Abstract Body: Introduction and aims: Infarcted brain tissue on non-contrast computed tomography (NCCT) causes hypodensity resulting from vasogenic edema. It is unknown if hypoperfusion outside of the ischemic core may result in density changes on NCCT. This study aimed to evaluate the presence of hypodensity in the CT Perfusion (CTP) based penumbra.

Methods: We included ischemic stroke patients with anterior circulation large vessel occlusions transferred from a primary to a comprehensive stroke center for consideration of thrombectomy from the CRISP2 study. Patients underwent baseline NCCT and CT Perfusion (CTP) at the referring hospital and MRI at the comprehensive center. All images were coregistered to the NCCT. We created relative NCCT (rNCCT) maps on baseline imaging, which is an automated NCCT analysis that compares voxel density to the corresponding area in the contralateral hemisphere. Density alterations on rNCCT were represented as percentages, e.g. -1% represented 1% relative hypodensity compared to the contralateral region. We analyzed relative voxel hypodensity on rNCCT within the core (defined as relative cerebral blood flow <30%) and penumbra (defined as time-to-maximum (Tmax) > 6 seconds minus core lesion volume) (Figure 1). Furthermore, we evaluated the relationship between relative density changes and hypoperfusion severity within the penumbra. To ensure that our findings were restricted to the penumbra, we performed a sensitivity analysis using the diffusion-weighted imaging (DWI) lesion at the receiving hospital to define the ischemic core.

Results: We included 169 patients with a median penumbra volume of 78 ml (IQR 51-112) and core volume of 1.3 ml (IQR 0-13.3) (Table 1). The median relative voxel hypodensity in the penumbra was 1.8% (p<0.001) and 3.4% in the core (p<0.001). Relative hypodensity in the penumbra was greater with increasing hypoperfusion severity: median 1.5% in areas with Tmax delay between 6 to 8 seconds; median 1.9% in Tmax 8 to 10 seconds; and median 2.2% in Tmax> 10 seconds (p<0.001) (Figure 2). Using the DWI lesion as the core did not alter the results.

Conclusions: In patients with anterior circulation acute ischemic stroke, we demonstrated relative hypodensity in penumbral tissue on NCCT. The hypodensity was greater in tissue with more severe hypoperfusion. A hypothesis for these findings is edema formation in the penumbra related to hypoperfusion severity. However, its significance remains to be investigated.