Validating Imaging Biomarkers of Cerebral Edema in Patients With Severe Ischemic Stroke

doi:10.1016/j.jstrokecerebrovasdis.2012.01.002

Journal of Stroke and Cerebrovascular Diseases

Volume 22, Issue 6, August 2013, Pages 742-749

https://doi.org/10.1016/j.jstrokecerebrovasdis.2012.01.002 Get rights and content

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.

Section snippets

Patient Selection

EPITHET was a phase II, prospective, randomized controlled trial of acute ischemic stroke patients who were treated with intravenous tissue plasminogen activator (IV tPA) or placebo between 3 and 6 hours after stroke onset and underwent serial MRI both before and 3 to 5 days after treatment and at 90 days. Patients were excluded if baseline noncontrast CT revealed intracranial hemorrhage or major early ischemic change (i.e., more than one-third of the MCA territory). The full methodology of

Baseline Demographics and Outcomes

Baseline demographics and outcomes are shown in Table 1. Of the 12 patients who met study criteria, the average age was 70.8 years (range 41-86 years); the median baseline NIHSS score was 18.5 (range 10-25). There were 4 (33.3%) females. Seven (58.3%) strokes involved the right hemisphere. The mean time from symptom discovery to baseline MRI was 231 minutes (range 142-320) minutes. The average baseline DWI lesion size was 137.7 cm³ (range 88.2-196.7 cm³).

Six (50%) patients received IV tPA. The

Discussion

Our findings show that within the first 3 to 5 days of severe hemispheric stroke onset, volumes of the cerebral hemisphere and lateral ventricle determined using MRI change in a manner consistent with edema formation. Specifically, there is significant growth in hemisphere volume and significant reduction in ventricular volume over time. Importantly, these measurements demonstrate excellent interrater agreement. In addition, we have shown that increases in hemisphere volume are predictive of

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: Drs. Yoo and Sheth contributed equally to this article.

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Original ArticleValidating Imaging Biomarkers of Cerebral Edema in Patients With Severe Ischemic Stroke

Background

Methods

Results

Conclusions

Section snippets

Patient Selection

Baseline Demographics and Outcomes

Discussion

Lancet Neurol

Lancet Neurol

Lancet Neurol

Natural history of perihematomal edema after intracerebral hemorrhage measured by serial magnetic resonance imaging

Stroke

Mechanisms of cerebral edema in traumatic brain injury: Therapeutic developments

Curr Opin Neurol

Aggravation of infarct formation by brain swelling in a large territorial stroke: A target for neuroprotection?

J Neurosurg

Prediction of malignant middle cerebral artery infarction by magnetic resonance imaging within 6 hours of symptom onset: A prospective multicenter observational study

Ann Neurol

Original Article
Validating Imaging Biomarkers of Cerebral Edema in Patients With Severe Ischemic Stroke