The overall goal of this new submission is to temporally differentiate subclinical oligemia above the threshold for clinical impairment (reduced CBF yet above a critical diffusion ADC threshold) from brain below thresholds of viability and at risk for hemorrhage. For each year of this 4-year study, 24 consecutive inpatients presenting with stroke-like symptoms between 6-24 hours of symptom onset will be studied. These patients will display a wide range of blood flow values and physiological states over which to determine the temporal dependences of perfusion on segmented ADC measures, yet be stable enough to undergo both the CT and MR studies needed to test the hypotheses. One important aspect of this study is to establish MR bolus-tracking as a quantitative perfusion method. We will improve the ability of perfusion-weighted MRI (PWI) to quantitatively map perfusion (Specific Aim 1) in order to establish temporal diffusion and flow thresholds in the setting of evolving acute clinical stroke (Specific Aim 2). To do this, we will acquire quantitative cerebral blood flow (CBF) maps derived from dualecho/ dual-shot gradient-echo GRE-EPI bolus tracking arterial input AIF-derived PWI images. We will test the hypothesis that CBF values measured from our automated AIF selection deconvolution routines will better correlate with the """"""""gold standard"""""""" XeCT values (acquired from the same patients at presentation) than will user-defined AIF selections. We will then co-register the MR perfusion (CBF, MTT, and CBV) and XeCT CBF values onto segmented gray and white matter diffusion (traceADC, 11-13 eigenvalues, and fractional anisotropy FA) distributions in these patients. Upon successful completion of these studies, we will have established a number of highly accurate predictive tools for evaluating brain ischemia using MRI by providing a snap-shot of the regional physiological status of evolving infarcts. We believe that this information will lead to new measures for clinical management and will eventually allow management decisions to be made within an individual patient's therapeutic time window as opposed to current conceptions of a rigid time window.
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