Defining the Ischemic Penumbra Using Magnetic Resonance Oxygen Metabolic Index

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, Weili Lin

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Purpose-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. Methods-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. Results-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. Conclusions-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.

Original languageEnglish (US)
Pages (from-to)982-988
Number of pages7
JournalStroke
Volume46
Issue number4
DOIs
StatePublished - Apr 20 2015
Externally publishedYes

Keywords

  • magnetic resonance imaging
  • reperfusion

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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