Ischemic stroke is a common and devastating disorder. The long-term goal of this project is to develop a tool to study the pathophysiology of stroke and in particular the ischemic penumbra. In the ischemic core blood flow is <20 percent of normal and metabolism is almost absent. The peripheral regions also have reduced blood flow (20 to 50 percent of normal) but are only slightly hypometabolic. This region is called the """"""""ischemic penumbra"""""""". It has been shown that this region can be salvaged with early treatment. These areas are also involved in active protein synthesis which is thought to endow ischemic tolerance. The applicant hypothesizes that in vivo magnetic resonance imaging (MRI) of oxygen consumption can distinguish penumbral regions from infarcted regions in the setting of focal ischemia. In order to test this hypothesis the applicant proposes to develop novel MR methods to image cerebral oxygen metabolism and blood flow. The methods are based on indirect detection of the 17-0 nucleus using 1H MRI, which has already been demonstrated to be a sensitive technique. The applicant will evaluate this method in normal rats and validate it against existing methods for measuring cerebral oxygen metabolism. He will then use this method to study a reversible model of stroke involving occlusion of middle cerebral artery. The phenomenon of ischemic tolerance will be investigated by correlating MR data with immunohistochemical assays for protein expression. In this way, he hopes to be able to correlate MR images with protein synthesis. This project will greatly enhance our understanding of the pathophysiology of stroke and possibly provide a tool with which to noninvasively assess genetic therapies.
