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 (MTTp(3_6)) and 6 and 24 hours (MTTp(6_24)) were calculated. A 2-step analysis was performed to evaluate the impact of MTTp(3_6) and MTTp(6_24) on tissue fate. First, a voxel-based multivariable logistic regression was performed for each individual patient with MTTp(3 h), MTTp(3_6), and MTT6_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 MTTp(3_6) and MTT6_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. MTT3_6 significantly influenced 1-month infarct probability across a wide range of baseline perfusion (MTTp 0-15 s). MTT6_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.