Hypodensity Beyond the Ischemic Core: Penumbral Changes Detected With Relative Noncontrast Computed Tomography

BACKGROUND: In acute ischemic stroke, infarcted tissue gradually becomes detectable on noncontrast computed tomography (NCCT) as a hypodensity representing vasogenic edema. We studied whether subtle NCCT density changes are also present in penumbral tissue. METHODS: This observational cohort study included patients with stroke with anterior circulation occlusions from the CRISP2 study (CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project 2) who were transferred from a primary to a comprehensive stroke center for consideration of endovascular thrombectomy. Patients received baseline NCCT and computed tomography perfusion at the referring hospital and magnetic resonance imaging at the receiving hospital. We created baseline relative NCCT images, which compare voxel density to the corresponding area in the contralateral hemisphere. We analyzed the relative density of rNCCT in the core and penumbra (based on computed tomography perfusion in referring hospitals). We also assessed the correlation between relative density and the degree of hypoperfusion in the penumbra, defined as the time-to-maximum of the tissue residue function. We studied the association between penumbral changes and functional outcomes on the full distribution of the modified Rankin Scale score at 90 days. RESULTS: From the 314 patients, 162 met inclusion criteria with a median (interquartile range) age of 73 (61–83) years, penumbra volume of 78 (52–113) mL, and core volume of 0.6 (0–13.0) mL; 54% were men. The relative density was reduced by a median of 1.8% ( P <0.0001) in the penumbra and 3.3% in the core ( P <0.0001). Relative hypodensity in the penumbra was more profound with increasing hypoperfusion: 1.5% in regions with time-to-maximum of 6- to 8-second region, 1.8% in time-to-maximum of 8- to 10-seconds, and 2.2% in time-to-maximum >10-second region ( P <0.0001). We identified a trend toward worse outcomes with more hypodense penumbra (odds ratio, 1.193 [95% CI, 0.996–1.430]). CONCLUSIONS: In patients with anterior circulation acute ischemic stroke, we identified relative hypodensity in penumbral tissue on NCCT with potential clinical relevance on 90-day functional outcomes. The hypodensity was more pronounced with increasing hypoperfusion severity.