Defining the ischemic penumbra using magnetic resonance oxygen metabolic index

Hongyu An; Jennifer Williams; Colin P Derdeyn; Andria L Ford; Yasheng Chen; Hongtu Zhu; Rosana Ponisio; Gyanendra Kumar; Amirali Modir Shanechi; Naim Khoury; Katie D Vo; Michael N Diringer; Peter Panagos; William J Powers; Jin-Moo Lee; Weili Lin

doi:10.1161/STROKEAHA.114.008154

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Defining the ischemic penumbra using magnetic resonance oxygen metabolic index

Journal article

Peer reviewed

Defining the ischemic penumbra using magnetic resonance oxygen metabolic index

Hongyu An, Jennifer Williams, Colin P Derdeyn, Andria L Ford, Yasheng Chen, Hongtu Zhu, Rosana Ponisio, Gyanendra Kumar, Amirali Modir Shanechi, Naim Khoury, …

Stroke (1970), Vol.46(4), pp.982-988

04/2015

DOI: 10.1161/STROKEAHA.114.008154

PMCID: PMC4533116

PMID: 25721017

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Abstract

Penumbral 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. Forty 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. The 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. OMI 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.

Biomarkers - metabolism

Reproducibility of Results

Prognosis

Cerebrovascular Circulation - physiology

Humans

Middle Aged

Stroke - diagnosis

Brain Ischemia - metabolism

Magnetic Resonance Imaging - methods

Cerebral Infarction - diagnosis

Male

Oxygen - metabolism

Stroke - metabolism

Cerebral Infarction - metabolism

Brain Ischemia - diagnosis

Female

Aged

Details

Title: Subtitle: Defining the ischemic penumbra using magnetic resonance oxygen metabolic index
Creators: Hongyu An
Jennifer Williams - 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.)
Colin P Derdeyn - 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.)
Andria L Ford - 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.)
Yasheng Chen - 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.)
Hongtu Zhu - 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.)
Rosana Ponisio - 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.)
Gyanendra Kumar - 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.)
Amirali Modir Shanechi - 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.)
Naim Khoury - 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.)
Katie D Vo - 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.)
Michael N Diringer - 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.)
Peter Panagos - 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.)
William J Powers - 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.)
Jin-Moo Lee - 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.). weili_lin@med.unc.edu leejm@neuro.wustl.edu
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.). weili_lin@med.unc.edu leejm@neuro.wustl.edu
Resource Type: Journal article
Publication Details: Stroke (1970), Vol.46(4), pp.982-988
DOI: 10.1161/STROKEAHA.114.008154
PMID: 25721017
PMCID: PMC4533116
NLM abbreviation: Stroke
ISSN: 0039-2499
eISSN: 1524-4628
Publisher: United States
Grant note: P50 NS055977 / NINDS NIH HHS 5P50NS055977 / NINDS NIH HHS K23 NS069807 / NINDS NIH HHS R01 NS082561 / NINDS NIH HHS R01 NS037312 / NINDS NIH HHS UL1 TR000448 / NCATS NIH HHS R01 NS054079 / NINDS NIH HHS
Language: English
Date published: 04/2015
Academic Unit: Neurology; Radiology; Iowa Neuroscience Institute; Neurosurgery
Record Identifier: 9984020620602771

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