Abstract WMP97: Regional Cerebral Oxygen Extraction is Elevated in Tissue at High Risk of Stroke in Pediatric Sickle Cell Disease

Abstract

Introduction: Children with sickle cell disease (SCD) are at high risk of stroke. Hemispheric oxygen extraction fraction (OEF) is a predictor of stroke in adults with carotid occlusion, but OEF has not been evaluated as a predictor of stroke in children with SCD. Hypothesis: OEF is elevated in SCD children compared to controls within a region at high risk of stroke as defined by an infarct heat-map created from a separate retrospective SCD cohort. Methods: A prospective MRI study enrolled 37 children aged 5-21: 17 with SCD and no stroke, 12 with SCD and silent infarcts (median infarct volume=0.3ml), and 8 sibling controls. None were on transfusions or had overt stroke history. Voxel-wise OEF was measured using an asymmetric spin echo sequence. In a separate retrospective cohort of 67 SCD children with overt and silent stroke, infarct regions on FLAIR were manually outlined and coregistered to an average T1 map to create an infarct heat-map (Fig A) which was used to define a “high risk” ROI (defined by >3% infarct density). This ROI was aligned to individual OEF maps from the prospective cohort (Fig B, average OEF map). OEF within the “high risk” ROI was compared between SCD children and controls; and between SCD children with and without infarction using Mann Whitney U tests. Results: The infarct heat-map from the retrospective cohort (Fig A) and the average OEF map from the prospective SCD cohort (Fig B) demonstrate striking co-localization of infarct density and elevated OEF. Within the “high risk” ROI, OEF was higher in SCD children compared to controls (39% [36, 46] vs. 23% [22, 27], p<0.0001 (Fig C). OEF within this “high risk” ROI did not differ between SCD children with and without infarcts (40% [38, 47] vs. 38% [35, 46], p=0.6). Conclusion: OEF in SCD children is elevated in the internal borderzone, a region with high stroke risk in SCD. Regional OEF may be a marker of cerebral metabolic stress that could be exploited to stratify stroke risk in this vulnerable population.