Validating imaging biomarkers of cerebral edema in patients with severe ischemic stroke.
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.
Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Albert J
AJ
Yoo
Kevin N
KN
Sheth
W Taylor
WT
Kimberly
Zeshan A
ZA
Chaudhry
Jordan J
JJ
Elm
Sven
S
Jacobson
Stephen M
SM
Davis
Geoffrey A
GA
Donnan
Gregory W
GW
Albers
Barney J
BJ
Stern
R Gilberto
RG
González
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001929:Brain Edema / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D002545:Brain Ischemia / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology*; D054022:Cerebrum / Q000187:drug effects / Q000473:pathology*; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D015203:Reproducibility of Results; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D015912:Thrombolytic Therapy; D013997:Time Factors
D005343:Fibrinolytic Agents