Abstract 182: Time is Brain on the Collateral Clock! Collaterals and Reperfusion Determine Tissue Injury

Abstract

Background: The pace of ischemic injury due to stroke may vary due to collaterals and degree of reperfusion. Previous linear models that estimate time is brain have not incorporated individual patient data from advanced imaging such as diffusion-weighted imaging (DWI) and angiographic assessment of collateral grade or reperfusion. We developed a realistic model of ischemic injury using detailed imaging data in a homogenous cohort of isolated M1 middle cerebral artery occlusions. Methods: Retrospective analysis of a consecutive series of isolated M1 occlusions was conducted at an expert core lab. ASITN collateral grade was assessed at baseline and extent of reperfusion after endovascular therapy (EVT) was scored with 3 distinct versions of TICI. A separate imaging expert measured DWI lesion volumes on serial MRI acquired from admission to discharge. Graphical analyses illustrated curves demarcating extent of injury over time, based on both collateral grade and extent of reperfusion. Results: 126 patients (median age 73; 88 women; median NIHSS 17; median time to 1 st DWI, 4h08min) with acute stroke due to M1 occlusion (61 proximal, 65 distal) underwent EVT during a 6-year period. Median collateral grade was 2 (range 0-4) and median TICI, 2B (range 0-3). mTICI scores were 0 (n=18), 1 (6), 2A (25), 2B (73), and 3 (4) with 24 TICI 2C scores when evaluated in detail. Total number of DWI scans was 323, with mean 2.5 per patient. Collateral grade strongly influenced pace of development of initial tissue injury (ASITN 0, 0.445 cc/min; 1, 0.276 cc/min; 2, 0.178 cc/min; 3, 0.106 cc/min; 4, 0.031 cc/min). The relationship between time and DWI lesion growth was not linear, but best fit logarithmically (R 2 = 0.985, RMSE 2.1 for log fit; R 2 = 0.757, RMSE 8.1 for linear fit). Individual lesion growth varied markedly with both collateral grade (ANOVA p<0.001) and the degree (TICI 2B/3 vs. 0,1,2A) of reperfusion (ANOVA p=0.013). Conclusions: Collateral grade and the degree of reperfusion strongly dictate the timecourse of ischemic injury in the brain after stroke onset. Advanced imaging and angiographic assessment of collaterals and reperfusion confirm a logarithmic, not linear, model that can be used to differentiate stroke patients and streamline therapeutic strategies.