Our overall goal is developing and optimizing a method for simultaneous MRI testing of myocardial perfusion and function and thus provide the means for using the high resolution qualities and low-risk nature of MRI for the early and wide-spread detection of ischemic heart disease. Radionuclide myocardial imaging with Tl-201 and technetium complexes has been so far employed to address the issue of early detection of Ischemic Heart Disease. Low spatial resolution, tissue attenuation, scatter, lack of ease of quantitation and of tomographic evaluation, and other technical factors, while continually improving, still have left room for alternative methods. MRI, by providing three-dimensional, high-resolution images of mobile protons, has the potential to assess in vivo distribution of a paramagnetic agent that distributes like Tl-201. This may ultimately lead to a means for early and sensitive detection of coronary artery disease. The immediate objective is to demonstrate the strength of the approach in the dog model in preparation for future clinical studies. To achieve this objective most efficiently, the Specific Aims below will address the following questions: 1) Whether the type of relatively persistent contrast agent we have developed is sufficient for highlighting the ischemic myocardial regions in the time flame of the imaging protocol most appropriate for the combined optimization of the detection of both perfusion and function abnormalities. 2) Which type of acquisition sequence, spiral or TFE, would create the optimal mix of advantage vs. disadvantage in the parameters most important for the combination detection by contrast agent-enhanced MRI. 3) What will be the lower limits of the agent's ability to show sufficient demarcation of the ischemic region as a function of the percent of reduction in coronary flow. 4) Under what optimized acquisition sequence would the best combination of MRI contrast and wall abnormality delineation be obtained in a relevant model of acute myocardial ischemia with stress created by dobutamine-enhanced demand for myocardial perfusion in conjunction with the creation of critical stenosis or with stress created by dipyridamole-induced redistribution of coronary flow, and to decide which stress agent is better suited for the dual purpose of the combination test. .
