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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS055977-03
Application #
8068720
Study Section
Special Emphasis Panel (ZNS1)
Project Start
Project End
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
3
Fiscal Year
2010
Total Cost
$328,732
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Goyal, Manu S; Hoff, Brian G; Williams, Jennifer et al. (2016) Streamlined Hyperacute Magnetic Resonance Imaging Protocol Identifies Tissue-Type Plasminogen Activator-Eligible Stroke Patients When Clinical Impression Is Stroke Mimic. Stroke 47:1012-7
An, Hongyu; Ford, Andria L; Eldeniz, Cihat et al. (2016) Reperfusion Beyond 6 Hours Reduces Infarct Probability in Moderately Ischemic Brain Tissue. Stroke 47:99-105
Chen, Yasheng; Dhar, Rajat; Heitsch, Laura et al. (2016) Automated quantification of cerebral edema following hemispheric infarction: Application of a machine-learning algorithm to evaluate CSF shifts on serial head CTs. Neuroimage Clin 12:673-680
Diringer, Michael N; Dhar, Rajat; Scalfani, Michael et al. (2016) Effect of High-Dose Simvastatin on Cerebral Blood Flow and Static Autoregulation in Subarachnoid Hemorrhage. Neurocrit Care 25:56-63
An, Hongyu; Ford, Andria L; Chen, Yasheng et al. (2015) Defining the ischemic penumbra using magnetic resonance oxygen metabolic index. Stroke 46:982-8
Dhar, Rajat; Diringer, Michael N (2015) Relationship between angiographic vasospasm, cerebral blood flow, and cerebral infarction after subarachnoid hemorrhage. Acta Neurochir Suppl 120:161-5
Curfman, David; Connor, Lisa Tabor; Moy, Hawnwan Philip et al. (2014) Accuracy of emergency medical services-reported last known normal times in patients suspected with acute stroke. Stroke 45:1275-9
Rubin, Michael A; Dhar, Rajat; Diringer, Michael N (2014) Racial differences in withdrawal of mechanical ventilation do not alter mortality in neurologically injured patients. J Crit Care 29:49-53
Sanelli, P C; Sykes, J B; Ford, A L et al. (2014) Imaging and treatment of patients with acute stroke: an evidence-based review. AJNR Am J Neuroradiol 35:1045-51
Vellimana, Ananth K; Yarbrough, Chester K; Blackburn, Spiros et al. (2014) Intravenous tissue-type plasminogen activator therapy is an independent risk factor for symptomatic intracerebral hemorrhage after carotid endarterectomy. Neurosurgery 74:254-61

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