Editors
Elena�Lazzeri, Alberto�Signore, Paola�Anna�Erba, Napoleone�Prandini, Annibale�Versari, Giovanni�D�Errico and Giuliano�Mariani

Radionuclide Imaging of Infection and Inflammation

A Pictorial Case-Based Atlas

2nd ed. 2021
Editors
Elena�Lazzeri
Regional Center of Nuclear Medicine, University Hospital of Pisa, Pisa, Italy
Alberto�Signore
Department of Medical-Surgical Sciences and of Translational Medicine, Sapienza University of Rome, Roma, Italy
Paola�Anna�Erba
Department of Translational Research and Advanced Technologies in Medicine and Surgery, Regional Center of Nuclear Medicine, University of Pisa, Pisa, Italy
Napoleone�Prandini
Nuclear Medicine Department, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
Annibale�Versari
Nuclear Medicine, Azienda Unit� Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
Giovanni�D�Errico
Nuclear Medicine Department, Private Hospital ?PIO XI?, Roma, Italy
Giuliano�Mariani
Department of Translational Research and Advanced Technologies in Medicine and Surgery, Regional Center of Nuclear Medicine, University of Pisa, Pisa, Italy
ISBN 978-3-030-62174-2e-ISBN 978-3-030-62175-9
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Foreword

Molecular imaging with positron emission tomography (PET) and single-photon computed tomography (SPECT) combined with computed tomography (CT) is increasingly being used in Nuclear Medicine to diagnose, characterize, and monitor disease activity in the setting of infections and inflammatory disorders. Hybrid PET/CT and SPECT/CT both produce images based on the biodistribution of radiopharmaceuticals able to localize the inflammatory changes and to describe their response to therapy. Although several textbooks have been published on this subject, the most successful so far has been Radionuclide Imaging of Infection and Inflammation: A Pictorial Case-Based Atlas (published by Springer in 2013) that presented and discussed a whole host of clinical cases and imaging examples illustrating the manifestations of the commonly encountered infectious and inflammatory conditions.

This new textbook is the second edition of the same Atlas, still edited by Elena Lazzeri, Alberto Signore, Paola Anna Erba, Napoleone Prandini, Annibale Versari, Giovanni D?Errico, and Giuliano Mariani. Until now the first edition has been considered an important and successful reference for medical students, residents in nuclear medicine and radiology, and for all physicians involved in the management of patients with infection and inflammation. The main added value of the Atlas was both the high level of its scientific contents and the original structure of its educational contents. Alongside the description of the most important inflammatory and infectious diseases, the authors presented in each chapter a series of illustrated teaching cases with images of the most frequent scintigraphic findings, as well the anatomic variants and technical pitfalls. Thus, the reader had the opportunity to understand the pathophysiologic basis of infections and inflammation and to learn how to correctly interpret the images obtained with these studies.

Several years have now elapsed since that first very lucky edition, which received the general appreciation of the clinical and scientific community. Over this period scientific knowledge of the molecular mechanisms and biology of the inflammatory response has changed. The same happened for infections, which today show different patterns versus those most frequently observed previously; in particular, the spectrum of pathogen agents, including viruses, has changed over time and new infections have emerged. New guidelines and recommendations have been developed by scientific societies, some of them with direct or indirect effects on the indications for some nuclear medicine imaging procedures. Furthermore, important technological advances have taken place in nuclear medicine concerning both imaging instrumentation and radiopharmaceuticals.

The above reasons stimulated the authors to implement, integrate, and enlarge the first edition of the Atlas to become this textbook. This second edition maintains the same excellent original structure based on accurate information on the diseases, technologies, and case reports with a high number of associated images, addressing the common questions and problems that arise in the daily practice. Furthermore, the number of chapters has been increased from 13 to 16, the new chapters being devoted to miscellaneous bone and joint conditions, to inflammatory vessels? disease (vasculitis and atherosclerosis), and to infections and inflammation in pediatrics. All the chapters have been modified and/or rewritten to address the latest advancements in the field. References have been carefully updated and new clinical cases have been included and discussed according to the most recent protocols and guidelines.

This new edition of the Atlas is still organized by clinical entity, and all issues are clearly presented, well illustrated, and referenced. Clinical cases at the end of each chapter offer a good teaching tool that refreshes and supports the concepts discussed in the main text. The illustrations are of very high quality, most of them being illustrated with hybrid imaging. The contents of the textbook cover all indications of nuclear medicine imaging in the current scenario of infections and inflammation. The book begins with the normal findings by using different radiopharmaceuticals and techniques, discussing variants and pitfalls. The following three chapters are devoted to imaging of soft tissue infections, bone and joint infections, and imaging of miscellaneous bone and joint conditions. Joint prosthesis infections and peripheral bone infections, vascular prosthesis infections, and nonorthopedic or cardiovascular implantable device infections are discussed in the following chapters. Other chapters are dedicated to some less known or less frequent conditions, such as inflammation of the head and neck region (including the central nervous system), infective endocarditis and cardiovascular implantable electronic devices, and fever of unknown origin. The textbook also presents abdominal infections and inflammations, diabetic foot infections, lung infections, chronic inflammatory diseases, inflammatory vascular diseases, vasculitis and atherosclerosis, and finally infections and inflammation in pediatrics.

In conclusion, this renewed Atlas continues to offer an excellent example of a modern and educational textbook, which is intended to disseminate worldwide the most up-to-date knowledge on the current role of nuclear medicine in the field. The authors, among the most experienced and distinguished professionals in this field, accomplished a great work to keep the contents of this text at the highest level, and through a multidisciplinary approach they have implemented an exceptional learning tool very useful for all physicians with interest in radionuclide imaging of infection and inflammation.

Emilio�Bombardieri
Bergamo, Italy
May 2020
Preface

Why a second edition of Radionuclide Imaging of Infection and Inflammation: A Pictorial Case-Based Atlas? This is the question that most people looking at this textbook will wonder about. The answer is easy: being an atlas of images and interesting cases, there are always more cases and more educational images to add, in order to improve the understanding of the role of nuclear medicine imaging in the field of infection and inflammation. Furthermore, in the time elapsed since the first edition the role of [18F]FDG PET/CT for imaging infection and/or inflammation has greatly expanded. At the same time, hybrid imaging with SPECT/CT has revived interest in single-photon imaging for infection, and new radiotracers are being developed for imaging of infection/inflammation.

It comes as a second consideration that this new edition is not intended to merely replace the first one, but rather to integrate it?so that the two editions will constitute a unicum, a full educational tool for all physicians with interest in radionuclide imaging of infection and inflammation.

As in the first edition of the book, we kept the same chapters, but raised the number from 13 to 16 in order to address the growing applications of radionuclide imaging for infection and inflammation, with particular emphasis on inflammatory vessels? conditions, such as vasculitis and atherosclerosis and on infection and inflammation in pediatrics.

Furthermore, the structure of each chapter has been modified to include learning objectives for each chapter and key learning points for each condition. This is an important modification that provides to the reader the possibility to quickly focus on the most relevant aspects for correct interpretation of images.

Finally, the most relevant feature of this second edition is that text and images have been prepared according to the multidisciplinary guidelines developed by the European Association of Nuclear Medicine (EANM) in conjunction with several other European societies of clinicians and radiologists; a list of the most relevant of such joint guidelines is reported in the next page. Therefore, this textbook is not the mere result of the experience of a group of Italian nuclear medicine physicians, but rather the summary of a wide international experience in the field. Indeed, some of the authors have been involved for several years in international task groups or committees of several world leading scientific societies.

This upgrade makes the book a modern and up-to-date reference manual for students and physicians who are approaching or already working in this field of nuclear medicine.

Alberto�Signore
Giovanni�D?Errico
Paola�Anna�Erba
Elena�Lazzeri
Napoleone�Prandini
Annibale�Versari
Giuliano�Mariani
Rome, ItalyRome, ItalyPisa, ItalyPisa, ItalyModena, ItalyReggio Emilia, ItalyPisa, Italy
April 2020
List of International Guidelines on Radionuclide Imaging of Infection/Inflammation Imaging (Most Recent Publications Listed First)

Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk RH, Ferrari VA, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: part 2 of 2?diagnostic criteria and appropriate utilization. J Nucl Cardiol. 2020;27:659?73.

Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk RH, Ferrari VA, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: part 1 of 2?evidence base and standardized methods of imaging. J Nucl Cardiol. 2019;26:2065?123.

Lazzeri E, Bozzao A, Cataldo MA, Petrosillo N, Manfr� L, Trampuz A, et al. Joint EANM/ESNR and ESCMID-endorsed consensus document for the diagnosis of spine infection (spondylodiscitis) in adults. Eur J Nucl Med Mol Imaging. 2019;46:2464?87.

Sconfienza LM, Signore A, Cassar-Pullicino V, Cataldo MA, Gheysens O, Borens O, et al. Diagnosis of peripheral bone and prosthetic joint infections: overview on the consensus documents by the EANM, EBJIS, and ESR (with ESCMID endorsement). Eur Radiol. 2019;29:6425-6438.

Signore A, Sconfienza LM, Borens O, Glaudemans AWJM, Cassar-Pullicino V, Trampuz A, et al. Consensus document for the diagnosis of prosthetic joint infections: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement). Eur J Nucl Med Mol Imaging. 2019;46:971?88.

Glaudemans AWJM, Jutte PC, Cataldo MA, Cassar-Pullicino V, Gheysens O, Borens O, et al. Consensus document for the diagnosis of peripheral bone infection in adults: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement). Eur J Nucl Med Mol Imaging. 2019;46:957?70.

Slart RHJA; Writing group; Reviewer group; Members of EANM Cardiovascular; Members of EANM Infection & Inflammation; Members of Committees, SNMMI Cardiovascular; Members of Council, PET Interest Group; Members of ASNC; EANM Committee Coordinator. FDG-PET/CT(A) imaging in large vessel vasculitis and polymyalgia rheumatica: joint procedural recommendation of the EANM, SNMMI, and the PET Interest Group (PIG), and endorsed by the ASNC. Eur J Nucl Med Mol Imaging. 2018;45:1250?69.

Signore A, Jamar F, Israel O, Buscombe J, Martin-Comin J, Lazzeri E. Clinical indications, image acquisition and data interpretation for white blood cells and anti-granulocyte monoclonal antibody scintigraphy: an EANM procedural guideline. Eur J Nucl Med Mol Imaging. 2018;45:1816?31.

Van den Wyngaert T, Strobel K, Kampen WU, Kuwert T, van der Bruggen W, Mohan HK, et al. The EANM practice guidelines for bone scintigraphy. Eur J Nucl Med Mol Imaging. 2016;43:1723?38.

Bucerius J, Hyafil F, Verberne HJ, Slart RH, Lindner O, Sciagr� R, et al. Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM) on PET imaging of atherosclerosis. Eur J Nucl Med Mol Imaging. 2016;43:780?92.

Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta JP, Del Zotti F, et al. 2015 ESC guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;36:3075?128.

Jamar F, Buscombe J, Chiti A, Christian PE, Delbeke D, Donohoe KJ, et al. EANM/SNMMI guideline for 18F-FDG use in inflammation and infection. J Nucl Med. 2013;54:647?58.

Panes J, Bouhnik Y, Reinisch W, Stoker J, Taylor SA, Baumgart DC, et al. Imaging techniques for assessment of inflammatory bowel disease: joint ECCO and ESGAR evidence-based consensus guidelines. J Crohns Colitis. 2013;7:556?85.

de Vries EF, Roca M, Jamar F, Israel O, Signore A. Guidelines for the labelling of leucocytes with 99mTc-HMPAO. Inflammation/Infection Taskgroup of the European Association of Nuclear Medicine. Eur J Nucl Med Mol Imaging. 2010;37:842?8.

Roca M, de Vries EF, Jamar F, Israel O, Signore A. Guidelines for the labelling of leucocytes with 111In-oxine. Inflammation/Infection Taskgroup of the European Association of Nuclear Medicine. Eur J Nucl Med Mol Imaging. 2010;37:835?41.

Contents
Giovanni�D?Errico, Emanuele�Casciani and Saadi�Sollaku
Giovanni�D?Errico, Emanuele�Casciani and Saadi�Sollaku
Giovanni�D?Errico, Emanuele�Casciani and Saadi�Sollaku
Paola�Anna�Erba, Francesco�Bartoli, Roberta�Zanca and Martina�Sollini
Martina�Sollini, Francesco�Bandera, Francesco�Bartoli, Roberta�Zanca, Elena�Lazzeri and Paola�Anna�Erba
Elena�Lazzeri, Roberta�Zanca and Martina�Sollini
Alberto�Signore, Tiziana�Lanzolla and Chiara�Lauri
Napoleone�Prandini and Andrea�Bedini
Martina�Sollini and Giuliano�Mariani
Annibale�Versari and Massimiliano�Casali
Riemer�H.�J.�A.�Slart, Florent�L.�Besson and Jan�Bucerius
Maria�Carmen�Garganese, Maria�Felicia�Villani and Giovanni�D?Errico
Index 353
Contributors
Francesco�Bandera
Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
Cardiology University Department, Heart Failure Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy
Francesco�Bartoli
Department of Translational Research and Advanced Technologies in Medicine and Surgery, Regional Center of Nuclear Medicine, University of Pisa, Pisa, Italy
Andrea�Bedini
Infectious Diseases Unit, Department of Medical and Surgical Sciences for Children and Adults, University Hospital ?Policlinico di Modena?, Modena, Italy
Florent�L.�Besson
Department of Biophysics and Nuclear Medicine-Molecular Imaging, H�pitaux Universitaires Paris-Saclay, Assistance Publique-H�pitaux de Paris, CHU Bic�tre, Le Kremlin Bic�tre, France
Universit� Paris Saclay, CEA, CNRS, Inserm, BioMaps, Orsay, France
Jan�Bucerius
Department of Nuclear Medicine, University Medicine G�ttingen, Georg-August-University G�ttingen, G�ttingen, Germany
Massimiliano�Casali
Nuclear Medicine, Azienda Unit� Sanitaria Locale-IRCCS of Reggio Emilia, Reggio Emilia, Italy
Emanuele�Casciani
Department of Nuclear Medicine, Private Hospital ?Pio XI?, Rome, Italy
Giovanni�D?Errico
Department of Nuclear Medicine, Private Hospital ?Pio XI?, Rome, Italy
Paola�Anna�Erba
Department of Translational Research and Advanced Technologies in Medicine and Surgery, Regional Center of Nuclear Medicine, University of Pisa, Pisa, Italy
Maria�Carmen�Garganese
Nuclear Medicine Unit, Department of Imaging, ?Bambino Ges�? Pediatric Hospital, Rome, Italy
Tiziana�Lanzolla
Nuclear Medicine Unit, AOU Sant?Andrea, Rome, Italy
Chiara�Lauri
Department of Medical-Surgical Sciences and of Translational Medicine, Sapienza University of Rome, Rome, Italy
Nuclear Medicine Unit, AOU Sant?Andrea, Rome, Italy
Elena�Lazzeri
Regional Center of Nuclear Medicine, University Hospital of Pisa, Pisa, Italy
Giuliano�Mariani
Department of Translational Research and Advanced Technologies in Medicine and Surgery, Regional Center of Nuclear Medicine, University of Pisa, Pisa, Italy
Napoleone�Prandini
Nuclear Medicine Department, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
Alberto�Signore
Department of Medical-Surgical Sciences and of Translational Medicine, Sapienza University of Rome, Roma, Italy
Nuclear Medicine Unit, AOU Sant?Andrea, Rome, Italy
Riemer�H.�J.�A.�Slart
Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Department of Biomedical Photonic Imaging, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands
Saadi�Sollaku
Department of Nuclear Medicine, Private Hospital ?Pio XI?, Rome, Italy
Martina�Sollini
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
Humanitas Clinical and Research Center - IRCCS, Rozzano, Italy
Annibale�Versari
Nuclear Medicine, Azienda Unit� Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
Maria�Felicia�Villani
Nuclear Medicine Unit, Department of Imaging, ?Bambino Ges�? Pediatric Hospital, Rome, Italy
Roberta�Zanca
Department of Translational Research and Advanced Technologies in Medicine and Surgery, Regional Center of Nuclear Medicine, University of Pisa, Pisa, Italy