This is a proposal for the further development of the investigator's magnetization transfer technique with application to the rat model of middle cerebral artery occlusion (MCAO). Conventional MR imaging is known to be insensitive and nonspecific in the detection of early ischemic events, and the newer diffusion-weighted imaging (DWI) method appears to show sensitivity at the earlier stages of ischemia but not necessarily at later stages. A pulse technique has been developed that is able to measure the forward magnetization transfer rates between bound and free protons (Kf) with good precision. The preliminary results demonstrated a sizable decrease in Kf during and after the period of ischemia; Kf contrast appeared to be irreversible upon reperfusion and correlated with known regions of cell damage. It is proposed to measure the temporal and spatial profile of Kf in rats subjected to permanent MCAO to provide a test of the hypothesis that a decrease in Kf will be associated with cell damage as seen by histopathology. The association between the post-ictal increase in T2 and decrease in Kf will also be investigated in the same rat model to test the hypothesis that the co-distribution of T2 and Kf can be segmented to provide information about ischemic cell damage, and in particular, that an increase of tissue water will cause an increase of T2 and a simultaneous decrease of Kf.
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