Abstract 95: Regional Very Low Cerebral Blood Volume with Subsequent Local Reperfusion Predicts Hemorrhagic Transformation in Acute Ischemic Stroke
Authors: Campbell Bruce C , Christensen Søren , Parsons Mark W , Desmond Patricia M , Barber P. Alan , Butcher Kenneth S , Levi Christopher R , De Silva Deidre A , Lansberg Maarten G , Mlynash Michael , Olivot Jean-Marc , Straka Matus , Bammer Roland , Albers Gregory W , Donnan Geoffrey A , Davis Stephen M ,   EPITHET-DEFUSE Investigators
Published: March 2022

Background and Purpose
Regions of very low cerebral blood volume (VLCBV) on MR perfusion imaging have been shown to predict hemorrhagic transformation (HT) following stroke thrombolysis. We tested the hypothesis that local reperfusion in a region of VLCBV is a pre-requisite for hemorrhagic transformation using pooled imaging data from the EPITHET and DEFUSE studies.

Methods
Standard CBV maps were calculated and smoothed (Gaussian) to reduce noise. The volume of VLCBV was calculated within the acute Tmax>4sec perfusion lesion using fully automated techniques and a range of VLCBV thresholds relative to CBV values in the non-stroke hemisphere. Receiver operating characteristic (ROC) analysis was used to determine the optimal definition and threshold of VLCBV to predict parenchymal hematoma (PH, ECASS definition). Regional reperfusion was assessed using co-registered subacute Tmax perfusion images (DEFUSE 3-6hrs post thrombolysis, EPITHET 3-5 days post thrombolysis/placebo). The risk of PH associated with VLCBV was assessed with and without exclusion of regions of VLCBV within persistently hypoperfused regions.

Results
Of 145 patients with baseline perfusion imaging, 22 (15.2%) had PH (13 PH1, 9 PH2). A VLCBV definition of either <2.5
th
percentile of the contralateral CBV distribution (VLCBV<2.5pctile) or <15% of the mean contralateral CBV (VLCBV<15%) had similar performance in predicting PH (AUC 0.73 for both). To achieve sensitivity of 95% required a VLCBV<2.5pctile threshold of >2mL (specificity 47%) or a VLCBV<15% threshold of >0.5mL (specificity 41%). There were 130 patients with subacute perfusion imaging, at which time 15 (11.5%) had developed PH. A further 3 patients (without reperfusion at subacute MRI) later developed PH and were excluded as reperfusion status at the time of PH was unknown. In the remaining 127 patients, the AUC for PH increased from 0.77 to 0.92 (p<0.001, VLCBV<2.5pctile definition) when regions of VLCBV without reperfusion on subacute imaging were excluded. The specificity of the >2mL threshold (VLCBV<2.5pctile) increased from 46 to 75%, positive predictive value increased from 20 to 35%, likelihood ratio for PH increased from 1.9 to 4.0 (sensitivity and negative predictive value were both 100% in these 127 patients). No patient developed PH at the time of subacute imaging in the absence of local reperfusion, including one patient where reperfusion of basal ganglia infarction had occurred (with CBV normalisation) prior to thrombolysis.

Conclusions
Local reperfusion is a critical factor in determining the risk of HT associated with regional VLCBV. This is consistent with the hypothesis that the severe ischemia represented by VLCBV is associated with focal blood-brain-barrier disruption and potential HT should reperfusion subsequently occur. Assessment of VLCBV can be automated and may be useful in clinical risk-benefit decisions regarding thrombolysis.