Computed Tomography-Based Quantification of Lesion Water Uptake Identifies Patients within 4.5 Hours of Stroke Onset: A Multicenter Observational Study

Objective: Many patients with stroke cannot receive intravenous thrombolysis because the time of symptom onset is unknown. We tested whether computed tomography (CT)-based quantification of water uptake in the ischemic tissue can identify patients with stroke onset within 4.5 hours, the time window of thrombolysis. Methods: Perfusion CT was used to identify ischemic brain tissue, and its density was measured in native CT and related to the density of the corresponding area of the contralateral hemisphere to quantify lesion water uptake. The optimal cutoff value of water uptake distinguishing stroke onset within and beyond 4.5 hours was calculated in patients with proximal middle cerebral artery occlusion (derivation cohort) with known time of symptom onset. The so-derived cutoff value was validated in a prospective cohort from other stroke centers. Results: Of 178 patients of the derivation cohort, 147 (82.6%) had CT within 4.5 hours. Percentage water uptake was significantly lower in patients with stroke onset within compared to beyond 4.5 hours. The area under the receiver operating characteristic curve for distinguishing these patient groups according to percentage water uptake was 0.999 (95% confidence interval=0.996-1.000, p<0.001) with an optimal cutoff value of 11.5%. Applying this cutoff to the validation cohort of 240 patients, sensitivity was 98.6%, specificity 90.5%, positive predictive value 99.1%, and negative predictive value 86.4%. Interpretation: Quantification of brain water uptake identifies stroke patients with symptom onset within 4.5 hours with high accuracy and may guide the decision to use thrombolysis in patients with unknown time of stroke onset.