The overall goal of the proposed research is the development and validation of an approach for detection of viable myocardium noninvasively with quantitative ultrasonic imaging techniques that can be performed at the bedside, repeated as often as necessary, and performed relatively inexpensively to identify viable myocardium and provide objective evaluations of the response of the myocardium to ischemia and therapeutic interventions. The hypothesis is that myocardial ultrasonic scattering properties are indicative of specific physical features of the tissue, that these are distinctive and amenable for real-time myocardial imaging via the measurement of integrated backscatter, and that characteristics indicative of viability, irreversible damage, and ischemia induced by stress testing can be ascertained at the bedside by ultrasonic tissue characterization. The primary specific aim includes the improved selection of patients with coronary artery disease for specific interventions by distinguishing between stunned, hibernating, and irreversibly damaged myocardium and quantification of the locus and quantities of each by quantitative ultrasonic tissue characterization.
The second aim proposes characterization of the origins of myocardial stunning and of hibernation in patients with coronary artery disease to allow development of more effective prevention and thereby maintenance of global and segmental ventricular function. In addition, we propose to extend ultrasonic tissue characterization for development of three novel diagnostic applications in patients with coronary artery disease: instantaneous quantification of ventricular segmental function, implementation of pressure-dimension indices of ventricular function, and refinement in quantitative myocardial contrast echocardiography. To accomplish these goals we propose to study patients with acute myocardial ischemia and chronic coronary artery disease utilizing conventional echocardiography, ultrasonic integrated backscatter imaging, frequency dependence of backscatter, dobutamine stress echocardiography and myocardial contrast echocardiography. Correlative studies with positron emission tomography and coronary angiography will be obtained and employed as standards. The two-pronged approach envisioned: (noninvasive assessment of myocardial structural features and delineation of its functional properties) is designed to permit a more robust and comprehensive evaluation of patients with acute myocardial ischemia and remote infarction with quantitative indexes of myocardial characteristics and performance in real-time. Results of these studies are designed to improve the objective selection of treatment strategies in patients with coronary artery disease based on noninvasive quantitative acoustic parameters of tissue structure and function. Progress in experimental animal studies and clinical investigations with ultrasonic tissue characterization to date suggests that differentiation of structural and pathophysiologic processes in tissue can be accomplished as outlined in the proposal.
