Abstract TMP12: Large Vessel Vasculopathy is Associated With Oxygen Metabolic Stress in Children and Young Adults With Sickle Cell Disease

Abstract

Background: Large-vessel vasculopathy (LVV), such as moyamoya syndrome, increases stroke risk with sickle cell disease (SCD). We hypothesized that tissue-based cerebral blood flow (CBF) and oxygen extraction fraction (OEF), as indicators of hemodynamic and metabolic stress, would differ in hemispheres with vs. without LVV. Methods: Patients underwent serial brain MRI and time-of-flight MRA to quantify voxel-wise CBF, OEF, and infarcts. LVV was defined as 75-99% stenosis of a major anterior circulation artery. Hemispheres with large vessel occlusion or revascularization surgery were excluded. Infarcted voxels were removed. Mean hemispheric (hemi-) CBF, OEF of the anterior circulation were extracted based on a vascular territory template. Hemi- OEF was normalized to whole brain OEF (nOEF). Hemi- cerebral metabolic rate of oxygen utilization (CMRO 2 ) was calculated from arterial oxygen content, hemi- CBF, and hemi- OEF. Mann-Whitney U was used to compare hemispheres with vs. without LVV. Effects of age, hemoglobin, and repeated MRIs were adjusted for in linear mixed model. Results: Of 158 patients, 221 MRI and MRAs were performed. At baseline, LVV occurred in 5% of hemispheres. Median infarct volume was larger in hemispheres with vs. without LVV (6.5 vs. 0.04 mL, p <0.001). In baseline univariate analysis, hemispheres with LVV had lower CBF (25.8 vs 31.3 mL/100g/min, p =0.04), non-significantly higher nOEF (0.99 vs. 0.96, p =0.067), and lower CMRO 2 (8.1 vs. 12.4 mL/100g/min, p =0.002) vs. without LVV. In mixed model, with all MRIs included, LVV was independently associated with nOEF (β = 0.03, p =0.04) and showed a trend for association with CBF (β = -5.4, p =0.09) and CMRO 2 (β = -35.2, p =0.08). Discussion: In SCD, hemispheric OEF was increased as a compensatory response to flow-limiting stenosis, yet may be inadequate to prevent infarction as CMRO 2 decreased. Hemispheric OEF, as an indicator of increased stroke risk, may guide medical management and surgical intervention.