The overall goal of this Phase II project is to develop a novel R1-based method for MRI quantification of postinfarct myocardial viability using a commercially available contrast agent Gd(DTPA). The commercial embodiment of this method will be a software package that will convert a set of 2D cardiac MRI images to a 3D myocardial viability map, the Percent Infarct Map (PIM) with a voxel-by-voxel resolution. In ultimate human clinical use, the package would be interfaced with commercial MRI scanners providing physicians with an immediately available diagnostic tool at the end of the scanning session. The main target market for this package will be either the major manufacturers of MRI scanners or an established company that creates and markets cardiac MRI software. We already have had interest expressed in our plans by one such major company, Medis (see letter from Medis). Assessment of viability is crucial in the monitoring of myocardial infarction (MI). A high spatial-resolution method that can distinguish quantitatively between areas of infarct and viable islets in the infarct areas would be useful for clinical decision making. The objective of Phase I was the validation (with statistical significance), in a canine model of reperfused MI, of the PIM method to provide a reliable viability maps in the canine model of reperfused MI. PIM was also compared with the current MRI standard, Delayed Enhancement (DE), in the same dogs and MRI sessions, to ensure comparison at the same time point. All objectives of Phase I have been achieved: PIM yielded accurate quantitative information about infarct size and distribution, agreed with the pathology gold standard, TTC-staining histochemistry, and was superior to DE. While the primary aim of the Phase II project will be the development and testing of the software package itself, we also want to enhance the desirability of this package in the eyes of clinicians so that market demands for it would be optimized. Clinical usefulness depends on the reliability of a technique not just at a single selected time point along the evolution of infarct, but rather at all relevant time points of infarct tissue development, both reperfused and non-reperfused. Thus we plan to demonstrate the utility of the package at several crucial time points of infarct evolution in both reperfused and non-reperfused myocardial infarction models. To aid in coregistration of MRI and histology, based on the success in Phase I. studies, we will also incorporate ex-vivo imaging and histology to validate our findings with MRI and the post-processing software.
