Cerebral vascular shunting and oxygen metabolism in sickle cell disease

Patients with sickle cell disease (SCD) are at elevated risk of silent cerebral infarcts and strokes; however, they frequently lack established stroke risk factors (e.g., macrovascular arterial steno-occlusion) and as such the mechanisms underlying such events are incompletely characterized. This study evaluated cerebral metabolism with respect to imaging markers of vascular shunting in 143 SCD participants, including 73 pediatric (6-17 years) and 70 adult (18-40 years) participants. Participants completed clinical and cerebral imaging assessments using 3-Tesla brain MRI to quantify cerebral hemo-metabolic measures. Vascular shunting was assessed in each patient using a previously published ordinal venous hyperintensity score (VHS=0, 1, or 2) on cerebral blood flow-weighted MRI. Relationships between age group (pediatric versus adults) and hemo-metabolic measures for varying VHS were investigated using two-way ANOVA. Participants with VHS=2, indicative of the most rapid arterio-venous transit, had significantly reduced blood oxygen content (CaO2=10.90±1.69 ml O2/100ml blood), oxygen extraction fraction (OEF=33.52±5.54%), and cerebral metabolic rate of oxygen consumption (CMRO2=2.91±0.69 ml O2/100g tissue/min) compared to their counterparts with VHS=0 (CaO2=12.42±1.58 ml O2/100ml blood; OEF=39.03±3.80%; CMRO2=3.77±0.84 ml O2/100g tissue/min) or VHS=1 (CaO2=11.86±1.73 ml O2/100ml blood; OEF=36.37±5.11%; CMRO2=3.59±0.78 ml O2/100g tissue/min). Both pediatric and adult SCD patients presenting with greater imaging evidence of vascular shunting had mildly reduced OEF and CMRO2. These findings highlight that imaging markers of vascular shunting are associated with significant, albeit mild, evidence of reduced OEF and CMRO2 in patients with SCD.