Table Of ContentMYOCARDIAL CONTRAST
TWO-DIMENSIONAL ECHOCARDIOGRAPHY
DEVELOPMENTS IN
CARDIOVASCULAR MEDICINE
VOLUME 99
Myocardial Contrast
Two-dimensional Echocardiography
edited by
SAMUEL MEERBAUM
Woodland Hills,
California, U.S.A.
RICHARD S. MELTZER
University of Rochester Medical Center,
Rochester, New York, U.S.A.
Kluwer Academic Publishers
DORDRECHT - BOSTON - LONDON
Library of Congress Cataloging in Publication Data
Myocardial contrast two-dimensional echocardiography / edited by Samuel Meerbaum,
Richard S. Meltzer.
p. cm. - (Developments in cardiovascular medicine)
Includes index.
1. Contrast echocardiography. 2. Two-dimensional echocardiography.
3. Heart-Infarction-Diagnosis. I. Meerbaum, Samuel. II. Meltzer, Richard S.,
1921- III. Series. [DNLM: 1. Contrast Media. 2. Echocardiography
methods. 3. Myocardium-pathology. WI DE997VME / WG 141.5.E2 M997j
RC683.5.U5M96 1989
616.l'207543-dc19
DNLM/DLC
for Library of Congress 89-2411
ISBN-13: 978-94-010-7556-5 e-ISBN-13: 978-94-009-2346-1
DOl: 10.1007/978-94-009-2346-1
Published by Kluwer Academic Publishers,
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Preface
To our knowledge, this is the first book dealing exclusively with myocardial
contrast two-dimensional echocardiography (MC-2DE), a new and exciting
diagnostic methodology for assessment of myocardial perfusion, which has
seen rapid development and has now entered the clinical stage. The experi
mental research and human applications have been described in technical
papers published in a variety of journals, but our objective is to provide the
reader with a comprehensive and concentrated overview of the field and of
the current state of the art. To facilitate appreciation of the significant ad
vances made and issues yet to be resolved, we are pleased to have several well
known specialists contribute their own assessment of specific aspects of MC-
20E and illustrate the method's principles as well as applications. We were
faced with inevitable overlaps and some repetitions in the discussion of quan
titative potentials or limilations of the methodology. Rather than strictly
'streamlining' the text, we decided to accept some redundancy in the interest
of presenting a diversity of points of views, reflecting the current evolutionary
state of MC-20E.
Following a brief reference to the established clinical contrast echocardiog
raphy, recent developments and validations of the specialized MC-2DE tech
nique are reviewed, bearing in mind that the field is in a flux and some of the
ongoing activities have not as yet been formally reported. Mechanisms of the
echo contrast and several new agents are decribed next, and an additional
chapter illustrates current thoughts-on optimizing the echo contrast medium.
The important safety aspects are dealt with by discussing the potential toxic
ity of MC-20E. Indicating the substantial promise of the MC-20E tech
nique, three chapters report on encouraging reliability of ischemic risk zone
determination, progress toward quantitation of myocardial perfusion, and
extension to study of reperfusion and retroperfusion. The initial clinical ex
perience with the MC-20E methodology is described by several authors,
applying new myocardial contrast agents and methods of analysis. A special
overview of the current state of clinical trials is presented. The still elusive
goal and issue of an intravenous MC-20E is considered in a separate chapter.
VI Preface
Other intensively investigated techniques for myocardial perfusion measure
ment are recognized, but comparisons with MC-2DE appear premature. The
final chapter reflects a personal view of current perspectives and future pros
pects for MC-2DE.
It is hoped that this book will contribute to an understanding of MC-2DE
and its applications. If, as expected, further development efforts resolve limi
tations and clinical trials validate the technique, one may confidently project
wider acceptance and incorporation of MC-2DE in the armamentarium of
cardiac diagnostics.
Samuel Meerbaum & Richard S. Meltzer
Contents
Preface v
List of contributors Xl
1. Introduction and general background
by Samuel Meerbaum 1
1. Evolution of echo contrast concepts 1
2. Assessment of cardiac structures and flow patterns 2
3. Development of echo contrast agents 3
4. Consideration of echo contrast mechanism and safety 5
References 5
2. Development and validation of MC-2DE methodology
by Samuel Meerbaum 7
1. Initial exploration of MC-2DE and its validity 7
2. Characteristics and studies of myocardial echo contrasts 17
3. Echo contrast safety and toxicity 21
4. Transpulmonary echo contrast investigations 24
5. Quantitative MC-2DE methods and their limitations 27
6. MC-2DE measurement of ischemic risk area and infarcts 30
7. Assessment of coronary stenosis and myocardial blood flow 32
8. Physiological studies and miscellaneous MC-2DE applications 35
9. Initial clinical MC-2DE reports 36
10. Potential surgical application of MC-2DE 39
References 40
3. Contrast agents for myocardial perfusion studies: Mechanisms,
state of the art, and future prospects
by Shimon A. Reisner, Janine R. Shapiro, Antonio F. Amico, and
Richard S. Meltzer 45
VIII Contents
1. Introduction 45
2. The source of ultrasonic contrast effect 45
3. Physical influences on ultrasonic contrast effect 46
3.1 Viscosity 46
3.2 Surfactant properties 46
3.3 Influence of pH 47
4. Specific agents reported as echocardiographic contrast agents 47
4.1 Carbon dioxide 47
4.2 Hydrogen peroxide 48
4.3 In vivo generation of contrast 48
4.4 Contrast formed by bubbles in gelatin or HaemaccelQ!> 49
4.5 Saccharide particles as ultrasound contrast agents 49
4.6 Heavy liquids: Fluorochemicals and fat emulsions 50
4.7 Highly viscous solutions 50
4.8 Sonicated albumin microbubble suspensions 51
5. The use of high intensity sonication for microbubble creation 52
5.1 Background 52
5.2 Animal studies using sonicated albumin 52
5.3 Human studies using sonicated albumin 52
6. Conclusion 53
Acknowledgements 56
References 56
4. Significance and selection of contrast solution for myocardial con
trast echocardiography
by Klaus Berwing, Martin Schlepper, Hassan Bahavar, and Amd
Buchwald 61
1. Introduction 61
2. Current echo contrast media 62
3. Properties of the ECM: Microbubble size, osmolality, viscosity,
and stability 63
3.1 Microbubble size 63
3.1.1 Preparation ofthe microbubbles 63
3.1.2 Physicochemical properties and effects on bubble
size 65
3.1.3 Effects of microbubble size on myocardial perfu-
sion 65
3.2 Osmolality, viscosity, and stability of the mixture of carrier
solution and microbubbles 66
4. Evaluation of the echo contrast media used so far 71
5. Echo contrast safety and effectiveness 72
6. Some conclusions 79
Acknowledgements 80
References 80
Contents IX
5. Side effects and potential toxicity of myocardial contrast echo-
cardiography
by Shimon Reisner, Janine R. Shapiro, and Richard S. Meltzer 85
1. Introduction 85
2. Possible mechanisms of toxicity 85
2.1 Adverse effects related to contrast media 85
2.2 Adverse effects related to microbubbles: Capillary plug-
ging 87
2.3 Cavitation/resonance and ultrasonic effects 87
2.4 Side effects related to injection technique 89
2.5 Patient related adverse effects 89
3. Animal studies 89
4. Human experience 92
5. Conclusions 94
References 94
6. Ischemic 'risk area' determination using myocardial contrast two-
dimensional echocardiography
by Sanjiv Kaul 97
1. What is the 'risk area'? 97
2. What is the significance of the 'risk area'? 98
2.1 Duration of coronary occlusion 98
2.2 Status of collateral circulation 99
2.3 Infarct size/'risk area' ration 99
3. A historical perspective to the measurement of 'risk area' 99
4. Role of MCE is the assessment of 'risk area' 101
4.1 Validation of the technique 101
4.2 'positive' versus 'negative' RA 101
4.3 Relationship of RA to extent of abnormal wall motion 104
4.4 Time-dependent changes in RA 105
4.5 Relationship of RA to infarct size 106
4.6 Relationship between RA and hemodynamic parameters 109
4.7 Relationship of RA and LV systolic function 110
5. The lateral borders of the 'risk area' 111
6. Summary 113
Acknowledgements 113
References 114
7. Quantitation of regional myocardial perfusion using myocardial
contrast two-dimensional echocardiography
by Sanjiv Kaul 117
1. Coronary blood flow versus nutrient (myocardial) blood flow 117
2. Large microbubbles and blood flow 118
x Contents
3. Small microbubbles and blood flow 119
3.1 Method of analysis 122
3.2 Subselective injection into a coronary artery 123
3.3 Selective injection into the left main coronary artery 126
3.4 Assessment of coronary blood flow reserve 129
3.5 Intraoperative assessment of blood flow 133
3.6 What is the best parameter to measure? 135
3.7 Epicardial versus endocardial flow 136
3.8 Assessment of myocardial flow following a venous injec-
tion of contrast 136
4. Summary 136
Acknowledgements 137
References 13 7
8. Coronary venous myocardial contrast echocardiography
by Samuel Meerbaum 141
1. The rational of retrograde infusions 141
2. Experimental retrograde MC-20E models 143
3. Experimental observations 144
4. Suitability and limitations of the retrograde MC-20E method 146
5. Future retrograde MC-20E potentials and prospects 148
References 150
9. Assessment of contrast decay half life by MC-20E: Preliminary
clinical experience
by Folkter J. Ten Cate and Hua ging Huangt 151
1. Introduction 151
2. Echocontrast agents 152
3. Registration of myocardial contrast echocardiograms 153
4. Analysis of MC-20E 'images 153
5. Tso values derived from MC-20E 155
6. SafetyofMC-2DE 158
7. Reproducibility of T 50 measurements 158
8. Clinicalapplications ofTso 159
9. Limitations and future prospects 159
References 160
10. Clinical trials with a new myocardial contrast agents
by Klaus Berwing, Martin Schlepper, Peter Kremer, and Hassan
Bahavar 163
1. Introduction 163
2. Qualitative contrast echocardiography in humans 163
3. Quantitative contrast echocardiography in humans 169
