Imaging biomarkers of cerebral edema automatically extracted from routine CT scans of large vessel occlusion strokes

Background and Purpose: Volumetric and densitometric biomarkers have been proposed to better quantify cerebral edema after stroke, but their relative performance has not been rigorously evaluated. Methods: Patients with large vessel occlusion stroke from three institutions were analyzed. An automated pipeline extracted brain, cerebrospinal fluid (CSF), and infarct volumes from serial CTs. Several biomarkers were measured: change in global CSF volume from baseline (ΔCSF); ratio of CSF volumes between hemispheres (CSF ratio); and relative density of infarct region compared with mirrored contralateral region (net water uptake [NWU]). These were compared to radiographic standards, midline shift and relative hemispheric volume (RHV) and malignant edema, defined as deterioration resulting in need for osmotic therapy, decompressive surgery, or death. Results: We analyzed 255 patients with 210 baseline CTs, 255 24-hour CTs, and 81 72-hour CTs. Of these, 35 (14%) developed malignant edema and 63 (27%) midline shift. CSF metrics could be calculated for 310 (92%), while NWU could only be obtained from 193 (57%). Peak midline shift was correlated with baseline CSF ratio (ρ = –.22) and with CSF ratio and ΔCSF at 24 hours (ρ = –.55/.63) and 72 hours (ρ = –.66/.69), but not with NWU (ρ =.15/.25). Similarly, CSF ratio was correlated with RHV (ρ = –.69/–.78), while NWU was not. Adjusting for age, National Institutes of Health Stroke Scale, tissue plasminogen activator treatment, and Alberta Stroke Program Early CT Score, CSF ratio (odds ratio [OR]: 1.95 per 0.1, 95% confidence interval [CI]: 1.52-2.59) and ΔCSF at 24 hours (OR: 1.87 per 10%, 95% CI: 1.47-2.49) were associated with malignant edema. Conclusion: CSF volumetric biomarkers can be automatically measured from almost all routine CTs and correlate better with standard edema endpoints than net water uptake.