The goal of this project is to develop, evaluate, and utilize several ultrasonic techniques in the measurement of blood flow, cardiac function, and myocardial perfusion in acute and chronically instrumented animal models of cardiovascular disease, and in patients during and after cardiovascular surgery and organ transplantation. The specific projects are: 1) To continue the development of the ultrasonic displacement technique by optimizing it to sense ventricular thickening and diameter in smaller animals such as rats and mice. This will complement pressure and Doppler flow measurements which are now feasible in conscious, chronically instrumented rats and permit more types of cardiovascular studies to be done in small animal models. 2) To develop an epicardial sensor for myocardial perfusion measurements utilizing echo-contrast agents and indicator dilution principles. This technique will be applied directly to animal studies as a replacement for or adjunct to radioactive microspheres. Much of the necessary validation work will apply as well to quantitative perfusion imaging in man. 3) To continue the application of the displacement technique to the measurement of regional LV function in man postoperatively. A Doppler crystal will be added to the epicardial thickening sensor to measure velocity simultaneously in an underlying native coronary artery. 4) To continue the application of the extractable Doppler flow sensor for postoperative monitoring of blood flow in man. The applications will be expanded from measuring flow in coronary bypass grafts to measuring flow to transplanted organs and cardiac output in adults and children. 5) To perfect a loop coupling method for Doppler and displacement sensors to eliminate percutaneous leads. This will have immediate applications in long-term studies using chronically instrumented animals and potential future applications in man for use with permanently implantable flow sensors. 6) All of the new devices will be integrated into the modular ultrasonic measurement system developed under this grant so that myocardial flow, function, and perfusion measurements can be made simultaneously in a given experiment. For example, endocardial vs epicardial thickening and perfusion will be measurable at several myocardial locations using multipurpose epicardial sensors while the volume flow and passage of echo-contrast sensed by a coronary artery flow sensor will be a measure of the input function needed to quantify absolute and relative perfusion.