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Background and Purpose: Post-ischemic hyperperfusion has been considered as a risk factor of hemorrhagic transformation and poor prognosis. To date, however, there is a lack of data about the pathological significance of hyperperfusion after reperfusion therapy. In this study, we evaluated the relationship between hemorrhagic transformation and post-ischemic hyperperfusion after reperfusion therapy by using arterial spin labeled perfusion MRI (ASL) and 123I IMP-SPECT.Methods: We retrospectively collected data of acute stroke patients with middle cerebral artery (MCA) occlusion who received intravenous thrombolysis and/or endovascular therapy, and underwent pulsed ASL using Q2TIPS-FAIR with 3D-TGSE readout and 123I IMP-SPECT using dual-table ARG method within 14 days of stroke onset from November 2015 to June 2016. Ipsilateral-contralateral regional cerebral blood flow ratio (IC ratio) was calculated by using three-dimensional stereotactic ROI template (3DSRT) software.Results: Among 47 consecutive acute stroke patients with the MCA occlusion who received reperfusion therapy, 21 underwent only ASL and 10 underwent both ASL and SPECT after reperfusion therapy. The IC ratio of ASL was well correlated with that of SPECT in the MCA territory (r=0.65, p <0.001). Hemorrhagic transformation was observed in 7 patients. IC ratio was higher in patients with hemorrhagic transformation after reperfusion therapy than those without hemorrhagic transformation (2.19±0.35 vs 0.99±0.19, p=0.005). Focal post-ischemic hyperperfusion (IC ratio >1.5) was detected in 7 of 31 patients (23%). The presence of post-ischemic hyperperfusion was significantly associated with hemorrhagic transformation after reperfusion therapy (odds ratio 9.3, 95% confidence interval 1.4 to 64.0, p=0.03).Conclusions: Post-ischemic hyperperfusion detected by ASL predicts hemorrhagic transformation after reperfusion therapy. ASL hyperperfusion may indicate the disruption of blood brain barrier after reperfusion therapy.