Predictors of cerebral blood flow in patients with and without anemia

Abstract

Sickle cell disease (SCD) is the most common cause of stroke in childhood and results primarily from a mismatch of cerebral oxygen supply and demand rather than arterial obstruction. However, resting cerebral blood flow (CBF) has not been examined in the general African American population, in whom obesity, hypertension, cerebrovascular disease, and diminished cerebrovascular reserve capacity are common. To better understand the underlying physiological substrate upon which SCD is superimposed, we measured CBF in 32 young (age 28 ± 10 yr), asymptomatic African American subjects with and without sickle cell trait (n= 14). To characterize the effects of chronic anemia, in isolation of sickle hemoglobin we also studied a cohort of 13 subjects with thalassemia major (n= 10), dyserythropoetic anemia (n= 1), or spherocytosis (n= 2). Blood was analyzed for complete blood count, hemoglobin electrophoresis, cell free hemoglobin, and lactate dehydrogenase. Multivariate regression analysis showed that oxygen content was the strongest predictor of CBF (r(2)= 0.33,P< 0.001). CBF declined rapidly in the second and third decades of life, but this drop was explained by reductions in cerebral gray matter. However, age effects persisted after correction for brain composition, possibly representing microvascular impairment. CBF was independent of viscosity, hemoglobin S%, and body mass index. Hyperoxia resulted in reduced CBF by 12.6% (P= 0.0002), and CBF changes were proportional to baseline oxygen content (r(2)= 0.16,P= 0.02). These data suggest that these hemoglobin subtypes do not alter the normal CBF regulation of the balance of oxygen supply and demand.

Pseudo continuous arterial spin labeling quantification in anemic subjects with hyperemic cerebral blood flow

“…Across all subjects, the phase contrast measured CBF was 78.6 ± 25.4 ml/100g/min and was tightly correlated with oxygen content, gray white matter ratio and age (previous results)(6,24). Control subjects with the AS (sickle cell trait) and AA genotype exhibited indistinguishable demographics, laboratory values (except mean corpuscular hemoglobin concentration), and cerebral blood flow by PC (64.4 ± 9.5 HbAA and 58.1± 7.7 HbAS, p =0.13) and ASL (75.6 ± 9.9 HbAA and 67.3± 8.1 HbAS p =0.18).…”

“…All studies were approved by an institutional review board (CCI-11-00083) and all patients provided informed consent/assent. Subjects were drawn from a larger patient cohort described elsewhere(6,24), but limited to subjects less than 25 years of age to enrich the prevalence of high CBF.…”

“…Phase contrast data was presented in a previous study and sequence details can be found therein(6,24). In short, a single 2D axial plane, non-gated phase contrast image was positioned 1-5 cms above the carotid bifurcation.…”

“…Phase contrast CBF estimates were stable over time with a coefficient of variation of 4.6 ± 3.0% over an average of 30.3 ± 9.5minutes(6). A 3D T 1 weighted sequence (1mm 3 isotropic resolution) was collected for calculation of total brain volume (Brainsuite.org, v.15a)(26).…”

“…Anemic subjects have elevated CBF(6), high blood velocities(7), shorter vascular transit times(8) and longer blood relaxation times(9,10). In sickle cell disease (SCD), quantification is complicated further by abnormal blood properties (shorter T1 for a given hematocrit(11)) and cerebrovascular disease (stroke(12,13), vessel tortuosity(14)).…”