Background and Purpose- Early selection of patients with acute middle cerebral artery infarction at risk for malignant edema is critical to initiate timely decompressive surgery. Net water uptake (NWU) per brain volume is a quantitative imaging biomarker of space-occupying ischemic edema which can be measured in computed tomography. We hypothesize that NWU in early infarct lesions can predict development of malignant edema. The aim was to compare NWU in acute brain infarct against other common predictors of malignant edema. Methods- After consecutive screening of single-center registry data, 153 patients with acute proximal middle cerebral artery occlusion fulfilled the inclusion criteria. A total of 29 (18.2%) patients developed malignant edema defined as end point in follow-up imaging leading to decompressive surgery and death as a direct implication of mass effect. Early infarct lesion volume and NWU were quantified in multimodal admission computed tomography; time from symptom onset to admission imaging was recorded. Results- Mean time from onset to admission imaging was equivalent between patients with and without malignant infarcts (mean±SD: 3.3±1.4 hours and 3.3±1.7 hours, respectively). Edematous tissue expansion by NWU within infarct lesions occurred across all patients in this cohort (NWU: 9.1%±6.8%; median, 7.9%; interquartile range, 8.8%; range, 0.1%-35.6%); 7.0% (±5.2) in nonmalignant and 18.0% (±5.7) in malignant infarcts. Based on univariate receiver operating characteristic curve analysis, NWU >12.7% or an edema rate >3.7% NWU/h identified malignant infarcts with high discriminative power (area under curve, 0.93±0.02). In multivariate binary logistic regression, the probability of malignant infarct was significantly associated with early infarct volume and NWU. Conclusions- Computed tomography-based quantitative NWU in early infarct lesions is an important surrogate marker for developing malignant edema. Besides volume of early infarct, the measurements of lesion water uptake may further support identifying patients at risk for malignant infarction.

Infarct growth from the early ischemic core to the total infarct lesion volume (LV) is often used as an outcome variable of treatment effects, but can be overestimated due to vasogenic edema. The purpose of this study was (1) to assess two components of early lesion growth by distinguishing between water uptake and true net infarct growth and (2) to investigate potential treatment effects on edema-corrected net lesion growth. Sixty-two M1-MCA-stroke patients with acute multimodal and follow-up CT (FCT) were included. Ischemic lesion growth was calculated by subtracting the initial CTP-derived ischemic core volume from the LV in the FCT. To determine edema-corrected net lesion growth, net water uptake of the ischemic lesion on FCT was quantified and subtracted from the volume of uncorrected lesion growth. The mean lesion growth without edema correction was 20.4 mL (95% CI: 8.2–32.5 mL). The mean net lesion growth after edema correction was 7.3 mL (95% CI: −2.1–16.7 mL; p < 0.0001). Lesion growth was significantly overestimated due to ischemic edema when determined in early-FCT imaging. In 18 patients, LV was lower than the initial ischemic core volume by CTP. These apparently “reversible” core lesions were more likely in patients with shorter times from symptom onset to imaging and higher recanalization rates.