One of the most important issues in clinical cardiology is the detection of injured but salvageable myocardium. Despite extensive study, the potential role of contrast MRI in detecting salvageable myocardium is not fully understood perhaps secondary to the complexity of myocardial injury and healing. In addition, new contrast enhancement patterns are observed with advances in MRI technology. We recognized that resolution of three key issues would provide important guidance for future investigations: 1) Do regions subjected to severe but reversible ischemic injury hyperenhance? 2) Does the spatial extent of hyperenhancement overestimate that of acute myocyte necrosis? 3) Do chronic infarcts (collagenous scar) hyperenhance? Over the past year we have studied these issues in chronically instrumented dogs (Appendix 1). We found that delayed hyperenhancement (images acquired >5 min after Gd-DTPA) does not occur following severe but reversible ischemic injury despite a persistent wall motion abnormality (Part 1 of Preliminary Studies). We found that at a spatial resolution of 500x500x500 mu m the size and shape of MRI hyperenhanced regions appear to be identical to those of acute myocyte necrosis at 2 hours (with reperfusion), l day (without reperfusion), and 3 days post- infarct (Part 2 of Preliminary Studies). We also found that collagenous scars hyperenhance and that scar size matches the size of hyperenhancement (Part 3 of Preliminary Studies). In the pathophysiologies investigated to date, the data suggest a potentially important hypothesis: to the limit of the spatial resolution of contrast MRI, myocardium that does not hyperenhance is viable irrespective of contractile function and infarct age. To investigate this further, we propose to determine the relation between the spatial extent of MRI hyperenhancement to that of myocyte necrosis and scar throughout the processes of injury and healing (Aim l), to determine the mechanisms which underlie contrast enhancement (Aim 2), and to understand how longitudinal changes in contrast enhancement patterns within individuals relate to the evolution of injury (Aim 3). This will be achieved by combining in vivo and ex vivo MRI with established techniques such as histochemical staining, light and electron microscopy, electron probe X-ray microanalysis and inductively-coupled plasma emission spectroscopy. Our proposed five-year plan will allow us to establish the relationship of MRI contrast enhancement patterns to the presence and extent of viable myocardium.
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