• Hongyu An, Andria L Ford, Yasheng Chen, Hongtu Zhu, Rosana Ponisio, Gyanendra Kumar, Amirali Modir Shanechi, Naim Khoury, Katie D Vo, Jennifer Williams, Colin P Derdeyn, Michael N Diringer, Peter Panagos, William J Powers, Jin-Moo Lee, and Weili Lin.
• From the Biomedical Research Imaging Center and Departments of Radiology (H.A., Y.C., W.L.), Biostatistics (H.Z.), and Neurology (W.J.P., W.L.), University of North Carolina at Chapel Hill; Department of Neurology (A.L.F., G.K., N.K., J.-M.L.), Department of Radiology (R.P., K.D.V., C.P.D., J.-M.L.), Department of Emergency Medicine (P.P.), and School of Medicine (A.L.F., G.K., N.K., J.-M.L., R.P., K.D.V., C.P.D., J.-M.L., A.M.S., P.P.), Washington University, St. Louis, MO; and Emergency Department, Barnes-Jewish Hospital, St. Louis, MO (J.W.).
• Stroke. 2015 Apr 1; 46 (4): 982-8.

Background And PurposePenumbral biomarkers promise to individualize treatment windows in acute ischemic stroke. We used a novel magnetic resonance imaging approach that measures oxygen metabolic index (OMI), a parameter closely related to positron emission tomography-derived cerebral metabolic rate of oxygen utilization (CMRO2), to derive a pair of ischemic thresholds: (1) an irreversible-injury threshold that differentiates ischemic core from penumbra and (2) a reversible-injury threshold that differentiates penumbra from tissue not-at-risk for infarction.MethodsForty patients with acute ischemic stroke underwent magnetic resonance imaging at 3 time points after stroke onset: <4.5 hours (for OMI threshold derivation), 6 hours (to determine reperfusion status), and 1 month (for infarct probability determination). A dynamic susceptibility contrast method measured cerebral blood flow, and an asymmetrical spin echo sequence measured oxygen extraction fraction, to derive OMI (OMI=cerebral blood flow×oxygen extraction fraction). Putative ischemic threshold pairs were iteratively tested using a computation-intensive method to derive infarct probabilities in 3 tissue groups defined by the thresholds (core, penumbra, and not-at-risk tissue). An optimal threshold pair was chosen based on its ability to predict infarction in the core, reperfusion-dependent survival in the penumbra, and survival in not-at-risk tissue. The predictive abilities of the thresholds were then tested within the same cohort using a 10-fold cross-validation method.ResultsThe optimal OMI ischemic thresholds were found to be 0.28 and 0.42 of normal values in the contralateral hemisphere. Using the 10-fold cross-validation method, median infarct probabilities were 90.6% for core, 89.7% for nonreperfused penumbra, 9.95% for reperfused penumbra, and 6.28% for not-at-risk tissue.ConclusionsOMI thresholds, derived using voxel-based, reperfusion-dependent infarct probabilities, delineated the ischemic penumbra with high predictive ability. These thresholds will require confirmation in an independent patient sample.© 2015 American Heart Association, Inc.

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