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NUCLEAR
CARDIAC
IMAGING
• PrindpLes 8c Applications •

AMI E. ISKANDRIAN
FADI G . HAGE
S1 X T H E O I T I O N

OXFORD
N UC L E A R CA RDI AC I MAGI NG
NUCLEAR CARDIAC IMAGING
Principles and Applications

SIXTH EDITION

Ami E. Iskandrian and Fadi G. Hage

Oxford University Press is a department of the University of Oxford. It furthers
the University’s objective of excellence in research, scholarship, and education
by publishing worldwide. Oxford is a registered trade mark of Oxford University
Press in the UK and certain other countries.

Published in the United States of America by Oxford University Press

198 Madison Avenue, New York, NY 10016, United States of America.

© Oxford University Press 2024

All rights reserved. No part of this publication may be reproduced, stored in

a retrieval system, or transmitted, in any form or by any means, without the
prior permission in writing of Oxford University Press, or as expressly permitted
by law, by license, or under terms agreed with the appropriate reproduction
rights organization. Inquiries concerning reproduction outside the scope of the
above should be sent to the Rights Department, Oxford University Press, at the
address above.

You must not circulate this work in any other form

and you must impose this same condition on any acquirer.

CIP data is on file at the Library of Congress

ISBN 978–​0–​19–​009565–​9

DOI: 10.1093/​med/​9780190095659.001.0001

This material is not intended to be, and should not be considered, a substitute for medical or other professional advice. Treatment for the conditions described
in this material is highly dependent on the individual circumstances. And, while this material is designed to offer accurate information with respect to the subject
matter covered and to be current as of the time it was written, research and knowledge about medical and health issues is constantly evolving and dose schedules for
medications are being revised continually, with new side effects recognized and accounted for regularly. Readers must therefore always check the product information
and clinical procedures with the most up-​to-​date published product information and data sheets provided by the manufacturers and the most recent codes of
conduct and safety regulation. The publisher and the authors make no representations or warranties to readers, express or implied, as to the accuracy or completeness
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incurred as a consequence of the use and/​or application of any of the contents of this material.

Printed by Integrated Books International, United States of America

To our wives, Sulaf Hage, MS, MD, and
Greta P. Iskandrian, MD
And to our children, their spouses and children
(our grandchildren)
Alexander, Gabrielle, and Diana Hage
Basil Iskandrian and Kimberly Iskandrian
(Szabba, Luca, and Roan)
Susan Buckingham, MD, and Brendhan Buckingham, MD
(Ella, Lilia, Ava, and Ian)
Kristen Connell, PhD, and Brian Connell (Beatrice and
Simone)
 CONTENTS

Preface ix 12. PHARMACOLOGIC STRESS TESTING 250

Contributors xi Efstathia Andrikopoulou, Ami E. Iskandrian, and
Fadi G. Hage
SECTION I. HISTORICAL, TECHNICAL, AND 13. DIAGNOSIS AND RISK ASSESSMENT WITH SPECT MPI 280
PHYSIOLOGIC CONSIDERATIONS Javier Gomez and Rami Doukky

1. NUCLEAR CARDIOLOGY: HISTORY AND MILESTONES
Barry L. Zaret and Frans J. Th. Wackers
2. RADIATION PHYSICS AND RADIATION SAFETY
Paul H. Murphy and James R. Galt
3 14. SPECT MPI FOR RISK ASSESSMENT IN SPECIAL
GROUPS: DIABETES MELLITUS, KIDNEY TRANSPLANT,
LIVER TRANSPLANT, ASYMPTOMATIC, OBESE 303
13 Alberto Cuocolo, Emilia Zampella, Valeria Gaudieri,
and Roberta Assante

3. SPECT AND PET INSTRUMENTATION: CONVENTIONAL 15. SPECT MPI AND RISK ASSESSMENT BEFORE NON-​
AND NEW 38 CARDIAC SURGERY 322

James R. Galt, Ernest V. Garcia and Ji Chen Daniel C. Fisher and Lawrence M. Phillips

4. KINETICS OF CONVENTIONAL AND NEW CARDIAC 16. EVALUATION OF PATIENTS WITH CHEST PAIN IN THE
RADIOTRACERS 61 EMERGENCY DEPARTMENT 338

Ran Klein, Robert A. deKemp, Benjamin Rotstein, Elona Rrapo Kaso and Jamieson M. Bourque
and Keiichiro Yoshinaga
17. ROLE OF PET IN DIAGNOSIS AND RISK ASSESSMENT
5. RADIONUCLIDE ANGIOGRAPHY 87 IN PATIENTS WITH KNOWN OR SUSPECTED CAD 357

Steven Port Christiane Wiefels, Brian A. Mc Ardle,

Jennifer M. Renaud, Robert A. deKemp,
6. GATED SPECT MPI: IMAGING PROTOCOLS AND Rob S. B. Beanlands, and Steven Promislow
ACQUISITIONS; PROCESSING AND QUANTIFICATION 126
18. NUCLEAR CARDIAC IMAGING IN WOMEN 379
Milena J. Henzlova, Sean R. McMahon,
and W. Lane Duvall Viviany R. Taqueti and
Ana Carolina do A. H. de Souza
7. ARTIFACTS 152
19. MYOCARDIAL VIABILITY ASSESSMENT BY NUCLEAR
William A. Van Decker TECHNIQUES 398
Vasken Dilsizian, Ines Valenta, and
SECTION II. DIAGNOSIS AND RISK ASSESSMENT Thomas H. Schindler

8. REGULATION OF MYOCARDIAL BLOOD FLOW 171

SECTION III. ROLE OF NUCLEAR IMAGING
Henry Gewirtz
BEYOND CAD
9. MEASUREMENT OF MYOCARDIAL BLOOD FLOW BY PET 187
20. IMAGING DYSSYNCHRONY 425
Heinrich R. Schelbert
Alessia Gimelli and Riccardo Liga
10. MEASUREMENT OF MYOCARDIAL BLOOD FLOW BY SPECT 208
21. IMAGING MYOCARDIAL INNERVATION BY SPECT AND PET 445
Juliana Brenande de Oliveira Brito, Gary R. Small,
Kathryn J. Ascah, R. Glenn Wells, and Mark I. Travin
Terrence D. Ruddy
22. IMAGING SARCOID HEART DISEASE 466
11. TREADMILL EXERCISE TESTING 230 David G. Rosenthal and Paco E. Bravo
Gregory S. Thomas and L. Samuel Wann
23. IMAGING AMYLOID HEART DISEASE 481 33. RADIONUCLIDE IMAGING IN PATIENTS WITH
CONGENITAL HEART DISEASES 655
John P. Bois, Martha Grogan, and
Panithaya Chareonthaitawee Sara L. Partington and Sharmila Dorbala

24. IMAGING INFECTION OF VALVES AND DEVICES 495

Thomas H. Schindler, Soraya El Ghannudi, and SECTION V. CHALLENGES FOR NUCLEAR
Alessio Imperiale CARDIOLOGY

25. IMAGING CARDIAC AND VASCULAR INFLAMMATION 511 34. PHYSICIAN CERTIFICATION AND LABORATORY
Sina Tavakoli and Mehran M. Sadeghi ACCREDITATION 673
Robert C. Hendel, Minnsun K. Park, and
26. RADIONUCLIDE IMAGING IN HEART FAILURE 531 Gursukhmandeep S. Sidhu
Daniel Shpilsky and Prem Soman
35. NUCLEAR CARDIOLOGY GUIDELINES AND APPROPRIATE
USE CRITERIA: AMERICAN COLLEGE OF CARDIOLOGY,
SECTION IV. ADVANCES IN NUCLEAR AMERICAN HEART ASSOCIATION, AND EUROPEAN
SOCIETY OF CARDIOLOGY 686
CARDIAC IMAGING
Timothy F. Christian
27. EVOLVING ROLE OF ECHOCARDIOGRAPHY, CARDIAC CT,
36. NUCLEAR CARDIOLOGY REPORT GENERATION 698
AND CARDIAC MRI IN CAD 543
Arnold C. T. Ng, Victoria Delgado, and Wael A. AlJaroudi
Jeroen J. Bax
37. RADIATION CONSIDERATIONS IN IMAGING 709
28. HYBRID IMAGING: SPECT/CCTA, PET/​MR, AND SPECT Andrew J. Einstein
CALCIUM SCORE: WHEN AND WHY? 582
38. STATISTICS IN NUCLEAR IMAGING 729
Philipp A. Kaufmann, Oliver Gaemperli,
and Ronny R. Buechel Charity J. Morgan and Anastasia M. Hartzes

29. ARTIFICIAL INTELLIGENCE AND NUCLEAR IMAGING 596
Robert J. H. Miller and Piotr J. Slomka
30. NUCLEAR IMAGING IN PATIENTS WITH SERIOUS
ARRHYTHMIAS 610
Ravi Venkatesh and Saurabh Malhotra
39. NUCLEAR IMAGING IN DEVELOPING COUNTRIES 742
Amalia Peix, Diana Paez, Joao V. Vitola,
Pilar Orellana, and Maurizio Dondi
SECTION VI. OVERVIEW

31. THE ROLE OF NUCLEAR CARDIOLOGY IN THE 40. ESSENTIALS OF NUCLEAR CARDIAC IMAGING:
MANAGEMENT OF CARDIOVASCULAR DISEASES IN ASK THE EXPERTS 757
PATIENTS LIVING WITH HIV 624 Ami E. Iskandrian, Fadi G. Hage,
Ahmed Aljizeeri and Mouaz H. Al-​Mallah Pradeep Bhambhvani, and Ernest V. Garcia

32. NUCLEAR IMAGING IN CARDIO-​ONCOLOGY 636 Index 781

Matthew E. Harinstein and Raymond Russell, III

viii
 PREFACE
W
e are pleased to bring you the sixth edition
of Nuclear Cardiac Imaging: Principles and
Applications. In keeping with the tradition of the
first edition of this book, which was published 35 years ago,
and the subsequent editions, we strived to give you a book
that is comprehensive, up to date, relevant, and yet easy to
read. We believe this edition will remain the ultimate refer-
ence on nuclear cardiology for the coming years.
While planning this edition, we appreciated the many
advances and innovations that have occurred in the field
since the last edition. Rather than updating the prior edi-
tion we put together an almost completely new book. A few
chapters have been updated, some have been deleted, others
have been combined with completely new content by dif-
ferent authors, and many are brand new. In doing so, we
have listened to our readers who wanted us to retain the
acclaimed features of the prior editions, which made the
book a huge success, while simultaneously making changes
to the organization and content to reflect the astounding
developments in nuclear cardiology.
Each chapter in the book is written by a leader in nu-
clear cardiology. Every chapter starts with 10 key points that
summarize the important information within the chapter.
Each chapter is enriched with plenty of tables, colored fig-
ures, and highly relevant references. The book has an online
version that includes downloadable figures and videos.
We are indebted to the authors for their sacrifices, es-
pecially during the COVID pandemic, when this work
was being done; they were all selected because of their ex-
cellence and enormous contributions to our field. We have
asked the authors not to shy away from controversy and
to express their views in an open and transparent manner.
Both of us have read all the chapters in their entirety and
provided the authors with feedback while writing. While
we tried our best to make the chapters consistent with each
other and with the prevailing literature, we wanted the
reader to appreciate the constantly evolving nature of some
topics and to retain the honest assessment and views of the
authors. For that reason, some overlap or repetition is una-
voidable and may actually be healthy. While all the credit
goes to the individual authors, the errors that remain are
entirely ours. It was our pleasure to work on this book day
in and day out with such a distinctive group of professionals
who made our job so much easier.
The book is divided into six sections. The first section
has seven chapters dealing with historical, technical, and
physiologic considerations (Chapters 1–​7). The second
section has 12 chapters dealing with diagnosis and risk
assessment (Chapters 8–​19). The third section has seven
chapters that address the role of nuclear imaging beyond
coronary artery disease (Chapters 20–​26). The fourth sec-
tion has seven chapters on advances in nuclear cardiac im-
aging (Chapters 27–​33). The fifth section consists of six
chapters that deal with challenges for nuclear cardiology
(Chapters 33–​39). The sixth and last section consists of
just one chapter, which provides an overview of the book.
Chapter 40 provides the essentials of nuclear cardiac im-
aging as a reference to the reader by answering 26 questions
encountered by practitioners in the field on a regular basis.
A new aspect to this edition is a Companion Atlas, which
will help readers apply the knowledge they acquired from the
chapters. The Atlas has chapters that mirror those included
in the book. Some chapters include case presentations with
a wealth of multimodality images to ground the topics in
clinical care. Others consist of multiple-​choice questions
and discussions to help solidify the knowledge gained. We
recommend reading the book chapter first in its entirety be-
fore moving on to the corresponding chapter in the Atlas
for maximum benefit. The last chapter in the Atlas is a self-​
assessment tool on the content of the book. This chapter
consists of 40 questions followed by multiple-​choice
answers. These questions were contributed by the authors of
the chapters and are followed by a quick discussion. For full
discussion, please refer back to the respective chapters.
We could not have edited this book without the un-
wavering support of our families. We are grateful for their
many sacrifices and especially for allowing us to carry this
monumental effort to its fruition. This book benefits from
our professional and personal interactions with our trainees
and colleagues who have helped transform this book into a
bridge between understanding principles and applying them
in clinical care. Our thanks are extended to the superb team
at Oxford University Press and especially to Katie Lakina
and Gnanambigai Jayakumar for their invaluable efforts.
Lastly, we would like to acknowledge three giants of the field
who passed away while working on this book: Drs. Barry
L. Zaret (Chapter 1), Keiichiro Yoshinaga (Chapter 4) and
Henry Gewirtz (Chapter 8). May their souls rest in peace
and their memory remain alive, in part through their enor-
mous contributions to nuclear cardiology.
x
We believe this edition of the book will be of great in-
terest and a reference standard to trainees in imaging, espe-
cially nuclear cardiology; those who perform and interpret
these images regardless of their specialty, place of work,
and affiliations; and also those who use these images for pa-
tient care.
We hope that you will enjoy and benefit from reading
this book as much as we did in bringing it to you.
Fadi G. Hage, MD, FACC, MASNC
Ami E. Iskandrian, MD, MACC, MASNC
 CONTRIBUTORS
Wael A. AlJaroudi, MD, EMBA, FACC, FASNC
Professor of Medicine
Wellstar Health Medical College of Georgia
Augusta, Georgia, USA
Ahmed Aljizeeri, MBBS
King Abdulaziz Cardiac Center, Riyadh, Kingdom of
Saudi Arabia
King Saud bin Abdulaziz University for Health
Sciences—​Riyadh, Kingdom of Saudi Arabia
King Abdullah International Medical Research
Center—​Riyadh, Kingdom of Saudi Arabia
Mouaz H. Al-​Mallah, MD, Msc
Beverly B. and Daniel C. Arnold Distinguished Chair,
Professor of Cardiology, Houston Methodist Academic
Institute and Professor of Medicine, Weill Cornell
Medicine.
Director, Cardiovascular PET, Houston Methodist
DeBakey Heart and Vascular Center, Houtson, Texas,
USA
Efstathia Andrikopoulou, MD, MBA, FACC
Assistant Professor of Medicine, Cardiovascular Disease,
University of Alabama at Birmingham,
Birmingham, AL, USA
Kathryn J. Ascah
Division of Cardiology, University of Ottawa Heart
Institute, Ottawa, Ontario, Canada
Roberta Assante, MD, PhD
Department of Advanced Biomedical Sciences, School of
Medicine, University of Naples Federico II, Naples, Italy
Jeroen J. Bax, MD, PhD
Department of Cardiology, Leiden University Medical
Centre, Leiden, The Netherlands
Rob S. B. Beanlands, MD, FRCP(C), FACC, MASNC,
FCCS
Deputy Director General, University of Ottawa Heart
Institute
Professor of Medicine—Division of Cardiology and
Distinguished Chair in Cardiovascular Imaging Research
University of Ottawa, Ontario, Canada
Pradeep Bhambhvani, MD
Professor of Radiology
The University of Alabama at Birmingham
Birmingham, Alabama, USA
John P. Bois, MD
Associate Professor of Medicine, Mayo Clinic,
Rochester, Minnesota, USA
Jamieson M. Bourque, MD, MHS
Professor of Medicine and Radiology, Medical Director of
Nuclear Cardiology and the Stress Laboratory, Medical
Director of Echocardiography, University of Virginia,
Charlottesville, Virginia, USA
Paco E. Bravo, MD
Divisions of Nuclear Medicine and Cardiothoracic
Imaging, Department of Radiology, and Division
of Cardiology, Department of Medicine, Hospital
of the University of Pennsylvania, Philadelphia,
Pennsylvania, USA
Juliana Brenande de Oliveira Brito
Division of Cardiology, University of Ottawa Heart
Institute, Ottawa, Ontario, Canada
Ronny R. Buechel, MD
Deputy Director and Professor,
University Hospital Zurich, Department of Nuclear
Medicine, Cardiac Imaging, Zurich, Switzerland
Panithaya Chareonthaitawee, MD
Professor of Medicine, Director of Nuclear Cardiology,
Mayo Clinic, Rochester, Minnesota, USA
Ji Chen, PhD
Head of Engineering, Acelerate
San Francisco Bay Area
Timothy F. Christian, MD, MPA
DeMatteis Research Center/​St Francis Hospital, Roslyn,
New York, USA
Alberto Cuocolo
Department of Advanced Biomedical Sciences, School of
Medicine, University of Naples Federico II, Naples, Italy
Robert A. deKemp, PhD
Head Imaging Physicist, University of Ottawa Heart
Institute, Ottawa, Ontario, Canada
Victoria Delgado, MD, PhD
Department of Cardiology, Leiden University Medical
Centre, Leiden, The Netherlands
Ana Carolina do A. H. de Souza, MD, PhD
Cardiovascular Imaging Program, Brigham and
Women’s Hospital, Harvard Medical School, Boston,
Massachusetts, USA
Vasken Dilsizian, MD
Chief, Division of Nuclear Medicine, Department
of Diagnostic Radiology and Nuclear Medicine,
University of Maryland School of Medicine, Baltimore,
Maryland, USA
Maurizio Dondi, MD
Division of Human Health, International Atomic Energy
Agency, Vienna, Austria
Sharmila Dorbala, MD, MPH
Director of Nuclear Cardiology, Professor of Radiology,
Brigham and Women’s Hospital, Harvard Medical
School, Boston, Massachusetts, USA
Rami Doukky, MD, MSc, MBA, FASNC
Chairman, Division of Cardiology
Cook County Health,
Chicago, Illinois, USA
xii
W. Lane Duvall, MD, FASNC
Director of Nuclear Cardiology, Hartford Hospital,
Hartford, CT, USA
Andrew J. Einstein, MD, PhD, FACC, FAHA, MASNC,
MSCCT, FSCMR
Professor of Medicine (in Radiology)
Director, Nuclear Cardiology, Cardiac CT, and Cardiac MRI
Director, Advanced Cardiac Imaging Fellowship
Seymour, Paul and Gloria Milstein Division of Cardiology,
Department of Medicine, Columbia University Irving
Medical Center/NewYork-Presbyterian Hospital
New York, New York, United States of America
Soraya El Ghannudi, MD, PhD
Departments of Radiology and Nuclear Medicine, Nouvel
Hôpital Civil—​University Hospitals of Strasbourg,
Strasbourg, France
Daniel C. Fisher, MD
Director, Stress Nuclear Laboratory, Bellevue Hospital,
New York, USA
Oliver Gaemperli, MD, FESC
Professor, Consultant Cardiologist, HeartClinic Zurich
AG, Hirslanden Hospital, Zurich, Switzerland, EU
James R. Galt, PhD
Professor of Radiology and Imaging Sciences, Emory
University School of Medicine, Atlanta, Georgia, USA
Ernest V. Garcia, PhD, FASNC
Professor of Radiology and Imaging Sciences (Retired)
Emory University School of Medicine, Atlanta, Georgia, USA
Valeria Gaudieri, MD, PhD
Department of Advanced Biomedical Sciences, School of
Medicine, University of Naples Federico II, Naples, Italy
Henry Gewirtz, MD†
Professor of Medicine, Harvard Medical School
Boston, Massachusetts, USA
Alessia Gimelli, MD, FESC
Head of Nuclear Cardiology Lab, Imaging Department,
Fondazione Toscana Gabriele Monasterio, Pisa, Italy
Javier Gomez, MD
Division of Cardiology, Cook County Health,
Chicago, Illinois. USA
Martha Grogan, MD
Associate Professor of Medicine, Department of
Cardiovascular Medicine, Mayo Clinic, Rochester,
Minnesota, USA
Fadi G. Hage, MD, FACC, FAHA, FSCCI, MASNC
Professor of Medicine, Cardiovascular Disease, University
of Alabama at Birmingham and the Birmingham VA
Medical Center, Birmingham, Alabama, USA
Matthew E. Harinstein, MD, MBA
SVP, COO, Associate CMO, UPMC International,
Associate Professor of Medicine, University of Pittsburgh
School of Medicine, Pittsburgh, Pennsylvania, USA
Anastasia M. Hartzes, PhD
Department of Biostatistics, University of Alabama at
Birmingham, Birmingham, Alabama, USA
Robert C. Hendel, MD, MACC, MASNC
Professor of Medicine and Radiology, Tulane University
School of Medicine, New Orleans, Louisiana, USA
Milena J. Henzlova, MD, PhD
Mount Sinai Medical Center
New York, NY, USA
Alessio Imperiale, MD, PhD
Department of Nuclear Medicine and Molecular Imaging,
Institut de Cancérologie de Strasbourg Europe
(ICANS), Strasbourg, France
Ami E. Iskandrian, MD, MACC, MASNC
Professor Emeritus
Heersink School of Medicine, University of Alabama at
Birmingham
Birmingham Alabama, USA
Philipp A. Kaufmann, MD
Professor and Chairman, Department of Nuclear
Medicine, University Hospital Zurich, Zurich, SZ
Ran Klein
Imaging Physicist, The Ottawa Hospital
Ottawa, Ontario, Canada
Riccardo Liga, MD, PhD, FESC
University of Pisa and University Hospital of Pisa,
Pisa, Italy
CONTRIBUTORS
Saurabh Malhotra, MD, MPH
Director of Advanced Cardiac Imaging, Cook County
Health, Chicago, Illinois, USA
Brian A. Mc Ardle, MD
Clinical Assistant Professor, University of British
Columbia, Victoria, British Columbia, Canada
Sean R. McMahon
Division of Cardiology, Hartford Hospital, Hartford
Heart and Vascular Institute, Hartford, CT, USA
Robert J. H. Miller, MD, FRCPC, FACC
Clinical Associate Professor, University of Calgary,
Calgary, Alberta, Canada
Charity J. Morgan, PhD
Professor, The University of Alabama at Birmingham
Birmingham, AL, USA
Paul H. Murphy, PhD
Professor Emeritus of Radiology, Baylor College of
Medicine, Houston, Texas, USA
Arnold C. T. Ng, MBBS, PhD
Department of Cardiology, Princess Alexandra Hospital,
University of New South Wales, Australia
Pilar Orellana, MD
Nuclear Medicine and Diagnostic Imaging Section,
Division of Human Health, International Atomic
Energy Agency, Vienna, Austria
Diana Paez, MD, MSc, Ed.
Head of the Nuclear Medicine and Diagnostic Imaging
Section, Division of Human Health, International
Atomic Energy Agency, Vienna, Austria
Minnsun K. Park, MD
Cardiology Fellow, Tulane University School of Medicine,
New Orleans, Louisiana, USA
Sara L. Partington, MD
Assistant Professor of Clinical Medicine, Hospital
of the University of Pennsylvania and Children’s
Hospital of Philadelphia, Philadelphia,
Pennsylvania, USA
Amalia Peix, MD, MSc, PhD
Nuclear Cardiologist, Master in Cardiac Magnetic
Resonance Francisco Vittoria University Spain,
Institute of Cardiology and Cardiovascular Surgery,
La Habana, Cuba
Lawrence M. Phillips, MD
Associate Professor of Medicine, Leon H. Carney Division
of Cardiology, NYU Grossman School of Medicine,
New York USA
Steven Port, MD
AdvocateAuroraHealth, Aurora Cardiovascular Services,
Milwaukee, Wisconsin, USA
Steven Promislow, MD, FRCPC
Assistant Professor of Medicine
Department of Internal Medicine, Section of Cardiology
University of Manitoba
Winnipeg, Manitoba, Canada
Jennifer M. Renaud, MSC
Research Scientist, INVIA Medical Imaging Solutions,
Ann Arbor, Michigan, USA
David G. Rosenthal, MD, FACC, FHRS
Swedish Medical Center,
Seattle, Washington, USA
Benjamin Rotstein, PhD
Associate Professor and Scientist
University of Ottawa and University of Ottawa Heart
Institute, Ottawa, Ontario, Canada
Elona Rrapo Kaso, MD
Division of Cardiovascular Medicine and the Cardiac
Imaging Center, Departments of Medicine and
Radiology, University of Virginia Health System,
Charlottesville, Virginia, USA
Terrence D. Ruddy, MD, FRCPC, FACC, FAHA,
FCCS, FSNMMI, MASNC
Consulting Cardiologist, Division of Cardiology,
Professor of Medicine and Radiology,University of
Ottawa Heart Institute, Ottawa, Ontario, Canada
Raymond Russell, MD, PhD, MASNC, FACC
Professor of Medicine, Institution Alpert Medical
School of Brown University, Providence, Rhode
Island, USA
xiv
Mehran M. Sadeghi, MD
Professor of Medicine (Cardiology), Yale School of
Medicine, New Haven, Connecticut, USA
Physician, VA Connecticut Healthcare System, West
Haven, Connecticut, USA
Heinrich R. Schelbert, MD, PhD
Department of Molecular and Medical Pharmacology,
David Geffen School of Medicine at UCLA,
University of California at Los Angeles, Los Angeles,
California, USA
Thomas H. Schindler, MD, PhD
Professor of Radiology and Medicine; Mallinckrodt
Institute of Radiology, Division of Nuclear Medicine,
Washington University in Saint Louis, School of
Medicine, Saint Louis, Missouri, USA
Daniel Shpilsky, MD
Division of Cardiology, University of Pittsburgh Medical
Center, Pittsburgh, Pennsylvania, USA
Gursukhmandeep S. Sidhu, MD
University of Illinois Chicago,
Chicago, Illinois, USA
Piotr J. Slomka, PhD
Departments of Medicine (Division of Artificial Intelligence
in Medicine), Imaging and Biomedical Sciences Cedars-​
Sinai Medical Center, Los Angeles, CA, USA
Gary R. Small
Division of Cardiology, University of Ottawa Heart
Institute, Ottawa, Ontario, Canada
Prem Soman, MD, PhD
Professor of Medicine, and Clinical and Translational
Science, University of Pittsburgh Medical Center,
Pittsburgh, Pennsylvania, USA
Viviany R. Taqueti, MD, MPH
Cardiovascular Imaging Program, Brigham and Women’s
Hospital and Cardiology Division, VA Boston
Healthcare, Harvard Medical School, Boston,
Massachusetts, USA
Sina Tavakoli, MD, PhD
Assistant Professor and Chief of the Division of
Cardiothoracic Imaging, Department of Radiology,
University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Gregory S. Thomas, MD, MPH, FACC, MASNC
MemorialCare Health System, Fountain Valley, California,
USA; Division of Cardiology, University of California,
Irvine, California, USA
Mark I. Travin, MD, FACC, MASNC
Division of Nuclear Medicine, Professor of Clinical
Radiology and Clinical Medicine, Montefiore Medical
Center. Albert Einstein College of Medicine, Bronx,
New York, USA
Ines Valenta, MD
Research Associate; Mallinckrodt Institute of Radiology,
Washington University in Saint Louis, School of
Medicine, Saint Louis, Missouri, USA
William A. Van Decker, MD
Professor of Medicine, Lewis Katz School of Medicine at
Temple University, Philadelphia, Pennsylvania, USA
Venkatesh Ravi, MD, FACC, FHRS
Clinical Cardiac Electrophysiologist, Adjunct Clinical
Assistant Professor, Saint Francis Health System,
Tulsa, Oklahoma, USA, Chicago, Illinois, USA
Joao V. Vitola, MD, PhD
Quanta Diagnóstico & Terapia, Curitiba, Brazil
Frans J. Th. Wackers, MD, PhD
Professor Emeritus of Diagnostic Radiology and Medicine
(Cardiology), Yale University School of Medicine, New
Haven, Connecticut, USA
CONTRIBUTORS
L. Samuel Wann, MD
Clinical Professor of Cardiovascular Medicine, University
of New Mexico Santa Fe, New Mexico
R. Glenn Wells
Division of Cardiology, University of Ottawa Heart
Institute, Ottawa, Ontario, Canada
Christiane Wiefels, MD, PhD
Assistant Professor of Medicine, Department of
Medicine, Division of Nuclear Medicine, University
of Ottawa, Canada
Keiichiro Yoshinaga, MD, PhD†
Team leader at the Department of Molecular Imaging
and Theragnostic, National Institute of Radiological
Sciences, Chiba, Japan
Emilia Zampella
Department of Advanced Biomedical Sciences, School
of Medicine, University of Naples Federico II,
Naples, Italy
Barry L. Zaret, MD†
Robert W. Berliner Professor Emeritus of Internal
Medicine (Cardiology), Yale University School of
Medicine, New Haven, Connecticut, USA
I.

HISTORICAL, TECHNICAL, AND

PHYSIOLOGIC CONSIDERATIONS
 1.

NUCLEAR CARDIOLOGY
HI STO RY A ND M I LESTONES

Barry L. Zaret and Frans J. Th. Wackers

K EY P OIN TS 10. New cardiac-​centered SPECT systems provide

1. The initial application of radioisotopes to cardiac high-​sensitivity, high-​resolution studies, allowing
studies occurred in the mid-​1920s. for radiation dose reduction and high-​quality
imaging studies.
2. Ventricular function was evaluated in the
1960s and 1970s by first-​pass and equilibrium
techniques. AB B R E v IAT IONS
3. Myocardial stress perfusion imaging was first
performed using potassium-​43 and exercise ERNA equilibrium radionuclide
in 1973. angiocardiography
4. Stress imaging rapidly evolved thereafter with FDG (F-​18) fluorodeoxyglucose
new tracers (thallium-​201 and technetium-​ FPRNA first-​pass radionuclide
99m-​labeled agents) and from planar to SPECT angiocardiography
approaches. LV left ventricular
LVEF left ventricular ejection fraction
5. Perfusion imaging rapidly proved its value MI myocardial infarction
diagnostically and in assessing prognosis. PET positron emission tomography
6. Acute infarct imaging reached its peak use in the PYP pyrophosphate
1970s but is now no longer employed. RVEF right ventricular ejection fraction
7. Advances in hybrid imaging, combining SPECT single-​photon emission computed
computed tomography with radionuclide tomography
imaging, have recently allowed attenuation Tc-​99m technetium-​99m
correction as well as providing the combination of
anatomic and physiologic data.
Nuclear cardiology is generally considered a clinical sub­
8. PET myocardial perfusion studies have recently specialty of the past four decades. However, the field
become a standard approach for evaluating has its roots in earlier times. This chapter focuses on
myocardial perfusion, absolute quantification of these historical roots as they have evolved into the pre-
coronary blood flow, and coronary flow reserve. sent era. Space constraints mandate focusing solely on
9. PET FDG studies of cardiac sarcoidosis have the highlights. Apologies to the many highly produc-
recently been established as a new approach for tive investigators and laboratories whose contributions
defining myocardial inflammation. helped the field grow to its current level, but who could
not be included.
 HEA RT FUNCTI O N AN D CI RCULATO RY for imaging with the sodium-​iodide crystal of the Anger
DY NA M ICS camera. Early pioneers in the field (such as Joseph Kriss)
demonstrated the ability to visualize cardiac structures
The initial application of radioisotopes to the study of circu- from rapid sequential radionuclide images following in-
lation occurred in the mid-​1920s (Table 1.1). A renowned jection of a bolus of Tc-​99m–​labeled radiotracers. From
5,6

cardiology investigator of that era, Hermann Blumgart, in these serial images, a number of inferences could be made
an elegant series of studies employing radon gas dissolved concerning cardiac pathophysiology and cardiac chamber
in saline as the radionuclide marker and a modified Wilson and great vessel size. Following these qualitative studies,
cloud chamber as the radiation detector, measured central quantitative techniques were developed for measuring left
circulation transit times in humans (Figure 1.1).1 These and right ventricular ejection fraction as well as the degree
studies, which were well ahead of their time, resulted in of left-​to-​right intracardiac shunting. For over a decade,
7,8

substantial improvement in the general understanding of first-​pass approaches to assess ventricular ejection frac-
cardiovascular function in a variety of disease states. They tion were widely used. Extensive studies were subsequently
were early forerunners of the studies of the 1950s and performed by many laboratories, particularly by Jones at al.
1960s, in which substantial attention was given to hemo- at Duke and by Zaret et al. at Yale, establishing efficacy and
dynamic characterization of both health and human disease clinical utility.
9–​12

states. Blumgart’s laboratory in Boston also served as fertile In 1971, the principle of electrocardiographic gating of
ground for training the next generation of cardiovascular the stable radiolabeled (equilibrium) blood pool to eval-
investigators. uate cardiac performance was first proposed by Zaret and
Not until the 1940s did Myron Prinzmetal build on this Strauss (Table 1.2). This forerunner of current ERNA
13,14

concept for potential clinical use, employing a simple so- required separate manual gating of the end-​systolic and
dium iodide probe to record transit of radiolabeled albumin end-​diastolic phases of the cardiac cycle for subsequent
through the central circulation. Prinzmetal, a practicing measurement of LVEF and assessment of regional function.
cardiologist, made important clinical observations using This was a cumbersome and time-​consuming procedure.
nonimaging Geiger tubes and scintillation detectors in However, once efficacy had been established, it was only a
a procedure called “radio-​cardiography” to define car- short time before automation of this technique occurred.
diac output, pulmonary blood volume, and pulmonary Michael V. Green demonstrated in 1975 that by using rel-
transit time.2 atively simple computerized techniques, the entire cardiac
However, the major impetus for the development of nu- cycle could be visualized in an endless loop display with
clear medicine technology occurred in the 1960s when Hal automated calculation of ventricular ejection fraction and
O. Anger, working in Berkeley, California, developed the visualization of the entire ventricular volume curve. For
15

first practical widely used high-​resolution dynamic imaging over a decade, this technique was the standard for meas-
device, the gamma (Anger) camera.3 At about the same uring ventricular function noninvasively. In 1977, Borer
time radiochemists Walter Tucker and Margaret Greene, et al. at the National Institutes of Health first reported
at the Brookhaven National Laboratories, invented the Tc-​ combining ERNA with supine bicycle exercise to evaluate
99m generator.4 Tc-​99m, because of the emitted energy at regional and global LV function under stress conditions in
140 keV, was a readily available radiotracer ideally suited coronary artery disease as well as other disease states, such
as valvular heart disease.16 In large part, echocardiography
has superseded ERNA in this context. However, for precise
TA B LE 1.1 MA JO R A DvA N CE S : B EF O RE 1 9 7 0
and reproducible serial measurements of LVEF, such as re-
Decade Investigator Advance quired for monitoring cardiotoxicity in patients receiving
1920s H. Blumgart Circulation times with radioisotopes
chemotherapy, the radionuclide technique remains the pro-
cedure of choice.17
1940s M. Prinzmetal Radiocardiography
Newer evolutionary advances in assessment of ventric-
1960s E. A. Carr Perfusion imaging in experimental MI ular function involve SPECT studies of global myocardial
E. A. Carr Hot spot imaging in experimental MI
motion on perfusion images or endocardial borders on
W. Tucker, M. Greene Tc-​99m generator equilibrium cardiac blood pool images. This allows a more
H. O. Anger Development of scintillation camera
comprehensive assessment of right and left ventricular
global and regional function.18 At present, with the marked
J. Kriss Quantitative FPRNA
advances in gated SPECT perfusion studies, ventricular

4 S E C T I O N I . H istorical , T echnical
TA B LE 2.3 N U C L I D E N O TAT IO N S Several models to explain nuclear forces have been
proposed, often relying on a sharing of fundamental
Name Definition Examples
particles, such as mesons, resulting in strong attractive
Isotopes Same Z, different N 15
O, 16O, 17O, 18O
forces between pairs of nucleons. This is analogous to
Isotones Same N, different Z 12
B, 13C, 14N, 15O sharing electrons between atoms to form molecules.
Isobars Same A, different Z 59
Fe, 59Co, 59Ni, 59Cu
Pairing of nucleons, implying stability, is observed in
the 249 known stable nuclear configurations.2 Of these
Isomers Same Z, same N, different 81m
Kr, 81Kr; 87mSr, 87Sr; 99mTc,
energy level 99
Tc; 113mIn, 113In
configurations, only four have an odd number of protons
and an odd number of neutrons. These are 2H, 6Li, 10B,
and 14N, the four smallest odd-​Z elements. All others have
atom is about 10–​8 cm. A particular nuclear configuration is even numbers of protons and neutrons, even numbers of
called a nuclide and is described by the number of protons, neutrons, or even numbers of protons. In addition to this
thus the element, and the number of nucleons (neutrons pairing observation for nucleus stability, another descrip-
+​ protons), thus the mass number. The conventional des- tive characteristic is the relationship between the number of
ignation is the chemical symbol, which implies the atomic neutrons and protons that yield stable configurations. For the
number (Z), and the mass number (A) as superscript. The lower-​atomic-​number stable nuclei, the proton-​to-​neutron
neutron number (N) is the difference between the mass ratio is approximately one to one. For the more massive,
number and the atomic number: N =​ A minus Z. Isotopes high-​atomic-​number stable nuclei, this ratio approaches 1.5
are nuclides that have the same number of protons and to 1. A plot of this relationship, shown in Figure 2.3, is re-
thus are the same element, but have different numbers of ferred to as the line of stability. The 249 data points define a
neutrons and therefore different mass numbers. Isotones narrow range for the neutron-​to-​proton ratio over the range
are nuclides with the same number of neutrons. Isobars are of elements observed in nature. Any other nuclear configu-
nuclides with the same mass number but different numbers ration will be unstable, meaning it will undergo transforma-
of protons. We will see that many of the nuclear transfor- tion by the process of radioactive decay to eventually arrive
mation modes of interest in gamma-​ray imaging are isobaric at a stable nuclear configuration. If a nucleus has a higher
transitions. Isomers are nuclides with the same number of neutron-​to-​proton ratio than neighboring stable nuclei, it
protons and neutrons but with different nuclear energy will undergo a nuclear transformation so that the neutron-​
states. To designate an excited energy state of a nucleus that to-​proton ratio will decrease. This will generally be in the
has a measurable lifetime, or a metastable state, a lower- form of beta (β–​) decay. Conversely, if the unstable nucleus
case m is appended to the mass number, for example 99mTc. has a neutron-​to-​proton ratio lower than its neighboring
An isomeric transition is one type of gamma-​ray emission stable nuclei, then the mode of radioactive decay will result
(Table 2.3). in an increase in the neutron-​to-​proton distribution, which

140

120

100
Line of stability
Neutron Number

Neutron excess
80

60
Line of identity
40

20

0
0 10 20 30 40 50 60 70 80 90
Proton Number

Figure 2.3 The relationship between the number of neutrons and protons for the stable nuclear configurations.

16 SECTION I. HISTORICAL, TECHNICAL, & PHYSIOLOGIC CONSIDERATIONS

Another random document with
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 To assist my father in writing, notwithstanding his blindness, I
made the machine shown in the illustration. It has been in use two
years, and proved thoroughly practical. It consists of a board, ¹⁄₂ by
11 by 13³⁄₄ in., on which the paper is held by a clip. Two stops, A,
insure a good alinement of the sheet. A T-square, B, slides in a
groove at the left side; the upper edge is beveled. At a distance of ³⁄₄
in. from this edge is stretched a brass guide wire, C, by means of
which the height of the script is gauged. The wire is supported on
brass strips, D. When the line is written, a pin, E, set in one of a row
of holes in the groove F, is raised, the T-square moved, and the pin
inserted in the next hole below, giving the correct spacing. As the
wire does not touch the paper, either ink or pencil can be used. The
board consists of four pieces, glued, and fastened with screws, as
detailed.—Arthur E. Tremaine, Brookline, Mass.
 Making Cardboard Tubes for Electrical Coils
It is often difficult to obtain cardboard tubes as foundations for
coils of special sizes, and the following is a practical method for
making them as desired: Cut a strip of cardboard somewhat wider
than the length of the tube desired and about 2 ft. long. Soak the
cardboard in water until it is quite pliable. Wrap it tightly around a
wooden rod of suitable size, gluing or shellacking each successive
layer. When the desired thickness has been obtained, bind the tube
with string, and place the whole in a moderately warm oven to dry.
The tube may then be cut to length.—Alexander V. Bollerer, New
Britain, Conn.
 An Army in a Small Box

By Reason of the Mirrors, a Few Soldiers Appear as an Army

A play device that will afford much amusement and which is

interesting for boys to make is that shown in the sketch. To make the
peephole cabinet, obtain a box of suitable size; fasten a piece of
looking-glass inside, at each end. Make a peephole at one end of the
box, and rub the silvering from the back of the looking-glass at the
hole. Place a few metal soldiers, horses, etc., along the sides of the
box 1 or 2 in. apart, one being set to hide the reflection of the hole.
By looking through the hole an endless army may be seen. Light is
provided through the skylight at the top, which is fitted with ground
glass or tissue paper. This device perplexes most persons who are
not familiar with its construction.—James E. Noble, Portsmouth,
Canada.
 Liquid-Filled Tray Carried Safely
In photographic work, and in the shop or laboratory, chemicals
carried in shallow trays are easily spilled. In photographic work,
especially, this endangers materials used, as the spilled liquid dries
and dust affected by it may spoil chemicals with which it comes into
contact. The tray should be carried in a larger pan or basin partly
filled with water, thus keeping the tray level.
 Making an Umbrella Handle Detachable

A parasol or umbrella with a detachable handle is a great

convenience in packing when traveling, and a handle may be made
detachable as follows: Remove the handle by using a block of wood
and a hammer. Clean out the hole, and polish the steel stem with
emery, as far as it goes into the handle. Cut off 1 in. from the end,
and then solder a section of brass tubing into this piece, and another
section into the end of the stem. The abutting ends are then tapped
to fit an 8-32 screw, which is then soldered into the shorter piece, as
shown. The latter is pushed into the handle, and a hole, ¹⁄₁₆ in. in
diameter, is drilled almost through the handle. A piece of wire nail is
driven into this hole. By making the screw fast in the handle rather
than in the stem, the threads are protected, and the length when
taken apart is correspondingly reduced.—John D. Adams, Phoenix,
Ariz.

¶To renew a typewriter ribbon, roll it on a spool and apply a very

small drop of glycerin at intervals of several inches, with a fountain-
pen filler, and permit the glycerin to soak in thoroughly.
Boys’ Athletic-Equipment Locker
The Boy Who Takes Pride in His Athletic Equipment will Find Much Pleasure
in Making This Cupboard for It

The boy should have a place in the home for his sports togs and
equipment, and a cupboard like that shown can be made easily for
the purpose. Its size will depend on the quantity of articles to be
stored. A good size is 12 by 30 in., by 5 ft. high. Plain boards are
used, and for the door they are fastened together with cleats and
screws. The drawer is convenient but not essential.—J. D. Hough,
Toledo, Ohio.
 Wire Compacts Bristles in Polish or Stencil
Brushes

The bristles of brushes used for applying shoe polish and for
painting through stencils often curl so much that the brush becomes
almost useless. In order to overcome this I bound the bristles with
several turns of wire and soldered them into place as shown. When
desirable, part of the wire may be removed by cutting it at the solder.
—Hugo Kretschmar, West Nyack, N. Y.
 Old Table Used as Wall Workbench
Good use was made of an old table, one leg of which was broken,
by removing two of the legs at one side and fitting the table against a
wall. A wide board was set on the back edge of the table, against the
wall, and provided a rack for tools. A drawer was fitted into the front
of the table, and a small iron vise was clamped at one end. The
arrangement provided a convenient bench for home shop work.
 Lettering Photo Prints without Marking Negative
Instead of scratching titles on photographic negatives, which often
produces a poor result, a good method is to write the title on the
sensitive paper with black ink before printing. Care must be taken
not to scratch the paper. The toning and fixing baths wash away the
ink, leaving the script or lettering white. The negative is thus
unmarred.
Rope Pad Prevents Slamming of Door
 An antislam pad, made of a piece of rope and fixed to the knobs of
doors, is in general use in a large hospital. The device is made by
forming loops on the end of a short section of rope, as shown, and
fitting them over the door knob. This also prevents the closing of the
door so that a patient may be heard in calling an attendant.—C. M.
Hall, St. Louis, Missouri.

¶Curtain rollers should be arranged so that the direction of pull on

the tacked edge of the curtain is away from the end.
 Box to Protect Extra Spark Plugs

The Spark Plugs are Fitted Compactly in the Case and are Protected from
Damage

Damage often results to spark plugs which are thrown in the tool
box of an automobile, and the use of a small case for the extra spark
plugs is desirable. Partitions may be fitted into an old box of suitable
size, or a case may be specially made. That shown was designed to
provide for six spark plugs in a minimum of space. It was made of ¹⁄₄-
in. wood, and of a length so that the spark plugs could be slipped in
the recesses only by turning the faces of adjoining plugs together. A
hinged cover keeps them firmly in place.—E. R. Mason, Danville, Ill.
 Homemade Spring Wagon Seat

Two ⁷⁄₈-in. boards, 12 in. wide, between which two 12-in. pieces of
2 by 4-in. wood are bolted, provide a strong spring seat for a wagon.
The boards are cut to a suitable length, and the 2 by 4-in. pieces are
set near the middle, and about 8 in. apart. This gives a spring seat at
each end of the device.
 Cushioned Chair Made of a Barrel
A strong barrel may be made into a comfortable chair by cutting it
halfway through at the middle and shaping the remaining upper
portion into an arm and back rest. Holes are bored at the seat level
and at the back, and wires woven through them to form a backing for
excelsior-stuffed cushions.
 Bicycle Fitted Up to Resemble Motorcycle

Comparison of the “Before and After” Illustrations Shows Strikingly the

Resemblance to a Motorcycle

The boy who cannot own a motorcycle but who has a bicycle, may
remodel it to resemble a power-driven machine by fitting it up with
equipment, much of which can be made in the home workshop. The
illustration shows how an ordinary bicycle was improved by several
practical fittings. The lower end of the mudguard of the rear wheel
was extended to form a clip, for the homemade stand A. Brackets
were made of strap iron to support the bundle carrier B, the basket of
which was made of wood. The tank C, 3 by 3 by 21 in., with two
compartments and doors, contains batteries and tools. It is fastened
to the frame by means of two bolted straps. The bracket D was
made of strap iron, to support the electric headlight E. The
handlebars were extended, as shown at F, and the horn G was
provided. The seat post was lengthened by welding a piece to it, and
reversed, as at H. A tail light, J, and a pump, K, held by straps, were
provided, and the front mudguard was fitted with a leather piece, L,
shaped as shown in the front view.—P. P. Avery, Garfield, N. J.
 Toy Submarine Made of Shade Roller

This Submarine’s “Engine” is Wound by Means of the Propeller

The submarine shown really goes, and was made of a bit of tin,
some lead, a few brads, and an old window-shade roller, with a good
spring. The spring is the submarine engine. Saw off the roller 3 in.
beyond the inner end of the spring, and shape it like the bow of a
submarine. Flatten a piece of lead, and fasten it to the bottom of the
boat for a keel. Experiment until the keel is of the right weight, and in
the proper place, permitting the boat to move evenly, just below the
surface of the water. For the propeller, cut a 2-in. tin disk as shown,
and bend the blades into shape. In the center make a hole to admit
the end of the spring, to which it is then soldered. Wind up the
“engine” by turning the propeller. The shade-roller spring can also be
used for other toy craft.—E. P. Sullivan, Arlington, Massachusetts.

¶Rub powdered graphite on rubber and asbestos gaskets so that

they may be removed easily when desired.