Validating imaging biomarkers of cerebral edema in patients with severe ischemic stroke

Albert J. Yoo, Kevin N. Sheth, W. Taylor Kimberly, Zeshan A. Chaudhry, Jordan J. Elm, Sven Jacobson, Stephen M. Davis, Geoffrey A. Donnan, Gregory W. Albers, Barney J. Stern, R. Gilberto González

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Background: There is no validated neuroimaging marker for quantifying brain edema. We sought to test whether magnetic resonance imaging (MRI)-based metrics would reliably change during the early subacute period in a manner consistent with edema and whether they would correlate with relevant clinical endpoints. Methods: Serial MRI studies from patients in the Echoplanar Imaging Thrombolytic Evaluation Trial with initial diffusion-weighted imaging (DWI) lesion volume >82 cm3 were analyzed. Two independent readers outlined the hemisphere and lateral ventricle on the involved side and calculated respective volumes at baseline and days 3 to 5. We assessed interrater agreement, volume change between scans, and the association of volume change with early neurologic deterioration (National Institutes of Health Stroke Scale score worsening of ≥4 points), a 90-day modified Rankin scale (mRS) score of 0 to 4, and mortality. Results: Of 12 patients who met study criteria, average baseline and follow-up DWI lesion size was 138 cm3 and 234 cm3, respectively. The mean time to follow-up MRI was 62 hours. Concordance correlation coefficients between readers were >0.90 for both hemisphere and ventricle volume assessment. Mean percent hemisphere volume increase was 16.2 ± 8.3% (P <.0001), and the mean percent ventricle volume decrease was 45.6 ± 16.9% (P <.001). Percent hemisphere growth predicted early neurologic deterioration (area under the curve [AUC] 0.92; P =.0005) and 90-day mRS 0 to 4 (AUC 0.80; P =.02). Conclusions: In this exploratory analysis of severe ischemic stroke patients, statistically significant changes in hemisphere and ventricular volumes within the first week are consistent with expected changes of cerebral edema. MRI-based analysis of hemisphere growth appears to be a suitable biomarker for edema formation.

Original languageEnglish (US)
Pages (from-to)742-749
Number of pages8
JournalJournal of Stroke and Cerebrovascular Diseases
Issue number6
StatePublished - Aug 2013
Externally publishedYes


  • Acute ischemic stroke
  • biomarker subject codes 44 and 45
  • cerebral edema
  • magnetic resonance imaging
  • malignant stroke

ASJC Scopus subject areas

  • Surgery
  • Rehabilitation
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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