Ischemic stroke is a common and devastating disorder lacking any definitive therapy. Therapies for salvaging viable tissue frequently entail substantial risk to the patient. The long term goal of this project is to develop a noninvasive diagnostic tool for detecting early ischemic regions of the brain and to study the pathophysiology of ischemic stroke. The strong coupling normally observed between cerebral blood flow and oxygen consumption is disturbed during episodes of cerebral ischemia. Acute stroke produces tissue regions with varying degrees of blood flow and oxygen metabolism. In the ischemic core the blood flow is typically <20% of normal and the metabolic consumption of oxygen is essentially absent. The region surrounding the ischemic core has reduced blood flow (between 25 to 50% of normal), but the metabolic utilization of oxygen may be normal or only slightly reduced. This region is referred to as the """"""""ischemic penumbra."""""""" Its ischemic condition has the potential for reversal and is the target of all therapies aimed at reversing the progress of an ischemic event. The hypothesis that will be tested is that in vivo Magnetic Resonance (MR) maps of cerebral oxygen consumption can unequivocally distinguish penumbral regions from infarcted regions during episodes of focal ischemia. In order to test this hypothesis, it is proposed to develop a novel MR method that can provide high resolution noninvasive maps of cerebral oxygen consumption and blood flow. This method, which is based on indirect detection of oxygen-17 using proton MR, has already been demonstrated as a sensitive technique for detecting small differences in oxygen concentration in tissue phantoms. The applicants proposed to further evaluate this technique in normal rat models and validate it against existing methods of measuring cerebral oxygen consumption. Following the validation in healthy rats this method will be evaluated by studying reversible stroke models of varying duration in a second set of rats. These data will be correlated with histological evaluation of the region of reversible ischemia. These results will be combined with other MR methods, which provide complementary information, to provide improved diagnostic sensitivity and specificity in addition to allowing for the evaluation of therapeutic efficacy for the reversal of cerebral ischemia. Once developed in animal models, these methods can be rapidly and easily adopted for human studies due to the noninvasive nature of the technique and the ready availability of clinical MRI scanners.
