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

CHAPTER 2

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 D