? The main thrust for this project is the validation of quantitative sodium MRI as a non-invasive means for estimating tissue viability during focal stroke using MRI. Stroke is a major public health concern in the United States. The introduction of reperfusion therapy using tissue plasminogen activator (tPA) revolutionized the treatment of stroke by providing an aggressive means to reverse the ischemic insult. The effectiveness of tPA reperfusion therapy is highly dependent on the status of the ischemic mass. Specifically, when the ischemic tissue is viable, use of tPA leads to improved clinical outcome. However, when the ischemic tissue is non-viable, reperfusion therapy can lead to intracerebral hemorrhage and/or an accelerated rate of ischemia formation. These in turn, can lead to increased intra-crannial pressure and a concomitant compromise of blood flow in areas not affected by the initial insult. Currently, there are no well-accepted, non-invasive means to assess tissue viability in stroke and, therefore, there are no direct measures to unambiguously gauge the relative benefits of the tPA therapeutic option prior to its application. Perfusion and diffusion weighted proton MRI (DW MRI) are well-established techniques for the early detection of brain ischemia. However, there is no direct correlation between measures of perfusion and/or diffusion MRI and the viability of the ischemic brain tissue. By contrast, tissue sodium concentration (TSC) exhibits a linear and reversible response for many hours after ischemia onset. Because sodium accumulation in tissue is closely related to its metabolic status, these findings have two immediate implications. First, ischemia duration should be linearly dependent on the measured TSC, and, second, there should be a threshold in TSC below which tissue reperfusion should lead to improved clinical outcome. To test the validity of these hypotheses we will perform sexual single and triple quantum filtered sodium MRI scans in a non-human primate model of temporary middle cerebral artery (MCA) occlusion. The use of a primate model of MCA occlusion will allow the study of the temporal and spatial distribution of the TSC accumulation and its relation to the deficits in cerebral blood flow. We believe that the findings from this research will provide important data that could lead to the development of useful guidelines for the clinical! management of acute stroke when sodium MRI is used in conjunction with diffusion and perfusion MRI. ? ?
