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Underlying principles of echocontrast effects are outlined in this section, which aims to reflect the recent advances and detailed reports presented in subsequent chapters. To place microbubble phenomena in context, it was deemed useful to consider parallel multidisciplinary efforts in such areas as hydrodynamic cavitation, diving physiology and bubbly flow processes. Although there are many applications of ultrasound contrast, one difficult but potentially realizable objective was singled out: the quantitation of myocardial perfusion with intravenously administered gaseous bubbles.

Other segments of this text report on the development and manifold applications of contrast echocardiography. In view of recent emphasis on quantitation, this chapter will review a number of mechanisms believed to be associated with observed echo-contrast effects. Emphasis will be on miscellaneous illustrative theoretical and experimental studies of gaseous microbubble dynamics in fluids and interactions of such bubbles with an ultrasound field.

Myocardial Contrast Two-Dimensional Echocardiography (MC-2DE) is an exciting new diagnostic technique, which is capable of combining the logistics and effectiveness of standard echocardiographic imaging with contrast enhanced delineation of myocardial regions and potential measurement of their perfusion. The real time capabilities for repeat in vivo measurements by MC-2DE have been pointed out, and evidence has been presented of quantitative assessment of ischemic risk zones and evaluation of the functional significance of coronary artery lesions in terms of myocardial perfusion. A good number of laboratory studies and clinical verifications have now been presented, so that it is possible to form a perspective regarding the current state of the art, and also appreciate the issues which do require further attention.

Mathematical modeling is a common approach to study the mechanics of the wall of the left ventricle. In designing such a model generally symplifying assumptions are proposed on left ventricular geometry, myocardial tissue properties and stress or strain distribution across the wall. Common assumptions on geometry are a spherical (6, 8), a cylindrical (2) or ellipsoidal (7,10,12) shape of the left ventricle. Generally myocardial tissue is considered to be isotropic despite its obviously anisotropic properties. We developed a cylindrical, thick-walled model (1,2) which differs from other models by considering anisotropy of myocardial tissue and torsion of the left ventricle. Torsion reflects rotation of the apex with respect to the base around the long axis of the left ventricle, and is associated with shear deformation of the outer surface (epicardium) of the left ventricle when using a cylindrical coordinate system.

Improved diagnostic evaluation of cardiac structures, function and myocardial perfusion have certainly motivated many past and current developmental efforts. Recent advances in instrumentation and sophisticated computer techniques have led to strikingly innovative systems for quantitative measurements, some of which are still being refined or validated. Thus, considerable current interest centers on technological development of methods such as magnetic resonance imaging, positron emission tomography, ultrasound tissue characterization, digital angiography, fast tomography, etc. At the same time, two-dimensional echocardiography (2DE) has become an important practical means for noninvasive assessment of cardiac structures and global as well as regional ventricular function. Many advances in Doppler evaluation of blood flow through cardiac chambers and valves have also been forthcoming, and are reflected in numerous clinical applications.

Experimental studies of cardiac function in normal states and during myocardial derangements have played an important role in providing an undertanding of physiologic mechanisms and formulating a rational basis for treatments. Fundamental to such studies are measurements of ventricular dimensions, volumes and segmental wall dynamics, all of which serve to define global and regional cardiac function. These measurements are essential to the assessment of progressive alterations such as the loss of contraction and increased myocardial stiffness which may supervene with ischaemic injury and infarction.

This chapter will provide an introductory review of the MC-2DE methodology, as it evolved since about 1980. A number of significant early exploratory studies and their conclusions are summarized. The chapter is functionally organized to help the reader become familiar with crucial aspects addressed by the MC-2DE investigations, i.e. the effectiveness of intracoronary myocardial echo contrasts, safety of the agents, transpulmonary contrast delivery, special methods of analysis and limitations, measurement of the ischemic risk area, estimation of infarct size, assessment of coronary stenosis, and evaluation of myocardial blood flow. Various MC-2DE research applications, initial clinical trials and potential use in the surgical setting will be pointed out.

1. Introduction and general background.- 1. Evolution of echo contrast concepts.- 2. Assessment of cardiac structures and flow patterns.- 3. Development of echo contrast agents.- 4. Consideration of echo contrast mechanism and safety.- References.- 2. Development and validation of MC-2DE methodology.- 1. Initial exploration of MC-2DE and its validity.- 2. Characteristics and studies of myocardial echo contrasts.- 3. Echo contrast safety and toxicity.- 4. Transpulmonary echo contrast investigations.- 5. Quantitative MC-2DE methods and their limitations.- 6. MC-2DE measurement of ischemic risk area and infarcts.- 7. Assessment of coronary stenosis and myocardial blood flow.- 8. Physiological studies and miscellaneous MC-2DE applications.- 9. Initial clinical MC-2DE reports.- 10. Potential surgical application of MC-2DE.- References.- 3. Contrast agents for myocardial perfusion studies: Mechanisms, state of the art, and future prospects.- 1. Introduction.- 2. The source of ultrasonic contrast effect.- 3. Physical influences on ultrasonic contrast effect.- 3.1 Viscosity.- 3.2 Surfactant properties.- 3.3 Influence of pH.- 4. Specific agents reported as echocardiographic contrast agents.- 4.1 Carbon dioxide.- 4.2 Hydrogen peroxide.- 4.3 In vivo generation of contrast.- 4.4 Contrast formed by bubbles in gelatin or Haemaccel(R).- 4.5 Saccharide particles as ultrasound contrast agents.- 4.6 Heavy liquids: Fluorochemicals and fat emulsions.- 4.7 Highly viscous solutions.- 4.8 Sonicated albumin microbubble suspensions.- 5. The use of high intensity sonication for microbubble creation.- 5.1 Background.- 5.2 Animal studies using sonicated albumin.- 5.3 Human studies using sonicated albumin.- 6. Conclusion.- Acknowledgements.- References.- 4. Significance and selection of contrast solution for myocardial contrast echocardiography.- 1. Introduction.- 2. Current echo contrast media.- 3. Properties of the ECM: Microbubble size, osmolality, viscosity, and stability.- 3.1 Microbubble size.- 3.1.1 Preparation of the microbubbles.- 3.1.2 Physicochemical properties and effects on bubble size.- 3.1.3 Effects of microbubble size on myocardial perfusion.- 3.2 Osmolality, viscosity, and stability of the mixture of carrier solution and microbubbles.- 4. Evaluation of the echo contrast media used so far.- 5. Echo contrast safety and effectiveness.- 6. Some conclusions.- Acknowledgements.- References.- 5. Side effects and potential toxicity of myocardial contrast echo Cardiography.- 1. Introduction.- 2. Possible mechanisms of toxicity.- 2.1 Adverse effects related to contrast media.- 2.2 Adverse effects related to microbubbles: Capillary plugging.- 2.3 Cavitation/resonance and ultrasonic effects.- 2.4 Side effects related to injection technique.- 2.5 Patient related adverse effects.- 3. Animal studies.- 4. Human experience.- 5. Conclusions.- References.- 6. Ischemic 'risk area' determination using myocardial contrast two-dimensional echocardiography.- 1. What is the 'risk area'?.- 2. What is the significance of the 'risk area' ?.- 2.1 Duration of coronary occlusion.- 2.2 Status of collateral circulation.- 2.3 Infarct size/'risk area' ration.- 3. A historical perspective to the measurement of 'risk area'.- 4. Role of MCE is the assessment of 'risk area'.- 4.1 Validation of the technique.- 4.2 'positive' versus 'negative' RA.- 4.3 Relationship of RA to extent of abnormal wall motion.- 4.4 Time-dependent changes in RA.- 4.5 Relationship of RA to infarct size.- 4.6 Relationship between RA and hemodynamic parameters.- 4.7 Relationship of RA and LV systolic function.- 5. The lateral borders of the 'risk area'.- 6. Summary.- Acknowledgements.- References.- 7. Quantitation of regional myocardial perfusion using myocardial contrast two-dimensional echocardiography.- 1. Coronary blood flow versus nutrient (myocardial) blood flow.- 2. Large microbubbles and blood flow.- 3. Small microbubbles and blood flow.- 3.1 Method of analysis.- 3.2 Subselective injection into a coronary artery.- 3.3 Selective injection into the left main coronary artery.- 3.4 Assessment of coronary blood flow reserve.- 3.5 Intraoperative assessment of blood flow.- 3.6 What is the best parameter to measure?.- 3.7 Epicardial versus endocardial flow.- 3.8 Assessment of myocardial flow following a venous injection of contrast.- 4. Summary.- Acknowledgements.- References.- 8. Coronary venous myocardial contrast echocardiography.- 1. The rational of retrograde infusions.- 2. Experimental retrograde MC-2DE models.- 3. Experimental observations.- 4. Suitability and limitations of the retrograde MC-2DE method.- 5. Future retrograde MC-2DE potentials and prospects 148 References.- 9. Assessment of contrast decay half life by MC-2DE: Preliminary clinical experience.- 1. Introduction.- 2. Echocontrast agents.- 3. Registration of myocardial contrast echocardiograms.- 4. Analysis of MC-2DE images.- 5. T50 values derived from MC-2DE.- 6. Safety of MC-2DE.- 7. Reproducibility of T50 measurements.- 8. Clinical applications of T50.- 9. Limitations and future prospects.- References.- 10. Clinical trials with a new myocardial contrast agents.- 1. Introduction.- 2. Qualitative contrast echocardiography in humans.- 3. Quantitative contrast echocardiography in humans.- 4. Future directions.- Acknowledgements.- References.- 11. Clinical evaluation of severity of coronary arterial stenosis by contrast echomyocardiography.- 1. Introduction.- 2. Method.- 3. Results.- 4. Discussion.- 4.1 Myocardial echo enhancement.- 4.2 Contrast agents.- 4.3 Quantitative analysis.- 4.4 Problems in clinical applications.- 5. Summary.- References.- 12. Clinical applications of myocardial contrast echocardiography.- 1. Introduction.- 2. Myocardial contrast echocardiography in relation to regional myocardial perfusion.- 3. Contrast echocardiography during coronary angioplasty.- 4. Assessment of coronary vascular reserve by myocardial contrast echocardiography.- 5. Safety of myocardial contrast echocardiography in humans.- 6. Limitations.- 7. Perspectives and future directions.- Acknowledgement.- References.- 13. The issue of an intravenous MC-2DE methodology. A typical early study.- Section One: Recapitulation of problems and potentials by the volume-editor Samuel Meerbaum.- Section Two: Evaluation of myocardial echo enhancement by intra venous contrast echomyography in dogs.- 2.1 Introduction.- 2.2 Method.- 2.2.1 Experimental preparation.- 2.2.2 Echocardiographic examination.- 2.2.3 Experimental protocol.- 2.3 Results.- 2.3.1 Variation of the echo intensity of the normal myocardium.- 2.3.2 Effects of ether on the enhancement of myocardial echo.- 2.3.3 Effects of hydrogen peroxide on myocardial echo enhancement.- 2.3.4 Echo enhancement of regional myocardium after ligation of the left anterior descending coronary artery.- 2.4 Discussion.- Section Three: Present developments, progress and prospects by the volume-editor Samuel Meerbaum.- 3.1 Introduction.- 3.2 Optimal MC-2DE agents.- 3.3 Ultrasound system improvement for intravenous MC-2DE.- References.- 14. Current perspective and future prospects.- 1. General MC-2DE capabilities and limitations.- 2. Quantitation of myocardial perfusion.- 3. Efforts aimed at clinical application.- 4. Future prospects.