Reperfusion beyond 6 hours reduces infarct probability in moderately ischemic brain tissue

Background and Purpose - We aimed to examine perfusion changes between 3 and 6 and 6 and 24 hours after stroke onset and their impact on tissue outcome. Methods - Acute ischemic stroke patients underwent perfusion magnetic resonance imaging at 3, 6, and 24 hours after stroke onset and follow-up fluid-attenuated inversion recovery at 1 month to assess tissue fate. Mean transit time prolongation maps (MTTp=MTT-[median MTT of contralateral hemisphere]) were obtained at 3 (MTTp_{3 h}), 6 (MTTp_{6 h}), and 24 hours (MTTp_{24 h}). Perfusion changes between 3 and 6 hours (ΔMTTp_3-6) and 6 and 24 hours (ΔMTTp_6-24) were calculated. A 2-step analysis was performed to evaluate the impact of ΔMTTp_3-6 and ΔMTTp_6-24 on tissue fate. First, a voxel-based multivariable logistic regression was performed for each individual patient with MTTp_{3 h}, ΔMTTp_3-6, and ΔMTT_6-24 as independent variables and tissue fate as outcome. Second, Wilcoxon signed-rank tests on logistic regression coefficients were performed across patients to evaluate whether ΔMTTp_3-6 and ΔMTT_6-24 had significant impact on tissue fate for varying severities of baseline perfusion. Results - Perfusion change was common during both time periods: 85% and 81% of patients had perfusion improvement during 3- to 6- and 6- and 24-hour time intervals, respectively. ΔMTT_3-6 significantly influenced 1-month infarct probability across a wide range of baseline perfusion (MTTp 0-15 s). ΔMTT_6-24 also impacted 1-month infarct probability, but its influence was restricted to tissue with milder baseline ischemia (MTTp 0-10 s). Conclusions - Brain tissue with mild to moderate ischemia can be salvaged by reperfusion even after 6 hours. Such tissue could be targeted for intervention beyond current treatment windows.