat planes or show greater contact than that described above are not necessarily irresectable, though the greater the degree of invasion and the extent of contact, the more likely it is that there is significant mediastinal involvement37. MRI does not appear to offer any advantages over CT for the routine diagnosis of mediastinal invasion, its role being limited to problem solving in specific cases (Fig. 18.16)8. Before the advent of multidetector CT (MDCT), the multiplanar capabilities of MRI (Fig.18.17) could be used to advantage to identify involvement of major mediastinal blood vessels8,40 and the tracheal carina. MDCT has largely obviated the need to proceed to MRI to take advantage of multiplanar imaging alone; however, MRI sequences optimized for evaluation of the heart and vessels may still offer advantages where there is concern about invasion of hilar or mediastinal vessels41, the heart or pericardium. Chest wall invasion The presence of chest wall invasion alone does not preclude surgical resection, though it does adversely affect prognosis42,43. The necessarily more extensive surgery is associated with increased morbidity and mortality and it therefore helps the surgeon to know the extent of any chest wall invasion pre-operatively.

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Figure 18.15

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(A) Extensive deep mediastinal invasion by primary bronchial carcinoma. (B) On lung windows there are pulmonary metastases.

Figure 18.16 MRI of involved mediastinal nodes in a patient with a right lower lobe non-small cell lung cancer.

Figure 18.17 MRI of a left lower lobe tumour that has directly invaded the aortic wall which has altered signal adjacent to the tumour.

The diagnosis of chest wall involvement adjacent to a tumour is unreliable on CT, unless there is clear-cut bone destruction or a large soft tissue mass38–40,42–45 (Fig. 18.18). Local chest wall pain remains the single most specific indicator of whether or not the tumour has spread to the parietal pleura or chest wall44. Contact with the pleura on CT examination, even if the pleura is thickened (see Fig. 18.21), does not necessarily indicate invasion, though the greater the degree of contact and the greater the pleural thickening, the more likely it is that the parietal pleura has been invaded, particularly if the extrapleural fat plane is obliterated45. A definite extrapleural mass that is not explicable by previous chest trauma is likely to be the result of invasion by tumour45, but even this sign may be misleading since soft tissue swelling may be due to inflammation and fibrosis rather than neoplasm46. Conversely, a clear extrapleural fat plane adjacent to the mass may be helpful, but again not definitive, in excluding chest wall invasion47 (Fig. 18.19). In selected cases MRI has proved to be better than CT in demonstrating chest wall48,49 and diaphragmatic invasion. MRI is regarded as the optimal modality for demonstrating the extent of superior sulcus tumours (Pancoast’s tumour) (Fig. 18.18), reliably diagnosing mediastinal invasion, extension into the root of the neck and involvement of vascular and neural structures. Transthoracic ultrasound can identify chest wall invasion with a high degree of accuracy; however, the technique is rarely used for this purpose in Europe or the USA50. 99m Tc radionuclide skeletal scintigraphy is a sensitive technique with which to assess bone invasion and it may be positive when the plain radiograph still shows no bony abnormality. Intrathoracic lymph node metastases The American Thoracic Society’s description of nodal stations is the most widely used system to define the anatomical position of lymph nodes. Lung cancers normally spread to ipsilateral hilar nodes, then

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Figure 18.18 Chest wall invasion by a Pancoast’s tumour. Involvement of the soft tissues of the chest wall is appreciated on the (A) coronal T1- and (B) T2-weighted MRI images. (C) This example from a different patient shows the better demonstration of bone involvement (arrows) on CT.

ipsilateral mediastinal, contralateral mediastinal and supraclavicular nodes. Though nodal spread is most often sequential, skip metastases to mediastinal nodes in the absence of hilar nodes is seen in 33% of cases51. Generally chest radiography is insensitive for nodal staging. However, the presence of enlarged hilar or paratracheal nodes has been shown to be specific (92%) for N2–N3 disease8. Lymph node assessment on CT and MRI is limited to size, shape and location, with size being the major criterion used to predict metastatic involvement (Fig. 18.20). Normal mediastinal lymph node size on CT or MRI varies according to the location of the nodes within the mediastinum, but a simple and reasonably accurate rule is that nodes with a short axis diameter of less than 10 mm fall within the 95th percentile and nodes above this size should, therefore, be considered enlarged. The problem with using size as the only criterion for malignant involvement is that intrathoracic lymph node enlargement

has many nonmalignant causes, including previous tuberculosis, histoplasmosis, pneumoconiosis, sarcoidosis and, most importantly, reactive hyperplasia to the tumour (Fig. 18.21) or associated pneumonia/atelectasis: it has repeatedly been shown that one-half to two-thirds of enlarged nodes draining postobstructive pneumonia/atelectasis are free of tumour52. Conversely, microscopic involvement by tumour can be present in normal sized nodes. It will, therefore, be clear that there is no measurement above which all nodes can be assumed to be malignant and below which all can be considered to be benign. The sensitivity and specificity of CT for diagnosing metastatic involvement of mediastinal lymph nodes varies greatly in different published series, reflecting different size criteria and the methods used to confirm or exclude lymph node metastases. A reasonable generalization in the USA (where fungal infection is endemic) is that both sensitivity and specificity are in the 50 to low 60% range when the cut-off point for normal is a short axis diameter of 1 cm8,53,54. Better specificity figures

Figure 18.19 Cavitating bronchogenic carcinoma. There is preservation of the extrapleural fat plane at the point of contact with the chest wall. Although the pleura may be involved the chest wall is likely to be otherwise spared.

Figure 18.20 True-positive CT for metastatic lymphadenopathy. There are several enlarged nodes in the right paratracheal area. The largest measured 16 mm in its short axis diameter (arrow). The primary tumour was a bronchial carcinoma in the right lung.

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Figure 18.21 False-positive CT for metastatic mediastinal lymphadenopathy. The largest of the right paratracheal nodes (arrow) is 17 mm in its short axis diameter. This node proved to be free of malignant tumour at thoracotomy. The enlargement was due to reactive hyperplasia. None of the hilar or mediastinal nodes in this patient was involved by tumour. The primary tumour can be seen in the right lung. It shows extensive contact with the right chest wall, but no definite evidence of invasion of the chest wall on CT. At surgery there was invasion of the soft tissues of the chest wall but no spread to the ribs.

have been obtained in Europe55 and Japan56, probably because the prevalence of coincidental histoplasmosis is much lower than in the USA.The positive predictive value for nodal metastatic disease may be improved (to up to 95%) by ensuring that nodes draining the tumour are larger than nodes elsewhere in the mediastinum55. The accuracy of MRI, despite its improved contrast resolution, is limited by the same constraint as for CT of overlap of features of benign and malignant causes of node enlargement. Although it is generally considered that the MRI signal within nodes is not a useful predictor of involvement, a recent study has reported that STIR imaging produces sufficient signal

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difference between normal and pathological nodal tissue to detect metastases with 93% sensitivity and 87% specificity57. The previously cited advantage of MRI over CT in nodal detection due to its ability to distinguish small nodes from vessels without intravenous enhancement has been effectively negated by the advantages of MDCT. Endoscopic ultrasound (EUS) can be used to assess the size and morphology of, and to guide fine needle aspiration (FNA) of, aortopulmonary, subcarinal and posterior mediastinal nodes58, achieving greater sensitivity and specificities for nodal involvement than CT and PET in some series59. Ultrasound assessment (± FNA) of supraclavicular lymph nodes improves sensitivity for detection of supraclavicular lymph node involvement; its routine use has been suggested as a method to improve the accuracy of pre-operative staging60. PET imaging with fluorodeoxyglucose (FDG) is increasingly used for staging lung carcinoma, with published studies consistently demonstrating greater accuracy compared to CT and MRI in the detection of nodal disease (Fig. 18.22). Falsepositive results still occur, most commonly due to inflammation and reactive hyperplasia. In one meta-analysis of nodal staging the sensitivity of PET was 79% and specificity was 91%, compared with 60% and 70% respectively for CT61. Fused PET–CT imaging provides registration of FDG metabolic activity with the anatomical detail of CT (Fig. 18.22); it has been reported to be more accurate than PET or CT alone in staging patients with non-small cell lung cancer62–64. Decision analysis studies have shown that PET can be incorporated into the work-up of lung cancer in a cost-effective manner, with savings derived from identifying inoperable patients before thoracotomy65,66. Mediastinoscopy and mediastinotomy remain the most widely employed techniques for mediastinal lymph node sampling. They have high sensitivity and specificity for detecting malignant disease and, although invasive, are indicated prior to thoracotomy when other forms of imaging suggest nodal involvement.

Figure 18.22 Recurrent malignant right hilar lymph nodes from a small peripheral non-small cell lung cancer. (A) CT demonstrates nodes at the right hilum. (B) The PET–CT image confirms high FDG uptake in keeping with malignant involvement.

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Pleural involvement may occur as a result of direct spread, lymphatic involvement, or tumour emboli. On occasion, adenocarcinoma takes the form of a sheet of lobular pleural thickening indistinguishable from malignant mesothelioma. A pleural effusion in association with a primary lung cancer designates the tumour as being T4. The exception is the few patients who have clinical evidence of another cause for the effusion (e.g. heart failure) and in whom cytology examinations of multiple pleural fluid samples are negative for tumour cells, in which case the effusion can be disregarded as a staging criterion. Attempts to characterize the nature of the pleural fluid based on density measurements at CT or signal intensities at MRI have not so far proved useful. Several studies suggest PET may have a role in the evaluation of pleural effusion in patients with lung cancer, although this requires further evaluation67–69. Summary Staging the intrathoracic extent of lung cancer is a multidisciplinary process utilizing imaging, bronchoscopy and biopsy. Chest radiography, CT and PET (where available) are currently the routine imaging procedures for assessing intrathoracic spread and determining resectability, with MRI and ultrasound reserved for specific indications. The essential points to establish when staging the intrathoracic extent of non-small cell cancers are: (A) whether or not the tumour has spread to hilar or mediastinal nodes; (B) if it has, which nodal groups are involved; (C) whether or not the tumour has invaded the chest wall or mediastinum; and (D) if it has, whether it is still potentially curable surgically. If chest radiography and CT ± PET show no evidence of spread beyond the lung (other than to ipsilateral hilar nodes) in a patient who is suitable for surgery, and in whom bronchoscopy shows the tumour to be resectable, then that patient should be offered surgical resection without further pre-operative invasive procedures. Spread to ipsilateral nodes, whilst not necessarily precluding surgical resection, has a significantly adverse effect on prognosis and if surgery is undertaken, it is performed with the understanding that 5-year survival rates are poor. The poor specificity of CT in determining nodal involvement must be appreciated. Nodal enlargement, whilst probably due to metastatic carcinoma, may also be due to coincidental benign disease, reactive hyperplasia to the presence of the tumour, or to any associated obstructive consolidation/atelectasis. Thus biopsy confirmation of neoplastic nodal involvement by mediastinoscopy, mediastinotomy, or needle aspiration is usually essential before a patient is denied surgery. Positive PET findings for nodal involvement do not obviate the need for histological confirmation of nodal involvement. However, in patients with no enlarged lymph nodes on CT and normal findings on PET, the likelihood of nodal involvement is so low that mediastinoscopy can be omitted. For lung cancers that have invaded the mediastinum or chest wall, it is important to decide whether the tumour is nevertheless resectable for possible cure, again recognizing that the prognosis will be poorer than for tumours confined to the lung. CT may show definitively that the tumour is too

extensive for resective surgery (i.e. that it is a T4 lesion)54. Alternatively CT may leave the issue in doubt and MRI may then help to solve the problem.

Extrathoracic staging of lung cancer Lung cancer is commonly associated with widespread haematogenous dissemination at the time of presentation. Sites of spread include the adrenal glands, bones, brain, liver and more distant lymph nodes. Detection of metastatic disease precludes surgical resection of the primary tumour. There is evidence to support the approach of extending the staging chest CT to include the liver and adrenals, with no further imaging being undertaken in the absence of clinical features suggesting metastatic disease. Currently, there is a lack of consensus regarding whether or not to perform more extensive extrathoracic screening in patients who otherwise have potentially operable disease. The increased availability of PET and PET–CT, with its greater sensitivity for detecting occult extrathoracic metastatic disease, may well result in a change in practice to include routine assessment for extrathoracic disease. In patients initially selected for curative resection using standard tumour staging, PET–CT has been reported to detect occult metastatic disease in 11–14% of patients, and to alter management in up to 40%61,70,71. A more detailed discussion of this topic is beyond the scope of this chapter.

Missed lung cancer Whether the failure to diagnose a lung cancer on an initial chest radiograph, seen only in retrospect, constitutes malpractice or whether such ‘misses’ are inevitable can be a difficult decision72,73. Forty-five of the 50 potentially visible primary peripheral lesions in one part of the National Cancer Institutes (NCI) screening programme had been overlooked on at least one previous chest radiograph, though it should be realized that the opacities in question were often very subtle74. Similarly, Heelan et al found that 65% of cancers had been overlooked in a yearly screening programme75. Lung cancers may also be overlooked at CT; the majority of missed cancers on CT are endobronchial or perihilar in location. If failure to diagnose a lung cancer at the first opportunity, however subtle the abnormality, were automatically to be regarded as malpractice, then radiologists would be found guilty of malpractice even though their radiographic reporting conformed to the same standards as those of a group of experienced chest radiologists. Clearly the dividing line between negligence and acceptable practice is difficult to define72. It is worth noting, however, that a legal case will sometimes hinge on the technical adequacy of the radiographs and appropriate communication of the findings, as well as on the issue of interpretation.

PULMONARY SARCOMA AND OTHER PRIMARY MALIGNANT NEOPLASMS The majority of pulmonary sarcomas in the lungs are metastases from extrathoracic primary tumours. Primary pulmonary sarcomas are rare, the most common primary forms

CHAPTER 18

being fibrosarcoma and leiomyosarcoma. Chondrosarcoma, fibroleiomyosarcoma, rhabdomyosarcoma, malignant fibrous histiocytoma, carcinosarcoma, liposarcoma and osteosarcoma are among the other sarcomas that may occasionally arise as primary airway or pulmonary tumours. All the above neoplasms present as a solitary pulmonary nodule or as a tracheal or endobronchial mass indistinguishable radiologically from bronchial carcinoma. Angiosarcomas of the pulmonary artery extend or arise intravascularly. The autoimmune deficiency syndrome (AIDS) epidemic has led to an increased number of cases of Kaposi’s sarcoma involving the lung. Kaposi’s sarcoma in the respiratory tract appears to be rare in the absence of cutaneous involvement76,77. Coincidental involvement of the tracheobronchial tree is relatively frequent but parenchymal involvement may occur in the absence of endobronchial disease. Imaging may show the disease to be focal or widespread78–80. Focal segmental or lobar opacities are usually due to the tumour itself, but endobronchial Kaposi’s sarcoma may result in atelectasis or postobstructive pneumonia81. Radiographically widespread disease is the more frequent pattern, with a tendency to perihilar predominance of linear, rounded, or reticulonodular shadowing, reflecting a bronchocentric distribution of the lesions79 (Fig. 18.23). The pulmonary opacities of Kaposi’s sarcoma do not fluctuate in severity, whereas the major differential diagnoses—pulmonary oedema and opportunistic infections—may do so. Intrathoracic hilar/mediastinal lymphadenopathy has been detected in 25–60% of cases in some series78,79,82. Pleural involvement is frequent78,83; pleural effusions are most commonly bilateral and may on occasion be large.

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Other rare malignant pulmonary neoplasms include haemangiopericytoma, pulmonary blastoma, plasmacytoma, choriocarcinoma, teratoma and Askin tumours. The most common malignant tumour of the trachea is invasion from an adjacent neoplasm, notably bronchial carcinoma. Primary malignant tracheal tumours are rare and are virtually confined to adults.The least infrequent is squamous cell carcinoma, followed by adenoid cystic carcinoma and mucoepidermoid carcinoma84,85 (Fig. 18.24). These three tumours make up over 90% of primary malignant tracheal tumours, the remaining 10% encompassing a wide variety of neoplasms, including sarcoma, lymphoma, adenocarcinoma, chondrosarcoma, plasmacytoma, small cell carcinoma and metastases. Some malignant tracheal tumours may present on imaging studies as a mural nodule with lobular or irregular contours, whereas some grow circumferentially as a stenosing lesion of variable length. All these tumours grow through the tracheal wall to produce a paratracheal mass, a feature most frequently seen with adenoid cystic carcinoma. Like bronchial carcinoid and various benign tumours, adenoid cystic carcinomas may calcify.

BENIGN PULMONARY TUMOURS Bronchial carcinoids Bronchial carcinoids are uncommon, constituting less than 5% of pulmonary tumours.The peak age at diagnosis is in the fifth decade, but the age range is wide and includes children. Two forms of bronchial carcinoid are described: typical (85– 90%) and atypical (10–15%).Typical carcinoids most commonly arise in central airways. Atypical carcinoids usually arise in the

Figure 18.23 Kaposi’s sarcoma in two patients with AIDS. (A) Plain chest radiograph showing extensive pulmonary shadowing consisting of a mixture of ill-defined rounded and bandlike shadows maximal in the perihilar regions and lower zones. (B) CT showing the peribronchial distribution of the illdefined pulmonary nodules. There is interlobular septal thickening, a feature that is also frequently identified on the chest radiograph.

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Pulmonary hamartoma

Figure 18.24 Adenoid cystic carcinoma of the trachea. There is irregular polypoid tumour within the tracheal lumen.

lung periphery. Despite their classification as benign neoplasms, bronchial carcinoids can invade locally and may metastasize to hilar and mediastinal lymph nodes as well as to the brain, liver and bone. The atypical carcinoids have histological and clinical features intermediate between typical bronchial carcinoid and small cell carcinoma of the lung86, and have a poorer prognosis. Bronchial carcinoid may present with wheeze, pneumonia, or haemoptysis. Even when small, tumours may secrete adrenocorticotropic hormone (ACTH) in sufficient quantities to cause Cushing’s syndrome. Carcinoid syndrome is very rare if the tumour is still confined to the lung. Radiographic appearances vary with location of the tumour87–89. There is no lobar predilection and on rare occasions carcinoids may arise in the trachea. Bronchial carcinoids, particularly those located centrally, may calcify and occasionally ossify. Calcification is seen on CT in up to one-third of cases, but is only occasionally visible on chest radiograph90. Marked contrast enhancement may be seen on CT. Carcinoids arising in central bronchi (80–90% of cases) often show a larger mass external to the bronchus than within the lumen (‘iceberg’ lesions), and the extrabronchial component may be visible as a hilar mass (Fig. 18.25). Central lesions usually produce partial or complete bronchial obstruction, resulting in atelectasis with or without pneumonia. Central bronchial obstruction may be complicated by development of distal bronchiectasis or lung abscess. Occasionally, a bronchial carcinoid in a segmental or subsegmental bronchus may obstruct bronchial secretions, thereby causing a mucocele. Peripheral lesions (10–20% of carcinoids) present as solitary spherical or lobular nodules, 2–4 cm in diameter, with a welldefined smooth edge. Noncalcified peripheral bronchial carcinoid tumours closely resemble bronchial carcinomas, both radiologically and cytologically and are therefore frequently removed surgically in the belief that they are carcinomas.

Hamartomas are tumour-like malformations composed of an abnormal mixture of mature tissues normally found in the organ in which the tumour occurs. Pulmonary hamartomas consist predominantly of masses of cartilage with clefts lined by bronchial epithelium and may contain large collections of fat. Malignant transformation is either nonexistent or extremely rare. Pulmonary hamartomas are very occasionally multiple. A triad of pulmonary chondroma(s) (often multiple), gastric epithelioid leiomyosarcoma (leiomyoblastoma) and functioning extra-adrenal paragangliomas, known as Carney’s triad, has been reported, as has a form with just pulmonary chondromas and gastric smooth muscle tumours91,92. The age range for hamartoma is from young adulthood to old age, with presentation peaking in the seventh decade; they are only occasionally seen in children. The distribution of pulmonary hamartomas is opposite to that seen with bronchial carcinoid: 90% are peripheral and present as a solitary pulmonary nodule, while the remaining 10% arise within a major bronchus. Central lesions may lead to major airway obstruction and the features are then identical to those seen with bronchial carcinoids. On plain chest radiography93,94 the tumour is seen as a spherical or slightly lobulated, well-defined nodule, usually less than 4 cm in size, with normal surrounding lung (Fig. 18.26). Some hamartomas show calcification, which may be spotty or linear or show the characteristic ‘popcorn’ configuration associated with calcification in cartilage (Fig. 18.26). The frequency of calcification increases significantly with the size of the lesion. Popcorn calcification, if present, is virtually diagnostic of a hamartoma (the only differential diagnosis is a chondrosarcoma). Central fat density on CT is another important finding, which, if present, establishes the diagnosis95. The lesions grow slowly, usually much more slowly than carcinoma of the bronchus, and cavity formation is almost unknown.

Other benign pulmonary neoplasms Fibroma, chondroma, lipoma, haemangioma, benign clear cell tumours, neurogenic tumours, chemodectoma and granular cell myoblastoma are benign neoplasms that are occasionally encountered in the trachea, bronchi, or lungs. The plain radiograph and CT findings vary with the size and location of the tumour mass, but no features distinguish any one of these lesions from any other, and therefore the specific diagnosis has to be made histologically. They are indistinguishable radiologically from carcinoid tumour and solitary metastasis. Leiomyoma of the lung may be a solitary lesion, radiographically indistinguishable from the other benign connective tissue neoplasms. Multiple leiomyomas present as multiple discrete nodules in the lungs96. They are given a wide variety of names, including benign metastasizing leiomyoma. In women these tumours may be very slow growing metastases from a uterine leiomyoma; women with multiple pulmonary leiomyomas often have a history of previous hysterectomy for uterine fibroids.

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Figure 18.25 Carcinoid tumour. (A) A small tumour is completely occluding the right main bronchus and causing extensive collapse in the right lung. The endoluminal component is well seen (arrows), but there is poor differentiation of the tumour from adjacent collapsed lung. (B) A well-defined perihilar carcinoid tumour (arrows) is demonstrated anterior to the artery to the right lower lobe. (C) On lung windows there is only a small band of atelectasis in the middle lobe. (D) A small peripheral carcinoid tumour indistinguishable from a number of other causes of a solitary pulmonary nodule.

Intrapulmonary teratomas are very unusual. Most are benign, though malignant lesions are occasionally encountered. Radiographically and on CT, intrapulmonary teratomas appear as lobulated masses that may show calcification or cavitation97.

to be viral in origin. Rarely, these papillomas are also present in the lung and are seen on plain chest radiography or CT as multiple, small, widely scattered and well-defined, round pulmonary nodules, frequently showing cavitation101,102.

Plasma cell granuloma of the lung (inflammatory pseudotumour) is the name given to a lesion that is presumed to be reactive inflammatory granulomatous tissue98. The age range is wide and includes children. Most patients present with an asymptomatic solitary pulmonary nodule. Cavitation and calcification have both been described.

Benign tumours of the trachea are rare. They are most frequent in children, in whom squamous papillomas are the most common type, the next most common being haemangiomas. Haemangiomas are often associated with cutaneous haemangiomas and frequently present in the first year of life with stridor; imaging examinations show them to be eccentrically located nodular masses, most often in the subglottic region.

Sclerosing haemangioma is a benign neoplasm99,100, which almost always presents as an asymptomatic solitary pulmonary mass. Calcification may be seen. Squamous papillomas of the trachea, bronchi and lungs are most commonly associated with laryngeal papillomatosis, a disease that usually commences in childhood and is believed

BENIGN LYMPHOPROLIFERATIVE DISORDERS Lymphocytic interstitial pneumonia Lymphocytic interstitial pneumonia (LIP) is an uncommon non-neoplastic lymphoproliferative disorder characterized by

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Figure 18.26 Hamartoma of the lung. (A,B) Round, completely smooth, hamartoma in a 57 year old asymptomatic man. There is typical coarse popcorn calcification in this lesion which is unusually large.

diffuse infiltration of the pulmonary parenchymal interstitium by lymphocytes and plasma cells98. Histological differentiation between benign proliferation and low grade lymphoma can be difficult. LIP may occur as an isolated entity (it is included in the classification of idiopathic interstitial pneumonias); however, this is rare. It is more commonly seen in association with an underlying immunological abnormality such as Sjögren’s syndrome and AIDS. The main imaging findings are of bilateral areas of ground-glass opacification and cysts103.

Follicular bronchiolitis Follicular bronchiolitis, also known as diffuse lymphoid hyperplasia, is characterized by hyperplasia of bronchial mucosa associated lymphoid tissue (MALT) in relation to airways. Reticular or reticular nodular shadowing with centrilobular nodules and ground-glass opacity and occasionally bronchial wall thickening, bronchial dilatation, interlobular septal thickening and peribronchovascular airspace consolidation, is seen104.

visible intrathoracic adenopathy, whereas in the non-Hodgkin’s lymphomas, isolated pulmonary involvement is not uncommon107. If the mediastinal and hilar nodes have been previously irradiated, then recurrence confined to the lungs may be seen in both Hodgkin’s and non-Hodgkin’s lymphoma. The radiographic appearances of lung involvement in malignant lymphoma vary108,109. The usual patterns are: (A) one or more areas of pulmonary consolidation resembling pneumonia (Fig. 18.27); (B) multiple pulmonary nodules (Fig. 18.28); and, occasionally (C) miliary nodulation or reticulonodular shadowing resembling lymphangitis carcinomatosa (Fig. 18.29). The areas of pulmonary consolidation, which may contain air bronchograms, may be segmental or lobar in shape, but often they radiate from the hila or mediastinum without conforming to segmental anatomy, in keeping with the concept that extension into the lungs is by direct invasion from involved hilar or mediastinal nodes. Peripheral subpleural masses or areas of consolidation without any visible connection to enlarged nodes in the mediastinum and hila are, however, common in both Hodgkin’s disease and non-Hodgkin’s lymphoma. Very rapid increase in the size of lymphomatous deposits in the lung, so rapid that the disease may be confused with pneumonia, has been reported with high grade non-Hodgkin’s lymphoma110. Primary lymphoma of the lung (see Fig 18.27) (i.e. lymphoma isolated to the lung at initial presentation) is very uncommon, non-Hodgkin’s lymphoma of MALT type being the most frequently encountered form. These are low grade B-cell lymphomas of MALT (also called bronchus associated lymphoid tissue or BALT), which consists of mucosal lymphoid follicles located in distal bronchi and bronchioles, particularly at airway bifurcations98. The second most common primary tumour, known as angiocentric immunoproliferative lesion or lymphoid granulomatosis, is high grade and may have B- or T-cell phenotype98. Primary pulmonary Hodgkin’s disease is notably rare.

MALIGNANT LYMPHOPROLIFERATIVE DISORDERS Lymphoma Only pulmonary parenchymal involvement by lymphoma is considered in this chapter. Pulmonary parenchymal involvement can be broadly divided into that occurring in association with existing or previously treated nodal disease, and that due to primary lymphoma of the lung (Hodgkin’s or non-Hodgkin’s). Parenchymal involvement is comparatively rare at initial presentation (10–15% of cases105), but it becomes considerably more common as the disease progresses. It is particularly frequent in patients who relapse after treatment106. Involvement of the lung appears to be three times as frequent in Hodgkin’s lymphoma as it is in non-Hodgkin’s lymphoma105. In Hodgkin’s lymphoma the lung disease is almost invariably accompanied by

Figure 18.27 Primary pulmonary lymphoma. This appearance had been very slowly progressive over several years.

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be a striking feature. A few of the lesions show cavitation, but calcification does not occur. MALT lymphomas are relatively rarely associated with pleural effusions despite contact with the pleura.

Other findings in pulmonary lymphoma

Figure 18.28 Pulmonary involvement by lymphocytic lymphoma showing multiple pulmonary masses.

The imaging features of MALT111–113 lymphomas are solitary or multifocal, round or segmental areas of pulmonary consolidation. There is no lobar predilection and the consolidations may be placed centrally or peripherally in the lung parenchyma. Air bronchograms are frequently visible and may

Lobar atelectasis caused by endobronchial lymphoma is occasionally encountered, but, somewhat surprisingly, atelectasis as a result of extrinsic compression by enlarged lymph nodes is rare, with encasement rather than obstruction being the usual pattern of disease. Pleural effusions are common except in MALT lymphoma. They are usually unilateral and accompanied by visible intrathoracic adenopathy. They frequently disappear once the mediastinal nodes have been irradiated; in such cases they are probably due to venous or lymphatic obstruction rather than neoplastic involvement of the pleura. The usual radiographic problem is in deciding whether the pulmonary abnormality is due to involvement by lymphomatous tissue, infection or a complication of therapy. It should be remembered that the pattern of pulmonary infection in patients with lymphoma is modified because they are immunocompromised hosts, owing either to their disease or, more often, to the drugs used for treating the disorder. In many instances, a biopsy is the only way to establish the precise diagnosis. Since Hodgkin’s disease is believed to spread from nodal sites, a useful guideline is that if a patient presents with Hodgkin’s lymphoma and a pulmonary opacity, but no evidence of hilar or mediastinal disease, it is more likely that the opacity represents something other than Hodgkin’s lymphoma114. A caveat here is that the patient should not previously have received radiation therapy to the mediastinum.

Leukaemia

Figure 18.29 Pulmonary involvement by non-Hodgkin’s lymphoma showing an appearance closely resembling lymphangitis carcinomatosa with widespread nodules and thickened septal lines.

The incidence of leukaemic infiltration of the lungs, mediastinal lymph nodes and pleura varies with the course of the disease. Pulmonary infiltration by leukaemic cells is found at autopsy in nearly two-thirds of patients who have leukaemia. However, provided those patients with leukostasis (see below) are considered separately, leukaemic infiltration of the lungs, though very common pathologically, is usually asymptomatic and is rarely a cause of significant pulmonary opacity on chest radiograph. When respiratory impairment is present, pulmonary infection, oedema or haemorrhage, are more likely causes of the patient’s symptoms115. Imaging features include diffuse bilateral reticulation and patterns resembling interstitial oedema; lymphangitic carcinomatosis, small nodules, ground-glass opacification and consolidation have also been described.116 Radiographically visible hilar and/or mediastinal lymph node enlargement may be present and pleural effusions are common, though it is not possible to state the cause of the effusion with any confidence. The distribution of nodal enlargement closely resembles that of the lymphomas. T-cell leukaemias may show massive mediastinal adenopathy that responds rapidly to chemotherapy or radiation treatment. Huge mediastinal masses of T-cell leukaemia may disappear within a few days following appropriate treatment.

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Pleural thickening due to a mass of leukaemic cells in patients with myeloid leukaemia, so-called granulocytic sarcoma or chloroma formation (because of its green appearance), may be encountered on rare occasions117–119. Leukostasis is seen in patients with acute myeloid leukaemia with very high white blood cell counts in the order of 100 000–300 000 cells mm−3. The patients may be dyspnoeic because of the obliteration of their small pulmonary blood vessels by the leukaemic cells117. The chest radiograph may be normal or show airspace shadowing, which is probably due to pulmonary oedema rather than directly to the accumulation of leukaemic cells in the lungs120,121.

METASTASES Pulmonary metastases122 in adults are usually from breast, gastrointestinal tract, kidney, testes, head and neck tumours or from a variety of bone and soft tissue sarcomas. The basic sign of haematogenous pulmonary metastasis is one or more discrete pulmonary nodules (Fig. 18.30), usually in the outer portions of the lungs, a distribution that is most evident on CT (Fig. 18.31). The nodules are usually spherical and well defined, but they may be almost any shape and can occasionally have a very irregular edge. Such irregular edges are seen particularly with metastases from adenocarcinomas (Fig. 18.32). Cavitation is occasionally seen in pulmonary metastases; it is a particular feature of squamous cell carcinoma123. Calcification is very unusual except in osteosarcoma and chondrosarcoma. Even if the primary tumour shows calci-

Figure 18.30 Typical pulmonary metastases showing multiple, welldefined spherical nodules in the lungs. Rib metastases with associated soft tissue swelling are also present (arrows). In this case the primary tumour was a synovial cell carcinoma.

Figure 18.31 Pulmonary metastases (arrow). CT demonstrating a single peripheral metastasis (arrow). There were multiple lesions at other levels. The volume loss and scarring in the left lung is secondary to previous resection of the primary bronchogenic carcinoma.

fication, e.g. in breast and colon, visible calcification in the pulmonary metastases is rare.The rate of growth of metastases is highly variable; in some choriocarcinomas and osteosarcomas, for example, it may be explosive and double the volume of the lesions in less than 30 d124. Alternatively, metastases can remain unchanged in size for a long time, as in some cases of thyroid carcinoma125. A solitary pulmonary metastasis may be the presenting feature in a patient without a known primary tumour. However, a metastasis is a rare cause of the asymptomatic pulmonary

Figure 18.32 Irregular pulmonary metastases due to metastatic adenocarcinoma from an unknown primary. The nodules are irregular in outline. A large left pleural effusion is also present.

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nodule in patients who do not have a known extrathoracic primary neoplasm, comprising no more than 2–3% of most series. The simplest technique for diagnosing pulmonary metastases is the plain postero-anterior (PA) and lateral chest radiograph. High-kV techniques are often used routinely, since substantial portions of the lungs are obscured on low-kV radiographs by overlying structures such as the diaphragm, heart, mediastinum, hila and ribs. Such radiographs will detect most lung metastases above 1 cm in diameter. Increasing sensitivity can be obtained with CT, in particular MDCT. The increase in sensitivity for small nodules is, however, at the cost of decreasing specificity. On CT, lesions smaller than 1 cm are regularly demonstrated, together with most lesions above 3 mm in diameter. Below 1 cm and particularly below 6 mm, the differential diagnosis from granulomas due to tuberculosis, histoplasmosis, or other fungi becomes difficult. Where calcification can be identified, metastases (except from osteogenic sarcoma or chondrosarcoma) can effectively be dismissed from consideration. If the nodules are not calcified, the best that can be done in most instances is to give a statistical probability of the nodules being metastases. With a plain chest radiograph showing multiple noncalcified nodules, the probability is high, well over 90%, even in areas endemic for fungus granulomas, and approaches 100% in areas where fungus granulomas are rare or nonexistent. With the smaller lesions detectable on CT, this probability diminishes. Depending on the prevalence of infectious granulomas in the community and the likelihood of a particular tumour metastasizing to the lung, the probability that a pulmonary nodule seen solely on CT is indeed a metastasis may drop to as low as 50%. The use of chest CT to detect pulmonary metastases should be limited to selected patients. There are no universally agreed guidelines but general indications include: 1 Investigation of patients with a normal chest radiograph in whom the likelihood of metastasis is high and in whom demonstration of the presence of pulmonary metastases would significantly alter management, e.g. patients with osteosarcoma, choriocarcinoma and testicular germ-cell tumours. 2 Investigation of patients who are being considered for surgical resection of a known pulmonary metastasis to look for further occult lesions. 3 Distinction of solitary from multiple pulmonary nodules in a patient with an extrathoracic primary tumour in whom the diagnostic question is metastasis versus new primary bronchial carcinoma. A truly solitary pulmonary nodule may represent a primary bronchogenic carcinoma, whereas multiple nodules make metastases more likely. Currently CT is the most cost-effective and widely used method of screening for pulmonary metastases. PET can be useful for detection of thoracic metastases for tumours such as melanoma, colon and breast. The major weakness of PET alone is the limited sensitivity for nodules less than 10 mm in diameter.

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Lymphangitic carcinomatosis Lymphangitic carcinomatosis is the name given to permeation of pulmonary lymphatics and/or their adjacent interstitial tissue by neoplastic cells.The most common tumours that spread in this manner are carcinomas of the bronchus, breast, stomach and prostate126. Lymphangitic carcinomatosis may develop secondary to blood-borne emboli lodging in smaller pulmonary arteries and subsequently spreading through the vessel walls into the perivascular interstitium and lymphatic vessels. Such spread tends to give rise to bilateral symmetric pulmonary abnormality. Alternatively, lymphangitic carcinomatosis may result from direct extension of tumour from hilar lymph nodes into peribronchovascular interstitium, from the pleura into adjacent interlobular septa, or from a primary carcinoma of the lung into the adjacent peribronchovascular interstitium. Tumour spreading by these mechanisms tends to be more localized98. The radiological findings are fine reticulonodular shadowing and/or thickened septal lines (Figs 18.33, 18.34). These signs occur because of a combination of dilated lymphatics and interstitial oedema, together with shadows due to the tumour cells themselves along with any desmoplastic response which may have been induced by the tumour98,126. Another useful sign of lymphangitis carcinomatosa is subpleural oedema resulting from lymphatic obstruction by tumour cells, a feature that is most readily visible as thickening of the fissures. Pleural effusion is common, seen in about 30%. As would be expected, CT is more sensitive than plain radiography in the detection of lymphangitic spread and may show changes in patients whose chest radiograph is normal. CT, particularly high-resolution CT127–130, shows nonuniform, often nodular, thickening of the interlobular septa and irregular thickening of the bronchovascular bundles in the

Figure 18.33 Unilateral lymphangitic carcinomatosis due to carcinoma of the bronchus, showing thickened septal lines and nodules confined to the right lung.

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Figure 18.34 Bilateral lymphangitic carcinomatosis showing bilateral thickened septal lines together with widespread nodulation of the lungs. The primary tumour in this 71 year old woman was presumed to be a bronchial carcinoma (a diagnosis based on sputum cytology).

Figure 18.35 High-resolution CT of lymphangitic carcinomatosis. Note the variable thickening of the interlobular septa and the enlargement of the bronchovascular bundle in the centre of the secondary pulmonary lobules. The polygonal shape of the walls (septa) of the secondary pulmonary lobules is particularly well shown anteriorly. The pulmonary nodule is due to a discrete metastasis, a relatively frequent finding in this condition.

Tumour emboli central portions of the lungs (Fig. 18.35). Small, peripherally located, wedge-shaped densities are sometimes seen as well; these may represent volume averaging of the thickened septa. There is often patchy airspace shadowing, but an important differential diagnostic feature from pulmonary oedema is that many of the acini subtended by thickened interlobular septa are normally aerated. Nodular shadows may be seen scattered through the parenchyma. The abnormalities may involve all zones of both lungs or they may be centrally or peripherally predominant; sometimes, particularly when lymphangitis is due to bronchial carcinoma, they are confined to a lobe or one lung. Hilar lymph node enlargement is seen in only some of the patients.

Unusual patterns of metastatic cancer Endobronchial metastases Endobronchial metastases are most unusual. Melanoma and renal, colorectal and breast carcinomas are the primary tumours that most frequently give endobronchial submucosal metastases131. In such cases the effect of airway obstruction is the dominant feature.

Miliary metastases Occasionally, innumerable tiny nodules closely resembling miliary tuberculosis are seen throughout both lungs, with no large masses and no evidence of lymphatic obstruction, such as is seen in lymphangitis carcinomatosa. Metastases are, however, one of the rarest causes of this pattern. The primary tumours that are most likely to produce miliary nodulation of the lungs are thyroid and renal carcinomas, bone sarcomas and choriocarcinoma.

Radiologically recognizable pulmonary arterial hypertension may occur on rare occasions as a result of tumour emboli blocking small pulmonary arteries132. Many tumours can embolize in this fashion, particularly hepatoma, carcinoma of the breast, kidney, stomach, and prostate and choriocarcinoma132.

EVALUATION OF THE SOLITARY PULMONARY NODULE A solitary pulmonary mass or nodule is defined as a solitary circumscribed pulmonary opacity with no associated pulmonary, pleural, or mediastinal abnormality, measuring less than 3 cm in diameter133. Many are discovered incidentally at chest radiography or CT. Although most are benign, up to 40% of these nodules may be malignant, with the relative incidence varying amongst different patient populations, e.g. there is a relatively higher incidence of granulomas in countries where fungal disease is endemic. Table 18.3 lists some of the causes of the solitary nodule, and Table 18.4 some of the mimics. The primary role of radiological investigation is to differentiate benign from malignant disease. It is as important to avoid a false-positive diagnosis of cancer with an unnecessary operation as to avoid a false-negative diagnosis leaving a potentially resectable cancer untreated. Chest radiography and CT are the primary imaging investigations used, with CT optimal for characterization. The following discussion reviews factors used to differentiate between the benign and malignant lesion. Of those listed below, the two primary criteria are rate of growth/stability over time and the attenuation of the nodule.

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Table 18.3

CAUSES OF A SOLITARY PULMONARY MASS

Bronchial carcinoma Bronchial carcinoid Granuloma Hamartoma Metastasis Chronic pneumonia or abscess Hydatid cyst Pulmonary haematoma Bronchocele Fungus ball Massive fibrosis in coal workers Bronchogenic cyst Sequestration Atriovenous malformation Pulmonary infarct Round atelectasis

Table 18.4

SIMULANTS OF A SOLITARY PULMONARY MASS

Extrathoracic artefacts Cutaneous masses Bony lesions Pleural tumours or plaques

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Attenuation and enhancement The attenuation of a pulmonary nodule on CT can be classified as soft tissue, calcification, fat and ground glass. A dense central nidus or laminated calcification are good indications of a granulomatous process (tuberculosis, histoplasmosis). Irregular ‘popcorn’ calcification is very suggestive of a hamartoma, but is comparatively uncommon in such tumours when they are less than 30 mm in diameter. Granular calcification on CT is seen in up to 7% of carcinomas, usually in large rather than small tumours. Sometimes the calcification represents tumour calcification, sometimes it is due to benign granulomatous calcification engulfed by a carcinoma. CT is of most value for the detection of fat, its presence being virtually diagnostic of hamartoma (present in 20–30% of cases). A lack of enhancement (< 15 HU) following an intravenous bolus of contrast medium is also indicative of benignity138 (Fig. 18.36). Recent studies of screening CT have found that mixed soft tissue and ground-glass attenuation nodules have a greater likelihood of malignancy compared to soft tissue nodules, and that groundglass attenuation nodules when malignant are more likely to be of bronchiolo-alveolar carcinoma cell type17.

Size The size of the mass is of little diagnostic value. Although only a small percentage of nodules under 1 cm in diameter are malignant, over 40% of malignant nodules are less than 2 cm and 15% are less than 1 cm in diameter15,139.

Encysted pleural fluid Pulmonary vessels

The age of the patient is also a significant distinguishing feature. Only 1% of solitary masses in patients under the age of 35 years will be carcinomas.

Margins The features of the margins of the mass are of some predictive value and are best demonstrated by high-resolution CT15. Carcinomas typically have ill-defined margins which are irregular, speculated, or lobulated and may exhibit umbilication or a notch. Unfortunately all these features can be seen with benign disease. On the other hand, a well-defined mass

Rate of growth/stability over time Considerable amounts of data have been accumulated on the growth rates of benign and malignant masses. The measure of growth is the volume doubling time. Benign lesions almost invariably have a doubling time of less than 1 month or more than 18 months, with the volume doubling time for most peripheral pulmonary carcinomas being between 1 and 18 months (median 3 months)134–136. Bronchiolo-alveolar carcinomas are an exception; they may grow slowly, with volume doubling times much longer than those usually quoted for bronchial carcinoma137. Monitoring of growth by serial radiography is now not recommended, but these data serve to underline the fact that a mass which has demonstrably not changed in size over a period of 2 years can be regarded as almost certainly benign, and emphasize the importance of obtaining old images for comparison wherever possible. Volumetric analysis tools on CT provide a more accurate determination of interval growth. Growth in and of itself does not indicate malignancy, but does increase the likelihood that a nodule is malignant.

Figure 18.36 Contrast-enhanced CT for the evaluation of a solitary pulmonary nodule. There is differential enhancement in this lesion that was due to a primary adenocarcinoma.

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with a perfectly smooth, pencil-sharp margin is unlikely to be bronchial carcinoma, although a metastasis may occasionally exhibit these features. PET or PET–CT has been shown to have sensitivity, specificity and accuracy of 90% or greater in the diagnosis of benign nodules133. False-positive results may occur in patients with infectious or inflammatory processes, and false-negative results may occur in slow growing malignancies such as bronchiolo-alveolar carcinoma. PET also has difficulty evaluating lesions less than 10 mm in diameter. In a patient with a known extrathoracic primary malignancy the lesion should be considered as a probable metastasis. There is no place for searching for an occult extrapulmonary primary malignancy which, as the source of an isolated metastasis, accounts for only 2% of all solitary pulmonary masses. Such a search is far more fruitfully conducted after surgical excision or needle biopsy of the mass, when there will be some indication of the primary site from the histology available. Sputum cytology provides a low yield in solid, as opposed to cavitating, masses, but is easy to perform and may provide a definitive diagnosis of malignancy. Whilst percutaneous biopsy has an extremely low falsepositive rate for malignancy (well under 1%), the false-negative rate is around 10%. Other limitations of the technique are the low yield of a specific diagnosis of many benign lesions and the imperfect correlation of cell type between the cytological sample and the eventual histology. Most of these series, however, relied on FNA cytology. Improved diagnostic rates of benign pathology may be achieved with cutting needle biopsy techniques140.

Summary When a solitary pulmonary mass is detected every attempt should be made to obtain old images to check for interval change in size. The margins of the lesion and the presence or absence of calcification should be assessed. This frequently involves the use of CT which may also demonstrate specific signs of a benign lesion (atriovenous malformation, bronchocele and fungus ball). Lesions that are unchanged in size over a 2-year period may be presumed to be benign and followed up at 6-monthly intervals for a further 2 years. The presence of central or ringlike calcification also places the lesion in the benign category. Solitary pulmonary masses in patients under 40 years of age which are truly spherical with a clear-cut margin are unlikely to be malignant. Whilst it may be difficult to firmly establish the benign nature of the lesion in this way, the absence of evidence of malignancy in a satisfactory specimen allows a ‘wait and see’ policy in some patients. The other indications for biopsy are a presumed solitary metastasis; a presumed bronchial carcinoma when thoracotomy is inadvisable owing to the general health of the patient or is contraindicated because the lesion is unresectable or there are known metastases; and for the investigation of the solitary pulmonary mass occurring in the immunosuppressed patient.

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49. Padovani B, Mouroux J, Seksik L et al 1993 Chest wall invasion by bronchogenic carcinoma: evaluation with MR imaging. Radiology 187: 33–38 50. Suzuki N, Saitoh T, Kitamura S 1993 Tumor invasion of the chest wall in lung cancer: diagnosis with US. Radiology 187: 39–42 51. Tateishi M, Fukuyama Y, Hamatake M, Kohdono S, Ishida T, Sugimachi K 1994 Skip mediastinal lymph node metastasis in non-small cell lung cancer. J Surg Oncol 57: 139–142 52. Webb W R, Gamsu G, Stark D D, Moore E H 1984 Magnetic resonance imaging of the normal and abnormal pulmonary hila. Radiology 152: 89–94 53. McLoud T C, Bourgouin P M, Greenberg R W et al 1992 Bronchogenic carcinoma: Analysis of staging in the mediastinum with CT by correlative lymph node mapping and sampling. Radiology 182: 319–323 54. Primack S L, Lee K S, Logan P M, Miller R R, Muller N L 1994 Bronchogenic carcinoma: utility of CT in the evaluation of patients with suspected lesions. Radiology 193: 795–800 55. Buy J N, Ghossain M A, Poirson F et al 1988 Computed tomography of mediastinal lymph nodes in nonsmall cell lung cancer. A new approach based on the lymphatic pathway of tumor spread. J Comput Assist Tomogr 12: 545–552 56. Ikezoe J, Kadowaki K, Morimoto S et al 1990 Mediastinal lymph node metastases from nonsmall cell bronchogenic carcinoma: reevaluation with CT. J Comput Assist Tomogr 14: 340–344 57. Ohno Y, Hatabu H, Takenaka D et al 2004 Metastases in mediastinal and hilar lymph nodes in patients with non-small cell lung cancer: quantitative and qualitative assessment with STIR turbo spin-echo MR imaging. Radiology 231: 872–879 58. Potepan P, Meroni E, Spagnoli I et al 1996 Non-small-cell lung cancer: detection of mediastinal lymph node metastases by endoscopic ultrasound and CT. Eur Radiol 6: 19–24 59. Fritscher-Ravens A, Davidson B L, Hauber H P et al 2003 Endoscopic ultrasound, positron emission tomography, and computerized tomography for lung cancer. Am J Respir Crit Care Med 168: 1293–1297 60. van Overhagen H, Brakel K, Heijenbrok M W et al 2004 Metastases in supraclavicular lymph nodes in lung cancer: assessment with palpation, US, and CT. Radiology 232: 75–80 61. Dwamena B A, Sonnad S S, Angobaldo J O, Wahl R L 1999 Metastases from non-small cell lung cancer: mediastinal staging in the 1990s—meta-analytic comparison of PET and CT. Radiology 213: 530–536 62. Antoch G, Stattaus J, Nemat A T et al 2003 Non-small cell lung cancer: dual-modality PET/CT in preoperative staging. Radiology 229: 526–533 63. Lardinois D, Weder W, Hany T F et al 2003 Staging of non-smallcell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 348: 2500–2507 64. Shim S S, Lee K S, Kim B T et al 2005 Non-small cell lung cancer: Prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging. Radiology 236: 1011–1019 65. Gambhir S S, Hoh C K, Phelps M E, Madar I, Maddahi J 1996 Decision tree sensitivity analysis for cost-effectiveness of FDG-PET in the staging and management of non-small-cell lung carcinoma. J Nucl Med 37: 1428–1436 66. Scott W J, Shepherd J, Gambhir S S 1998 Cost-effectiveness of FDGPET for staging non-small cell lung cancer: a decision analysis. Ann Thorac Surg 66: 1876–1883 67. Bury T, Paulus P, Dowlati A, Corhay JL, Rigo P, Radermecker MF 1997 Evaluation of pleural diseases with FDG-PET imaging: preliminary report. Thorax 52: 187–189 68. Erasmus J J, McAdams H P, Rossi S E, Goodman P C, Coleman R E, Patz E F 2000 FDG PET of pleural effusions in patients with non-small cell lung cancer. Am J Roentgenol 175: 245–249 69. Schaffler G J, Wolf G, Schoellnast H et al 2004 Non-small cell lung cancer: evaluation of pleural abnormalities on CT scans with 18F FDG PET. Radiology 231: 858–865

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70. Valk P E, Pounds T R, Hopkins D M 1995 Staging non-small cell lung cancer by whole-body positron emission tomographic imaging. Ann Thorac Surg 60: 1573–1582 71. Dietlein M, Weber K, Gandjour A et al 2000 Cost-effectiveness of FDGPET for the management of solitary pulmonary nodules: a decision analysis based on cost reimbursement in Germany. Eur J Nucl Med 27: 1441–1456 72. Potchen E J, Bisesi M A 1990 When is it malpractice to miss lung cancer on chest radiographs? Radiology 175: 29–32 73. Woodring J H 1990 Pitfalls in the radiologic diagnosis of lung cancer. Am J Roentgenol 154: 1165–1175 74. Muhm J R, Miller W E, Fontana R S, Sanderson D R, Uhlenhopp M A 1983 Lung cancer detected during a screening program using fourmonth chest radiographs. Radiology 148: 609–615 75. Heelan R T, Flehinger B J, Melamed M R et al 1984 Non-small cell lung cancer: results of the New York screening program. Radiology 151: 289–293 76. Lemlich G, Schwam L, Lebwohl M 1987 Kaposi’s sarcoma and acquired immunodeficiency syndrome. Postmortem findings in twenty-four cases. J Am Acad Dermatol 16: 319–325 77. Nash G, Fligiel S 1984 Kaposi’s sarcoma presenting as pulmonary disease in the acquired immunodeficiency syndrome: diagnosis by lung biopsy. Hum Pathol 15: 999–1001 78. Davis S D, Henschke C I, Chamides B K, Westcott J L 1987 Intrathoracic Kaposi sarcoma in AIDS patients: Radiographic pathologic correlation. Radiology 163: 495–500 79. Sivit C J, Schwartz A M, Rockoff S D 1987 Kaposi’s sarcoma of the lung in AIDS: radiologic–pathologic analysis. Am J Roentgenol 148: 25–28 80. Naidich D P, Tarras M, Garay S M, Birnbaum B, Rybak B J, Schinella R 1989 Kaposi’s sarcoma. CT–radiographic correlation. Chest 96: 723–728 81. Huang R M, Naidich D P, Lubat E, Schinella R, Garay S M, McCauley D I 1989 Septic pulmonary emboli: CT–radiographic correlation. Am J Roentgenol 153: 41–45 82. Zibrak J D, Silvestri R C, Costello P et al 1986 Bronchoscopic and radiologic features of Kaposi’s sarcoma involving the respiratory system. Chest 90: 476–479 83. Hannon F B, Easterbrook P J, Padley S, Boag F, Goodall R, Phillips R H 1998 Bronchopulmonary Kaposi’s sarcoma in 106 HIV-1 infected patients. Int J STD AIDS 9: 518–525 84. Gelder C M, Hetzel M R 1993 Primary tracheal tumours: a national survey. Thorax 48: 688–692 85. Allen M S 1993 Malignant tracheal tumors. Mayo Clin Proc 68: 680–684 86. Choplin R H, Kawamoto E H, Dyer R B, Geisinger K R, Mills S E, Pope T L 1986 Atypical carcinoid of the lung: radiographic features. Am J Roentgenol 146: 665–668 87. Altman R L, Miller W E, Carr D T, Payne W S, Woolner L B 1973 Radiographic appearance of bronchial carcinoid. Thorax 28: 433–434 88. Forster B B, Muller N L, Miller R R, Nelems B, Evans K G 1989 Neuroendocrine carcinomas of the lung: clinical, radiologic, and pathologic correlation. Radiology 170: 441–445 89. Nessi R, Basso R P, Basso R S, Bosco M, Blanc M, Uslenghi C 1991 Bronchial carcinoid tumors: radiologic observations in 49 cases. J Thorac Imaging 6: 47–53 90. Zwiebel B R, Austin J H, Grimes M M 1991 Bronchial carcinoid tumors: assessment with CT of location and intratumoral calcification in 31 patients. Radiology 179: 483–486 91. Carney J A 1983 The triad of gastric epithelioid leiomyosarcoma, pulmonary chondroma, and functioning extra-adrenal paraganglioma: a five-year review. Med Balt 62: 159–169 92. Mazas-Artasona L, Romeo M, Felices R et al 1988 Gastro-oesophageal leiomyoblastomas and multiple pulmonary chondromas: an incomplete variant of Carney’s triad. Br J Radiol 61: 1181–1184 93. Bateson E M, Abbott E K 1960 Mixed tumors of the lung, or hamartochondromas. A review of the radiological appearances of cases published in the literature and a report of fifteen new cases. Clin Radiol 11: 232–247 94. Poirier T J, van Ordstrand H S 1971 Pulmonary chondromatous hamartomas. Report of seventeen cases and review of the literature. Chest 59: 50–55

95. Siegelman S S, Khouri N F, Scott W W Jr et al 1986 Pulmonary hamartoma: CT findings. Radiology 160: 313–317 96. Martin E 1983 Leiomyomatous lung lesions: a proposed classification. Am J Roentgenol 141: 269–272 97. Morgan D E, Sanders C, McElvein R B, Nath H, Alexander C B 1992 Intrapulmonary teratoma: a case report and review of the literature. J Thorac Imaging 7: 70–77 98. Muller N L, Fraser R S, Lee K S, Johkoh T 2003 Diseases of the Lungs, 1st edn. Lippincott Williams & Wilkins, Philadelphia 99. Katzenstein A L, Gmelich J T, Carrington C B 1980 Sclerosing hemangioma of the lung: a clinicopathologic study of 51 cases. Am J Surg Pathol 4: 343–356 100. Sugio K, Yokoyama H, Kaneko S, Ishida T, Sugimachi K 1992 Sclerosing hemangioma of the lung: radiographic and pathological study. Ann Thorac Surg 53: 295–300 101. Kwong J S, Muller N L, Miller R R 1992 Diseases of the trachea and main-stem bronchi: correlation of CT with pathologic findings. RadioGraphics 12: 645–657 102. McCarthy M J, Rosado-de-Christenson M L 1995 Tumors of the trachea. J Thorac Imaging 10: 180–198 103. Johkoh T, Muller N L, Pickford H A et al 1999 Lymphocytic interstitial pneumonia: thin-section CT findings in 22 patients. Radiology 212: 567–572 104. Howling S J, Hansell D M, Wells A U, Nicholson A G, Flint J D, Muller N L 1999 Follicular bronchiolitis: thin-section CT and histologic findings. Radiology 212: 637–642 105. Filly R, Bland N, Castellino R A 1976 Radiographic distribution of intrathoracic disease in previously untreated patients with Hodgkin’s disease and non-Hodgkin’s lymphoma. Radiology 120: 277–281 106. Cobby M, Whipp E, Bullimore J, Goodman S, Davies E R, Goddard P 1990 CT appearances of relapse of lymphoma in the lung. Clin Radiol 41: 232–238 107. Jenkins P F, Ward M J, Davies P, Fletcher J 1981 Non-Hodgkin’s lymphoma, chronic lymphatic leukaemia and the lung. Br J Dis Chest 75: 22–30 108. Au V, Leung A N 1997 Radiologic manifestations of lymphoma in the thorax. Am J Roentgenol 168: 93–98 109. Lee K S, Kim Y, Primack S L 1997 Imaging of pulmonary lymphomas. Am J Roentgenol 168: 339–345 110. Dunnick N R, Parker B R, Castellino R A 1976 Rapid onset of pulmonary infiltration due to histiocytic lymphoma. Radiology 118: 281–285 111. King L J, Padley S P, Wotherspoon A C, Nicholson A G 2000 Pulmonary MALT lymphoma: imaging findings in 24 cases. Eur Radiol 10: 1932–1938 112. Lee D K, Im J G, Lee K S et al 2000 B-cell lymphoma of bronchusassociated lymphoid tissue (BALT) : CT features in 10 patients. J Comput Assist Tomogr 24: 30–34 113. Wislez M, Cadranel J, Antoine M et al 1999 Lymphoma of pulmonary mucosa-associated lymphoid tissue: CT scan findings and pathological correlations. Eur Respir J 14: 423–429 114. Bragg D G 1987 Radiology of the lymphomas. Curr Probl Diagn Radiol 16: 177–206 115. Maile C W, Moore A V, Ulreich S, Putman C E 1983 Chest radiographic– pathologic correlation in adult leukemia patients. Invest Radiol 18: 495–499 116. Heyneman L E, Johkoh T, Ward S, Honda O, Yoshida S, Muller N L 2000 Pulmonary leukemic infiltrates: high-resolution CT findings in 10 patients. Am J Roentgenol 174: 517–521 117. Siegel M J, Shackelford G D, McAlister W H 1981 Pleural thickening. An unusual feature of childhood leukemia. Radiology 138: 367–369 118. Neiman R S, Barcos M, Berard C et al 1981 Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer 48: 1426–1437 119. Lee M J, Grogan L, Meehan S, Breatnach E 1991 Pleural granulocytic sarcoma: CT characteristics. Clin Radiol 43: 57–59 120. van Buchem M A, Wondergem J H, Kool L J et al 1987 Pulmonary leukostasis: radiologic-pathologic study. Radiology 165: 739–741

CHAPTER 18

121. Vernant J P, Brun B, Mannoni P, Dreyfus B 1979 Respiratory distress of hyperleukocytic granulocytic leukemias. Cancer 44: 264–268 122. Coppage L, Shaw C, Curtis A M 1987 Metastatic disease to the chest in patients with extrathoracic malignancy. J Thorac Imaging 2: 24–37 123. Chaudhuri M R 1970 Cavitary pulmonary metastases. Thorax 25: 375–381 124. Ishihara T, Kikuchi K, Ikeda T, Yamazaki S 1973 Metastatic pulmonary diseases: biologic factors and modes of treatment. Chest 63: 227–232 125. Schaner E G, Chang A E, Doppman J L, Conkle D M, Flye M W, Rosenberg S A 1978 Comparison of computed and conventional whole lung tomography in detecting pulmonary nodules: a prospective radiologic-pathologic study. Am J Roentgenol 131: 51–54 126. Janower M L, Blennerhassett J B 1971 Lymphangitic spread of metastatic cancer to the lung. A radiologic–pathologic classification. Radiology 101: 267–273 127. Johkoh T, Ikezoe J, Tomiyama N et al 1992 CT findings in lymphangitic carcinomatosis of the lung: correlation with histologic findings and pulmonary function tests. Am J Roentgenol 158: 1217–1222 128. Munk P L, Muller N L, Miller R R, Ostrow D N 1988 Pulmonary lymphangitic carcinomatosis: CT and pathologic findings. Radiology 166: 705–709 129. Ren H, Hruban R H, Kuhlman J E et al 1989 Computed tomography of inflation-fixed lungs: the beaded septum sign of pulmonary metastases. J Comput Assist Tomogr 13: 411–416 130. Stein M G, Mayo J, Muller N, Aberle D R, Webb W R, Gamsu G 1987 Pulmonary lymphangitic spread of carcinoma: Appearance on CT scans. Radiology 162: 371–375 131. Baumgartner W A, Mark J B 1980 Metastatic malignancies from distant sites to the tracheobronchial tree. J Thorac Cardiovasc Surg 79: 499–503 132. Chan C K, Hutcheon M A, Hyland R H, Smith G J, Patterson B J, Matthay R A 1987 Pulmonary tumor embolism: a critical review of clinical, imaging, and hemodynamic features. J Thorac Imaging 2: 4–14

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133. Hartman T E 2005 Radiologic evaluation of the solitary pulmonary nodule. Radiol Clin North Am 43: 459–465, vii 134. Hayabuchi N, Russell W J, Murakami J 1983 Slow-growing lung cancer in a fixed population sample. Radiologic assessments. Cancer 52: 1098–1104 135. Nathan M H, Collins V P, Adams R A 1962 Differentiation of benign and malignant pulmonary nodules by growth rate. Radiology 79: 221–232 136. Steele J D, Buell P 1973 Asymptomatic solitary pulmonary nodules. Host survival, tumor size, and growth rate. J Thorac Cardiovasc Surg 65: 140–151 137. Hill C A 1984 Bronchioloalveolar carcinoma: a review. Radiology 150: 15–20 138. Swensen S J, Morin R L, Schueler B A et al 1992 Solitary pulmonary nodule: CT evaluation of enhancement with iodinated contrast material—a preliminary report. Radiology 182: 343–347 139. Gurney J W 1993 Determining the likelihood of malignancy in solitary pulmonary nodules with Bayesian analysis. Part I. Theory. Radiology 186: 405–413 140. McLoud T C 1998 Should cutting needles replace needle aspiration of lung lesions? Radiology 207: 569–570

SUGGESTIONS FOR FURTHER READING Hansell D M, Armstrong P, Lynch D A, McAdams H P 2005 Imaging of diseases of the chest, 4th edn. Elsevier, Philadelphia Muller N L, Fraser R S, Lee K S, Johkoh T 2003 Diseases of the lung, 1st edn. Lippincott Williams & Wilkins, Philadelphia

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High-Resolution Computed Tomography of Interstitial and Occupational Lung Disease

19

David M. Hansell, Zelena A. Aziz and Nestor L. Müller

• High-resolution computed tomography patterns of interstitial lung disease • Idiopathic interstitial pneumonias • Sarcoidosis • Hypersensitivity pneumonitis • Langerhans cell histiocytosis • Lymphangioleiomyomatosis • Connective tissue diseases • Systemic vasculitides • Drug-induced lung disease • Occupational lung disease

The pulmonary interstitium is the network of connective tissue fibres that supports the lung. It includes the alveolar walls, interlobular septa and the peribronchovascular interstitium. The term interstitial lung disease (ILD) is used to refer to a group of disorders that mainly affects these supporting structures. Although the majority of these disorders also involve the airspaces, the predominant abnormality is thickening of the interstitium which may be due to the accumulation of fluid, cells, or fibrous tissue. The chest radiograph remains part of the initial assessment of ILD, but the radiographic pattern is often non-specific, observer variation is considerable1 and it is relatively insensitive to early ILD2–4. High-resolution computed tomography (HRCT) has revolutionized the imaging of ILD as it enables early detection of disease, allows a histospecific diagnosis to be made in certain cases, and provides insight into disease reversibility and prognosis.

HIGH-RESOLUTION COMPUTED TOMOGRAPHY PATTERNS OF DIFFUSE LUNG DISEASE Diffuse abnormalities of the lung on HRCT may be broadly classified into one of the following four patterns: (A) reticular

or linear; (B) nodular; (C) ground-glass opacity through to consolidation; and (D) areas of decreased lung attenuation.

Reticular pattern A reticular pattern on CT almost always represents significant ILD. Morphologically, a reticular pattern may be caused by thickened interlobular or intralobular septa or honeycomb (fibrotic) destruction. Numerous thickened interlobular septa indicate an extensive interstitial abnormality and causes include infiltration by fibrosis (interstitial fibrosis), abnormal cells (lymphangitis carcinomatosa), or fluid (pulmonary oedema). Although thickened interlobular septa can be a consequence of infiltration by fibrosis, this feature is not a frequent finding in idiopathic pulmonary fibrosis (IPF). Interlobular septal thickening is usually described as smooth (seen in pulmonary oedema and alveolar proteinosis) or irregular (lymphangitic spread of tumour), but the distinction is not always easily made. Sarcoidosis causes nodular septal thickening although this pattern is not usually the dominant feature5. Intralobular septal thickening manifests as a fine reticular pattern on HRCT and is seen in all ILDs but most commonly in IPF. Often, the intralobular septal thickening may be so fine that HRCT does not demonstrate discrete intralobular opacities but a generalized increase in lung density (ground-glass opacification). Severe pulmonary fibrosis usually results in a coarse reticular pattern made up of interlacing irregular linear opacities. The reticular pattern of end-stage fibrotic (honeycomb) lung is characterized by cystic airspaces surrounded by irregular walls. The distortion of normal lung morphology by extensive fibrosis results in irregular dilatation of segmental and subsegmental airways (traction bronchiectasis/bronchiolectasis); in the periphery of the lung, it can be difficult to distinguish dilated airways from true honeycomb change.

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Nodular pattern A nodular pattern is a feature of both interstitial and airspace disease.The distribution and density of nodules can help narrow what can be a lengthy differential diagnosis. Nodules within the lung interstitium, especially those related to the lymphatic vessels, are seen in the interlobular septa, subpleural and peribronchovascular regions; a distribution seen most commonly in sarcoidosis but also in lymphangitis carcinomatosa. Centrilobular nodules are seen in several conditions (Table 19.1). In particular, distinguishing between subacute hypersensitivity pneumonitis and respiratory bronchiolitis–interstitial lung disease (RB–ILD) can be difficult, because both cause relatively low density, poorly defined centrilobular nodules which may look identical on HRCT. A random distribution of very small well-defined nodules is seen in patients with haematogenous spread of tuberculosis, pulmonary metastases, pneumoconiosis and rarely in pulmonary sarcoidosis.

lung disease. In the first two processes, the decreased attenuation (‘black’) lung is abnormal; in infiltrative lung disease it is the ‘grey’ lung that is abnormal. In a study of 70 patients in whom a mosaic attenuation pattern was the dominant abnormality, Worthy et al showed that small airways disease and infiltrative lung disease were correctly identified but the mosaic attenuation pattern caused by occlusive vascular disease was frequently misinterpreted6. Bronchial abnormalities and the presence of air trapping on expiratory CT are the most useful discriminatory features in identifying small airways disease as the cause of mosaic attenuation. However, the phenomenon of hypoxic bronchodilatation in chronic occlusive vascular disease7, and the demonstration that air trapping is seen on expiration in acute pulmonary embolism8 complicates the interpretation. Nevertheless, the differentiation between the three basic causes of a mosaic attenuation pattern is usually easily made when clinical and physiological information is taken into account.

Ground-glass pattern A ground-glass pattern on HRCT is defined as a generalized increase in opacity that does not obscure pulmonary vessels. At a microscopic level, the changes responsible for ground-glass opacity are complex and include partial filling of the airspaces, considerable thickening of the interstitium, or a combination of the two. Ultimately though, the pattern of groundglass opacity on HRCT results from displacement of air from the lungs. Many conditions result in the non-specific pattern of ground-glass opacity but the most common causes include subacute hypersensitivity pneumonitis, acute respiratory distress syndrome (ARDS), acute interstitial pneumonia (AIP), non-specific interstitial pneumonia (NSIP) and diffuse pneumonias, particularly Pneumocystis jirovecii (carinii) pneumonia in patients with acquired immune deficiency syndrome (AIDS). The definite identification of dilated airways within areas of ground glass is usually an indication of fine fibrosis and thus usually indicates irreversible disease. The caveat is that, in certain entities (e.g. organizing pneumonia), dilated airways that are present within areas of ground glass in the acute setting may completely resolve following successful treatment.

Mosaic attenuation pattern The term mosaic attenuation pattern refers to regional attenuation differences demonstrated on HRCT.The attenuation of a given area of lung depends on the amount of blood, parenchymal tissue and air in that area, and thus the sign of a mosaic attenuation pattern is non-specific. It is the dominant abnormality in three completely different types of diffuse pulmonary disease: small airways disease, occlusive vascular disease and infiltrative

Table 19.1 CONDITIONS CHARACTERIZED BY PROFUSE CENTRILOBULAR NODULES IN HRCT Subacute hypersensitivity pneumonitis Respiratory bronchiolitis–interstitial lung disease Diffuse panbronchiolitis Endobronchial spread of tuberculosis or bacterial pneumonia Cryptogenic organizing pneumonia (unusual pattern)

IDIOPATHIC INTERSTITIAL PNEUMONIAS The term idiopathic interstitial pneumonia (IIP) is applied to a group of disorders with no known cause, and with more or less distinct histological and radiological appearances. Over the years, there have been additions and subtractions to the classification, but in 2001 an American Thoracic Society (ATS)/ European Respiratory Society (ERS) consensus panel consisting of clinicians, radiologists and pathologists sought to clarify the nomenclature by combining the histopathological pattern seen on lung biopsy with clinical and radiological features9. The current classification of IIPs is outlined in Table 19.2. Current guidelines recommend a multidisciplinary approach to the diagnosis of the IIPs and a recent study has demonstrated that dynamic interaction between clinicians, radiologists and pathologists improves interobserver agreement and diagnostic confidence10.

Usual interstitial pneumonia/idiopathic pulmonary fibrosis Usual interstitial pneumonia (UIP) is the most common histopathological pattern in patients with the clinical presentation of cryptogenic fibrosing alveolitis (CFA)/IPF. Under the new classification, the term IPF is exclusively reserved for patients with the idiopathic clinical syndrome associated with the morphological pattern of UIP. Other causes of a UIPtype pattern on histology include chronic hypersensitivity pneumonitis, asbestosis, connective tissue disease and rarely drugs. The pathological features of UIP are the presence of fibroblastic foci, normal areas, dense fibrosis and honeycombing; the crucial finding is of areas of fibrosis at different stages of maturity. The number of fibroblastic foci on lung biopsy is an important predictor of survival11. Classic chest radiographic features include bilateral asymmetric peripheral reticular opacities most profuse at the lung bases associated with lung volume loss, although in the presence of coexisting emphysema, lung volumes may be preserved or increased. The characteristic and virtually pathognomonic appearance of IPF on HRCT is of a predominantly subpleural bibasal

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HIGH-RESOLUTION COMPUTED TOMOGRAPHY OF INTERSTITIAL AND OCCUPATIONAL LUNG DISEASE

Table 19.2 HISTOLOGICAL AND CLINICAL CLASSIFICATION OF THE IDIOPATHIC INTERSTITIAL PNEUMONIAS Clinico–radiological–pathological criteria

Histological pattern

HRCT features

Idiopathic pulmonary fibrosis

Usual interstitial pneumonia

Reticular opacities Honeycombing Areas of ground-glass opacity associated with traction bronchiectasis

Non-specific interstitial pneumonia

Non-specific interstitial pneumonia

Areas of ground-glass opacity ± traction bronchiectasis Honeycombing minimal

Cryptogenic organizing pneumonia

Organizing pneumonia

Peripheral or peribronchial consolidation Areas of ground-glass opacity Perilobular pattern (increasingly recognized)

Acute interstitial pneumonia

Diffuse alveolar damage

Consolidation (dependent lung) Areas of ground-glass opacity Traction bronchiectasis (organizing phase)

Respiratory bronchiolitis–interstitial lung

RB–ILD

disease (RB–ILD)

Poorly defined centrilobular nodules Areas of ground-glass opacity Bronchial wall thickening Limited emphysema

Desquamative interstitial pneumonia (DIP)

DIP

Areas of ground-glass opacity Features of interstitial fibrosis

Lymphoid interstitial pneumonia (LIP)

LIP

Areas of ground-glass opacity Centrilobular nodules Thickened interlobular septa Thin-walled discrete cysts

reticular pattern within which there are areas of honeycomb destruction (Fig. 19.1)12. As the disease progresses, it often appears to ‘creep’ around the periphery of the lung to involve the anterior aspects of the upper lobes (Fig. 19.2); the finding of upper lobe irregularities (reticulation) is an important discriminator between UIP and other conditions with similar

Figure 19.1 Usual interstitial pneumonia. HRCT abnormalities predominate in the posterior, subpleural regions of the lower lobes and comprise honeycombing and traction bronchiectasis within the abnormal lung.

clinical presentations13. In the study by Hunninghake et al, the presence of both honeycombing and upper lobe irregularities increased the specificity for UIP from 69% (honeycombing alone) to 81%13. The presence of ground-glass opacification is not a dominant feature and when present, there is usually obvious traction bronchiectasis and bronchiolectasis. Mediastinal lymphadenopathy (up to 2 cm) unrelated to infection or malignancy is a frequent accompaniment14.

Figure 19.2 Usual interstitial pneumonia. In the upper lobes anteriorly there are peripheral irregular lines with areas of honeycombing.

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Studies have demonstrated that when a confident diagnosis of IPF is made on HRCT, the diagnosis is invariably correct15,16, and it has been suggested that a confident diagnosis of IPF made by experienced observers should obviate biopsy16. HRCT also has a role in predicting survival. A study by Flaherty et al suggested that patients with histological UIP who had definite or probable UIP by HRCT criteria had a worse prognosis than those who had interdeterminate HRCT findings17. The rapid development of a diffuse increase in the attenuation of lung parenchyma in patients with IPF should raise the possibility of an opportunistic infection (such as PCP), an accelerated phase of the disease (Fig. 19.3)18, or concurrent pulmonary oedema. Other complications include lung cancer19 and pulmonary tuberculosis (Fig. 19.4); the latter usually has atypical appearances on CT due to the presence of underlying lung fibrosis20.

Figure 19.4 Tuberculosis on a background of usual interstitial pneumonia. Biopsy of the area of consolidation in the right lower lobe confirmed tuberculosis.

Non-specific interstitial pneumonia NSIP is characterized by varying degrees of interstitial inflammation and fibrosis without the specific features that allow a diagnosis of UIP or desquamative interstitial pneumonia (DIP)21. While NSIP may have significant fibrosis, it is usually of uniform temporality (in comparison to UIP), and fibroblastic foci and honeycombing, if present, are scanty. Although the clinical features of NSIP resemble those of UIP, prognosis is considerably better22,23. Non-idiopathic NSIP is most often found on lung biopsy in patients with connective tissue disease and may be the pattern identified in some cases of drug-induced lung disease and hypersensitivity pneumonitis. On HRCT, NSIP is characterized by a predominant pattern of ground-glass opacification in a predominantly basal and subpleural distribution with or without associated distortion of airways (Fig. 19.5). A reticular pattern is common but honeycombing is sparse or absent24. In general, NSIP may be distinguished from UIP on CT by a more prominent component of ground-glass attenuation and a finer reticular pattern in the absence of honeycombing25. However, the variability of CT appearances reflects the heterogeneity of the pathological processes encompassed by NSIP and a confident diagnosis of NSIP based on CT alone is less readily made than in cases of UIP. Consolidation is reportedly a highly variable feature (0–98%24,25) and this discrepancy probably reflects the fact that some patients with non-idiopathic NSIP have significant amounts of histological organizing pneumonia, making classification of individual cases difficult.

Cryptogenic organizing pneumonia Figure 19.3 Usual interstitial pneumonia. HRCT performed (A) before and (B) after clinical deterioration in a patient with biopsy proven usual interstitial pneumonia. HRCT obtained during the accelerated phase of the disease demonstrates a generalized increase in lung attenuation and progression of both the reticular and honeycomb patterns.

A component of organizing pneumonia is identifiable in a variety of different contexts, including infection26, malignancy27, drug-related lung injury28 and in association with connective tissue disease29. However, in 1983, Davison et al30 described a clinicopathological entity of isolated organizing pneumonia in patients without an identifiable associ-

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HIGH-RESOLUTION COMPUTED TOMOGRAPHY OF INTERSTITIAL AND OCCUPATIONAL LUNG DISEASE

distribution is typically seen in patients with polymyositis or dermatomyositis. Ground-glass opacification, subpleural linear opacities and a distinctive perilobular pattern (Fig. 19.7)34 are also commonly encountered. The histopathological appearance of organizing pneumonia is a uniform temporal appearance of mild interstitial chronic inflammation associated with an intraluminal organizing fibrosis in distal airspaces. The lung architecture is generally well preserved. A complete response to a long (2–3 months) course of high-dose steroid treatment is the general rule, although in a minority of patients the process progresses with the incorporation of the organizing pneumonia into the alveolar walls as mature fibrosis35.

Respiratory bronchiolitis–interstitial lung disease and desquamative interstitial pneumonia

Figure 19.5 Non-specific interstitial pneumonia. The predominant abnormality is patchy, bilateral ground-glass opacification, mild reticulation and traction bronchiectasis. There is no frank honeycombing destruction.

ated disease. In 1985, Epler et al31 described the same entity and used the term bronchiolitis obliterans organizing pneumonia (BOOP). The ATS/ERS Consensus statement9 recommends that the term cryptogenic organizing pneumonia (COP) be used because it avoids confusion with airway diseases such as constrictive obliterative bronchiolitis. On a chest radiograph the most frequent feature of COP is patchy, often subpleural and basal, areas of consolidation with preservation of lung volumes. The areas of airspace consolidation have a propensity to progress and change location over time. On HRCT, consolidation corresponding to areas of organizing pneumonia is the cardinal feature found more frequently in the lower zones, with either a subpleural or a peribronchial distribution (Fig. 19.6)32,33; the peribronchial

Figure 19.6 Cryptogenic organizing pneumonia. HRCT through the upper lobes demonstrates areas of consolidation in a subpleural and peribronchial distribution in association with areas of ground-glass opacification (left upper lobe).

These two entities are considered together because of their strong association with cigarette smoking. All cigarette smokers have, to some degree, inflammation around their small airways (‘respiratory bronchiolitis’) but this is clinically unimportant and not considered further here. Patients generally present with an insiduous onset of dyspnoea and cough. The chest radiograph is relatively insensitive for the detection of RB–ILD and DIP and a normal chest radiograph has been reported in up to 20% of patients with RB–ILD36 and 25% in DIP37. On HRCT, the features of RB–ILD include areas of patchy ground-glass opacification (resulting from macrophage accumulation within alveolar spaces and alveolar ducts) and poorly defined low attenuation centrilobular nodules (Fig. 19.8). In addition, upper lobe centrilobular emphysema, usually of very limited extent and areas of air trapping, reflecting that the bronchiolitic element of this entity may be present38. Some patients show thickening of the interlobular septa and features of interstitial fibrosis, but this is unusual36. Ground-glass opacification is also the dominant feature seen in DIP (Fig. 19.9). The distribution is typically

Figure 19.7 Biopsy proven organizing pneumonia. There are poorly defined arcade-like and polygonal opacities (the perilobular pattern) in the subpleural and posterior regions of both lungs. The opacities resemble ill-defined thickened interlobular septa.

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Figure 19.8 Respiratory bronchiolitis–interstitial lung disease. HRCT shows (A) subtle areas of ground-glass opacification and (B) ill-defined centrilobular nodules.

and Langerhans cell histiocytosis (LCH) and interstitial fibrosis, the global term smoking related-interstitial lung disease (SRILD) has been proposed to encompass DIP, RB–ILD, LCH and interstitial fibrosis (Fig. 19.10)36,40,41.

Acute interstitial pneumonia

Figure 19.9 Several areas of non-specific ground-glass opacification in the right middle lobe and both lower lobes.

lower zone, peripheral and may be patchy39. In some patients there are HRCT features of established fibrosis (in the form of architectural distortion with dilatation of some bronchi), usually of limited extent. The majority of patients with DIP or RB–ILD have a relatively stable clinical course. Smoking cessation is an important part of the management of patients but the influence of smoking on the clinical course of these patients has not been fully delineated; some patients have persistent abnormalities on HRCT even with smoking cessation and corticosteroid therapy. Because of the significant overlap between the clinical, imaging and histological features of DIP and RB–ILD and to a lesser extent between these two patterns

Acute interstitial pneumonia (AIP) can be regarded as an idiopathic form of the ARDS and is histologically (and clinically) distinct from the other interstitial pneumonias. The histological pattern seen in AIP is that of diffuse alveolar damage (DAD), which is also found in infection, connective tissue disease, drug toxicity, toxic inhalation, uraemia and sepsis. DAD has an acute exudative phase and a subsequent organizing and fibrotic phase. Lung biopsy shows diffuse involvement with temporal homogeneity, which may imply lung injury due to a single event42. The chest radiograph shows bilateral patchy airspace opacification43. HRCT demonstrates a combination of ground-glass opacification, consolidation, bronchial dilatation and architectural distortion44. Ground-glass opacification on HRCT is found in all three phases of AIP, but coexistent traction bronchiectasis probably reflects the incorporation of established fibrosis in the proliferative and fibrotic phases45. Follow-up CT studies in survivors demonstrate clearing of the ground-glass attenuation and consolidation, leaving reticular opacities consistent with residual fibrosis. Anterior nondependent fibrotic damage in survivors secondary to barotrauma has also been reported46.

Lymphoid interstitial pneumonia The term lymphoid interstitial pneumonia (LIP) was proposed by Liebow and Carrington47 to describe a disease entity characterized by a widespread interstitial lymphoid infiltrate

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Figure 19.10 Smoking related-interstitial lung disease. Images of the (A) upper and (B) lower lobes of a 42 year old man with a 25-pack year smoking history and dyspnoea. The combination of a fine reticular pattern representing fibrosis and ground-glass opacification on a background of emphysema suggests a diagnosis of smoking related-interstitial lung disease.

of the lung, resembling lymphoma but with a clinical course more akin to a chronic interstitial pneumonia. Although in the past LIP has been considered by some to be a pulmonary lymphoproliferative disorder, evolution to frank lymphoproliferative disease is rare and thus LIP remains within the group of interstitial pneumonias9. Classically, LIP occurs in association with autoimmune diseases, most often Sjögren’s syndrome. Other diseases associated with LIP include dysproteinaemias, autologous bone marrow transplantation and viral, mycobacterial and human immunodeficiency virus (HIV) infections. Intrathoracic Castleman’s disease is frequently associated with LIP48. The incidence of LIP is approximately two-fold greater in women and symptoms of progressive cough and dyspnoea usually predominate. Common HRCT findings are nodules of varying sizes (which may be ill-defined), areas of groundglass opacification, thickened bronchovascular bundles, interlobular septal thickening and thin-walled cysts (1–30 mm) (Fig. 19.11)49,50. Airspace disease, large nodules and pleural effusions are rare in these patients. The cysts in LIP are usually discrete, are not found in clusters and are found deep within the lung parenchyma49. The cysts have been postulated to result from the lymphocytic infiltrate compressing bronchioles, causing stenosis or obstruction and subsequent postobstructive bronchiolar ectasia.

SARCOIDOSIS Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. As a consequence, the diagnosis of this syndrome is defined by the presence of characteristic clinical and radiological data along with histological evidence of noncaseating granuloma. Granulomas in the lung have a characteristic distribution along the lymphatics in the bronchovascular sheath and, to a lesser extent, in the interlobular septa and subpleural lung regions. Sarcoidosis is a disease of young

Figure 19.11 Lymphocytic interstitial pneumonitis. There is a background of ground-glass opacification and a few thin-walled cystic airspaces (the pathogenesis of these cysts is unclear).

adults, with a peak incidence in the second to fourth decades. The hilar and mediastinal nodes and the lungs are affected clinically much more commonly than any other organ or system. They are followed in decreasing order of frequency by the skin (26%), peripheral lymph nodes (22%), eyes (15%), spleen (6%), central nervous system (4%), parotid glands (4%) and bones (3%)51. Pulmonary involvement accounts for most of the morbidity and mortality associated with sarcoidosis. Sarcoidosis is traditionally staged according to its appearance on the chest radiograph: stage I, lymphadenopathy; stage II, lymphadenopathy with parenchymal opacity; stage III, parenchymal opacity alone52. Low stages at presentation are reported to have a

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better prognosis than high stages, although the precision and clinical usefulness of such ‘staging’ is questionable.

Lymphadenopathy Sarcoidosis is characterized by bilateral, symmetrical hilar and paratracheal lymphadenopathy. Some degree of lymphadenopathy is evident on a chest radiograph in about 70–80% of patients at some time during the course of the condition. Hilar lymph node enlargement ranges from the barely detectable to the massive and gives the hila a lobulated and usually well-demarcated outline. Occasionally hilar lymphadenopathy appears to be asymmetrical or, in 1–5% of cases, may even be strictly unilateral although this is distinctly unusual53,54. Marked asymmetry that is confirmed by CT is sufficiently unusual to bring the diagnosis into question. Clinically significant compression of adjacent airways, arteries and veins is extremely unusual, even though lymph node enlargement is often massive. Paratracheal lymphadenopathy may be bilateral or unilateral and in the latter instance is usually right sided. The most common manifestation of left-sided lymphadenopathy is enlargement of the aortopulmonary window nodes—a common and characteristic feature on the chest radiograph. Other mediastinal nodes (anterior prevascular, posterior and subcarinal) are often not identified as being enlarged on the chest radiograph but on CT are seen to be affected in about half of patients55. In 90% of patients with lymphadenopathy, nodal enlargement is maximal on the first radiograph and usually disappears within 6–12 months. In about 5%, however, large nodes persist more or less indefinitely and these can be a source of confusion. Recurrence of lymphadenopathy is exceedingly rare. The lymph nodes may calcify, sometimes in a characteristic eggshell fashion. This latter feature is shared by only a few conditions (Table 19.3). Although lymph node calcification is seen on the radiograph in 5% or less of patients with sarcoidosis, it may be evident on CT in up to 40% of patients with long-standing disease56. The calcification is of variable intensity but may be relatively light, and the affected lymph nodes are usually small in volume and evenly distributed throughout the mediastinum and hila (very different from calcified nodes due to tuberculous infection which usually follow a drainage path)57. About 40% of patients presenting with nodal enlargement will develop parenchymal opacities, usually within a year, and of these about one-third will go on to have persistent (fibrotic) shadowing. Nodal enlargement does not develop after parenchymal opacities have appeared.

Table 19.3 CAUSES OF EGGSHELL NODAL CALCIFICATION Sarcoidosis Silicosis Histoplasmosis Lymphoma (postirradiation) Blastomycosis Amyloidosis

Parenchymal changes Parenchymal changes probably occur histologically in all patients but are only detected on the chest radiograph in 50–70% of cases. Characteristically, parenchymal abnormalities appear as the nodal enlargement is subsiding (in lymphoma such abnormalities tend to progress in unison).The most common radiographic pattern, seen in 75–90% of patients with parenchymal opacities, is of rounded or irregular nodules 2– 4 mm in diameter, which are usually moderately well defined. Smaller or larger opacities are not uncommon, though they rarely exceed 5 mm.Very small aggregated opacities sometimes give a ground-glass appearance. All zones tend to be affected but there is usually a mid and upper zonal predominance. The second most common pattern, seen in 10–20% of patients with parenchymal opacity, is patchy airspace consolidation. Opacities sometimes contain air bronchograms and have ill-defined margins that commonly break up into a nodular pattern. They tend to involve predominantly the peribronchovascular regions of the middle and upper lungs zones, although they may be diffuse or, occasionally, have a subpleural predominance. The parenchymal opacities described above will clear completely in about two-thirds of cases and progress to fibrosis in one-third. Permanent fibrotic shadowing is unusually coarse with a mid and upper zone predominance. The radiographic pattern consists of coarse linear opacities with evidence of volume loss and ring shadowing caused by bullae or traction bronchiectasis. Occasionally a conglomerate opacity develops resembling progressive massive fibrosis. Cor pulmonale, bullous disease with or without mycetoma formation, and pneumothorax are all recognized complications of this fibrotic stage.

High-resolution computed tomography features Parenchymal opacities are well demonstrated on HRCT (Fig. 19.12)5,58 and HRCT appearances have a high sensitivity and specificity for the diagnosis. The most consistent pulmonary parenchymal abnormality is the presence of nodular opacities (1–5 mm) distributed in a perilymphatic fashion, predominantly along the bronchovascular bundles and subpleurally and, to a lesser extent, along interlobular septa. Other findings include irregular and beaded interfaces, larger ill-defined nodules with/without an air bronchogram, patchy groundglass opacities and occasional interlobular septal thickening. In advanced disease there is evidence of fibrosis, predominantly in the perihilar regions of the middle and upper lung zones (Fig. 19.13). Air trapping is a common HRCT feature of sarcoidosis and its presence shows a good correlation with indices of small airways disease on pulmonary function tests59.The combination of a peribronchovascular, subpleural distribution, small well-defined nodules, fibrosis and a mid and upper zone distribution has been highlighted as the features most helpful in making a diagnosis of sarcoidosis. In a very small number of cases, sarcoidosis has been shown to mimic IPF with intralobular septal thickening and ground-glass opacity seen predominantly in the basal subpleural regions of the lung60. Despite the better delineation of parenchymal disease on HRCT, it is not recommended as part of the initial diagnostic work-up in patients with suspected sarcoidosis; its greatest use being

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Sarcoidosis. Typical HRCT features are (A) nodular opacities which (B) may become confluent, and (C) interlobular septal thickening.

They are seen most often in the context of established disease and are subacute, lasting weeks or months. The prevalence of effusions is about 2%.

Bronchial stenosis and airflow obstruction Mild large airway narrowing may be due to nodal compression, but significant lesions are usually due to intrinsic mural sarcoidosis. Stenoses may be single or multiple and particularly affect larger airways to segmental level65. Such stenoses are very rare but can cause significant airflow obstruction or atelectasis, particularly in the middle lobe. However, the functional severity of airflow obstruction seems to be largely determined by the extent of a reticular pattern, representing established fibrosis, on HRCT66.

Figure 19.13 Fibrotic sarcoidosis. There are areas of conglomerate fibrosis in a perihilar distribution with associated bronchial distortion and volume loss. The appearances superficially mimic progressive massive fibrosis seen in the pneumoconioses.

in patients who present with an atypical chest radiograph61. Previous HRCT studies have shown that areas of parenchymal consolidation and ground-glass opacity are usually reversible, whereas little resolution is identified following treatment in patients with reticulation and architectural distortion56,62. Despite this distinction between reversible and irreversible disease on HRCT, studies comparing HRCT assessment of disease activity to clinical, scintigraphic and bronchoscopic findings have yielded contradictory results63,64. Hence, HRCT is not generally used to guide prognosis in patients with sarcoidosis.

Other thoracic findings Pleural thickering and effusions Pleural thickening and effusions are unusual manifestations of sarcoidosis and do not occur in isolation. Effusions, though commonly unilateral, may be bilateral and are usually small.

HYPERSENSITIVITY PNEUMONITIS Hypersensitivity pneumonitis, also known as extrinsic allergic alveolitis, is an immunologically mediated lung disease characterized by an inflammatory reaction to specific antigens contained in a variety of organic dusts67. Common causes include avian proteins (e.g. bird breeder’s lung) and thermophilic bacteria present in mouldy hay (farmer’s lung), mouldy grain (grain handler’s lung), or heated water reservoirs (humidifier or air conditioner lung). A more comprehensive list is given in Table 19.4. These antigens reach the alveoli where they provoke an immunological reaction that includes both type III (immune complex response) and type IV (cell-mediated) mechanisms. The cell-mediated response results in a delayed hypersensitivity reaction and the presence of granulomatous inflammation within the pulmonary interstitium. Interestingly, several studies have shown that cigarette smoking has a suppressive effect that interferes with the immunopathological process that ultimately leads to hypersensitivity pneumonitis68,69. The clinical features of hypersensitivity pneumonitis are characteristic. Approximately 6 h after exposure the patient develops fever, chills, dyspnoea and cough.There is no eosinophilia, and

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Table 19.4 MAJOR CAUSES OF HYPERSENSITIVITY PNEUMONITIS Agent

Source

Disease

Aspergillus

Mouldy hay

Farmer's lung

Thermophilic actinomyces

Compost

Mushroom worker's lung

Trichosporum asahii

Tatami mats

Japanese summer-type hypersensitivity pneumonitis

Isocyanates

Paint sprays, plastics Isocyanate hypersensitivity pneumonitis

Mycobacterium avium complex

Hot tubs

Unknown

Metal working fluids Metal worker's lung

Bird proteins

Bird feathers, excrement

Hot tub lung

Bird fancier's lung

wheeze is not a prominent feature. The radiological findings are influenced by the stage of the disease. A chest radiograph taken during the acute episode can be normal70, but typical radiographic findings include diffuse ground-glass opacification and a fine nodular or reticulonodular pattern; these two features become more prominent in the subacute phase71. Between acute attacks the radiograph may return to normal and the fluctuating nature of changes on serial radiographs is highly suggestive of the diagnosis. In chronic hypersensitivity pneumonitis, fibrosis with upper lobe retraction, reticular opacity, volume loss and honeycombing may be seen. On HRCT, the nodules of hypersensitivity pneumonitis are typically poorly defined, < 5 mm in diameter72, centrilobular70 and seen throughout the lung, although a mid to lower lung zone predominance has been variably reported (Fig. 19.14)73. Ground-glass opacity is most common in the acute phase but may also be a feature of subacute and chronic hypersensitivity pneumonitis, especially if there is ongoing exposure74. A mosaic attenuation pattern is common in hypersensitivity pneumonitis; the presence of lobular areas of decreased vascularity that show air trapping on expiratory HRCT, reflecting the coexisting bronchiolitis caused by antigen deposition in the small airways (Fig. 19.15)75. The combination on HRCT

Figure 19.14 Subacute extrinsic allergic alveolitis. HRCT shows numerous poorly defined, relatively low attenuation nodules.

Figure 19.15 Hypersensitivity pneumonitis. (A) Inspiratory image shows patchy density differences reflecting both the interstitial infiltrate of subacute hypersensitivity pneumonitis and coexisting small airways disease. (B) End-expiratory image enhances the density differences revealing several secondary pulmonary lobules of decreased attenuation.

of features of infiltrative (ill-defined nodules and ground-glass opacity) and small airways disease may be remarkably similar to that seen in patients with RB–ILD; however, the distinction can usually be made with knowledge of the smoking history. Lymph node enlargement (smaller than 20 mm) has been described in both acute and subacute hypersensitivity pneumonitis14, and the presence of thin-walled lung cysts is also an occasional feature in subacute hypersensitivity pneumonitis. Cysts range in size from 3 to 25 mm and resemble those seen in lymphocytic interstitial pneumonia76, although their pathogenesis remains uncertain. Emphysema is a reported sequela of farmer’s lung and a study has demonstrated that in hypersensi-

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tivity due to farmer’s lung, emphysema was a more prominent feature than honeycombing/fibrosis (even in never smokers) and was seen in approximately one-third of patients74. This is in comparison to pigeon breeder’s disease, where lung fibrosis is the major complication. The chronic stage of hypersensitivity pneumonitis is characterized by fibrosis, although evidence of active disease is often present. Radiological findings include intralobular and interlobular interstitial thickening, traction bronchiectasis and honeycomb destruction (Fig. 19.16)77. In some cases, there is a mid zone predominance, but the fibrotic appearance may be seen in the upper or lower lobes73. Patients with hypersensitivity pneumonitis may exhibit histological and imaging features of NSIP78,79 or UIP80,81, and thus should be considered as a differential diagnosis when either IPF or NSIP is being considered on HRCT appearances. Imaging

Figure 19.16 Chronic hypersensitivity pneumonitis. The reticular pattern with distortion of the lung parenchyma indicates established fibrosis in this case of chronic hypersensitivity pneumonitis.

features that favour hypersensitivity pneumonitis over IPF include an upper or mid zone predominance, the presence of ground-glass opacity and air trapping81.

LANGERHANS CELL HISTIOCYTOSIS Langerhans cell histiocytosis (LCH), formerly known as pulmonary histiocytosis X or eosinophilic granuloma of the lung, is a granulomatous disorder characterized histologically by the presence of large histiocytes containing rod- or racket-shaped organelles (Langerhans cells)67. The male-to-female ratio is about 4:1, and the vast majority of adult patients are cigarette smokers. In the earliest stages, patients are often asymptomatic. Others present with dyspnoea, cough, constitutional symptoms or a spontaneous pneumothorax. Pulmonary involvement is widespread, bilateral and usually symmetrical. At presentation, usually because of dyspnoea or a pneumothorax, the chest radiograph is abnormal. Typical appearances are of reticulonodular shadowing in the mid and upper zones of the lungs that are of normal or increased volume82. The nodules vary in size from micronodular to approximately 1 cm in diameter and, although histopathological examination will often demonstrate cavitation83, this feature is often difficult to appreciate on chest radiography. The classical appearances of LCH on HRCT are nodules (ranging in size from a few millimetres to 2 cm), several of which show cavitation (this feature often clinches the diagnosis) and have bizarre shapes (Fig. 19.17). At this stage of the disease, there are no obvious features of fibrosis. The distribution of disease is a useful diagnostic pointer and the typical sparing of the extreme lung bases and anterior tips of the right middle lobe and lingula is preserved even in end-stage disease84. The typical nodules of LCH85 tend to show a predictable progression through the following stages: cavitation of the nodules, thin-walled cystic lesions, and finally emphysematous and fibrobullous destruction86.

Figure 19.17 Langerhans cell histiocytosis. (A) Shows the characteristic combination of thin-walled cysts and poorly defined nodules, some of which are just beginning to cavitate. (B) Image from a patient with more advanced disease. There are numerous irregularly-shaped cysts bilaterally and a pneumothorax on the right.

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LYMPHANGIOLEIOMYOMATOSIS Lymphangioleiomyomatosis (LAM) is a disease characterized histologically by two key features: cysts and proliferation of atypical smooth muscle cells (LAM cells) of the pulmonary interstitium, particularly in the bronchioles, pulmonary vessels and lymphatics67. LAM is a rare disease seen almost exclusively in women, the vast majority of cases being diagnosed during childbearing age. Similar pulmonary abnormalities can be seen in approximately 1% of patients with tuberous sclerosis. The most commonly described radiographic manifestation of LAM is a pattern of generalized, symmetrical, reticular, or reticulonodular opacities with normal or increased lung volumes87,88. Pleural effusions occur in 10–40% of patients89–91 (these may be unilateral or bilateral) and pneumothoraces in approximately 50% of cases.The effusions are chylous and result from involvement of the thoracic duct by the leiomyomatous tissue. The CT manifestations of LAM are distinctive, characterized by numerous thin-walled cysts randomly distributed throughout the lungs with no zonal predilection92 (Fig.19.18). Imaging features that help distinguish LAM from LCH include a more diffuse distribution of cysts typically with no sparing of the bases, more regularly shaped cysts and normal intervening lung parenchyma. Occasionally HRCT may demonstrate interlobular septal thickening88 (attributed to dilatation of lymphatic channels secondary to obstruction of pleuropulmonary lymphatics) or patchy areas of ground-glass attenuation (presumably the result of pulmonary haemorrhage)89.

in each disease separately, depending upon whether imaging, physiological, or histological criteria are used to judge involvement. Although the radiographic and HRCT appearances are not specific for any of the collagen vascular disorders, they frequently provide good corroborative evidence in substantiating what is often a difficult clinical diagnosis.

Rheumatoid disease Rheumatoid arthritis (RA) is a connective tissue disease characterized by a symmetrical inflammatory arthritis. The majority of patients have extra-articular disorders, thus the term rheumatoid disease is commonly used to emphasize the systemic nature of the disorder. RA is associated with a broad spectrum of pleural and pulmonary manifestations. Most, but not all, patients with pleuropulmonary disease have other clinical evidence of RA. In a significant minority of patients with rheumatoid disease, pleuropulmonary disease antedates the development of arthritis and in general, pleuropulmonary involvement is not related to the severity of the arthritis. The most frequently encountered manifestations of rheumatoid disease in the chest are listed in Table 19.5. Pleural involvement, either manifesting as effusions or thickening, is common. Pleural effusions can be unilateral or bilateral, are usually small or moderate in size, and the majority resolve spontaneously93.

Table 19.5 INTRATHORACIC MANIFESTATIONS OF RHEUMATOID DISEASE Pleural effusion or thickening

CONNECTIVE TISSUE DISEASES

Interstitial fibrosis (most frequently usual interstitial pneumonia type) Constrictive obliterative bronchiolitis

The connective tissue diseases form a heterogeneous group of chronic inflammatory and immunologically mediated disorders, all of which affect the lung and pleura to a variable extent and in various ways. Although the lung is a particularly vulnerable target organ, the frequency of pleuropulmonary involvement varies widely within the spectrum of disease and also

Bronchiectasis Organizing pneumonia Follicular bronchiolitis Drug-induced lung disease (methotrexate) Necrobiotic nodules/Caplan's syndrome

Figure 19.18 Lymphangioleiomyomatosis. (A) There is a profusion of thin-walled cystic airspaces scattered evenly throughout the lungs. The cysts are relatively uniform in size. (B) In a more advanced case of LAM, note the small left-sided pleural effusion.

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ILD in RA is more common in men with seropositive disease. The most common histopathological pattern in RA-associated ILD is UIP with HRCT features that are indistinguishable from idiopathic cases; namely reticular opacities with honeycombing predominantly in the subpleural regions of the lung (Fig. 19.19)94. It is thought that the prognosis for RA–ILD is better than for idiopathic cases; Flaherty et al have demonstrated that patients with a connective tissue disease-associated UIP pattern had fewer fibroblastic foci and better survival when compared with patients with the idiopathic type95. NSIP is also seen but is less prevalent than in the other connective tissue diseases such as systemic sclerosis. Other pulmonary abnormalities seen in RA include follicular bronchiolitis, bronchiectasis (in up to 30% of cases) (Fig. 19.20)96,97, obliterative bronchiolitis (this

Figure 19.19 Rheumatoid arthritis with a usual interstitial pneumonia (UIP)-type pattern. In this case the HRCT appearances of peripheral reticular abnormality and honeycombing are indistinguishable from that of UIP.

can occur in patients who are on penicillamine, gold or no treatment)98, methotrexate-induced pneumonitis and organizing pneumonia94. Rheumatoid (necrobiotic) pulmonary nodules are an uncommon feature of the disease.They are usually associated with the presence of subcutaneous nodules, and like them may wax and wane. They may be single or multiple, vary in size from a few millimetres to several centimetres, are well circumscribed and may cavitate99.They are usually asymptomatic and may occur in association with pulmonary fibrosis and pleural changes. Radiologically identical nodules, characteristically appearing rapidly and in crops, may occur in patients with rheumatoid arthritis who have been exposed to silica. Radiographic findings of pneumoconiosis may be present but usually are not a prominent feature100. This phenomenon was originally described in Welsh coalminers (Caplan’s syndrome). These nodules contain dust particles and are quite different from necrobiotic nodules on histological examination. Follicular bronchiolitis (discussed here because of its frequent association with rheumatoid disease) is part of the spectrum of lymphoproliferative disease and is characterized histologically by a diffuse peribronchiolar proliferation of hyperplastic lymphoid follicles and mild, if any, alveolar interstitial inflammation101. Clinically the patients usually present during young adulthood or middle age with insidious dyspnoea102. Most cases of follicular bronchiolitis are associated with connective tissue disease, especially RA, Sjögren’s syndrome and scleroderma, but it is also seen in association with immunodeficiency syndromes including AIDS, pulmonary infections, or ill-defined hypersensitivity reactions. The cardinal features of follicular bronchiolitis on HRCT consist of centrilobular nodules measuring 1–12 mm in diameter, variably associated with peribronchial nodules and patchy areas of ground-glass opacity103. Nodules and ground-glass opacities are generally bilateral and diffuse in distribution. Mild bronchial dilatation with wall thickening and a tree-inbud pattern are less frequent findings104.

Sjögren’s syndrome

Figure 19.20 Rheumatoid arthritis. HRCT demonstrates both mild cylindrical bronchiectasis and constrictive obliterative bronchiolitis (reflected by areas of low attenuation in which there is a reduction in the number of vessels present) in this patient with rheumatoid arthritis.

Sjögren’s syndrome (SjS) is a chronic autoimmune inflammatory disease characterized by a triad of clinical features: dry mouth (xerostomia), dry eyes (keratoconjunctivitis sicca) and arthritis105. SjS can occur alone as primary SjS or in association with other autoimmune diseases—secondary SjS. A recent study evaluating the radiological and pathological manifestations of lung diseases associated with primary SjS found that NSIP was the most common entity; other pathologies included bronchiolitis, lymphoma, amyloid and atelectasis106. HRCT studies have demonstrated LIP in patients with Sjögren’s syndrome107,108; the imaging findings of which are described under the section on the IIPs. The association of LIP and amyloidosis (manifesting on HRCT as multiple irregular nodules) in patients with SjS is recognized (Fig. 19.21)107, but as these patients are also at increased risk of pulmonary lymphoma108, the finding of LIP on HRCT in conjunction with multiple nodules in a patient with SjS should at least prompt the consideration of a neoplastic process.

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Figure 19.21 Sjögren’s syndrome—lymphoid interstitial pneumonia and amyloid. There are numerous thin-walled cysts in association with multiple irregular solid nodules, some of which are heavily calcified. Histopathological examination showed marked thickening of the interstitium with an infiltrate of small, mature lymphocytes and plasma cells. Multiple deposits of amyloid were seen throughout the specimen and there was no evidence of malignancy.

Progressive systemic sclerosis (scleroderma) Progressive systemic sclerosis (SSc) is a collagen vascular disease characterized by the deposition of excessive extracellular matrix with vascular occlusion involving several organs. It commonly affects the skin (scleroderma), peripheral vasculature, kidneys, oesophagus and lungs. As with systemic lupus erythematosus, SSc occurs more frequently in women. Cutaneous features dominate the clinical picture, at least in the early stages, although the prognosis is usually determined by involvement of the heart, lungs and kidneys. ILD is common in patients with SSc and causes considerable morbidity and

mortality. The interstitium and pulmonary vasculature are the predominant sites that are affected109,110. The HRCT findings of interstitial fibrosis in SSc include peripheral reticular opacities, ground-glass attenuation associated with traction bronchiectasis and occasionally honeycomb destruction111,100. At microscopy, NSIP is increasingly regarded as the more prevalent histological pattern in patients with SSc112,113, and indeed CT studies have confirmed that patients with SSc typically have HRCT features more akin to idiopathic NSIP with a less coarse fibrosis when compared with IPF and a greater proportion of ground-glass opacification (Fig. 19.22)114. A UIP pattern is thought to occur in 5–10% of cases113. Pleural disease is much less common in SSc than in other connective tissue diseases; pleural thickening being seen on HRCT in approximately 10% of patients115. As in other diffuse fibrosing lung diseases, enlarged mediastinal lymph nodes (which histologically show reactive hyperplasia) are a frequent finding on CT116.

Polymyositis/dermatomyositis Polymyositis (PM) is an idiopathic autoimmune inflammatory myopathy that results in proximal muscle weakness117. Dermatomyositis (DM) is similar except that it is accompanied by a skin rash. Pulmonary complications of PM/DM are important determinants of the clinical course with aspiration pneumonia being the most important pulmonary disease due to its prevalence as well as its associated morbidity and mortality118. Respiratory muscle weakness and a poor cough reflex are responsible for the high prevalence of recurrent aspiration. ILD in PM/DM was first described in 1956119 and occurs in an estimated 5–47% of patients. Initial clinical presentation is with cough, dyspnoea and fever, prior to musculoskeletal manifestations of arthralgia, myalgia and weakness in 30%, with simultaneous occurrence in only 20%120. NSIP is thought to

Figure 19.22 Scleroderma. (A,B) Two patients with scleroderma showing ground-glass opacification in association with traction bronchiectasis and a fine reticular pattern. The pattern of fibrosis is closest to that of non-specific interstitial pneumonia. Note the dilated oesophagus in both examples.

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be the most common histological pattern seen in PM/DM120. The ILD can be acute and aggressive, similar to AIP, with some series reporting up to 10.5% mortality29,121, or more slowly progressive. In some, the lung disease is responsive to steroids and immunosuppression121. At presentation, the most common HRCT features of PM/DM are linear opacities with a lower lung predominance, ground-glass opacities, irregular interfaces and areas of consolidation (Fig. 19.23). Parenchymal micronodules and honeycombing are less frequently observed29. Histologically, organizing pneumonia is the correlate of consolidation and ground-glass opacification seen on HRCT. DAD is demonstrated in some cases and is associated with widespread involvement, dense dependent consolidation and extensive diffuse ground-glass opacification. Organizing pneumonia in PM/DM can also be admixed with interstitial fibrosis with a predominance of reticular elements and architectural distortion, traction bronchiectasis and honeycombing, and this overlap entity is associated with a poor prognosis122. When comparing patients with PM/DM ILD as a whole, the 3-year survival is 74.7% and 5-year survival 60.4%120, which is better than in IPF, but not significantly different from patients with idiopathic NSIP.

Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic multisystem disease of unknown origin characterized by the presence of autoantobodies against various cell nuclear antigens123. SLE is associated with widespread inflammatory changes in the connective tissues, vessels and serosal surfaces. Pleuropulmonary disease will occur in more than half of patients with SLE at some point during the course of their illness124. Although pleuritis is the most common manifestation of SLE, diverse thoracic manifestations which range from diaphragmatic dysfunction (shrinking lung syndrome) to life-threatening pneumonitis or

pulmonary haemorrhage are encountered. A list of the other pulmonary complications may be found in Table 19.6. Pleural effusions are the most common radiographic abnormality. They are frequently bilateral, usually only small in volume and, unlike those in rheumatoid disease, are often associated with pleuritic pain. Thick horizontal band shadows at the lung bases due to linear atelectasis may be secondary to the pleurisy or, more likely, restricted diaphragmatic movement. Pulmonary consolidation in patients with SLE may cause diagnostic difficulty as it may be a consequence of infection (the incidence of respiratory tract infection in patients with SLE is high due to the immunological abnormalities, immunosuppression from steroids and respiratory muscle weakness), pulmonary oedema, lupus pneumonitis, or pulmonary haemorrhage. Pulmonary oedema may be secondary to renal

Table 19.6 INTRATHORACIC MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS Pleural effusion Segmental or subsegmental collapse Lupus pneumonitis Pulmonary infection Pulmonary oedema Diaphragmatic dysfunction Interstitial fibrosis (rare) Pericardial effusion Pulmonary vascular disease Pulmonary arterial hypertension Vasculitis/capillaritis Pulmonary embolism Pulmonary veno-occlusive disease

Figure 19.23 Polymyositis/dermatomyositis. HRCT features include (A) reticular opacities and (B) areas of ground-glass opacification. The appearances of (B) are compatible with organizing pneumonia being incorporated as fibrosis.

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disease or cardiac failure. Acute lupus pneumonitis is a wellrecognized but rare manifestation of the disease that is characterized by fever, severe hypoxaemia and diffuse pulmonary infiltrates125. Radiological features are typically patchy consolidation and focal atelectasis seen predominantly in the lower lung zones with concomitant pleural effusions. Histological findings are not diagnostic but include alveolar wall damage, inflammatory cell infiltration and haemorrhage125. Compared with many other collagen vascular diseases, SLE is not commonly associated with chronic diffuse ILD. When present, reported HRCT findings include irregular linear and bandlike opacities (in part atelectasis), ground-glass opacities and interlobular septal thickening. Honeycombing which can resemble IPF is extremely rare100. Loss of lung volume is sometimes a prominent feature and is secondary to a myopathy of the diaphragmatic muscle. Diffuse alveolar haemorrhage is a rare but dramatic complication of SLE126, which manifests radiologically as widespread ground-glass opacity and consolidation. SLE is associated with increased risk of malignancy, with lymphoma being the most common124.

Ankylosing spondylitis Ankylosing spondylitis is a chronic inflammatory disease that affects mainly the axial skeleton, particularly the costovertebral, apophyseal and sacroiliac joints127. The majority of patients with ankylosing spondylitis have airway and interstitial abnormalities evident on HRCT, but these are usually mild and seldom evident on the chest radiograph128. Apical fibrosis, evident on chest radiography, is seen in approximately 1% of patients100. The upper lobe fibrosis causes upward retraction of the hila, and is often associated with bullous formation and apical pleural thickening. The changes are usually bilateral but may be unilateral, especially initially, and are indistinguishable from tuberculosis. Occasionally pulmonary changes may antedate the spondylitis. Ankylosing spondylitis is one of a number of causes (albeit a very rare one) of upper lobe fibrosis (Table 19.7). As with tuberculosis, mycetomas may form within the upper lobe cavities. The HRCT findings of ankylosing spondylitis include apical fibrosis, mild peripheral interstitial fibrosis, parenchymal bands, bronchiectasis and bullae128,129.

SYSTEMIC VASCULITIDES A number of disorders are characterized histologically by a systemic vasculitis in which the primary pathogenetic mechanism is the deposition of immune complexes in the walls of Table 19.7 CAUSES OF BILATERAL UPPER LOBE FIBROSIS Tuberculosis (including atypical mycobacterial infections) Sarcoidosis Histoplasmosis Allergic bronchopulmonary aspergillosis Chronic extrinsic allergic alveolitis Ankylosing spondylitis Progressive massive fibrosis (distinctive mass-like opacities)

blood vessels. The systemic vasculitides that most commonly affect the lung are Wegener’s granulomatosis, Churg–Strauss syndrome and Behçet’s disease. Only Churg–Strauss syndrome and Wegener’s granulomatosis will be covered in this section.

Wegener’s granulomatosis Wegener’s granulomatosis is a multisystem disease with variable clinical expression. It is characterized histologically by necrotizing granulomatous inflammation of the upper and lower respiratory tracts, the lungs being involved in approximately 90% of cases; focal necrotizing glomerulonephritis; and a small vessel vasculitis affecting arteries, capillaries and veins130. The majority of patients present with symptoms referable to the nose, paranasal sinuses, or chest; in some patients, the disease manifests solely in the respiratory tract and is known as limited (nonrenal) Wegener’s granulomatosis131. Chest symptoms include cough, dyspnoea, pleuritic chest pain and haemoptysis. Multiple nodules or masses are the most common imaging finding in Wegener’s granulomatosis, being seen in approximately 70% of cases132. Nodules range in size from a few millimetres to 10 cm, are frequently multiple, and increase in size and number as the disease progresses. Nodules are bilateral in 75% of cases, have no predilection for any lung zone, and usually show cavitation at about 2 cm in size133. HRCT may demonstrate nodules not apparent on radiography and is superior in demonstrating the presence of cavitation. Airspace consolidation and ground-glass opacities also may occur with or without the presence of nodules. Several patterns of consolidation have been described: (A) peripheral wedge-shaped lesions abutting the pleura mimicking pulmonary infarcts134; (B) a peribronchial distribution of consolidation135; and (C) a region of focal consolidation with or without cavitation (Fig. 19.24). Diffuse bilateral areas of ground-glass opacification are often a consequence of pulmonary haemorrhage132, but may also be related to necrotizing granulomatous inflammation similar to that associated with nodules. Rarely, Wegener’s granulomatosis may present as a fibrosing lung disease (closest to a UIP-type pattern) on HRCT136. Histopathologists have also described bronchocentric granulomatosis137 and organizing pneumonia138 in patients with Wegener’s granulomatosis, all of whom also demonstrated typical features of necrotizing vasculitis. Unilateral or bilateral pleural effusions are present in about 10% of patients and hilar or mediastinal lymphadenopathy has also been reported. Airway involvement is common in Wegener’s granulomatosis which may lead to subglottic, tracheal or bronchial narrowing (the latter resulting in segmental or lobar atelectasis). Mild bronchiectasis is an additional feature in Wegener’s granulomatosis occurring in up to 40% of cases134.

Churg–Strauss syndrome Churg–Strauss syndrome is an antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis affecting small arteries and veins. It is characterized histologically by the presence of necrotizing vasculitis and extravascular granulomatous inflammation rich in eosinophils, and clinically by the presence of asthma, fever and blood eosinophilia130. While the vasculitis affects both arteries and veins, predominant small vessel involvement is rarely encountered, and it is therefore not sur-

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Figure 19.24 Wegener’s granulomatosis. Images through the (A) mid and (B) upper zones in a patient with Wegener’s granulomatosis. Thick-walled cavitating mass in the left upper lobe (A). Note also the focal narrowing of the mid intrathoracic trachea (B) reflecting focal involvement by Wegener’s granulomatosis.

prising that diffuse pulmonary haemorrhage is an uncommon manifestation of Churg–Strauss syndrome. HRCT appearances largely reflect the eosinophilic infiltrate and are largely nonspecific. HRCT features include ground-glass opacities, areas of airspace consolidation, centrilobular nodules (some of which may display cavitation) and airways abnormalities attributable to asthma (Fig. 19.25)139. Histologically the airspace disease is due to eosinophilic infiltrate or foci of organizing pneumonia139. Interlobular septal thickening may be seen as a result of interstitial pulmonary oedema secondary to cardiac involvement. However, a significant proportion (up to 25%) of patients with Churg–Strauss syndrome have few or no imaging abnormalities and imaging is often of little help in making this somewhat elusive diagnosis. Even when HRCT abnormalities exist they

are not specific and the diagnostic accuracy for Churg–Strauss syndrome was less than 50% in one study140.

DRUG-INDUCED LUNG DISEASE The lung is less commonly the site of drug-induced disease than other organs such as the skin and gastrointestinal tract. Nevertheless, approximately 350 drugs can cause injury to the lungs, and the list of drugs and patterns of involvement continues to increase. Respiratory disease secondary to drugs may be the result of the pharmacological action of the drug in normal or excessive dosage, or caused by an allergic or idiosyncratic reaction. The radiological manifestations of drug-induced ILD, although heterogeneous and non-specific,

Figure 19.25 Churg–Strauss syndrome. Spectrum of HRCT features: (A) areas of ground-glass opacification, (B) small cavitating nodules,

Continued

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Figure 19.25, Cont’d (C) thickened interlobular septa, and (D) an area of airspace opacification, likely to be a peripheral infarct.

enable many alternative diagnoses to be excluded. There is no specific radiological pattern of parenchymal change associated with drug-induced lung disease and in the early stages of disease, patients with symptoms secondary to drug reaction may have a normal chest radiograph. Furthermore, data based on a small number of cases suggest that the different histological patterns of drug reaction are not always reflected by distinctive HRCT findings141. Despite these limitations, it is reasonable to understand the radiological manifestations of drug-induced lung disease via an appreciation of the underlying histological patterns of drug-induced disease142. The most common histological manifestations can be classified into DAD, chronic interstitial pneumonia (a vague term used by histopathologists which incorporates drug-induced lung disease with histologiTable 19.8

cal features that resemble either NSIP or less commonly UIP), hypersensitivity pneumonitis, organizing pneumonia and eosinophilic pneumonia142. Most drugs typically cause more than one type of histological pattern. Table 19.8 lists the drugs associated with the different histological patterns.

Diffuse alveolar damage Chemotherapeutic drugs such as busulphan, cyclophosphamide, carmustine (BCNU) and bleomycin constitute the largest group of drugs associated with this pattern of lung toxicity141. DAD usually develops a few weeks or months after initiating therapy and disease onset is heralded by progressive dyspnoea.The corresponding radiological features, not surprisingly, are similar to those found in ARDS with bilateral patchy or homogeneous

HISTOLOGICAL PATTERN OF DRUG-INDUCED LUNG DISEASE

Diffuse alveolar damage

Diffuse alveolar haemorrhage

Non-specific interstitial pneumonia

Organizing pneumonia

Eosinophilic pneumonia

Amiodarone

Amphotericin B

Amiodarone

Amiodarone

Ampicillin

Bleomycin

Cyclophosphamide

Carmustine

Carbamazepine

Captopril

Methotrexate

Nitrofurantoin

Busulphan

Interferon

Chlorpropamide

Nitrofurantoin

Amiodarone

Methotrexate

Methotrexate

Ethambutol

Carmustine

Anticoagulants

Nitrofurantoin

Sotalol

Indomethacin

Busulphan

Penicillamine

Melphalan

Nitrofurantion

Mesalazone

Sulphasalazine

Streptokinase

Phenytoin

Minocycline

Naproxen

Vinblastine

Haloperidol

Simvastatin

Phenytoin

Tetracycline Ranitidine Propranolol

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airspace consolidation involving mainly the middle and lower lung zones. HRCT demonstrates extensive bilateral groundglass opacities and dependent areas of airspace consolidation (Fig. 19.26)143. In most circumstances there are no histological features that allow separation of drug toxicity from other potential causes of DAD and the diagnosis of drug-induced lung disease requires vigorous exclusion of other potential aetiologies, most importantly opportunistic infection.

Non-specific interstitial pneumonia Drugs reported to cause an NSIP-type pattern include amiodarone, busulphan, carmustine, methotrexate, phenytoin and simvastatin142. Descriptions of HRCT findings are available for a limited number of agents, but demonstrate the same range of abnormalities described in patients with the idiopathic form of NSIP (Fig. 19.27)143,144. With disease progression, there may be evidence of fibrosis with development of a reticular pattern and traction bronchiectasis. The fibrosis is patchy in distribution and predominantly peribronchovascular,

a pattern most commonly seen in patients receiving nitrofurantoin. In some cases, however, HRCT features suggestive of irreversible fibrosis may show complete resolution on cessation of nitrofurantoin145. NSIP is the most common manifestation of amiodarone-induced lung disease146. HRCT features that have been described with amiodarone-induced lung disease include ground-glass opacities in association with fine intralobular reticulation seen predominantly in a peripheral distribution. Foci of consolidation have also been described147, and are likely to represent areas of organizing pneumonia.

Hypersensitivity pneumonitis Several drugs have been associated with a pattern of lung toxicity with radiological and histopathological features indistinguishable from hypersensitivity pneumonitis144, although in general, this pattern is an uncommon manifestation of drug-induced lung disease. Methotrexate is the best known offender; similar changes have been attributed to cyclophosphamide, fluoxetine, nitrofurantoin and amitriptyline. The radiological and HRCT findings are similar to those seen in hypersensitivity pneumonitis secondary to the inhalation of organic dust and consist of bilateral ground-glass opacities (Fig. 19.28) and/or small, poorly defined centrilobular nodular opacities141,144. HRCT and lung biopsies in methotrexate toxicity show features more characteristic of NSIP in the majority of patients with a pattern resembling hypersensitivity pneumonitis seen in only a few patients142.

Organizing pneumonia

Figure 19.26 Diffuse alveolar damage secondary to amiodarone. There is extensive bilateral ground-glass opacification and airspace consolidation. Note also the bilateral pleural effusions.

Figure 19.27 Non-specific interstitial pneumonia secondary to bleomycin. The dominant abnormality is ground-glass opacification in association with a fine reticular pattern. The pattern of fibrosis most closely resembles non-specific interstitial pneumonia.

An organizing pneumonia-like reaction has been reported most frequently in association with methotrexate, cyclophosphamide, gold, nitrofurantoin, amiodarone, bleomycin and busulphan141. The chest radiograph shows patchy bilateral areas of consolidation, masses or nodules, which may be asymmetric or symmetric. HRCT may demonstrate patchy asymmetrical ground-glass opacity and areas of consolidation which often have a predominantly peripheral or peribronchiolar distribution (Fig. 19.29)144.

Figure 19.28 Hypersensitivity pneumonitis secondary to sertraline. HRCT shows extensive bilateral ground-glass opacification and lobular areas of air trapping (arrows).

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Figure 19.29 Organizing pneumonia secondary to (A,B) nitrofurantoin and (C) amiodarone. The HRCT features of ground-glass opacification and consolidation (A,C) and a perilobular pattern (B) are in keeping with organizing pneumonia. The areas of consolidation in (C) are both peribronchial and perilobular in distribution.

Eosinophilic pneumonia Eosinophilic pneumonia is characterized histologically by the accumulation of eosinophils in the alveolar airspaces and infiltration of the adjacent interstitial space by eosinophils and variable numbers of lymphocytes and plasma cells. Peripheral blood eosinophilia is present in around 40% of patients. Eosinophilic pneumonia secondary to drug reaction is seen most commonly in association with methotrexate, sulphasalazine, para-aminosalicylic acid, nitrofurantoin and non-steroidal anti-inflammatory drugs. Chest radiography and HRCT show bilateral airspace consolidation, which tends to involve mainly the peripheral lung regions and the upper lobes141,143. The diagnosis of drug-induced disease will be missed unless specifically sought as a cause of unexplained diffuse pulmonary shadowing in patients at known risk with clinical symptoms of lung disease. It is particularly important, though often difficult, to differentiate between drug-induced disease, infections (particularly of the opportunistic variety) and metastatic malignancy in patients who are susceptible to a combination of these processes.

OCCUPATIONAL LUNG DISEASE Diseases of the lung caused by workplace and environmental exposures are common throughout both developed and developing worlds, and as industrial techniques continue to evolve, new occupational diseases will be recognized. The following section highlights the imaging features of the main pneumoconioses—silicosis, coal worker’s pneumoconiosis and asbestos-related pulmonary disease. Table 19.9 summarizes some of the other main occupational lung diseases. Hypersensitivity pneumonitis is covered in the preceding section on ILD. Work-related asthma is one of the most frequently reported occupational lung diseases in a number of industrialized countries148 but as these patients are not frequently imaged (and the contribution of imaging is negligible), this topic is not further discussed.

The International Labour Office Classification The International Labour Office (ILO) International Classification of Radiographs for the Pneumoconioses is a system

Table 19.9 EXAMPLES OF OCCUPATIONAL EXPOSURES THAT CAUSE LUNG PATHOLOGY Occupational lung disease Flock worker's lung

Pathology

Radiology

Lymphocytic bronchiolitis

Ground-glass opacities with centrilobular nodules181

Flavour worker's lung Obliterative (flavouring agents used bronchiolitis in microwave popcorn)

Mosaic attenuation pattern, air trapping, bronchial wall thickening182

Berylliosis

Noncaseating granulomas (indistinguishable from sarcoidosis) accompanied by mononuclear cell infiltrates and interstitial fibrosis

Nodules with a similar distribution to sarcoidosis, ground-glass opacities, thickened interlobular septa, reticular opacities and honeycombing (rare)183,184. Mediastinal adenopathy is less common than in sarcoidosis. Conglomerate masses are seen in advanced disease

Hard metal pneumoconiosis (alloys of tungsten carbide and cobalt, titanium and tantalum)

Giant cell interstitial pneumonia

Ground-glass attenuation and consolidation. Cysts and reticular abnormality may also occur185

used for the recording of chest radiographic abnormalities related to the inhalation of dusts. Its intent was to improve health workers’ health surveillance by facilitating international comparisons of pneumoconiosis statistics and research reports149. Thus, it was designed primarily for population epidemiology, rather than for individual diagnosis. In the ILO system, the size, shape and profusion of opacities on radiographs are classified in a detailed manner by trained observers using a set of standard radiographs. Rounded or nodular opacities are graded as p (< 1.5 mm diameter), q (1.5–3 mm), or r (3–10 mm). Irregular opacities are classified as s, t, or u, using the same size criteria. Large opacities (> 10 mm) are graded as A, B and C based on the combined dimensions of all large opacities present. The classification also scores the extent and thickness of plaques, pleural thickening, fissural thickening and

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calcified nodules. Profusion of the opacities is classified into four categories (0–3); category 0 indicating that there is no excess of small opacities above normal. The use of two profusion categories is useful when appearances lie between those of the standard radiographs. Thus, 1/0 indicates that appearances most closely resemble category 1, but that the reader has also considered category 0. Despite acknowledged limitations and problems with the ILO classification (interobserver variability, the presence of background opacities that are unrelated to dust exposure, the relative insensitivity of the chest radiograph to early disease, and the misuse of the classification in legal settlements for compensation), it remains a useful shorthand whose meaning is widely understood for population studies. HRCT classification systems for the pneumoconioses have been developed150, but it is too early to gauge whether such a classification will be widely accepted and adopted.

Silicosis/coal worker’s pneumoconiosis Silicon dioxide or silica is the most abundant mineral on earth and is formed from the elements silicon and oxygen under conditions of increased heat and pressure. Any occupation that disturbs the earth’s crust or exposes the worker to the use or processing of silica-containing rock or sand has potential risks. Mining, tunnelling through rock, quarrying, stone cutting and foundry work, amongst others, are potentially hazardous occupations. Coal worker’s pneumoconiosis (CWP) is a consequence of the inhalation of coal dust. Both coalmine dust and silica predispose workers to chronic bronchitis, simple pneumoconiosis, emphysema, complicated pneumoconiosis (progressive massive fibrosis [PMF]), lung cancer (in excess of that expected from smoking alone) and mycobacterial pulmonary infection—the risk for tuberculosis is increased three-fold in patients with chronic silicosis151. As coal also contains a variable proportion of quartz, it has often been difficult to separate the pulmonary effects of coal dust from that of silica; in general, coal of high rank (high carbon content), such as anthracite, is associated with a higher incidence of CWP. Silica causes three distinct clinical patterns of lung disease (Table 19.10) which are related to both level and duration of exposure. The earliest radiographic changes of silicosis and CWP are nearly identical. Typical appearances are a profusion

Table 19.10 EXPOSURE

of small (1–3 mm) round nodules distributed in the posterior aspects of the upper two-thirds of the lung152. Radiologically, the only difference between simple CWP and simple silicosis is that the nodules in CWP are often smaller (typically p, rather than q opacities, according to the ILO classification). With advancing disease, the nodules increase in size and number to involve all lung zones. The nodules are sometimes calcified. Hilar and mediastinal lymph node enlargement with calcification of the eggshell type is not uncommon and may be seen on the chest radiograph or CT. On CT, the micronodules are sharply defined and distributed throughout the lungs but are frequently most numerous in the upper lung zones. The nodules may be centrilobular or subpleural in location; the subpleural micronodules may become confluent, forming a ‘pseudo-plaque’153. PMF refers to the coalescence of large nodules and is much more common in silicosis than in CWP. On the chest radiograph, PMF is seen as mass-like opacities, typically in the posterior upper lobes and associated with contraction of the upper lobes and hilar elevation. Sequential evaluation of these masses often demonstrates migration towards the hila, leaving a peripheral rim of cicatricial emphysema. The outer margins of PMF often parallel the contour of the adjacent chest wall. CT confirms the architectural distortion associated with PMF (Fig. 19.30). Large lesions (> 5 cm) often show irregular low attenuation regions on CT indicative of necrosis. Frank cavitation is a less frequent finding and when present should always raise the suspicion of tuberculosis (conventional or atypical). Unilateral or asymmetric PMF may be distinguished from lung cancer by the presence of lobar volume loss and peripheral emphysema. Acute silicoproteinosis develops after exposure to high concentrations of crystalline silica. The dominant feature is the presence of an alveolar proteinaceous exudate, similar to that found in pulmonary alveolar proteinosis, hence the term acute silicoproteinosis.The chest radiograph demonstrates widespread alveolar opacity with an upper and mid zone dominance. Air

PATTERNS OF DISEASE CAUSED BY SILICA

Clinical pattern

Duration and level of exposure

Acute silcoproteinosis

Occurs in response to a massive inhalation of silica (e.g. in sandblasting) usually within a few weeks to 4–5 years after exposure

Accelerated silicosis

Develops less than 10 years after first inhalation of high concentrations of silica. Its more rapid development than in simple silicosis indicates that the worker is at great risk for the development of progressive massive fibrosis

Chronic simple silicosis

The most common manifestation usually developing after 10–50 years of low level silica exposure

Figure 19.30 Progressive massive fibrosis in coalworker’s pneumoconiosis. Mass-like opacities are seen bilaterally in the upper lobes in association with multiple small nodules and calcified mediastinal lymphadenopathy.

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bronchograms may be seen initially and hilar and mediastinal adenopathy also occur. Studies have shown that silica workers have an increased risk of IPF154,155, although epidemiological data are currently insufficient firmly to establish an aetiological link between exposure to silica and IPF-like diseases156. In addition, there has been a long-recognized association of silicosis with connective tissue disease (CTD)157. Among the CTDs, the association of silicosis and rheumatoid arthritis (Caplan’s syndrome) is more common than systemic sclerosis (Erasmus syndrome). In the development of CTD, it appears that exposure to very fine silica dust (silica flour) is necessary; this exposure may be experienced by dental technicians and workers exposed to fine scouring powders158.

Asbestos-related disease Asbestos is the generic term for a group of fibrous silicates that share the property of heat resistance. They are classified into two groups: the serpentines and the amphiboles.The only serpentine asbestos used commercially is chrysolite, which accounts for more than 90% of the asbestos used in the USA. The pathological hallmark of asbestos exposure is the asbestos body consisting of an asbestos fibre usually 2–5 µm in width. These bodies can be identified in tissue sections in interstitial fibrous tissue and intra-alveolar macrophages in broncho-alveolar lavage (BAL) fluid. The effects of asbestos on the lung are diverse and clinical manifestations of these abnormalities typically do not appear until 20 years or more after initial exposure, apart from asbestos-related pleural effusions which may be present as early as 5 years post exposure.

Benign pleural effusions The exact prevalence of benign pleural effusions is unknown, as many are subclinical. The effusions are typically haemorrhagic exudates of mixed cellularity and usually do not contain asbestos bodies. Their diagnosis is therefore reliant largely on the exclusion of other causes of effusions in an asbestos-exposed patient.The development of effusions is thought to be exposure dependent159.The effusions are often small, may be persistent or recurrent and may be simultaneously or sequentially bilateral160. Diffuse pleural thickening is the usual consequence.

Pleural plaques The most common manifestation of asbestos exposure is pleural plaques which macroscopically are discrete foci of pearly white fibrous tissue, usually 2–5-mm thick. They involve the parietal pleural almost exclusively and on the chest radiograph are classically distributed along the posterolateral chest wall between the 7th and 10th ribs, lateral chest wall between the 6th and 9th ribs, the dome of the diaphragm and the mediastinal pleura161. CT also demonstrates anterior and paravertebral plaques that are not well demonstrated on chest radiography. Calcification is reported in 10–15% of cases161. At histological examination, the plaques are relatively acellular, with a ‘basket-weave’ appearance of collagen bundles. Asbestos fibres (usually chrysolite) are often seen, but asbestos bodies are usually absent. CT is undoubtedly more sensitive for the detection of pleural plaques. Only

50–80% of cases of documented pleural thickening are detected by chest radiography162,163; on chest radiography pleural plaques were most commonly missed in the paravertebral and posterior regions of the costal pleural164. Studies have suggested that pleural plaques are not associated with significantly impaired lung function165,166.

Diffuse pleural thickening The frequency of diffuse pleural thickening increases with time from first exposure and is thought to be dose related. It results from thickening and fibrosis of the visceral pleura, which leads to fusion with the parietal pleura and may be caused by extension of interstitial fibrosis to the visceral pleura, consistent with the pleural migration of asbestos fibres. Diffuse pleural thickening superimposed on circumscribed plaques has been observed, often after a pleural effusion. Histologically, there is a similarity between pleural thickening and plaques, except that fusion of the pleural layers is suggestive of more intense inflammation. It has been shown that workers with diffuse pleural thickening have a significant reduction in forced vital capacity (FVC) and gas transfer (DLCO)167. CT is more sensitive and specific than chest radiography in the detection of diffuse pleural thickening168 and is better at the distinction between mild pleural disease and extrapleural fat169. Although oblique views can enhance detection of pleural abnormalities in cases in which HRCT is unavailable, they may also fail to distinguish plaques from extrapleural fat170.

Round atelectasis Round atelectasis, also known as folded lung, is a form of parenchymal collapse that occurs most commonly in the peripheral lung in the dorsal regions of the lower lobes. Pathological examination shows pleural fibrosis overlying the abnormal parenchyma as well as invaginations of fibrotic pleura into the region of collapse. The appearance suggests that retraction of collagen in the pleura as it matures is the cause of the collapse. Because of the pathogenetic association with fibrosis, the areas of atelectasis are always seen adjacent to the visceral pleura. A characteristic finding is the presence of crowding of bronchi and blood vessels that extend from the border of the mass to the hilum (‘comet tail’ sign)171. In most cases, the collapsed lung has a rounded or oval shape; however, wedgeand irregularly-shaped masses can also occur (Fig. 19.31).Volume loss of the affected lobe is invariably present and often associated with hyperlucency of the adjacent lung172. Serial examinations show a relatively stable appearance, and the differentiation from a lung neoplasm is usually straightforward on CT.

Asbestosis Asbestosis is defined as pulmonary parenchymal fibrosis secondary to inhalation of asbestos fibres. The lag between exposure and onset of symptoms is usually 20 years or longer. Histologically, fibrosis is first seen in the interstitium of respiratory bronchioles, particularly in the lower lobes adjacent to the visceral pleura. With advancing disease, the fibrous tissue extends into the adjacent alveolar septa, eventually involving the entire lobule173. In the

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most severe cases there is diffuse interstitial fibrosis associated with parenchymal remodelling and honeycombing. Asbestos bodies are almost always identifiable microscopically in the fibrous tissue or macrophages in residual airspaces. Early CT changes indicative of asbestosis are the presence of subpleural curvilinear lines and dots, pleural-based nodular irregularities, parenchymal bands and septal lines164.The fine reticulation eventually progresses to a coarse linear pattern with honeycombing (Fig. 19.32). These abnormalities are usually most severe in the subpleural regions of the lower lobes. HRCT–pathological correlation studies have shown that subpleu-

ral dots and branching structures correspond to peribronchiolar fibrosis174. The sensitivity of HRCT over the chest radiograph for the identification of early fibrosis in asbestos-exposed individuals is well established175,176; however, sensitivity is not 100% and a histopathological diagnosis of asbestosis can be present in patients with normal or near-normal HRCTs177.The diagnosis of asbestosis has significant implications for the patient in terms of prognosis, work ability and the possibility of receiving legal compensation.Although both the chest radiograph and HRCT can confirm previous exposure, the diagnosis of asbestosis is largely inferential and based on

Figure 19.31 Atelectasis. Two examples of rounded atelectasis in association with (A) pleural thickening and (B) a pleural effusion. In both cases, there is evidence of lobar volume loss as evidenced by displacement of fissures. The most common location of rounded atelectasis is in the lower lobes.

Figure 19.32 Asbestosis. (A) HRCT features of early asbestosis include subpleural lines (arrowheads) and fine reticulation (arrows). These subtle abnormalities persisted on prone sections. (B) In more advanced disease, a coarse reticular pattern with honeycombing, often indistinguishable from usual interstitial pneumonia on HRCT, is seen. Note the calcified pleural plaques in both examples.

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demonstrating a compatible structural lesion, an appropriate exposure history with a suitable latency, and the exclusion of other plausible conditions. One of the problems in interpreting the presence of interstitial fibrosis, whether on chest radiography or HRCT, is the fact that asbestos-exposed individuals are as likely as the rest of the population to develop other causes of fibrosis such as IPF178. Distinguishing asbestosis from IPF is also desirable, as asbestosis is associated with a much slower rate of progression and hence better prognosis. Discrimination between the two by HRCT appearances is by no means straightforward and is usually impossible. It has been suggested that subpleural dot-like or branching opacities are significantly more common in patients with asbestosis, whereas honeycombing, traction bronchiectasis with areas of confluent fibrosis and a mosaic perfusion pattern resulting from air trapping are more common in patients with IPF179. Additionally, pleural disease may be a discriminator: in Akira et al’s study, pleural disease was found in 83% (66/80) of patients with asbestosis but only in 4% (3/80) of patients with IPF179. Copley et al found no statistically significant differences in the coarseness of fibrosis between individuals with asbestosis and a cohort of individuals with biopsy-proven UIP, although the CT findings of asbestosis were strikingly different from NSIP; the quality of fibrosis was coarser, there was a lower proportion of ground-glass opacification, and a higher likelihood of a basal and subpleural distribution180.

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138. Uner A H, Rozum-Slota B, Katzenstein A L 1996 Bronchiolitis obliterans-organizing pneumonia (BOOP)-like variant of Wegener’s granulomatosis. A clinicopathologic study of 16 cases. Am J Surg Pathol 20: 794–801 139. Silva C I, Müller N L, Fujimoto K et al 2005 Churg–Strauss syndrome: high resolution CT and pathologic findings. J Thorac Imaging 20: 74–80 140. Johkoh T, Müller N L, Akira M et al 2000 Eosinophilic lung diseases: diagnostic accuracy of thin-section CT in 111 patients. Radiology 216: 773–780 141. Cleverley J R, Screaton N J, Hiorns M P et al 2002 Drug-induced lung disease: high-resolution CT and histological findings. Clin Radiol 57: 292–299 142. Myers J L, Limper A H, Swensen S J 2003 Drug-induced lung disease: A pragmatic classification incorporating HRCT appearances. Semin Respir Crit Care Med 24: 445–453 143. Rossi S E, Erasmus J J, McAdams H P et al 2000 Pulmonary drug toxicity: radiologic and pathologic manifestations. RadioGraphics 20: 1245–1259 144. Ellis S J, Cleverley J R, Müller N L 2000 Drug-induced lung disease: high-resolution CT findings. Am J Roentgenol 175: 1019–1024 145. Sheehan R E, Wells A U, Milne D G et al 2000 Nitrofurantoin-induced lung disease: two cases demonstrating resolution of apparently irreversible CT abnormalities. J Thorac Imag 24: 259–261 146. Kennedy J I, Myers J L, Plumb V J et al 1987 Amiodarone pulmonary toxicity. Clinical, radiologic, and pathologic correlations. Arch Intern Med 147: 50–55 147. Vernhet H, Bousquet C, Durand G et al 2001 Reversible amiodaroneinduced lung disease: HRCT findings. Eur Radiol 11: 1697–1703 148. Goe S K, Henneberger P K, Reilly M J et al 2004 A descriptive study of work aggravated asthma. Occup Environ Med 61: 512–517 149. International Labour Office 1980 Guidelines for the use of the ILO international classification of radiographs of the pneumoconioses, revised edition. International Labour Office, Geneva 150. Hering K G, Tuengerthal S, Kraus T 2004 Standardized CT/HRCTclassification of the German Federal Republic for work and environmental related thoracic diseases. Radiologe 44: 500–511 151. American Thoracic Society Committee of the Scientific Assembly on Environmental and Occupational Health 1997 Adverse effects of crystalline silica exposure. Am J Respir Crit Care Med 155: 761–768 152. Bergin C J, Müller N L, Vedal S et al 1986 CT in silicosis: correlation with plain films and pulmonary function tests. Am J Roentgenol 146: 477–483 153. Remy-Jardin M, Beuscart R, Sault M C et al 1990 Subpleural micronodules in diffuse infiltrative lung diseases: evaluation with thinsection CT scans. Radiology 177: 133–139 154. Brichet A, Wallaert B, Gosselin B et al 1997 “Primary” diffuse interstitial fibrosis in coal miners: a new entity? Study Group on Interstitial Pathology of the Society of Thoracic Pathology of the North. Rev Mal Respir 14: 277–285 155. Honma K, Chiyotani K 1993 Diffuse interstitial fibrosis in nonasbestos pneumoconiosis—a pathological study. Respiration 60: 120–126 156. De Vuyst P, Camus P 2000 The past and present of pneumoconioses. Curr Opin Pulm Med 6: 151–156 157. Rosenman K D, Moore-Fuller M, Reilly M J 1999 Connective tissue disease and silicosis. Am J Ind Med 35: 375–381 158. Koeger A C, Lang T, Alcaix D et al 1995 Silica-associated connective tissue disease. A study of 24 cases. Medicine (Baltimore) 74: 221–237 159. Epler G R, McLoud T C, Gaensler E A 1982 Prevalence and incidence of benign asbestos pleural effusion in a working population. JAMA 247: 617–622 160. Hillerdal G 2005 Non-malignant asbestos pleural disease. Thorax 36: 669–675 161. Peacock C, Copley S J, Hansell D M 2000 Asbestos-related benign pleural disease. Clin Radiol 55: 422–432 162. Friedman A C, Fiel S B, Fisher M S et al 1988 Asbestos-related pleural disease and asbestosis: A comparison of CT and chest radiography. Am J Roentgenol 150: 269–275

163. Schwartz D A, Galvin J R, Yagla S J et al 1993 Restrictive lung function and asbestos-induced pleural fibrosis. A quantitative approach. J Clin Invest 91: 2685–2692 164. Oksa P, Suoranta H, Koskinen H et al 1994 High-resolution computed tomography in the early detection of asbestosis. Int Arch Occup Environ Health 65: 299–304 165. Van Cleemput J, De Raeve H, Verschakelen J A et al 2001 Surface of localized pleural plaques quantitated by computed tomography scanning: no relation with cumulative asbestos exposure and no effect on lung function. Am J Respir Crit Care Med 163: 705–710 166. Sette A, Neder J A, Nery L E et al 2004 Thin-section CT abnormalities and pulmonary gas exchange impairment in workers exposed to asbestos. Radiology 232: 66–74 167. Kee S T, Gamsu G, Blanc P 1996 Causes of pulmonary impairment in asbestos-exposed individuals with diffuse pleural thickening. Am J Respir Crit Care Med 154: 789–793 168. Jarad N A, Poulakis N, Pearson M C et al 1991 Assessment of asbestos induced pleural disease by computed tomography—correlation with chest radiograph and lung function. Respir Med 85: 203–208 169. Lee Y C, Runnion C K, Pang S C et al 2001 Increased body mass index is related to apparent circumscribed pleural thickening on plain chest radiographs. Am J Ind Med 39: 112–116 170. Ameille J, Brochard P, Brechot J M et al 1993 Pleural thickening: a comparison of oblique chest radiographs and high-resolution computed tomography in subjects exposed to low levels of asbestos pollution. Int Arch Occup Environ Health 64: 545–548 171. Schneider H J, Felson B, Gonzalez L L 1980 Rounded atelectasis. Am J Roentgenol 134: 225–232 172. Lynch D A, Gamsu G, Ray C S et al 1988 Asbestos-related focal lung masses: Manifestations on conventional and high-resolution CT scans. Radiology 169: 603–607 173. Craighead J E, Mossman B T 1982 The pathogenesis of asbestosassociated diseases. N Engl J Med 306: 1446–1455 174. Akira M, Yamamoto S, Yokoyama K et al 1990 Asbestosis: Highresolution CT–pathologic correlation. Radiology 176: 389–394 175. Akira M, Yokoyama K, Yamamoto S et al 1991 Early asbestosis: evaluation with high-resolution CT. Radiology 178: 409–416 176. Gamsu G 1989 High-resolution CT in the diagnosis of asbestosrelated pleuroparenchymal disease. Am J Ind Med 16: 115–117 177. Gamsu G, Salmon C J, Warnock M L et al 1995 CT quantification of interstitial fibrosis in patients with asbestosis: a comparison of two methods. Am J Roentgenol 164: 63–68 178. Gaensler E A, Jederlinic P J, Churg A 1991 Idiopathic pulmonary fibrosis in asbestos-exposed workers. Am Rev Respir Dis 144: 689–696 179. Akira M, Yamamoto Y, Inoue Y et al 2003 High-resolution CT of asbestosis and idiopathic pulmonary fibrosis. Am J Roentgenol 181: 163–169 180. Copley S, Wells A, Sivakumaran P et al 2003 Asbestosis and idiopathic pulmonary fibrosis: comparison of thin-section CT features. Radiology 229: 731–736 181. Weiland D A, Lynch D A, Jensen S P et al 2003 Thin-section CT findings in flock worker’s lung, a work-related interstitial lung disease. Radiology 227: 222–231 182. Akpinar-Elci M, Travis W D, Lynch D A et al 2004 Bronchiolitis obliterans syndrome in popcorn production plant workers. Eur Respir J 24: 298–302 183. Newman L S, Buschman D L, Newell J D Jr, Lynch D A 1994 Beryllium disease: assessment with CT. Radiology 190: 835–840 184. Harris K M, McConnochie K, Adams H 1993 The computed tomographic appearances in chronic berylliosis. Clin Radiol 47: 26–31 185. Akira M 1995 Uncommon pneumoconioses: CT and pathologic findings. Radiology 197: 403–409

SUGGESTED FURTHER READING

Books/book chapters Hansell D M, Armstrong P, Lynch D A, McAdams H P (eds) 2005 Basic HRCT patterns of lung disease. Drug- and radiation-induced

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Reviews/papers diseases of the lung. Idiopathic interstitial pneumonias and immunologic diseases of the lung. Miscellaneous diffuse lung diseases. In: Hansell DM (ed) Imaging of Diseases of the Chest, 4th edn. Philadelphia, Elsevier Mosby, pp 143–181, 485–533, 535–629, 631–709 Franquet T 2005 High resolution computed tomography of the lungs. In: Wells A U, Denton C P (eds) Handbook of systemic autoimmune diseases, vol 2. Elsevier BV Lynch D A, Newell J D, Lee J S (eds) 1999 Imaging of diffuse lung disease. Elsevier, Ontario Schwarz M I, King Jr T E (eds) 2003 Interstitial lung disease, 4th edn. BC Decker Inc, Ontario Webb W R, Müller N L, Naidich D P (eds) 2001 High-resolution CT of the lung, 3rd edn. Lippincott-Raven, Philadelphia

Akira M 2002 High-resolution CT in the imaging of occupational and environmental disease. Radiol Clin North Am 40: 43–59 American Thoracic Society/European Respiratory Society 2002 International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med 165: 277–304 Cleverley JR, Screaton NJ, Hiorns MP et al 2002 Drug-induced lung disease: high-resolution CT and histological findings. Clin Radiol 57: 292–299 Kim J S, Lynch D A 2002 Imaging of non-malignant occupational lung disease. J Thoracic Imaging 17: 238–260 Lynch D A, Travis W D, Müller N L et al 2005 Idiopathic interstitial pneumonias: CT features. Radiology 236: 10–21 Myers J L, Limper A H, Swensen S J 2003 Drug-induced lung disease: A pragmatic classification incorporating HRCT appearances. Semin Respir Crit Care Med 24: 445–453

CHAPTER

Thoracic Trauma and Related Topics

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John H. Reynolds

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Chest wall, lungs and pleura The diaphragm The mediastinum Thoracic imaging in the intensive care patient Lung transplantation Surgical treatment of emphysema

The major organs within the chest, namely the heart, lungs and major blood vessels, play a crucial role in providing oxygen to the tissues of the body and removing carbon dioxide. This occurs by means of pulmonary ventilation, gaseous exchange at the alveoli and the transport of oxygen and carbon dioxide by the cardiovascular system. Major trauma to the chest can disrupt one or more of these processes and consequently there is a range of serious and potentially life-threatening thoracic injuries, including aortic rupture, tracheal transection, haemothorax, haemopericardium and tension pneumothorax. In developed countries, trauma is the main cause of death in children and adults under 40 years of age. Approximately 20% of trauma deaths are directly related to chest trauma and of these around two-thirds occur as a result of motor vehicle accidents. Other causes of significant chest trauma include falls from a height, occupational injuries including falls and crush injuries, knife and gunshot injuries and domestic accidents. Trauma can be broadly divided into two categories, blunt and penetrating. Blunt trauma imparts kinetic energy to the body, which leads to tissue damage either by direct impact or by inducing shearing forces within body tissues. Penetrating injuries include knife and bullet wounds which, as well as damaging structures within the body, can also introduce infection1. Major chest injuries seldom occur in isolation. Commonly associated injuries include those to the head, extremities, spine, abdomen and pelvis2. Major trauma patients are managed on arrival at hospital in accordance with the Advanced Trauma Life Support (ATLS) protocol devised by the Committee on Trauma of the American College of Surgeons3. Patients are initially assessed with a primary survey that includes evaluation of the airway, breathing and circulation, followed by a

more detailed secondary survey once the immediate threats to life have been dealt with. Radiographs (antero-posterior [AP] supine) of the chest and pelvis are performed as adjuncts to the primary survey and the initial clinical and radiographic assessment may lead to further imaging. Protocols for the imaging of acutely injured patients have been undergoing a period of evolution in recent years. Although the chest radiograph remains a pivotal investigation in the rapid triage of trauma patients, computed tomography (CT) is a more accurate technique for the characterization of virtually all thoracic injuries, particularly those of the heart, pericardium, thoracic spine, mediastinum, aorta and lungs. Many trauma patients require imaging of several body areas and current multidetector CT (MDCT) systems are able to perform a whole body study in a matter of seconds. As well as allowing a detailed cross-sectional study of the trauma patient, these advanced CT machines minimize the time the patient has to spend away from the emergency department where he/ she can be cared for more safely. The quantity of image data obtained can be problematical—one solution may be to have a brief overview of the CT study at the time the patient is in the CT unit for triage purposes followed by a more detailed interrogation of the images by the radiologist once the patient has returned to the emergency unit. Concerns about the radiation dose relating to MDCT need to be kept in mind but the low threshold for the use of CT can save the patient from other radiological procedures such as radiography of the spine or catheter angiography4.

CHEST WALL, LUNGS AND PLEURA Rib fractures Rib fractures can occur in up to 50% of patients with blunt chest trauma. More than 50% of acute fractures are missed on initial radiographs owing to the superimposition of structures or because the fracture line is not tangential to the X-ray beam5. Additional lateral or oblique views to assess the ribs are inappropriate in the acute trauma patient. They are time consuming and do not alter clinical management as rib fractures

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are almost invariably treated conservatively. The main purpose of the chest radiograph is to detect complications such as pneumothorax, haemothorax, or pulmonary contusion. Rib fractures lead to local bleeding and may result in an extrapleural haematoma. This is visible on the chest radiograph or CT study as a convex soft tissue bulge projecting towards the lung (Fig. 20.1). Fractures of the 1st to 3rd ribs imply severe trauma and may be associated with vascular, brachial plexus, spinal, or tracheobronchial injury. In one series of 730 patients, vascular injuries were seen in 24% of multiple trauma patients with 1st rib fractures6. Fractures of the 10th to 12th ribs, often better seen on an abdominal radiograph, are associated with injuries to the liver, spleen, or kidneys. Further imaging of these organs is mandatory when such fractures are detected2,7. In children, rib fractures are uncommon and are usually of the greenstick variety. Rib fractures are rare in accidental injury in children and their presence should raise the possibility of nonaccidental injury, particularly if they involve the posterior aspects of the ribs7. In children, teenagers and young adults the ribs have great elasticity. Major blunt trauma in this age group may well lead to significant intrathoracic injury, such as tracheobronchial, diaphragmatic, or aortic rupture without any associated rib fracture2. Double fractures of three or more adjacent ribs, or adjacent combined rib and sternal or costochondral fractures, result in a flail segment which moves paradoxically during the respiratory cycle (Figs 20.2, 20.3). This injury, referred to as ‘flail chest’, can lead to impaired ventilation and pulmonary atelectasis. There is usually severe associated pulmonary contusion which, together with associated injuries, contributes to a high mortality (in the region of 40%)2.

Figure 20.2 Flail chest. Chest radiograph with multiple left-sided lateral and posterior rib fractures resulting in a flail chest. There is associated left lung contusion.

Figure 20.3 Flail chest. CT image of a left-sided flail chest with a segment of the chest wall pushed inwards. This is known as a ‘stove-in-chest’.

Other chest wall injuries

Figure 20.1 Blunt trauma. CT image following blunt trauma to the right side of the chest demonstrating a rib fracture with associated extrapleural haematoma (arrowhead).

Sternoclavicular joint dislocations account for 3% of all dislocations5. Posterior dislocation of the clavicle is potentially dangerous as compression of the trachea or brachiocephalic vessels may result. This injury should be evident on clinical examination but will be better appreciated on CT. Sternal fractures occur in 8–10% of patients after major blunt trauma2. Mortality is high at 25% owing to associated injuries, which can include cardiac contusion, pulmonary contusion and haemothorax. The diagnosis can be made on a lateral radiograph. However, CT will allow assessment of associated injuries and coronal reformatted images may reveal subtle undisplaced fractures8. Fractures of the thoracic spine occur in around 9% of multiple trauma cases and around one-third of these will have

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cord injuries with neurological deficit. Fractures typically occur in the T9–T11 region and result from hyperflexion and/or axial loading, usually in motor vehicle accident victims or following a fall from a height9. Thoracic spine fractures are often missed initially as the clinical and radiographic signs can be overshadowed by other injuries (Fig. 20.4)10. An initial evaluation of the thoracic spine should be made on the chest radiograph performed on arrival in the emergency department.The radiograph should be sufficiently well exposed to allow this assessment. Any concern about overall alignment, vertebral body height, the pedicles, or widening of the paraspinal lines should raise suspicion of a spinal injury and be evaluated further. It has been traditional practice to perform spinal radiography in cases where there has been clinical suspicion of spinal fracture or where the patient’s conscious level does not allow a reliable clinical assessment. Plain radiographs are still used in clinical practice but MDCT is increasingly used in cases of non-trivial thoracic trauma. A number of studies have shown improved sensitivity of MDCT compared with plain radiographs. Wintermark et al studied 67 spinal fractures in 26 patients and found that sensitivity and interobserver agreement were much better with MDCT than with radiographs11. Sensitivity for fracture detection was 97.2% with CT compared with 33.3% with radiographs and the authors concluded that MDCT could replace plain radiography in the assessment of traumatic spinal injury.

Pneumothorax Pneumothorax is a common complication of blunt or penetrating trauma, occurring in 20–30% of major trauma victims5. In blunt trauma, the pneumothorax can result from pulmonary laceration from a fractured rib fragment or from a sudden rise in intra-alveolar pressure. On the chest radiograph a pneumothorax is diagnosed by visualizing the visceral pleura as a sharp thin line with absent lung markings beyond. Difficulty may occur with supine radiographs where air collects anterior to the lung and there is no visible lung edge. In

• THORACIC TRAUMA AND RELATED TOPICS

this situation a pneumothorax can produce an unusually sharp mediastinal border and hemidiaphragm and an abnormally deep costophrenic sulcus (Fig. 20.5)8. CT is much more sensitive than the chest radiograph and can detect the smallest of pneumothoraces (Fig. 20.6)4. Detection is important as even a small pneumothorax can increase in size rapidly if the patient receives positive-pressure mechanical ventilation. A tension pneumothorax develops if air can enter but not leave the pleural space. This may be rapidly fatal as the mediastinal shift to the contralateral side impedes venous return to the chest. Tension pneumothorax should be evident clinically. The radiograph may reveal mediastinal displacement, absent lung markings on the affected side and eversion of the diaphragm. A tension pneumothorax can develop even in the presence of a chest tube if the tube is occluded or malpositioned (Fig. 20.7)8.

Haemothorax Post-traumatic pleural haemothorax is found in 50% of major trauma victims5. The effusion is small if blood originates from the low-pressure pulmonary circulation as a result of lung contusion or laceration, but can be large and life-threatening if bleeding arises from large pulmonary vessels or from systemic vessels, such as the internal mammary arteries. On the chest radiograph an effusion may produce a meniscus appearance but, with the patient supine, it is likely that blood will accumulate posterior to the lung and will result only in a diffuse increase in density of the affected hemithorax (Fig. 20.8). Both ultrasound and CT can identify a haemothorax if the chest radiograph is equivocal12.

Pulmonary contusion Pulmonary contusion occurs in up to 75% of cases of blunt chest trauma5. In simple contusion the basic lung structure remains intact. Shock waves from blunt trauma lead to intra-alveolar and interstitial haemorrhage from the rupture of microvessels, associated with alveolar and interstitial oedema. Radiographically, contusion presents as nonsegmental consolidation typically

Figure 20.4 Thoracic spine fracture. (A) Chest radiograph, (B) localized view of the central chest and (C) thoracic spine MRI of a young man injured in a motorcycle road accident. A variety of injuries including a left-sided pneumothorax lead to the thoracic spine fracture being overlooked, but loss of height of one of the upper thoracic vertebral bodies can be seen on the localized view. MRI confirmed the fracture and demonstrated cord contusion.

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Figure 20.7 Pneumothorax. CT image demonstrating a post-traumatic pneumothorax. Despite the presence of an intercostal drain, a tension pneumothorax was developing as the drain was blocked with congealed blood. The right-sided pneumothorax is situated anteriorly and the mediastinum is displaced to the left due to the tension.

Figure 20.5 Left-sided pneumothorax seen on a supine chest radiograph demonstrating the deep sulcus sign and an unusually sharp left heart border.

adjacent to the ribs, spine, or heart—kinetic energy from the impact tends to be absorbed by the lung tissue at interfaces between tissues of different densities (Fig. 20.9)13.The extent of the consolidation depends on the severity of the injury. Radiographic opacities appear within 6 h of impact and typically clear within 3–10 d5. Shadowing that increases in the days following admission is unlikely to be due to simple contusion and should alert those responsible for the management of the patient to other possibilities, such as infection, aspiration, fat embolism, or acute respiratory distress syndrome (ARDS)13. CT will detect areas of contusion not visible on the chest radiograph4.

Figure 20.6 Pneumothorax. CT image demonstrating a very small right anterior post-traumatic pneumothorax.

Pulmonary laceration Severe blunt trauma may induce shearing forces that lead to parenchymal disruption13. Owing to the elastic recoil of the lung, the resultant tear quickly becomes a space that can fill with blood, creating a haematoma, or with air, resulting in a pneumatocele, or both. Haematomas and pneumatoceles are usually small (2–5 cm) but can be larger (Figs 20.10, 20.11). They initially may be obscured by surrounding contusion and typically resolve over a period of months. Lung herniation is a rare complication of blunt chest trauma, the lung herniating through a defect caused by rib

Figure 20.8 Haemothorax. Chest radiograph of a 22 year old female pedestrian hit by a bus. The hazy opacification within the right hemithorax is due to the presence of a large haemothorax caused by a ruptured intercostal artery.

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• THORACIC TRAUMA AND RELATED TOPICS

Figure 20.10 Pneumatocoele. CT image following blunt trauma to the left side of the chest demonstrating left-sided contusion and a traumatic pneumatocoele in the periphery of the right lung, representing a contrecoup injury.

fractures or shoulder girdle dislocation. Most cases are treated conservatively13. Lung torsion is extremely rare and tends to occur in children or in adults who have undergone a lobectomy. Initially the chest radiograph shows an abnormal configuration of the pulmonary vessels but if the lung infarcts then complete opacification of the hemithorax will occur13.

THE DIAPHRAGM

Figure 20.9 Pulmonary contusion. (A) CT image in the axial plane and (B) coronal reformatted image illustrating bilateral post-traumatic pulmonary contusion. Note the subpleural predominance of the contusion.

The diaphragm can be ruptured by both blunt and penetrating trauma. In the UK blunt trauma is the more common cause, whilst in the USA the reverse is true14,15. Up to 70% of diaphragmatic tears are missed initially5. An increasing tendency for surgeons to manage injuries such as splenic rupture conservatively places a greater onus on radiologists to detect

Figure 20.11 Haematoma. (A) Axial and (B) sagittal reformatted CT images showing a large post-traumatic haematopneumatocoele involving the left lower lobe and lingular segments of the left upper lobe. Despite its large size, this lesion resolved spontaneously over a period of 6 months.

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diaphragmatic injury16. Prompt surgical repair of diaphragmatic tears resulting from blunt trauma is essential in order to reduce the risk of subsequent complications such as bowel herniation or strangulation. Herniated bowel may itself rupture leading to contamination of the pleural space and empyema. Abdominal contents adjacent to the lung lead to impaired ventilation and atelectasis. Penetrating injuries of the diaphragm, such as may occur from a knife or bullet injury, are usually small, measuring 2 cm in length or less. They are normally diagnosed by surgical exploration in the region of the wound, including laparoscopic or thoracoscopic techniques. Imaging plays little part in their diagnosis15. Diaphragmatic rupture occurs in 0.8–5% of patients with major blunt thoraco-abdominal trauma17. A frontal impact to the abdomen leads to a massive, sudden rise in intra-abdominal pressure, which results in the rupture. In this situation, tears are usually 10 cm or more in length, are radially orientated and occur at the weakest part of the diaphragm, namely the musculotendinous junction in a posterolateral location15,17. Lateral impacts in motor vehicle accidents create a particularly high risk in that they cause compression of the thorax towards the vertebral body, which tends to stretch and tear the diaphragm16. Most clinical series show an increased incidence of left-sided tears (72–88%) in blunt trauma compared with right-sided tears17,18. Bilateral tears occur infrequently. This left-sided preponderance has been ascribed to the protective effect of the liver and the relative weakness of the left hemidiaphragm. Autopsy series, however, tend to show a more equal incidence of leftand right-sided tears19 and it is likely that many right-sided tears are missed.The smooth dome of the right lobe of the liver herniating through a right-sided tear can easily be mistaken for a normal diaphragmatic contour on the chest radiograph. If sufficient kinetic energy has been applied to the torso to rupture the diaphragm, there are usually significant associated injuries. With right-sided tears these are likely to be intra-abdominal injuries, such as hepatic, splenic, or bowel laceration. Left-sided tears are associated particularly with splenic injuries and with thoracic injury such as haemothorax and traumatic aortic injury17. The chest radiograph is relatively insensitive in diagnosing diaphragmatic rupture. In one series chest radiographs were diagnostic in only 20 of 44 patients with left-sided rupture and in 1 of 6 patients with right-sided rupture18. Radiographic findings in right-sided rupture include apparent elevation of the hemidiaphragm, loss of the diaphragmatic contour and shift of the mediastinum to the left side. Signs of left-sided tears include apparent diaphragmatic elevation, the presence of hollow viscera within the thorax, an obscured or discontinuous diaphragmatic contour and contralateral mediastinal shift. A nasogastric tube coiled within the left hemithorax is characteristic of a rupture (Fig. 20.12)17,18. Associated atelectasis, pleural effusions, lung contusion, or phrenic nerve paralysis may mask or mimic diaphragmatic tears8. Delayed imaging performed up to 6 h later may be of value in clarifying an initial equivocal chest radiograph18.This is particularly true in patients undergoing positive-pressure mechanical ventilation in whom the herniation of abdominal contents into the chest may be delayed20.

Figure 20.12 Diaphragmatic rupture. Chest radiograph showing a left-sided diaphragmatic rupture. Bowel can be seen herniating into the left hemithorax, the mediastinum is displaced to the right and there is a nasogastric tube seen coiled within an intrathoracic stomach. (Courtesy of Dr L. C. Morus, Birmingham, UK.)

Ultrasound has not gained widespread acceptance as a means of diagnosing diaphragmatic injury. The operatordependent nature of the technique together with practical difficulties such as dressings getting in the way and difficulties in interpretation in the presence of pneumothoraces or pneumoperitoneum have limited its usefulness. In practice, CT should be used whenever there is clinical or radiological suspicion of diaphragmatic injury. Before helical CT, the restriction of CT images to the axial plane created difficulties in assessing the diaphragm, which is best assessed by means of coronal or sagittal images. Despite this, certain CT signs of diaphragmatic rupture were recognized: in one series, abnormalities were found in 9 of 11 patients with surgically proven diaphragmatic rupture21 and in another CT was found to have a sensitivity of 61% and a specificity of 87% in detecting traumatic tears22. The key findings of diaphragm rupture on CT21,23 are: • discontinuity of the diaphragm • herniation of the abdominal organs into the chest • constriction of the stomach or colon as it passes through the tear (the ‘collar sign’) • dependent viscera sign whereby organs such as the spleen or liver have an abnormally posterior location due to the lack of the normal support from the diaphragm. The use of helical CT, with good quality coronal and sagittal reformatted images, should increase accuracy. Killeen et al detected 78% of left-sided and 50% of right-sided ruptures in a series of 41 patients, though cases of rupture still went undetected, particularly if no abdominal contents were herniating into the thorax at the time of data acquisition24. The advent of MDCT in the late 1990s should further enhance the role of CT with regard to diaphragmatic injury due to improved z-axis resolution and reduction in acquisition times with consequent reductions in motion artefact (Fig. 20.13).

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• THORACIC TRAUMA AND RELATED TOPICS

Figure 20.13 Rupture of the left hemidiaphragm following blunt trauma due to a road accident. (A) Chest radiograph reveals left mid zone contusion. (B) Axial and (C) sagittal reformatted CT images reveal a ruptured diaphragm on the left side with the stomach herniating through into the thorax. The stomach is constricted as it passes through the diaphragmatic tear—the so-called ‘collar sign’.

Magnetic resonance imaging (MRI) is well suited to visualizing the diaphragm, particularly on the left side. Even small tears in the region of the dome of the diaphragm can be shown by direct coronal and sagittal images (Fig. 20.14). In a study from Baltimore, MRI accurately diagnosed a diaphragmatic tear in seven patients and confirmed that the diaphragm was intact in nine25. T1-weighted images are useful as these sequences clearly show the diaphragm as a low signal intensity line with high intensity mediastinal and abdominal fat on either side. Tears are clearly depicted as defects in the low intensity line with herniation of omental fat or upper abdominal organs. Faster sequences can also be employed (e.g. fast gradient echo with fat suppression); the diaphragm is again seen as a hypodense line. Intravenous gadolinium can be helpful as it enhances contused lung and adjacent atelectasis16. Cardiac and respiratory gating is required to minimize motion artefact. MRI has the drawback that the life support devices required by the traumatized patient may not be MRI compatible and difficulties will occur in respect of patient monitoring. In practice, MRI is only performed in haemodynamically stable patients. A strategy for suspected diaphragmatic rupture has been suggested by Iochum et al16. A supine chest radiograph on admission is likely to remain the initial investigation for the foreseeable future. In the acute setting, MDCT of the chest, abdomen and pelvis should be the next investigation. If the state of the diaphragm remains in question then MRI in inspiration and expiration should be performed once the patient’s clinical condition allows.

THE MEDIASTINUM Pneumomediastinum Pneumomediastinum occurs in up to 10% of cases of blunt chest trauma. In a minority of cases, pneumomediastinum is caused

Figure 20.14 Diaphragmatic tear. Sagittal MRI showing a post-traumatic diaphragmatic tear. (Courtesy of Dr M. Bull, Sheffield, UK.)

by tracheobronchial or oesophageal rupture. In more than 95% of cases, it results from alveolar rupture due to lung trauma or positive-pressure ventilation or both. Following alveolar rupture, air tracks through the pulmonary interstitium along peribronchovascular sheaths and into the mediastinum, a process known as the Macklin effect26.Air may also enter the mediastinum from the neck or retroperitoneum. On the chest radiograph, a pneumomediastinum is manifested by lucent streaks that outline

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mediastinal structures, elevate the mediastinal pleura and often extend into the neck or chest wall. Although the signs may be better seen on a lateral radiograph, CT is more sensitive (Fig. 20.15)27.

Tracheobronchial rupture Tracheobronchial rupture is relatively uncommon and occurs in up to 2.0% of cases of major blunt trauma28. In 90% of cases the tear is located within a mainstem bronchus and in 10% it is located in the trachea, within 2 cm of the carina5. The mechanism is that of sudden chest compression against a closed glottis. Associated injuries are common and include upper rib, sternal and thoracic spine fractures13. Bronchoscopy remains the definitive investigation8. Radiographic findings include pneumomediastinum and pneumothorax, the latter typically failing to respond to a chest drain. With complete rupture of a mainstem bronchus, the lung may sag to the floor of the pleural cavity—the ‘fallen lung sign’—as the intact vessels are unable to support the lung (Fig. 20.16)13. Chen et al reviewed findings with helical CT in a series of patients of whom 14 had tracheal rupture28. CT showed direct signs of rupture in 10 cases (71%) when either a defect or wall deformity was seen. All patients with tracheal rupture had pneumomediastinum and extraluminal air within the deep cervical soft tissues. Overall, CT had a sensitivity of 85% for detecting tracheal injury and the authors concluded that CT could detect injury directly or reveal pneumomediastinum, which in either case should lead to an early bronchoscopic assessment.

Traumatic aortic rupture Traumatic aortic rupture is the cause of 16% of motor vehicle accident deaths29. Rapid deceleration at impact leads to shearing forces at the aortic isthmus, the junction between the relatively mobile arch and the descending thoracic aorta. Contributory factors include tethering by the ligamentum arteriosum and the ‘osseous pinch’, which occurs between the anterior chest wall and the thoracic spine at impact.

Figure 20.15 Extensive pneumomediastinum seen on CT following a high speed road accident. Air can be seen around the trachea though no tracheal injury was seen at bronchoscopy.

Fig. 20.16 Fallen lung sign. Chest radiograph in a patient injured in a farming accident. The right lung is seen sagging to the floor of the right hemithorax (the ‘fallen lung sign’) and a completely ruptured right main bronchus was found at surgery.

In clinical series, 90% of aortic ruptures occur at the isthmus, just distal to the origin of the left subclavian artery. In autopsy series, 20–25% of aortic injuries occur in the ascending aorta30; ruptures at this site are usually rapidly fatal owing to exsanguination or haemopericardium and cardiac tamponade. Consequently these injuries account for only 5% of cases in clinical series. Approximately 1% of aortic ruptures due to blunt trauma occur at the level of the diaphragm5. In the majority of survivors the tear involves the intima and media with the adventitia remaining intact and maintaining aortic integrity for a time. The saccular outpouching that develops in this situation is known as a pseudoaneurysm and is normally lined by a thin layer of adventitia and surrounding tissues31. This is referred to as an incomplete aortic rupture. With complete rupture the adventitia is also disrupted and is normally associated with mediastinal haemorrhage which (if the patient survives) may progress to apical pleural capping and haemothorax5. Seventy per cent of all patients with aortic rupture die at the scene of trauma and 80–90% die before they can be treated in hospital. About 10–20% of patients with aortic injury will reach hospital and of these, 60–70% will survive, compared with only 2% who survive if the diagnosis is missed or delayed29,30. Untreated survivors invariably develop a chronic pseudoaneurysm at the site of the tear5. Early and accurate diagnosis is essential for maximum patient survival. The initial study in suspected traumatic aortic rupture is likely to be the supine chest radiograph. Portable radiographic equipment, monitoring devices in the field of view, the AP projection, gravitational effects on mediastinal vessels and adjacent pulmonary contusion all contrive to make interpretation difficult. The chest radiograph must be sufficiently well exposed to allow visualization of the aorta, the lateral aspect of which should be visible as a smooth contour

CHAPTER 20

from the aortic knuckle to the diaphragm. The radiograph must be studied for signs of mediastinal haematoma13 and therefore possible aortic rupture (Fig. 20.17). These signs include: • Widening of the mediastinum. As a guide, a wide mediastinum can be regarded as one with a width above the level of the carina of 8 cm or more or, alternatively, the mediastinum forms more than 25% of the width of the chest at this level. Too much weight, however, should not be placed on these absolute values if the subjective impression is of a wide mediastinum. Body habitus, radiographic projection, magnification and diminished inspiration all cause further diagnostic difficulties. • Blurring of the contours of the aortic arch and filling in of the aortopulmonary window. • A left apical pleural cap due to extrapleural haematoma and possibly a left pleural effusion. • Deviation of the trachea or a nasogastric tube to the right and depression of the left mainstem bronchus. • Widening of the right paratracheal stripe and the paraspinal lines. Although not practical in many trauma patients owing to haemodynamic instability and concerns over spinal injury, an erect PA chest radiograph, if it can be performed, will remove some of the interpretational difficulties seen with the supine radiograph. Despite the potential problems in its interpretation, the chest radiograph is of importance in deciding on the need for further imaging. Although occasional cases have been reported, it is very rare for a patient with traumatic aortic rupture to have a normal chest radiograph—the normal chest radiograph has a negative

Figure 20.17 Aortic rupture and mediastinal haematoma. Chest radiograph in a patient with a post-traumatic aortic rupture and mediastinal haematoma. Features present include a widened mediastinum, filling in of the aortopulmonary bay and the development of a left apical pleural cap. (Courtesy of Dr L. C. Morus, Birmingham, UK.)

• THORACIC TRAUMA AND RELATED TOPICS

predictive value of 96–98% for aortic rupture32.The chest radiograph does however lack specificity as, in the majority of cases, mediastinal haematoma is secondary to bleeding from small mediastinal veins. Only 12–25% of cases of mediastinal haematoma correspond to aortic rupture at angiography5. The difficulties in interpreting the chest radiograph in the acute trauma setting mean that further investigation is often necessary in cases of suspected traumatic aortic rupture, either to confirm or exclude aortic injury. Historically, catheter angiography has been the investigation of choice for this role. However, the increasing availability and improved image quality of MDCT, coupled with the need for CT of the head or spine, all make CT (rather than angiography) the second-line investigation after the chest radiograph. Furthermore, catheter angiography is time consuming and, although relatively safe, is not entirely without risk. Arterial puncture, catheter manipulation and the injection of contrast medium all pose a small risk to the patient33. Initially there was scepticism about the validity of using CT for this purpose but a number of large studies have now been performed which confirm the accuracy of CT in assessing the aorta34–36. The studies that have been performed have consistently demonstrated that good quality helical CT has a very high negative predictive value for aortic injury—usually at or approaching 100%34,35. This is of great practical importance as it means that when the aortic contour is smooth and clearly defined with uniform density of surrounding mediastinal fat, the aorta can be regarded as intact. Haematoma not adjacent to the aorta and without direct signs of aortic injury can be ascribed to bleeding from mediastinal veins. Peri-aortic haematoma with no direct signs of injury is more problematical and in some centres may lead to further assessment with angiography. The CT signs of aortic injury can be subdivided into direct and indirect. The direct signs consist of pseudoaneurysms and intimal flaps, whilst peri-aortic haematoma is regarded as an indirect sign (Figs 20.18, 20.19)37. In a review of 34 cases, pseudoaneurysm was seen in 97% of cases and intimal flaps in 91% and one or other of these signs was seen in all cases. Peri-aortic haematoma was identified in 91% of cases37. With advances in image quality more subtle aortic injuries are now being recognized. The term minimal aortic injury is used to describe lesions such as small intramural haematoma or intimal thrombus. Such lesions may be treated conservatively and serial CT studies may show resolution of the abnormality over time4. Surgical repair has been the traditional treatment for traumatic aortic rupture but recently endovascular stenting has been used with increasing frequency. MDCT allows effective follow-up of patients treated in this way31. Angiographic signs of traumatic aortic rupture include irregularity of the aortic isthmus, pseudoaneurysm formation and the presence of a linear radiolucency across the aorta5. The advances with regard to the assessment of trauma patients with CT mean that angiography is now seldom performed as a diagnostic study but may be performed as an adjunct to endovascular stent insertion.

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Figure 20.18 Aortic dissection. (A) Axial and (B) sagittal reformatted CT images following a high speed road accident. An acute post-traumatic aortic dissection can be seen along with a small amount of mediastinal haematoma.

In many centres, transoesophageal echocardiography (TOE) is used effectively to assess aortic integrity as it gives good visualization of the intima in the region of the ligamentum arteriosum38. TOE has drawbacks in that it is operator dependent, does not assess the ascending aorta and is contraindicated in patients with maxillofacial injuries and in those in whom cervical spine or oesophageal injury is suspected.

swallow examination will reveal the site of a tear in 90% of cases. In most centres a water-soluble contrast agent is used initially, followed by a barium study if this is negative. Prompt diagnosis and treatment is required if mediastinitis is to be avoided39.

The oesophagus

Pneumopericardium can result from penetrating and, less frequently, from blunt trauma8. On the chest radiograph, air within the pericardium outlines the heart and only extends as far superiorly as the pericardial reflection at the root of the great vessels. The CT findings of blunt cardiac trauma include pneumopericardium, haemopericardium and intrapericardial contrast medium extravasation from a ruptured cardiac chamber8. Myocardial contusion, which is associated with sternal fracture, is relatively common but rarely clinically significant13.

The oesophagus may be ruptured by blunt or penetrating trauma though most perforations are iatrogenic, being due to endoscopy with or without therapeutic dilatation. Chest radiography in oesophageal perforation may show a pneumomediastinum and a left-sided pleural effusion. A contrast medium

The heart Pneumopericardium

Thoracic duct Thoracic duct disruption is almost always the result of penetrating trauma, with surgery being the most common cause13. The result is a chylous pleural effusion. Initial management is with chest tube drainage in the hope that this will encourage pleural adhesion and seal the leak. If this is unsuccessful, surgical ligation will be necessary39. An assessment of the site of rupture may be made with lymphoscintigraphy.

THORACIC IMAGING IN THE INTENSIVE CARE PATIENT Figure 20.19 Pseudoaneurysm. CT image following blunt trauma with aortic injury. A pseudoaneurysm is visible at the aortic isthmus (arrowhead) but in addition some extravasation of contrast has occurred indicating that there has been a complete disruption of the aortic wall. (Courtesy of Dr J. Poels, Birmingham, UK.)

The chest radiograph in the postoperative or critically ill patient on an intensive care unit (ICU) can present interpretational difficulties.The clinical problems are often complex and rapidly changing, yet the chest radiograph remains central to the diagnostic assessment. CT and ultrasound are useful adjuncts for

CHAPTER 20

when the chest radiograph alone cannot answer a clinical question. The AP projection, short tube–radiograph distance and less than full inspiration lead to lack of sharpness and particular difficulty in assessing the cardiac shadow and lung bases. The use of computed radiography and of grids can improve image quality but interpretation remains challenging.

Cardiopulmonary disease Atelectasis Atelectasis is a common finding in the critically ill patient and represents areas of nonaerated lung. Retained secretions is the most common cause. The extent can vary from linear bands of subsegmental atelectasis through to more extensive opacification to lobar collapse40. Air bronchograms may be visible. Atelectasis is usually basal with a particular predominance in the left lower lobe following cardiac surgery40.

Aspiration Aspiration factors that predispose to aspiration include a reduced conscious level and the presence of a nasogastric tube which disrupts the function of the oesophagogastric sphincter. Radiographic infiltrates normally appear within a few hours of aspiration of gastric contents and often progress for 24–48 h. There is usually a more pronounced radiological abnormality when acidic gastric contents are aspirated—pH neutral fluids such as blood may produce little or no abnormality. When present, the infiltrates are usually patchy and diffuse. They are usually bilateral or mainly right sided and are most commonly seen in the bases or superior segments of the lower lobes. Most cases show evidence of regression after 72 h. Persistent or increasing radiographic shadowing after this time raises the possibility of complicating infection or retained secretions. Any CT on an ICU patient showing dependent consolidation should raise the possibility of aspiration or infection (Fig. 20.20)41.

Pulmonary oedema Pulmonary oedema in the ICU patient may be due to a number of aetiologies.The most common causes are cardiac failure and overhydration41.

• THORACIC TRAUMA AND RELATED TOPICS

With cardiac failure the heart is typically enlarged and pleural effusions are common. Upper lobe blood diversion is a normal finding on a supine radiograph so this sign, useful in the erect situation, cannot be used. Cardiogenic pulmonary oedema results in diffuse airspace opacity in association with interstitial lines (Kerley A and B lines) and peribronchial cuffing. An enlarged vascular pedicle (the width of the mediastinum just above the aortic arch) may also be seen41. Overhydration oedema may be radiologically indistinguishable from cardiogenic oedema. Overhydration features a more central distribution of oedema and a wider vascular pedicle compared with cardiogenic oedema41. A comparison of the key radiographic features of cardiogenic versus noncardiogenic oedema is provided in Table 20.1.

Pneumonia Nosocomial, or hospital acquired, pneumonia is estimated to occur in about 10% of ICU patients and the most common infecting organisms are Gram-negative bacteria, Staphylococcus aureus and fungi42. The infection may be difficult to detect as the clinical features of outpatient pneumonia, such as fever, leukocytosis, or sputum production may not be present. The radiological appearances of pneumonia in the intensive care patient are non-specific41. There may be lobar or segmental consolidation containing air bronchograms. Consolidation without loss of lung volume is particularly suggestive of infection. Some patients may have more diffuse consolidation with air bronchograms that may be symmetrical or asymmetrical and may be indistinguishable from pulmonary oedema. The development of a cavity within an area of consolidation increases the likelihood of the presence of infection with necrosis or abscess formation. An associated pleural effusion may be parapneumonic. Loculation of pleural fluid would be suggestive of an empyema. Infection in the ICU patient may result from haematogenous spread with the development of septic emboli. Radiographically, these manifest as multiple rounded areas of consolidation which typically have a peripheral and basal predominance. The areas of consolidation typically cavitate—this is generally easier to appreciate on CT than on plain radiographs41. Pulmonary haemorrhage can produce consolidation that may mimic infection. This may occur following trauma or following surgical or other interventional procedures.

Table 20.1 COMPARISON OF RADIOGRAPHIC APPEARANCES IN CARDIAC VERSUS NONCARDIAC OEDEMA40

Figure 20.20 Recurrent aspiration. Axial CT image in a patient with oesophageal dysfunction due to systemic sclerosis. Multiple areas of airspace opacity in the lower zones of the lungs are due to recurrent aspiration.

Signs

Cardiac

Renal

ARDS

Cardiomegaly

Present

Present

Absent

Vascular redistribution

Present

Present

Absent

Widened vascular pedicle

Present

Present

Absent

Interstitial lines

Present

Present

Absent

Peribronchial cuffing

Present

Present

Absent

Airspace opacification

Diffuse perihilar

Central perihilar

Patchy, peripheral

Pleural effusions

Present

Present

Absent

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Pulmonary embolism Pulmonary embolism is a common cause of morbidity and mortality in the ICU patient. Trauma patients are particularly susceptible to this complication. Predisposing factors include prolonged immobilization and the frequency of surgical procedures. The clinical signs are non-specific. The chest radiograph is of limited value. It may be normal or reveal non-specific atelectasis. A peripheral area of more or less wedge-shaped consolidation may indicate associated infarction (the so-called ‘Hampton’s hump’). Regional oligaema with sharp cut-off of a pulmonary embolism may be seen (the Westermark sign). Traditional investigations have included ventilation perfusion scintigraphy and pulmonary angiography but CT pulmonary angiography (CTPA) has become the preferred technique for confirming or excluding the presence of pulmonary embolism in the ICU patient. Studies have shown that CTPA has a very high sensitivity and specificity with a high negative predictive value for the detection of pulmonary embolism. CTPA may also identify other causes for the patient’s symptoms such as an undetected pneumothorax43.

Haemorrhage Bleeding can occur following thoracic surgery or other thoracic interventional procedures.The coagulation disturbances that are part of cardiopulmonary bypass predispose to a certain amount of postoperative bleeding, which normally results in a small quantity of blood passing out from mediastinal drains. More extensive bleeding may produce radiographic abnormality, depending on its location. Haemorrhage into the mediastinum may produce a widened mediastinum on the chest radiograph with displacement of drains or tubes. Haemorrhage into a lung will produces consolidation that can mimic a pneumonia44. Diffuse alveolar haemorrhage can occur as a complication of bone marrow transplantation. This typically produces bilateral airspace opacity on the chest radiograph, similar to that seen in pulmonary oedema45.

Table 20.2 CAUSES OF ACUTE RESPIRATORY DISTRESS SYNDROME48 Pulmonary causes

Extrapulmonary causes

Pulmonary contusion

Nonpulmonary injury (accidental and following surgery)

Aspiration of gastric acid contents

Burns

Smoke inhalation

Hypovolaemia

Near drowning

Hypoperfusion

Pneumonia

Massive blood transfusion

Fat embolism

Systemic sepsis

oedema, capillary congestion and airspace filling with oedema and red blood cells. Pulmonary vascular abnormalities including microvascular thromboses are also common. This phase is followed by the proliferative phase which occurs 7–14 d after initial injury and is characterized by organization of the airspace exudates by macrophages and fibroblasts. Cellular proliferation is accompanied by synthesis and deposition of collagen. If sufficient collagen is deposited, the patient may enter a fibrotic phase with parenchymal fibrosis, though in many patients much of the lung abnormality resolves with little or no residual histopathological or functional abnormality46. The earliest radiographic findings in the exudative phase of ARDS are those of patchy, ill-defined airspace opacities in both lungs (Fig. 20.21). Interstitial oedema is variably present46. The patchy opacities may progress to more diffuse consolidation. The airspace opacities tend to have a more peripheral distribution than those seen in relation to cardiogenic pulmonary oedema and pleural effusions are seldom seen on the supine radiographs obtained on such patients46. After a week or so, reticular opacities can be seen, corresponding to the fibrosis observed pathologically.

Acute respiratory distress syndrome A variety of direct and indirect insults to the lung can result in increased permeability of the pulmonary microvasculature, allowing protein rich fluid to pass into the alveolar spaces of the lung at normal hydrostatic pressures. Such patients may go on to develop the clinical syndrome of ARDS which is characterized by respiratory failure refractory to oxygen administration, diminished pulmonary compliance, normal pulmonary capillary wedge pressure and diffuse parenchymal infiltrates on the chest radiograph46,47. The terms ARDS and acute lung injury (ALI) describe essentially the same clinicopathological process.The difference is merely one of severity: ALI is defined as a ratio of arterial to inspired fraction of oxygen of less than 300 mmHg while ARDS is the more severe form of the disease with a ratio less than 200 mmHg48. The common causes of ARDS are summarized in Table 20.2. The pathological changes within the lung in patients within ARDS are described by pathologists as diffuse alveolar damage. Broadly speaking this can be divided into three phases. Initially there is an exudative phase, characterized by interstitial

Figure 20.21 Acute respiratory distress syndrome (ARDS). Chest radiograph in a patient with ARDS due to extrathoracic trauma. Bilateral airspace opacity is seen.

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CT findings in ARDS are characterized by diffuse groundglass opacity and gravity-dependent atelectasis. It has emerged that there are tendencies towards different patterns of CT abnormality depending on the underlying cause for the lung injury. Injuries that may lead to ARDS can be subdivided into direct causes, such as pneumonia, aspiration and near drowning and indirect (or extrapulmonary) causes such as sepsis, hypovolaemic shock, acute pancreatitis and non-thoracic trauma. Goodman et al studied 33 patients with ARDS with CT and found that ground-glass opacity was the dominant abnormality in patients with ARDS due to extrathoracic causes whilst with direct pulmonary injury, ground-glass opacity and consolidation were equally prevalent. Direct injury tended to cause asymmetrical consolidation whereas extrapulmonary causes tended to result in symmetrical ground-glass opacity. Air bronchograms were almost universal in both groups and small pleural effusions were seen in about a half of the patients49. Desai et al reviewed the CT appearances of 41 patients with ARDS. They found that what they referred to as a typical appearance of ARDS occurred more frequently in cases with an extrapulmonary cause50.The so-called typical feature of ARDS more strongly associated with an extrapulmonary cause is consolidation in the dependent, posterior parts of the lung with the density reducing more anteriorly. The reduction in density is usually gradual with consolidation merging with areas of ground-glass opacity with normal lung in the most anterior portion of the chest. With ARDS from pulmonary causes, the overall extent of consolidated lung and ground-glass opacity is about the same but the opacities tend to be patchily distributed throughout the lungs, without the gradation from dependent to nondependent areas (Fig. 20.22). Cystic spaces were a feature of the atypical appearance of ARDS. It is thought that the areas of dependent consolidation or opacification in ARDS represent areas of atelectatic lung which is compressed by overlying oedematous parenchyma50. Nondependent pulmonary opacities (seen primarily from pulmonary causes of ARDS) are likely to represent simple consolidation.The patterns of airspace opacity noted in the studies comparing pulmonary with extrapulmonary causes of ARDS can serve as a useful guide to the clinician but may not allow a specific cause to be identified. In many patients the causes of ARDS are multifactorial with a combination of pulmonary and extrapulmonary causes being present. Desai et al analysed the CT findings in long-term survivors of ARDS51. The most common abnormality in the survivors was a reticular pattern (indicating fibrosis) and this had a striking anterior distribution (Fig. 20.23). A suggested explanation for this anterior distribution is that the more dependent collapsed and consolidated lung is protected from injury due to barotrauma related to mechanical ventilation.

Extrapulmonary air Air may escape from the normal airways in the lung due to blunt or penetrating trauma. In the ICU setting alveolar disruption from barotrauma may lead to an air leak. Surgery and other medical procedures are another cause of extrapulmonary air. Possible locations for extrapulmonary air are:

• THORACIC TRAUMA AND RELATED TOPICS

Figure 20.22 Acute respiratory distress syndrome (ARDS). CT images in two patients. (A) This patient’s ARDS was due to an extrapulmonary cause and the CT shows increased opacification in the posterior, dependent portions of the lungs and ground-glass opacity more anteriorly. A right-sided intercostal tube is also present and part of a Swan–Ganz catheter can be seen in the left main pulmonary artery. (B) This patient’s ARDS was related to pulmonary infection and there is patchy airspace opacity present with no gradation from dependent to nondependent lung being seen.

• • • • •

interstitial pulmonary spaces the mediastinum the pleural space the pericardium subcutaneous tissues.

Interstitial pulmonary air in adults is difficult to recognize radiographically. Escaped air dissects along bronchovascular structures towards the mediastinum. The appearance may superficially appear as air bronchograms, but, unlike air bronchograms, the lucencies do not branch or taper towards the lung periphery52. Pneumomediastinum results in linear streaking of air density within the mediastinum. Depending on the amount of air present, normal anatomical structures may become visible.The thymus may be visible; air may be seen anterior to the pericardium (best appreciated on a lateral radiograph); air surrounding the pulmonary arteries can produce a ringlike lucency; air on either side of a bronchial wall results in unusually sharp

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ing radiographically occult effusions. When performing ultrasound on the ICU it is important to evaluate the posterior, dependent aspect of the hemithorax in question in order that effusions are not overlooked—this will usually involve some manœuvring of the patient.

Support and monitoring apparatus Airway

Figure 20.23 Post acute respiratory distress syndrome (ARDS) fibrosis. CT image following recovery from ARDS. Reticular opacities and traction bronchiectasis can be seen anteriorly indicating fibrosis.

delineation of the wall—the double bronchial wall sign; and air over the diaphragmatic surface leads to the continuous diaphragm sign53. As has been discussed in the prior section on thoracic trauma, diagnosing a pneumothorax on a supine AP chest radiograph can be challenging. The classical appearance of a lung edge with absent lung markings beyond may well not be present. In the supine position, air preferentially accumulates anterior to the lungs and abuts the mediastinal structures. Unusually sharp demarcation of a heart border or mediastinal vascular structure such as the superior vena cava may be the only indication on the radiograph of a pneumothorax. An unusually deep costophrenic sulcus (the ‘deep sulcus sign’) is another indicator of pneumothorax on an anterior radiograph (see Fig. 20.5)52. With a subpulmonary pneumothorax there may be a hyperlucent upper quarter of the abdomen and a sharply demarcated diaphragmatic surface52. Pneumopericardium may result as a consequence of barotrauma in children but in adults is more likely to be a consequence of a cardiothoracic surgical procedure. Features indicating pneumopericardium rather than pneumomediastinum include outlining of the superior pericardial reflection around the great vessels with air and visualization of the main pulmonary artery52.

Pleural effusions Pleural effusions are common in the ICU setting and may be related to trauma, congestive cardiac failure, fluid overload, pneumonia, or surgery. In the erect patient an effusion manifests as blunting of the costophrenic angle with increased basal radiographic density. In the supine patient, pleural fluid, when free rather than loculated, tends to collect in a posterobasal location. This results in a diffuse, hazy increase in density over the lower lungs through which bronchovascular markings may still be seen. Fluid in a subpulmonary location may cause apparent elevation of the hemidiaphragm41. In cases of uncertainty both CT and ultrasound can be of value in detect-

Monitoring the presence and position of the various tubes and catheters used in the critically ill patient is an important aspect of reading an ICU chest radiograph. Endotracheal tubes are inserted to maintain an airway and administer oxygen. The ideal position for the tip is in the mid trachea about 5 cm cranial to the carina.This allows for a degree of upward or downward movement which can occur when the head is moved. A tube positioned too inferiorly will tend to enter the right main bronchus leading to impaired ventilation and, ultimately, collapse of the left lung54. For longer periods of intubation a tracheostomy tube is likely to be employed. These have the advantage of not moving with movement of the head. The tip of the tube should lie between one-half and two-thirds of the distance between the stoma and the carina.The cuff should fill but not distend the trachea wall54.

Intravascular devices Catheters are commonly inserted to monitor central venous pressure (CVP). On the chest radiograph the tip of the catheter should be projected between the medial end of the 1st rib, at the junction of the brachiocephalic vein and superior vena cava, or within the superior vena cava itself. Peripherally inserted central catheters (PICC) have a small calibre and can be left in place for longer durations to allow completion of a course of intravenous therapy. Ideally, PICCs should terminate within the superior vena cava54. Monitoring of left-sided cardiac pressures using pulmonary capillary wedge pressure (PCWP) is critical for maintaining accurate blood volume. The Swan–Ganz catheter normally used for this purpose is introduced into the pulmonary artery about 5 cm distal to the main pulmonary artery bifurcation. A balloon is then inflated to allow the catheter to float into the wedge position.The catheter, when in use, should not extend beyond the proximal interlobar arteries on the chest radiograph—more distal positioning increases the risk of associated pulmonary infarction54. Other devices that may be encountered include intra-aortic balloon counterpulsation devices, transvenous and epicardial pacing wires, thoracostomy tubes and nasogastric tubes. The main tubes and lines encountered on ICU images are summarized in Table 20.3.

LUNG TRANSPLANTATION Lung transplantation is widely accepted as a form of therapy for a range of end-stage lung and pulmonary vascular diseases. Surgical options include heart–lung, single lung or bilateral lung transplantations. Single lung transplantation has the advantage of increasing the overall number of patients who can potentially receive a

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Table 20.3

• THORACIC TRAUMA AND RELATED TOPICS

LINES AND TUBES ENCOUNTERED ON AN ICU CHEST RADIOGRAPH40,44

Appliance

Function

Optimum location of tip

Endotracheal tube

Ventilatory support

3–8 cm above carina

Swan–Ganz catheter

Wedge and right heart pressures

Right or left pulmonary artery

Central venous pressure catheter

Central venous pressure

Superior vena cava

Left atrial catheter

Left atrial pressure

Left atrium

Peripherally inserted central catheter line

Intravenous therapy

Superior vena cava

Mediastinal drains

Mediastinal fluid evacuation

Anterior mediastinum or posterior pericardium

Pleural tubes

Pleural space evacuation

In pleural space via mid axillary line, 6th to 8th rib spaces. Directed anteriorly for pneumothorax and posteriorly for effusion

Temporary pacing wires

Cardiac pacing

Over right heart

Nasogastric tube

Gastric evacuation

Left upper quadrant of abdomen, with side-holes in stomach

lung and is the preferred method in cases of nonsuppurative lung disease, such as emphysema, idiopathic pulmonary fibrosis, sarcoidosis, or lymphangioleiomyomatosis. Bilateral sequential lung transplantation is performed for suppurative lung diseases, such as cystic fibrosis and bronchiectasis and also for severe pulmonary hypertension. Heart–lung transplantation is performed in cases of combined heart and lung disease55. Aspects of imaging in relation to lung transplantation can be subdivided into pre-operative, peri-operative and postoperative.

Pre-operative imaging Typical imaging procedures performed before lung transplantation include the PA and lateral chest radiograph, chest CT and quantitative ventilation–perfusion scintigraphy. Pre-operative imaging can help determine the optimum side for a single lung transplant procedure and screen for potential lung cancer. The chest radiograph can also be used for donor–recipient size matching55.

Peri-operative imaging Most patients are extubated within 24–48 h of transplantation. In some cases, complications such as infection or early graft dysfunction may necessitate a longer period of ventilation, in which case the patient usually undergoes a tracheostomy.

Reperfusion oedema Reperfusion oedema (also known as the re-implantation syndrome) is caused by increased capillary permeability. Causes include interruption of lymphatic drainage in the donor lung, underlying donor lung injury, surfactant deficiency and ischaemic damage to pulmonary capillaries55. In the series reported by Kundu et al56, reperfusion oedema was found to be nearly universal, occurring in 44 of 45 patients. Radiographic signs were non-specific but appeared most commonly as airspace opacity in the mid and lower zones. Linear or reticular radiographic shadowing was also commonly seen. Anderson et al57 found radiographic signs of reperfusion oedema in 97% of a series of 105 lung transplant patients.There is poor correlation between the degree of radiographic abnormality and physiological measurements56. Peak radiographic shadowing usually occurs around day 456 and in most patients the shadowing will have cleared by the 10th postoperative day55.

Early graft dysfunction Early graft dysfunction is a general term that describes a range of early injuries, including reperfusion oedema, ARDS and graft failure. Although potentially related to a range of underlying problems, patients show a common clinical pattern of presentation which includes radiographic abnormalities, poor oxygenation and biopsies, if performed, demonstrate diffuse alveolar damage or organizing pneumonia55. Radiographic abnormalities range from mild changes of airspace opacity associated with reperfusion oedema through to complete lung opacification55.

Postoperative imaging Infection The lung transplant patient is particularly vulnerable to infection due to a variety of causes such as immunosuppressive therapy, lost cough reflex and impaired mucociliary function in the denervated transplanted lung. Organisms that may infect the post-transplant lung include bacterial, viral, fungal, mycobacterial and mycoplasma species. In a review of patients with post-transplant infection, the most common infecting organisms were cytomegalovirus, pseudomonas and aspergillus. The most common CT findings were consolidation, ground-glass opacity, septal thickening, multiple or single nodules and pleural effusion. No significant difference in the prevalence of the CT signs was seen between the different groups of infecting organism—imaging may identify signs of infection but does not allow the specific organism to be recognized58.

Acute rejection Acute rejection occurs in virtually all transplanted lungs and usually within the first 3 months. The diagnosis is confirmed histopathologically with a transbronchial biopsy which typically demonstrates perivascular and interstitial mononuclear infiltrates. The rejection is graded from 0 to 4 depending on the severity of the biopsy changes and the majority of cases respond to intravenous methylprednisolone therapy55. Radiographic findings are non-specific and include new or persisting airspace opacities 5–10 d following transplantation, pleural effusions and interstitial lines without other signs of heart failure. High-resolution CT (HRCT) signs are similarly non-specific though ground-glass opacity and septal lines may

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be the predominant findings when acute rejection occurs after the first post-operative month55.

Bronchial anastomotic complications The bronchial anastamoses following transplantation may be complicated by dehiscence or stenosis (Fig. 20.24). Dehiscence (or separation of the two airway ends) tends to occur in the first few months following transplantation and may be associated with infection55. Factors that contribute to airway problems include ischaemia, acute allograft rejection, low cardiac output and prolonged postoperative ventilation55.

Obliterative bronchiolitis Long-term survival following lung transplantation is limited primarily by the development of obliterative bronchiolitis (OB). OB is characterized histopathologically by the presence of fibrosis in small airways associated with intimal thickening and sclerosis of vessels. The process is thought to represent chronic allograft rejection55. Episodes of acute rejection increase the likelihood of developing OB. Although it can occur as early as 2 months following transplantation, most cases are diagnosed 6–12 months following surgery. The chest radiograph in OB may be normal in the early stages though as the disease progresses signs of lung overinflation and subtle attenuation of peripheral airways may become apparent59. HRCT findings include areas of decreased lung attenuation associated with vessels of decreased calibre. Images acquired at end-expiration can reveal air trapping (Fig. 20.25)60. Air trapping on expiratory CT is the most sensitive and may be the only radiological sign of OB61. Redistribution of pulmonary blood flow to more normal areas of lung may lead to a mosaic attenuation pattern60. Bronchiectasis is commonly present60,62.

Post-transplantation malignant disease Post-transplantation lymphoproliferative disease (PTLD) occurs in 5–20% of lung transplant recipients, usually in the first year after transplantation55. Histological findings may range from benign hyperplasia of lymphocytes through to malignant lymphoma. PTLD is thought to be caused by

Figure 20.24 Post-transplant stenosis. (A) Axial plane and (B) three-dimensional reconstruction showing a post-transplant stenosis of the distal right main bronchus.

proliferation of donor B lymphocytes infected with the Epstein–Barr virus55. The most common CT manifestations are of multiple nodules, frequently in a predominantly peribronchovascular or subpleural distribution63.

Recurrence of the primary disease This has been described with a number of conditions, with sarcoidosis being the disease that recurs most commonly64.

SURGICAL TREATMENT OF EMPHYSEMA As described in Chapter 16, emphysema is defined as a condition of the lung characterized by permanent, abnormal enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis. The caveat relating to the absence of fibrosis was inserted to make emphysema distinct from honeycomb fibrosis but this has been controversial as some degree of inflammation and fibrosis can occur in association with emphysema65,66. Put simply, emphysema is thought to be caused by an imbalance between elastolytic enzymes, which tend to destroy lung tissue and anti-elastolytic proteins. Cigarette smoking can lead to recruitment of cells such as neutrophils and macrophages around bronchioles and these can initiate a local increase in elastolytic enzymes. Genetic deficiency of α1-antitrypsin can also predispose to emphysema. Typical features of emphysema on the chest radiograph include hyperinflation (flattened, depressed hemidiaphragms, increased retrosternal space), hyper-transradiancy and attenuated vessels. CT has a high sensitivity for the detection of emphysema and HRCT is more sensitive than conventional CT67. The four recognized subtypes of emphysema68—centrilobular emphysema, panlobular emphysema, paraseptal emphysema and irregular or ciccatricial emphysema—are described in Chapter 16.

Surgical options in emphysema Over the last century a number of surgical procedures have been used to attempt to relieve the distressing symptoms of advanced emphysema. Many of these have not stood the test of time but

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Figure 20.25 Post-lung transplantation obliterative bronchiolitis. The lungs are overinflated with mild cylindrical bronchiectasis and attenuation of pulmonary vessels. Areas of patchy ground-glass opacity in the periphery of the lung were thought to be due to cytomegalovirus pneumonitis. The patient died within a month of this examination.

three procedures are in current use.These are bullectomy, transplantation and lung volume reduction surgery (LVRS).

Bullectomy This consists of the excision of a large bulla or bullae by thoracostomy or by video-assisted thoracoscopic surgery (VATS). Bullectomy is considered in patients with a single or several large bullae identified on the chest radiograph and CT, usually with compression of adjacent lung parenchyma. The technique is usually reserved for patients with dyspnoea or recurrent pneumothoraces69.

Lung transplantation Lung transplantation can offer a marked improvement in the quality of life of the patient with advanced emphysema but the limited availability of donor organs is a major disadvantage. Transplantation is usually reserved for patients younger than 60–65 years of age and such patients will normally have resting hypoxia, hypercapnoea and a dependence on supplementary oxygen. Patient selection is based primarily on clinical and physiological criteria.The main roles of imaging in the preoperative patient are to assess whether alternative treatment such as LVRS might be more appropriate and to exclude incidental lung cancer.

Lung volume reduction surgery The surgical removal of the most emphysematous area of lung was first attempted in the 1950s by Professor Otto Brantigan from the University of Maryland, USA. Initially the technique did not gain widespread acceptance due to a relatively high operative mortality of 16%. During the 1990s, Joel Cooper of the Division of Cardiothoracic Surgery, Washington University School of Medicine, St Louis, USA revisited the technique and achieved an acceptable postoperative mortality of 4%70.

• THORACIC TRAUMA AND RELATED TOPICS

LVRS involves the removal of the most severely emphysematous portions of lung in the upper lobes. Typically about 30% of each lung is removed using either a median sternotomy or a video-assisted thoracoscopic technique. Air leaks from the lung can be a problem following LVRS. The use of bovine pericardial strips to buttress the staple line and the use of a ‘pleural tent’ to cover the staple line have kept this problem at an acceptable level70. LVRS is thought to have a beneficial effect by two main mechanisms: improved respiratory mechanics brought about by repositioning of the chest wall and diaphragm; and redistribution of ventilation which improves gas exchange.Advantages of LVRS include the relief of dyspnoea for patients without the problems of organ transplantation. Work so far has shown that a successful outcome depends on specific anatomical and physiological characteristics in the patient’s lungs and so careful patient selection is essential70. Patient selection Cooper’s results were encouraging but other centres which adopted the procedure did not have such successful outcomes and acceptable mortality rates. The use of LVRS became controversial towards the late 1990s and a number of trials were established to confirm the efficacy and safety of the technique. The most influential of these was the National Emphysema Treatment Trial (NETT) carried out in the USA71. The NETT recruited 1218 patients and of these 610 were randomized to medical treatment and 608 to surgical treatment, of whom 508 underwent surgery. The NETT overall showed improved exercise capacity in patients undergoing LVRS but no difference in survival between patients given medical or surgical therapy. With subgroup analysis, a survival advantage was seen for patients with predominantly upper lobe emphysema (Figs 20.26, 20.27) and a low baseline exercise capacity. Imaging plays a pivotal role in patient selection for LVRS. CT is the preferred method of assessing patients for LVRS but the chest radiograph remains a useful first-line investigation. The majority of patients will have a radiograph demonstrating hyperinflation with flattening of the hemidiaphragms. CT allows for more sensitive detection of emphysema and a more accurate assessment of disease distribution. Incidental lung cancers will also be more readily detected— such cancers do not preclude LVRS as, depending on their location, they may be removed by wedge excision at the same time as the volume reduction surgery (Fig. 20.28)72. An interim report from the NETT announced that patients with a forced expiratory volume in 1 s (FEV1) of less than 20% predicted value and either a homogeneous distribution of emphysema or a carbon monoxide diffusing capacity less than 20% predicted value were at higher risk of death following LVRS (16% 30-d mortality), thus reaffirming the importance of carefully assessing emphysema distribution with CT73. The severity and distribution of emphysema can be assessed either with a visual scoring system or by means of a density mask technique which identifies pixels below a predetermined value (usually around −910 HU)74.

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Figure 20.26 Upper zone emphysema. Axial (A) upper zone and (B) lower zone CT images of a patient with upper zone predominant emphysema that would be potentially suitable for treatment with lung volume reduction surgery.

Figure 20.27 Panlobular emphysema. Axial (A) upper zone, (B) lower zone and (C) coronal reformatted CT images of a patient with panlobular emphysema due to α1-antitrypsin deficiency. Emphysema of this type would not be suitable for lung volume reduction surgery though lung transplantation would be a possible option.

Perfusion scintigraphy can provide useful information about regional perfusion differences in the lung reflecting the distribution of emphysema. Although there is generally good correlation between CT and scintigraphy, Cederlund et al found that a combination of the two provided the best pre-operative assessment of disease heterogeneity75. Postoperative imaging In clinical practice, chest radiographs are routinely performed following LVRS but CT is only used to deal with specific clinical problems. Complications following LVRS are generally the same as those following any thoracic surgical procedure but particular attention needs to be given to the possibility of prolonged air leak. The staple line with pericardial buttress is always seen on CT and sometimes on the postoperative chest radiograph and this may cause some confusion in interpretation (Fig. 20.29). If a pleural tent has been performed then this may be mistaken for a pneumothorax in the early postoperative period. Aside

from air leaks, other complications reported in the NETT included pneumonia and cardiac arrhythmias71,76. A number of studies have performed quantitative analyses of lungs following LVRS using CT. Lung volumes measured with CT typically reduce by around 25% following LVRS and the average lung parenchymal density increases by around 25 HU77. Summary of the role of imaging The key roles of imaging in possible LVRS cases can be summarized as follows: • Confirming that the patient does have emphysema and identifying the subtype. • Assessing the distribution of emphysema. Means of assessment and criteria for surgery have varied from study to study but in practice the emphysema needs to be primarily of the centrilobular type with an upper zone predominance. There should be complete or relative sparing of the lower zones. As a useful rule of thumb, the emphysema should be

CHAPTER 20

• THORACIC TRAUMA AND RELATED TOPICS

predominant emphysema related to α1-antitrypsin deficiency. Only a minority of patients referred for consideration of LVRS will ultimately prove suitable for the technique71.

REFERENCE

Figure 20.28 Upper zone emphysema. CT image from a patient with upper zone predominant emphysema. The mass in the left upper lobe is a probable lung cancer but this could potentially be resected at the same procedure as the lung volume reduction surgery.

Figure 20.29 Postoperative CT image after lung volume reduction surgery. The staple line with bovine pericardium buttresses can be seen (arrowhead).

twice as severe in the upper zones as in the lower zones before a patient can be considered for possible LVRS. • Identifying incidental cancers. Depending on their location, these may not necessarily preclude LVRS. • Excluding other lung diseases which could lead to intra-operative or postoperative problems and thus may represent absolute or relative contraindications to surgery. These include severe bronchiectasis and diffuse parenchymal lung diseases, such as idiopathic pulmonary fibrosis. • Postoperative assessment—routine assessment with chest radiography and CT when there are specific clinical questions to be addressed. Emphysema is a common problem worldwide and LVRS can provide improved physiology, lung function and survival in certain patients. The emphysema distribution that is most favorable is that of upper lobe predominance and in practice this means centrilobular emphysema related to cigarette smoking—there is currently no role for LVRS in lower zone

1. Boot D A 1999 Epidemiology of accidents. In: Alpar EK, Gosling P (eds) Trauma: a scientific basis for care. Edward Arnold, London, pp 1–19 2. Besson A, Saegessor F 1982 A colour atlas of chest trauma and associated injuries. Wolfe Medical, Weert, the Netherlands 3. Committee on Trauma of the American College of Surgeons 1997 Advanced trauma life support for doctors: student course manual, 6th edn. American College of Surgeons, Chicago, 1997 4. Rivas L A, Fishman J E, Munera F, Bajayo D E 2003 Multislice CT in thoracic trauma. Rad Clin North Am 41: 599–616 5. Stark P 1993 The radiology of thoracic trauma. Andover Medical, Boston 6. Gupta A, Jamshidi M, Rubin J R 1997 Traumatic first rib fractures: is angiography necessary? Cardiovasc Surg 5: 48–53 7. Rao P, Carty H 1999 Non-accidental injury: review of the radiology. Clin Radiol 54: 11–24 8. Shanmuganathan K, Mirvis S E 1999 Imaging diagnosis of non-aortic thoracic injury. Rad Clin North Am 37: 533–551 9. Reid D C, Henderson R, Soboe L, Miller J D R 1987 Etiology and clinical course of missed spinal fractures. J Trauma 27: 980–986 10. Meek S 1988 Fractures of the thoraco-lumbar spine in major trauma patients. BMJ 317: 1442–1443 11. Wintermark M, Mouhsine E, Theumann N et al 2003 Thoracolumbar spine fractures in patients who have sustained severe trauma: Depiction with multi-detector row CT. Radiology 227: 681–689 12. Ma O J, Mateer J R 1997 Trauma ultrasound examination versus chest radiography in the detection of haemothorax. Ann Emerg Med 29: 312–316 13. Dee P 1992 The radiology of chest trauma. Rad Clin North Am 30: 291–306 14. Bekassy S M, Dave K S, Wooler G H, Ionescu M I 1972 Spontaneous and traumatic rupture of the diaphragm. Ann Surg 177: 320–323 15. Shackleton K L, Stewart E T, Taylor A J 1998 Traumatic diaphragmatic injuries: spectrum of radiographic findings. Radiographics 18: 49–59 16. Iochum S, Ludig T, Walter F, Sebbag H, Grosdidier G, Blum A G 2002 Imaging of diaphragmatic injury: A diagnostic challenge? RadioGraphics 22: S103–S116 17. Boulanger B R, Milzman D P, Rosati C, Rogriguez A 1993 Comparison of right and left blunt traumatic diaphragmatic injury. J Trauma 35: 255–260 18. Gelman R, Mirvis S E, Gens D 1990 Diaphragmatic rupture due to blunt trauma: sensitivity of plain chest radiographs. Am J Roentgenol 156: 51–57 19. Estrera A S, Platt M R, Mills L J 1979 Traumatic injuries of the diaphragm. Chest 75: 306–313 20. Shapiro M J, Heiberg E, Durham R M et al 1996 The unreliability of CT scans and initial chest radiographs in evaluating blunt trauma induced diaphragmatic rupture. Clin Radiol 51: 27–30 21. Worthy S A, Kang E Y, Hartman T E et al 1995 Diaphragmatic rupture: CT findings in 11 patients. Radiology 194: 885–888 22. Murray J G, Caoili E, Grunden J F et al 1996 Acute rupture of the diaphragm due to blunt trauma: diagnostic sensitivity and specificity of CT. Am J Roentgenol 166: 1035–1039 23. Bergin D, Ennis R, Keogh C et al 2001 The “dependent viscera sign” in CT diagnosis of blunt traumatic diaphragmatic rupture. Am J Roentgenol 177: 1137–1140 24. Killeen K L, Mirvis S E, Shanmuganathan K 1999 Helical CT of traumatic diaphragmatic rupture. Am J Roentgenol 173: 1611–1616 25. Shanmuganathan K, Mirvis S E, White C S, Pomerantz S M 1996 MR imaging evaluation of hemidiaphragms in acute blunt trauma: experience with 16 patients. Am J Roentgenol 167: 397–402

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26. Wintermark M, Wicky S, Schnyder P, Capasso P 1999 Blunt traumatic pneumomediastinum: using CT to reveal the Mackilin effect. Am J Roentgenol 172: 129–130 27. Bevjan S M, Godwin J D 1996 Pneumomediastinum: old and new signs. Am J Roentgenol 166: 1041–1048 28. Chen J D, Shanmuganathan K, Mirvis S E, Killeen K L, Dutton R P 2001 Using CT to diagnose tracheal rupture. Am J Roentgenol 176: 1273–1280 29. Trerotola S O 1995 Can CT replace aortography in thoracic trauma? Radiology 197: 13–15 30. Ledbetter S, Stuk J L, Kaufman J A 1999 Helical (spiral) CT in the evaluation of emergent thoracic aorta syndromes. Rad Clin North Am 37: 575–589 31. Alkadhi H, Wildermuth S, Desbiolles L et al 2004 Vascular emergencies of the thorax after blunt and iatrogenic trauma: multi-detector row CT and three-dimensional imaging. RadioGraphics 24: 1239–1255 32. Mirvis S E, Bidwell J, Buddmeyer E 1987 Value of chest radiography in excluding traumatic aortic rupture. Radiology 163: 487–493 33. Groskin S A 1992 Selected topics in chest trauma. Radiology 183: 605–617 34. Mirvis S E, Shanmuganathan K, Miller B H, White C S, Turney S Z 1996 Traumatic aortic injury: diagnosis with contrast-enhanced thoracic CT—five-year experience at a major trauma center. Radiology 200: 413–422 35. Gavant M L, Menke P G, Fabian T, Flick P A, Graney M J, Gold R E 1995 Blunt traumatic aortic rupture: detection with helical CT of the chest. Radiology 197: 125–133 36. Wicky S, Capasso P, Meuli R, Fischer A, von Segesser L, Schnyder P 1998 Spiral CT aortography: an efficient technique for the diagnosis of traumatic aortic injury. Eur Radiol 8: 828–833 37. Cleverley J R, Barrie J R, Raymond G S, Primack S L, Mayo J R 2002 Direct signs of aortic injury on contrast enhanced CT in surgically proven traumatic aortic injury: a multi-centre review. Clin Radiol 57: 281–286 38. Driscoll P A, Hyde J A J, Curzon I et al 1996 Traumamatic disruption of the thoracic aorta: a rational approach to imaging. Injury 27: 679–685 39. Hyde J A J, Shetty A, Graham T R 1998 Mediastinal trauma. In: Driscoll P, Skinner D (eds) Trauma care: beyond the resuscitation room. BMJ Publishing, London, pp 53–66 40. Trotman-Dickenson B 1998 Radiography in the critical care patient. In: McLeod T C (ed) Thoracic radiology: The requisites. Mosby, St Louis, pp 151–172 41. White C S, Pugatach R D 2003 Thoracic imaging in the intensive care unit. In: Mirvis S E, Shanmuganathan K (eds) Imaging in trauma and critical care, 2nd edn. W B Saunders, Philadelphia, pp 725–740 42. Lipchik R J, Kuzo R S 1996 Nosocomial pneumonia. Rad Clin North Am 34: 47–58 43. Remy-Jardin M, Mastora I, Remy J 2003 Pulmonary embolus imaging with multislice CT. Rad Clin North Am 41: 507–519 44. Henry D A 1996 Radiologic evaluation of the patient after cardiac surgery. Rad Clin North Am 34: 119–135 45. Winer-Muram H T, Gurney J W, Bozeman P M, Krance R A 1996 Pulmonary complications after bone marrow transplantation. Rad Clin North Am 34: 97–118 46. Muller N L, Fraser R S, Kyung S L, Johkoh T 2003 Pulmonary edema. In: Muller N L, Fraser R S, Kyung S L, Johkoh T (eds) Diseases of the lung: radiologic and pathologic correlations. Lippincott, Williams and Wilkins, Philadelphia, pp 255–265 47. Goodman L R 1996 Congestive heart failure and adult respiratory distress syndrome: new insights using computed tomography. Rad Clin North Am 34: 33–46 48. Sutcliffe A J 1999 ARDS: pathophysiology related to cardiorespiratory management. In: Alpar E K, Gosling P (eds) Trauma: a scientific basis for care. London: Edward Arnold, London, 142–152 49. Goodman L R, Fumagalli R, Tagliabue P et al 1999 Adult respiratory distress syndrome due to pulmonary and extrapulmonary causes: CT, clinical and functional correlations. Radiology 213: 545–552

50. Desai S R, Wells A U, Suntharalingam G, Rubens MB, Evans TW, Hansell D M 2001 Acute respiratory distress syndrome caused by pulmonary and extrapulmonary injury: A comparative CT study. Radiology 218: 689–693 51. Desai S R, Wells A U, Rubens M B, Evans T W, Hansell D M 1999 Acute respiratory distress syndrome: CT abnormalities at long-term follow-up. Radiology 210: 29–35 52. Tocino I, Westcott J L 1996 Barotrauma. Rad Clin North Am 34: 59–81 53. Zylak C M, Standen J R, Barnes G R, Zylak C J 2000 Pneumomediastinum revisited. RadioGraphics 20: 1043–1057 54. Henschke C I, Yankelevitz D F, Wand A, Davis S D, Shiau M 1996 Accuracy and efficacy of chest radiography in the intensive care unit. Rad Clin North Am 34: 21–31 55. Collins J 2002 Imaging of the chest after lung transplantation. J Thorac Imaging 17: 102–112 56. Kundu S, Herman S J, Winton T L 1998 Reperfusion edema after lung transplantation: radiographic manifestations. Radiology 206: 75–80 57. Anderson D C, Glazer H S, Semenkovich J W et al 1995 Lung transplant edema: chest radiography after lung transplantation—the first 10 days. Radiology 195: 275–281 58. Collins J, Muller N L, Kazerooni E A, Paciocco G 2000 CT findings of pneumonia after lung transplantation. Am J Roentgenol 175: 811–818 59. Skeens J L, Fuhrman C R, Yousem S A 1989 Bronchilitis obliterans in heart–lung transplantation patients: radiologic findings in 11 patients. Am J Roentgenol 153: 253–256 60. Leung A N, Fisher K, Valentine V et al 1998 Bronchiolitis obliterans after lung tranplantation: detection using expiratory HRCT. Chest 113: 365–370 61. Arakawa H, Webb W R 1998 Air trapping on expiratory high-resolution CT scans in the absence of inspiratory scan abnormalities: correlation with pulmonary function tests and differential diagnosis. Am J Roentgenol 170: 1349–1353 62. Worthy S A, Muller N L, Kim J S et al 1997 Bronchiolitis obliterans after lung transplantation: high resolution CT findings in 15 patients. Am J Roentgenol 169: 673–677 63. Collins J, Muller N L, Leung A N et al 1998 Epstein–Barr-virus-associated lymphoproliferative disease of the lung: CT and histologic findings. Radiology 208: 749–759 64. Collins J, Hartman M J, Warner T F et al 2001 Frequency and CT findings of recurrent disease after lung transplantation. Radiology 219: 503–509 65. Snider G L, Kleinerman J, Thurlbeck W M 1985 The definition of emphysema: report of a National Heart, Lung and Blood Institute, Division of Lung Disease Workshop. Am Rev Respir Dis132: 182–185 66. Muller N L, Fraser R S, Lee K S, Johkoh T 2003 Emphysema. In: Muller N L, Fraser R S, Lee K S, Johkoh T (eds) Diseases of the lung: radiologic and pathologic correlations. Lippincott, Wiliams and Wilkins, Philadelphia, pp 239–254 67. Webb W R 1997 Radiology of obstructive pulmonary disease. Am J Roentgenol 169: 637–647 68. Foster W L Jr, Giminez E I, Roubidoux M A et al 1993 The emphysemas: radiologic-pathologic correlation. RadioGraphics 13: 311–328 69. Snider G L 1996 Reduction pneumoplasty for giant bullous emphysema. Implications for surgical treatment of non-bullous emphysema. Chest 109: 540–548 70. Cooper J D 1997 The history of surgical procedures for emphysema. Ann Thorac Surg 63: 312–319 71. National Emphysema Treatment Trial Research Group 2003 A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med 348: 2059–2073 72. McKenna R J Jr, Fischel R J, Brenner M, Gelb A F 1996 Combined operations for lung volume reduction surgery and lung cancer. Chest 110: 885–890 73. National Emphysema Treatment Trial Research Group. Patients at High Risk of Death after Lung-Volume-Reduction Surgery. N Engl J Med 2001; 345:1075-1083. 74. Muller NL, Staples CA, Miller RR, Abboud RT 1988 “Density mask”: an objective method to quantitate emphysema using computed tomography. Chest 94: 782–787

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75. Cederlund K, Hogberg S, Jorfeldt L et al 2003 Lung perfusion scintigraphy prior to lung volume reduction surgery. Acta Radiol 44: 246–251 76. Slone R M, Gierada D, Yusen R M 1998 Preoperative and postoperative imaging in the surgical management of pulmonary emphysema. Rad Clin North Am 36: 57–89 77. Screaton N J, Reynolds J H 2006 Lung volume reduction surgery for emphysema: what the radiologist needs to know. Clin Radiol 61: 237−249

SUGGESTIONS FOR FUTHER READING Books Mirvis S E, Shanmuganathan K (eds) 2003 Imaging in trauma and critical and critical care. W B Saunders, Philadelphia

• THORACIC TRAUMA AND RELATED TOPICS

Schnyder P, Wintermark M 2000 Radiology of blunt trauma of the chest. Springer-Verlag, Berlin Journal articles Mirvis S E, Shanmuganathan K 1999 Imaging diagnosis of nonaortic thoracic injury. Rad Clin North Am 37: 533–551 Rivas L A, Fishman J E, Munera F, Bajayo D E 2003 Multislice CT in thoracic trauma. Rad Clin North Am 41: 599–616

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Airspace Diseases

21

Praveen Peddu and Sujal R. Desai

• • • • • • • •

Radiological approach to diagnosis of airspace disease Pulmonary oedema Diffuse pulmonary haemorrhage Wegener’s granulomatosis Cryptogenic organizing pneumonia Eosinophilic lung disease Alveolar proteinosis Miscellaneous causes of airspace opacification

RADIOLOGICAL APPROACH TO DIAGNOSIS OF AIRSPACE DISEASE Disease processes that principally involve the airspaces are reasonably common. Not surprisingly, airspace opacification is a frequent radiological finding. The approach to diagnosis is potentially daunting since opacification of the airspaces is a non-specific radiological sign (Table 21.1). In essence, any pathological process that displaces air from the alveoli will lead to radiographic airspace opacification; this pattern is most commonly seen when either fluid accumulates (as in pulmonary oedema) or there are inflammatory cells (as with infection) in the airspaces. The plain chest radiograph is usually the first investigation requested in patients with suspected lung disease.With experience, the radiologist can usually offer a sensible diagnosis or, at worst, a limited list of differential diagnoses. In this regard, an appreciation of the clinical features, the distribution of radiographic abnormalities and the changes on serial examination are often invaluable. A review of the radiology together with the clinical features may be diagnostic in some instances: e.g. lobar opacification in a patient with pyrexia and a productive cough is most likely to be due to infection (Fig. 21.1). Alternatively, in a patient with known left ventricular dysfunction, it would be entirely reasonable to suggest that the presence of bilateral airspace opacification is likely to represent pulmonary oedema. Recognition of the distribution of airspace opacities on the plain radiograph can be another helpful differentiating feature.

In cryptogenic organizing pneumonia, areas of consolidation may be most pronounced in the periphery and lower zones of the lungs1 (Fig. 21.2), whereas in patients with chronic eosinophilic pneumonia, the changes tend to be in the upper zones and characteristically parallel to the chest wall2. A review of serial radiographs, to ascertain disease progression or regression, should also be part of the radiologist’s routine. Relatively rapid changes (occurring over a period of hours or, at most, a few days rather than weeks) are more in keeping with pulmonary oedema (Fig. 21.3) or intra-alveolar haemorrhage than with pneumonic consolidation. On the other hand, opacities that are transient and migratory, unaccompanied by significant constitutional disturbance, should prompt the radiologist to propose a diagnosis of an eosinophilic pneumonia. Computed tomography (CT) is frequently requested in patients with airspace disease and, in the appropriate clinical context, the CT features are occasionally characteristic enough to permit a reasonably confident diagnosis. An example which comes readily to mind (with a few important caveats3) is the so-called ‘crazy-paving’ pattern of alveolar proteinosis4. However, in other instances, the radiologist may only be able to limit the list of diagnostic possibilities based on the additional information from CT, e.g. CT may reveal cavitation that may not have been evident on plain radiographs. In such a case it would be reasonable to propose Wegener’s granulomatosis or septic emboli as possible diagnoses. Except in the select circumstances highlighted above, the advantages of CT over plain radiography in the diagnosis of airspace diseases are not clearly defined5. This chapter considers some of the common and a few of the more unusual causes of airspace opacification in clinical practice. Airspace diseases due to infection and malignancy are considered in detail elsewhere (see Chapters 15 and 18).

Anatomical considerations Before considering the causes of airspace opacification it is pertinent to revise relevant aspects of pulmonary anatomy.The terminal bronchioles are the last purely conducting airways of the bronchial tree6 and the region of lung subtended by a terminal bronchiole is termed the acinus (comprising the

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Table 21.1 CAUSES OF AIRSPACE OPACIFICATION • Oedema Cardiogenic Noncardiogenic • Inflammation/infection Wegener’s granulomatosis Cryptogenic organizing pneumonia • Blood Idiopathic pulmonary haemosiderosis Antibasement membrane antibody disease Systemic lupus erythematosus • Miscellaneous causes Eosinophilic pneumonia Alveolar proteinosis Alveolar cell carcinoma Alveolar microlithiasis Lymphoma (MALToma) Sarcoidosis

Figure 21.2 (Noninfective) organizing pneumonia in a patient following allogeneic bone marrow transplantation. (A) Chest radiograph and (B) CT through the lower zones demonstrating characteristic bilateral mid and lower zone airspace opacification.

Figure 21.1 Pneumonia. Chest radiograph in a young male patient. The presence of focal (cavitating) consolidation in a patient with pyrexia and a productive cough should prompt a radiological diagnosis of pneumonia.

respiratory bronchioles, alveolar ducts, alveolar sacs and alveoli). Important pathways of collateral ventilation (the pores of Kohn) link different alveolar units7 and help to maintain lung inflation in the presence of proximal airway obstruction. Thus certain disease processes (most notably infections) can spread readily into adjacent alveolar units. Another important unit of lung structure, the secondary pulmonary lobule, is the smallest unit of lung bounded by

connective tissue septa8. Individual lobules are irregular polyhedral units, best seen sub-pleurally, measuring between 5 and 30 mm in diameter, and incorporating 3–24 acini9; the centrilobular bronchiole and adjacent artery form the core structures. The centrilobular arteries (with a diameter of 0.2 mm) can be resolved on high-resolution computed tomography (HRCT) in the normal lung, whereas normal bronchioles with a diameter below 2 mm are generally not seen10. Infiltration of the interlobular interstitium by oedema fluid or malignant cells, or thickening by fibrosis, will render individual secondary pulmonary lobules visible on HRCT11.

Radiological signs of airspace disease One of the limitations of imaging studies such as chest radiography and CT is that a multitude of pathological processes

CHAPTER 21

• AIRSPACE DISEASES

Figure 21.3 (A–C) Rapid changes in radiographic appearances in pulmonary oedema. Serial chest radiographs over roughly a 48-h period show striking changes in the extent/severity of airspace opacification reflecting relatively rapid shifts of fluid between the intravascular compartment and the airspaces/interstitium.

in the airspaces manifest in only a limited number of ways: thus, for most airspace diseases, a nodular pattern, ground-glass opacification and consolidation represent the range of radiological abnormalities. A nodular pattern (defined as rounded opacities that are at least moderately well differentiated and no greater than 3 cm in maximum diameter12) as a sole manifestation of airspace disease is relatively uncommon. Historically, the term ‘acinar nodules’ or ‘acinar rosettes’ has been used to describe the appearance of a patchy nodular infiltrate on chest radiography13 (Fig. 21.4). However, the diagnostic value of localizing disease to the acinus has been questioned; in pathological studies, the acinar pattern on plain radiographs does not correspond to filling of acini as defined

anatomically14. This notwithstanding, the so-called acinar pattern is most frequently encountered in the context of bacterial infection15. Ground-glass opacification is a common manifestation of airspace disease on chest radiography and CT. On plain radiography ground-glass opacification is seen as an increase in lung density which obscures vessel markings12. By comparison, because of the greater contrast medium resolution of CT, this pattern appears as a hazy increase in lung attenuation but with preservation of the bronchial and vascular markings12 (Fig. 21.5); there may or may not be an associated air bronchogram. However ground-glass opacification is a non-specific radiological sign which may indicate disease within the airspaces and/or the interstitium16 (Fig. 21.6). Occasionally, ground-glass opacification on CT is extremely subtle. In cases of uncertainty, comparison of the (air) density within airways with that of lung parenchyma (the ‘black bronchus’ sign) may be useful (Fig. 21.7); normally the two densities are roughly comparable. Consolidation refers to an increase in parenchymal density in which the margins of vessels and airways are obscured both on chest radiography and CT (Fig. 21.8). As with ground-glass opacification, an air bronchogram may be seen. This radiological pattern occurs when air in the airspaces is replaced with either transudate or exudate.

PULMONARY OEDEMA

Figure 21.4 Nodular airspace opacities on chest radiography. Targetted image of the right lung showing numerous ill-defined nodules in a patient with disseminated pulmonary tuberculosis.

Pulmonary oedema, defined as an excess of extravascular lung water, may be due to an increase in hydrostatic pressure (sometimes called cardiogenic oedema) or vascular permeability (termed noncardiogenic oedema) (Table 21.2). Whilst being practical, the utility of this apparently simple and dichotomous classification of pulmonary oedema has been questioned17,18. Cardiogenic or hydrostatic pulmonary oedema occurs when there is shift of fluid out of the vascular compartment secondary to an increase in pulmonary venous and capillary pressure. A common cause of increased hydrostatic pressure is left heart failure but rarely, a reduction in plasma osmotic pressure (as in hypoalbuminaemic states) will lead to pulmonary oedema.

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Figure 21.5 Ground-glass opacification on (A) chest radiography and (B) CT in a patient with pulmonary cytomegalovirus reactivation following bone marrow transplantation. On plain chest radiography there is veil-like opacification in the mid and lower zones of both lungs, which obscures vessel markings. In comparison, on CT, bronchovascular markings are clearly visible within regions of increased opacification.

Figure 21.6 Variable causes of ground-glass opacification on CT due to airspace and/or interstitial processes. (A) Diffuse pulmonary haemorrhage in a patient with disseminated malignancy. (B) Ground-glass opacification and thickened inter- and intra-lobular septa in pulmonary oedema. (C) Ground-glass opacification due to a predominant interstitial lung disease; there are grossly dilated segmental and subsegmental airways (‘traction bronchiectasis’) within ground-glass indicating fine fibrosis.

Noncardiogenic pulmonary oedema occurs when there is an increase in the permeability of the alveolar–capillary barrier. A good example of this type of pulmonary oedema is the acute respiratory distress syndrome (ARDS).

Chest radiographic signs

Figure 21.7 ‘Black bronchus’ sign on CT: there is an almost imperceptible increase in lung density. However, air within the segmental bronchi is clearly of lower attenuation than the surrounding parenchyma.

Plain chest radiography is more sensitive than clinical examination in the detection of early pulmonary oedema19. Indeed, chest radiography is an important investigation in patients with suspected pulmonary oedema. Because fluid passes from the intravascular compartment into the interstitium and only then into the alveoli, the radiographic changes of interstitial oedema generally precede frank airspace opacification20. Whilst the division into interstitial and alveolar oedema is perhaps too simplistic, for clarity these will be discussed separately in the following sections.

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• AIRSPACE DISEASES

Interstitial oedema. One of the classical radiographic manifestations of interstitial oedema is thickening of the interlobular septa. The characteristic Kerley B lines, which represent fluid in the interlobular septa (typically 1–2-mm wide and 30–60-mm long), are mainly seen in the sub-pleural lung, perpendicular to the pleural surface (Fig. 21.9). In comparison, Kerley A lines are longer (up to 80–100 mm), occasionally angulated and cross the inner two-thirds of the lung in varying directions but tend to point medially towards the hilum. In left heart failure, septal lines become visible as they distend with increasing extravascular fluid. Note that the visualization of oedematous septal lines may be hampered when neighbouring alveoli are also opacified. However, the demonstration of thickened interlobular septa is not diagnostic of pulmonary oedema; fibrosis and malignant infiltration (as in lymphangitis carcinomatosa) may also increase the conspicuity of interlobular septa. Another sign of interstitial oedema on chest radiographs is peribronchial cuffing in which, on a frontal radiograph, the normally thin and well defined wall of the airway appears thickened and somewhat indistinct (Fig. 21.10). A loss of conspicuity of the central pulmonary vessels (termed a perihilar haze) also occurs and, as with peribronchial cuffing, is assumed to be due to oedema of the perivascular interstitium. Because of the anatomical arrangement of septa in relation to the visceral pleura, oedema fluid may collect in the sub-pleural space. On chest radiography this is manifest as thickening of the interlobar fissures or as a lamellar ‘effusion’ in the costophrenic recesses.

Figure 21.8 (A) Consolidation on plain chest radiography in a patient with proven tuberculosis; there is evidence of cavitation within the area of consolidation. (B) Consolidation on CT in a patient with adenovirus infection following allogeneic bone marrow transplantation. In both cases, there is obscuration of bronchovascular markings by areas of dense parenchymal opacification.

Table 21.2

CAUSES OF PULMONARY OEDEMA

• Cardiogenic (hydrostatic) oedema • Noncardiogenic (increased permeability) oedema (Iatrogenic) fluid overload Drowning Drug-induced (e.g. narcotics, non-steroidal anti-inflammatory drugs, intravenous contrast) Acute respiratory distress syndrome High altitude Rapid re-expansion of collapsed lung Intracranial disease (cerebrovascular accident, raised intracranial pressure)

Figure 21.9 Magnified view of the left costophrenic region demonstrating multiple interstitial (Kerley B) lines. Each line is roughly perpendicular to the chest wall and extends to the pleural surface.

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Figure 21.11 Asymmetrical distribution of airspace opacification in a patient with pulmonary oedema. There is patchy opacification in the right lung with relative sparing of the left.

Figure 21.10 (A) Normal appearance of segmental bronchus seen ‘end-on’ (arrow) adjacent to its accompanying pulmonary artery branch. The wall of the bronchus is well defined and thin. (B) Peribronchial cuffing. The wall of the anterior segmental bronchus appears thickened and ill-defined (arrows) in early interstitial oedema due to (iatrogenic) fluid overload.

Alveolar oedema Airspace opacification becomes evident on the chest radiograph as oedema fluid passes from the interstitium into the alveoli. The distribution of changes is variable and frequently random (Fig. 21.11) but, in general, there is sparing of the apices and extreme lung bases. Typically, there is bilateral opacification, although pulmonary oedema apparently confined to one lung on the chest radiograph also occurs21. On occasion, the central lungs are more affected, producing the characteristic ‘butterfly’ or ‘bat’s wing’ distribution (Fig. 21.12)22. As oedema progresses, opacities may coalesce to produce a general ‘whiteout’. An air bronchogram or alveologram may be seen when

Figure 21.12 Pulmonary oedema on chest radiography demonstrating the characteristic ‘bat’s wing’ distribution, with airspace opacification principally within the central lung.

there is intra-alveolar oedema. Resolution of airspace opacification on serial radiographs may be rapid (hours compared to days or weeks) and is a useful indicator that airspace disease is due to pulmonary oedema rather than any other process (Fig. 21.13). Redistribution of blood to the upper zones is seen in some patients with elevated pulmonary venous pressure23; when this occurs, vessels in the upper zones appear larger than comparable vessels in the lower zones (this appearance is called upper lobe blood diversion) (Fig. 21.14). Although not an invariable

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• AIRSPACE DISEASES

Figure 21.13 (A–C) Serial chest radiographic changes in pulmonary oedema. There is progressive clearing of airspace opacification over a 48-h period.

feature, the redistribution of blood is a recognized feature in both acute and chronic cardiac dysfunction24.The mechanisms underlying blood flow redistribution are interesting but not entirely clear; however, in the upright patient, oedema accumulates in the more dependent lung and it has therefore been suggested that interstitial oedema at the bases may compress the vessels, thereby increasing the resistance to flow and preventing the transmission of hydrostatic distending forces25. In some patients the radiographic appearances of intraalveolar oedema will be modified. The distribution of pulmonary oedema may vary with posture; in patients lying on one side for a prolonged period, for example, the dependent lung becomes more oedematous and pulmonary oedema may then be unilateral. Coexisting disease can also affect the distribution of extravascular lung water. In smokers, the distribution of oedema may be patchy owing to the destruction of lung parenchyma by emphysema. Similarly, in patients with pulmonary fibrosis, there may be more rapid fluid accumulation in the alveolar spaces in comparison with the interstitium26.

Radiographic differentiation of cardiogenic and noncardiogenic pulmonary oedema Plain chest radiography is probably more accurate than clinical examination in distinguishing between hydrostatic and increased permeability oedema27. However, whether chest radiography can consistently differentiate between cardiogenic and noncardiogenic oedema is more debatable28,29. In one early study, the pattern of blood flow (i.e. upper zone versus lower zone), the distribution of oedema (i.e. peripheral versus central) and the width of the vascular pedicle were considered to be discriminatory features28. In 50% of patients with cardiogenic oedema there was upper lobe blood diversion, whereas in patients with increased permeability oedema due to ARDS, only 10% showed this inverted pattern; normal or ‘balanced’ flow were more commonly seen in ARDS28. A peripheral distribution of oedema was strikingly absent in patients with cardiogenic oedema but was the most common pattern seen in patients with ARDS. Based on these findings and some ancillary features, the authors claimed an overall accuracy for chest radiography of 86–89%28. However, this conclusion has been refuted by the findings of subsequent studies29,30. Although there is high specificity for the finding of patchy or peripherally-distributed oedema in increased permeability oedema, Aberle et al showed that the sensitivity was below 50%29. Similarly, the discriminatory value of signs of interstitial fluid accumulation and pleural effusions have been questioned29,31. In summary, analysis of the radiographic pattern will sometimes allow a distinction to be made but the inconsistency of the radiographic signs suggests that differentiation between the various forms of pulmonary oedema, based on radiographic features alone, is unreliable.

Computed tomography

Figure 21.14 Upper lobe blood diversion. Vessels in the upper zones (arrows) are prominent in comparison to those in the lower lung zones.

The appearances of pulmonary oedema on CT are variable. As with chest radiography, the changes on CT may be bilateral or indeed confined to one lung and may be modified by co-existent disease. Because of its superior contrast medium resolution, CT may detect abnormalities before the transudation of fluid into the interstitium and airspaces: in an animal model of fluid overload there was an increase in background lung attenuation, attributed to an expansion of intracapillary

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volume32. With more florid transudation, peribronchovascular cuffing, prominent interlobular septa, ground-glass opacification and consolidation become evident (Fig. 21.15).A perihilar distribution may be seen in some patients but is by no means invariable.

Table 21.3 CLASSIFICATION OF DIFFUSE PULMONARY HAEMORRHAGE SYNDROMES (MODIFIED FROM33) Nonimmunocompromised patients • Antibasement membrane antibody disease/Goodpasture’s syndrome • Diseases of presumed immune aetiology, with or without nephropathy Systemic lupus erythematosus

DIFFUSE PULMONARY HAEMORRHAGE

Rheumatoid arthritis Systemic sclerosis

Bleeding into the airspaces is a surprisingly frequent event in many common pulmonary diseases. It is well known that patients with lung cancer, bronchiectasis, or pneumonia frequently aspirate blood into the airspaces. However, because the bleeding tends to be localized in these cases and there is often an established underlying cause, the diagnosis is generally straightforward. In addition to these common clinical scenarios there are a number of pulmonary haemorrhage syndromes characterized by diffuse intra-alveolar bleeding. The severity of haemorrhage is variable, ranging from small symptomless bleeds to life-threatening episodes. A practical scheme for classifying diffuse pulmonary haemorrhage (DPH) categorizes syndromes according to whether or not the patient is immunocompromised33 (Table 21.3). In immunocompetent patients, DPH may be immunologically mediated (e.g. antiglomerular basement membrane disease), have a presumed immunological basis (e.g. systemic lupus erythematosus,Wegener’s granulomatosis), or have a nonimmunological mechanism (e.g. idiopathic pulmonary haemosiderosis, drug reactions). In immunocompromised patients, infection, tumours and blood dyscrasias account for the majority of cases of DPH. The clinical presentation of the DPH syndromes varies34. Recurrent haemoptyses, dyspnoea and chronic cough are the typical, but not invariable, symptoms. Non-specific clinical features, including intermittent pyrexia, headache, lethargy, basal crackles on auscultation and clubbing, may also be present. On

Systemic necrotizing vasculitis Wegener’s granulomatosis Microscopic polyarteritis • Diseases with no known immune aetiology Idiopathic pulmonary haemosiderosis Rapidly progressive glomerulonephritis without immune complexes Fibrillary glomerulonephritis Drug-induced (anticoagulants, trimellitic anhydride, cocaine) Valvular heart disease Disseminated intravascular coagulation Acute lung injury Tumours Immunocompromised patients • Blood dyscrasias • Infection • Tumours

histopathological examination blood and haemosiderin-laden macrophages are the key findings within the alveoli35. With repeated episodes there is thickening of alveolar septa due to fibrosis36, which can occasionally become florid37. Of the many DPH syndromes, idiopathic pulmonary haemosiderosis and antibasement membrane antibody disease (Goodpasture’s syndrome) have received greatest attention. These two entities are considered briefly below.

Idiopathic pulmonary haemosiderosis Idiopathic pulmonary haemosiderosis (IPH) is a rare disorder of unknown aetiology.The clinical picture is that of episodic intraalveolar haemorrhage, haemoptyses, iron-deficiency anaemia and airspace opacification on chest radiographs. The majority of patients are children (typically in the first decade) or young adults in the second to third decades36,38; sporadic cases in older subjects have been recorded39.The prognosis of patients with IPH varies: survival may range from a few days (following a severe episode of bleeding) to years.The pathogenesis of IPH is not clear although a number of hypotheses have been proposed38.

Antibasement membrane antibody disease

Figure 21.15 Pulmonary oedema on CT. There is diffuse groundglass opacification, smooth thickening of multiple interlobular septa and peribronchovascular cuffing. Bilateral pleural effusions are also seen.

The link between renal disease and diffuse intra-alveolar bleeding has long been established40.Whilst the historical term Goodpasture’s syndrome (referring to the entity in which circulating antibodies are directed against components of basement membrane in the lungs and kidneys) remains in common parlance, the term antibasement membrane antibody (ABMA) disease is now preferred to the eponymous title. ABMA disease

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typically affects young men with a male:female ratio of around 3:141. The pulmonary manifestations of ABMA disease often dominate the clinical presentation, though evidence of renal disease is present in the majority of cases.

Radiology The plain radiographic features of DPH syndromes are similar regardless of the underlying aetiology. Therefore, differentiation between different causes of DPH is generally not possible on the basis of radiological findings alone. Following an acute episode the chest radiograph is usually, but not invariably, abnormal. However, in individual patients, the radiographic appearances will vary depending on the extent of haemorrhage and the timing of the examination relative to individual bleeding episodes: acutely there is widespread ground-glass opacification or consolidation42. The changes tend to be more pronounced in the perihilar region of the mid and lower zones. A useful diagnostic clue is that, compared to other causes of airspace opacification (with the notable exception of pulmonary oedema), the changes of diffuse intra-alveolar haemorrhage typically clear over a few days. This is a consequence of the relatively efficient removal of blood by pulmonary alveolar macrophages (Fig. 21.16). With repeated episodes ill-defined nodular or reticulonodular opacities are seen and there may be enlargement of hilar lymph nodes. The CT abnormalities in the ‘subacute’ phase have been described in one study of six patients43. A nodular pattern with no zonal predilection was the dominant CT finding. Nodules measured 1–3 mm in diameter and corresponded on histopathological examination to conglomerates of haemosiderin-laden macrophages within alveoli. There was patchy or uniform ground-glass opacification and abnormal thickening of interlobular septa in the majority of cases.

WEGENER’S GRANULOMATOSIS Wegener’s granulomatosis is a multisystem disease of unknown aetiology characterized by varying proportions of (A) a necrotizing vasculitis involving medium- and small-sized vessels; (B) granulomatous necrosis; and (C) elements of both acute and chronic inflammation44. The disease affects men and women about equally and can present at virtually any age; indeed, there are reports of Wegener’s granulomatosis presenting both in childhood and in patients in the eighth decade45–47. The clinical manifestations of Wegener’s granulomatosis are both varied and non-specific48. However, the majority of patients complain of respiratory symptoms. The upper and lower respiratory tract are commonly involved and the typical patient with Wegener’s granulomatosis will also has evidence of renal disease. A ‘limited’ form of Wegener’s granulomatosis, in which disease is confined to the respiratory tract, is also recognized49. Without treatment, the disease is almost invariably fatal50. However, the outlook for patients with Wegener’s granulomatosis has improved dramatically with cyclophosphamide and corticosteroid therapy.

• AIRSPACE DISEASES

Radiology The spectrum of radiographic abnormalities in Wegener’s granulomatosis is wide. Nodules are seen in most patient and vary in size from a few millimeters to several centimeters in diameter51,52. There is no particular zonal predilection (Fig. 21.17). In most patients there are multiple nodules but in some, there may be a solitary pulmonary lesion. On CT a feeding vessel leading to the nodule may be identified and there may be air bronchograms within lung nodules. Linear bands, spiculation and pleural tags may also be seen in relation to pulmonary nodules. With treatment, nodules generally regress, but it is important to remember that the chest radiograph may not return to normal for up to a month following the initiation of therapy53. Furthermore, there may be residual parenchymal scarring on CT despite resolution of nodules and pulmonary consolidation54. Cavitation is generally regarded as the classical radiological finding in pulmonary Wegener’s granulomatosis and the demonstration of this sign is a useful pointer to the diagnosis (Fig 21.18). However, cavitation is by no means an invariable feature and thus, the absence of this sign should not preclude a diagnosis of Wegener’s granulomatosis. Consolidation and ground-glass opacities are recognized features on CT but are less common than nodules. Interestingly, the converse is apparently true in children, in whom nodules are seen less frequently55. As with nodules, foci of consolidation may cavitate. With CT it has been possible to highlight the more unusual abnormalities in Wegener’s granulomatosis such as bronchovascular thickening and frank bronchiectasis (Fig. 21.19). The other reported ancillary features of Wegener’s granulomatosis include areas of lobar or segmental atelectasis, pleural effusions or thickening, and rarely, hilar and mediastinal lymph node enlargement.

CRYPTOGENIC ORGANIZING PNEUMONIA The entity of cryptogenic organizing pneumonia (COP), first reported by Davison et al, refers to the histological pattern of an organizing pneumonia of unknown aetiology56. The characteristic finding on biopsy is of buds of granulation tissue in the alveoli and alveolar ducts with cellular infiltrates (mainly mononuclear cells and macrophages) in the surrounding airspaces56. It is important to realize, at the outset, that organizing pneumonia is simply a histological pattern and not a diagnosis in itself; the label ‘cryptogenic’ is only applied when other potential causes of an organizing pneumonia pattern (including a host of infections, certain drugs and connective tissue disorders) have been excluded57. In the past, the more confusing term idiopathic brochiolitis obliterans organizing pneumonia (BOOP) has also been used to describe this histological entity58. However, because the airway changes are thought to be secondary to the dominant process in the airspaces and there is no evidence of a ‘bronchiolitis obliterans’, the term COP is now preferred59. Patients with COP usually present with a short history of cough, dyspnoea,

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Figure 21.16 (A–C) Chest radiographs and (D) HRCT in a patient with idiopathic pulmonary haemosiderosis. (A) There is diffuse groundglass opacification with no zonal predilection during an acute hospital admission with haemoptysis. (B) Radiograph taken 4 d later shows striking (but incomplete) resolution of airspace opacities. There is residual opacification around the right hilum. (C) Chest radiograph obtained 1 month following admission demonstrates ground-glass opacification in the right mid zone. (D) HRCT through the lower zones (concurrent with the radiograph in [A]) shows patchy ground-glass opacification with a somewhat unusual geographical distribution; there are thickened interlobular septa in areas of groundglass opacification.

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Figure 21.17 Wegener’s granulomatosis. (A) Multiple intrapulmonary nodules within both lungs on chest radiography in a patient with elevated c-ANCA titres. (B) CT through the lower zones also demonstrates multiple pulmonary nodules. However, there is clear evidence of cavitation (not seen on the chest radiograph) in one of the lesions in the right lower lobe.

Figure 21.18 HRCT through the lower lobes in a patient with biopsy-proven Wegener’s granulomatosis. There is multifocal consolidation and a thick-walled cavity in the left lower lobe.

Figure 21.19 Bronchocentric disease in Wegener’s granulomatosis; many of the segmental and subsegmental bronchi are thick walled (arrows). (Courtesy of Dr Kate Pointon, Nottingham City Hospital, UK.)

fever, weight loss, chills and myalgia. Whilst spontaneous resolution can occur, most patients treated with corticosteroids undergo relatively rapid and generally complete response occurs60. Disease relapse is relatively common but does not appear adversely to influence the long-term prognosis.

vascular regions in around two-thirds of patients (Fig. 21.21) but cavitation is only rarely seen. More recently, multifocal areas of ground-glass opacification with a surrounding rim of consolidation (known as the ‘reverse halo’ sign) have also been described63. Nodules, sometimes measuring up to 1 cm in diameter and representing focal areas of organizing pneumonia, are seen in some patients and, in occasional subjects, these may be the sole radiographic manifestation of COP61,62; as with areas of consolidation, there is no definite zonal predilection. In some patents nodules are large enough to simulate a neoplasm64. Murphy et al have described linear opacities as the dominant HRCT abnormality in some patients with COP65. Two types of opacity (termed Type I and II) were identified. Type I opacities are intimately related to bronchi and extend radially towards the pleura. Type I opacities measure 2–4 cm in

Radiology The radiological signs of COP may be predicted from a knowledge of the histopathological changes. Bilateral patchy areas of consolidation, which tend to be peripheral, are the cardinal features on chest radiography61 (Fig. 21.20). Although earlier radiographic series suggested a predilection for the mid and lower zones, data from CT indicate that all lung zones may be equally affected62. The changes of COP may be confined to one lung but this is an infrequent finding61. Consolidation in COP has a propensity for the sub-pleural and/or peribroncho-

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Figure 21.20 Cryptogenic organizing pneumonia. (A) Patchy multifocal consolidation in the mid and upper zones in a patient presenting with a cough, breathlessness and weight loss. (B) One month after commencing corticosteroids there is complete clearing of the airspace opacities. (C) Five months after stopping treatment there is recurrence with consolidation in the right mid zone.

length and 1–2 mm in thickness. Areas of consolidation may coexist with Type I linear opacities. Type II linear opacities are sub-pleural and, unlike the Type I pattern, are not related to airways.Type II linear opacities tend to be parallel to the pleural surface but like Type I changes are frequently associated with multifocal airspace consolidation. Importantly, regardless of the type of opacity, there was radiological resolution on follow-up in the majority of patients. Another unusual manifestation of COP on CT, recently reported by Ujita et al, is a perilobular pattern in which curvilinear opacities (of greater thickness but less well defined than interlobular septa) give rise to an arcadelike appearance66 (Fig. 21.22).

EOSINOPHILIC LUNG DISEASE The eosinophilic lung diseases are a diverse group which, like the DPH syndromes, have proved difficult to classify. In one early attempt the pulmonary eosinophilias were defined as any condition in which pulmonary infiltration on the radiograph is accompanied by blood eosinophilia in a patient in whom pneumonia, hydatid disease of the lung, Hodgkin’s disease and sarcoidosis had been excluded67. A simplified classification of the pulmonary eosinophilias is given in Table 21.468, and some of the entities encompassed within the broad category of ‘eosinophilic pneumonia’ are discussed below.

Simple pulmonary eosinophilia (Löffler’s syndrome) In 1932, Löffler reported on a series of patients who presented with evidence of infiltrates on chest radiography, two of whom had a peripheral blood eosinophilia69. The term Löffler’s syndrome (synonymous with simple pulmonary eosinophilia) describes patients with transient radiographic infiltrates, minimal constitutional upset and an elevated eosinophil count in peripheral blood. The airspace opacification in Löffler’s syndrome is fleeting and may be either unior bi-lateral. Resolution of opacities within a period of days and, by definition, within a month is the rule. In many cases, no underlying aetiological factor is uncovered but there is an association with parasitic infection, in particular infestation with Ascaris lumbricoides.

Acute eosinophilic pneumonia Some patients with pulmonary eosinophilia have a more fulminant clinical course. In these subjects, there may be a brief history of a febrile illness, followed by respiratory distress with marked hypoxia, diffuse airspace opacification on chest radiography and elevated eosinophil levels in broncho-alveolar fluid; the term acute eosinophilic pneumonia has been applied to this entity70, which can occur at any age including in childhood. The clinical improvement with corticosteroids is often dramatic with fever and radiographic changes resolving within days and with very little risk of relapse on withdrawal of ther-

Figure 21.21 Cryptogenic organizing pneumonia (COP). CT through the (A) apex, (B) carina and (C) lower lobes in COP. Multifocal consolidation and ground-glass opacification are seen, predominantly in the peripheral lung. Note that all lung zones are affected.

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Table 21.4 MODIFIED CLASSIFICATION OF EOSINOPHILIC LUNG DISEASE • Idiopathic Simple pulmonary eosinophilia (Löffler’s syndrome) Acute eosinophilic pneumonia Chronic eosinophilic pneumonia Hypereosinophilic syndrome • Drug-induced Aminosalicylic acid Para-aminosalicylic acid Non-steroidal anti-inflammatory drugs Captopril Cocaine Minocycline Nitrofurantoin Phenytoin • Infection Parasitic (ascariasis, paragonomiasis, tropical eosinophilia) Fungal (aspergillus) Bacterial (tuberculosis, atypical mycobacterial infection, brucella) Viral (respiratory syncytial virus) • Immunological diseases Wegener’s granulomatosis Churg–Strauss syndrome Rheumatoid disease Sarcoidosis • Neoplasms

Figure 21.22 Cryptogenic organzing pneumonia in a young female patient. CT at (A) the level of the carina and (B) the lung bases demonstrating an arcade-like appearance due to perilobular curvilinear opacities.

apy. Spontaneous resolution of acute eosinophilic pneumonia, without therapy, also occurs71. On plain chest radiographs, there is bilateral airspace opacification and/or reticular infiltrates72. Pleural effusions are common. Areas of ground-glass opacification and consolidation are seen on CT and there may be smooth thickening of interlobular septa.

Chronic eosinophilic pneumonia The clinical and radiological features of chronic eosinophilic pneumonia are strikingly different from the entities described above. As the term suggests, the clinical course of chronic eosinophilic pneumonia is generally more protracted and the symptoms are often more marked than in patients with simple pulmonary eosinophilia. Pyrexia, cough, breathlessness, weight loss and night sweats are the common clinical features of chronic eosinophilic pneumonia; occasional patients also complain of haemoptysis and chest pain68. There is frequently eosinophilia in the peripheral blood and lung function tests reveal a restrictive defect with impaired gas transfer. Fortunately the prognosis is good and most patients respond to corticosteroid therapy with rapid clearing of their radiographic

Brochogenic carcinoma Bronchial carcinoid Lymphoma (Hodgkin’s, non-Hodgkin’s)

infiltrates, though the withdrawal of, or a reduction in, such therapy is not uncommonly associated with relapse. The plain radiographic abnormalities in chronic eosinophilic pneumonia may be characteristic: patchy, nonsegmental areas of consolidation are typical in the mid and upper zones2. A distinctive feature is that the opacities are peripheral and seem to parallel the chest wall, a finding that has been called the ‘photographic negative of pulmonary oedema’ (Fig. 21.23)2. Not surprisingly, the peripheral location of the airspace opacities is more readily appreciated on CT.

ALVEOLAR PROTEINOSIS Alveolar proteinosis (synonymous with alveolar lipoproteinosis and alveolar phospholipoproteinosis) is a rare disease characterized by the accumulation of a periodic acid-Schiffpositive lipoproteinaceous material within the alveoli73. The aetiology of alveolar proteinosis is unknown, although a defect of surfactant metabolism has long been suspected. In some cases, alveolar proteinosis is consequent on a pulmonary insult: exposure to inorganic dusts and some infections has been associated with so-called secondary alveolar proteinosis. Interestingly,

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Figure 21.23 Chronic eosinophilic pneumonia. (A) Chest radiograph in a male patient with a dry cough, weight loss and marked blood eosinophilia. There is ill-defined airspace opacification in both upper zones and the changes appear to parallel the chest wall. (B) HRCT through the upper lobes with bilateral (but asymmetrical) areas of ground-glass opacification and a fine reticular component in a peripheral distribution.

there is also a recognized link between alveolar proteinosis and some adult haematological malignancies (i.e. lymphoma and leukaemia), and with immunodeficiency states in children74. The disease usually affects adults aged 20–50 years, but has been described in children, in whom the prognosis is generally worse. Men are affected more frequently than women. The clinical manifestations of alveolar proteinosis are variable but exertional dyspnoea and a non-productive cough are the most common symptoms; pyrexia, chest pain and haemoptysis are occasionally reported. Patients with alveolar proteinosis may have digital clubbing and inspiratory crackles can be heard on auscultation. Paradoxically, in some patients, there may be minimal clinical signs despite extensive radiographic changes. The diagnosis of alveolar proteinosis may be supported by the electron microscopic features of lung tissue, lavage samples or sputum, and histopathological examination is then required only in cases of uncertainty. Although spontaneous resolution may occur, the majority of patients require therapeutic (whole lung) broncho-alveolar lavage, a technique that has improved the outlook of patients with alveolar proteinosis75. Symptomatic improvement following lavage may be rapid and sustained but repeated treatments are frequently required.

Radiology The chest radiographic changes of alveolar proteinosis are nonspecific. In general, both lungs are involved and airspace opacification is most pronounced in the central lung (Fig. 21.24).The CT features are much more suggestive (although not entirely pathognomonic) of alveolar proteinosis: on thin-section images a ‘crazy-paving’ pattern (made up of a striking geographical distribution of ground-glass opacification and thickened interlobular septa) is the characteristic feature4 (Fig. 21.25). This pattern, which has traditionally been associated with alveolar proteinosis, is not specific: an indistinguishable CT appearance can be seen in some patients with (mucinous) bronchiolo-alveolar carcinoma, exogenous lipoid pneumonia and a variety of other diffuse lung diseases3.

Figure 21.24 Alveolar proteinosis. Chest radiograph in a 28 year old woman with alveolar proteinosis. There is bilateral symmetrical airspace opacification in the mid and lower zones with a predilection for the central lung, an appearance which can simulate the ‘bat’s wing’ appearance of pulmonary oedema.

MISCELLANEOUS CAUSES OF AIRSPACE OPACIFICATION Pulmonary alveolar microlithiasis is characterized by the deposition of tiny stones (calcipherites) within alveoli. The calcipherites are composed mainly of calcium and phosphorus and are of unknown origin. There is a characteristic radiographic appearance in which innumerable discrete high-density opacities (resembling grains of sand) are seen in both lungs; when profuse there may be a ‘white-out’ and the tiny stones are then best demonstrated on an overexposed radiograph. The disease exhibits a strong familial tendency, and whilst it has been recorded over a wide age range (the peak incidence is between 30 and 50 years), it seems likely that the process begins in early life. Most patients

CHAPTER 21

• AIRSPACE DISEASES

are asymptomatic at the time of diagnosis and disease progression is variable. However, there is a tendency for pulmonary fibrosis and the development of cor pulmonale. The fibrosis of alveolar microlithiasis is associated with the formation of bullae, particularly at the apices. Airspace opacification on chest radiography and CT is a feature of some malignant pulmonary diseases. In patients with bronchiolo-alveolar cell carcinoma (depending to some extent on the histological subtype), there may be consolidation and/ or ground-glass opacities. Similarly, multifocal consolidation is seen on CT in primary pulmonary lymphoma (Fig. 21.26), a rare malignancy (previously called ‘pseudolymphoma’) arising from mucosa-associated lymphoid tissue and considered to be a low grade B-cell lymphoma. Figure 21.25 HRCT of the ‘crazy paving’ pattern in alveolar proteinosis: patchy but geographical ground-glass opacification is seen and there are numerous thickened interlobular septa in areas of groundglass opacification.

Figure 21.26 Primary pulmonary lymphoma. (A) Chest radiograph and (B) CT through the lower zones in a patient with pulmonary non-Hodgkin’s lymphoma. There are bilateral foci of consolidation; the bronchocentric nature of the disease can be easily appreciated on CT.

REFERENCES 1. Haddock J A A, Hansell D M 1992 The radiology and terminology of cryptogenic organizing pneumonia. Br J Radiol 65: 674–680 2. Gaensler E A, Carrington C B 1977 Peripheral opacities in chronic eosinophilic pneumonia: the photographic negative of pulmonary oedema. Am J Roentgenol 128: 1–13. 3. Johkoh T, Itoh H, Müller N L et al 1999 Crazy-paving appearance at thin-section CT: spectrum of disease and pathologic findings. Radiology 211: 155–160 4. Murch C R, Carr D H 1989 Computed tomography appearances of pulmonary alveolar proteinosis. Clin Radiol 40: 240–243 5. Johkoh T, Ikezoe J, Kohno N et al 1996 Usefulness of high-resolution CT for differential diagnosis of multi-focal pulmonary consolidation. Radiat Med 14: 139–146 6. Lui Y M, Taylor J R, Zylak C J 1973 Roentgen–anatomical correlation of the individual human pulmonary acinus. Radiology 109: 1–5 7. Van Allen C M, Lindskog G E 1931 Collateral respiration in the lung: rôle in bronchial obstruction to prevent atelectasis and to restore patency. Surg Gynecol Obstet 53: 16–21 8. Miller W S 1947 Historical sketch. In: Miller W S (ed) The lung, 2nd edn. Springfield: Charles C Thomas, Springfield, pp 162–202 9. Itoh H, Murata K, Konishi J, Nishimura K, Kitaichi M, Izumi T 1993 Diffuse lung disease: pathologic basis for the high-resolution computed tomography findings. J Thorac Imaging 8: 176–188 10. Murata K, Itoh H, Todo G et al 1986 Centrilobular lesions of the lung: demonstration by high-resolution CT and pathologic correlation. Radiology 161: 641–645 11. Webb W R, Müller N L, Naidich D P 2001 High-resolution computed tomography findings of lung disease. In: Webb W R, Müller N L, Naidich D P (eds) High-resolution CT of the lung, 3rd edn. Lippincott Williams & Wilkins, Philadelphia, pp 71–192 12. Austin J H M, Müller N L, Friedman P J et al 1996 Glossary of terms for computed tomography of the lungs: recommendations of the nomenclature committee of the Fleischner Society. Radiology 200: 327–231 13. Gamsu G, Thurlbeck W M, Macklem P T, Fraser R G 1971 Roentgenographic appearance of the human pulmonary acinus. Invest Radiol 6: 171–175 14. Recavarren S, Benton C, Gall E A 1967 The pathology of acute alveolar diseases of the lung. Semin Roentgenol 2: 22–32 15. Itoh H, Tokunaga S, Asamoto H et al 1978 Radiologic–pathologic correlations of small lung nodules with special reference to peribronchiolar nodules. Am J Roentgenol 130: 223–231 16. Collins J, Stern E J 1997 Ground-glass opacity at CT: the ABCs. Am J Roentgenol 169: 355–367 17. Crapo J D 1993 New concepts in the formation of pulmonary oedema. Am Rev Respir Dis 147: 790–792 18. Ketai L H, Godwin J D 1998 A new view of pulmonary oedema and acute respiratory distress syndrome. J Thorac Imaging 13: 147–171

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19. Harrison M O, Conte P J, Heitzman E R 1971 Radiological detection of clinically occult cardiac failure following myocardial infarction. Br J Radiol 44: 265–272 20. Staub N C, Nagano H, Pearce M L 1967 Pulmonary edema in dogs, especially the sequence of fluid accumulation in lungs. J Appl Physiol 22: 227–240 21. Youngberg A S 1977 Unilateral diffuse lung opacity. Radiology 123: 277–281 22. Fleischner F G 1967 The butterfly pattern of acute pulmonary oedema. Am J Cardiol 20: 39–46 23. Friedman W F, Braunwald E 1966 Alterations in regional pulmonary blood flow in mitral valve disease studied by radioisotope scanning: a simple nontraumatic technique for estimation of left atrial pressure. Circulation 34: 363–376 24. Baumstark A, Swensson R G, Hessel S J et al 1983 Evaluating the radiographic assessment of pulmonary venous hypertension in chronic heart disease. Am J Roentgenol 141: 877–884 25. West J B, Dollery C T, Heard B E 1964 Increased vascular resistance in the lower zone of the lung caused by perivascular oedema. Lancet 2: 181–183 26. Zwickler M P, Peters T M, Michel R P 1994 Effects of pulmonary fibrosis on the distribution of edema: computed tomographic scanning and morphology. Am J Respir Crit Care Med 149: 1266–1275 27. Pistolesi M, Miniati M, Milne E N C, Giuntini C 1985 The chest roentgenogram in pulmonary edema. Clin Chest Med 6: 315–344 28. Milne E N C, Pistolesi M, Miniati M, Giuntini C 1985 The radiologic distinction of cardiogenic and noncardiogenic edema. Am J Roentgenol 144: 879–894 29. Aberle D R, Wiener-Kronish J P, Webb W R, Matthay M A 1988 Hydrostatic versus increased permeability pulmonary edema: diagnosis based on radiographic criteria in critically ill patients. Radiology 168: 73–79 30. Smith R C, Mann H, Greenspan R H, Pope C F, Sostman H D 1987 Radiographic differentiation between different etiologies of pulmonary edema. Invest Radiol 22: 859–863 31. Wiener-Kronish J P, Matthay M A 1988 Pleural effusions associated with hydrostatic and increased permeability pulmonary edema. Chest 93: 852–858 32. Herold C J, Wetzel R C, Robotham J L, Herold S M, Zerhouni E A 1992 Acute effects of increased intravascular volume and hypoxia on the pulmonary circulation: assessment with high-resolution CT. Radiology 183: 655–662 33. Miller R R 1995 Diffuse pulmonary hemorrhage. In: Thurlbeck W M, Churg A M (eds) Pathology of the lung, 2nd edn. Thieme Medical Publishers, New York, 365–373 34. Collard H R, Schwarz M I 2004 Diffuse alveolar hemorrhage. Clin Chest Med 25: 583–592 35. Travis W D, Colby T V, Koss M N, Rosado-de-Christenson M L, Müller N L, King T E Jr 2002 Idiopathic interstitial pneumonia and other diffuse parenchymal lung diseases. In: Travis W D, Colby T V, Koss M N, Rosado-de-Christenson M L, Müller N L, King T E Jr (eds) Atlas of nontumor pathology: non-neoplastic disorders of the lower respiratory tract. 1 (Fascicle 2) ed. American Registry of Pathology and the Armed Forces Institute of Pathology, Washington, DC, pp 49–231 36. Morgan P G M, Turner-Warwick M 1981 Pulmonary haemosiderosis and pulmonary haemorrhage. Br J Dis Chest 75: 225–242 37. Buschman D L, Ballard R 1993 Progressive massive fibrosis associated with idiopathic pulmonary hemosiderosis. Chest 104: 293–295 38. Ioachimescu O C, Sieber S, Kotch A 2004 Idiopathic pulmonary haemosiderosis revisited. Eur Respir J 24: 162–169 39. Scadding J G 1956 Pulmonary fibrosis and collagen diseases of the lungs: a symposium. I: clinical problems of diffuse pulmonary fibrosis. Br J Radiol 29: 633–641 40. Goodpasture E W 1919 The significance of certain pulmonary lesions in relation to the etiology of influenza. Am J Med Sci 158: 863–870 41. Briggs W A, Johnson J P, Teichman S, Yeager H C, Wilson C B 1979 Antiglomerular basement membrane antibody-mediated glomerulonephritis and Goodpasture’s syndrome. Medicine 58: 348–361

42. Bruwer A J, Kennedy R L J, Edwards J E 1956 Recurrent pulmonary hemorrhage with hemosiderosis: so-called idiopathic pulmonary hemosiderosis. Am J Roentgenol 76: 98–107 43. Cheah F K, Sheppard M N, Hansell D M 1993 Computed tomography of diffuse pulmonary haemorrhage with pathological correlation. Clin Radiol 48: 89–93 44. DeRemee R A, Colby T V 1995 Wegener’s granulomatosis. In: Thurlbeck W M, Churg A M (eds) Pathology of the lung, 2nd edn. Thieme Medical Publishers, New York, pp 401–402 45. Hoffman G S, Kerr G S, Leavitt R Y et al 1992 Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 116: 488–498 46. Singer J, Suchet I, Horwitz T 1990 Paediatric Wegener’s granulomatosis: two case histories and a review of the literature. Clin Radiol 42: 50–51 47. Cordier J F, Valeyre D, Guillevin L, Loire R, Brechot J-M 1990 Pulmonary Wegener’s granulomatosis: a clinical and imaging study of 77 cases. Chest 97: 906–912 48. Langford C A, Hoffman G S 1999 Rare diseases 3: Wegener’s granulomatosis. Thorax 54: 629–637 49. Carrington C B, Liebow A A 1966 Limited forms of angiitis and granulomatosis of Wegener’s type. Am J Med 41: 497–527 50. Langford C A 2003 Treatment of ANCA-associated vasculitis. N Engl J Med 349: 3–4 51. Kuhlman J E, Hruban R H, Fishman E K 1991 Wegener granulomatosis: CT features of parenchymal lung disease. J Comput Assist Tomogr 15: 948–952 52. Lohrmann C, Uhl M, Kotter E, Burger D, Ghanem N, Langer M 2005 Pulmonary manifestations of Wegener granulomatosis: CT findings in 57 patients and a review of the literature. Eur J Radiol 53: 471–477 53. Grotz W, Mundinger A, Würtemberger G, Peter HH, Schollmeyer P 1994 Radiographic course of pulmonary manifestations in Wegener’s granulomatosis under immunosuppressive therapy. Chest 105: 509–513 54. Attali P, Begum R, Ben Rhomdhane H, Valeyre D, Guillevin L, Brauner M W 1998 Pulmonary Wegener’s granulomatosis: changes at follow-up CT. Eur Radiol 8: 1009–1113 55. Wadsworth D T, Siegel M J, Day D L 1994 Wegener’s granulomatosis in children: chest radiographic manifestations. Am J Roentgenol 163: 901–904 56. Davison A G, Heard B E, McAllister W A C, Turner-Warwick M E H 1983 Cryptogenic organizing pneumonitis. Q J Med 52: 382–394 57. Cordier J F 2000 Organising pneumonia. Thorax 55: 318–328 58. Epler G R, Colby T V, McLoud T C, Carrington C B, Gaensler E A 1985 Bronchiolitis obliterans organizing pneumonia. N Engl J Med 312: 152–158 59. Travis W D, King T E Jr, and the Multidisciplinary Core Panel 2002 American Thoracic Society/European Respiratory Society international multidiscplinary consensus classification of idiopathic interstitial pneumonias. Am J Respir Crit Care Med 165: 277–304 60. Cordier J F 2004 Cryptogenic organizing pneumonia. Clin Chest Med 25: 727–738 61. Flowers J R, Clunie G, Burke M, Constant O 1992 Bronchiolitis obliterans organizing pneumonia: the clinical and radiological features of seven cases and a review of the literature. Clin Radiol 45: 371–377 62. Lee K S, Kullnig P, Hartman T E, Müller N L 1994 Cryptogenic organizing pneumonia: CT findings in 43 patients. Am J Roentgenol 162: 543–546 63. Kim S J, Lee K S, Ryu Y H et al 2003 Reversed halo sign on highresolution CT of cryptogenic organizing pneumonia: diagnostic implications. Am J Roentgenol 180: 1251–1254 64. Akira M, Yamamoto S, Sakatani M 1998 Bronchiolitis obliterans organizing pneumonia manifestating as multiple large nodules or masses. Am J Roentgenol 170: 291–295 65. Murphy J M, Schnyder P, Verschakelen J, Leuenberger P, Flower C D R 1999 Linear opacities on HRCT in bronchiolitis obliterans organising pneumonia. Eur Radiol 9: 1813–1817 66. Ujita M, Renzoni E A, Veeraraghavan S, Wells A U, Hansell D M 2004 Organizing pneumonia: perilobular pattern at thin-section CT. Radiology 232: 757–761 67. Crofton J W, Livingstone J L, Oswald N C, Roberts A T M 1952 Pulmonary eosinophilia. Thorax 7: 1–35

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68. Fraser R S, Müller N L, Colman N, Paré P D 1999 Eosinophilic lung disease. In: Fraser R S, Müller N L, Colman N, Paré P D (eds) Diagnosis of diseases of the chest, 4th edn. W B Saunders, Philadelphia, pp 1743–1756 69. Löffler W 1932 Zur differential-diagnose der lungen infiltreierunger: III uber fluchtige succendan—infiltrate (mit eosinophilia). Beitr Klin Tuberk 79: 368–392 70. Allen J N, Pacht E R, Gadek J E, Davis W B 1989 Acute eosinophilic pneumonia as a reversible cause of noninfectious respiratory failure. N Engl J Med 321: 569–574 71. Hayakawa H, Sato A, Toyoshima M, Imokawa S, Taniguchi M 1994 A clinical study of idiopathic eosinophilic pneumonia. Chest 105: 1462–1466

• AIRSPACE DISEASES

72. Cheon J E, Lee K S, Jung G S, Chung M H, Cho Y D 1996 Acute eosinophilic pneumonia: radiographic and CT findings in six patients. Am J Roentgenol 167: 1195–1199 73. Fraser R S, Müller N L, Colman N, Paré P D 1999 Metabolic pulmonary disease. In: Fraser R S, Müller N L, Colman N, Paré P D (eds) Diagnosis of diseases of the chest, 4th edn. W B Saunders, Philadelphia, pp 2699–2735 74. Prakash U B S, Barham S S, Carpenter H A, Dines D E, Marsh H M 1987 Pulmonary alveolar phospholipoproteinosis: experience with 34 cases and a review. Mayo Clin Proc 62: 499–518 75. Ramirez R J 1967 Pulmonary alveolar proteinosis: treatment by massive bronchopulmonary lavage. Arch Int Med 119: 147–156

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Cardiac Anatomy and Imaging Techniques

22

George G. Hartnell and Julia Gates

• Normal cardiac anatomy • Cross-sectional assessment of cardiac enlargement • Cardiac imaging techniques

Cardiac imaging is challenging for many reasons. No other target organ is in constant motion; essential to life; or as commonly affected by potentially lethal disease. For these reasons cardiac imaging is very common, often costly, and may put patients at risk. There are major financial implications for health care professionals, hospitals, vendors and payers. There are disputes over appropriate utilization of, and responsibility for performing and receiving payment for, studies1. Imaging capabilities change rapidly and the relative value of each technique requires constant re-evaluation2. For this reason it is important to understand the anatomy of the heart, the current capabilities of each available imaging technique and the best methods for imaging each clinical problem. The use of chest radiography in cardiac diagnosis has been largely replaced by echocardiography. Many regard echocardiography as an integral part of the cardiac examination, providing essential information of cardiac function and anatomy. Angiography is mainly used to evaluate coronary artery anatomy, while nuclear imaging is used mainly in the evaluation of ischaemic heart disease (see Ch. 25). Interest in cardiac imaging by magnetic resonance imaging (MRI) and computed tomography (CT) has waxed and waned. There have been periods of enthusiasm associated with the introduction of cine-magnetic resonance angiography (MRA), coronary MRA and electron beam or ultrafast CT (EBCT or UFCT). These developments, although academically significant, had relatively little impact on routine cardiac care. More recently both MRI and CT have developed to the stage where reliable, economic, and comprehensive assessment of cardiac function, perfusion, viability and coronary artery anatomy is possible as part of routine care3. The heart may be studied by the conventional projection imaging techniques of chest radiography, angiography and radionuclide imaging, or by the two-dimensional (2D) imaging techniques of echocardiography, cardiac CT and cardiac MRI and MRA (CMR). When used appropriately in suit-

able subjects, echocardiography, multidetector CT (MDCT), UFCT and CMR provide similar information concerning anatomy and function, and can often be used interchangeably, although echocardiography is used most widely for cardiac diagnosis. In this chapter, MDCT, CMR and angiographic anatomy are used to illustrate the orientation of the heart and its internal structure. Although much cardiac anatomy is conventionally shown by angiography, this is being replaced in many cases by echocardiography MDCT and CMR.

NORMAL CARDIAC ANATOMY Orientation of the cardiac chambers The relationship of the cardiac chambers to each other, the positions and inclinations of the cardiac septae and valves (Table 22.1), and the great vessel relationships are shown by casts of chambers of the heart (Figs 22.1, 22.2). The right atrium forms the right border of the heart. The superior vena cava enters the upper posterior aspect of the right atrium. The atrial septum forms the posteromedial wall of the right atrium.

Table 22.1 ORIENTATIONS OF MAJOR CARDIAC STRUCTURES WHEN ASSESSED BY MRI4 Mean angle

SD

Optimum projection

Aortic arch

−28

8

LAO 62 (P)

Interventricular septum

+56

12

LAO 56 (E)

Interatrial septum

+61

10

LAO 61 (E)

Mitral valve ring

−38

10

RAO 38 (E)

Tricuspid valve ring

−42

11

RAO 43 (E)

Origin right coronary

−17

13

LAO 73 (P)

Origin left coronary

−66

15

LAO 14 (P)

Long axis left ventricle

+48

12

RAO 42 (P)

Long axis right ventricle

+65

9

RAO 25 (P)

Right pulmonary artery

−64

8

RAO 26 (P)

Left pulmonary artery

+37

8

LAO 53 (P)

LAO = left anterior oblique, RAO = right anterior oblique. E = structure best viewed from end-on perspective; P = structure best viewed from perpendicular perspective.

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The aortic root, lying in the middle of the heart, is anteromedial to the right atrium. To the left and anterior to the right atrium lies the right ventricle, separated from the atrium by the tricuspid valve.The right ventricle forms the bulk of the front of the heart. The pulmonary valve, at the top of the right ventricular infundibulum, lies cephalad, anterior and to the left of the aortic root. The curved ventricular septum bulges into the right

ventricle, narrowing it from behind and the left.The curvature of the septum varies from anterior to posterior and from above downwards. The posterior aspect of the heart is formed by the left atrium: the left atrial appendage projects anteriorly and to the left from its upper left border. The pulmonary veins enter the posterior left atrium. The left atrium is flattened antero-posteriorly. The left atrium and ventricle are separated by the mitral valve,

Figure 22.1 Anatomy of the right heart cavities. Cast of the right heart cavities compared with maximum intensity projection (MIP) and volume rendered (VRT) CTA. (A) Frontal and (B) left lateral. The black area on the cast represents the intraventricular component of the membranous septum (m) under the septal leaflet of the tricuspid valve. The white area (s) represents that component of the membranous septum that lies above the tricuspid valve and separates the left ventricle from the right atrium. The entry of the main draining vein of the heart, the coronary sinus (cs), into the right atrium between the inferior vena cava and the tricuspid valve is seen. (C,D) Coronal 3D reconstruction of the right heart chambers using MDCTA. Right anterior oblique views of the right heart shown by (C) CTA (maximum intensity projection [MIP]) and (D) volume rendered (VRT) shows the right coronary artery (RCA, arrows in C) running in the low attenuation fat of the anterior atrioventricular groove. Continued

CHAPTER 22

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CARDIAC ANATOMY AND IMAGING TECHNIQUES

Figure 22.1 Cont’d (E,F) Sagittal 3D reconstruction of the right heart chambers using MDCTA by (E) MIP and (F) VRT showing the position of the pulmonary valve (white arrows). Mitral valve leaflets indicated by black arrows on (E). Ao = aortic root, CSV = crista supraventricularis, DA = descending aorta, fo = foramen ovale, Inf = infundibulum separating the right ventricular inflow and outflow, IVC = inferior vena cava, MPA = main pulmonary artery, pb = parietal band, PV = pulmonary valve (between white arrows), RA = right atrium, RAA = right atrial appendage, RV = right ventricle, sb = septal band, SVC = superior vena cava, TV = tricuspid valve.

Figure 22.2 Anatomy of the left heart cavities. Cast of the left heart chambers. (A) Frontal. The left atrium (LA) can be seen at the back with its appendage (LAA) protruding to the left. The carrot-shaped left ventricle points anteriorly, inferiorly and to the left, and hence is foreshortened. Three components of the ventricular septum can be seen. The membranous septum (ms) between the right and noncoronary sinuses of Valsalva provides the right attachment to the anterior leaflet of the mitral valve. The smooth muscular septum (sms) curves round the upper part of the left ventricle, almost forming part of the left border of the left ventricle. Below lies the trabeculated muscular septum (ts). The right coronary sinus, seen en face, is indicated by the origin of the right coronary artery (rca). (B) Left lateral. The left ventricle is foreshortened as it points to the left as well as downwards and forwards. The lack of a muscular infundibulum in the left ventricle allows the upper left ventricle to reach up between the right coronary and left coronary sinuses of the aortic root. The origin of the anterior papillary muscle (apm) of the mitral valve from the left ventricular free wall may be identified (in this cast, it lies superimposed on the posterior papillary muscle). The right coronary sinus of Valsalva is indicated by the origin of the right coronary artery. (C–G) 3D reconstructions of the left heart chambers using MDCTA. (C) Coronal view of the left heart (maximum intensity projection [MIP]) shows the position (white line) for setting up a fourchamber view. (D) The four-chamber view shows the right coronary artery (RCA) running in the low attenuation fat of the anterior atrioventricular groove and the circumflex coronary artery (CX) running in the low attenuation fat of the posterior atrioventricular groove. Note the prominent crista terminalis (CT) in the wall of the right atrium, a normal structure commonly mistaken for a mass. The white line indicates the position for setting up a two-chamber view of the left heart. Continued

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Figure 22.2 Cont’d (E) Oblique coronal MIP reconstruction of the left heart chambers (E) showing the relationship of the LAD running in the anterior interventricular groove and the position of the bifurcation of the LMCA. (F) Volume rendered (VRT) image (left anterior cranial) showing the relationship of the ventricles, the origins of the ascending aorta and pulmonary artery and positions of the left anterior descending coronary artery (LAD) and right coronay artery (RCA). (G) VRT image (left lateral) showing the relationship of the left ventricle (LV) to the LAD, coronary sinus (CS) and CX. AA = ascending aorta, AV = aortic valve, CT = crista terminalis, PA = main pulmonary artery, RA = right atrium, RV = right ventricle.

which lies in the right anterior oblique plane. The left ventricle, which forms the bulk of the left heart border, lies anterior to the left atrium. The atrial and ventricular septae lie in approximately the same left anterior oblique plane, forming the septal plane of the heart, and separate the right heart chambers anteriorly and on the right from the left heart chambers posteriorly and on the left (Fig. 22.2D,F). The plane of the ventricular septum is marked on the surface of the heart by the interventricular groove encircling the ventricular mass. The aortic valve lies in the centre of the cardiac mass with the left main (LMCA) and right (RCA) coronary arteries arising from the aortic root about 1 cm cephalad to the valve ring (Fig. 22.3).The left anterior descending (LAD) coronary artery (a branch of the left coronary artery) runs in the anterior interventricular groove to supply the anterior aspect of the ventricular septum (Figs 22.2F, 22.4). Septal branches pass perpendicularly from the LAD into the septal myocardium (Fig. 22.4B). Diagonal branches pass from the LAD over the posterior surface of the heart (Fig.

22.4C). In about 10% a large diagonal branch arises from the bifurcation of the LMCA to form the ramus intermedius artery (Fig. 22.5C). The posterior descending coronary artery, which may be a branch of the right or left coronary arteries, lies in the postero-inferior interventricular groove and supplies the posterior base of the ventricular septum.The relative contributions of these arteries to septal blood supply can vary considerably. The atrioventricular plane is marked on the surface of the heart by the atrioventricular groove.The right coronary artery passes anteriorly in the right (anterior) atrioventricular groove (Figs 22.1C,D, 22.6); the circumflex branch of the left coronary artery lies in the left (posterior) atrioventricular groove. The atrioventricular and posterior interventricular grooves intersect on the postero-inferior surface of the heart at the crus (crux) of the heart. The coronary artery that reaches the crux and supplies the posterior interventricular branch is termed the dominant coronary artery. This is usually the right coronary artery (85%) but there may be circumflex dominance (8%) or mixed dominance (7%).

CHAPTER 22

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Figure 22.3 Evaluation of aortic valve and coronary artery origins using ECG-gated MDCTA. (A) Coronal MDCTA image shows the positions for imaging the coronary artery origins and the aortic valve. (B) Short axis view through the aortic valve clearly shows the position of the three raphe of the aortic valve (arrows). There is a small and clinically insignificant amount of calcification on the noncoronary cusp. (C) Image just superior to (B) shows the origins of the main coronary arteries with a calcified moderate proximal stenosis of the left main coronary artery (LMCA). Note the ability to image even small vessels such as the sinus node artery and proximal diagonal artery. AA = Ascending aorta, Ao = aortic root, D = diagonal coronary artery, LA = left atrium, LAD = left anterior descending coronary artery, LMCA = left main coronary artery, LV = left ventricle, RA = right atrium, RCA = right coronary artery, RV = right ventricle, RVOT = right ventricular outflow tract, SNA = sinus node artery.

Individual heart chambers Right atrium The right atrium (Fig. 22.1) has a smooth globular body and a triangular, trabeculated appendage pointing upwards, forwards, and to the left. A muscular ridge, the crista terminalis, separates the body of the atrium from the appendage (Fig. 22.2D). The broad-based, squat right atrial appendage characterizes the morphological right atrium, and in complex congenital heart disease distinguishes it from the left atrium (Figs 22.1C,D, 22.2C). The superior and inferior venae cavae enter the posterior wall of the right atrium some way from its centre (but not at the upper and lower ends). The fossa ovalis, surrounded by the slight elevation of its limbus, lies in the middle of the interatrial septum, which forms the left posterior wall of the right atrium. The tricuspid valve opens to the left and anteriorly from the body of the right atrium. The coronary sinus (Figs 22.2G, 22.4C), the major draining vein of the heart, enters the posterior wall of the right atrium between the tricuspid valve and the inferior vena cava. On a frontal image, a catheter or pacing wire in the coronary sinus may appear to lie in the right ventricular outflow tract, but a lateral view will show it to be posterior. The right atrium forms the right margin of the heart (Fig. 22.1). Three features characterize right atrial internal morphology: 1 the limbus of the fossa ovalis on the septal aspect 2 the crista terminalis 3 a squat, broad-based appendage Right atrial size is estimated by echocardiography, CT, or CMR in the same way as that of the left atrium, particularly using an apical four-chamber view or its equivalent. Causes of right atrial enlargement are listed in Table 22.2.

Right ventricle The right ventricle has a complex shape (Fig. 22.1). From the front it resembles a triangle (although with four distinct edges) based on the diaphragm. Superiorly a muscular conus or infundibulum separates the pulmonary valve from the tricuspid valve (Figs 22.1D, 22.7B). On the left and inferiorly is a coarsely trabeculated apex. The lower end of the septal aspect of the conus has a discrete muscular elevation, the crista supraventricularis, extending to the right and forwards over the tricuspid valve to the right ventricular free wall to form the parietal band. The normal right ventricle makes virtually no contribution to the cardiac silhouette in the frontal projection (Fig. 22.1D). In the lateral view the right ventricle forms the anterior aspect of the heart (Fig. 22.1E,F), with the lower half normally in contact with the sternum. Three features characterize right ventricular morphology: 1 a muscular conus or infundibulum separating the entry atrioventricular valve from the exit semilunar valve by a ring of muscle 2 a tricuspid atrioventricular valve which is in part connected to the septum of the chamber, either by direct chordal attachment or through a small papillary muscle of the conus 3 coarse trabeculation of the septal aspect of the ventricle (Fig. 22.7) Restricted acoustic access often makes it difficult to image the right ventricle by echocardiography, and it is more completely evaluated by CT or CMR. Causes of right ventricular enlargement are listed in Table 22.3.

Left atrium The left atrium (Figs 22.2, 22.4) usually receives the four pulmonary veins at the ‘corners’ of its posterior surface (Fig. 22.8) and empties through the mitral valve in its left lower

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Figure 22.4 Evaluation of left coronary artery anatomy by ECG-gated MDCTA. (A) Axial MDCTA source image showing positions for imaging the left anterior descending coronary artery. (B) Oblique thin maximum intensity projection (MIP) reconstruction along the line of the left anterior descending coronary artery (LAD) with calcified plaque at several levels as well as the origin of the circumflex coronary artery and several small septal arteries (S). (C) Oblique thin MIP reconstruction posterior to (B) showing the distal LAD and the origin of a large diagonal branch (arrows). Note the visibility of the coronary sinus (CS) and its branches, which should not be confused with arteries. (D) Curved thin MIP reconstruction along line shown (inset) to demonstrate length of the LAD. Arrows indicate plaque causing variable degrees of stenosis in both the right coronary artery and the LAD. Ao = aortic root, LA = left atrium, LAA = left atrial appendage, LV = left ventricle, MCV = middle coronary vein, MV = mitral valve, PA = pulmonary artery, PM = papillary muscle, RAA = right atrial appendage, S = septal branches from the LAD.

anterior aspect. The long finger-like forward-projecting left atrial appendage is its only characteristic morphological feature (Figs 22.4C, 22.5C). The left atrium makes no definite contribution to the normal cardiac silhouette in the frontal view as the normal left atrial appendage is buried in the epicardial fat and does not produce a discrete shadow (Fig. 22.9). In the lateral view (Fig. 22.2G), the left atrium contributes to the upper posterior border of the heart, but normally the left atrium is not in contact with the air-containing lung and there is no properly defined outline. The features that characterize left atrial morphology are an absence of those suggesting right atrial morphology, and more positively the long finger-like atrial appendage.

The left atrium is posterior to the aortic root (Fig. 22.3). Left atrial enlargement is usually measured using echocardiography but parallel images, from CMR or MDCT, can also be used to measure atrial volumes. Causes of selective left atrial enlargement are listed in Table 22.4.

Left ventricle The left ventricle (Figs 22.2, 22.4) is a cone-shaped structure with a long axis pointing inferiorly, anteriorly and to the left. Its base is the fibrous skeleton of the mitral and aortic valves and its apex usually forms the apex of the cardiac shadow as seen on the frontal chest radiograph. The left ventricle has no conus or infundibulum: the mitral and

CHAPTER 22

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CARDIAC ANATOMY AND IMAGING TECHNIQUES

Figure 22.5 Vascular relationships to the left heart using ECG-gated MDCTA. (A) Axial MDCTA source image showing the positions (from anterior to posterior) of coronal reconstructions illustrated in B–D. This image shows the origin of the left main coronary artery from the aortic root. (B) Thin maximum intensity projection (MIP) coronal reconstruction through the centre of the aortic valve shows part of the left anterior descending coronary artery (LAD) passing obliquely through the image. (C) A more posterior image shows a complex high attenuation (calcified) and low attenuation (fatty) plaque at the origin of the left main coronary artery (left main coronary artery [LMCA]). Note the trifurcation of the LMCA due to the presence of a ramus intermedius artery. The same image shows the origin of the circumflex coronary artery and the left atrial appendage superior to the left ventricular myocardium. The characteristic ridged appearance of the left atrial appendage must be differentiated from thrombus. High attenuation at the base of the posterior mitral leaflet may be an early sign of mitral annulus calcification. (D) The most posterior image shows the upper part of the coronary sinus running in the posterior atrioventricular groove and inflow of the right upper pulmonary vein. AA = ascending aorta, Ao = aortic root, AV = aortic valve leaflets, CS = coronary sinus, CX = circumflex coronary artery, DA = descending aorta, LA = left atrium, LAA = left atrial appendage, LPA = left pulmonary artery, LV = left ventricle, MV = mitral valve, PA = pulmonary artery, RA = right atrium, RAA = right atrial appendage, RI = ramus intermedius coronary artery, RPA = right pulmonary artery, RUPV = right upper pulmonary vein.

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Figure 22.6 Evaluation of right coronary artery anatomy by ECG-gated MDCTA. (A) Axial MDCTA source image showing positions for imaging the proximal RCA. Usually the same orientation will image the proximal circumflex coronary artery (CX). (B) Oblique reconstruction showing the origin of the right coronary artery (RCA) in the anterior atrioventricular groove. (C) Adjacent more posterior image showing a long length of RCA running to the inferior margin of the heart. In all these images it is important to avoid confusing the coronary arteries and cardiac veins, structures which are not usually seen on coronary arteriography. (D) Curved thin maximum intensity projection (MIP) reconstruction along line shown (inset) to demonstrate length of the RCA. Areas of coronary stenosis are indicated by black and white arrows. Ao = aortic root, AV = aortic valve leaflets, CS = coronary sinus, LA = left atrium, LAA = left atrial appendage, LV = left ventricle, MCV = middle coronary vein, PMV = posterior mitral valve leaflet, RA = right atrium, RCA = right coronary artery, RV = right ventricle, SNA = sinus node artery.

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Table 22.2

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CAUSES OF A LARGE RIGHT ATRIUM

Volume overload Tricuspid regurgitation. Most commonly due to congestive cardiac failure with right ventricular dilatation* Atrial septal defect (due to increased flow from left atrium) Atrioventricular canal (due to shunt into right atrium and atrioventricular valve regurgitation) Pulmonary hypertension (usually with a degree of tricuspid regurgitation) Anomalous pulmonary venous drainage to right atrium Sinus of Valsalva fistula Pressure overload Right ventricular failure Tricuspid stenosis (with mitral stenosis when rheumatic aetiology; con genital tricuspid stenosis is very rare) Restrictive cardiomyopathy (especially in diabetes mellitus) Right atrial myxoma or other tumours causing tricuspid valve obstruction (very rare) Acquired tricuspid stenosis (carcinoid syndrome; more commonly causes tricuspid regurgitation) *Tricuspid regurgitation is also seen in Ebstein's anomaly, arrhythmogenic right ventricular dysplasia, carcinoid syndrome, endomyocardial fibrosis and fibro-elastosis.

aortic valves are in fibrous continuity, the anterior leaflet of the mitral valve arising from the noncoronary and part of the left coronary sinuses of Valsalva of the aortic valve. The mitral valve is bicuspid.The inflow valves are an integral part of their respective ventricles. The ventricular septum lies obliquely from right posterior to left anterior. It is a curved structure arching over the ventricle so that the membranous part of the ventricular septum faces to the right under the noncoronary and right coronary sinuses of Valsalva. The smooth muscular septum derived from the conus cushions of the cardiac tube faces to the left under the right and left coronary sinuses of Valsalva. The distal ventricular septum is finely trabeculated. The feature that best characterizes left ventricular morphology is fibrous continuity of the entry atrioventricular valve and the exit semilunar valve, due to the lack of any conus or infundibulum. The conical shape and relatively fine trabeculation (absent on the upper septum) are not helpful. In diastole, the mitral valve is usually open wide and the aortic valve is closed. Contraction should be concentric, and filling defects about the middle of the anterior and inferior walls are usually due to the papillary muscles (Fig. 22.4C). Left ventricular volume can reliably be estimated by echocardiography, which is the most frequently used method for assessing left ventricular dimensions and function. A number of methods have been described, using combinations of apical four-chamber, apical two-chamber, or multiple short axis views. Left ventricular myocardial thickness can readily be measured by echocardiography, MDCT, or CMR. The thickness of the posterior wall is the distance from the anterior border of the endocardium to that of the epicardium, excluding the pericardial space. When measuring septal thickness, it is essential to exclude the trabeculum septomarginalis, which runs alongside the interventricular septum within the right ventricular cavity. The distribution of

Figure 22.7 Axial MRI in mitral stenosis. (A) Axial ECG-gated spin-echo image of patient with mitral stenosis leading to right heart failure. Slow flow in the left atrium has produced high signal in that chamber. (B) Oblique coronal breath-hold cine-MRA image of the heart. There is dilatation of the right atrium (RA) and right ventricle (RV). There is mild tricuspid regurgitation (jet of flow dephasing = open arrow). aa = Ascending aorta, la = left atrium, sb = septal band, t = tricuspid valve, inf = infundibulum of RV. The pulmonary valve is shown between the black arrows.

Table 22.3

CAUSES OF A LARGE RIGHT VENTRICLE

Left heart failure (most common cause, particularly associated with mitral valve disease) Pulmonary artery hypertension due to lung disease (cor pulmonale) Chronic thromboembolic disease Left-to-right shunt Vasculitis Idiopathic pulmonary hypertension Tricuspid regurgitation Pulmonary regurgitation Pulmonary arteriovenous malformations Severe pulmonary stenosis

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Figure 22.8 Left atrial and pulmonary vein anatomy. (A) High signal or attenuation allows better 3D image reconstruction with a wide range of reconstruction techniques. Also, the larger the structure being imaged the more accurate the reconstruction. Contrast-enhanced MRA for pulmonary venography provides very high signal compared with background. (B) Using thin-slice maximum intensity projection (MIP) reconstruction the inflow of the pulmonary veins (RPVS, LPVS) into the left atrium is accurately represented. (C) When this type of high contrast image with a uniform signal level surface shaded (SSD) reconstruction can be used to guide ablation procedures. This posterior view shows late confluence of the right lower lobe apical pulmonary vein (arrow) within 1 cm of the pulmonary vein ostium (over incorporation). AA = Aortic arch, AO = upper descending aorta, DA = lower descending aorta, LA = left atrium, LPV = left pulmonary vein, RPV = right pulmonary vein.

left ventricular hypertrophy is well demonstrated by echocardiography and is particularly important in patients with hypertropic cardiomyopathy. Hypertrophy is often asymmetrical with severe secondary hypertrophy, and localized basal septal hypertrophy is a common finding particularly in the elderly. Causes of selective left ventricular enlargement are listed in Table 22.5.

CROSS-SECTIONAL ASSESSMENT OF CARDIAC ENLARGEMENT Echocardiography is very useful in establishing the cause of cardiomegaly and is the usual method for determining inter-

nal cardiac dimensions. Both MDCT and CMR can serve the same functions, with CMR being probably the more accurate technique. Normal dimensions should be corrected for patient size. It is not uncommon for several abnormalities to be present in one patient. Thus aortic (stenosis or regurgitation) or mitral (regurgitation) disease cause left ventricular dilatation and increased wall thickness. In these patients, left ventricular enddiastolic pressure rises, so that left atrial size is increased while associated fluid retention may produce a pericardial effusion. Chronic left-sided heart disease, eventually causing right heart failure, may lead to right atrial and ventricular dilatation with secondary valvar regurgitation (Fig. 22.7).

Table 22.4

CAUSES OF A LARGE LEFT ATRIUM

Due to volume overload Mitral regurgitation (often with left ventricular failure) Ventricular septal defect Patent ductus arteriosus Atrial septal defect with shunt reversal (i.e. pulmonary hypertension) Atrial septal defect with tricuspid atresia (obligatory shunt reversal) Aortopulmonary window Due to pressure overload Mitral stenosis Noncompliant left ventricle: hypertension, hypertrophic cardiomyopathy, aortic stenosis

Figure 22.9 Coronal MRA. Oblique breath-hold cine-MRA in a patient with mild aortic regurgitation (black arrow) shows the left atrial appendage (LAA) embedded in epicardial fat. There is mild dilatation of the ascending aorta (aa) as a result of the aortic regurgitation. Between curved arrows = aortic valve. lv = Left ventricle, pa = pulmonary artery, RA = right atrium.

Left ventricular failure (often with secondary mitral regurgitation) Left atrial myxoma Other causes (both rare) Atrial fibrillation Isolated/idiopathic

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Table 22.5

CAUSES OF A LARGE LEFT VENTRICLE

Any cause of myocardial damage Myocardial ischaemia (most common cause, with or without myocardial infarction) Cardiomyopathy (including ischaemic and hypertensive disease) Myocarditis Chronic volume overload Mitral regurgitation Ventricular septal defect (congenital or acquired) Patent ductus arteriosus Aortopulmonary window Atrioventricular canal High cardiac output Chronic anaemia Thyrotoxicosis Large arteriovenous fistula Extensive Paget's disease of bone* Chronic pressure overload (ventricular dilatation is a late feature which indicates a worsening of prognosis in aortic stenosis, systemic hypertension, and coarctation of the aorta) *

Paget's disease is frequently listed as a cause of left ventricle dilatation resulting from a high-output state and is said to be due to shunting through involved bones. In reality, by far the most common cause of an enlarged heart in patients with Paget's disease is unrelated hypertensive or ischaemic heart disease.

Ventricular volumes can be rapidly estimated, with reasonable accuracy, using 2D images from echocardiography, CT and CMR, and applying one of several formulae (e.g. Simpson’s rule, see below), which make assumptions about ventricular geometry (the normal left ventricle is assumed to be a prolate ellipse). These methods become less accurate in the dilated ventricle.

Biventricular enlargement In most adults with acquired heart disease, the disease process, although beginning on the left side of the heart, eventually involves the pulmonary circulation and the right heart chambers, leading to gross cardiac enlargement (Table 22.6). When this occurs, all the cardiac chambers are likely to be involved, and it is not possible to determine the contribution of each chamber with plain radiography.The heart takes on a globular shape when all chambers are enlarged.

Table 22.6 CAUSES OF GROSS CARDIAC ENLARGEMENT Multiple valve disease (usually initially due to aortic or mitral valve disease, particularly regurgitation, which progresses to left and then right heart failure) Pericardial effusions (no single chamber enlargement identifiable) Dilated cardiomyopathy Ebstein's anomaly (frequently mimics pericardial effusion) Arrhythmogenic right ventricular dysplasia Heterotropic cardiac transplantation

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CARDIAC IMAGING TECHNIQUES Planar imaging orientation and cross-sectional imaging planes There are many ways to obtain imaging information about the heart. Each technique has advantages, disadvantages, costs and risks. The choice depends on the nature of the data required, availability of imaging equipment, interpretative and operator skills; all work well and are accurate enough in most routine cases. A detailed discussion of the capabilities of each technique is less important than understanding the anatomy and pathology, and then using the appropriate technique well. For example, left ventricular systolic function can be assessed with similar accuracy by echocardiography, CT angiography (CTA), MRA, nuclear imaging and angiocardiography. The decision on which to use depends on the need for reproducibility (favouring MRA or nuclear imaging); patient mobility (echocardiography is best for unstable patients where imaging must go to the patient); need for other imaging (selective coronary angiography with angiocardiography); viability (MRI or nuclear imaging); and assessment of valve function (echocardiography). Nuclear imaging (planar) and angiography are planar techniques, which require image acquisition in the correct orientation and depend on the configuration and orientation of the heart. For ventriculography (nuclear or angiographic) this will usually be in a right anterior oblique (RAO; Fig 22.10) orientation (and occasionally left anterior oblique [LAO]) profiling the long axis of the left ventricle. Sectional (2D) imaging by echocardiography or CMR requires acquisition to be positioned to best identify the abnormality using a variety of imaging planes (short axis, two- and four-chamber long axis approaches).

Quantitative assessment of cardiac performance Assessment of cardiac performance is important since it reflects the heart’s ability to adapt to a pathological state. Poor ventricular function causes symptoms and also predicts those patients with a reduced life expectancy, whether due to ischaemic heart disease, valve disease, or other pathologies. Regional abnormalities may identify areas of viable but ischaemic or nonviable myocardium or other focal disease (such as right ventricular dysplasia). Systolic ventricular function can be assessed by echocardiography, CTA (to some extent), cine-MRA, nuclear imaging and angiocardiography. Quantitative analysis can be applied with varying degrees of accuracy and ease to all these techniques. The accuracy of assessment depends on temporal resolution (the faster the frame rate the better), spatial resolution and ability to define the entire endocardial surface accurately (best for echocardiography and MRA), freedom from artefact (angiocardiography may be affected by arrhythmia during contrast medium injection), and ability to apply computer analysis techniques. Quantitative estimation of pump performance is usually limited to the left ventricle and to the events occurring during the ejection of blood. The ejection fraction is the most

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Figure 22.10 (A,B) Normal left ventriculogram, right anterior oblique (RAO). (A) Diastole. The aortic valve (arrows) is closed. The mitral valve is not seen in profile, due to inadequate obliquity, but its site could be identified by nonopaque blood passing through it (asterisk). (B) Systole. There has been good emptying with concentric contraction so that anterior wall, apex and inferior wall of the left ventricle (LV) have all moved equally. The aortic valve is open and the mitral valve closed. Filling defects in the contrastfilled left ventricle indicate the papillary muscles (white arrowhead = anterior, black arrowhead = posterior, open black arrow = contribution of the septum to the left ventricular outline). (C,D) Normal left ventricle on breath-hold cine-MRA (RAO equivalent). (C) Enddiastole. The closed mitral valve is well seen (between white arrows), as is the posterior papillary muscle (black arrow). (D) End-systole. There has been good emptying with concentric contraction of the LV so that anterior wall, apex and inferior wall have all moved equally. The mitral valve (between white arrows) is again closed. Signal defects in the left ventricle indicate thickening of the papillary muscle (black arrow).

common index of pump performance and is calculated from the expression: EF =

(LVEDV–LVESV) LVEDV

where LVEDV is the left ventricular end-diastolic volume and LVESV the left ventricular end-systolic volume calculated from 2D images. The most accurate measurements are obtained using multiple contiguous short axis views and calculating volumes using Simpson's rule (which can also be used with CT and CMR). Simpson's rule is a method for volume or mass calculation based on dividing the ventricular volume into a series of slices equidistant along the long axis of the ventricle. It makes no assumption about the shape of the ventricle. Modifications, based on the assumption that the left ventricle is a prolate ellipse, can be applied to single 2D long axis sections.

Echocardiography General principles Ultrasound examination of the heart, or echocardiography, offers a wealth of anatomical and physiological information without ionizing radiation, patient discomfort, or significant risk. It is therefore well suited to the initial assessment of cardiac disease and to serial studies. Echocardiography is so widely available and provides such useful information on nearly all aspects of cardiac disease that many regard it as an integral part of the clinical examination of the heart. The experience of the examiner or the centre in which it is used will determine its relationship to other techniques of diagnosis and management. For example, one centre may consider echocardiography information sufficient to proceed with surgical therapy while another centre may demand confirmatory data be obtained by cardiac catheterization, CMR, or other imaging techniques. The evolving capabilities of Doppler, power Doppler and 3D echocardiography continue to extend its uses2.

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Two-dimensional echocardiography This is the imaging tool used most frequently to evaluate the anatomy and function of the heart. The ultrasound beam is directed mechanically or more usually electronically through a plane intersecting the chosen cardiac or great vessel structures. This allows imaging of a large segment of the heart and great vessels from a small, often limited, acoustic window on the chest wall. Commercially available ultrasound systems may generate real-time, 2D images at frame rates up to or greater than 100 Hz depending on the total sector angle and distance of the structures from the transducer. When a transthoracic approach is inadequate, transoesophageal echocardiography (TOE) often provides the best images of the heart. In addition, the portability of echocardiography often means that it is the most appropriate method for very sick patients (Fig. 22.11). Through computer reconstruction of 2D images, 3D echocardiograms have become possible. Similar to other forms of tomographic imaging with 3D reconstruction (e.g. CMR, CT), the approach involves obtaining multiple 2D images to produce a 3D image. New, faster techniques are making realtime viewing of 3D images possible5.With improving technology, speed of acquisition and reconstruction, these techniques continue to find increasing clinical use. Current uses have been to determine ventricular size, mass and function, qualitative and quantitative assessment of anatomy, and the placement of medical devices.

Doppler echocardiography The display of blood or tissue velocity can be used qualitatively as an intracardiac stethoscope to validate the source of heart sounds and murmurs. Measurement of blood velocity can lead to quantitative estimation of blood flow and pressure gradients. Assessment of tissue velocity can yield information on the motion of cardiac muscle.

Figure 22.11 Transoesophageal echocardiography (TOE) of aortic dissection. TOE view of the aortic root through the left atrium showing the dissection flap (arrows) in acute Type A aortic dissection. This provides the highest spatial and temporal resolution of any cross-sectional imaging technique, and is the best way to demonstrate the precise anatomy of the aortic root in acute aortic dissection. (Courtesy of Hani Aziz, MD.)

Doppler colour flow mapping presents spatially oriented velocity data in real-time superimposed on an M-mode or 2D image for anatomical and temporal reference (Fig. 22.12). Components of velocities towards or away from the transducer are represented as shades of red or blue, respectively. Since the velocity data are displayed in real-time, the video image correctly gives the impression of blood moving through the cardiac chambers and vessels. With faster computers, 3D colour Doppler imaging has also become possible.

Figure 22.12 Transoesophageal echocardiography (TOE). (A) TOE is usually the most accurate method for imaging valve disease, as in this patient with endocarditis of the aortic valve complicated by perforation of a cusp (arrow). It is doubtful that any other imaging technique could approach the clarity of this image. (B) Echocardiography also has the advantage that accurate flow information is easily obtained along with anatomical information. Here colour flow Doppler shows severe aortic regurgitation (between arrows). Ao = aortic root, LV = left ventricle, LA = left atrium, RV = right ventricle. (Courtesy of Hani Aziz, MD.)

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Pulsed Doppler echocardiography displays velocity information recorded from a well-localized area or sample volume identified on the 2D image. Most machines display this sample volume along a cursor identical to that used to obtain an M-mode echocardiogram. Pulsed Doppler echocardiography is used to assess localized valve stenosis or regurgitation, to quantify flow at a specific point in a chamber or vessel, and to detect abnormal flow patterns. Continuous wave Doppler echocardiography simultaneously displays the velocities of all volumes of blood intersected by the 1D cursor. In return for not being able to provide spatial separation of velocities, it is able to record blood velocities far in excess of the pulsed Doppler method.

Contrast medium echocardiography Contrast medium echocardiography is an exceptionally useful adjunct to ultrasound imaging, especially with the development of newer contrast agents6. The intravascular contrast effect can be produced when microbubbles of gas, present in solution, are injected into a peripheral vein or the injection of stable solutions of microbubbles prepared in advance. Some agents contain very small microbubbles which traverse the pulmonary vascular bed. Other agents filtered by the lungs opacify the left heart only when a right-to-left shunt is present. Contrast medium echocardiography may clarify anatomy incompletely identified by 2D imaging, or improve the definition of endocardial boundaries, improving the detection of wall motion abnormalities (see Fig. 25.10B).Valvular regurgitation and intracardiac or pulmonary shunts may be assessed by peripheral or catheter injection. Finally, myocardial perfusion can be evaluated by contrast medium enhancement after intracoronary or venous contrast injection.

There are two approaches to overcoming this problem, one of which now allows much more widespread use of CT for cardiac diagnosis, including coronary artery imaging8–10. The first but less commonly used approach is EBCT (Fig. 22.13, see Fig. 25.3). This approach uses an electronically steered beam of electrons aimed at a series of tungsten rings to generate X-rays. This allows very rapid pulsing and rotation of the X-ray beam producing typical exposure times of 33, 50, or 100 ms at up to 30 frames s−1, a level of performance not matched by MDCT. Pulsing the X-ray beam can be ECG triggered, minimizing blurring due to cardiac motion, and reducing radiation dose as exposure occurs only during useful image acquisition. Although there are many potential advantages to using this approach for cardiac imaging, for numerous technical and historical reasons there are relatively few EBCT machines in operation. The major current interest in cardiac CT focuses on the development of MDCT11. The development of MDCT (typically 16 or more rows of static detectors) with fast tube rotation, ECG triggering of image acquisition and ECG controlled modulation of tube current (and therefore of X-ray output), along with sophisticated post-processing, has opened up a wide range of options for cardiac imaging. Slice thickness can be collimated to as little as 0.4 mm. Fast tube rotation (which may be as little as 330 ms) and ECG triggering mean that image data can be acquired during only a short portion (typically 100– 200 ms) of the tube rotation (partial rotation reconstruction). When data are acquired toward the end of diastole, when there is usually the least cardiac motion, blurring and other artefacts are minimized (Fig. 22.14). Even the fastest current MDCT

Clinical applications Echocardiography can be helpful in clarifying the presence or absence of heart disease but is not recommended for routine screening of patients with ‘innocent’ murmurs, and should not replace thorough history taking and physical examination7.The value of echocardiography is seen in the diagnosis, differential diagnosis, or follow-up of virtually all types of cardiac disease, as well as risk stratification and assessment of cardiac function. Stress echocardiography incorporates the same techniques used to assess function at rest (e.g. shortening fraction, ejection fraction, cardiac output, segmental wall motion analysis) with a stressor such as exercise or a pharmacological agent such as dobutamine infusion (see Fig. 25.4). Doppler echocardiography can estimate changes in flow during exercise. Sensitivity and specificity depend on the protocol used, choice of correlative imaging, patient population (overall accuracy may be better in men), and nature of the disease (more sensitive for LAD disease when imaging single vessel disease, more sensitive for multivessel disease), and are quoted to be between 80% and 100%.

Computed tomography For many years CT had limited use in the evaluation of heart disease. The slow image acquisition led to image blurring.

Figure 22.13 Axial electron beam CT (EBCT) showing heavy calcification (straight arrows) anteriorly in the pericardium following localized radiotherapy and mitral annulus (curved arrow). Note the clear definition of the normal thickness pericardium (open arrow), which is well shown using the very short exposure (100 ms) possible with EBCT.

CHAPTER 22

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Figure 22.14 Pulsatility artefact on CTA. (A) Axial CTA image through the ascending aorta (AA) reconstructed without ECG gating. Note the double shadows (arrows) in the ascending aorta. The double densities in the aorta prevent confident exclusion of aortic dissection, and obscure the separation of the aorta from the right ventricular outflow (RV). There is also marked blurring of calcification in the distal left main coronary artery (arrowheads). (B) Axial CTA image through the ascending aorta (AA) now reconstructed with ECG gating at end-diastole using the same acquisition as in (A). The wall of the aorta is now clearly defined, as is calcification in the coronary arteries. In addition, areas of low attenuation plaque (arrows) are now visible. (C) Pulsatility effects are evident when viewing 3D reconstructions. Here an oblique maximum intensity projection reconstruction (MIP) shows a step artefact in the ascending aorta (AA, arrows) due to pulsatility. (D) The same 3D reconstruction using ECG-gated source images reconstructed at enddiastole produces a smooth wall of the ascending aorta (AA). There is also clearer definition of the coronary sinus (white arrows) running below the left atrium, calcification in the distal right coronary artery (white arrowhead) and calcification in the aortic valve ring (black arrow).

acquisition is longer than for EBCT and especially for coronary angiography (typically acquisition times of only 10 ms). Reliable imaging by MDCT requires a regular, relatively slow heart rate (< 75 beats min−1 is recommended), which may require medication, such as beta-blockers. Images are reconstructed in three dimensions to represent the complex anatomy of the coronary arteries12,13. Comprehensive evaluation may require extensive

post-processing using maximum intensity projection (MIP; Figs 22.1–22.6), curved multiplanar reconstruction (MPR; Figs 22.4D, 22.6D, see Fig. 25.7), surface shaded (SSD; Fig. 22.8C), and volume rendering techniques (VRT; Figs 22.1D,F, 22.2F,G, see Fig. 25.8). When done manually this is time consuming but semi-automatic methods are being developed which reduce processing time14.

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Cardiac evaluation Cardiac CT can be performed with or without contrast medium. Useful information has long been obtainable with conventional CT but image quality is markedly improved by ECG gating, especially when evaluating small structures. CT without contrast medium can show abnormalities characterized by differences in attenuation due to fat (e.g. lipomatous hypertrophy of the atrial septum, fatty degeneration of the myocardium; Fig 22.15), or calcification (coronary artery, aneurysm, valves, etc; Fig 22.13, see Fig. 25.3). Pericardial effusion or thickening is outlined between lung and epicardial fat. The position of implants and postoperative complications (such as focal fluid collections) can be seen (Fig. 22.16). Some anomalous coronary artery anatomy can be revealed even without the use of contrast medium, although accuracy is greatly increased with CTA (see Fig. 25.19). The use of intravenous contrast medium allows better evaluation of the cardiac chambers and adjacent vascular anatomy8–11. MDCT and EBCT are used to evaluate great vessel anatomy (arterial and venous), cardiac dimensions, ventricular function, viability, perfusion and coronary artery anatomy, including obstructive disease. With the exception of great vessel anatomy, where CTA is of proven accuracy and value, cardiac CT in these applications is in evolution. Artefacts due to metal are less of a problem than with CMR and some patients with implantable devices cannot be imaged by CMR (Fig. 22.16).

Three-dimensional image reconstruction High quality CTA and MRA produce a huge amount of image data. Although 2D source images can be used for diagnosis, this is time consuming and cumbersome. Most 3D datasets are best viewed using one of several 3D reconstruction

techniques. The best technique depends on the nature of the source data and the anatomy being viewed. For small diameter vessels, such as coronary arteries, submillimetre voxel dimensions should be used. Several techniques are widely used to present these data10,14.

Figure 22.15 CT diagnosis based on detection of low attenuation structures. The ability of CT to identify low attenuation areas allows some specific diagnoses even without contrast medium. This ECG-gated axial image shows low attenuation (indicating fat) in the interatrial septum (white arrows), right ventricular myocardium (white arrowheads) and left ventricular myocardium (indicating fatty degeneration of the myocardium; black arrows). Arrhythmogenic right ventricular dysplasia is also characterized by low attenuation but this is usually limited to the right ventricular free wall, and occasionally the septum.

Figure 22.16 Imaging by CTA in the presence of implanted devices. (A) CTA is less frequently used for evaluation of congenital heart disease than CMR, but in patients with contraindications to CMR (such as pacemakers and implantable defibrillators) CTA is useful, although still affected by metal artefacts. In this patient with anatomically corrected transposition of the great arteries, wires (white arrows) from a pacing system in the superior vena cava and right atrial appendage (RAA) produce some artefact. Note the abnormal anterior and left-sided position of the ascending aorta (AA) relative to the pulmonary artery (PA) as well as the abnormal origins of the coronary arteries (black arrows). (B) Artefact from denser material in the right atrial components of the pacing system (white arrows) obscures atrial anatomy and the transposed connection of the right atrium to the left ventricle (LV). A metal tricuspid valve replacement (black arrow) separates the left atrium (LA) from the transposed right ventricle (RV), identified by the presence of a prominent moderator band (M). (C) An oblique multiplanar reconstruction (MPR) reconstruction shows the abnormal relationship of the PA to the more anterior and left-sided AA as well as the infundibulum (I) which identifies the ventricle connecting to the AA as being a transposed morphological RV. Artefact (arrows) from pacing wires in the transposed anterior LV is included in this image although the wires are not in fact in this position.

CHAPTER 22

Multiplanar reconstruction This technique is used to view any desired 2D slice or section from a 3D dataset. When nearisometric voxels are acquired, the spatial resolution and image quality is the same for any orientation of the image. The use of MPR facilitates a view of relevant anatomy from an appropriate perspective; e.g. the coronary arteries can be viewed in a similar perspective as seen on conventional coronary arteriography. Thin sections should be used (typically only a few millimetres) as thicker sections may superimpose image data obscuring detail. Curved MPR sections can be generated manually or automatically to follow tortuous anatomy, which is especially useful when evaluating the coronary arteries (Figs 22.4D, 22.6D). Maximum intensity projection In this method the highest attenuation voxels (CTA) or highest signal voxel (MRA) along any ray (line) through the image are identified and projected into a 3D image; images of any required thickness can be rotated and viewed from any appropriate direction (Figs 22.1–22.5). This method is widely used in contrast-enhanced 3D MRA as well as CTA (Fig. 22.8B). Surface shaded display All voxels with an attenuation or signal above a certain level are represented as a 3D image which can be rotated in any direction. An imaginary source of illumination is used to provide a 3D perspective of the surface. This technique has been largely replaced by VRT for CTA. It can be useful for demonstrating large structures with uniform high attenuation or signal, such as the pulmonary veins using CTA or contrast-enhanced MRA (Fig. 22.8C). Volume rendered techniques Volumes with a certain range of attenuations or signal intensity are assigned a colour or grey scale density (Figs 22.1–22.5). Colours and threshold levels are varied depending on the application. This technique can be used for CTA or contrast-enhanced MRA, as well as imaging the airways, bowel and bone. Three-dimensional reconstruction benefits from editing of the 3D dataset to remove areas of high attenuation (e.g. bone for CTA) or signal (e.g. fat for MRA) from the image, which might obscure the area of interest. Such image reconstruction facilitates understanding of spatial relationships and allows evaluation of very large quantities of imaging data, but there is a significant potential for errors of interpretation if undue reliance is placed on just one type of image reconstruction15, or if the operator is not fully aware of the range of anatomical variations15,16. Typically, CTA covering 20 cm of the chest for cardiac imaging, using a 0.65-mm slice thickness, can generate over 300 source images. Although these images may need to be reviewed to identify other abnormalities, the vascular anatomy is usually best understood by reviewing the 3D images.

Arterial and venous great vessel anatomy Even before the widespread availability of ECG-gated CT, aortic and major venous anatomy was well demonstrated by CT, with or without contrast medium. Dimensions and branch vessel relationships are well shown along with major congenital anomalies of arterial connection (Fig. 22.16) and

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venous drainage (Fig. 22.8). With ECG gating and contrast enhancement, CT is a definitive method for evaluating aortic dissection, planning endovascular aortic repair and assessing pulmonary venous anatomy, an increasingly important application in patients with atrial arrhythmias treated with radiofrequency ablation of the pulmonary veins.

Cardiac dimensions The assessment of cardiac dimensions and mass has long been an accepted application for EBCT. Although EBCT assessment of ventricular size and configuration has been shown to be accurate in many conditions, and especially superior to echocardiography when evaluating the right ventricle, the need to give contrast medium and to use radiation, as well as the limited availability of EBCT, has prevented its widespread use. Multidetector CTA (MDCTA) with ECG gating is also accurate but the limitations imposed by the need for iodinated contrast medium and radiation remain. Usually echocardiography is more than adequate. In situations where echocardiography is limited due to poor acoustic access or reproducibility, MRI is usually the preferred method, with a high level of accuracy established over nearly two decades. MDCTA is useful in patients who cannot have MRI.

Ventricular function EBCT has long been used to assess systolic cardiac function, but has not been accepted into widespread routine practice. MDCT can assess left ventricular function but there are concerns about the accuracy of endomyocardial definition due to the long period of image acquisition. For a heart rate of 70 beats min−1, systole lasts about 300 ms, allowing acquisition of only three 100-ms systolic images using conventional MDCTA.Although the images presented to support this application appear well defined, the precision with which systolic events in particular are demonstrated is in doubt. By comparison echocardiography, EBCT and cine-MRA typically provide 30-ms images for frame rates of 30 frames s−1 or more. At present MDCTA can be used to assess systolic function as part of a comprehensive cardiac evaluation, but with less precision than other techniques.

Assessment of myocardial viability and perfusion Passage of contrast medium through the myocardium can be analysed in a similar way to perfusion echocardiography and MRI, as well as first-pass studies on nuclear scintigraphy. Delayed enhancement may also indicate poor viability17. The usefulness of this approach is as yet unclear. There is much more experience and validation with nuclear techniques, while echocardiography and MRI techniques do not have the limitations of contrast medium-related toxicity inherent in CT perfusion techniques. There are reports of CT perfusion studies providing useful information as part of a comprehensive cardiac study in patients where contrast medium administration is not a major concern. To do this accurately requires careful attention to correction for contrast medium dilution as it passes through the heart, beam hardening effects as contrast enhancement progresses, and potential nonlinear attenuation due to the use of partial rotation reconstruction with data

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acquired through different volumes of lung and bone. At present other techniques using scintigraphy, MRI, or ultrasound contrast agents are usually preferred.

Coronary computed tomography angiography Coronary angiography using noninvasive imaging by CTA (Figs 22.3–22.6) or MRA has long been the focus of substantial research. Although there have been promising reports of techniques using EBCT and a variety of MRA techniques, none has generated as much enthusiasm for real world clinical use as MDCTA3,14. Technical developments allowing thinner (< 0.5 mm) slice acquisition, rapid imaging and retrospective data reconstruction during a short period at end-diastole provide worthwhile coronary artery imaging18.19. There are limitations related to heavy calcification, which may prevent visualization of the artery lumen (see Fig. 25.12) and imaging of vessels smaller than 2 mm. In spite of this, MDCTA is already accepted as a definitive technique for demonstrating congenital coronary anomalies (see Fig. 25.19), bypass graft patency (Fig. 22.17, see Fig. 25.15), and ruling out significant coronary stenosis in low risk patients (see Ch. 25).

Magnetic resonance imaging The diagnostic power of MRI lies in its ability to provide a wide range of information, including anatomy, function, flow and chemistry, with minimal risk. Cardiovascular MRI (CMR) is well established, particularly for the assessment of congenital heart disease, cardiac function, tumours and diseases of the aorta and pericardium20,21.Technological improvements (e.g. 3T imaging, faster gradient switching, more powerful gradient amplifiers and new pulse sequences) have continued to expand the utility of CMR. Images, including cine-MRA,

can be acquired in one breath-hold period (which eliminates respiratory artefact). Different sequences can be used to assess anatomy (spin-echo, fast spin-echo, half-Fourier single-shot turbo spin-echo), function (time-of-flight or phase-contrast cine-MRA), perfusion or viability (with contrast enhancement) and vascular anatomy (time-of-flight, phase-contrast or contrast-enhanced MRA). The key to achieving accurate CMR is to establish a good ECG trace and to choose the appropriate imaging sequences to assess the clinical problem (Figs 22.18, 22.19). In general black blood imaging (spin-echo, turbo spin-echo) is used for anatomical imaging (Figs 22.7, 22.19A), while cine-MRA (white blood imaging) is used to assess dynamic function (Figs 22.10, 22.18). Phase-contrast imaging is used to measure blood flow velocity. Contrast enhancement can be used for extracardiac angiography using 3D gradient-echo sequences (Figs 22.8, 22.20), while inversion recovery type sequences (with or without contrast medium injection) can be used to identify areas of myocardial injury22. A variety of well validated analysis and 3D reconstruction techniques are available to provide accurate assessment of cardiac dimensions, wall motion, perfusion, flow and 3D anatomy. Used correctly, CMR is a definitive, stand-alone cardiac imaging technique with no need for alternative corroborative imaging. It is only in the search for coronary artery stenosis that CMR has as yet failed to make a significant impact.

Cardiac gating CMR studies are degraded by motion artefact unless cardiac gated or the more difficult ‘one-shot’ technique is used. Quantitative measurement of flow requires cardiac synchronization to avoid errors. Even with synchronization, some errors occur

Figure 22.17 CTA of coronary artery bypass grafts. (A) Thin maximum intensity projection (MIP) showing patent saphenous vein bypass graft (arrows) to the distal right coronary artery. Also note thrombus in the left pulmonary arteries (arrowheads). (B) VRT 3D image shows three patent grafts passing towards the right coronary artery and two left-sided branches (arrows). AA = Ascending aorta, LA = left atrium, PA = pulmonary artery, RA = right atrium, RV = right ventricle, SVC = superior vena cava.

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Figure 22.18 Correct choice of MRA imaging sequence. (A) Four-chamber long axis view of the left ventricle (LV) using cine-FLASH sequence shows poor definition of the endocardial surface of the LV and left atrium (LA). This is a reflection of low signal from slow, in-plane flow. There is higher signal from the right atrium (RA) and right ventricle (RV) where the flow is passing obliquely through the imaging plane. (B) Four-chamber long axis view of the LV using cine-FISP in the same slice position in the same patient. This sequence produces higher signal and much better definition of the endocardial surfaces (arrows).

Figure 22.19 Tissue characterization using multiple CMR sequences. (A) Axial, turbo spin-echo MRI image shows a high signal in a smooth, possibly cystic, well-defined mass (C) posterior to the left atrium (LA). High signal suggests fluid or viscous contents. (B) Sagittal, cine-FISP image shows that the lesion behind the LA has high signal similar to that of flowing blood in the cardiac chambers, suggesting the contents are fluid. (C) Coronal, T1-weighted HASTE image shows high signal in the mass and confirms that it is well defined. (D) Coronal, inversion recovery HASTE image shows intermediate signal. This combination of signal characteristics in a well-defined, rounded mass in this position indicates that this is a benign cyst, in this position most probably a bronchial cyst. This was confirmed at surgery.

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Figure 22.20 Multi-sequence comprehensive evaluation of postoperative changes. (A) Axial ECG-gated spin-echo image showing bifurcation of the pulmonary artery (PA) directly anterior to the ascending aorta (AA) in an 8 year old patient following surgical correction of transposition of the great arteries. The vessel lumens are black (signal void due to flow). 3D image reconstruction with this type of image is possible but difficult. (B). Coronal thin maximum intensity projection (MIP) reconstruction from coronal acquisition. Contrast-enhanced MRA shows dilatation of the ascending aorta (AA) separating the left (LPA) and right (RPA) pulmonary arteries. (C) Lateral view MIP from the same CE-MRA shows the relationship of the aorta to the main pulmonary artery (MPA) as well as minor narrowing at the site of repair of coarctation (arrow). DA = descending aorta, LV = left ventricle, RA = right atrium, RV = right ventricle.

due to beat-to-beat variations resulting from a number of physiological variations including respiration. There are two forms of cardiac gating. Prospective gating detects the QRS complex of the ECG, which then triggers the application of the sequence, such that the image is formed from a specific part of the cardiac cycle. For cine-MRA, the sequence is repeated rapidly in order to acquire images at a number of stages of the cardiac cycle; the repeat time and number of pulse repetitions are adjusted such that, when added to the initial delay, they require slightly less time than the shortest expected R–R interval. The other form of cardiac synchronization is retrospective gating. For this approach, the sequence is repeated continuously with a constant repeat time while the ECG is monitored. The data are sorted at the completion of the sequence and adjusted to give images at specific parts of the cardiac cycle. In this way variations in the R–R interval can be corrected. Prevention of respiratory motion is especially important in coronary artery imaging. Coronary MRA using breathhold acquisition is difficult because patients are required to breath-hold at the same diaphragm position and therefore slice misregistration is common. In addition, the signal-tonoise ratio and spatial resolution are inherently low because of the limited acquisition time of a single breath-hold. Navigator techniques monitor respiratory motion by tracking the position of the diaphragm in real-time, which is used to select and reconstruct only data acquired in a selected part of the respiratory cycle23.

The heart under stress Cardiac function in patients with coronary artery disease may be within normal limits at rest and unless it is possible to study the effects of stress on such patients, the value of CMR is lim-

ited. Stressing patients in the MR machine using an exercise apparatus is possible but difficult. Pharmacological stress, using dobutamine or adenosine, can be applied and is well established for assessing myocardial ischaemia24,25.This technique is used in a similar way to stress echocardiography, but has no limitations from restricted acoustic access. The level of stress is increased while monitoring wall motion, with the development of a new wall motion abnormality (which precedes ECG changes) indicating ischaemia. This technique can be combined with perfusion and viability imaging using a contrast agent.

Contrast agents The most widely clinically used MR contrast agents are paramagnetic compounds that influence the relaxation times of adjacent tissues26. Gadolinium is a powerful paramagnetic substance which when complexed with ligands such as diethylenetriaminepenta-acetic acid (DTPA) is no longer toxic. The main indications for the use of contrast agents in CMR are: assessment of myocardial perfusion, contrast-enhanced MRA, improved demarcation of normal and infarcted myocardium and delineation of viability after coronary occlusion (Fig. 22.21, see Fig. 25.15)22,24.

Pulse sequences There are innumerable pulse sequences, often known by acronyms for ease of recall. In cardiac imaging the most important are the spin-echo, gradient-echo and velocity mapping sequences. Spin-echo imaging In spin-echo images the myocardium and vascular wall appear bright and the blood is dark (black blood imaging). Spin-echo CMR is useful for high-definition anatomical imaging of the heart and vessels but it is rather slow (Figs 22.7A, 22.20A).Variable signal from slow or in-plane

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Figure 22.21 Evaluation of cardiac perfusion and viability by CMR. Multiplanar cine-MRA is used to evaluate systolic cardiac function in multiple orientations including usually four-chamber long axis and short axis. (A) Four-chamber long axis view from cine-FISP MRA at end-diastole shows apical myocardial thinning. The position of the perfusion image (C) and scout images (D–H) used to assess optimum inversion times for viability imaging is shown (white line). (B) Four-chamber long axis view from cine-FISP MRA at end-systole shows persisting apical myocardial thinning (arrows) while the basal myocardium thickens normally. (C) Short axis view obtained during first pass of contrast (gadopentetate) through the myocardium shows reduced enhancement in the septum (arrows). (D–H) Five images from a series of 10 acquired at varying inversion times (TT) to identify the best parameters to null signal in the normal myocardium (F, asterisk) compared with delayed enhancement of nonviable myocardium best shown at 182 ms (F, arrows). (I) Delayed enhancement four-chamber long axis image shows extensive apical and septal enhancement (arrows) indicating nonviable myocardium.

blood flow produces artefacts. Fast spin-echo (FSE; Fig. 22.19A), half-Fourier single-shot turbo spin-echo (HASTE; Fig. 22.19C,D) and multi-echo, spin-echo sequences that change the phase-encode gradient for each echo allow acquisition of multiple lines of k-space in a given repetition time (TR). This significantly reduces imaging time. Using different

pulse sequences, different signals can be extracted from lesions to indicate the nature of the tissue (Fig. 22.19D). Gradient-echo imaging In this sequence, blood produces a higher signal (white blood imaging) as only one radiofrequency (RF) pulse is used and there is less time for blood to

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move out of the imaging plane between slice selection and data acquisition. The gradient-echo sequence can be repeated more rapidly with a reduced RF flip angle, allowing the acquisition of cine loops (Figs 22.10, 22.18). Cine acquisitions are useful for the assessment of valves and regional contractile function of the myocardium. Turbulent and other irregular flow types, which contain higher order motion, produce signal loss on gradient-echo images (e.g. valve stenosis or regurgitation). Shortening echo times (TE) reduces phase incoherence and loss of signal. The shorter the TE, the higher the threshold of turbulence intensity at which signal is lost. Phase-shift velocity mapping The MR signal has three components: frequency, amplitude and phase, which are used in image reconstruction. It is possible to construct an image to display phase changes caused by special sequences. If a gradient is applied in the direction of blood flow for a finite time and then turned off, the relationship of phase will change in relation to the two ends of the gradient. The protons at the stronger end of the gradient precess at a faster rate during its application than those at the weaker end. When the gradient is turned off, the rate of precession becomes constant again in the slice, but the phase relationship has changed and the phase signature remains. When the gradient is reversed and applied for the same period of time as the original gradient, the phase signature of still material is cancelled, but flowing blood moving during the gradients to a different phase territory retains a phase change proportional to velocity (Fig. 22.22).

Quantification of myocardial contraction Myocardial tagging has been used to study regional wall motion and myocardial strain (see Fig. 25.6). In this technique modulation of the MRI is achieved using alternating RF pulses and magnetic gradients such that narrow planes of very low signal appear in a latticework. Computer analysis can derive quantitative measurements of intrinsic myocardial mechanics by tracking the motion of the points of intersection of the tagging lines. The results are observer independent and objective. This technique should become more widely used once the computer analysis issues have been ironed out and made more widely available. Myocardial motion can also be quantified using MR velocity mapping.

Magnetic resonance angiography (see also Chs 6, 27 and 28) Tomographic imaging is not ideal for demonstrating tortuous vessels and 3D imaging methods are often required. Although 3D imaging can be performed using time-of-flight or phasecontrast MRA, the bulk of extracardiac studies are performed using contrast-enhanced MRA. Contrast-enhanced MRA has become increasingly popular as it can be acquired during a single breath-hold (> 20 s). Contrast-enhanced MRA relies on fast acquisition of images after the administration of a gadolinium contrast agent (Figs 22.18, 22.21), which produces signal enhancement due to the shortening of the T1-relaxation time of blood26. The result is optimal when data collection (in particular the centre of the k-space) occurs when the contrast agent arrives at the targeted vessel. Therefore timing of the data acquisition with respect to the intravenous injection of contrast agent is important. Contrast-enhanced MRA is particularly useful for the comprehensive evaluation of aortic disease and major branch vessel abnormalities (renal, mesenteric, peripheral, carotid), as well as venous disease (Fig. 22.23). The use of contrast-enhanced MRA for evaluating many aspects of congenital heart disease is well defined (Figs 22.20, 22.22).

Clinical applications Myocardial function at rest CMR images are dimensionally accurate.The volume of a chamber can be measured in systole and diastole by summing the areas in contiguous images.Ventricular stroke volumes are now commonly measured using multiple contiguous fast cine gradient-echo imaging acquired during a breath-hold to cover the ventricles.The end-diastolic and end-systolic volumes are computed from the endocardial outlines. Volume measurements by these methods are independent of cavity shape, unlike other methods where geometric assumptions usually have to be made, and are ideal for the right ventricle. In theory, it does not matter which plane is used for the measurements, but the short axis plane appears to be the best because of the good contrast between blood and myocardium, although endocardial measurements at the base

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Figure 22.22 Gradient-echo images in a coronal plane acquired during ventricular (A) systole and (B) diastole in a patient with Marfan's syndrome and aortic valve regurgitation (arrow). aa = ascending aorta, lv = left ventricle, pa = pulmonary artery, ra = right atrium. (C) Flow volume curves in the ascending aorta (AA) and descending thoracic aorta (DA) measured from the complete line acquisition. Note the large reverse flow during diastole.

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Figure 22.23 Comprehensive cardiovascular evaluation in complex congenital heart disease using contrast-enhanced MRA. (A) An advantage of contrast-enhanced MRA is that multiple vascular territories can be evaluated safely with the same study. In particular the major veins and arteries which may be affected by complications of surgical treatment of congenital heart disease are well shown. In this 18 month old patient with central line-related endocarditis following closure of a patent foramen ovale and repair of a ventricular septal defect, a coronal, thin (6-mm thick) maximum intensity projection (MIP) image shows thrombus (arrow) in the superior vena cava (SVC). (B) A more posterior thin MIP generated from the same 3D acquisition shows a shelf (arrow) at the level of a coarctation and a large false aneurysm (FA) of the abdominal aorta. There are areas of reduced pulmonary enhancement (arrowheads) indicating pulmonary infarction from emboli. (C) As the imaging acquisition generates a 3D dataset with isometric voxels it is possible to reconstruct images in the best orientations to visualize the abnormalities detected. A sagittal, thin MIP through the descending aorta shows the eccentric shelf of the coarctation (arrow). (D) A sagittal, thin MIP through the SVC shows the thrombus (arrow) attached to the anterior wall of and partly obstructing the SVC. AA = ascending aorta, LA = left atrium, PA = pulmonary artery, RA = right atrium, RV = right ventricle.

can be difficult in the short axis. Muscle volume and hence mass can also be measured.

assessed. Myocardial tagging has been used to study regional wall motion, myocardial strain and myocardial viability.

Myocardial function during stress Cardiac function at rest may be normal in the presence of severe coronary artery disease. Abnormal function may represent neither coronary artery disease nor irreversible damage (hibernation). Therefore, a full assessment of cardiac function should include stress assessment for inducible ischaemia and reversible dysfunction21,23. This may also be achieved using similar ultrasound and nuclear imaging techniques. Reversible myocardial ischaemia can be shown on cineMRA, following pharmacological stress, by the development of abnormal wall motion. Using low dose dobutamine infusion, residual myocardial mass (viability) in areas of asynergy can be

Myocardial perfusion and viability Myocardial perfusion imaging can be combined with wall motion analysis, stress testing and evaluation of viability (Fig. 22.21, see Fig. 25.15). MR contrast agents equilibrate quickly with the extracellular compartment and are washed out rapidly. They are therefore neither blood pool tracers nor fixed in the myocardium. Nevertheless, by treating them mainly as extracted tracers, it is possible to measure myocardial perfusion from the peak myocardial enhancement. The model assumes a linear relationship between tracer concentration and signal enhancement. This is only true for gadolinium–DTPA at low concentrations, which appears to be the case in animal experiments and in clinical

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practice. Ultrafast gradient-echo imaging can provide at least one image of each cardiac cycle during the passage of the tracer; measurement of myocardial perfusion is feasible as part of the routine evaluation of ischaemic heart disease (Fig. 22.21C). Delayed contrast enhancement shown by inversion recovery techniques which null the signal from normally perfused viable myocardium (Fig. 22.21D–I, see Fig. 25.15C) shows promise in assessing the size of myocardial infarction and detecting nonviable myocardium with accuracy similar to nuclear imaging, stress echocardiography and positron emission tomography27. Delayed hyperenhancement on contrast-enhanced MRI can identify recent myocardial infarction or nonviable myocardium in those with chronic ischaemia (Fig. 22.21, see Fig. 25.15). Absence of hyperenhancement correlates well with nuclear imaging and echocardiographic determinations of viability, regardless of resting contractile function. Coronary arteries and bypass grafts Coronary MRA can be performed using a variety of techniques23,28,29. Although patency can be determined by 2D breath-hold techniques the best 3D images of the coronary arteries and bypass grafts are obtained using 3D techniques combined with navigator techniques and using contrast enhancement23,29,30. Coronary MRA is useful for the assessment of anomalous coronary arteries, patency of the infarct-related coronary artery and saphenous vein graft patency28. Although good images of coronary arteries are obtained fairly easily in normal volunteers, current techniques are less reliable for defining coronary artery stenosis30. Valvular heart disease In valvular heart disease, CMR information complements and can go beyond that obtainable by echocardiography31. Although CMR is less suitable than echocardiography for visualizing valve leaflets and suspensory apparatus or infective vegetations, it can, in most cases, measure regurgitation. CMR velocity mapping allows measurement of peak velocities across stenoses. Cine-MRA provides a wide, unrestricted view of dimensions, movements and relations of chambers and visualization of jets (Figs 22.7, 22.9). CineMRA in multiple contiguous slices allows accurate, reproducible measurements of ventricular volume and myocardial mass, which can be important in relation to valve disease. CMR provides quantification of valvular regurgitation and stenosis, assesses atrial and ventricular size and function, visualizes associated intracardiac thrombus, detects paravalvar abscesses and fistulas, and assesses prosthetic valves. Gradient-echo sequences show turbulent blood flow as areas of signal loss within the high blood signal. The degree of signal loss is dependent on the echo time, field strength and other acquisition parameters.The severity of stenosis can be evaluated using phase-contrast MRA and the Modified Bernoulli Equation, which in its simplest form is: ∆P = 4V 2 where ∆P = pressure drop across the stenosis (mmHg) and V = velocity (m s−1). This assumes that the blood velocity upstream of the stenosis is negligible. This calculation can be easily applied to determine the peak instantaneous gradient and the mean gradient across the stenosis. It can be used to determine the pressure difference between two chambers with a regurgitant valve.

Other established applications of CMR20,21 These include: • Pericardium: tumour invasion, pericardial thickness, pericardial effusion, congenital absence of the pericardium. • Cardiac thrombus and tumours: detection of thrombus and tumours, identification of tumour types from signal characteristics; this is mainly limited to lipomas (high signal) and fibromas (low signal)32. • Cardiomyopathy: identification and assessment of the three main types of cardiomyopathies: hypertropic, dilated and restrictive. • Arrhythmogenic right ventricular dysplasia: focal thinning and abnormal motion of the right ventricle with or without signal changes in the involved myocardium. • Acute myocarditis: focal wall motion with abnormal high signal on T2-weighted images and contrast enhancement on T1-weighted images33. • Cardiac infiltration: sarcoidosis (high signal on T2-weighted images; contrast enhancement on T1-weighted or delayed contrast-enhanced MRI); amyloidosis (thickening of the myocardium, interatrial septum, valves, leaflets and papillary muscles, atrial dilatation, pleural and pericardial effusions; high signal on T2-weighted images; and contrast enhancement on T1-weighted or DE-MRI); myocardial iron overload (diffuse reduction in contraction, reduced myocardial signal). • Congenital heart disease: definition of great vessels and attachments, atrioventricular connection, extracardiac shunts, postoperative changes.

Limitations CMR has long been touted as a potential means of providing comprehensive cardiac imaging. Although CMR provides some of the most accurate information on cardiac anatomy, function, perfusion and viability, there are limitations. Coronary MRA is still not robust enough to replace routine coronary angiocardiography. Up to 4% of the normal population is claustrophobic and some unstable patients may not tolerate an examination. Controversy surrounds the safe MR of patients with pacemakers or implanted defibrillators. Some metal implants are a contraindication, although many extracerebral metallic objects such as sternal wires, metallic clips and prosthetic valves are not ferromagnetic and are safe in current clinical scanners34. However, prosthetic material gives little MR signal and metal causes a localized image defect due to distortion of the magnetic field. The defect is small for spinecho images but larger for some gradient-echo images, making it difficult to assess velocities and blood flow around the prosthesis. Other limitations include long acquisition times (which are getting shorter), poor image quality in patients with cardiac arrhythmias and cost.

Nuclear cardiac imaging Nuclear cardiology is an established subspecialty that has grown significantly in recent years because of developments in imaging hardware, software and tracers. Alongside these technical developments, there has been an increasing appreciation of the role that the functional information provided by nuclear techniques can play in clinical cardiology. This chapter covers

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only basic principles of nuclear cardiology and the most commonly used techniques, and it reviews some more common clinical applications, emphasizing the role of myocardial perfusion imaging.

Techniques (see also Ch. 7) Single photon emission computed tomography (SPECT) Tomography is an extension of the multiprojection method of acquiring planar images. Multiple planar projections are acquired as the camera rotates around the patient. The images are reconstructed into tomograms and presented as images in orthogonal planes parallel and perpendicular to the long axis of the left ventricle. SPECT is used routinely for myocardial perfusion studies, with accuracy approaching that of PET35. Its advantages include a true 3D display of the distribution of radionuclide, improved image contrast because of the elimination of overlying structures, and the potential for quantification of tracer uptake. Positron emission tomography (PET) Positrons travel a very short distance in matter before an annihilation reaction with an electron causes the emission of two gamma photons in opposite directions. Photons sensed simultaneously by opposing detectors are presumed to come from annihilation along the line between the detectors. Coincidence detection allows tissue attenuation to be determined accurately, which has important implications for quantifying tracer uptake. PET has several advantages over SPECT for cardiac imaging, including better spatial resolution, higher sensitivity and the ability to measure tracer distribution in absolute terms as a function of time30. PET is relatively expensive and is not widely available, but a conventional gamma camera can be used, either by using a high-energy collimator designed for 511 keV photons, or by using opposing detectors without collimation but with coincidence imaging. Radiopharmaceuticals Thallium-201 is still commonly used for myocardial perfusion studies. It is administered intravenously as thallous chloride and the usual dose is 80–110 MBq (maximum 80 MBq in the UK). Approximately 88% is cleared from the blood after the first circulation, with 4% of the injected dose localizing in the myocardium. Distribution in the myocardium is proportional to perfusion over a wide range of values, although at high rates of flow, extraction may become rate limiting. Thallium is an excellent tracer of myocardial perfusion and it has been used clinically for more than two decades, but has significant limitations. The long physical half-life results in a radiation dose of the same order as coronary angiography. The relatively low injected dose results in a low signal-tonoise ratio and images can be suboptimal, especially in obese patients. Third, the relatively low-energy emission leads to low-resolution images and significant attenuation by soft tissue. Technetium-99m (99mTc) compounds do not have these limitations and this has encouraged the development of such tracers.

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99m

Tc-labelled tracers include 99mTc-2-methoxy-isobutyl-isonitrile (MIBI), 99mTc-1, 2-bis[bis(2-ethoxyethyl) phosphino] ethane (tetrofosmin) and 99mTc-teboroxime. Each of these agents has specific attributes but all have advantages over thallium due to the superior imaging characteristics of 99m Tc. Positron-emitting radiopharmaceuticals A number of positron-emitting radiopharmaceuticals can be used as tracers of myocardial perfusion. [15O]-Labelled water can be administered either intravenously or by inhalation of [15O]CO2 with rapid transformation to water by carbonic anhydrase in the lungs. Tracers such as nitrogen-13 ammonia (as [13N]NH4+), rubidium-82 and potassium-38 have also been used. Kinetic models of these tracers have also been used to calculate myocardial perfusion. Tomography is now almost universally used for myocardial perfusion imaging, although planar imaging is sometimes used with older equipment or if the patient is unable to lie still and flat for the duration of tomographic imaging. The best imaging protocol depends upon the tracer used, the dose given, the type of collimator and the number of heads of the camera. Thallium is usually given at peak exercise with exercise continued for 2 min in order to maintain stable conditions over the period of extraction by the myocardium. Imaging starts within 5–10 min of injection and should be completed within 30 min. During this period the distribution of thallium within the myocardium is relatively fixed and the images reflect myocardial distribution at the time of injection. Thallium washes out of the myocardium at a slower rate in underperfused than normally perfused myocardium. Areas with decreased initial uptake appear to have a relative increase in uptake when imaged 2–4 h later, a phenomenon known as redistribution. Comparison between the stress and redistribution images distinguishes between the reversible defect of inducible hypoperfusion and the fixed defect of myocardial necrosis, although in some cases redistribution may be incomplete at 4 h. A second injection of thallium can then be given and re-injection images acquired for a more accurate assessment of myocardial viability. Technetium-labelled tracers Unlike thallium, MIBI and tetrofosmin are essentially fixed in the myocardium with no redistribution, and separate injections are used to assess stress and resting perfusion (see Fig. 25.5) with a high degree of accuracy37. The 6-h half-life of 99mTc means that the two studies should be performed on separate days to allow for the decay of activity from the first injection. The 2-d protocol is performed with an initial stress study, followed by a resting study on a different day using a similar dose. Imaging starts 30–60 min after injection.The two studies can be performed on the same day if a larger dose is given on the second occasion in order to swamp residual activity from the first injection, and some time is allowed also for the first injection to decay.When the diagnosis of ischaemia is important, the stress study should be performed first in order to avoid reducing the contrast of a stress-induced defect by a previous normal resting study. Conversely, if the objective is to detect viable myocardium and reversibility of a

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defect, perhaps in a patient with previous infarction, then it is better to perform the rest study first. Image interpretation Normal myocardial perfusion and hence tracer distribution is uniform. Regional defects indicate either reduced perfusion in viable myocardium, or a reduced amount of viable myocardium, or a combination of both. If a stress defect returns to normal in the resting images, this indicates an inducible perfusion abnormality, which is sometimes referred to as inducible ischaemia (see Fig. 25.26). Areas of infarction show defects on both stress and rest images and the depth of the defect indicates the myocardial loss differentiating large from small infarcts (see Figs 25.16, 25.17). Ischaemia can be superimposed upon partial thickness infarction and in this case a stress defect may be only partially reversible at rest. Fixed perfusion defects can also occur due to overlying soft tissue, something to be especially considered in women, even with SPECT (Fig. 22.24). Movement can produce uneven signal distribution (Fig. 22.25), potentially obscuring significant perfusion defects. Reverse distribution is the term used to describe a defect in redistribution thallium images that is less apparent in the stress images. When the phenomenon is seen, it is often the result of artefact or other technical differences between images and, in this case, it is not strictly speaking reverse redistribution. When true reverse redistribution is seen, it is the result of rapid washout of tracer as might occur in an area of partial thickness infarction supplied by a patent artery after angio-

Figure 22.25 Motion artefact. Movement during image acquisition for cardiac scintigraphy blurs the image and by obscuring or even producing areas of reduced activity can produce nondiagnostic studies. Here movement during the stress phase (rows A and C) of a nuclear stress perfusion study shows distortion of activity with artefactual thickening (arrows) of the myocardium, not seen at rest (rows B and D). The imaging agent is 99mTc-Tetrofosmin (Myoview, Amersham Health, Arlington Heights, IL). The images in rows A and B are short axis views; those in rows C and D are vertical long axis views. (Courtesy of Laurie Gianturco, MD.)

plasty or thrombolysis. It is not associated with future coronary events and it is not normally clinically significant. Perfusion defects are not always the result of coronary artery disease. Abnormalities can be seen with coronary spasm, anomalous arteries, muscle bridges, small vessel disease as may occur in diabetes or syndrome X, the dilated and hypertropic cardiomyopathy, hypertrophy caused by outflow obstruction or hypertension, infiltrative disorders such as sarcoidosis and amyloidosis, connective tissue disorders and conduction defects such as left bundle branch block. True perfusion defects must also be distinguished from artefact caused by motion and by attenuation. Attenuation can be seen as reduced counts in the inferior wall, often in slim men, or in the anterior wall, often from breast attenuation in women.

Figure 22.24 Attenuation artefact. There are several causes of artefactual reduction of activity on cardiac scintigraphy. Increased overlying tissue as with the female breast (shown here), breast augmentation, or a high diaphragm, can reduce activity and mimic a fixed perfusion defect (arrows; row A stress, row B rest). The imaging agent is 99mTc-Tetrofosmin (Myoview, Amersham Health, Arlington Heights, IL). (Courtesy of Laurie Gianturco, MD.)

Stress techniques The response to stress is central to the assessment of most aspects of cardiovascular function. This is particularly so for coronary artery disease because resting coronary flow is normal until the luminal area of a coronary artery is reduced by approximately 85–90% (equivalent to a 60–75% reduction in diameter), and resting ischaemia only occurs when the artery is virtually occluded. The most commonly used technique is dynamic exercise. This has the advantage that it mimics the stress that may provoke symptoms in patients with coronary artery disease. However, many patients with coronary artery disease are unable to exercise adequately.

CHAPTER 22

The potent coronary arteriolar dilator dipyridamole increases myocardial perfusion by between 250% and 600%. Perfusion reserve is reduced by a coronary stenosis, and the differential flow between territories served by normal and by stenosed arteries may produce a defect of uptake, even though flow may be increased in the abnormal area. The radiotracer is given 4 min after the end of the dipyramidole infusion, at which time vasodilatation is maximal. Myocardial perfusion remains near peak levels for up to 10 min, returning to baseline over 30 min. Adenosine has a very short plasma half-life, which increases mean coronary flow by 4.4 times the resting value. During infusion there is a slight fall in blood pressure with an increase in heart rate, cardiac output and pulmonary capillary pressure. Sideeffects are more common, occurring in up to 80% of patients. Dobutamine may be used in patients with asthma or other contraindications to dipyridamole or adenosine. Dobutamine increases perfusion in normal myocardium approximately twofold (similar to exercise) by a combination of coronary vasodilatation and increased myocardial oxygen demand by increasing myocardial work, leading to a secondary increase in myocardial perfusion. Dobutamine is safe in patients with coronary artery disease, and serious complications are uncommon. Imaging ventricular function Ventricular function can be imaged either by following the first pass of a tracer after injection, or by labelling the blood pool for an equilibrium study. Imaging of the cardiac blood pool is normally performed in the left anterior oblique projection that best separates the left and right ventricles: the ‘best septal projection’. Fifteen to 30 degrees of caudal tilt also separates the left ventricle and atrium. ECG gating is used to acquire 16–32 frames through the cardiac cycle. Once the background is subtracted, the left ventricular ejection fraction can be calculated from maximum and minimum counts within the left ventricular region of interest as follows:

EF = ED − ES ED Where EF = Ejection fraction, ED = End-diastole counts and ES = End-systole counts. This method makes no assumptions about ventricular geometry, and it is therefore superior to techniques such as echocardiography and X-ray ventriculography, particularly for abnormal and irregular ventricles. First-pass studies are also performed to measure shunting in patients with congenital heart disease. The pulmonary activity–time curve from a first-pass study shows a single peak as the bolus passes through the lungs, and a later more diffuse one as it recirculates. Myocardial infarction imaging A number of compounds localize in areas of myocardial infarction, including derivatives of tetracycline and dicarboxylates, and the bone-seeking agents such as pyrophosphate. 99mTc-pyrophosphate and 111Inlabelled antimyosin have been used most extensively.

Clinical applications Diagnosis of coronary artery disease—chronic chest pain Published figures for sensitivity and specificity of myocardial

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CARDIAC ANATOMY AND IMAGING TECHNIQUES

perfusion imaging vary widely depending upon the population studied (sex, presenting symptoms, medication, presence of previous infarction), the imaging technique used, and the experience of the diagnostic centre. Using SPECT imaging, good accuracy can be achieved with sensitivity of 91% and specificity of 89%. This is significantly better than exercise electrocardiography, for which a large meta-analysis reported sensitivity of 68% and specificity of 77%. Commercially available tracers have similar accuracy for the detection of coronary artery disease. Thallium has better uptake characteristics and, in theory, provides defects with greater contrast, but 99mTc-based images are superior in terms of resolution and susceptibility to attenuation artefact. Diagnosis of coronary artery disease—acute chest pain In general terms, nuclear techniques are less commonly used in patients presenting with acute chest pain, mainly because of the logistical problems of imaging in the emergency department or coronary care unit. A resting perfusion defect has a high positive predictive value for acute infarction in patients without previous infarction, particularly if associated with a wall motion abnormality38. A normal perfusion scintigraphy excludes acute infarction and suggests that exercise ECG or stress perfusion imaging should be the next diagnostic step. Prognosis in coronary artery disease Beyond diagnosis, the most valuable contribution that perfusion imaging can make to the management of known or suspected coronary artery disease is to assess the likelihood of a future major coronary event39. Prognosis is strongly influenced by the extent and severity of inducible perfusion abnormality and this can guide the need for invasive investigation and revascularization. Myocardial perfusion imaging is a better indicator of prognosis than clinical assessment, exercise ECG, or coronary angiography, and it provides incremental prognostic value even after the other tests have been performed. The addition of SPECT information on ventricular function provides further useful prognostic information. Preoperative risk assessment A common clinical problem is that of assessing cardiac risk in patients who require noncardiac surgery. In this as in other clinical settings, perfusion imaging provides useful prognostic information although these patients are generally at low cardiac risk and the predictive value of a normal perfusion study is greater than that of an abnormal study. The decision on whether investigations for risk assessment are required should be based upon the urgency for surgery and its own cardiac risk, the risk factors of the individual and his/her exercise tolerance. Patients with only minor clinical predictors (older than 70 years, abnormal resting ECG, history of stroke or hypertension) who are scheduled for low to moderate risk surgery are not at high risk and do not require further investigation. Patients with intermediate clinical predictors (mild angina, prior cardiac infarction, treated heart failure, or diabetes) or with minor predictors and impaired exercise tolerance need further assessment if they are to undergo moderate or high risk surgery. Patients at high clinical risk (recent infarction or

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unstable angina, severe heart failure, or significant arrhythmias) may require investigation even for low risk surgery. Management after myocardial infarction An important aspect of management after infarction is to identify patients at high risk of further events and to intervene to prevent them. Indicators of high risk in the acute phase include hypotension, left ventricular failure and malignant arrhythmias. These patients are candidates for early coronary angiography. After the acute phase, however, prognosis is related to the degree of left ventricular dysfunction and the extent and severity of residual ischaemia. Left ventricular ejection fraction (LVEF) at the time of discharge or 10–14 d after infarction predicts mortality40. Patients with impaired LV function, in particular, can benefit from perfusion imaging to assess viability of the infarct zone and determine whether remote myocardium is also ischaemic. Patients without high risk clinical markers or severely impaired LV function are at lower risk, but some form of stress testing is required in order to assess exercise tolerance and the presence of residual ischaemia. Viability and positron emission tomography Positronemitting radionuclides can assess myocardial perfusion and metabolism36. This relies on the detection of reduced resting perfusion assessed by [13N]ammonia with normal or increased fluorodeoxyglucose (FDG) uptake (perfusion–metabolism mismatch), as opposed to a matched reduction of perfusion and metabolism in fully infarcted myocardium or scar. The reported positive and negative accuracies for predicting recovery of regional function range from 72% to 95% and from 75% to 100%, respectively. Mismatch also predicts improvement in global left ventricular function after revascularization. Thallium is also widely used to identify viability and hibernation. Because redistribution can be slow or incomplete in regions of reduced perfusion, the usual stress/redistribution protocol can underestimate myocardial viability, and additional steps to ensure complete assessment of viability are required. These include late redistribution imaging at 8–72 h after stress injection, re-injection of tracer at rest after redistribution imaging and a resting injection on a separate day with both early and delayed imaging. 99m Tc-labelled agents have also been used for the detection of viable and hibernating myocardium. In theory these tracers may underestimate viability in areas with reduced resting perfusion because they are combined tracers of viability and perfusion without the property of redistribution that allows viability to be assessed independently. Other myocardial disease Many agents, including alcohol, drugs, viruses and metabolic defects, can damage the myocardium. Heterogeneous uptake of perfusion and metabolic tracers is seen in most patients with dilated cardiomyopathy although the findings are not specific.The distinction between idiopathic dilated and ischaemic cardiomyopathy cannot be made with certainty. Radionuclide ventriculography is of value for monitoring ventricular function and is standard practice for patients

receiving cardiotoxic chemotherapy such as doxorubicin. Cessation of chemotherapy when the ejection fraction falls below normal leads to stabilization of the ventricular function and avoids the development of heart failure.

REFERENCES 1. Lipton M J, Boxt L M, Hijazi Z M 2000 Role of the radiologist in cardiac diagnostic imaging. Am J Roentgenol 175: 1495–1506 2. Gibbons R J, Araoz P A 2005 The year in cardiac imaging. J Am Coll Cardiol 46: 542–550 3. Fuster V, Fayad Z A, Moreno P R, Poon M, Corti R, Badimon J J 2005 Atherothrombosis and high-risk plaque part II: Approaches by noninvasive computed tomographic/magnetic resonance imaging. J Am Coll Cardiol 46: 1209–1218 4. Hartnell G G, Bradley F M 1993 Correct positioning for cardiac angiography—insights from MRI. Cathet Cardiovasc Diagn 30: 101–103 5. Nosir Y F M, Salustri A, Kasprzak J D, Breburda C S, Ten Cate F J, Roelandt J R T C 1998 Left ventricular ejection fraction in patients with normal and distorted left ventricular shape by three-dimensional echocardiographic methods: a comparison with radionuclide angiography. J Am Soc Echocardiogr 11: 620–630 6. De Maria A N 1997 A new generation of ultrasound contrast agents for echocardiography. Clin Cardiol 20 (suppl I): 1–48 7. Duvall W L, Croft L B, Goldman M E 2003 Can hand-carried ultrasound devices be extended for use by the noncardiology medical community? Echocardiography 20: 471–476 8. Araoz P A 2003 Computed tomography for functional evaluation of the heart. Semin Roentgenol 38: 303–308 9. Boxt L M, Lipton M J, Kwong R Y, Rybicki F, Clouse M E 2003 Computed tomography for assessment of cardiac chambers, valves, myocardium and pericardium. Cardiol Clin 21: 561–585 10. Hofmann L K, Becker C R, Flohr T, Schoepf U J 2003 Multidetector-row CT of the heart. Semin Roentgenol 38: 135–145 11. Chan F P 2003 Cardiac multidetector-row computed tomography: principles and applications. Semin Roentgenol 38: 294–302 12. Wintersperger B J, Nikolaou K 2005 Basics of cardiac MDCT: techniques and contrast application. Eur Radiol 15 (suppl 2): B2–9 13. Mahnken A H, Wildberger J E, Koos R, Gunther R W 2005 Multislice spiral computed tomography of the heart: technique, current applications, and perspective. Cardiovasc Interven Radiol 28: 388–399 14. Lawler L P, Pannu H K, Fishman E K 2005 MDCT evaluation of the coronary arteries, 2004: How we do it—data acquisition, postprocessing, display, and interpretation. Am J Roentgenol 184: 1402–1412 15. Nakanishi T, Kayashima Y, Inoue R, Sumii K, Gomyo Y 2005 Pitfalls in 16-detector row CT of the coronary arteries. RadioGraphics 25: 425–440 16. Broderick L S, Brooks G N, Kuhlman J E 2005 Anatomic pitfalls of the heart and pericardium. RadioGraphics 25: 441–453 17. Koyama Y, Matsuoka H, Mochizuki T et al 2005 Assessment of reperfused acute myocardial infarction with two-phase contrastenhanced helical CT: prediction of left ventricular function and wall thickness. Radiology 235: 804–811 18. Raff G L, Gallagher M J, O'Neill W W 2005 Diagnostic accuracy of noninvasive coronary angiography using 64-slice spiral computed tomography. J Am Coll Cardiol 46: 552–557 19. Heuschmid M, Kuettner A, Schroedr S et al 2005 ECG-gated 16-MDCT of the coronary arteries: Assessment of image quality and accuracy in detecting stenoses. Am J Roentgenol 184: 1413–1419 20. Constantine G, Shan K, Flamm S D, Sivananthan M U 2004 Role of MRI in clinical cardiology. Lancet 363: 2162–2171 21. Boxt L M 1999 Cardiac MR imaging: A guide for the beginner. RadioGraphics 19: 1009–1025 22. Schneider G, Ahlhelm F, Seidel R et al 2003 Contrast-enhanced cardiovascular magnetic resonance imaging. Top Magn Reson Imaging 14: 386–402

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23. Botnar R M, Stuber M, Kissinger K V, Manning W J 2000 Free-breathing 3D coronary MRA: the impact of ‘isotropic’ image resolution. J Magn Reson Imaging 11: 389–393 24. Hundley W G, Hamilton C A, Rerkpattanapipat P 2003 Magnetic resonance imaging assessment of cardiac function. Curr Cardiol Rep 5: 69–74 25. Paetsch I, Jahnke C, Wahl A et al 2004 Comparison of dobutamine stress magnetic resonance, adenosine stress magnetic resonance, and adenosine stress magnetic resonance perfusion. Circulation 110: 835–842 26. Edelman R R 2004 Contrast-enhanced MR imaging of the heart: overview of the literature. Radiology 232: 653–668 27. Ibrahim T, Nekolla S G, Hornke M et al 2005 Quantitative measurement of infarct size by contrast-enhanced magnetic resonance imaging early after acute myocardial infarction: comparison with single photin emission tomography using Tc99M-sestaMIBI. J Am Coll Cardiol 45: 544–552 28. Langerak S E, Vliegen H W, de Roos A et al 2002 Detection of vein graft disease using high-resolution magnetic resonance angiography. Circulation 105: 328–333 29. Larson A C, Simonetti O P, Li D 2002 Coronary MRA with 3D undersampled projection reconstruction TrueFISP. Magn Reson Med 48: 594–601 30. Fuster V, Kim R J 2005 Frontiers in cardiovascular magnetic resonance. Circulation 112: 135–144 31. Glockner J F, Johnston D L, McGee K P 2003 Evaluation of cardiac valvular disease with MR imaging: qualitative and quantitative techniques. RadioGraphics 23: e9 32. Sparrow P J, Kurian J B, Jones T R, Sivananthan M U 2005 MR imaging of cardiac tumors. RadioGraphics 25: 1255–1276

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33. Roditi G H, Cohen M C, Hartnell G G 2000 MRI changes in myocarditis—evaluation with spin echo, cine MR angiography and contrast enhanced spin echo imaging. Clin Radiol 55: 752–758 34. Shellock F G, Crues J V 2004 MR procedures: biologic effects, safety, and patient care. RadioGraphics 232: 635–652 35. Chen E Q, MacIntyre W J, Go R T et al 1997 Myocardial viability studies using fluorine-18-FDG SPECT: a comparison with fluorine-18-FDG PET. J Nucl Med 38: 582–586 36. Shagam J Y 2001 Positron emission tomography. Radiol Technol 72: 551–569 37. Gunning M G, Anagnostopoulos C, Knight C J et al 1998 Identification of hibernating myocardium. A comparison of Tl-201, Tc-99m tetrofosmin and dobutamine cine magnetic resonance imaging. Circulation 98: 1869–1874 38. Kontos M C, Jesse R L, Schmidt K L, Ornato J P, Tatum J L 1997 Value of acute rest sestamibi perfusion imaging for evaluation of patients admitted to the emergency department with chest pain. J Am Coll Cardiol 30: 976–982 39. Marie P Y, Danchin N, Durand J F et al 1995 Long-term prediction of major ischemic events by exercise thallium-201 single-photon emission computed tomography. Incremental prognostic value compared with clinical, exercise testing, catheterization and radionuclide angiographic data. J Am Coll Cardiol 26: 879–886 40. Sharir T, Germano G, Kavanagh P B et al 1999 Incremental prognostic value of post-stress left ventricular ejection fraction and volume by gated myocardial perfusion single photon emission computed tomography. Circulation 100: 1035–1042

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CHAPTER

Congenital Heart Disease: General Principles and Imaging

23

Ronald G. Grainger, Andrew M. Taylor and Christine Reek General principles • Embryology • Diagnosis of congenital heart disease • Conventional radiology Imaging of congenital heart disease • Magnetic resonance imaging

• • • •

Computed tomography Sequential segmental analysis Acyanotic heart disease Cyanotic heart disease

GENERAL PRINCIPLES Ronald G. Grainger

EMBRYOLOGY The fetal heart develops from a series of very complex and very rapid changes that occur between the second (total fetal length 2 mm) and eighth week of intrauterine life. It is during the third to fifth weeks of intrauterine life (when the forelimbs are developing) that the cardiac structures develop most actively and are therefore most susceptible to adverse external influence (e.g. rubella virus or drugs such as thalidomide), resulting in congenital heart disease (CHD). By 8 weeks, the heart has already assumed its definitive form. Table 23.1 lists the embryological precursors and the more frequent important abnormalities that may result from aberrations in their development during the first 3–5 weeks of intrauterine life. The right and left atria are separated from, but connected to, the corresponding right and left ventricle by the tricuspid (right) and mitral (left) atrioventricular valves which develop from the atrioventricular endocardial cushions arising from the margins of the primitive atrioventricular groove. Between the second and seventh week of intrauterine life, the primitive cardiac tube grows in length much more rapidly than does the fetal trunk. The caudal and cephalad ends of the cardiac tube are therefore relatively fixed, and the rapidly elongating cardiac tube is compelled to bend into a loop, to twist and to rotate.

The loop or curve so formed is almost always convex to the right of the fetus—the D or dextro loop as viewed from the front. The axial rotation or twist of the looped cardiac tube is almost always clockwise viewed from the caudal end of the fetus. This axial rotation results in the definitive orientation of cardiac chambers after birth with the right atrium anterior and on the right, left atrium posterior, right ventricle anterior and left ventricle posterior and on the left. The fetal right atrium receives both superior vena cava (SVC) (desaturated blood from the head and myocardium) and inferior vena cava (IVC) blood (partially oxygenated from the fetal placenta and the veins from the lower part of the body). There is almost no blood flow to the fetal airless lungs because of the very high pulmonary vascular resistance.The only blood supply to the fetal left heart and therefore the systemic arteries is via (a) an atrial right atrium-to-left atrium shunt through the patent foramen ovale; and (b) a fetal pulmonary artery shunt to the descending thoracic aorta through the large patent ductus arteriosus (PDA). Normal fetal development is only sustained by the continued patency of these two essential right-to-left shunts throughout fetal life (Fig. 23.1).

Fetal circulation and circulatory changes at birth The only oxygen supply of the fetus is obtained from the oxygenated maternal blood in the placenta supplied by branches from the maternal abdominal aorta. The oxygenated maternal

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Table 23.1 MORE COMMON ANOMALIES OF CARDIAC DEVELOPMENT Embryological precursor

Abnormality

Sinus venosus and tributaries

Anomalous systemic venous drainage*

Interartrial septum and atria

Persistent foramen ovale* Ostium secundum defect* Sinus venous defect Ostium primum defect

Endocardial cushions

Ostium primum defect Endocardial atrioventricular defect Tricuspid atresia/stenosis Ebstein's anomaly Cor triatrium

Interventricular septum and ventricles

Ventricular septal defect (membranous, muscular) Common ventricle Hypoplastic left ventricle† Uhl's dysplastic right ventricle

Bulbus cordis and ventricular

Pulmonary stenosis (valve/infundibular)*

outflow

Aortic stenosis (valve/subaortic)*

anoxic vasoconstriction of the fetal pulmonary arterioles. This major fall in fetal pulmonary arteriolar pressure permits a major increase in pulmonary arterial and venous flow which distends the left atrium and closes the flap valve of the foramen ovale. Thus within a few days of postnatal life, the rightto-left shunting is abolished through both the foramen ovale and PDA. The success of the fetal circulation (Fig. 23.1) in oxygenating and nourishing the rapidly developing fetus depends on: 1 The crossing of two streams of blood (partially oxygenated blood from the fetal IVC and desaturated blood from the fetal SVC and coronary veins) which remain reasonably distinct with a minimum of mixing. 2 The open fetal foramen ovale permitting a right atriumto-left atrium shunt of partially oxygenated blood returning to the fetal heart from the placenta via the fetal IVC. 3 The patency of the fetal arterial duct (PDA) permitting a major right-to-left shunt (pulmonary artery to descending aorta) of poorly oxygenated blood from the SVC via the right ventricle to perfuse the lower half of the fetus, including the placenta where the fetal blood becomes fully oxygenated.

Tetralogy of Fallot*† Ventriculo-arterial discordance (uncorrected and corrected transposition)*† Truncus arteriosus

Common arterial trunk, persistent truncus ateriosus*† Aortopulmonary window Uncorrected transposition (discordance ventricles and great arteries)*† Congenitally corrected transposition of great arteries Pulmonary arterial trunk atresia

Branchial (aortic) arches

Double aortic arch: aortic rings Right aortic arch either isolated or with congenital heart disease* Aberrant right subclavian artery* Interruption or absence of right or left pulmonary artery Patent arterial duct (ductus arteriosus)* Supravalvular aortic stenosis Coarctation of the aorta*

*

†

Most frequent anomalies; usually cyanotic.

blood transmits oxygen through the capillaries of the placenta to the fetal desaturated blood from the fetal placental arteries. At the very moment of birth, the placenta is shed and this source of oxygen supply to the fetus is permanently removed and is replaced by the atmospheric air inhaled into the infant's lungs. This momentous development necessitates major essential changes within the fetal heart, lungs, aorta and pulmonary artery and arterial duct (PDA). Immediately after birth, there is a major increase in the infant's pulmonary blood flow as the infant's lungs become fully expanded with inhaled air, which greatly reduces the

Figure 23.1 Normal fetal circulation. Oxygenated blood (black) is carried by the umbilical vein (UV) through the ductus venosus (DV) and inferior vena cava into the right atrium (RA) within which it is directed to pass through the flap valve foramen ovale (O) into the left atrium (LA) and thence into the left ventricle and aorta and systemic arteries. Mixed venous (superior and inferior venae cavae) blood (light grey) is passed by the venae cavae into the RA, thence the RV into pulmonary artery (PA). The peripheral pulmonary arteries (pp) are very small in the fetus due to the nonfunction of the fetal lungs and high resistance of the peripheral arterial circulation. Most of the output of the right ventricle therefore passes through the large valveless patent ductus arteriosus (D) into the descending aorta to supply the lower parts of the fetus and the fetal umbilical arteries which supply the fetal placental plexus with poorly oxygenated blood for oxygenation in the placenta. The dark grey colour indicates blood having an oxygen content intermediate between mixed venous blood (light grey) and fully oxygenated blood (black).

CHAPTER 23

DIAGNOSIS OF CONGENITAL HEART DISEASE Types of abnormality The great majority of anomalies of cardiac development can be categorized as: 1 An abnormal communication [e.g. atrial septal defect (ASD), ventricular septal defect (VSD), PDA] between the right and left sides of the heart or between their main vessels. 2 An obstruction usually involving or near a heart valve in the pathway of blood flow (e.g. tricuspid atresia, pulmonary, mitral and aortic valve stenosis, coarctation of the aorta). 3 Common (combined right and left) chambers, i.e. common atrium, ventricle, or great artery (common arterial trunk) receiving both oxygenated and desaturated blood. 4 Abnormal connections (discordance) between the cardiac chambers and great arteries (e.g. right ventricle to transposed aorta, left ventricle to transposed pulmonary artery)— uncorrected transposition of great arteries (UTGA). 5 The discordance may be congenitally uncorrected (UTGA) or congenitally corrected (CCTGA) by atrioventricular inversion whereby the right atrium connects to the left ventricle (which gives rise to the discordant pulmonary artery), and the left atrium connects to the right ventricle (which gives rise to the discordant aorta). 6 Abnormal situs (position) of the heart chambers (see below). These cardiac abnormalities may exist singly or in combination, enabling a useful but not invariable classification into (A) cyanotic; and (B) non-cyanotic congenital heart disease.

Cyanotic congenital heart disease For clinically detectable central cyanosis, there must be at least 5 g of reduced haemoglobin per 100 ml of aortic blood. The entry of desaturated blood into the aorta (to cause central cyanosis) may occur in three ways: 1 Direct right-to-left shunt of desaturated venous blood into an otherwise normal systemic circuit. This usually entails a septal defect plus a more distal right heart obstruction that increases the pressure of the proximal right-sided chamber sufficiently to make the shunt go from right to left (e.g. tetralogy of Fallot) (Table 23.2). 2 Transposition (discordance) of the great arteries (UTGA). The infant right ventricle pumps systemic desaturated venous Table 23.2

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CONGENITAL HEART DISEASE: GENERAL PRINCIPLES AND IMAGING

return directly into the aorta and thence to the systemic arteries of the body, causing intense central cyanosis. The infant's left ventricle pumps fully oxygenated pulmonary venous return straight back via the transposed pulmonary artery to the lungs (a useless exercise). For the infant to be viable, there must be mixing of the right and left circulations. 3 Common mixing situations account for most of the other causes of central cyanosis. At some point in the circulation, the systemic venous (desaturated) and pulmonary venous (oxygenated) bloods return to the heart and are obliged to mix. Examples are common atria, common ventricles and persistent truncus arteriosus. Central cyanosis may be present within a few hours after birth. This indicates a very severe abnormality, such as UTGA, in which the aorta arises from the right ventricle (ventriculoarterial discordance) and thus conveys desaturated blood to the systemic circulation. Such an anomaly is not compatible with life unless there is shunting (ASD, VSD and PDA) which enables mixing of oxygenated and desaturated blood. Alternatively, central cyanosis may develop within the next few months or years. Infants with tetralogy of Fallot usually develop this delayed cyanosis, due to an increasing degree of obstruction of the outflow of the right ventricle by muscle hypertrophy and fibro-elastosis.

CONVENTIONAL RADIOLOGY The single most important radiograph is the erect frontal chest radiograph taken in full inspiration (total lung capacity) with a radiographic exposure showing the peripheral pulmonary vessels, the right and left bronchi (indicating the atrial situs, see below), and the location of the aortic arch. A high kV filtered frontal chest exposure may be necessary to demonstrate the important mediastinal anatomy. The type of CHD abnormality and its natural history and haemodynamic consequences may be evident on a single frontal chest radiographic exposure, such as ASD, pulmonary valve stenosis (PVS), coarctation of the aorta, and Eisenmenger reaction (see Fig. 23.4). However, it is often impossible to make a specific diagnosis from the chest radiograph, particularly in the supine infant. It may only be possible to suggest the broad classification, such as a left-to-right shunt, without being able to localize the site

SHUNTS: ACYANOTIC LEFT-TO-RIGHT SHUNT AND CYANOTIC RIGHT-TO-LEFT SHUNT Acyanotic

Abnormal communication

Left-to-right shunt if no obstruction

Cyanotic Abnormal communication + distal right heart obstruction

Shunt reversal with distal obstruction. Right-to-left shunt

ASD

LA → RA

TS/PS/ER

RA → LA

VSD

LV → RV

PS/ER

RV → LV

PDA

Ao → PA

ER

PA → Ao

APW

Ao → PA

ER

PA → Ao

Ao = aorta, APW = aortopulmonary window, ASD = atrial septal defect, LA = left atrium, LV = left ventricle, PA = pulmonary artery, PDA = patent ductus arteriosus, PS = pulmonary stenosis or atresia, RA = right atrium, RV = right ventricle, TS = tricuspid stenosis or atresia.

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of the abnormal communication. Conventional chest images become more reliable as the child grows. Clinical, ECG, echocardiographic, angiocardiographic, catheter pressure and oximetry data, and cross-sectional imaging [computed tomography (CT) and magnetic resonance imaging (MRI)] are of great and usually decisive importance in establishing the diagnosis. Major recent developments in the noninterventional techniques very often obviate the need for interventional catheter techniques (see below).

Diagnostic features The pulmonary vasculature (normal, plethoric, oligaemic, congested) The radiological assessment of the pulmonary circulation is probably the most important observation on the plain chest radiograph. Radiologically normal pulmonary vascularity is present in CHD if the patient is not in heart failure, if no large shunt is present, and if there is no extreme pulmonary stenosis. The pulmonary vasculature may, however, look normal on the conventional radiograph even in the presence of substantial CHD. Increased pulmonary perfusion (pulmonary plethora) is recognized by enlarged central and peripheral pulmonary arteries and veins in all zones (Fig. 23.2), as in ASD, VSD and PDA with large left-to-right shunts (Table 23.3).

Table 23.3

INCREASED PULMONARY PERFUSION (PLETHORA)

Level of shunt

Anomaly

Atrium

Ostium primum defect* Ostium secundum defect* Sinus venosus defect Anomalous pulmonary veins†

Atrioventricular valves

Endocardial cushion defects Ostium primum defect* Muscular ventricular septal defect (VSD)*

Ventricles

Membranous VSD* Bulvar VSD* Double outflow ventricle Single ventricle

Aorta

Patent arterial duct* Aortopulmonary window Common arterial trunk (persistent truncus arteriosus)† Coronary artery-to-right heart fistula Uncorrected transposition of the great arteries with atrial or venous septal defect

* Most common causes of plethora without cyanosis; †most common causes of plethora with cyanosis.

Decreased pulmonary perfusion (oligaemia) (Fig. 23.3) may be difficult to assess even on good quality radiographic images, and this becomes impossible if the image is overexposed. Isolated obstruction of the right heart, such as PVS, may not cause radiologically demonstrable pulmonary oligaemia unless the obstruction is very severe with a considerable proximal right-to-left shunt (Table 23.4). Pulmonary venous congestion and oedema is the result of the failure of the left heart to clear all the blood delivered to it. The underlying cause may be pump (left ventricular) failure, e.g. fibro-elastosis of the left ventricle, or a severe obstructive lesion anywhere from the pulmonary veins to the aorta, e.g. severe mitral or aortic obstruction (Table 23.5).

Figure 23.2 Pulmonary plethora in atrial septal defect. Large heart, large central and peripheral pulmonary arteries. Note the recruitment of the upper zone vessels into the active pulmonary circulation.1 There is no evidence of pulmonary congestion or oedema. (Reprinted from Clin Radiol, 21, Grainger R G, Transposition of the great arteries and of the pulmonary veins, including an account of cardiac embryology and chamber indentification, 335–354, 1970, with permission from The Royal College of Radiologists©.)

Figure 23.3 Pulmonary oligaemia. Very sparse small calibre vessels in all zones and small hila (tetralogy of Fallot).

CHAPTER 23

Table 23.4

•

CONGENITAL HEART DISEASE: GENERAL PRINCIPLES AND IMAGING

DECREASED PULMONARY PERFUSION (ANOMALY) Anomaly*

Level of abnormality Tricuspid valve

Tricuspid atresia Tricupid stenosis Ebstein's anomaly

Right ventricular outflow

Pulmonary infundibular stenosis (severe) Pulmonary valvar stenosis (severe) Tetralogy of Fallot Uhl's disease (right ventricular hypoplasia)

Pulmonary arterial

Pulmonary artery or trunk atresia Right or left pulmonary artery interruption Peripheral pulmonary artery interruption or stenosis Common arterial trunk (persistent truncus) (Type IV) Transposition (ventriculo-arterial discordance) with pulmonary valve stenosis Eisenmenger reaction (lung periphery only)

*

Most of these abnormalities may cause central cyanosis if the foramen ovale is patent or if proximal septal defect is present.

The diagnostic radiological features of pulmonary venous congestion and oedema in CHD are essentially the same as in acquired heart disease (see Ch. 26) with both alveolar and interstitial oedema and thickened, oedematous pleural fissures. Severe obstructive pulmonary arterial hypertension (Eisenmenger reaction or syndrome) is due to a greatly increased peripheral pulmonary arteriolar resistance, which is a response to a left-to-right shunt. The central pulmonary arteries enlarge (Fig. 23.4) and the peripheral pulmonary arteries become smaller than normal. The increase in size of the central pulmonary arteries and possible calcification of the wall of the central pulmonary arteries (and patent arterial duct) are more marked when the Eisenmenger reaction

Table 23.5 PULMONARY OEDEMA AND VENOUS CONGESTION IN CONGENITAL HEART DISEASE Level of anomaly Pulmonary veins

Anomaly Obstruction by septa Total anomalous pulmonary venous drainage obstructed (especially infradiaphragmatic Type 3)

Left atrium

Cor triatrium Mitral valve stenosis or atresia Mitral valve incompetence (including atrioventricular cushion defect)

Left ventricle

Hypoplastic left ventricle Fibro-elastosis of left ventricle Cardiomyopathy

Aorta

Aberrant left coronary artery from pulmonary artery Aortic, supravalvar or valve stenosis or atresia Coarctation

Figure 23.4 Obstructive pulmonary arterial hypertension (Eisenmenger syndrome) complicating a large atrial septal defect with previous major left-to-right shunt. Very large central pulmonary arteries with small peripheral vessels. Linear calcification of the central pulmonary arteries. Moderate cardiac enlargement.

complicates a previous long-standing severe left-to-right shunt (as in ASD) compared to Eisenmenger VSD. Increased bronchial circulation1 An increased bronchial arterial circulation may be recognizable in cyanotic CHD by a nodular lung pattern in the central third of the lung parenchyma, with many small rounded opacities representing many enlarged bronchial arteries seen end-on. Increased bronchial artery circulation occurs in cyanotic CHD as an adaptive mechanism1 whereby the enlarged bronchial arteries containing partially desaturated blood can gain oxygen from the alveolar air and transmit it usefully to the pulmonary veins. The usual cause in CHD is severe tetralogy of Fallot.

Size of the heart Mechanical outflow obstruction before heart failure develops causes muscular hypertrophy of the obstructed ventricle and not dilatation of its cavity. The heart enlarges in two different haemodynamic situations: (a) diastolic volume overload (increased preload); and (b) pump failure, which may be intrinsic or secondary to increased afterload (distal obstruction). Diastolic volume overload indicates that the heart chamber(s) must accommodate an excessive volume of blood during its filling phase whenever there is a major left shunt in order to maintain increased cardiac output, or when there is severe valvular regurgitation. Pump failure may affect either the right or left ventricle, causing considerable enlargement of that chamber and a marked

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reduction in its ejection fraction. In CHD this may result from an inherent pump weakness such as fibro-elastosis, or from failure of the ventricle to overcome a severe mechanical challenge such as very severe obstruction of its outflow.

Shape of the heart This is influenced by the size, shape and position of its different chambers and great vessels. Classic descriptions, e.g. coeur en sabot in tetralogy of Fallot, figure of 8 in total superior anomalous pulmonary venous drainage (Type 1), are now much less frequently seen as early diagnosis and corrective surgery prevent the development of major cardiac changes and the adoption of the characteristic shapes.

Position, size and shape of the ascending aorta and its arch The side of the aortic arch is almost always clearly visible on the frontal chest radiograph of an adolescent or adult, but may be much more difficult to detect in the infant and young child. The side of the aortic arch can usually be inferred to be on that side of the trachea where there is more mediastinal soft tissue at the level of the third and fourth dorsal vertebrae: if there is any doubt, confirmation will be obtained by cross-sectional imaging—MRI or CT, or a barium swallow which will demonstrate a concave indentation and displacement of the oesophagus away from the side of the aortic arch. In right-sided aortic arch with associated CHD, there is usually mirror image branching of the aortic arch, i.e. the first branch is the left innominate (which divides into the left common carotid and left subclavian arteries), followed by the right carotid and right subclavian arteries. No major arterial branch usually passes behind the oesophagus, which is therefore rarely indented from behind as it often is by the left subclavian artery in isolated right aortic arch without associated cardiac anomaly. The position of the ascending aorta is of considerable importance. In a normally positioned heart (laevocardia) in situs solitus, the ascending aorta usually forms a gently convex right border to the superior mediastinum. In uncorrected transposition (UCTA)2, the ascending aorta is usually only very slightly to the right of the midline in front of the midline pulmonary arterial trunk, so producing a vascular pedicle which is narrow in the frontal view and wide on the lateral radiograph. In congenitally corrected transposition (CCTGA), the ascending aorta may produce a long convexity on the left upper mediastinal contour—a very significant diagnostic feature. A dilated ascending ‘aorta’, rising high in the mediastinum to form a high prominent ‘aortic’ arch, is seen typically in persistent arterial truncus (up to 50% have a right arch) or tetralogy of Fallot (20–30%). An abnormally shaped aortic arch is seen in many cases of coarctation and high cervical arch (pseudocoarctation). The appearances of the aortic arch in these two conditions may be identical (deformed high aortic knuckle, sharp forward kink of the upper descending aorta, an indented aortic arch left border, figure of 3 indentation deformity of the left border of the oesophagus). The distinguishing radiological feature between these two conditions is rib notching in a haemodynamically significant coarctation, denoting a compensating collateral intercostal circulation

conveying blood to the descending aorta.There is no rib notching in persistent cervical arch (pseudocoarctation) as there is usually minimal or no stenosis of the aortic lumen.

Situs (position) of the viscera, bronchi (and by inference of the atria) The normal position of the viscera (heart and stomach on the left, liver on the right, short right bronchus, longer left bronchus) is known as situs solitus. Cardiac situs is discussed further below.

Presence of associated features, e.g. skeletal changes The most important skeletal feature seen on the conventional chest radiograph of a patient with CHD is rib notching of the lower margin of the third to eighth ribs in aortic coarctation due to the enlarged, tortuous intercostal arteries supplying blood to (instead of conducting blood from) the descending aorta. (The notching is not usually seen in children younger than 5 years.) It is usually bilaterally symmetrical but may be exclusively on the right (aortic coarctation involving the left subclavian artery), or only on the left (aberrant right subclavian artery arising below the coarctation). Several genetic, metabolic and skeletal disorders are associated with congenital malformations of the heart. CHD is more frequent when the upper limbs are deformed, probably because the forelimbs develop at the same time as the heart in the first 3–5 weeks of intrauterine life, i.e. before the lower limbs. Trisomy chromosome 21 (Down’s syndrome, mongolism) is complicated in about 25% of cases by heart malformation usually involving atrioventricular endocardial cushion defects. Turner's and Noonan’s syndromes are often associated with aortic coarctation and/or pulmonary artery stenosis. Holt– Oram syndrome (absent or hypoplastic forearms and thumbs) may be associated with ASD and other CHD. Ellis van Creveld syndrome (chondro-ectodermal dysplasia) may be complicated by a common atrial chamber. Thalidomide toxicity produces phocomelic changes (small undeveloped limbs), more extreme but similar to Holt–Oram syndrome, and 17% of affected patients are said to have a cardiac malformation. Post-surgical stigmata such as surgically deformed ribs, unilateral rib notching, surgical sutures and valve and conduit prostheses are most valuable evidence and must always be carefully looked for on the plain radiographs.

Chamber identification The geographical position of the four individual heart chambers and of the great vessels relative to each other, their spatial orientation within the thorax, and their interconnections may all be abnormal and these criteria cannot therefore be used for chamber identification. It is essential therefore positively to identify the different cardiac chambers by their intrinsic anatomical or morphological characteristics2, regardless of their intrinsic connections or their

CHAPTER 23

spatial orientation (see section on sequential segmental analysis below). For most of the 20th century, catheter angiocardiography was the undisputed gold standard for identifying the detailed

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CONGENITAL HEART DISEASE: GENERAL PRINCIPLES AND IMAGING

anatomy of the heart chambers and the detailed diagnosis of CHD2. That position has been recently very successfully displaced by noninterventional echocardiography and crosssectional imaging—CT and MRI (see below).

IMAGING OF CONGENITAL HEART DISEASE Andrew M. Taylor and Christine Reek CHD has an incidence of 6–8 per 1000 at birth3,4. The diagnosis of CHD has increased because of improvements in diagnosis and treatment, leading to more patients surviving into adulthood. There is an increasing number of children with acquired heart disease, in particular related to anthracylcine cardiotoxicity following treatment for oncological disease in early childhood. Management of patients with CHD relies very heavily on imaging. Echocardiography is the first-line investigation6. It can be used to assess accurately anatomy and function, is not very expensive, is portable, and is easy to use in experienced hands. However, echocardiography may be limited by poor acoustic windows, can be poor at imaging the vessels beyond the heart, and is very user dependent.These problems are exacerbated in patients with CHD, as it is often the right ventricle and pulmonary arteries that require assessing (both of which are difficult to assess at echocardiography), and patients may have undergone multiple operations, which can further reduce acoustic window access. Traditionally, more detailed anatomical and functional assessment has been acquired with X-ray cardiac catheterization. Cardiac catheterization gives good definition of vascular anatomy and enables assessment of haemodynamics (vascular stenosis, quantification of cardiac shunting and pulmonary vascular resistance), but is associated with risks due to the invasive nature of the procedure and the exposure to ionizing radiation. In addition, X-ray fluoroscopy provides a projection image and has only limited three-dimensional (3D) capabilities. Radionuclide imaging has been used to quantify left-toright shunts in order to avoid cardiac catheterization and to assess the relative pulmonary perfusion, but this also involves significant exposure to ionizing radiation7. More recently, cross-sectional cardiovascular imaging (MRI8 and CT9) has become a very important tool for diagnosis and follow-up of patients with CHD, both in adults [grown-up congenital heart (GUCH) disease] and in children. Not only does cross-sectional imaging allow accurate description of cardiac and vascular anatomy in relation to the other structures of the chest8,9, but MRI in particular can provide accurate quantification of cardiac function and vascular flow in vivo. This section describes the common types of CHD and stresses the role of the chest radiograph, MRI and CT. A detailed discussion of the echocardiography is beyond the scope of this chapter.

MAGNETIC RESONANCE IMAGING10 The majority of cardiovascular MR images are acquired using cardiac (ECG) gating during a single breath-hold to

reduce the artefacts associated with cardiac and respiratory motion. For a complex case, MRI is performed over approximately 1 h, though this time can be considerably reduced if a focused question is being addressed. Imaging sequences can be broadly divided into: • ‘Black blood’ spin-echo images, where signal from blood is nulled and thus not seen—for accurate anatomical imaging. • ‘White blood’ gradient-echo or steady-state free precession (SSFP) images, where a positive signal from blood is returned—for anatomical, cine imaging and quantification of ventricular volumes, mass and function. • Phase-contrast imaging, where velocity information is encoded—for quantification of vascular flow. • Contrast-enhanced MR angiography (MRA), where nonECG-gated 3D data are acquired after gadolinium contrast medium has been administered—for thoracic vasculature imaging. All these sequences can be acquired in a single breath-hold, reducing the overall time in the MR machine, and enabling the acquisition of accurate data in the majority of patients. Importantly, ‘white blood’ cine images can be acquired in a continuous short axis stack along the heart, enabling accurate quantification of right and left ventricular function. Imaging should be performed in the presence of a cardiovascular MRI expert in conjunction with an MRI technician to ensure that the appropriate clinical questions are answered. Currently, the authors' own practice is to perform all cardiovascular MRI in children younger than 8 years of age under general anaesthesia as this enables the safe acquisition of accurate data (reduced movement and respiratory artefact). With the development of even faster sequences, breath-holding may become less of a necessity, and MRI data may then be acquired more easily during sedation.

COMPUTED TOMOGRAPHY9 With the development of multidetector CT (MDCT), it is now possible to acquire volumes of CT data that can be reformatted in any imaging plane. MDCT images of the entire thorax can be acquired in 3–10 s, depending on the size of the patient. Using iodinated contrast agents, CT angiography (CTA) can now be rapidly performed, and 3D imaging algorithms applied to create 3D images which considerably aid in the 3D appreciation of complex vascular anatomy. At present, ECG gating for cardiac CT is limited to patients with slow heart rates (< 60 beats min−1), which excludes many subjects

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with CHD. Cardiac CT images of intracardiac anatomy are often blurred and of limited value; however, with the advent of 64- and potentially 256-slice CT machines, this will improve in the near future. With the speed of MDCT acquisition, most young children can be imaged either with sedation or unsedated with feed and wrap. Contrast medium injection should optimally be through a large (20 G minimum) cannula with pump injection, but a hand injection may also produce adequate results. Contrast agent bolus timing is important and may be crucial for optimal image quality, vessel delineation and diagnostic confidence. This is best achieved by triggering the data acquisition after visually watching contrast medium arrive in the appropriate vessel. Data are acquired in an axial spiral, with a reconstruction slice width of 0.75–1.5 mm, during a single breath-hold or, if not possible, shallow respiration. Images are then transferred to a workstation for the creation of 3D images. MRI is currently the 3D imaging investigation of choice, as it allows accurate assessment of intracardiac anatomy, function, and flow without a radiation burden or potential complications of iodinated contrast media. However, cardiac CT may be preferred, particularly for vascular imaging in young patients, who would otherwise require a general anaesthetic for adequate MRI, and in those for whom MRI is contraindicated or when additional information may be acquired from CT (e.g. airways and lung).

SEQUENTIAL SEGMENTAL ANALYSIS

3

The nomenclature of complex CHD is based on sequential segmental analysis. This requires description of atrial position (situs), atrioventricular and ventriculo-arterial connections, and other associated lesions3.

Step 1—Atrial situs In the normal heart, the morphological right atrium is located to the right of the morphological left atrium (situs solitus). Abnormalities in the atrial situs are often associated with major cardiac malformations and abnormal abdominal and thoracic anatomy. In situs solitus, the IVC is to the right of the abdominal aorta, with a right-sided liver and a left-sided spleen.The rightsided bronchus is much shorter than the left-sided bronchus. In situs inversus, the mirror image of the normal anatomy is present and is usually easily demonstrated with echocardiography. In situs ambiguus, atrial situs is uncertain. The most common lesions are right or left isomerism in which both atrial chambers have features of the same-sided atrium. In isomeric lesions, there is often an endocardial cushion defect with varying degrees of atrioventricular septal defect (AVSD). The atrial appendages are the best method of determining atrial identification. The right atrial appendage is triangular with a wide base, whilst the left atrial appendage is a tubular structure. The presence of the terminal crest and pectinate muscle in the appendage are more specific internal characteristics of the right atrium and its appendage.

Right isomerism is usually associated with bilateral (short) right bronchi, trilobed lungs and bilateral right atrial appendages, asplenia and a midline liver. Left isomerism is usually associated with bilateral left (long) bronchi, bilobed lungs, left atrial appendages, polysplenia and IVC interruption. All of these abnormalities can be determined with MRI, particularly 3D balanced-SSFP techniques. Both right- and left-sided isomerism are associated with gut malrotation (Table 23.6).

Step 2—Atrioventricular connection Determination of ventricular morphology allows analysis of atrioventricular and ventriculo-arterial connection or concordance. Irrespective of atrioventricular concordance, the atrioventricular valve is concordant with the ventricle, i.e. the tricuspid valve always connects to the right ventricle and the mitral valve connects to the left ventricle.The septal insertion of the tricuspid valve is nearer the cardiac apex than that of the mitral valve, and allows determination of the ventricular morphology. The right ventricle is more coarsely trabeculated than the left ventricle, with a muscular infundibulum separating the inflow and outflow valves, and there is a mid ventricular ‘moderator band’. The size, thickness and shape of the ventricles, although different in normal subjects, are not good indicators of ventricular origin in CHD as they are dependent on load effects.

Step 3—Ventriculo-arterial connection Description of ventriculo-arterial connections represents the final element of sequential segmental analysis. The aorta and pulmonary arteries are identified by their typical branching and distribution patterns and not by the chambers to which they are connected. Cross-sectional imaging is very useful in

Table 23.6 ASSOCIATIONS WITH ATRIAL ISOMERISM Defect

Right isomerism

Left isomerism

Atrioventricular septal defect

Yes

Yes

Anomalous pulmonary veins

Yes

No

Bilateral superior vena cavae

Yes

Yes

Vena azygos continuation

No

Yes

Double outflow right ventricle

Yes

No

Pulmonary stenosis/atresia

Yes

Yes

Dextrocardia

Cardiac

Yes

Yes

Transposition ventriculo-arterial Yes discordance

No

Complete heart block

No

Yes

Bronchi

Bilateral short right

Bilateral long left

Lungs

Bilateral trilobed lungs

Bilateral bilobed lungs

Liver

Central large

Central

Spleen

Asplenia

Polysplenia

Gut

Malrotation

Malrotation

Noncardiac

CHAPTER 23

determining the arrangement of the great vessels and their ventricular connections.

Step 4—Identification of other abnormalities Other abnormalities to be considered include abnormal venous connections, ASD,VSD, AVSD and valve abnormalities. In CHD, most abnormalities are single lesions (e.g. PVS, coarctation of the aorta) that are easily described. Many patients with CHD have a combination of anomalies (e.g. tetralogy of Fallot and transposition of the great arteries). Almost any combination of abnormalities and connections can occur, and using the sequential segmental analysis method the description of all conceivable combinations and diagnoses is possible although not commonly required.

ACYANOTIC HEART DISEASE Congenital anomalies of the aorta Aortic coarctation Coarctation occurs in 6–8% of live CHD births with a predominance of boys4. There is an area of narrowing in the thoracic aorta in the region of insertion of the arterial duct (aortic isthmus).There is a risk of systemic hypertension, atherosclerosis and end-organ damage, even in patients who have undergone surgical repair. Treatment in infancy is usually surgical excision of the narrowing, though in older subjects balloon angioplasty may be undertaken, and following re-coarctation, aortic stenting can be used. In the neonatal population, echocardiography is used in the initial diagnosis. Echocardiography can also be used in followup, but as children grow this becomes more difficult and imaging with MRI (Fig. 23.5A) and CT is required in later life to establish if there is re-coarctation after repair (3–35% of patients), aneurysmal dilatation, or left ventricular hypertrophy secondary to hypertension. MRI is preferred if there are no contraindications, as this reduces population radiation.

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CONGENITAL HEART DISEASE: GENERAL PRINCIPLES AND IMAGING

Imaging is crucial for management decisions in order to establish the location and degree of stenosis, length of coarctation segment, associated aortic arch involvement (such as tubular hypoplasia), the collateral pathways (internal mammary and posterior mediastinal arteries), relationship to aberrant subclavian artery, post-stenotic dilatation and left ventricular hypertrophy. Three-dimensional contrast-enhanced MRA may display the severity and extent of involvement (Fig. 23.5B). MRI flow mapping can define the severity of the stenosis by measuring velocity jets at the level of coarctation. Assessment of collateral flow can also be performed by measuring flows in the proximal and descending aorta. Reassessment of collateral flow following treatment can be used to assess the success of the treatment. MRI can also be used to assess secondary pathology in patients with coarctation, e.g. aortic root for dilatation secondary to a bicuspid aortic valve—frequency in coarctation of 15%; aortic valve incompetence and stenosis; and ventricular function and left ventricular mass (an indirect indicator of increased left ventricular after-load). Discrete localized stenoses may be amenable to balloon dilatation. MRI is very useful for noninvasive follow-up and directing further treatment if necessary.

Anomalies of the aortic arch Embryologically, the left fourth branchial arch persists and the right fourth arch involutes, except for the proximal segment, which forms the proximal right subclavian artery. Understanding the various potential anomalies that may occur is based on Edward's embryonic hypothetical double aortic arch schema (Fig. 23.6). Atretic aortic segments may persist (including right and left arterial ducts), which may not be visualized on imaging, and which may have the potential to cause complete vascular compressive rings (Table 23.7). In double aortic arch, the right arch is usually larger than the left (which may be atretic or hypoplastic) and may result in the formation of a vascular ring, which may compress the trachea and oesophagus. The arterial duct is usually left sided, but can be right sided or even bilateral and increase the compression. Two further potential vascular rings can occur: (a) the left pulmonary artery sling (the left pulmonary artery arises from the proximal right pulmonary artery and then turns abruptly posteriorly and then to the left, indenting and compressing the trachea in anteriorly and the oesophagus posteriorly in order to reach the left hilum); and (b) a right aortic arch, aberrant left subclavian artery, connected to the fibrosed left arterial duct.

Congenital supravalvular aortic stenosis

Figure 23.5 Aortic coarctation. (A) Oblique sagittal, ‘black-blood’ turbo spin-echo image through a severe, discrete aortic coarctation (arrowhead). (B) 3D, volume-rendered MRA image of another severe aortic coarctation (arrow), with multiple collaterals (asterisk).

This is a rare congenital heart defect that is often associated with Williams' syndrome of infantile hypercalcaemia. The luminal stenosis is due to local thickening of the proximal ascending aortic wall. The main roles of cardiovascular MRI are pre-operative anatomical and functional assessment of the stenosis and postoperative assessment of possible restenosis. Contrast-enhanced MRA or CTA is an accurate and less traumatic method than catheter angiography of assessing the type

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Figure 23.6 A schematic representation of Edward's hypothetical double aortic arch, showing right and left aortic arches and bilateral arterial ducts. (A) Division of the double arch along the bold line in (B) gives a normal left-sided arch, ringed trachea and striated oesophagus posteriorly. (C) A double arch with the ringed trachea and vertically striated oesophagus within the vascular ring. (Courtesy of Professor Robert H Anderson, Dr Andrew C Cook and Gemma Price, Cardiac Unit, Institute of Child Health.)

and severity of the defect as well as its relationship to the aortic valve.

Septal defects These consist of ‘holes’ or defects in the atrial septum, ventricular septum, or a combination of the two.They may be simple, isolated lesions, or may be associated with more complex CHD.

Atrial septal defects Atrial septal defects are the most common congenital heart defect detected in adults, with an incidence of 941 per million live births4. Ostium secundum defects form about 80% of all ASDs and are located in the fossa ovalis. The ostium primum defect, although previously regarded as an ASD, is actually a partial AVSD (see below). The sinus venosus defect is found at the junction of either of the caval veins and the right atrium. This type of ASD is rare and is often associated with partial anomalous pulmonary venous drainage.

Table 23.7 VASCULAR RINGS Symptoms Usually symptomatic

Anatomy Double aortic arch Right aortic arch with right descending aorta + aberrant left subclavian artery + persistent left arterial duct Left aortic arch with right descending aorta + right arterial ductus Left pulmonary sling

Occasionally symptomatic

Anomalous right innominate artery Anomalous left common carotid artery Right aortic arch with left descending aorta + left ductus

Usually asymptomatic

Left aortic arch + aberrant right subclavian artery Left aortic arch with right descending aorta Right aortic arch with right descending aorta + mirror image branching Right aortic arch with right descending aorta + left aberrant subclavian artery Right aortic arch with right descending aorta + isolation of left subclavian artery

Pathological consequences of ASDs are secondary to atrial left-to-right shunting. This volume overload leads to atrial dilatation, predisposing to tachyarrythmias and biventricular volume overload. The presence of an ASD or patent foramen ovale is also a risk factor for paradoxical thromboembolic stroke. Evaluation of ASDs requires definition of type and location of the defect, quantification of the shunt, detection of any intra-atrial thrombus, assessment of right ventricular function, and visualization of the pulmonary venous anatomy. Management of ASDs may be with transcatheter ASD mechanical closure devices or open surgical closure for larger defects. Trans-thoracic echocardiography has a limited ability to visualize small ostium secundum and sinus venosus defects: detection of pulmonary venous abnormalities is very difficult. Transoesophageal echocardiography has become the main imaging technique used to assess ASDs. However, it cannot be used to quantify the shunt (Qp:Qs) accurately and it may be difficult to delineate pulmonary venous anatomy. Cardiovascular MRI can be used if there remains doubt with regard to the anatomical rim of the defect or the functional significance of ASDs, imaging data that compare well with operative findings.

Atrioventricular septal defects Atrioventricular septal defects and, possibly, migraine are caused by abnormal development of the endocardial cushion, and can be categorized into partial with a defect of the atrial septum alone (previously described as primum ASD) or complete with defects of both the atrial and ventricular septa (Fig. 23.7). AVSDs can further be divided into balanced (relatively equal sized atrioventricular valves and ventricles) or unbalanced, when inflow through the atrioventricular valves is predominantly into one of the ventricles. AVSDs are relatively complex lesions, and although they are listed here as an acyanotic condition, they may be associated with other complex anomalies (e.g. atrial isomerism or double outlet right ventricle).There is also a high incidence of AVSDs in patients with Down's syndrome (trisomy 21).

Ventricular septal defects (VSDs) Ventricular septal defects (VSDs) are the most common congenital heart lesions with an incidence of 3570 per million live

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CONGENITAL HEART DISEASE: GENERAL PRINCIPLES AND IMAGING

Patent arterial duct Although the arterial duct is essential for life in the fetus, if it fails to close after birth, a persistent communication is left between the aorta and pulmonary artery. The consequences will depend on the size of the duct with a large duct resulting in a large left-to-right shunt. A small duct may not be detected for many years but still has a risk of infective endocarditis. Closure may be surgical or by catheter device depending on the anatomy and associated conditions. A large duct left unclosed may result in Eisenmenger syndrome of pulmonary arterial hypertension (PAH) and therapeutic closure is then contraindicated.The duct and the central pulmonary arteries may become calcified and may be visible on the chest radiograph along with evidence of PAH.

Eisenmenger syndrome Figure 23.7 Complete atrioventricular septal defect. Balanced steady-state free precession four-chamber view MRI. Arrowhead = small ventricular septal defect, asterisk = complete absence of the atrial septum, white arrow = left atrioventricular valve, dashed arrow = position of right atrioventricular valve.

births4.VSDs are a heterogeneous group of lesions with shunting at the ventricular level. Assessment in the first instance is with echocardiography. The haemodynamic effects of VSDs are dependent on the shunt volume and may vary from insignificant up to left heart failure and pulmonary vascular disease, and the severity determines treatment. Quantification of leftto-right shunts using velocity-encoded phase-contrast MRI compares well to invasive catheterization. Invasive catheterization may still be used to quantify pulmonary vascular resistance to exclude pulmonary hypertension in some long-standing cases before defect closure. Perimembranous lesions account for 80% of all VSDs and are characterized by the relationship with ventricular inlet or outlet. The majority of perimembranous VSDs will close spontaneously. Large perimembranous VSDs are unlikely to close and may lead to the development of obstructive pulmonary vascular (Eisenmenger) disease. In these patients, the VSD must not be therapeutically closed. Between 5% and 20% of VSDs occur in the muscular interventricular septum. Muscular VSDs are an extremely heterogeneous group and can be difficult to close surgically. Optimum treatment (either operative or transcatheter) depends on accurate demonstration of theVSD anatomy. Muscular defects often have a complex 3D structure with multiple defects—‘Swiss cheese appearance’—which are more accurately represented by MRI than echocardiography. Approximately 50% of patients with a VSD have an associated additional cardiac abnormality. Coarctation of the aorta and aortic stenosis are particularly important and are associated with posterior malalignment of the VSD. Cardiovascular MRI is useful in the assessment of both.

The Eisenmenger syndrome of obstructive PAH may develop in any patient with a left-to-right shunt and transmitting near systemic pressures to the pulmonary arteries. This results in atheromatous hypertensive reaction of the pulmonary arteries, which is progressive and may eventually become irreversible. The syndrome involves a high pulmonary vascular resistance with reversed or bidirectional shunt. This may occur early in life, especially if the shunt is large and either aortopulmonary or interventricular. The Eisenmenger syndrome tends to occur earlier in life in VSD and patent ductus, but after 30–40 years in large shunt ASD. In the latter cases, the central pulmonary arteries become very large and may become calcified (see Fig. 23.4). The prevalence of Eisenmenger syndrome has declined as diagnosis and surgical closure of shunts has greatly improved. However, once PAH is established and irreversible, the balanced physiology should not be disturbed. The remaining surgical option is heart–lung transplantation when end-stage heart and lung disease has developed. Anatomy and flow rates can be assessed by MRI, but investigation of pulmonary vascular resistance and its reversibility still requires cardiac catheterization.

Pulmonary valvular stenosis Pulmonary valvular stenosis is frequently associated with ASD or patent foramen ovale, and a dysplastic pulmonary valve is often seen in patients with Noonan's syndrome. Obstruction to the right ventricular outflow tract is also considered in the section on tetralogy of Fallot and pulmonary atresia below. When severe, pulmonary valvular stenosis can present in the neonatal period. The right ventricle may be small in these patients, and presentation and management are similar to those of pulmonary atresia with intact ventricular septum (see below). In older children with normal cardiac output, pulmonary stenosis is graded according to the gradient across the valve: mild—25–50 mmHg; moderate—50–70 mmHg; and severe > 70 mmHg. Diagnosis is usually based on clinical suspicion and findings at echocardiography. Angiocardiography demonstrates convex doming of the pulmonary valve and post-stenotic dilatation of the main and left pulmonary arteries, but this invasive

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procedure is now rarely indicated. Patients with moderate to severe pulmonary stenosis can be treated with balloon valvuloplasty in the first instance (cardiac catheterization or surgery). Cross-sectional imaging, in particular MRI, can be used for the follow-up of these patients.The sequelae of pulmonary incompetence are of particular importance in these patients, and may require surgical or transcatheter (percutaneous pulmonary valve implantation11) intervention at a later date (see tetralogy of Fallot below).

CYANOTIC HEART DISEASE Tetralogy of Fallot Tetralogy of Fallot is the most common cyanotic congenital heart defect with an incidence of approximately 420 per million live births4. It is caused by malalignment of the infundibular septum, which leads to right ventricular outflow (RVOT) obstruction, a subaortic VSD with aortic override and right ventricular hypertrophy (Fig. 23.8). Trans-thoracic echocardiography is the imaging modality of choice for initial diagnosis and assessment. Initial chest radiographic appearances (Fig. 23.9) may include right ventricular heart silhouette, a boot-shaped heart, small hila, pulmonary oligaemia or asymmetry and concave pulmonary artery segment.The aortic arch is right sided in about 30%. The anatomy can be confirmed by conventional angiography (Fig. 23.8) or by noninvasive cross-sectional imaging.

LSCA

RSCA

DAD C Ao

Current management consists of early single stage reconstructive surgery, with closure of the VSD, and relief of the RVOT obstruction, with possible placement of a transannular patch. Staged reconstruction is still required if there is significant hypoplasia of the central pulmonary arteries, with placement of a modified Blalock–Taussig (BT) shunt—a systemic-to-pulmonary anastomosis, usually between the innominate artery and the right pulmonary artery. This shunt is then taken down during subsequent definitive repair. Cross-sectional imaging has a role in delineating pulmonary artery anatomy in the younger child, defining whether reconstructive pulmonary artery surgery is required prior to definitive surgery. However, the main role of imaging in patients with tetralogy of Fallot is the assessment of postoperative complications (Fig. 23.10). Chest radiography at this stage may show evidence of previous BT shunt surgery, asymmetric pulmonary circulation, and calcification of the transannular patch. The most common late postoperative complication is pulmonary regurgitation secondary to transannular patch reconstruction of the RVOT/pulmonary annulus, and is often associated with aneurysmal dilatation of the RVOT. Surgical or transcatheter valve replacement is the current method of managing patients with severe pulmonary regurgitation11 (Fig. 23.10). Accurate quantification of regurgitation and assessment of RVOT anatomy and right ventricular function are particularly important in deciding the type, timing and multiplicity of procedures. Branch pulmonary stenosis may also be present in this patient group and is best imaged by MRA.This can contribute to right ventricular dysfunction, and significant obstructions should be repaired at the same time as valve replacement. The final role of MRI is in evaluating right ventricular function. This is important for timing of invasive therapeutic measures and evaluating the effect of any invasive procedure. It has been shown that, using a combination of MR ventricular volumetry and tricuspid and pulmonary flow maps, precise information about global and diastolic ventricular function can be assessed in patients with repaired tetralogy of Fallot.

LPA

RPA

RVOT

RV

Figure 23.8 Tetralogy of Fallot. Right ventricular angiogram showing long stenosis of the right ventricle outflow tract (RVOT). Immediate opacification of the right aortic arch. Immediate opacification of the proximal right pulmonary artery (RPA): interruption of the proximal left pulmonary artery. The distal left pulmonary artery opacifies later and fainter via collaterals from the aorta (Ao), left subclavian artery (LSCA), and from other collaterals (C).

Figure 23.9 Tetralogy of Fallot. Boot-shaped heart, small hila and pulmonary oligaemia.

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Figure 23.10 Repaired tetralogy of Fallot. (A) Balanced steady-state free precession four-chamber image showing right ventricular dilation (asterisk). (B) 3D, volume-rendered MRA image of the right ventricular outflow tract (RVOT) and proximal pulmonary arteries—lateral view. Note the large RVOT aneurysm is seen at the site of previous transannular patch repair (dashed arrow), the pulmonary trunk (arrowhead), and the narrowed proximal left pulmonary artery (long complete arrow). (C) Flow plotted against time for the aorta and pulmonary artery demonstrating pulmonary incompetence (regurgitant fraction = 30%); data acquired from phase-contrast velocity maps (not shown).

Pulmonary atresia Pulmonary atresia is defined as a lack of continuity between the RVOT and the central pulmonary arteries with a variable degree of hypoplasia of these structures. Pulmonary atresia can be separated into two groups depending on the presence of a VSD. As the diagnosis and subsequent management of these two groups is different, it is useful to consider them separately.

Pulmonary atresia with a ventricular septal defect This is the more common variant and is considered by some to be a severe form of tetralogy of Fallot, with a subaortic VSD, overriding aorta and often major aortopulmonary collaterals (MAPCAs). Surgical repair aims to establish RVOT to the pulmonary artery continuity with a homograft, repair the VSD and bring the aortopulmonary collaterals into the pulmonary circulation. As with tetralogy of Fallot, the main role of MRI in patients with pulmonary atresia and a VSD is assessment of postoperative complications.The most common long-term complication is homograft failure; usually mixed stenosis and regurgitation leading to right ventricular dysfunction. Conduit stenosis is often secondary to calcification of the nonviable homograft,

and although calcified tissue is difficult to visualize using MRI, it is clearly seen on CT. Other long-term complications are similar to those found in tetralogy of Fallot.

Pulmonary atresia with an intact ventricular septum This is the less common variant of pulmonary atresia, and is associated with a variable degree of right ventricular hypoplasia. The type of surgical repair depends on the size and shape of the right ventricular cavity. The presence of a right ventricular infundibulum allows a biventricular repair. If the right ventricular cavity is small then single ventricular physiology is established and angiography demonstrates large venous sinusoids in the right ventricular wall. MRI assessment is considered in the section below on the single ventricle.

Transposition of the great arteries2 Transposition of the great arteries (TGA) is the second most common cyanotic CHD in the first year of life with an incidence of 315 per million live births4. It is defined as ventriculo-arterial discordance with an anterior aorta arising from the anterior right ventricle, and the pulmonary artery arising from the posterior left ventricle (Fig. 23.11). Forty per cent of patients with

Figure 23.11 Transposition of the great arteries. (A) Balanced steady-state free precession (SSFP) sagittal image; the aorta (Ao) arises anteriorly from the hypertrophied right ventricle (arrowhead); the posterior pulmonary artery (PA) arises from the left ventricle (dashed arrow). LV = left ventricle, RV = right ventricle. (B) Balanced SSFP images of intra-atrial baffles in a patient who has undergone the atrial switch Senning operation—pulmonary venous blood into the right atrium (asterisk), systemic venous blood into the left atrium, superior pathway of systemic venous blood (dashed arrow), inferior pathway (arrow). (C) 3D volume-rendered MRA of the aorta (Ao) after the arterial switch operation. Anterior pulmonary arteries are marked: asterisk = pulmonary trunk, arrow = left pulmonary artery.

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TGA have a VSD and 30% of these patients have subpulmonary stenosis. Surgical therapy for this condition was revolutionized in about the 1960s with the introduction of the Senning and Mustard procedure, in which blood is diverted by an intra-atrial baffle from the right atrium to the left ventricle, and from the left atrium to the right ventricle. Both procedures produce a physiologically normal, but an anatomically very abnormal circulation (systemic venous return to the left atrium, then to the left ventricle, and then to the transposed discordant pulmonary artery; pulmonary venous return diverted to the right atrium, then to the right ventricle and then to the transposed aorta). In 1975, the first arterial switch operation was performed. In this operation, the aorta and main pulmonary artery are transected just above the origin of the coronary arteries, switched and re-anastomosed to the correct ventricle. The coronary arteries and a small portion of aortic sinus are excised when the aorta is transected, and re-implanted once the aorta is connected to the left ventricular outflow track. This results in both a physiological and anatomically normal circulation, and for this reason, the arterial switch operation has become the procedure of choice for TGA. The arterial switch operation is performed in the first few days of life, and currently trans-thoracic echocardiography is the imaging modality of choice for pre-operative diagnosis and assessment. The role of cross-sectional imaging is mainly in the diagnosis of postoperative complications, particularly those that develop as the child grows older. The main complications of the arterial switch operation are RVOT or branch pulmonary artery obstruction. Due to the unusual position of the pulmonary arteries immediately behind the sternum, trans-thoracic echocardiography is poor at detecting these lesions. Cardiovascular MRI is ideal for imaging the RVOT and branch pulmonary arteries in this group of patients (Fig. 23.11). Contrast-enhanced MRA can be used to visualize the relationship between the pulmonary arteries and the aorta, while spin-echo sequences are used to assess accurately the degree of stenosis. A less common complication of the arterial switch operation is coronary stenosis secondary to the re-implantation procedure. Although the majority of coronary complications cause early postoperative mortality, a subset of patients suffers from late coronary events. In this group, coronary catheter angiography probably represents the modality of choice for investigation. However, coronary MRA and MDCT angiography are useful noninvasive methods for investigating the coronary arteries, particularly the proximal segments. Although intra-atrial baffle repair has been superseded by the arterial switch operation, there is a sizeable population that has undergone either a Senning or Mustard operation. The most common complications of intra-atrial repair are baffle obstruction or leak, arrhythmias and right ventricular dysfunction. A combination of contrast MRA, and spin-echo and phase-contrast MRI techniques allows comprehensive assessment of intra-atrial baffles (Fig. 23.11).

Congenitally corrected transposition Congenitally corrected transposition is a rare disorder characterized by both atrioventricular discordance and ventricle–arterial

discordance (right atrium to left ventricle to pulmonary artery to lung; and left atrium to right ventricle to aorta). Thus, although the heart is anatomically abnormal, it is physiologically normal in terms of the pulmonary and systemic circuits. This deformation does not usually cause cyanosis; however, many of the problems are similar to those experienced by patients with TGA. Congenitally corrected transposition (CCTGA) may be asymptomatic and in some patients is an incidental finding. However, the majority of patients with CCTGA have associated cardiac lesions, the most common being VSD. Pulmonary stenosis is present in approximately 50% of cases and tricuspid valve abnormalities (i.e. Ebstein's abnormality) are found in 20% of cases. Even without associated abnormalities, the majority of patients with CCTGA eventually develop systemic ventricular failure. The main role of MRI is in evaluation of associated lesions, quantification of ventricular function, and assessment of postoperative complications.

Double outlet right ventricle In double outlet right ventricle (DORV), both great vessels emerge from the right ventricle, with the left ventricle emptying through a VSD into the right ventricle.The clinical picture and type of surgical correction depend on the arrangement of the great vessels and the anatomy of the VSD. The most common variant is a normal arrangement of the great vessels and a subaortic VSD. This variant is often referred to as the ‘Fallot's type’, as it is often associated with pulmonary stenosis and has a similar presentation. DORV may also be associated with an anterior aorta and a subpulmonary VSD, known as the ‘Taussig–Bing’ anomaly. Surgical correction for the ‘Fallot type’ variant consists of patch closure of the VSD, which redirects blood to the aorta, and correction of any pulmonary stenosis. For the ‘Taussig– Bing’ anomaly the surgical approach depends on the presence of pulmonary obstruction. In the absence of pulmonary obstruction, correction consists of patch closure of the VSD and arterial switch. In the presence of obstruction, left ventricular flow is tunnelled through the VSD to the aorta, and a right ventricle–pulmonary artery pathway is established—the Rastelli procedure. MRI plays an important role in pre-operative assessment. The 3D anatomy of the VSD and the arrangement of the great vessels are well visualized by MRI and are particularly important when deciding the type of surgery. Spin-echo black blood MRI of the VSD has been shown to compare well with surgical findings and is able to indicate the optimal type of repair.

Common arterial trunk Common arterial trunk (truncus arteriosus) is defined as a single arterial trunk arising from both ventricles, which overrides a large misaligned VSD.The pulmonary, systemic and coronary arteries originate from the single common arterial trunk. The classification of common arterial trunk relies on the branching pattern of the pulmonary artery. In Type I, a short main pulmonary artery arises from the common trunk and subsequently divides. In Type II, the right and left pulmonary arteries originate from the posterior wall of the common trunk

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and in Type III, the right and left pulmonary arteries emerge from the lateral wall of the common trunk. The truncal valve is often abnormal with varying degrees of stenosis and insufficiency. About 40% of truncal arches are on the right side: most truncal arches rise higher in the mediastinum than the normal aortic arch. Surgical repair consists of reconstruction of the common trunk to produce a systemic vessel from the left ventricle, patch closure of the VSD and establishment of a right ventricle-to-pulmonary artery conduit. The main role of MRI is in assessment of postoperative complications (homograft failure, truncal valve regurgitation,VSD patch leak). MRA can be used to better delineate the vascular anatomy before surgery.

The single ventricle The single ventricle can be either an anatomical entity, e.g. in tricuspid atresia (single left ventricle) or hypoplastic left heart syndrome (single right ventricle), or a functional entity, where two ventricles are connected by a large VSD. Even when anatomically there is a single ventricle, there is usually a vestigial remnant of the other ventricle. Depending on the size of the ventricles, and the great vessel anatomy, it may be possible surgically to ‘septate’ the ventricles to create a biventricular circuit. If the ventricular sizes are not potentially equal, separation of the pulmonary and aortic circulations is required (the Fontan circulation) (Fig. 23.12), such that the single ventricle pumps blood into the systemic circulation, and systemic venous return is directed to the pulmonary circulation. The creation of this single ventricle circuit is performed in a stepwise surgical fashion (Fig. 23.12).

Bidirectional Glenn circulation The first stage in the creation of a single ventricular circulation is the bidirectional Glenn operation (or hemi-Fontan operation). In this procedure, a side-to-side anastomosis is created between the SVC and the pulmonary arteries, and a patch is inserted to divide the SVC from the right atrium. Any previous surgical systemic-to-pulmonary artery shunts are also

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CONGENITAL HEART DISEASE: GENERAL PRINCIPLES AND IMAGING

taken down at this time. MRI can be used to assess branch pulmonary artery narrowing and pulmonary venous obstruction prior to completion of the Fontan circulation, otherwise the circulation may fail.

Fontan circulation The Fontan circulation (Fig. 23.12) is completed by either anastomosis of the right atrium to the Glenn shunt (classical Fontan operation) or creation of a lateral or extracardiac tunnel between the IVC and the Glenn shunt [total caval pulmonary connection (TCPC)]. The latter procedure is now the preferred option; there remains, however, a sizeable population with a standard Fontan circulation who require diagnostic assessment. Right atrial dilatation is the major complication of the Fontan procedure and the 3D anatomy of the atrium can be delineated by MRI. Right atrial dilatation may cause pulmonary vein compression, which can lead to failure of the Fontan circulation. MRI also evaluates the branch pulmonary arteries and tunnels, and can be used accurately to assess ventricular function.

Hypoplastic left heart syndrome Hypoplastic left heart syndrome (HLHS) is the fourth most common cardiac malformation to present in the first year of life, with an incidence of approximately 266 per million live births. HLHS constitutes a spectrum of CHD with hypoplasia or atresia of the left heart components, and normal relation of the great vessels. At birth, the right ventricle supplies both the systemic and pulmonary circulations via the pulmonary artery and patent arterial duct. After birth, closure of the PDA and the presence of a restrictive patent foramen ovale lead to increasing cyanosis, heart failure and early death. Surgical treatment has been revolutionized by the introduction of the Norwood procedure in 1980 with subsequent conversion to a total cavopulmonary connection (TCPC). At all stages MRI is used to assess fully 3D anatomy, complications, function and flow.

Figure 23.12 Fontan circulation. 3D volume-rendered MRA. (A) Bidirectional Glenn shunt (blue), posterior view. Arrowhead = right pulmonary artery, arrow = left pulmonary artery, asterisk = superior vena cava, dashed arrow = descending aorta. (B) Classical Fontan circulation showing severe right atrial dilation (arrowhead). Arrow = right atrial appendage, asterisk = inferior vena cava drainage. (C) Total caval pulmonary connection (TCPC) lateral tunnel Fontan circulation. Arrowhead = lateral tunnel.

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Abnormal pulmonary venous drainage MRI can help evaluate the course of the pulmonary veins, differentiating forms of partial anomalous pulmonary venous return (e.g. right upper pulmonary vein to SVC in association with ASD–sinus venosus defect) and total anomalous pulmonary venous return. In total anomalous pulmonary venous drainage (TAPVD) the pulmonary veins coalesce posterior to the left atrium, but do not drain into it. Drainage from this venous confluence to the right atrium may be: (a) via either an ascending vein to the innominate vein, and then to the SVC (supracardiac, Type I) (Fig. 23.13A,B); (b) the coronary sinus directly into the right atrium (cardiac, Type II); or (c) via a descending vein, which passes through the diaphragm into either the IVC or portal venous system (infracardiac, Type III) (Fig. 23.13C). The infracardiac type (Fig. 23.13C) is the least common variant and makes up approximately 12% of TAPVD cases. There is a usually a degree of obstruction as the descending vein passes through the diaphragm. Thus, unlike the supracardiac and cardiac variants, which present with a left to right shunt and cardiac failure, the clinical picture for infracardiac TAPVD is one of pulmonary congestion with tachypnoea, tachycardia, liver enlargement, cyanosis, pulmonary oedema and respiratory distress. Symptoms usually appear within 24– 36 h of birth. Importantly, the diagnosis of infracardiac TAPVD can be missed at echocardiography, and must always be considered in the differential diagnosis of pulmonary oedema on the neonatal chest radiograph.

Associations of TAPVD are complex cardiac anomalies such as heterotaxy syndromes (in particular right isomerism), AVSD, pulmonary stenosis, DORV, HLHS, common arterial trunk, transposition of the great arteries and aortic coarctation. The anomalous pulmonary venous connection is easily visualized with ultrasound, but in patients with poor echocardiography acoustic windows, cross-sectional imaging with MRI and CT is very useful, often avoiding the need for a diagnostic X-ray catheterization.

Ebstein's anomaly Ebstein's anomaly is a congenital abnormality of the tricuspid valve. The septal and mural leaflets are more apically placed than normal, resulting in a malfunctioning, regurgitant tricuspid valve and atrialization of the proximal right ventricle5.The consequence is gross right atrial enlargement and raised right atrial pressure. The anomaly is usually associated with an ASD and there is thus right-to-left shunting at the atrial level and subsequent cyanosis. Ultimately, Ebstein's anomaly results in gross enlargement of the cardiac contour with a prominent curved right atrial border on the plain chest radiograph.Treatment is problematical, though expert surgical repair of the tricuspid valve is possible in some centres. MRI can be used to assess the valve morphology, quantify ventricular function and size the right atrial enlargement.

Cor triatrium This is a rare congenital anomaly in which the pulmonary veins and the immediately related left atrium are separated from the main body of the left atrium by a perforated

Figure 23.13 Supracardiac total anomalous pulmonary venous drainage (TAPVD). (A) Angiogram with contrast medium injected into the pulmonary artery. The pulmonary veins (single black arrows) join behind the heart to form a vertical vein (double black arrows) which passes upwards to join the left innominate vein which passes to the right to enter the superior vena cava which enters the right atrium. (From Grainger R G 1970 Transposition of the great arteries and of the pulmonary veins, including an account of cardiac embryology and chamber identification. Clin Radiol 21: 335–354.) (B) Dextrocardia with complex cardiac anomalies. 3D volume-rendered MDCT angiogram viewed from the left anterior oblique showing a supracardiac total anomalous pulmonary venous drainage. The pulmonary veins (white arrows) drain into an ascending vein (asterisk) and then into the brachiocephalic vein (white arrowhead and black crossed arrow) and the superior vena cava, which drains into the right atrium. Double arrow = descending aorta. (C) Total anomalous infradiaphragmatic pulmonary venous drainage (Type 3). Contrast medium injected into the main pulmonary artery illustrates all the pulmonary veins joining behind the heart to form a vertical vein which descends (arrow) through the oesophageal hiatus to enter the portal veins. The vertical vein is often compressed in its lower segment which can contribute to pulmonary oedema. (From Grainger R G 1970 Transposition of the great arteries and of the pulmonary veins, including an account of cardiac embryology and chamber identification. Clin Radiol 21: 335–354.) (With permission from the Royal College of Surgeons.)

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CONGENITAL HEART DISEASE: GENERAL PRINCIPLES AND IMAGING

Figure 23.14 Anomalous coronary arteries. Maximum intensity projection images reconstructed from the 3D coronary MRAs. (A) Oblique sagittal view demonstrating an anomalous origin of the left circumflex (asterisk) from the right coronary artery (arrow). (B) Coronal view demonstrating an anomalous accessory left anterior descending artery (arrowhead) arising from the same ostia as the right coronary artery (dashed arrow).

fibromuscular septum. Cor triatrium is often associated with septal defects, anomalous pulmonary venous drainage and tetralogy of Fallot. Symptoms depend on the size of the orifice in the septum and may present with a syndrome similar to mitral valve stenosis with pulmonary venous congestion and oedema. Diagnosis is best by echocardiography.Treatment is by surgical excision of the obstructing membranous septum.

Coronary arteries Anomalous coronary arteries Although the anomalous origin and epicardial course of the coronary arteries are uncommon entities, they may be the cause of chest pain and sudden cardiac death, often in a younger asymptomatic patient. Together with hypertropic cardiomyopathy and arrhythmogenic right ventricular dysplasia, anomalous origin of the left coronary artery from the right coronary or pulmonary artery is one of the most frequent causes of sudden cardiac death in competitive young athletes. The prevalance of anomalous coronary arteries has been reported to be between 0.3% and 1.0% of the normal population, although this is likely an underestimate, as many asymptomatic individuals may be unrecognized. From an anatomical point of view, the anomalies are classified according to the coronary artery involved, the origin of the anomalous coronary artery, and the anatomical course of the proximal segment. From a clinical point of view, the anomalies are divided into ‘benign’ and ‘malignant’ lesions (Fig. 23.14). The latter, especially those of left coronary artery origin from the pulmonary artery and in which the anomalous artery passes between the aortic root behind and right ventricular outflow tract or pulmonary artery in front, have an increased risk for developing myocardial ischaemia and sudden cardiac death. Even with multiple projections, the precise location of the proximal course of the vessel in a patient with an abnormal origin of a coronary artery can be difficult to depict with conventional angiography. However, MRA and CT angiography provide reliable visualization of the root of the arteries, and the coronary artery tree (Fig. 23.14).

CONCLUSION Cardiovascular imaging is important for the diagnosis and follow-up of children and adults with CHD. In young patients, echocardiography is the first-line imaging modality; however, when echocardiography cannot provide a complete diagnosis, cross-sectional imaging with MRI and CT is rapidly becoming the next line of investigation, with interventional catheter angiography reserved for problem solving, the assessment of the coronary arteries and pulmonary vascular resistance, and for catheter-guided therapeutic procedures. In older children and adults, where echocardiography is less easy (poor acoustic windows and multiple operations), crosssectional imaging is essential. MRI in particular is important in this setting, as there is no radiation burden, and both anatomy and function can be assessed in order to suggest optimal follow-up and timing of future interventions. Used in combination, echocardiography, MRI, CT and Xray catheter angiography can provide a complete assessment of patients with CHD.The further application of MRI and CT to CHD should enable radiologists to take a more proactive role in the assessment of CHD in a multidisciplinary team setting.

Acknowledgements We would like to acknowledge the following for their help and support: Professor Jan Bogaert, Professor Steven Dymarkowski, Professor Reza Razavi, Dr Vivek Muthurangu, Dr. Sanjeet Hegde, Professor John Deanfield, Professor Philipp Bonhoeffer, Dr. Catherine Owens and Springer-Verlag.

REFERENCES 1. Grainger R G 1985 The pulmonary circulation: The radiology of adaptation. Clin Radiol 36: 103–116 2. Grainger R G 1970 Transposition of the great arteries and of the pulmonary veins, including an account of cardiac embryology and chamber identification. Clin Radiol 21: 335–354 3. Anderson R H, Baker E J, Macartney F J, Rigby M L, Shinebourne E A, Tynan M (eds) 2002 Paediatric cardiology, 2nd edn. Churchill Livingstone, London, 2002

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4. Hoffman J I, Kaplan S 2002 The incidence of congenital heart disease. J Am Coll Cardiol 39: 1890–1900 5. Anderson R H, Razavi R, Taylor A M 2004 Cardiac anatomy revisited. J Anat 205: 159–177 6. Snider A R, Serwer G A, Ritter S B 1997 Echocardiography in pediatric heart disease. Mosby, St Louis 7. Iskandrian A E, Verani M S (eds) 2002 Nuclear cardiac imaging: Principles and applications. Oxford University Press, New York 8. Bogaert J, Dymarkowski S, Taylor A M (eds) 2005 Clinical cardiac MRI. Springer, New York

9. Ohnesorge B M, Becker C R, Flohr T G, Reiser M F (eds) 2005 Multi-slice CT in cardiac imaging: Technical principles, imaging protocols, clinical indications and future perspective. New York, Springer 10. Gatzoulis M A, Webb G A, Piers Daudeney P (eds) 2003 Diagnosis and management of adult congenital heart disease. Churchill Livingstone, London 11. Khambadkone S, Coats L, Taylor A et al 2005 Percutaneous pulmonary valve implantation in humans – Results in 59 consecutive patients. Circulation 112: 1189–1197

CHAPTER

Nonischaemic Acquired Heart Disease

24

Hrudaya Nath and Satinder P. Singh

• Role of imaging • Valvular heart disease • Prosthetic cardiac valves • Diseases of the heart muscle (cardiomyopathies) • Tumours of the heart • Trauma to the heart

The incidence of cardiac disease is steadily rising all over the world, and at the beginning of the 21st century, cardiovascular disease caused nearly half the deaths in the developed world, and about 25% in the developing world1. Coronary arterial disease accounts for slightly greater than half of these cases2. The remainder form a heterogeneous group of diseases, including acquired valve diseases, diseases of the heart muscle (most resulting from hypertension), cardiac tumours, and trauma. These nonischaemic causes of acquired heart disease (NIHD) are the subject of this chapter.

ROLE OF IMAGING The diagnosis, assessment, and follow-up of NIHD have changed considerably over the years. While chest radiography is still useful in judging cardiac size and pulmonary haemodynamics, echocardiography and cardiac magnetic resonance imaging (MRI) have become increasingly useful. Echocardiography remains the most important imaging method in assessing ventricular function and status of the cardiac valves, and estimating transvalvar gradient as well as pulmonary artery pressures. Helical computed tomography (CT), particularly the emerging faster multidetector CT systems (MDCT) using ECG gating, is beginning to make inroads into the assessment of NIHD. This technology has the potential to become even more important in patients with contraindications for MRI.

Chest radiography While very non-specific, postero-anterior (PA) and lateral views of the chest are the most frequently performed radio-

graphic examinations in the evaluation of cardiac disease. In many conditions of NIHD, the chest radiographs are normal. However, when abnormalities are noted, they are quite useful in judging the functional state of the heart and for serial follow-up. Cardiomegaly (when the cardiothoracic ratio in a PA view of the chest exceeds 50%) is a very useful sign in detecting cardiac dysfunction, and is often due to ventricular enlargement. Right atrial enlargement and pericardial effusion, in the absence of ventricular enlargement, are far less common causes of enlargement of cardiac silhouette. Chest radiographs can also frequently detect moderate to significant left atrial enlargement (Fig. 24.1). It is not possible to confidently distinguish between right and left ventricular enlargement and detection of mild degrees of enlargement of any cardiac chamber (e.g. compared to chamber dimensions from echocardiography or MRI). Chest radiography may also detect abnormal cardiac calcifications, most notably that of the aortic valve (Fig. 24.2) and mitral annulus (Fig. 24.3). Chest radiographs are also useful in assessing pulmonary venous hypertension and pulmonary oedema (Fig. 24.4). However, in patients with chronic, compensated congestive failure, often the only radiographic abnormality is cardiac enlargement.

Echocardiography Echocardiography is a noninvasive, portable imaging technique that allows high-resolution, two- and three-dimensional (2D and 3D) views of the cardiac chambers, valves, and pericardium.These techniques, either with a transthoracic or semi-invasive transoesophageal approach, can assess cardiac anatomy and ventricular function. When combined with Doppler and colour Doppler techniques, valvar regurgitation and transvalvar pressure gradients can also be assessed. Echocardiography is the most commonly performed imaging examination in the assessment of NIHD.

Magnetic resonance imaging Cardiac magnetic resonance imaging (CMR) is rapidly becoming a very useful imaging method in the assessment of NIHD. Its role is most valuable in (A) serial measurement of

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Figure 24.3 Lateral view of chest shows C-shaped dense calcification of the mitral annulus (arrows). Figure 24.1 Classical appearance of rheumatic mitral stenosis. PA view of the chest. The heart size is normal. The enlarged left atrium (A) displaces the left bronchus upwards (asterisk) and creates a right retrocardiac double density. The left atrial appendage is enlarged (arrowheads). There is severe pulmonary venous hypertension.

ventricular function in patients with cardiomyopathy (considered superior to echocardiography in reproducibility); (B) evaluation of valve function, including stenosis and regurgitation; (C) morphology and extent of involvement in cardiac tumours; and (D) value of post-contrast delayed enhancement in determining prognosis in hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), as well as many types of infiltrative myocardial diseases including sarcoidosis and myocarditis.

Figure 24.2 Aortic valve calcification. Lateral chest radiograph shows several calcifications in the aortic valve (arrow).

Computed tomography Until recently, conventional computed tomography (CT) had little role in the evaluation of NIHD. While electron beam CT is comparable to echocardiography and CMR in assessing cardiac function, its limited availability was a drawback to its widespread use. The increasing use of ECG-gated helical CT techniques coupled with greater than 16-detector MDCT has

Figure 24.4 PA view of the chest. Severe mitral re-stenosis following closed mitral commissurotomy. The heart is enlarged. Note the concavity in the region of the left atrial appendage resulting from closed commissurotomy (arrows). Compare to Fig. 24.1 (typical mitral stenosis).

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the potential to make cardiac CT a viable alternative in assessing cardiac function. More recently cardiac CT was shown to be useful in the assessment of valvar function3. However, at present, CT has no demonstrable advantage over echocardiography and CMR in the evaluation of NIHD.

VALVULAR HEART DISEASE In the past few decades the aetiology of acquired valve disease shifted from rheumatic and infective causes to degenerative diseases, with increasing prevalence of mitral regurgitation and aortic stenosis compared to the higher incidence of mitral stenosis and aortic insufficiency. Consequently, the age at which these diseases become clinically evident also has advanced. Many of these disease processes have few radiographic findings, and their evaluation primarily involves echocardiography4.

Mitral valve disease5 In the western world, non-rheumatic mitral valve disease is now the most common manifestation of mitral valve abnormality. Rheumatic heart disease, with the virtual disappearance of rheumatic fever, has become a relative rarity in the western world. Worldwide, rheumatic heart disease still remains a prevalent and dangerous condition.

Non-rheumatic mitral valve disease Non-rheumatic disease is usually manifest as mitral regurgitation: non-rheumatic mitral stenosis is extremely rare. Many conditions can result in significant mitral regurgitation (Table 24.1). Mitral valve prolapse6 Elongation of the chordae tendineae associated with myxomatous degeneration of the valve leaflets allows prolapse of the mitral valve leaflets back into the left atrium in ventricular systole. The condition most commonly

Table 24.1

CAUSES OF MITRAL REGURGITATION

Abnormalities of valve leaflets Mitral valve prolapse (idiopathic, Marfan’s syndrome) Bacterial endocarditis Prosthetic mitral valve leaks Mitral commissurotomy/balloon valvuloplasty Congenital (endocardial cushion defect, etc.) Mucopolysaccharidosis Systemic lupus erythematosis Rheumatoid arthritis

Abnormalities of supporting structures Dilatation of mitral valve annulus Ruptured chordae tendineae Ischaemic heat disease causing papillary muscle Dysfunction, rupture Hypertrophic cardiomyopathy Mitral annular calcification Atrial myxoma

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occurs alone but may also occur in Marfan’s syndrome and is frequently seen in patients with atrial septal defect. The diagnosis is made by 2D ultrasound (US), mitral prolapse also being visible on CMR (Fig. 24.5) and conventional left ventriculography (Fig. 24.6). The severity of the pathological change varies from involvement of one of the three scallop-shaped segments of the posterior leaflet of the mitral valve, to the whole of both leaflets. Prolapse of the mitral valve may be associated with chest pain and ECG changes, which may suggest ischaemic heart disease. Chordal rupture Mitral regurgitation may also result from rupture of groups of chordae tendineae, which may complicate bacterial endocarditis or less frequently myocardial infarction or connective tissue diseases.This allows part of a leaflet to flail, preventing proper co-aptation in systole and producing severe mitral regurgitation.The murmur is usually mid to late systolic in onset. When this event occurs suddenly, acute pulmonary oedema may occur, with normal cardiac size (Fig. 24.7). The severity of mitral regurgitation can be estimated with CMR and echocardiography, where signal loss due to turbulent regurgitant flow allows semiquantitative assessment of regurgitation (Fig. 24.8). More accurate estimates of the severity of mitral regurgitation use phase-contrast CMR, comparing forward mitral flow with forward aortic flow7. In the absence of aortic regurgitation or a ventricular septal defect, the difference indicates the amount of mitral regurgitation. One of the most widely used applications of intra-operative transoesophageal US is in determining the functional status of mitral valve repair by detecting and quantifying mitral regurgitation during the repair, thus allowing further correction if necessary. Bacterial endocarditis may lead to mitral regurgitation by causing cusp perforation or chordal rupture. Vegetations and penetrating abscesses may also interfere with valve function. While these abnormalities can be well shown by transthoracic US or MRI, transoesophageal US may be required to best show paravalvar abscesses or cusp perforation. Subacute bacterial endocarditis usually, but not invariably, affects abnormal valves, while acute bacterial endocarditis can affect normal or abnormal valves. Papillary muscle dysfunction/rupture Mitral regurgitation may also result from papillary muscle dysfunction. This is the presumed origin of the systolic murmurs that are commonly heard in the course of inferior myocardial infarction, though the amount of regurgitation is rarely significant.When the papillary muscle ruptures as the result of myocardial infarction, the degree of regurgitation is massive and often rapidly fatal, unless it can be urgently corrected surgically. Functional mitral regurgitation Mitral regurgitation may also result from dilatation of the left ventricle (possibly by causing tethering of chordae tendinae), or mitral annulus dilatation, as

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Figure 24.5 Mitral valve prolapse. (A) M-mode echocardiography shows late systolic prolapse of the posterior mitral leaflet (arrows). (B) 2D echocardiography (parasternal long axis) in the same patient shows posterior mitral leaflet prolapse (arrow) into the left atrium. (C) Colour Doppler (apical four-chamber) in the same patient shows an eccentric jet of mitral regurgitation (following direction of arrows). Gradient-echo cine-MRI (D) four-chamber projection and (E) left ventricular outflow tract (LVOT) view. There is bulging of the posterior cusp of the mitral valve into the left atrium (arrow). There is moderate mitral regurgitation (arrowheads), better seen on the LVOT view (E). Ao = Ascending aorta, LA = left atrium, LV = left ventricle, RA = right atrium, RV = right ventricle.

occurs in dilated cardiomyopathy or ischaemic cardiac failure9. Mitral regurgitation in these situations is very common, but is rarely severe. The appearances on chest radiography depend on the duration and severity of the mitral regurgitation and any other associated heart disease. Acute, severe, non-rheumatic mitral regurgitation may present with pulmonary oedema, but with a virtually normal heart size and shape. After an interval, the heart usually compensates by developing left ventricular dilatation, which may be marked (Fig. 24.9). Selective left atrial enlargement may be absent, slight, or moderate, and the left atrial appendage is usually not enlarged. Pulmonary vascular changes reflect the haemodynamic derangement and the effects of treatment. Mitral annulus calcification10 Calcification occurs in the angle between the left ventricle wall and the mitral valve cusps, and is readily recognized on the chest radiograph as a C-shaped open ring (see Fig. 24.3); the gap in the ring occurs where the anterior mitral leaflet base is in contact with the posterior aortic valve ring. Calcification rarely occurs before the age of 70 years and is more common in women. The mitral annulus calcification is not always benign, since it may be associated with transient ischaemic attacks due to

emboli or carotid stenosis, and atrioventricular conduction disturbances11. Mitral valve function may be affected, most commonly leading to mild mitral regurgitation, but significant mitral stenosis from heavy annulus calcification has been described. The risk of infective endocarditis may be increased. There is suggestion that mitral annular calcification is another marker for atherosclerosis, and premature calcification may be seen in hypercalcaemic states, particularly in patients with end-stage renal disease.

Rheumatic mitral valve disease Acute rheumatic carditis results in a pancarditis. During this phase, mitral regurgitation is often present, resulting from myocarditis. Such mitral regurgitation is usually transient and reversible, as the myocarditis subsides. Chronic rheumatic mitral valve disease often results in stenosis. This is the result of fusion of the commissures, thickening and shortening of the chordae tendineae, with fibrosis of the papillary muscles. Often there is a combination of all these features, in varying degrees. Depending on the severity of the process, pure valve regurgitation results if there is extensive leaflet destruction. Pure stenosis results if commissural fusion occurs with virtually normal leaflets, but the most common result is a mixture of mitral stenosis and regurgitation, either of which may be

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Figure 24.6 Non-rheumatic mitral regurgitation due to mitral valve prolapse. Left ventriculography (right anterior oblique [ROA] projection). (A) Diastole. Arrows indicate the recess under the mitral valve, which persists in diastole. (B) Early systole. Prolapse of the mitral valve (arrows) is just appearing. (C) Mid systole. Mitral valve prolapse (arrows) has reached its fullest extent. (D) Late systole. After maximum prolapse, reflux into the left atrium (arrowhead) begins.

worsened by chordal involvement. Now it is believed that the valve stenosis results from a combination of the smouldering rheumatic process as well as abnormal turbulence from the flow across the fused commissures, resulting in fibrosis of the valve structures and superimposed calcification12. Mitral stenosis, if present, limits the amount of regurgitation, so that both cannot be severe at the same time. Other acquired causes of mitral stenosis are extremely rare and congenital mitral stenosis is quite uncommon. Valve replacement or valvuloplasty is indicated for severe stenosis (valve area 0.8–1.2 cm2 depending on the exercise tolerance required). Mitral valve disease increases left atrial pressure: this is transmitted back to the pulmonary veins and, when severe, leads first to interstitial and then to alveolar pulmonary oedema. Parenchymal lung changes of haemosiderosis and intrapulmonary ossification may appear after several years of pulmonary venous congestion (Fig. 24.10B). Secondary pulmonary arterial hypertension may develop and lead to pulmonary valve regurgitation, right ventricular dilatation, and functional tricuspid regurgitation. There may also be organic involvement of the tricuspid valve by the rheumatic process, leading to either tricuspid stenosis and/

or regurgitation. Long-standing mitral stenosis can result in atrial fibrillation, complicated by thrombi in the left atrium. These thrombi can result in systemic emboli. Clinical features After the attack of rheumatic fever, mitral valve damage may remain asymptomatic until stenosis becomes critical or regurgitation becomes severe, when clinical cardiac failure develops. In western countries a history of rheumatic fever is often absent. Acute cardiac failure may be precipitated by the development of atrial fibrillation, an almost inevitable consequence of rheumatic mitral valve disease. Chest radiography The cardinal radiological feature of rheumatic mitral valve disease is left atrial enlargement. The left atrial appendage is particularly affected; when it is seen to be enlarged this suggests a rheumatic aetiology. The appearances vary from a simple straightening of the left heart border (see Fig. 24.1) to a large bulge in the characteristic site of the appendage, immediately below the left main bronchus (Fig. 24.10). The left atrium, when grossly dilated, can also enlarge to the right (Fig. 24.11) posteriorly causing dysphagia.

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Figure 24.7 Acute mitral regurgitation due to chordal rupture in a patient with mitral valve prolapse. (A) Baseline PA view of the chest which appears normal apart from hiatus hernia. (B) At the time of acute mitral regurgitation, note the enlarged heart, left atrial and ventricular enlargement, and greater pulmonary oedema in the right lung.

The features of enlargement of the left atrium vary from being visible on the plain chest radiograph as a ‘double density’ through the heart (see Fig. 24.1), to ‘aneurysmal enlargement’ when the left atrium reaches to within an inch or so of the chest wall on one or both sides of the chest.Very large left atria are more commonly seen in long-standing mitral regurgitation with atrial fibrillation. Occasionally, a large left atrium may displace the oesophagus backwards and to the left instead

Figure 24.8 Mitral regurgitation. Axial gradient-echo systolic MRI shows a jet-like signal void in the left atrium due to moderate mitral regurgitation. LA = Left atrium, LV = left ventricle, RA = right atrium, RV = right ventricle.

of the more frequent displacement to the right. Enlargement of the left ventricle is not a feature of pure mitral stenosis but is seen with significant mitral regurgitation. Calcification may occur, either in the wall of the left atrium, or in clot lining the wall (Fig. 24.12).The calcification is usually curvilinear, at least in part, and lies fairly high in the cardiac shadow, higher than is usually seen with pericardial calcification. The lateral radiograph shows calcification in the upper posterior aspect of the heart at the top of the left atrium. Fluoroscopy or CT can be used to detect dystropic calcification that takes place in the mitral valve in long-standing rheumatic valve disease. It occurs in the mitral valve, lying between the left atrium and left ventricle, near the postero-inferior aspect of the heart in the lateral view. Unlike the J- or C-shape of mitral annulus calcification (see Fig. 24.3), calcification in the mitral valve itself is strongly suggestive of a rheumatic aetiology. The right ventricle is enlarged if there is pulmonary arterial hypertension, pulmonary valve regurgitation, or tricuspid valve regurgitation. Tricuspid valve disease, stenosis, or regurgitation may be suspected if there is right atrial enlargement. The constantly present left atrial hypertension is reflected back into the pulmonary veins and produces changes in the pulmonary vascularity and the lungs that may be seen on the plain chest radiograph (see Figs 24.1, 24.4). Symptomatic mitral stenosis of such severity as to require surgical treatment may, however, be present with an entirely normal chest radiograph, particularly if diuretic treatment is vigorous. Closed mitral valvotomy, with amputation of the left atrial appendage to access the valve via the left atrium, produces

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Figure 24.9 (A) Acute mitral regurgitation, ruptured chordae tendineae. Acute onset of dyspnoea. The heart size is normal with some straightening of the left heart border. The lungs show upper lobe blood diversion and pulmonary oedema. (B) Compensated phase (another patient). The physical signs of non-rheumatic mitral regurgitation were present. The heart shows compensatory left ventricular enlargement but no evidence of left atrial enlargement.

a concavity in the left heart border below the left bronchus (see Fig. 24.4).This may give the heart a left ventricular configuration, making left ventricular enlargement difficult to assess. The relative contribution of mitral stenosis and regurgitation cannot be recognized with certainty, and might be due to an associated aortic valve lesion. If the left atrium is very large, mitral regurgitation should be suspected. Echocardiography is the best method for routine assessment of mitral valve disease.

Other imaging techniques In mitral stenosis, CMR shows restricted opening of the mitral valve and thickened leaflets (Fig. 24.13). Phase-contrast CMR can be used as a substitute for Doppler in assessing valve area. In mitral regurgitation, CMR can be used as a semiquantitative method for assessing mitral regurgitation in the same way as colour Doppler13. Cardiac catheterization and angiocardiography is used in those rare situations where US has failed to elucidate the contribution of each

Figure 24.10 (A) Severe mitral valve disease. The left atrial appendage is large, producing a convex bulge (arrow). The heart is considerably enlarged. (B) Pulmonary haemosiderosis in mitral stenosis. Long-standing severe mitral stenosis. The heart and left atrium are enlarged. Bilateral nodular interstitial prominence is due to pulmonary haemosiderosis.

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Figure 24.11 Severe mitral valve disease. (A) The left atrium (white arrow) has enlarged to the right, protruding well beyond the border of the right atrium (black arrowheads). (B) It is also enlarged posteriorly, displacing the barium-filled oesophagus (and the left bronchus) posteriorly. The left atrial appendage is not grossly enlarged.

valve lesion, or when coexistent coronary artery disease needs assessment.

Tricuspid valve disease The tricuspid valve may be directly involved by rheumatic disease, producing organic regurgitation (Fig. 24.14) or, less commonly, stenosis. The tricuspid valve may also become functionally regurgitant when the right ventricle becomes dilated in the presence of pulmonary hypertension, e.g. secondary to mitral valve disease. Severe tricuspid regurgitation is now being seen more often in patients who have undergone mitral valve replacement many years previously. In Ebstein’s anomaly (Fig. 24.15), the insertion of the septal cusp of the tricuspid valve is displaced towards the apex of the right ventricle. Severe tricuspid regurgitation can also occur in

endomyocardial fibrosis when the papillary muscles become scarred and retracted. In carcinoid syndrome, the valve cusps are mildly thickened and shortened; in long-standing cases they may not be identifiable. There is subendocardial fibrosis of the right ventricle, increasing its stiffness. Carcinoid syndrome usually causes tricuspid regurgitation but may also cause tricuspid stenosis.

Other causes of tricuspid valve abnormality The tricuspid valve may be made regurgitant by endocarditis, a frequent cause where intravenous drug abuse is widespread. Infective emboli to the lungs may cause cavitating pneumonia.The tricuspid valve may be disrupted by trauma. It may be abnormal in congenital heart disease, especially in congenital stenosis, Ebstein’s anomaly (Fig. 24.15), and corrected transposition of the great arteries.

Figure 24.12 Mitral stenosis and regurgitation following mitral commissurotomy. (A) PA and (B) lateral views of the chest. There is massive left atrial dilatation and partly calcified mural thrombus in the dilated left atrium (arrows in B). Note the left thoracotomy.

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Figure 24.15 Ebstein’s anomaly. Gradient-echo axial MRI. Due to adherence of septal and posterior leaflets of tricuspid valve to the right ventricle, the free portion of the leaflets (arrows) is located at a variable distance below the atrioventricular annulus within the right ventricle (RV) (downward displacement). The right atrium (RA) and the atrialized portion of the RV (asterisk) are enlarged with reduced functional RV chamber size.

Figure 24.13 Mitral stenosis. (A) CMR, four-chamber projection (diastolic image) shows a large right heart due to chronic mitral stenosis with an atrial septal defect (ASD) (open arrow)—Lutembacher syndrome. There is restricted opening of the mitral valve (between curved arrows). The left atrium is not significantly enlarged due to the coexisting ASD. (B) CMR, four-chamber projection. There is fusion of commissures and doming of the mitral valve (arrows).

The clinical recognition of tricuspid valve disease can be difficult. High venous pressure with a big ‘v’-wave and a pulsating enlarged liver suggests tricuspid regurgitation. A slow ‘y’ descent in neck vein pulsation suggests tricuspid stenosis. The murmurs of tricuspid and mitral valve disease are similar.

Figure 24.14 Tricuspid valve regurgitation (arrows). CMR, fourchamber projection, systolic image. LA = Left atrium, RA = right atrium.

Tricuspid valve disease produces a large right atrium, bulging to the right and increasing the curvature of the right heart border, or by detecting enlargement of right atrial appendage in the lateral projection, seen as increased retrosternal density in the lateral projection superior to the expected location of the right ventricle. This is usually seen just below the level of the aortic arch. A prominent right atrium developing in rheumatic heart disease always suggests tricuspid valve involvement (Fig. 24.16). Sometimes regression of right atrial enlargement may be seen in functional tricuspid regurgitation when mitral valve disease is treated. In the authors’ experience, right atrial enlargement, unless gross, is difficult to assess when other cardiac chambers are enlarged. Rheumatic tricuspid valve calcification is almost unknown. As with mitral disease, US is usually the definitive investigation. When regurgitation is very severe, the pressure

Figure 24.16 Tricuspid valve disease. Gross right atrial enlargement (arrow), extending to the right, developing in a patient with severe mitral valve disease, leading to right heart failure.

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drop across the valve is low or, in the absence of effective resistance at the level of the orifice, it may be absent altogether. Velocities are therefore low, with peak values occurring early in right ventricular ejection, and equilibration of right ventricular and right atrial pressures before the end of systole. Severe regurgitation can usually be recognized on colourflow Doppler or CMR, although it should be remembered that when the valve is effectively absent, regurgitant velocities may be so low that they do not cause aliasing, and so may not immediately be recognized.

Aortic valve disease Aortic stenosis This section considers acquired stenosis of the aortic valve in adults14. Congenital aortic stenosis, supravalvar and subvalvar aortic stenosis are considered in Chapter 23. Acquired aortic stenosis may be degenerative or inflammatory. Calcific aortic stenosis The changes in the natural history of valve disease not only refer to rheumatic heart disease but also to the aortic valve. Previously, aortic stenosis in adults was most commonly due to calcification on a congenitally deformed bicuspid valve. This condition occurs in patients over 30 years old, especially men.The predominant cause of aortic stenosis in western industrialized countries now appears to be degenerative calcific disease in middle-aged or elderly patients15. Unlike in mitral stenosis, where calcium is deposited on an already stenosed valve, calcific aortic stenosis results from the deposition of masses of calcium on the aortic cusps which obstruct outflow by their bulk as well as by stiffening the cusps. Thus

calcification causes the stenosis. Other common causes include rheumatic heart disease and degeneration of a normal trileaflet aortic valve (usually in a more elderly population). Clinical presentation may include breathlessness, chest pain, or syncope. The ejection click of the bicuspid aortic valve, detected in earlier life, disappears as the cusps become rigid and is replaced by an ejection systolic murmur. Usually left ventricular hypertrophy is seen on the ECG.The clinical diagnosis and assessment of severity are usually straightforward, though in the elderly with severe aortic stenosis and heart failure, recognition of the systolic murmur can be very difficult.The chief differential diagnostic problem is presented by the combination of a systolic murmur and left ventricular hypertrophy, and this may be due to aortic stenosis, non-rheumatic mitral regurgitation, or hypertrophic cardiomyopathy. Echocardiography distinguishes between these. Chest radiography Rounding of the cardiac apex may suggest left ventricular hypertrophy; however, there is usually some degree of cardiac dilatation, which may be marked if there is aortic regurgitation. Localized prominence of the ascending aorta may indicate post-stenotic dilatation, but in older patients the whole thoracic aorta may be widened from atherosclerosis (Figs 24.17, 24.18). The lateral view may show aortic valve calcification (see Fig. 24.2). This is best seen by fluoroscopy or CT (Fig. 24.19). The extent of calcification has only a rough relationship to the severity of the stenosis. Significant aortic stenosis may be present with a virtually normal frontal image, though there is usually evidence of left ventricular enlargement on the lateral view. There may be no visible aortic abnormality.

Figure 24.17 Aortic valve calcification. (A) PA and (B) lateral views of chest. A 45 year old male with calcific stenosis of bicuspid aortic valve. There is prominence of the ascending aorta in the PA view (arrows). In the lateral view, left ventricular hypertrophy is identified by the positive Rigler sign. Arrows = Calcified aortic valve, arrowheads = outline of inferior vena cava.

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Figure 24.18 Complications of aortic valve replacement. (A) PA and (B) lateral views of the chest. There is aneurysm of the ascending aorta with a Bjork–Shiley aortic valve prosthesis inserted 10 years ago. CT (not shown) demonstrated chronic proximal aortic dissection with aneurysm of the false channel.

Other imaging techniques Calcification in the aortic valve leaflets and adjacent aortic root is well shown by CT17 (Fig. 24.19), which may lead to the diagnosis before the development of symptoms. Ultrafast CT can assess the severity of aortic stenosis by imaging the aortic valve opening but this is not used routinely. CMR can demonstrate impaired aortic valve opening, morphology of the valve (bicuspid or tricuspid, presence of calcification), and assess stenosis, although less accurately than Doppler (Fig. 24.20).The area of systolic flow dephasing seen in the aortic root on CMR has a loose relationship to the severity of aortic stenosis (Fig. 24.20). However, phase-contrast techniques and

planimetry of the aortic valve during systole in gradient-echo sequences obtained in a view optimized to demonstrate the aortic valve in its cross-section (Fig. 24.21) have fair accuracy and compare favorably with US18. During phase-contrast imaging, care should be taken to set theVENC value sufficiently high to detect the highest peak velocity. Left ventricular function and hypertrophy are accurately measured by CMR, which is probably the most accurate method for determining ventricular mass. Associated aortic regurgitation is shown by diastolic flow dephasing in the left ventricular outflow tract (Fig. 24.22). On CMR the cross-sectional area of the flow dephasing immediately below the aortic valve is probably the best guide to the severity of aortic regurgitation, although some advocate phase-contrast MRI19. In older adults with aortic stenosis, there is frequent association of coronary artery disease, and coronary angiography is necessary before surgery for valve replacement. Rheumatic aortic stenosis is caused by inflammatory fusion of the commissures of the aortic valve cusps. It is often associated with aortic regurgitation and usually involvement of the mitral valve.The clinical features are similar to those of calcific aortic stenosis, but dyspnoea is usually pronounced because of associated mitral disease. Additional valve lesions complicate clinical assessment, and US is often required to determine the relative severity of each lesion.

Figure 24.19 Aortic valve calcification. Axial CT at aortic valve level shows calcification of the aortic leaflets (arrows).

Chest radiography The appearances of rheumatic aortic stenosis are commonly dominated by the presence of associated mitral valve disease, producing left atrial enlargement and making recognition of any left ventricular disorder difficult. Post-stenotic dilatation of the aorta is rare in rheumatic aortic stenosis, though the aorta may be dilated if there is also aortic regurgitation. Gross aortic valve calcification is rare in rheumatic disease.

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Figure 24.20 Tricuspid aortic stenosis. CMR of (A) aortic valve view, diastolic image, (B) left ventricular outflow tract (LVOT) view, systolic image, and (C) coronal, ascending aorta view. In the aortic valve view (A), fusion of the commissures of a markedly thickened valve is noted (arrowheads). Doming of the valve leaflets is noted in the LVOT projection (arrowheads) (B). The systolic image demonstrates the turbulent jet (arrows) from aortic stenosis (C). AO = ascending aorta, LA = left atrium, LV = left ventricle, PA = pulmonary artery, RA = right atrium, RV = right ventricle. (D) 2D US, short-axis view, showing distribution of calcification in the aortic valve cusps (arrows). The true valve area cannot be seen due to limited spatial resolution and acoustic shadowing by calcifications. (E) 2D US in same patient, parasternal long axis view, showing the stenosed aortic valve (open arrow). There is left ventricular hypertrophy due to aortic stenosis. The posterior wall of the left ventricle is thickened (between curved arrows) and there is a large posterior pericardial effusion (p).

Figure 24.21 Severe aortic stenosis. (A) Short-axis CMR of the aortic valve (diastole) in severe aortic stenosis shows a trileaflet appearance with areas of irregular low signal intensity indicating areas of calcification (arrows). (B) Short-axis CMR of the aortic valve in the same patient (systole) shows restricted opening of the aortic valve (arrow = valve orifice).

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In rheumatic aortic regurgitation, there is a slow destruction of the free edges of the cusps, often with commissural fusion. Rheumatic aortic regurgitation may occur alone or in association with aortic stenosis, but almost always with involvement of the mitral valve. The slow onset of chronic aortic regurgitation allows the left ventricle to dilate to receive the regurgitant flow, compliance increases, and end-diastolic pressure remains low until cardiac failure develops. Aortic regurgitation remains asymptomatic until the patient develops heart failure. Once cardiac failure develops, the prognosis is markedly worsened but the natural history is difficult to predict; many patients may remain asymptomatic for many years. It is as important to avoid too early a valve replacement as it is to delay too long, when irreversible ventricular dysfunction may have developed. Deterioration is heralded by a changing ECG and an enlarging heart as detected by US or chest radiography. Figure 24.22 CMR in aortic regurgitation due to aortic dilatation. Left anterior oblique equivalent view shows the dilated aortic root and a jet of signal loss in the left ventricular outflow due to aortic regurgitation (arrow).

Aortic regurgitation Aortic regurgitation may result from disease of the cusps of the

aortic valve, or from disease of the aortic walls (Table 24.2). Cusp involvement may precipitate acute aortic regurgitation in bacterial endocarditis or, rarely, after trauma or as a result of acute avulsion of a leaflet into the left ventricle in aortic dissection. Chronic aortic regurgitation may be the result of congenital deformity (bicuspid aortic valve or subarterial ventricular septal defect) or rheumatic heart disease. Aneurysms of the ascending aorta may cause dilatation of the valve ring, leading to aortic regurgitation. Chronic aortic regurgitation The common causes of acquired aortic regurgitation are complications of a congenital abnormality of the valve or rheumatic heart disease.The congenital deformity is often a bicuspid valve in which the inadequately supported cusps allow progressive development of aortic regurgitation; there may be some degree of stenosis because of inadequate development of the valve commissures or dystropic calcification.

Table 24.2 CAUSES OF AORTIC REGURGITATION Degenerative Congenital (bicuspid or unicuspid valve) Rheumatic (with or without coexistent aortic stenosis) Subacute or acute bacterial endocarditis Aortic dissection Takayasu’s arteritis Marfan’s syndrome Ankylosing spondylitis Rheumatoid arthritis Ehlers–Danlos syndrome Syphilis Trauma Surgical or balloon valvoplasty

Chest radiography Chronic aortic regurgitation may produce dramatic appearances, with enlargement of the left ventricle which may be very severe. Enlargement parallels the severity of the condition and is one factor suggesting the need for surgical intervention. After surgery the reduction in heart size may be considerable (Fig. 24.23). The whole thoracic aorta may be moderately enlarged, unless there is aortitis or chronic aortic dissection, when aortic dilatation may be considerable. Valve calcification is not as marked but flecks of calcium may be seen. When mitral valve disease is present, left atrial enlargement may dominate the appearance, obscuring significant left ventricular enlargement. Other imaging techniques US is the main imaging technique for most patients with aortic valve disease. The complications of endocarditis such as paravalvar abscess may be better seen with CMR. Aortic root diseases such as annuloaortic ectasia or dissection are best investigated by CT angiography (CTA) or CMR20, and the severity of aortic regurgitation can be estimated from the extent of signal loss on CMR (see Fig. 24.22). In stable patients, CMR is the most accurate method for delineating almost all diseases of the thoracic aorta and simultaneous evaluation of the left ventricular function27,28. The evolving ECG-gated cardiac CT can provide similar information, and is a satisfactory alternative to CMR, particularly when the latter is contraindicated. There is a limited role for conventional aortography if good CMR or CT is available. As with aortic stenosis in adults, coronary angiography may be necessary in some patients with aortic regurgitation. In patients with large aneurysms of the aortic root, selective catheterization of the coronary arteries may be very difficult. In such patients, coronary CTA may provide all the necessary information in presurgical planning. Acute aortic regurgitation results from acute damage to the cusps, usually by bacterial endocarditis, very rarely by trauma, or even by spontaneous avulsion of the cusps. It may also result from acute dissecting aneurysms of the aorta. Severe aortic

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Figure 24.23 Chest radiographs in pure aortic regurgitation. (A) Pre-operative radiograph. There is marked left ventricular enlargement. The aorta is slightly prominent but there is no post-stenotic dilatation. (B) Radiograph 8 years later after aortic valve replacement. There has been a marked reduction in the heart size.

regurgitation develops rapidly, with increasing left ventricular end-diastolic pressure and the acute onset of heart failure. In those patients who survive, left ventricular dilatation may occur and the condition may become compensated and chronic. The clinical diagnosis is usually obvious when the characteristic early diastolic murmur of aortic regurgitation is first detected in the course of an otherwise unexplained febrile illness, or in association with an acute attack of chest pain and clinical evidence of aortic dissection. In acute aortic regurgitation, ventricular compliance cannot compensate, and a relatively small regurgitant volume produces a very large rise in the ventricular end-diastolic pressure. This limits regurgitant flow as well as precipitating cardiac failure. The limited regurgitant flow means that the murmur may be soft or inaudible and the diagnosis missed. Chest radiography Depending on speed of onset, the heart may be normal in size or show only minor left ventricular enlargement. If there is left heart failure, there will be upper lobe blood diversion or overt pulmonary oedema. Acute aortic regurgitation is an important cause of pulmonary oedema in

a patient with a normal-sized heart. The aorta is usually unremarkable unless there is associated aortic disease causing dilatation as well as aortic regurgitation, as in Marfan’s syndrome. Other imaging techniques Acute aortic regurgitation is usually caused by infective endocarditis or aortic dissection. Both conditions can be well studied by 2D US. Transthoracic US can usually delineate aortic vegetations more than 2–3 mm in size. Transoesophageal US is very useful in both conditions, being more sensitive in detecting aortic vegetations than transthoracic US, particularly when the valve cusps are independently thickened by pre-existing disease. It is the technique of choice for displaying cusp perforation and aortic root abscess29. Abscess cavities may extend into the interventricular septum, the right side of the heart, the left atrium, or the wall of the ascending aorta. Abscesses may also be shown by CT or MRI. In aortic dissection, CTA and CMR are very valuable. Both can demonstrate the intimal flap, its relation to the coronary ostia, and any associated haemopericardium. CMR allows detection of the aortic regurgitation (see Fig. 24.22) as well as the morphology of the aortic valve (Fig. 24.24).

Figure 24.24 Calcified, stenotic bicuspid aortic valve. CMR, aortic valve view in (A) diastole and (B) systole. The calcified leaflets result in a signal void in diastolic frame (arrowheads). In systole the signal outlines the small opening of the stenotic valve orifice. (C) Left ventricular outflow tract view shows signal loss in the ascending aorta due to aortic stenosis. Note the doming of the aortic valve (arrowheads) and dilated ascending aorta (Ao). LA = Left atrium, RA = right atrium, RV = right ventricle. Compare to Fig. 24.21.

CHAPTER 24

PROSTHETIC CARDIAC VALVES Heart valve replacement with mechanical, donor, or bioprosthetic valves has resulted in an improved quality of life for patients with cardiac valvular disease. Since Harken et al38 in 1959 and Starr and Edwards22 in 1960 successfully implanted the first caged ball prosthesis in the mitral and aortic areas, continuous improvement in operative mortality, prosthetic design, and postoperative complication rates has been achieved23. Malfunctions, however, continue to occur. Five per cent of patients with aortic valve replacement die within 5 years, and 14% with mitral valve replacement with a St Jude prosthesis die due to intrinsic heart disease or to complications related to the prosthesis24. Two major types of artificial valves are currently available for both the aortic and atrioventricular positions. These are mechanical valves and bioprostheses. Either type should be of lasting structural durability, capable of successful implantation in the native valve annulus, and be chemically inert, free of thrombogenicity, and offer little resistance to blood flow25. Normal as well as abnormal function of the valve should be readily evaluated by minimally invasive or noninvasive diagnostic techniques25–27. The role of diagnostic imaging is complicated because there are over 40 types of cardiac valves, with different modes of action and complication rates, designed for use in the aortic, mitral, and tricuspid areas, as well as for vascular conduits. As each prosthesis has different inlet and outlet diameters and flow patterns, a knowledge of the inlet–outlet relationship is critical for proper identification of blood flow efficiency through the prosthesis. After the native valve has been removed and replaced with a tissue or mechanical prosthesis, complications are often found which are characteristic of specific models or classes of prosthesis.These include: paravalvar leak due to sewing ring dehiscence, occluder variance, or erosion; structural complications

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such as strut fracture; pseudoaneurysm; thrombosis; and bland vegetations or tissue overgrowth. Infective endocarditis and primary valve failure with regurgitation, usually occurring in bioprostheses, are additional complications. Other complications to be considered are those of anticoagulation, embolism, and post-pericardiotomy syndrome. The primary method of evaluation of a prosthetic valve is with echocardiography. The role of the diagnostic radiologist in identifying the complications of prosthetic valves is based on the findings seen on plain chest radiography27–29, fluoroscopy, and CT16, and angiography30 can help to solve problems in individual cases. At present, the artefacts caused by almost all the prosthetic valves limit their evaluation with CMR. Valves have differing rates and types of early and late failure depending on their specific type. Knowledge of the anticipated mechanism of failure is essential for evaluation of a prosthetic valve. It is valuable to perform baseline 2D and Doppler echocardiography after the valve is implanted, for comparison with follow-up studies which may be undertaken when and if there is a suspicion of malfunction or altered cardiac status.The normal diagnostic parameters for many of the more widely used prostheses have been published and are available for guidance to the diagnostician26,31–33.

Cardiac valve prostheses in current use and of historical interest Central ball occluder valve This valve (Fig. 24.25) consists of a spherical occluder or poppet and a base ring located within the valve annulus. A metallic cage limits excursion of the occluder. This type of prosthesis is large and occupies enough space to reduce blood flow in those patients with a small left ventricular chamber or aortic root. Both thromboembolism and haemolysis are troublesome

Figure 24.25 Three Starr–Edwards prostheses in a 53 year old patient with rheumatic valvular disease. Chest radiograph in (A) frontal and (B) lateral views. Note the perpendicular orientation of the atrioventricular valves to the aortic valve. 1 = Aortic position, 2 = mitral position, 3 = tricuspid position.

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complications of central ball occluder valves. Examples include the Starr–Edwards, Harken, Smelloff–Cutter, Braunwald–Cutter, and Magovern–Cromie valves. These valves have not been implanted for many years, and the central ball occluder valve will only rarely be seen today.

Central caged disc occluder valve Low profile valves have the advantage of minimal intrusion into a small valve orifice or cardiac chamber. However, over time the disc edge erodes and valvar regurgitation will develop. Examples include the Beall and Starr–Edwards 6500 series.

Eccentric monocuspid disc valve Until recently, the eccentric monocuspid disc was the most commonly used type of mechanical valve. Its advantages include a large cross-sectional area in the open position, so that flow is less inhibited than with other valves. As a result, haemolysis is trivial. Specific models of one monocuspid valve, the Bjork–Shiley concavoconvex occluder valve, developed an alarming number of outlet strut fractures and disc embolization (see page 487)34. This problem led the manufacturers to recall the unimplanted valves, including the Bjork–Shiley, Omniscience, and Medtronic–Hall valves.

Bileaflet disc valve This valve (Fig. 24.26) consists of two semilunar discs which pivot into position, eliminating supporting struts. There is good hydraulic function with a low incidence of thromboembolism. They are in common use today and include the popular St Jude33 and the Carbomedics and Sorin bicarbon valves (Figs. 24.26, 24.27).

Bioprosthesis In common use are the Carpentier–Edwards porcine prosthesis (Fig. 24.28), the Hancock porcine bioprosthesis, and the Ionescu–Shiley bovine pericardial bioprosthesis (Fig. 24.29). All have metallic components that permit recognition on chest radiographs. Recent introductions include the Stentless Porcine Xenografts for the aortic position. Since

Figure 24.27 Cine-fluoroscopy of St Jude prosthesis in aortic position. Tangential view in (A) open and (B) closed position. The leaflets form an angle of 35 degrees in (A) and 125 degrees in (B), indicating stenosis of the prosthesis in this patient, as the normal angle between the open leaflets is about 10 degrees. Thrombosis was demonstrated at surgery (see also Fig. 24.31C). In the open position, there are three streams of blood, one between the almost parallel discs and one on the outer side of each disc.

Figure 24.26 Bileaflet valve. Implanted Duramedic valve (replaced mitral valve) in the open position.

the stent decreases the effective valve area, and causes more stress on the leaflets, the stentless valves are considered to have more physiological flow, and are increasingly used in patients with small aortic roots. This group of prostheses includes the Toronta SPV stentless valve34, the Edwards stentless valve35, and the Medtronic Freestyle valve36. Their long-term prosthetic durability and survival are not yet established. The major advantage of the bioprosthetic valves is that anticoagulants can be discontinued after several months of therapy. These valves are used preferentially in women of child-bearing age who plan to have further children, in older patients, and in very young patients, and particularly those patients for whom anticoagulation is a serious risk.

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Figure 24.28 Carpentier–Edwards prosthesis. (A) Photography from outlet aspect. The commissures of the heterograft aortic valve are supported by three struts. (B,C) Two frames from cine-fluoroscopy, showing the usual displacement of the base support during the cardiac cycle. The estimated displacement in this patient is less than 2 degrees.

Figure 24.29 Heterograft valves. (A) Hancock porcine valves—only the supporting ring is radio-opaque. (B) Carpentier–Edwards porcine bioprosthesis with metal frame. (C) Ionescu–Shiley calf pericardial tissue valve.

Cardiac valve reconstruction and annuloplasty Surgical valvuloplasty for treatment of mitral insufficiency sometimes requires the use of a metallic ring (Carpentier– Edwards or Duran ring37) to reduce the diameter of a patulous tricuspid or mitral valve annulus. A flexible annuloplasty ring has recently been introduced for this purpose. The radioopaque ring is inserted in the annulus of the mitral valve38 (Fig. 24.30).

Diagnostic imaging following valve implantation Chest radiography During the immediate postoperative period, interpretation of valve position and integrity will usually be based on the frontal bedside chest radiograph. In the frontal projection, the aortic valve prosthesis is oriented in partial profile along the direction of flow as determined by the occluder position in a mechanical aortic valve.The mitral valve is usually more vertically oriented and is more likely than the aortic valve to be visualized en face. The direction of flow in the case of the mitral valve is towards the cardiac apex28.

Perhaps the most useful role for plain chest radiography is the identification of the signs of increased pulmonary venous pressure due to new valvar regurgitation secondary to paravalvar leak29. Plain chest radiography is particularly valuable in the identification of strut fracture, occluder embolization39,40, or calcification of a degenerated bioprosthesis41,42. If malfunction occurs, echocardiography is the study of choice for characterization of the location and extent of regurgitant flow.

Fluoroscopic evaluation of selected prosthetic valves Fluoroscopic examination with videotape or digital recording is helpful in analysing the integrity of the radio-opaque components of prosthetic valves (Fig. 24.31). However, in practice fluoroscopy is reserved for analysis of older mechanical valves and in selected cases when echocardiography does not clearly answer the question addressed. Some important features to assess are: motion of the occluder and base ring, integrity of the opaque struts, and calcification of tissue valves and surrounding supporting structures.

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Figure 24.30 Mitral valve annuloplasty in a patient with severe mitral insufficiency. (A) Carpentier–Edwards ring has been inserted in the mitral annulus. (B) Sculptor flexible annuloplastic ring in mitral annulus in another patient with mitral insufficiency. (C) Lateral view of chest shows Duran band for reconstruction of an incompetent mitral valve.

Calcifications of the aorta, coronary arteries, and head and neck vessels can be studied at the same time. Since normal motion of the base ring differs for each valve model and for each patient, a baseline examination is helpful for future reference. The normal and abnormal ranges of motion of many of the valves has been described, including the St Jude25,43, the Bjork–Shiley30,44,45, Starr–Edwards, Medtronic–Hall, and Beall valves. To visualize an aortic central occluding valve in profile, left anterior oblique views with cranial or caudal angulation are necessary.The right anterior oblique view with cranio/caudal angulation is appropriate for examination of the mitral valve. In the opposite oblique position, the base ring is positioned in an en face projection, so that the occluder or calcifications can be observed through the base ring. Carm fluoroscopy is helpful for obtaining a completely en face projection, by angling the tube into the sagittal as well as the axial plane46. The position of the mitral valve annulus in relation to the base ring can be appreciated by locating the fat plane of the atrioventricular groove. A partially separated mitral valve prosthesis may lie above the fat line of the atrioventricular groove within the left atrium47, or below the fat line within the left ventricle48,49. The range of motion of the base ring of a prosthetic aortic valve is generally smaller than that of a mitral valve, probably due to the greater variation in residual tissue in the mitral

annulus after surgery. The normal range of motion of the aortic sewing ring has been described as up to 9 degrees (6–9 degrees). The normal range of motion of the mitral prosthesis is 9–12 degrees31,50.The Bjork–Shiley prosthesis, when in the open position, forms an angle of 60 degrees to the axis of the base ring. An aperture of 45 degrees is considered appropriate for this valve. Bileaflet prosthesis (e.g. St Jude) The St Jude valve51 is a low-profile central-flow device consisting of two semicircular discs that pivot in position without supporting struts. Blood flow occurs in three streams: a central stream between the discs and two outer streams on the outer side of each disc.The orifice ring is impregnated with tungsten to provide faint radio-opacity. Fluoroscopy with craniocaudal angulation appears to be most useful to study the St Jude aortic valve (see Fig. 24.27). Placing the patient in a slight left anterior oblique position provides an en face view31,33. CT is useful in demonstrating this valve to advantage because of the high temporal resolution of this technique (Fig. 24.32). When a St Jude prosthesis is observed en face, the base ring appears as a circle and the leaflets in the open position as two almost parallel lines. In the tangential view, the leaflets in open position appear to form an angle of approximately 10 degrees. The leaflets make an angle of 120 degrees in the closed position for a prosthesis of 19–25 mm; the closing angle for valves of 27–33 mm is 130 degrees (see Figs 24.27, 24.32).

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Figure 24.31 Cine-fluoroscopic findings with commonly implanted prosthetic valves. (A) Starr–Edwards aortic valve in the closed position during diastole and a Beall mitral valve in the open position (upper panel). The lower panel shows the Starr–Edwards valve in the open position during systole and the mitral central occluding the disc Beall valve in the closed position. (B) Upper panel shows a Bjork–Shiley valve in the closed mitral position. Lower panel shows the disc to be 50 degrees from the horizontal baseline (ring) during systole in the open position. (C) In the upper panel, the St Jude aortic bileaflet valve is in the closed position during diastole. In the lower panel, it is in the open position during systole, permitting two blood streams at the outer sides of the leaflets and one stream between the leaflets.

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Figure 24.32 Ultrafast CT in the axial plane at the level of the aortic root demonstrates a St Jude bileaflet valve (between arrows which define the closure line between the two leaflets) in the closed position. (Courtesy of William Stanford, MD.)

models. Since there are few Beall valves in place today, this problem is an historical one.

Porcine bioprosthesis The major problem with porcine bioprostheses is their poor durability. Cusp tears, degeneration, perforation, fibrosis, and

Tissue valves Fluoroscopy is of limited value in detecting abnormalities of tissue valve function, but abnormal tilting of the radio-opaque base ring will suggest dehiscence, and calcification of the tissue components will indicate degeneration25,26.

Complications of prosthetic valves Strut fracture and poppet embolization Strut fractures have been reported in some types of mechanical valves. During the past decade, fractures of the concavoconvex Bjork–Shiley valve affecting the outlet struts have been reported in a highly significant number of patients, particularly those with the larger size mitral values. Plain chest radiography using microfocus, fluoroscopy, and CT have been useful in identifying fractures of these radioopaque components (Figs 24.33, 24.34). The high incidence of disc embolization with the Beall valve is related to severe grooving and wear occurring in the Teflon® disc of the earlier

Figure 24.33 Broken struts. Cine-fluoroscopy demonstrates two broken struts in this DeBakey aortic valve. (Reproduced with permission from Zumbro et al39.)

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Infection typically develops in the coronary ostia, the ascending aorta, and the aortic annulus, related to high-pressure regurgitant jets of blood which damage valve attachments and cause development of local abscesses (Fig. 24.35). Pannus and vegetations obstruct flow through the valve orifice or limit occluder motion (Fig. 24.36). Sinus of Valsalva and perivalvar pseudoaneurysms may develop (Fig. 24.37)53. Paravalvar insufficiency occurs as tissue fragments and sutures loosen with infection. Two-dimensional echocardiography is useful in demonstrating the site, form, and size of vegetations or thrombi on a tissue valve prosthesis. However, transoesophageal echocardiography (TEE), CT, and CMR have also been useful in identifying vegetations, particularly pseudoaneurysms53. Contrast angiography is also useful for detecting pseudoaneurysm and evidence of infection (Fig. 24.37). Cine-fluoroscopy has been disappointing for detecting vegetations, but if the vegetation is large enough to interfere with valve motion, decreased excursion of the occluder may be recognized53.

Valve regurgitation

Figure 24.34 Bjork–Shiley disc embolized following strut fracture. The strut is in the proximal left common iliac artery (lower arrow). The disc is in the abdominal aorta at the T12–L1 interspace (upper arrow). (Reproduced with kind permission of Springer Science and Business Media, from Morse et al47.)

calcification appear on about the fifth postoperative year, and by the 10th year 20% have failed and require re-implantation. Fortunately, bioprostheses seldom require urgent replacement, so that replacement can be carried out on an elective basis. Fracture of the stent is rare in this type of prosthesis.

Minor regurgitation is found normally with many mechanical valves, but major regurgitation usually occurs as a result of sewing ring dehiscence, thrombus, disc wear, and sticking, cocking, or vegetations of the valve leaflets. Perivalvar leak occurs more frequently after mechanical valve implantation than with bioprostheses. Dehiscence with valve detachment may occur in a heavily calcified annulus or when there is underlying defective collagen, as in Marfan’s syndrome39,54. Perivalvar regurgitation or valve dysfunction should be suspected when sudden cardiac enlargement and pulmonary oedema occur: a regurgitant murmur will occur in 80% of patients with regurgitation. In the mitral position, normal motion of the prosthesis is anterior and posterior along the long axis of the left ventricle, and side to side along the vertical axis. Strain on the suture line is greatest at the medial and lateral aspects of the sewing ring. If a suture breaks in one of these locations, the adjacent sutures suffer additional strain, eventually causing complete dehiscence, leading to detachment and possible embolization. The incidence of leakage

Infective endocarditis Prosthetic valve endocarditis is an infrequent complication of cardiac valve replacement. The overall incidence of infective endocarditis ranges from 0.9 to 4.4%, and is most frequent within 6 months of valve implantation. Potential sources of infection include contaminated blood products, surgical field contamination, and pre-existing infection. Postoperative sources include indwelling catheters, endotracheal tubes, and pacemakers. Organisms most frequently involved are coagulase-negative staphylococci, Serratia marcescens, streptococci, Candida albicans, and Staphylococcus aureus. Diphtheroids are seen more frequently in early infective endocarditis, and there is a lower incidence of Gramnegative bacilli and fungal infections52. Pre-operative factors that predispose to the development of infection are previous endocarditis and post-surgical wound infection.

Figure 24.35 Transoesophageal echocardiography through the aortic valve in a patient with aortic prosthesis. An abscess (AB) is seen involving the aorta at the site of the noncoronary cusp. LA = Left atrium, LV = left ventricle, PAV = prosthetic aortic valve, RA = right atrium. (Courtesy of N Nanda, MD.)

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sensitive than fluoroscopy in identifying dehiscence and other causes of prosthetic regurgitation.

Thromboembolism

Figure 24.36 Transoesophageal echocardiographic view in a patient with aortic valve endocarditis. There is a marked thickening of the aortic leaflets with a vegetation involving the aortic annulus at its arterial side. LA = Left atrium, LV = left ventricle, PAV = prosthetic aortic valve, RV = right ventricle, V = vegetation. (Courtesy of N. Nanda, MD.)

Thrombosis in the valve orifice will reduce the excursion of the occluding ball, disc, or leaflet. Prosthetic mitral valve thrombosis is more common than aortic valve thrombosis. The frequency of thrombosis has decreased markedly during the past few years. With the early prostheses, the incidence of thromboembolism was 24–37%. Since the introduction of cloth-covered prostheses, the incidence has decreased to 3–5%. The risk of embolism diminishes with time after implantation and is similar for single or multiple valve replacements55. The incidence of St Jude prosthetic valve thrombosis is as low as 0.2% per patient per year56. Fluoroscopy is helpful in demonstrating the abnormal motion of the occluder due to thrombus (see Fig. 24.27). M-mode and 2D imaging are useful in characterizing the thrombus, as are CT and MRI if the thrombus is large enough. Obstruction may occur because of spontaneous thrombosis, despite adequate anticoagulation. The patient will present with a low-output state, and the normal circulatory sounds of the valve are not audible. Since this phenomenon is a surgical emergency, immediate valve replacement or intervention by catheter remobilization and intracardiac thrombolysis, is required57.

Effect of magnetic resonance on the prosthetic valve

Figure 24.37 Mycotic aneurysm in the ascending aorta in a patient with infective endocarditis. There is a Bjork–Shiley valve in the aortic position. (Reproduced with kind permission of Springer Science and Business Media, from Morse et al47.)

produced by dehiscence is near to zero in noninfected valves. Factors which predispose to dehiscence are infective endocarditis and calcium in the annulus of the recipient valve. Rocking of the mitral valve radio-opaque base ring by more than 9–12 degrees and of the aortic valve by more than 10 degrees is highly suggestive of dehiscence. However, there must be at least a 40% continuous suture interruption around the circumference of the base ring before abnormal tilting motion will occur; thus, fluoroscopy without contrast medium is helpful only in advanced cases. Echocardiography is more

In an in vitro study, nine different mechanical bioprosthetic valves were studied with medium- and high-field MRI magnets. At 1.5T, six mechanical valves deflected 0.25–3.0 degrees. The largest deflections were observed in several Starr–Edwards models, which are made of dense cobalt–nickel alloy (Stellite)58. Other investigators found no significant temperature increase in a series of commonly used valves, or evidence of significant image distortion. A recent in vitro study using a 4.5-T system revealed highest deflection with the Duran Mitral annuloplasty ring59. CMR demonstration of the valves yields no significant information about valve condition. The diagnostic value of CMR in detecting regurgitation in prosthetic valves was compared with the transoesophageal colour Doppler echocardiography study by Deutsch et al60. They found 96% agreement between the methods in distinguishing physiological and pathological regurgitation across a prosthetic valve. The degree of regurgitation was detected by a signal void emanating from the prosthesis (Fig. 24.38). However, with many of the metallic prostheses, the artefacts from the metallic cage can obscure small paravalvar leaks. In addition, CMR is well suited to study the cardiac function that may be affected by prosthetic valve dysfunction61.

DISEASES OF THE HEART MUSCLE (CARDIOMYOPATHIES) Cardiomyopathies are a heterogeneous group of disorders in which the dominant feature is diseased cardiac muscle itself,

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Figure 24.38 Prosthetic valve insufficiency. Gradient-echo CMR in transverse section, showing a prosthetic valve in the mitral position (curved arrow) with paravalvar leakage. The signal void from eccentric regurgitation (wide short arrow) originates from the septal insertion of the prosthesis. LA = Left atrium, LV = left ventricle, RA = right atrium, RV = right ventricle. (Reprinted from Deutsch H J, Bachmann R, Sechtem U, Curtius J M, Jungehulsing M, Schicha H, Hilger H H 1992 Regurgitant flow in cardiac valve prosthesis: Diagnostic value of gradient echo nuclear magnetic resonance imaging in reference to transesophageal two-dimensional color Doppler echocardiography. J Am Coll Cardiol 19:1500–1507 with permission from The American College of Cardiology Foundation.)

often leading to heart failure. By definition, this group of diseases is not the result of congenital, valvular, pericardial, or hypertensive disease. Since the most common cause of congestive heart failure is coronary artery disease, these disorders must also be distinguished from the sequela of myocardial ischaemia. The most widely recognized classification of cardiomyopathy is by the World Health Organization (WHO) and the International Society and Federation of Cardiology (ISFC)62. In this scheme, the cardiomyopathies are classified on the basis of their pathophysiological features. When the muscle disease is part of a generalized or particular cardiac disorder, they are referred to as ‘specific cardiomyopathies’ (Table 24.3).

Dilated cardiomyopathy Also known as congestive cardiomyopathy (CCM), dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy. There is global impairment of contractility with Table 24.3 SPECIFIC CARDIOMYOPATHIES Ischaemic cardiomyopathy Valvular cardiomyopathy Hypertensive cardiomyopathy Inflammatory cardiomyopathy Metabolic cardiomyopathy General systemic disease Muscular dystrophies Neuromuscular disorders Sensitivity and toxic reactions Peripartum cardiomyopathy

dilatation of all chambers, particularly the left ventricle (Fig. 24.39), presenting clinically as congestive cardiac failure. Sometimes symptoms may be noticed after an acute influenza-like illness, hinting that a myocarditis may have been the underlying cause. Chest pain is very unusual. There is a familial form63. Physical signs of heart failure may be accompanied by mitral regurgitation due to dilatation of the mitral ring.There may be a pericardial effusion but tamponade is rare. Mimics of DCM are the specific myopathies, e.g. alcoholic heart disease; diffuse, silent ischaemic disease; and critical aortic stenosis, when the murmur may be inaudible. The course of the illness is variable, often with a good response to initial drug therapy. Sooner or later, periods of relapse end in death from low cardiac output; DCM is the most common reason for cardiac transplantation. At necropsy the left ventricle is found to be dilated, its wall is thickened (to a variable degree), and its trabeculae are effaced.There may be clot within the ventricle. Other cardiac chambers are usually dilated to a variable degree. Histological examination reveals cardiac muscle fibre hypertrophy and interstitial fibrosis, appearances that are not specific and may be seen in any form of left ventricular failure.

Imaging The plain chest radiograph is almost always abnormal at clinical presentation and most often the only abnormality is cardiac enlargement. The configuration of the heart may be solely left ventricular, or all chambers may be enlarged, although there is usually left ventricular prominence. In the untreated patient, upper lobe blood diversion and a variable degree of pulmonary oedema are usually seen. A good response to treatment is indicated by clearing of the pulmonary oedema and a reduction of the heart size (Fig. 24.40). Radionuclide ventriculography, echocardiography, and MRI can all show the dilated left ventricle and its reduced systolic contractility. Mild regional variations in contractility may mimic the irregular distribution of ischaemic myocardial disease, or the ventricle may exhibit global hypokinesis. CMR may be a particularly useful noninvasive test to distinguish DCM from ischaemic heart disease. Regional wall thinning may be obvious in short axis views. Use of MR contrast agents is particularly useful in recognizing the presence of infarcted myocardium, from both first-pass perfusion images and delayed enhancement of the infarcted segments. It is suggested that contrast-enhanced CMR is currently the best imaging method to categorize various forms of cardiomyopathies and more specifically, to distinguish the far more common ischaemic myocardial disease (Fig 24.41).When the DCM is secondary to active myocarditis, there may be delayed enhancement due to active inflammation. Such enhancement may be patchy, and can mimic infarcted myocardium. However, the perfusion images will be normal, and often there will be no focal thinning of the myocardium. The right ventricle is usually similarly affected but to a less obvious degree due to its lower working pressure—a normal right ventricle should raise suspicions of global left ventricular impairment due to multiple infarctions from ischaemic heart disease. Severe right ventricular dilatation is a poor prognostic sign64.

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Figure 24.39 Left ventriculography in congestive cardiomyopathy (same patient as in Fig. 24.40). (A) Systole and (B) diastole corresponding to Fig. 24.40A (before treatment). In (A) and (B) the ventricle is markedly dilated with little change in size from diastole to systole. The shape is slightly globular and the trabeculae are effaced. There was mitral incompetence, demonstrated by opacification of the left atrium (LA). (C) Systole and (D) diastole corresponding to Fig. 24.40B (after treatment). Although much smaller, the ventricle remains significantly dilated, even though the heart appears normal on plain radiography. Mitral incompetence is no longer present. At end systole (C), the left ventricle is much smaller than in (A).

Figure 24.40 Congestive cardiomyopathy (same patient as Fig. 24.39). (A) Before treatment. The heart is large with some prominence of the left ventricle, though all chambers are enlarged. There is a small right pleural effusion, redistribution of blood to the upper zones, and slight pulmonary oedema. (B) After treatment. The heart has reverted to normal size and the lungs are clear.

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Figure 24.41 Differentiation of (A,B) dilated and (C–E) ischaemic cardiomyopathy using CMR. (A) Four-chamber projection shows dilatation of all four chambers with greater involvement of the left ventricle (LV). (B) Same patient, post gadolinium administration delayed image, two-chamber projection. There is no regional hyperenhancement of the LV myocardium. (C) Short axis, mid ventricular level precontrast gradient-echo image. (D,E) Post contrast medium, delayed inversion recovery sequence. Before injection of contrast medium, LV wall thinning involving the posterior wall is seen. Post contrast medium delayed images show extensive hyperenhancement involving anterior, apical, septal, and posterior segments (arrowheads). LA = Left atrium, RA = right atrium, RV = right ventricle.

In all patients suspected of having DCM, the aortic valve must be examined in detail in order to exclude end-stage aortic stenosis. The two conditions may have very similar clinical presentations. It is very important to identify this presentation of aortic stenosis, because the response to valve replacement is frequently excellent. Echocardiography and CMR are very useful in recognizing the aortic stenosis.

Hypertrophic cardiomyopathy Hypertrophic cardiomyopathy (HCM), which is often familial and much less common than DCM, is characterized by excessive hypertrophy of the left ventricular myocardium, the myocytes showing a very disorganized orientation when compared to the regular alignment of ordinary left ventricular hypertrophy. HCM must be distinguished from ventricular hypertrophy resulting from hypertension and left ventricular outflow obstructions, including aortic stenosis. In a small proportion of patients, perhaps 25%65, the upper interventricular septum is most affected, resulting in a subvalvular obstruction. This form is also referred to as asymmetric septal hypertrophy or idiopathic hypertrophic subaortic stenosis (IHSS). However, the ventricular hypertrophy is symmetrical in the majority of patients with HCM; the right ventricle may also be involved. The myocardium may outgrow its blood supply, cause anginal pain, and show diffuse fibrosis. There may rarely be associated myocardial infarction. Ventricular arrhythmia is common and death may be the mode of presentation. Similar pathological

changes may be seen in the hearts of patients with Noonan’s syndrome and Friedreich’s ataxia. A rare variant affects only the apex of the left ventricle66. In most cases, contractility is good or even hyperdynamic, and together with the hypertrophy leads to a very small endsystolic left ventricular volume. As a consequence, the chordae of the mitral valve may become slack, allowing the tip of the anterior leaflet to float towards the septum: once it strays into the left ventricular outflow tract it is picked up by the flow of blood and slammed against the interventricular septum, rather like a sail caught by the wind. In doing so it partially obstructs the subaortic region, causing an end-systolic gradient and giving further stimulus to left ventricular hypertrophy. This mechanism is called systolic anterior motion of the mitral valve (SAM). This abnormality can also contribute to the left ventricular outflow obstruction. The distortion of the mitral leaflet also causes mitral regurgitation, usually mild. Occasionally there is a preterminal phase when the ventricle dilates; SAM is then lost and the picture more closely resembles DCM.

Imaging The plain chest radiographic appearances67 may vary from a heart that is entirely normal in size and shape to varying degrees of left ventricular shape, sometimes with unusual bulges, and the left atrium is sometimes enlarged. The dilated phase will resemble DCM. The lungs may reflect left atrial hypertension. The cardiac silhouette may remain unchanged

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for years, but it grows in size with clinical deterioration, often associated with the onset of atrial fibrillation68. Echocardiography has played a major part in elucidating the pathophysiology and natural history of HCM. The condition, and particularly SAM, is well displayed by cross-sectional echocardiography (Fig. 24.42).

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the left ventricle is irritable and catheterization may produce arrhythmias. Coronary angiography usually shows little or no arterial disease: the vessels are typically large and the septal perforators may show compression during left ventricular systole. Careful pressure measurement with an end-hole catheter shows the subaortic gradient together with any valvar aortic stenosis that may be coincidental or causative. On left ventriculography, the characteristic angiographic appearances depend on the classical distribution of hypertrophy. The left ventricular cavity (Fig. 24.44) is usually of normal size in diastole, but the shape varies from virtually normal to the characteristic curved shape, almost like a banana, when gross septal hypertrophy is present. Left ventricular trabeculation is usually coarser than normal and the free wall of the left ventricle may be obviously thickened.

CMR can demonstrate the pattern of hypertrophy, and assess left ventricle mass and mitral regurgitation (Fig. 24.43). Recent investigations have identified a subset of patients in whom echocardiography fails to demonstrate left ventricular hypertrophy or more severe thickening of the anterolateral wall (the latter is associated with a high risk for sudden cardiac death)69. Serial measurement of left ventricle mass by CMR is the best technique to follow the natural history of the disease. Postcontrast CMR may demonstrate patchy delayed enhancement, which is also associated with increased risk for sudden cardiac death (Fig. 24.43).

Restrictive cardiomyopathy70

Cardiac catheterization and angiography usually add little to the diagnosis or assessment and can be dangerous because

Heart failure due to impaired contractility of the left ventricle is easily understood. Less easy, but often as important, is failure of the ventricle to fill properly, initially hindering the

RV

RV Se

Se

LV

Ao

LV LA

LA

Figure 24.42 Hypertrophic cardiomyopathy. (A) M-mode echocardiogram, showing systolic anterior motion (SAM) of mitral valve apparatus. In addition, the diastole closure rate of the mitral valve is very low, so that it remains in apposition to the septum throughout diastole. IVS = interventricular septum, PW = posterior wall. (B ,C) Cross-sectional echocardiogram, long-axis parasternal view. (B) Diastole—the increase in septal thickness is apparent. (C) Systole—the anterior leaflet of the mitral valve has moved forward to touch the septum and obstruct the outflow tract.

Figure 24.43 Hypertrophic cardiomyopathy. CMR, left ventricular outflow tract view of (A) systolic and (B) diastolic phases show massive hypertrophy of the left ventricle, with near complete obliteration of the left ventricle (LV) cavity in systole (A). Ao = Ascending aorta, LA = left atrium.

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Figure 24.44 Left ventriculography in hypertrophic cardiomyopathy. Right anterior oblique (RAO) projection. (A) Diastole. The left ventricular cavity is of normal size and has a curved axis and coarse trabeculations. Some left ventricular wall thickening is present. There is mitral regurgitation into the left atrium (la). (B) Systole. There is almost complete emptying of the left ventricle with some contrast medium remaining under the aortic valve. The mid cavity filling defect of the posterior papillary muscle is seen (arrows). The indentation by the hypertrophic upper septum can be seen (arrowheads). Contrast medium is trapped at the apex of the left ventricle. Mitral incompetence is present, as shown by opacification of the left atrium (la).

expected increase in stroke volume with exercise and eventually reducing the resting cardiac output. Elements of diastolic dysfunction often coexist with systolic dysfunction as mentioned above, notably in HCM, hypertension, and ischaemic heart disease. This section will discuss those pathologies in which diastolic dysfunction is the predominant mechanism. In general terms there are two situations. First, the ventricle(s) may have stiff walls which fail to relax and require high filling pressures in order to achieve a reasonable stroke volume; this is typical of the myocardial infiltrative conditions. Alternatively, there may be a fixed maximum volume for the ventricle, which can easily be achieved with normal filling pressure, but beyond which there is only an abrupt rise in pressure but no further expansion; this is very similar to constrictive pericarditis. The differentiation between the two mechanisms is often blurred and they may well coexist with systolic impairment. Classification is therefore not as easy as for DCM and its differential. Mitral inflow Doppler studies during echocardiography or phase-contrast CMR underline the difference, with volume restriction giving rapid, early diastolic filling and the stiffened (low compliance) ventricles showing low velocity, protracted filling with accentuation of the atrial contraction wave (A wave). However, a mixture of the two can yield a spuriously normal wave form. The great majority of patients with restrictive cardiomyopathy have a ‘stiff ’ (diminished compliance) left ventricle.This is frequently seen in patients with hypertension, myocardial ischaemia, and advanced stages of HCM. However, these groups of patients are not labelled as restrictive cardiomyopathy. The common cause of the latter is from myocardial infiltration by a systemic disease process.

Amyloid heart disease Cardiac amyloidosis is a classic example of low compliance restrictive cardiomyopathy. Different forms of amyloidosis are

classified by the composition of the amyloid fibril, which infiltrates the involved organ. AL amyloidosis (previously known as primary amyloidosis) is derived from light-chain immunoglobulin produced by the monoclonal plasma cells. This is the most severe form, and the most common type encountered in the USA, and commonly involves the kidneys, liver, heart, and peripheral nerves. Familial amyloidosis is an uncommon autosomal dominant disease resulting from the production of an unstable variant of the serum protein transerythretin (ATTR amyloidosis), causing cardiac and/or neurological dysfunction. Senile systemic amyloidosis is the result of the deposition of wild-type transerythretin and is almost exclusively limited to cardiac involvement. This disease is becoming more prevalent, due to the ageing of the general population. Cardiac involvement in all these forms not only indicates a poor prognosis, but also predicts poor tolerance to high dose chemotherapy and stem cell transplantation71. Therefore, recognizing cardiac involvement in patients with amyloidosis is very important. The condition presents clinically in an intractable form of lowoutput cardiac failure, often with low pulse and blood pressures. There are usually no murmurs. The ECG is often of low voltage.The process leads to a combination of systolic dysfunction in which the heart does not pump properly, and diastolic dysfunction in which the stiff ventricles do not allow proper filling. Echocardiography is considered the noninvasive test of choice in the diagnosis of amyloidosis in a selected subset of patients with low output heart failure, but lacks specificity when co-morbid conditions such as hypertension are present. Gadolinium-enhanced CMR may give more specific findings, including decreased T1 of the myocardium and qualitative global and subendocardial delayed enhancement72. Both echocardiography and CMR can demonstrate systolic and diastolic dysfunction as well as any related atrioventricular valve regurgitation. CMR can also be helpful in excluding the presence of constrictive pericarditis.

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Sarcoidosis Sarcoid granulomas in the myocardium can give rise to cardiac arrhythmia as well as restrictive cardiomyopathy. Involvement of the papillary muscles may give rise to mitral regurgitation. Pericardium is uncommonly involved. Only 5% of patients with systemic sarcoid have clinical evidence of cardiac involvement, but at autopsy 20–30% have histological evidence of granulomas in the heart. Myocardial biopsy, the most specific test, can be falsely negative, due to patchy involvement of the myocardium. CMR can identify sarcoid granulomas as high signal areas in T2-weighted images with fat suppression, or as areas of hyperenhancement after administration of gadolinium (Fig. 24.45). These findings are nonspecific, and can be observed in many other inflammatory states. However, in patients with known sarcoidosis, these findings may help in identifying the site for endomyocardial biopsy and/or monitoring results of therapy.

Haemochromatosis Haemochromatosis can be a primary, inherited autosomal recessive disease, in which iron deposition occurs in the liver, heart, and pancreas. Secondary haemochromatosis results commonly from repeated blood transfusions, and less commonly from long-term haemodialysis and alcohol abuse. This form involves the liver and spleen, while iron deposition in primary haemochromatosis spares the spleen. Cardiac involvement results in diastolic dysfunction and in advanced stages systolic dysfunction as well, resembling DCM. Since iron reduces tissue T1- and T2-relaxation rates, haemochromatosis can be diagnosed by CMR. The amount of signal decrease in T2-weighted images correlates with iron level in the tissues, and CMR can be used to monitor the results of treatment of haemochromatosis73.

Volume-restricted cardiomyopathy Idiopathic volume-restricted cardiomyopathy is mainly a disease of children74 and includes some contracted-type endocardial fibro-elastosis with no other associated pathology, but is

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mostly a mixed group of dysplastic ventricles. Systolic contractility is often near normal and stiffness may be minimal. Chest radiographs may show a normal heart size but dilatation of the atria often causes an enlarged cardiac shadow. Pulmonary congestion is usual and there may be severe secondary pulmonary hypertension. US and MRI typically show large atria with normal sized ventricles, and the mitral inflow Doppler shows rapid early diastolic filling typical of volume restriction. In the occasional adult case, much of this is shared with constrictive pericarditis. Endocardial irregularity and bizarre ventricular modelling may be easily seen on US but is often best visualized by angiography. Volume-restricted cardiomyopathy in the adult is usually due to endomyocardial fibrosis (EMF)75. This condition predominantly affects the peoples of equatorial Africa, southern India, Sri Lanka, and Brazil, but it is also recognized in caucasians (Loeffler’s endocarditis) in Europe and North America. It is characterized by the deposition of a layer of fibrous tissue on the ventricular endocardium, beginning at the apex and spreading proximally to encroach on the atrioventricular valve. Either ventricle or both may be affected.Thrombus may deposit on the endocardium and become organized, resembling a ventricular tumour. The fibrosis does not initially severely affect left ventricular contractile function and the ventricles empty reasonably well, but the fibrosis prevents them from expanding fully in diastole. Valve involvement may lead to atrioventricular valve incompetence. In non-caucasians, the pathological process usually involves the right heart, either alone or more severely than the left, leading to right heart failure with the murmur of tricuspid incompetence. In caucasians, when the condition is often associated with present or past evidence of eosinophilia23, the left heart and mitral valve tend to be more severely involved. Imaging in endomyocardial fibrosis In right heart involvement, on the plain chest radiograph the heart is enlarged with a right heart or globular configuration. The right atrium may be very large. The lungs may be clear if there is no left heart involvement. Pleural effusions may be seen. Caucasian cases may have a normal heart silhouette or some left ventricular and left atrial enlargement and pulmonary congestion. Very rarely, curvilinear calcification due to endocardial calcification may be seen.

Left ventricular noncompaction

Figure 24.45 Cardiac sarcoid. CMR, short axis view. Post gadolinium delayed image demonstrating focal area of myocardial enhancement (arrow) in a patient with known pulmonary sarcoidosis. LV = Left ventricle, RV = right ventricle.

Left ventricular noncompaction (LVNC) is a rare form of congenital cardiomyopathy, resulting in arrest of normal intrauterine developmental progression of the loose myocardial fibre network. Two forms of LVNC are recognized: a nonisolated form associated with other congenital heart diseases, such as ventricular septal defect or hypoplastic left ventricle; and an isolated form that is often undetected and more common in adults. The latter type is becoming increasingly recognized in adults76–78. The involved myocardium (more often the left ventricle) has a ‘spongy’ appearance with more trabeculations and deep intertrabecular recesses. The latter tend to have sludging of the intracavitary blood and form

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thrombi. The disorder is often familial. The clinical presentation may range from the absence of symptoms to cardiac arrhythmias, embolic events, and severe heart failure. Echocardiographic criteria for diagnosis of LVNC are based upon trabeculations in the ventricular apex and thickness of the left ventricular free wall in end diastole. CT and CMR can demonstrate similar findings (Fig. 24.46). Some reports suggest that CMR may be more sensitive in the diagnosis of

LVNC than echocardiography78. CMR appearances range from increased left ventricular trabeculations, to abnormal wall motion, to the presence of two myocardial layers with different degrees of tissue compaction77.

Less common ‘specific’ causes of cardiomyopathy Hurler’s syndrome79 Cardiac failure may be due to involvement of the myocardium or the mitral or aortic valves. Thyrotoxicosis in the elderly may present with atrial fibrillation unresponsive to the usual methods of treatment. In the younger patient, the characteristic cardiac abnormality is high output cardiac failure with enlargement of all chambers. Myxoedema usually causes a pericardial effusion that resolves when the myxoedema is brought under control, but cardiac dilatation may occur. Acromegaly Hypertension and coronary artery disease are the usual features of this endocrine condition, but it is generally believed that there is a specific heart muscle abnormality that is associated with cardiac failure. Beri-beri Deficiency of thiamine (vitamin B1) may lead to cardiac failure, commonly of high output but occasionally of low output type. Both types show a large heart and pulmonary congestion, and they respond dramatically to thiamine. Alcoholic heart disease80 Alcohol appears to have a direct effect on the myocardium, rather than an indirect effect from a poor diet. There is no specific test for alcoholic heart disease, and withdrawal of alcohol may not improve function. Beta-blocking drugs These have a negative inotropic action (i.e. they depress myocardial contraction). When administered in large doses, particularly to control angina, they may precipitate congestive cardiac failure in the already diseased heart.The cardiac failure is reversible when the drug is discontinued. Cytotoxic drugs81 Among many cytotoxic drugs used for the treatment of malignant disease, doxorubicin is the most likely to precipitate a syndrome of congestive cardiomyopathy. This may remit if the drug is stopped. Postpartum cardiomyopathy usually remits entirely but may recur in subsequent pregnancies.

Figure 24.46 Left ventricular noncompaction. (A) Contrast-enhanced CT at mitral valve level shows increased trabeculations (arrows) near the apex of the left ventricle (LV). The heart is enlarged. This young patient was being investigated for arrhythmia and a follow-up echocardiography confirmed the presence of noncompaction. (B) CMR of a different patient, two-chamber projection, shows markedly increased fine trabeculations in the LV wall more marked near the ventricular apex with a faint line of demarcation between ‘normal’ and ‘abnormal’ segments (arrowheads). LA = Left atrium, LV = left ventricle, RV = right ventricle.

Neuromuscular disorders82 In a number of familial muscular disorders, death ultimately occurs from congestive cardiac failure due to heart muscle involvement.The radiological appearances are of non-specific cardiac dilatation and failure. Endocardial fibroelastosis This condition is characterized by the deposition of elastic tissue on the inside of the left ventricle, commonly involving the mitral valve and producing mitral regurgitation. Two forms are recognized: the dilated variety that occurs in the absence of other cardiac abnormality and produces a clinical syndrome identical to that of DCM; and a

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contracted form that occurs in association with various forms of left ventricular outflow obstruction.The dilating form is the most common type of heart muscle disease in childhood. In the dilated form, echocardiography shows the left ventricular cavity to be dilated and the ejection fraction to be reduced (Fig. 24.47). The thickened endocardium may be visible as a bright line adjacent to the ventricular cavity and separating it from the underlying myocardium. The right ventricle may be involved in a similar way. Mural thrombus may be present in either ventricle. Doppler may demonstrate functional mitral and/or tricuspid regurgitation. Hypertensive heart failure This is a form of congestive cardiac failure, the cause of which is obvious when the high systemic blood pressure is known, but may be obscured if the blood pressure falls as a result of cardiac failure. Rarely, hypertension may lead to the development of aortic incompetence. Echocardiography is useful in determining the degree of left ventricular hypertrophy and contractile impairment. Severe left ventricular hypertrophy may cause cardiac enlargement on the plain chest radiograph, but usually left ventricular enlargement is due to dilatation, and the picture may resemble a dilated cardiomyopathy, although some septal hypertrophy characteristically persists in the latter. Hypertension is a risk factor in the development of coronary artery disease, which may have its own effects on the ventricle. Anaemia, when severe, may precipitate cardiac failure, particularly when pre-existing heart disease is present. Radiation damage83 to the heart may involve pericardium, myocardium, or coronary arteries. Glycogen storage disease (Pompe’s disease) Most patients with glycogen storage disease present with ‘floppy baby’ syndrome with macroglossia. Rarely, the condition may present as heart failure before the characteristic general muscle weakness becomes obvious.The plain chest radiograph reveals gross cardiomegaly with either a left ventricular or a non-specific

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dilatation. Often the liver may be enlarged.The left ventricle is large and poorly contracting, but the left ventricle wall is very markedly increased in thickness and irregular in outline on its inner aspect, giving characteristic echocardiographic and ventriculographic appearances84. Fabry’s disease is similar to Pompe’s disease but the myocardial wall thickening is gross.

TUMOURS OF THE HEART Metastatic tumours to the heart and pericardium are 20–40 times more common than primary heart tumours. Among primary cardiac tumours, benign tumours are more common than malignancy. Cardiac tumours can clinically present as heart failure, arrhythmia, chest pain, or embolic disease85.The diagnosis is usually obvious when clinical evidence of cardiac involvement, arrhythmias, or (haemorrhagic) pericardial effusion develops in a patient with a known primary malignant neoplasm. Intrathoracic, extracardiac tumours, benign or malignant, may produce cardiac symptoms and signs by compressing the heart and great vessels, and mimic obstructive lesions of these vessels. Obstructive murmurs developing in the course of the malignant disease are well recognized. Cardiac tumours and ventricular and aortic aneurysms may resemble each other radiographically. Echocardiography has been the imaging technique of choice for the diagnosis of intracardiac tumours. Real-time imaging can show tumour mobility and distensibility features which are typically seen in atrial myxomas and less likely in sarcomas and metastases. CT and MRI can be used accurately to image the heart and the surrounding mediastinum. CT can depict calcifications and fat, and may allow tissue diagnosis of some masses such as lipomas. MRI allows better soft tissue characterization than CT and can provide functional information such as flow direction and velocity, as well as a more reliable diagnosis of true invasion of cardiac structures by intrathoracic tumours86,87.

Metastasis

Figure 24.47 Endocardial fibro-elastosis, cross-sectional echocardiogram, apical two-chamber view. Note the enlargement of the left ventricular (LV) cavity size. The cavity is abnormally round, and the amplitude of endocardial (En) and subendocardial echoes is increased.

There are three ways of cardiac involvement by metastases: (A) direct mediastinal infiltration by lung cancer, breast cancer, or lymphoma; (B) haematogenous metastasis from a systemic tumour such as malignant melanoma, lymphoma, leukaemia, or sarcoma; and (C) transvenous spread, from the inferior vena cava (renal or hepatic tumours) (Fig. 24.48A) and via the pulmonary vein (Fig. 24.48B) or superior vena cava in cases of lung cancer. CT is extremely useful in tumour localization and staging for surgical resection. CT features that suggest a malignant nature of a cardiac neoplasm are wide attachment to the wall of the heart, destruction of the cardiac chamber wall, involvement of more than one cardiac chamber, invasion of the pericardium, especially with haemorrhage, extension into the pulmonary artery, pulmonary vein, or cava, and involvement beyond the pericardium, lung, or mediastinum (Figs 24.49, 24.50).

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Figure 24.48 Intravascular extension of tumours into the heart. (A) Contrast-enhanced CT in a patient with hepatocellular carcinoma extending directly into the right atrium via the inferior vena cava (arrows). Renal cell carcinoma and adrenal carcinoma also commonly spread this way. (B) Direct extension of lung cancer via the pulmonary vein into the left atrium. Contrast-enhanced CT in a patient with right lower lobe bronchogenic carcinoma (T) shows tumour growing into the left atrium via the right inferior pulmonary vein (arrows). C = Inferior vena cava; L = left atrium; LV = left ventricle; R = right atrium; RV = right ventricle.

CT is not an accurate technique for detecting direct invasion of the mediastinum and cardiovascular structures by lung cancer. The sensitivity for assessment of mediastinal invasion by CT ranges from 40 to 78% and specificity from 67 to 99%88. The contact area between the thoracic mass and adjacent mediastinal structure, and the obliteration of intervening fat are the commonly used CT features for local invasion, but neither is reliable. The sliding motion between two contacting areas can be the definitive evidence of absence of invasion and this feature can be detected by MRI86.

Primary cardiac tumours Primary tumours of the heart89–92 are rare and the great majority are benign, the malignant tumours being sarcomas. Myxomas are by far the most common tumours, followed by rhabdomyomas and fibromas. The clinical features of these tumours depend on their sites of origin. Intracavity tumours

are commonly pedunculated and may impact on and/or occlude the valves, or fill cardiac chambers, leading to obstruction, arrhythmias, and cardiac failure. Extension of tumours to the pericardium may produce haemorrhagic pericardial effusion that may lead to tamponade.

Cardiac myxoma This most common primary cardiac tumour commonly arises in the left (75%) or right atrium (20%), and rest in either ventricle. Myxoma tends to be solitary, pedunculated or polypoid, occurs more commonly in women than men, and in 85% of cases is characteristically attached to the interatrial septum near the fossa ovalis93. Patients may be asymptomatic or have the triad of peripheral embolic phenomena, symptoms and signs of mitral valve obstruction, and constitutional symptoms of fever, anaemia, raised ESR, and sometimes finger clubbing mimicking infective endocarditis. Blood cultures,

Figure 24.49 Undifferentiated sarcoma. (A–C) Contrast-enhanced CT of the chest shows a large lobulated mass beginning near the tricuspid valve (arrows in A,B), extending into the right ventricular outflow tract (C). A similar mass is also present in the left ventricle (M) in (A); both confirmed at echocardiography. LA = left atrium, LV = left ventricle, RA = right atrium, RV = right ventricle.

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Figure 24.50 Metastasis to the right ventricular myocardium from carcinoma of the vulva. Axial, contrast-enhanced chest CT. There is irregular infiltration of the anterior free wall of the right ventricle (arrows). LA = left atrium, LV = left ventricle, RA = right atrium, RV = right ventricle.

however, are sterile and splenomegaly does not occur. Familial myxomas constitute fewer than 10% of all myxomas, tend to present earlier (median age 20 years), are more likely to have multiple myxomas at atypical locations and to develop recurrent tumours, and have associated dermatological and endocrine abnormalities (Carney complex).94 On chest radiography, the heart is commonly enlarged and there is often evidence of selective left atrial enlargement (Fig. 24.51A), though rarely is there a large appendage (Fig. 24.51B), which would suggest rheumatic heart disease. Pulmonary venous hypertension, pulmonary oedema, or even pulmonary

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arterial hypertension may be present. The appearances of the chest radiograph may, however, be normal. The rare calcified myxoma may be identified on chest radiograph or CT (Fig. 24.52), and at fluoroscopy it moves forward through the mitral valve in ventricular diastole. Both MRI and MDCT95 are capable of demonstrating cardiac tumours, MRI being particularly good at showing muscle invasion. Myxomas demonstrate an intermediate but variable signal intensity on spin-echo images similar to that of myocardium. On gradient-echo images, myxomas often have a low signal intensity caused by partial calcification, and higher signal intensity is seen on T2-weighted sequences. Intratumoural subacute or chronic haemorrhage appears as high signal intensity on both T1- and T2-weighted sequences. A moderate contrast enhancement after Gd-DTPA is caused by increased vascularization96 (Fig. 24.53). A cine-MRI display may show the mobility of the tumour. Echocardiography shows the tumour as a rounded, mobile mass often prolapsing through the mitral orifice in ventricular diastole (Fig. 24.54). Atrial myxoma must be distinguished from thrombus. Thrombus usually occurs in an enlarged chamber, atrial appendage is commonly involved, and atrial fibrillation is likely to be present (Figs 24.55A–C).Thrombi are usually sessile and do not demonstrate contrast enhancement which is seen to a variable degree in myxomas. Myxomas can be sessile or pedunculated and are commonly attached to the interatrial septum. Purely from the imaging perspective, other cardiac tumours and valvular vegetations may also present as intracardiac masses. Clinical features help in differentiating one from the other. Besides the presence of clinical symptoms and signs of endocarditis, vegetations are always related to a cardiac valve (Fig. 24.55D). Once diagnosed, myxoma should be removed without delay.

Figure 24.51 Left atrial myxoma. (A) PA view of the chest shows a large heart with all chambers involved. There is interstitial pulmonary oedema. (B) Chest radiograph in a patient with known left atrial myxoma demonstrating enlargement of the left atrial appendage (arrows). This finding is commonly seen in rheumatic mitral valve disease and is rare in atrial myxoma.

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Hypoxic spells similar to tetralogy of Fallot have been reported. These tumours are often inoperable because they are commonly deep seated, poorly demarcated, and multiple.

Fibroma

Figure 24.52 Left atrial myxoma. Unenhanced CT at the level of the aortic root shows a faintly calcified soft tissue mass (arrows) in the left atrium (LA) attached to the interatrial septum. Ao = Aortic root, LV = left ventricle, RA = right atrium.

Lipomas Lipomas can occur in the myocardial free wall or the septae. These lesions are easily identified on CT as low density masses. Lipomatous hypertrophy of the interatrial septum is now a well known entity and is often found incidentally on routine chest CT. Lipomas have high signal intensity on MRI due to their short T1 and long T2 relaxation, consistent with fat (Fig. 24.56).

Rhabdomyomas These are the most common paediatric primary cardiac tumours and occur in association with tuberous sclerosis in up to 50% of cases, where they may be congenital and manifest in the neonatal period.They are usually intramural and start in the interventricular septum, encroaching on the ventricular cavities as they enlarge. Arrhythmias, which may be fatal, are their main presenting feature.

A fibroma is usually a single tumour of the ventricular wall, generally on the left, and may be resectable. The presentation is with arrhythmia or congestive cardiac failure, and plain radiographs show a large heart. Though the tumour is rare, it is of radiological interest in that it may calcify and show characterizing whorls of calcium, which may suggest the specific diagnosis. On MRI, fibromas are iso- to hyper-intense on T1-weighted spin-echo images when compared to skeletal muscle. Due to the short T2-relaxation time of the fibrous tissue, fibromas show a decrease in signal intensity relative to the myocardium on T1- and T2-weighted spin-echo images.

Hydatid disease Hydatid disease may involve the heart, the cysts behaving as a benign myocardial tumour; they may calcify.

Primary malignant tumours of the heart Sarcomas96 Sarcomas account for nearly all primary malignant cardiac neoplasms (Fig. 24.57, see Fig. 24.49). Angiosarcoma is the most common malignant tumour of the heart. Most exhibit a strong male prevalence and arise in childhood. The right atrium and then the right ventricle are the chambers most commonly affected. The tumours are mainly intramural and infiltrating, though they may encroach on the cavity of the chamber. They usually present with intractable arrhythmias or relentless cardiac failure, features of obstruction to the vena cava, the tricuspid or pulmonary valves, or more rarely the mitral and aortic valves. Cardiac pain may occur. Involvement of the pericardium leads to pericardial effusion, often haemorrhagic, and this may lead to tamponade.The

Figure 24.53 Left atrial myxoma. CMR (A) gradient-echo and (B) post gadolinium contrast-enhanced axial images demonstrate lobulated soft tissue mass (M) in the left atrium attached to the interatrial septum, exhibiting significant enhancement after contrast medium administration (B). The typical location and post contrast enhancement helps in differentiating myxoma from thrombus. Compare to Fig. 24.55. LV = Left ventricle, RA = right atrium, RV = right ventricle.

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Figure 24.54 Left atrial myxoma. (A) Transoesophageal echocardiogram shows a large tumour (T) in the left atrium (LA) in ventricular systole. (B) In diastole it prolapses through and obstructs the mitral annulus, dragging down its septal attachment.

Figure 24.55 Other masses in the atria. (A,B) Left atrial thrombus in a patient with mitral stenosis. (A) Contrast-enhanced CT of the chest shows a large filling defect in the left atrium (LA) extending into the left atrial appendage (LAA). (B) More caudal image. The left atrium is dilated and dense calcification is seen in the stenotic mitral valve. (C) Right atrial thrombus. Contrast-enhanced chest CT. A large intraluminal nonenhancing mass is seen in the right atrium away from the interatrial septum. Compare to Fig. 24.53. (D) Valvular vegetation. Contrast-enhanced CT at the level of the inferior vena cava–right atrium (RA) junction shows an intraluminal filling defect (arrows) protruding into the right atrium. This patient has a history of intravenous drug abuse and there were multiple cavitating lesions in both lungs suggestive of septic emboli (not shown). This lesion may represent thrombus, RA myxoma, or valvular vegetation. At surgery a Eustachian valve vegetation was found. LA = Left atrium, LV = left ventricle, RV = right ventricle.

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Figure 24.56 Fat-containing cardiac masses. Lipomatous hypertrophy of interatrial septum. (A) CT and (B) T1-weighted axial MRI shows extensive fatty infiltration (F) in the interatrial septum, extending into the posterior atrial walls. (C) Left ventricular lipoma. Spin-echo CMR. High signal intensity mass (M) is seen in the left ventricular cavity. Due to short T1- and long T2-relaxation properties of fat, lipomas are bright on T1- and T2-weighted images. LA = Left atrium, LV = left ventricle, RA = right atrium, RV = right ventricle.

cardiac shadow is usually enlarged on the plain radiograph, and echocardiography will show a mass which is atypical of myxoma, with or without an effusion. MRI will show the extent of the lesion to greater advantage, and coronary angiography may demonstrate abnormal vascularity. However, this is not necessarily typical of sarcoma and may be seen in tumours such as myxomas, or even long-standing thrombi.

Lymphoma Lymphoma (Fig. 24.58) may affect the heart with little evidence of involvement elsewhere. Characteristically it takes the form of a diffuse infiltration of the myocardium, particularly of the right ventricular outflow tract. Both primary and metastatic (secondary) cardiac lymphoma occur more commonly in immunocompromised individuals. Patients who are positive for human immunodeficiency virus (HIV) disease are more prone to all forms of extranodal lymphoma, which are typically aggressive B-cell lymphomas. Primary cardiac lymphoma typically involves the right atrium, and involvement of other chambers is less common.

Figure 24.57 Angiosarcoma of the right atrium. Contrast-enhanced chest CT. There is a heterogeneous soft tissue abnormality lateral and anterior to the right atrium (RA). There are associated pericardial (P) and bilateral pleural effusions.

Most patients have pericardial extension, but valves are rarely involved97,98.

TRAUMA TO THE HEART99,100 Penetrating trauma Gunshot and knife wounds that penetrate the heart usually lead to haemorrhage and pericardial tamponade. This clinical situation is usually too critical to allow for more than supine radiography. When penetration is in the location of the heart, and resuscitation has not been successful with adequate blood transfusion, tamponade is assumed and the pericardium is surgically explored. After the acute phase, retained foreign bodies need to be carefully located by radiography (Fig. 24.59) and angiocardiography before attempts are made to remove them.

Blunt trauma101,102 (Fig 24.60) The clinical effects of blunt cardiac trauma may be delayed and may cause subsequent insidious deterioration of cardiac func-

Figure 24.58 Patient with human immunodeficiency virus (HIV) infection and aggressive B-cell lymphoma invading the mediastinum and heart. A large heterogeneous soft tissue mass is invading the mediastinum, pericardium, heart, and left pleural space displacing the cardiac structures to the right. Ao = Aortic root; LA = left atrium; R = right atrial appendage.

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tion.Traumatic pericarditis with haemorrhage may result from blunt trauma, as may traumatic haemorrhage with necrosis of the myocardium. In the latter, involvement of small areas may be clinically silent or of no great significance, but necrosis of large areas of the myocardium may be fatal. The lesion resembles myocardial infarction. The pericardium may be disrupted in blunt trauma, allowing herniation and strangulation of parts of the heart, or the abdominal or thoracic contents may enter the torn pericardium.

Injury common to both types of trauma Perforation of the ventricular septum Though more common with penetrating than with blunt trauma, perforation of the septum may occur with both types. The development of a murmur of ventricular septal defect following chest trauma points to the diagnosis. A shunt of haemodynamic significance should be surgically repaired. The clinical presentation often is subacute and usually allows full investigation by echocardiography, cardiac catheterization, and angiocardiography.The ventricular septal defect tends to be low or apical in the ventricular septum. Coronary arteriography is usually performed at the same time in order to recognize atheromatous coronary artery disease and the possibility of trauma to the coronary arteries, as damage to either may lead to septal infarction and perforation.

False aneurysms False aneurysms may develop when rupture or perforation of the free wall myocardium is held in check by pericardium. Such aneurysms increase in size (Fig. 24.61) and commonly rupture, either early or after many years. They may first present as an abnormal cardiac contour on chest radiography. If

Figure 24.59 Contrast-enhanced CT in a patient after gunshot injury shows bullet with streak artefacts lodged in the right side of the interventricular septum.

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present for several years, they may calcify. False aneurysms may be seen at ventriculography and can be distinguished from postinfarction aneurysms, as they usually fill through a narrow neck from the free wall of the left ventricle. Usually the coronary arteries are not very abnormal but trauma may transect or thrombose a coronary artery and lead to myocardial infarction and possible false aneurysm formation.

Valve disruption Any of the cardiac valves may be damaged by trauma, but the aortic valve is the most commonly affected, leading to aortic incompetence. Tricuspid incompetence may be virtually without symptoms, but traumatic mitral incompetence usually requires urgent correction. The characteristic murmur of valvar incompetence occurring after chest trauma suggests the correct diagnosis.

Trauma to the coronary arteries Trauma to the coronary arteries may lead to laceration of the artery, with haemorrhage that may require surgical control. Traumatic thrombosis may lead to myocardial infarction, the extent of which depends on the size of the vessel that is occluded. Rarely, trauma may lead to a coronary artery to cardiac cavity (cameral) fistula. A continuous murmur developing for the first time after major chest trauma should suggest this complication. False aneurysms may develop after trauma to the coronary arteries.

Trauma to the pericardium Pericardial tamponade is one of the most common causes of death after trauma to the heart. Traumatic pericarditis may calcify but rarely leads to constriction.

Figure 24.60 Blunt chest trauma causing rupture of right atrial appendage. There is a large anterior mediastinal haematoma (H) and haematoma surrounding the right atrial appendage (arrows). At surgery, rupture of the right atrial appendage near its junction with the right atrium was noted. Ao = aortic root, RA = right atrium.

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SECTION 2 • THE CHEST AND CARDIOVASCULAR SYSTEM

Figure 24.61 Traumatic false aneurysm. Plain radiographs (A) immediately after a car accident involving chest trauma, showing an insignificant bulge on the left heart border, and (B) 16 months later, a large bulge has developed in the mid left heart border. (C) Left ventriculogram shows that the bulge is a narrow-necked false aneurysm filling from the upper left ventricular cavity.

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