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 Hybrid Imaging in
Cardiovascular Medicine
http://taylorandfrancis.com
 Hybrid Imaging in
Cardiovascular Medicine

Edited by
Yi-Hwa Liu, PhD
Albert J. Sinusas, MD, FACC, FAHA
Yale University School of Medicine
CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742

© 2018 by Taylor & Francis Group, LLC

CRC Press is an imprint of Taylor & Francis Group, an Informa business

No claim to original U.S. Government works

Printed on acid-free paper

International Standard Book Number-13: 978-1-4665-9537-8 (Hardback)

This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to
publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materi-
als or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material
reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained.
If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint.

Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in
any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, micro-
filming, and recording, or in any information storage or retrieval system, without written permission from the publishers.

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Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identifi-
cation and explanation without intent to infringe.

Visit the Taylor & Francis Web site at

http://www.taylorandfrancis.com

and the CRC Press Web site at

http://www.crcpress.com
I dedicate this book to my wife, Michele, for her love and support and most importantly her patience and
understanding of my work schedule. I would also like to acknowledge the support and guidance of my
colleagues at Yale University and the many research and clinical fellows that I have had the pleasure of
working with and mentoring over the years.
Albert Sinusas
http://taylorandfrancis.com
Contents

Series preface ix
Preface xi
Acknowledgments xiii
Editors xv
Contributors xvii

Part 1 PRINCIPLES, INSTRUMENTATION, TECHNIQUES, APPLICATIONS,

AND CASE ILLUSTRATIONS OF HYBRID IMAGING 1

1 Principles and instrumentation of SPECT/CT 3

R. Glenn Wells
2 Cardiovascular PET-CT 27
Etienne Croteau, Ran Klein, Jennifer M. Renaud, Manuja Premaratne,
and Robert A. DeKemp
3 Development of a second-generation whole-body small-animal SPECT/MR imaging system 57
Benjamin M.W. Tsui, Jingyan Xu, Andrew Rittenbach, James W. Hugg,
and Kevin B. Parnham
4 Integrated PET and MRI of the heart 75
Ciprian Catana and David E. Sosnovik
5 CT-MRI 95
James Bennett and Ge Wang
6 Hybrid x-ray luminescence and optical imaging 117
Raiyan T. Zaman, Michael V. McConnell, and Lei Xing
7 X-ray fluoroscopy–echocardiography 137
R. James Housden and Kawal S. Rhode
8 Combined ultrasound and photoacoustic imaging 153
Doug Yeager, Andrei Karpiouk, Nicholas Dana, and Stanislav Emelianov
9 Hybrid intravascular imaging in the study of atherosclerosis 185
Christos V. Bourantas, Javier Escaned, Carlos A.M. Campos, Hector M. Garcia-Garcia,
and Patrick W. Serruys

Part 2 MULTIMODALITY PROBES FOR HYBRID IMAGING 211

10 Preclinical evaluation of multimodality probes 213

Yingli Fu and Dara L. Kraitchman
11 Multimodality probes for cardiovascular imaging 237
James T. Thackeray and Frank M. Bengel

vii
viii Contents

Part 3 QUANTITATIVE ANALYSES AND CASE ILLUSTRATIONS OF HYBRID IMAGING 267

12 Recent developments and applications of hybrid imaging techniques 269

Piotr J. Slomka, Daniel S. Berman, and Guido Germano
13 Multimodality image fusion 299
Marina Piccinelli, James R. Galt, and Ernest V. Garcia
14 Quantitative cardiac SPECT/CT 319
Chi Liu, P. Hendrik Pretorius, and Grant T. Gullberg
15 Evaluations of cardiovascular diseases with hybrid PET-CT imaging 351
Antti Saraste, Sami Kajander, and Juhani Knuuti
16 Quantitative analyses and case studies of hybrid PET-MRI imaging 365
Leon J. Menezes, Eleanor C. Wicks, and Brian F. Hutton
17 Merging optical with other imaging approaches 377
Doug Yeager, Nicholas Dana, and Stanislav Emelianov

Part 4 FUTURE CHALLENGES OF HYBRID IMAGING TECHNIQUES 413

18 Hybrid instrumentation versus image fusion: Path to multibrid visualization 415

Ernest V. Garcia and Marina Piccinelli
19 Concerns with radiation safety 425
Mathew Mercuri and Andrew J. Einstein
20 Future directions for the development and application of hybrid cardiovascular imaging 439
Albert J. Sinusas

Index 445
Series preface

Advances in the science and technology of medical imaging and radiation therapy are more profound and
rapid than ever before since their inception over a century ago. Further, the disciplines are increasingly
cross-linked as imaging methods become more widely used to plan, guide, monitor, and assess treatments in
radiation therapy. Today, the technologies of medical imaging and radiation therapy are so complex and so
computer driven that it is difficult for the persons (physicians and technologists) responsible for their clinical
use to know exactly what is happening at the point of care when a patient is being examined or treated. The
persons best equipped to understand the technologies and their applications are medical physicists, and these
individuals are assuming greater responsibilities in the clinical arena to ensure that what is intended for the
patient is actually delivered in a safe and effective manner.
The growing responsibilities of medical physicists in the clinical arenas of medical imaging and radiation
therapy are not without their challenges, however. Most medical physicists are knowledgeable in either radia-
tion therapy or medical imaging and expert in one or a small number of areas within their discipline. They
sustain their expertise in these areas by reading scientific articles and attending scientific talks at meetings.
In contrast, their responsibilities increasingly extend beyond their specific areas of expertise. To meet these
responsibilities, medical physicists periodically must refresh their knowledge of advances in medical imag-
ing or radiation therapy, and they must be prepared to function at the intersection of these two fields. How to
accomplish these objectives is a challenge.
At the 2007 annual meeting of the American Association of Physicists in Medicine in Minneapolis, this
challenge was the topic of conversation during a lunch hosted by Taylor & Francis Group and involving a
group of senior medical physicists (Arthur L. Boyer, Joseph O. Deasy, C.-M. Charlie Ma, Todd A. Pawlicki,
Ervin B. Podgorsak, Elke Reitzel, Anthony B. Wolbarst, and Ellen D. Yorke). The conclusion of this discussion
was that a book series should be launched under the Taylor & Francis banner, with each volume in the series
addressing a rapidly advancing area of medical imaging or radiation therapy of importance to medical physi-
cists. The aim would be for each volume to provide medical physicists with the information needed to under-
stand technologies driving a rapid advance and their applications to safe and effective delivery of patient care.
Each volume in the series is edited by one or more individuals with recognized expertise in the technologi-
cal area encompassed by the book. The editors are responsible for selecting the authors of individual chapters
and ensuring that the chapters are comprehensive and intelligible to someone without such expertise. The
enthusiasm of volume editors and chapter authors has been gratifying and reinforces the conclusion of the
Minneapolis luncheon that this series of books addresses a major need of medical physicists.
Imaging in Medical Diagnosis and Therapy would not have been possible without the encouragement and
support of the series manager, Lu Han of Taylor & Francis Group. The editors and authors, and most of all I,
are indebted to his steady guidance of the entire project.

William Hendee
Founding Series Editor
Rochester, Minnesota

ix
http://taylorandfrancis.com
Preface

Hybrid cardiovascular imaging holds incredible promise for preclinical research and clinical practice, pro-
viding simultaneous acquisition and coregistration of anatomical, functional, and molecular data from a
target of interest and achieving extraordinary comprehensive information about the targeted object. Over
the past decade, the developments of hybrid imaging technology have drawn tremendous attention from the
research and clinical communities, particularly in the area of molecularly targeted imaging. With recent
advancements of imaging system design and computing power, multiple imaging systems with different
functionalities can be integrated into one system to simultaneously acquire the composite information about
the object, from the macro level of organs (e.g., heart) to microcellular details (e.g., myocytes). The innovation
of high-sensitivity detectors and fast circuitry associated with improved iterative image reconstruction algo-
rithms further enables the acquisition and reconstruction of high-quality images with reduced acquisition
and processing time. These innovative hybrid imaging technologies and reconstruction algorithms have also
propelled the field of quantitative analysis of molecularly targeted imaging to the next level, increasing the
reliability and reproducibility of hybrid imaging data.
Although hybrid imaging techniques have been introduced and developed over several decades with appli-
cation in both the clinical or research settings, to our knowledge, a textbook encompassing a wide spectrum
of hybrid imaging systems and applications is not currently available. We hope that this book will provide not
only comprehensive reviews on the principles and techniques of various hybrid imaging modalities but also
up-to-date applications and clinical and preclinical cases illustrations with an emphasis on cardiovascular
medicine. While this book, as reflected from its title, is mainly focused on the latest multimodality imaging
technology and quantification for the detection of cardiovascular diseases, applications of the hybrid imaging
instrumentation and technology described herein are not limited to cardiovascular medicine per se. More
specifically, other clinical and preclinical studies of hybrid imaging are also covered by this book in which
image illustrations and quantitative results of preclinical and clinical studies from in vitro or in vivo stud-
ies in experimental animal models or human subjects are presented. Due to the wide range of the contents
and more general applicability, it is also our expectation that this book will be beneficial to basic research
scientists and engineers, as well as a large audience of medical specialists in radiology, medicine, and surgery.
This book contains a total of 20 chapters, contributed by 50 distinguished authors who are renowned
experts in their respective fields. The book is divided into four parts and organized as follows: There are nine
chapters in Part I dedicated to the review of the principles, instrumentation, techniques and applications
of hybrid imaging with specific case illustrations, including single-photon emission computed tomography
(SPECT)-computed tomography (CT) (Chapter 1), positron emission tomography (PET)-CT (Chapter 2),
SPECT-magnetic resonance imaging (MRI) (Chapter 3), PET-MRI (Chapter 4), CT-MRI (Chapter 5), x-ray-
optical (Chapter 6), x-ray fluoroscopy-echocardiography (Chapter 7), photoacoustic imaging (Chapter 8),
and intravascular imaging (Chapter 9). Part II includes two chapters focused on multimodality probes for
hybrid imaging; preclinical evaluation of multimodality probes (Chapter 10) and multimodality probes for
molecular imaging (Chapter 11). The methods and illustrations for quantitative image analyses are described
and presented in Part III, which contains six chapters (Chapters 12 through 17) dedicated to numerous state-
of-the-art quantitative analytic methods and computer algorithms for quantification of the images acquired
using the hybrid imaging systems and probes described in Parts I and II of this book. Finally, the book is
concluded with Part IV, on future challenges of hybrid imaging, which elaborates on potential challenges
associated with hybrid imaging (Chapter 18) and some concerns of radiation safety (Chapter 19) and suggests
future directions for the developments and applications of hybrid imaging techniques (Chapter 20).

xi
xii Preface

Potential readership and usage of this book may include but is not limited to (1) medical physicists,
chemists, molecular biologists, and other basic scientists, (2) medical students, interns, fellows, research-
ers, and clinical professionals whose primary interests and practices are in cardiovascular imaging, and
(3) ­engineering/science graduate students focused on instrumentation development and studies of medical
physics and/or imaging science. Additionally, this book can be used as a textbook for a graduate-level course,
potentially entitled, “New Techniques and Applications for Advanced Hybrid Medical Imaging Systems and
Quantitative Analyses.” For a full-year course, an instructor can make good use of all the materials covered
by this book and offer the entire course in two semesters, the first focused on Parts I and II and the second
on Parts III and IV. However, as an alternative, the course can also be offered in a condensed manner in one
semester with a specific focus on one or two of the major sections or selected chapters from the book. The use
of this book in a graduate course would provide students a detailed and up-to-date review of multimodality
medical imaging techniques and new quantitative analytic methods with abundant preclinical and clinical
cases and illustrations having high relevance to both basic scientists and medical specialists in training.

Yi-Hwa Liu
Albert J. Sinusas
Acknowledgments

We heartily appreciate all the contributors for their great dedications and efforts to this book. We also thank
the anonymous reviewers for their helpful and invaluable suggestions and comments for this book.

xiii
http://taylorandfrancis.com
Editors

Yi-Hwa Liu, PhD, is a senior research scientist in cardiovascular medicine at Yale University School of
Medicine, New Haven, Connecticut; an associate professor (adjunct) of Biomedical Imaging and Radiological
Sciences at National Yang-Ming University, Taipei, Taiwan; and a professor (adjunct) of biomedical engineer-
ing at Chung Yuan Christian University, Taoyuan, Taiwan. He is an elected senior member of the Institute of
Electrical and Electronic Engineers and a full member of Sigma Xi of The Scientific Research Society of North
America. He has served for many a years on the editorial boards of the World Journal of Cardiology, Journal of
Clinical and Experimental Cardiology, American Journal of Nuclear Medicine and Molecular Imaging, Current
Molecular Imaging Journal, and American Journal of Nuclear Medicine and Molecular Imaging. He has also
served as a National Member of the American Heart Association grants review committee since 2004 and
as associate editor of Medical Physics since 2009. Dr. Liu earned his BS degree in biomedical engineering
at Chung Yuan Christian University, Taoyuan, Taiwan; MS degree in electrical and computer engineering
at University of Missouri, Columbia, Missouri; and PhD degree in electrical and computer engineering at
Rensselaer Polytechnic Institute, Troy, New York. He completed post-doc trainings in electrophysiology and
cardiovascular physiology at Georgetown University School of Medicine and in nuclear cardiology at Yale
University School of Medicine. He joined the faculty at Yale University School of Medicine as assistant profes-
sor (1998–2004) and associate professor of medicine (2004–2014). His primary research involves noncoher-
ent image restoration, nuclear cardiac image reconstruction, and quantification. He is one of the pioneers
in the fields of fluorescence microscopic image restoration and nuclear cardiac image reconstruction and
quantification. He is the author of over 50 peered review publications, the leading editor of a book entitled
Cardiovascular Imaging (CRC Press, Taylor & Francis Group, London, UK) and coinventor of the Wackers-
Liu CQ SPECT Quantification Method, Food and Drug Administration-approved Commercial Software
Package.

Albert J. Sinusas, MD, FACC, FAHA, is professor of medicine (Section of Cardiovascular Medicine) and
radiology and biomedical imaging at Yale University School of Medicine, director of the Yale Translational
Research Imaging Center, and director of Advanced Cardiovascular Imaging at Yale New Haven Hospital.
He earned his BS degree from Rensselaer Polytechnic Institute and his MD degree from University of
Vermont, College of Medicine, and completed training in internal medicine at the University of Oklahoma
and training in cardiology and nuclear cardiology at the University of Virginia. He joined the faculty at Yale
University School of Medicine in 1990, where he has remained. Dr. Sinusas has served as a standing member
of the Clinical and Integrated Cardiovascular Sciences and Medical Imaging study sections of the National
Institutes of Health. Dr. Sinusas has been a member of the Board of Directors of the Cardiovascular Council
of the Society of Nuclear Medicine (SNM), the SNM Molecular Imaging Center of Excellence, and the
American Society of Nuclear Cardiology. He was the 2008 recipient of the SNM Hermann Blumgart Award.
His research is directed at development, validation, and application of noninvasive cardiovascular imaging
approaches for the assessment of cardiovascular pathophysiology, including the targeted molecular assess-
ment of myocardial ischemic injury, angiogenesis, arteriogenesis, and postinfarction atrial and ventricular
remodeling. The investigation of these biological processes involves ex vivo and in vivo imaging in animal
models of cardiovascular disease and humans. This translational research employs the three-dimensional
modalities of x-ray computed tomography (CT) and fluoroscopy, single-photon emission CT/CT, positron

xv
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