Abstract

Background: We have previously shown that the borderzone region demonstrates ischemic physiology, with low cerebral blood flow (CBF) and increased oxygen extraction fraction (OEF), in pediatric sickle cell anemia (SCA). This region is vulnerable in SCA as evidenced by increased infarct burden. Here we studied healthy adults to determine if borderzone physiology exists in the absence of apparent vascular disease. Methods: Healthy (N=17, 33 ± 9 yr) and SCA (N=13, 28 ± 7 yr) adults were recruited from a tertiary care SCA clinic. Individuals with vascular risk factors or chronic medical or neurological diseases were excluded. SCA subjects were excluded for stroke, vasculopathy, or transfusion therapy. Brain MRIs were prospectively obtained including: T1, FLAIR, dynamic susceptibility contrast (CBF), and asymmetric spin echo (OEF). Within each subject, 3 regions of low CBF were derived by normalizing CBF to its peak CBF. For gray matter (GM), regions were: < 25 th %, 25-50 th %, and 50-75 th % of mean thalamic CBF. For white matter (WM), regions were: < 25 th %, 25-35 th %, and 35-45 th % of mean GM CBF. Mean OEF across the 3 CBF regions were compared using Friedman test to account for repeated measures (Fig*). Results: Figure demonstrates the approximated borderzone with heatmaps (# of subjects with WM CBF < 25 th %) for healthy and SCA adults, alongside average OEF maps for each cohort. Both in healthy and SCA adults, GM and WM OEF were elevated in the region of lowest CBF. Furthermore, relative tissue volumes of CBF < 25 th % were higher in SCA than controls (GM: 16 vs 11%, p<0.001; WM: 33 vs 23% p<0.001), suggesting disease may redistribute CBF, effectively enlarging the borderzone. Conclusion: We found ischemic physiology (low CBF / high OEF) in the borderzone of healthy adults. Additional stressors limiting cerebral oxygen delivery such as chronic anemia in SCA or carotid occlusion may lead to enlargement of the borderzone, further elevation of OEF, and a heightened vulnerability to infarction.

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