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

J Stroke Cerebrovasc Dis. 2013 Aug;22(6):742-9. doi: 10.1016/j.jstrokecerebrovasdis.2012.01.002. Epub 2012 Feb 9.

Abstract

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 cm(3) 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 cm(3) and 234 cm(3), 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.

Keywords: Acute ischemic stroke; biomarker subject codes 44 and 45; cerebral edema; magnetic resonance imaging; malignant stroke.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Edema / diagnosis*
  • Brain Edema / drug therapy
  • Brain Edema / pathology
  • Brain Ischemia / diagnosis*
  • Brain Ischemia / drug therapy
  • Brain Ischemia / pathology
  • Cerebral Ventricles / drug effects
  • Cerebral Ventricles / pathology*
  • Cerebrum / drug effects
  • Cerebrum / pathology*
  • Disability Evaluation
  • Disease Progression
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Reproducibility of Results
  • Risk Factors
  • Severity of Illness Index
  • Stroke / diagnosis*
  • Stroke / drug therapy
  • Stroke / pathology
  • Thrombolytic Therapy
  • Time Factors

Substances

  • Fibrinolytic Agents