During my years of training and practice, I have become convinced that a significant amount of scientific work has to be done in the field of clinical medicine to make its practice more objective and thus ultimately more useful. One of the areas that has interested me is regional myocardial perfusion and function and the inadequacy of coronary angiography in determining the significance of coronary stenosis. During my work with myocardial contrast agents, I became interested in their potential use for determining absolute regional myocardial perfusion. In addition, if the current limitations inherent in the quantitative assessment of regional myocardial function could be overcome, two-dimensional echocardiography would become an ideal and readily available tool for simultaneously assessing regional myocardial perfusion and function. This proposal deals in detail with what I think has to be investigated in order for myocardial contrast echocardiography to become a suitable modality for measuring regional perfusion and function. The relationship between contrast effect and blood flow has to be established; the effect of size and distribution of microbubbles on myocardial contrast effect has to be determined; the fate of microbubbles in the microvasculature has to be studied and the effect of these bubbles on the microvasculature has to be documented; the agent producing the least reactive hyperemic response has to be identified and its toxicity in intact animal and man studied. Finally, preliminary work has to be attempted in humans demonstrating significant advantages over currently available techniques of measuring myocardial blood flow. After developing a new algorithm for measuring regional myocardial function, studies involving flow-function relationships have to be performed.
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