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 (MTTp3 h), 6 (MTTp6 h), and 24 hours (MTTp24 h). Perfusion changes between 3 and 6 hours (ΔMTTp3_6) and 6 and 24 hours (ΔMTTp6_24) were calculated. A 2-step analysis was performed to evaluate the impact of ΔMTTp3_6 and ΔMTTp6_24 on tissue fate. First, a voxel-based multivariable logistic regression was performed for each individual patient with MTTp3 h, ΔMTTp3_6, and ΔMTT6_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 ΔMTTp3_6 and ΔMTT6_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. ΔMTT3_6 significantly influenced 1-month infarct probability across a wide range of baseline perfusion (MTTp 0-15 s). ΔMTT6_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.