The widespread therapeutic use of thrombolytic agents to effect reperfusion of acute myocardial infarction has created the need for a routine diagnostic procedure which can document success of the treatment and estimate relative composition of viable and nonviable myocardial cells in the post ischemic territory. The current proposal will test the potential of two methods, both of which employ magnetic resonance imaging (MRI) in conjunction with extravascular contrast media, for providing the needed information. Two classes of contrast media will be used; one increases the longitudinal relaxation rate (R1) and the second increases transverse relaxation rate (R2) of nearby myocardial water protons. In both cases the change in relaxation rate is, in part, related to the fractional distribution volume of the contrast agent within tissue. The hypotheses to be tested in this project are that (a) the fractional distribution volumes can be derived from measured changes in the respective relaxation rates following administration of the contrast agents, and (b) the measured fractional distribution volumes are proportional to the fraction of necrotic cells within the myocardium. The first two specific aims of this application test these hypotheses for the two types of contrast materials by comparing measured changes in relaxation rates of normal myocardium and reperfused infarcted myocardium containing varied fractions of nonviable myocardial cells with (a) the concentrations of contrast agent or of a similar tracer molecule in the respective myocardial regions, and (b) the fraction of total cells in the post ischemic area that exhibit microscopic features of severe damage. The final two specific aims subject the R1-enhancing compound to further examination because it represents the group of clinically approved MRI contrast agents and its quantification by relaxometry is less complicated.
In specific aim #3 potential error caused by physiologic features of reperfused myocardial infarction, such as interstitial edema, the """"""""no- reflow"""""""" phenomenona, and a potential for contrast agent to penetrate ischemic but viable myocytes, is estimated. Then it is attempted to monitor potential evolving changes in the viable cell fraction within the infarction zone during prolonged reflow. In the specific aim #4, a series of studies is conduct ed using a clinical scanner, a widely available MRI sequence, and clinically relevant myocardial injury models to determine the potential of R1 relaxometry to provide useful diagnostic or prognostic information. While the technique of R1 relaxometry can be applied to patient studies immediately, this work is designed to provide a basis for this application.
