In this project it is proposed to determine the feasibility of measuring in vivo, noninvasively, the regional blood flow and regional blood volume of the myocardium using an ultrasonic contrast imaging approach. Three developments contribute to this effort: first, the development of a stable albumin microbubble preparation which is now available. The microbubbles constitute an intravascular tracer small enough to pass through capillaries and which reflect ultrasound energy effectively. Second, the development and construction of a digital ultrasound system which appears on preliminary tests to record approximately linear signals proportional to microbubble concentrations on 9-track magnetic tape for subsequent computer processing. Third, the development of a mathematical model based strictly on classical dye dilution theory which permits explicit determination of tissue perfusion, tissue blood volume and mean transit time of blood passing through the myocardial muscle from simultaneous measurements of microbubble concentrations in the muscle and in the main blood vessels supplying the muscle. Additional independent values of tissue blood volume, tissue perfusion and mean transit times may be obtained by varying experimental parameters and methods of analysis. It is proposed to establish a firm basis for producing data linear with tracer concentrations using in vitro standards and realistic phantoms, and to validate external measurements made in dogs using radioactive solid microspheres to determine regional myocardial blood flow and labeled plasma and red cells to determine regional tissue blood volume. The basic hypothesis is that while this approach appears theoretically feasible, the extent to which it must be refined and the achievable degree of accuracy remain to be determined. To support this approach, pilot data and additional protocols designed to test the feasibility of quantifying myocardial perfusion with contrast echo techniques are now incorporated into this grant proposal. The clinical applicability and value of such an approach, if successful, is self evident.
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