Although clinical studies imply that the therapeutic time-window for the treatment of acute ischemic stroke is fixed for a given intervention, these studies provide aggregate data averaging therapeutic efficacy among a population of patients. It is likely that the actual therapeutic time-window varies among individuals, depending on a variety of physiological variables. Therefore, an imaging modality capable of delineating viable brain tissue at risk for infarction with the potential for salvage would be invaluable for identifying patients that may benefit from therapy beyond the empirically-determined time-window. Two thresholds of injury are directly relevant for this purpose: one which defines irreversibly injured tissue, and another which delineates reversibly injured tissue (the latter is the target for therapy). Several lines of evidence derived from positron emission tomography (PET) studies suggest that measures of cerebral metabolic rate of oxygen utilization (CMRO2) during acute stroke may identify viable tissue at risk for infarction. Furthermore, theoretical predictions suggest that CMRO2 thresholds may be time-invariant, unlike other hemodynamic measures (e.g. cerebral blood flow - CBF). Although PET is a currently available modality to measure CMRO2, the need for an onsite cyclotron has limited its utility in the acute setting of stroke. Towards this end, we have recently developed an MR imaging approach capable of obtaining an oxygen metabolic index (MR-OMI). In this application we propose to utilize this MR-OMI to determine the two thresholds values that identify reversibly and irreversibly injured brain tissue in a population of acute ischemic stroke patients. We will determine the predictive values of these thresholds, compared to other well-studied MRIderived indices. In addition, we will examine variables that may modify these thresholds of injury, including timeto- imaging, tissue type (gray vs. white matter), and baseline clinical characteristics. An imaging modality capable of distinguishing live brain tissue from dying tissue may guide future stroke therapies, permitting the individualization of therapeutic time-windows. Such a technique may permit treatment of some patients beyond the current 3-hour time-window defined for tPA.
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