In broad terms, our research seeks to apply principles of cardiac ultrasound imaging and myocardial contrast echocardiography to the study of coronary physiology and ischemic heart disease. Our research pursuits have three discrete but related foci: The first emphasizes the development and validation of new echocardiographic approaches to study the microcirculation based on novel and inherent properties of microbubble ultrasound agents. The second concerns the use of these validated approaches to answer basic physiologic questions concerning the coronary microcirculation in ischemic heart disease or other states affecting myocardial perfusion. The third, evolving area of research, investigates the combined diagnostic and therapeutic use of ultrasound and contrast agents in ischemic heart disease. Within this framework, my research spans in vitro and ex vivo experimental models, in vivo animal studies, and clinical trials in human populations. Specific research activities include the following: (1) The study of interactions between endothelial cells and microbubbles used in myocardial contrast echocardiography - this area of investigation is based on the premise that microbubble adhesion to cells may provide an in vivo approach to identifying or characterizing different molecular epitopes on biologic surfaces. (2) Therapeutic applications of microbubbles - we are testing the hypothesis that gene transfection rates increase when genes are delivered on microbubbles in the presence of ultrasound (which disrupts the microbubbles). (3) Studies using ultrasound contrast agents in human populations - we are assessing myocardial perfusion in patients with different pathophysiologic conditions using myocardial contrast echocardiography.