Cerebral Oxygen Metabolism in Adults with Sickle Cell Disease

In sickle cell disease (SCD), oxygen delivery is impaired due to anemia, especially during times of increased metabolic demand, and cerebral blood flow (CBF) must increase to meet changing physiologic needs. But hyperemia limits cerebrovascular reserve (CVR) and ischemic risk prevails despite elevated CBF. The cerebral metabolic rate of oxygen (CMRO 2 ) reflects oxygen supply and consumption so may be more insightful than flow-based CVR measures for ischemic risk in SCD. We hypothesized that adults with SCD have impaired CMRO 2 at rest and that a vasodilatory challenge with acetazolamide would improve CMRO 2 . CMRO 2 was calculated from CBF and oxygen extraction fraction (OEF), measured with arterial spin labeling and T 2 -prepared tissue relaxation with inversion recovery (T 2 -TRIR) MRI. We studied 36 adults with SCD without a clinical history of overt stroke and 9 healthy controls. As expected, CBF was higher in patients with SCD versus controls (mean ± standard deviation: 74±16 vs 46±5 mL/100g/min, P<.001), resulting in similar oxygen delivery (SCD: 377±67 vs controls: 368±42 μmol O 2 /100g/min, P=.69). OEF was lower in patients versus controls (27±4 vs 35±4 %, P<.001), resulting in lower CMRO 2 in patients versus controls (102±24 vs 127±20 μmol O 2 /100g/min, P=.002). After acetazolamide, CMRO 2 declined further in patients (P<.01) and did not decline significantly in controls (P=.78), indicating that forcing higher CBF worsened oxygen utilization in SCD patients. This lower CMRO 2 could reflect variation between healthy and unhealthy vascular beds in terms of dilatory capacity and resistance whereby dysfunctional vessels become more oxygen-deprived, hence increasing the risk of localized ischemia.