Deterioration of Peri-Infarct Microvascular Hemodynamics Following Successful Reperfusion in Acute Ischemic Stroke Predicts Infarct Growth

BACKGROUND: Microvascular hemodynamic deterioration is a proposed mechanism underlying the no-reflow phenomenon in acute ischemic stroke. Experimental studies suggested that relative heterogeneity of capillary transit time (RTH) is a potential imaging biomarker of microvascular impairment. We investigated the relationship between peri-infarct RTH and infarct growth, measured on immediate post-thrombectomy (PT) perfusion magnetic resonance imaging (MRI), and functional outcomes in patients with acute ischemic stroke with successful reperfusion. METHODS: In this retrospective case-control study from the University of California, Los Angeles, patients with acute ischemic stroke from 2015 to 2020 were included if they had excellent reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2c) and diffusion- and perfusion-weighted MRIs at baseline, immediately PT, and 24 to 48 hours after thrombectomy. Peri-infarct regions were defined as time to maximum ≥6-second regions on baseline MRI that were not infarcted on immediate PT MRI. Following image coregistration, quantitative values of perfusion parameters, including RTH, were obtained from peri-infarct regions on immediate PT MRI. Two primary outcomes were assessed: (1) infarct growth ≥10 mL and (2) poor functional outcome (90-day modified Rankin Scale score >2). Associations between clinical and imaging parameters and outcomes were evaluated using univariate analysis. Age, sex, and covariates that were significant in univariate analysis were included in logistic regression analyses. RESULTS: Among 47 patients included in the analysis (62% female; mean age, 72±13 years; median National Institutes of Health Stroke Scale score, 14), 20 (43%) patients had substantial infarct progression and poor functional outcome. Peri-infarct RTH was significantly ( P =0.005) higher in patients with infarct growth >10 mL than those without and remained as an independent predictor (odds ratio, 1.4 per 10% increase [95% CI, 1.0–2.0]; P =0.04). Similarly, the peri-infarct RTH was significantly higher ( P <0.001) in patients with poor functional outcomes than those with good functional outcomes and remained as a significant predictor of poor functional outcome (odds ratio, 1.4 per 10% increase [95% CI, 1.0–1.9]; P =0.03). CONCLUSIONS: Increased peri-infarct RTH on immediate PT MRI predicts substantial infarct progression and poor functional outcomes in successfully reperfused patients with acute ischemic stroke. Results highlight the role of microvascular dysfunction depicted by elevated RTH as a potential marker of no-reflow phenomenon despite excellent macrovascular reperfusion.