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

41 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

Bibliographical note

Funding Information:
Dr. Yoo has received support from Penumbra, Inc for core imaging laboratory activities. Dr. Sheth is supported by research funding from the American Academy of Neurology Clinical Research Award, American Heart Association Clinical Research Award, and Remedy Pharmaceuticals, Inc. Dr. Kimberly is supported by an American Academy of Neurology Clinical Research Award, Clinical Investigator Training Program: Beth Israel Deaconess Medical Center, Harvard Medical School, in collaboration with Pfizer, Inc and Merck & Co (NIH 1K23NS076597). Mr. Jacobson is the CEO of Remedy Pharmaceticals. Dr. Davis serves on the advisory boards of PAION, Servier, and Novo Nordisk, and has received honoraria from Novo Nordisk, Sanofi-Aventis, Pfizer, and Boehringer Ingelheim. Dr. Donnan serves on the advisory boards of Boehringer Ingelheim, PAION, Servier, and Sanofi-Aventis; has received honoraria or consulting payments from and has had costs of participating in scientific meetings reimbursed by Boehringer Ingelheim, Sanofi-Aventis, and Servier; and has received grant funding from Sanofi-Aventis and grants and consultancy payments from Boehringer Ingelheim. Dr. Albers has received grant funding from the National Institutes of Health and Lundbeck; is a consultant for Lundbeck; and holds equity in iSchemaView. Dr. Stern is supported by the National Institutes of Health. Drs. Chaudhry, Elm, and Gonzalez have no conflicts of interest to declare.


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


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