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Introduction: Children with sickle cell disease (SCD) are a high risk population for pediatric stroke. Young children with SCD have a higher stroke incidence than older children. Cerebral oxygen metabolism, the product of CBF, OEF and arterial oxygen content (CaO2, [oxygen saturation (SpO2) x hemoglobin (Hb) x 1.36]) is age-dependent in healthy children, peaking at 5-9 years of age. CBF is age-dependent, but OEF variation across childhood is not well-studied. In non-SCD adults, elevated OEF confers higher stroke risk. Children with SCD have higher CBF and OEF than healthy controls, but also have lower CaO2. It is unknown if age independently influences CBF and OEF. We hypothesized that age, sex and CaO2 influence components of cerebral oxygen metabolism, as measured by MRI.Methods: Subjects with SCD and sibling/relative controls without SCD underwent brain MRI with measurement of CBF and OEF by pseudocontinuous arterial spin labeling and asymmetric spin echo sequences, respectively. Blood samples were obtained for Hb and hematocrit values. A fast inversion recovery sequence measured T1 values in the superior sagittal sinus. A multiple regression model determined significant factors influencing CBF and OEF (age, sex, CaO2).Results: We scanned 25 subjects without SCD (ages 6-27) and 56 subjects with SCD (ages 5-28). In multiple regression analysis, age (p=0.0009) and CaO2 (p < 0.0001) were significantly predictive of CBF, controlling for sex. Age (p=0.027) and CaO2 (p<0.0001), were also significantly predictive of OEF, controlling for sex.Conclusion: Age is an independent predictor of CBF and OEF. Younger children have higher CBF and OEF, even after controlling for the lower CaO2 associated with SCD. This may explain the increased stroke incidence in young children with SCD.