Association of 24‐Hour Computed Tomography Infarct Density on Functional Outcomes in Stroke: Secondary Analysis From the AcT Trial

Background The final infarct volume has been historically considered the most critical radiological outcome in ischemic stroke. Yet, discrepancies between final infarct volume and functional outcomes occur frequently. We aim to evaluate whether 24-hour computed tomography (CT) infarct density modifies the relationship between 24-hour CT infarct volume and functional outcomes and is associated with outcomes in acute ischemic stroke. Methods Data are from the AcT (Alteplase Versus Tenecteplase in AIS [Acute Ischemic Stroke] Within 4.5 Hours) trial. Patients with detected 24-hour CT infarct and no parenchymal hematoma were included. To capture within-lesion heterogeneity, "24-hour CT standardized infarct density" was calculated as mean Hounsfield Unit/SD for every patient. Primary outcome was the 90-day ordinal modified Rankin Scale score. We assessed effect modification using interaction terms and performed adjusted regression analyses. Results Of 1577 patients, 839 (53.2%) were included (median age 75 years [interquartile range, 64-84], 414 [9.3%] female). Median infarct volume was 7.5 mL (interquartile range, 1.6-28.0), and median standardized infarct density was 4.8 standardized-Hounsfield Units (interquartile range, 4.0-5.8). Standardized infarct density significantly modified the effect of infarct volume on modified Rankin Scale score (P-interaction=0.001) and mortality (P-interaction=0.014). Higher standardized infarct density (ie, less severe infarct degree) was associated with better 90-day modified Rankin Scale score (adjusted common odds ratio [acOR], 0.87 [95% CI, 0.80-0.96] per 1-standardized-Hounsfield Unit increase), whereas infarct volume was not (acOR, 0.96 [95% CI, 0.90-1.01] per 5-mL increase). Conclusions CT infarct density modifies the effect of infarct volume on outcomes and is independently associated with better outcomes. These findings suggest that 24-hour CT infarct volume and density may provide complementary information on the infarct burden.