Elevated cerebral blood flow in distal and intermediate arterial territories in pediatric sickle cell anemia.

INTRODUCTION: Children with sickle cell anemia (SCA) are at increased risk of cerebrovascular complications due to chronic anemia and progressive vascular injury, yet how their cerebral hemodynamics are altered remains poorly understood. Previous research has shown that overall cerebral blood flow (CBF) is often higher in SCA, likely as an adaptive response to their chronic anemia, while this CBF increase is also linked to a greater risk of stroke, silent infarcts, and cognitive deficits. Distinguishing when this elevation reflects effective compensation versus early pathophysiology is critical. METHODS: This study examined spatial patterns of cerebral blood flow (CBF) and their relationship with transcranial Doppler (TCD) velocity to better characterize hemodynamic adaptation in pediatric SCA. CBF was quantified using arterial spin labeling MRI in 32 children with HbSS or HbS/β0-thalassemia (median age, 12.3 years; range, 7.2-17.8) across the anterior (ACA), middle (MCA), and posterior (PCA) cerebral artery territories, and their proximal, intermediate, and distal sub-territories in gray and white matter. RESULTS: Across all three territories, distal and intermediate sub-territories exhibited significantly higher CBF than proximal regions (p < 0.0001), and these sub-territory differences increased with age (p ≤ 0.04). Distal CBF was significantly lower than intermediate CBF (p < 0.0001) in only MCA but not in PCA and ACA. Although none of the patients had abnormal TCD velocities and only five showed conditionally elevated TCD velocities in one territory, 38% showed silent cerebral infarctions. CBF and TCD velocities in corresponding territories were not significantly correlated, except in the left ACA and right MCA gray matter, where weak inverse correlations were observed. CONCLUSIONS: These findings suggest that compensatory increases in CBF in response to chronic anemia occur primarily at the microvascular level within distal and intermediate sub-territories, highlighting the vulnerability of the distal microcirculation especially in MCA. Territorial perfusion mapping may therefore reveal early hemodynamic adaptations not captured by global CBF measures or detectable by conventional TCD screening. This approach may improve early detection and support better treatment strategies in patients.