Abstract
Sickle cell disease (SCD) is a genetic blood disorder that has profound effects on the brain. Chronic anemia combined with both macro- and microvascular perfusion abnormalities that arise from stenosis or occlusion of blood vessels increased blood viscosity, adherence of red blood cells to the vascular endothelium, and impaired autoregulatory mechanisms in SCD patients all culminate in susceptibility to cerebral infarction. Indeed, the risk of stroke is 250 times higher in children with SCD than in the general population. Unfortunately, while transcranial Doppler ultrasound (TCD) has been widely clinically adopted to longitudinally monitor macrovascular perfusion in these patients, routine clinical screening of microvascular perfusion abnormalities is challenging with current modalities (e.g., positron emission tomography and magnetic resonance imaging) given their high-cost, requirement for sedation in children year, and need for trained personnel. We assess the feasibility of a low-cost, noninvasive optical technique known as diffuse correlation spectroscopy (DCS) to quantify an index of resting-state cortical cerebral blood flow (BFI) in 11 children with SCD along with 11 sex- and age-matched healthy controls. As expected, BFI was significantly higher in SCD subjects compared to healthy controls ( ). Within SCD subjects, BFI was inversely proportional to resting-state arterial hemoglobin levels ( ), consistent with expected anemia-induced compensatory vasodilation that aims to maintain adequate oxygen delivery to the tissue. Further, in a subset of patients measured with TCD ( ), DCS-measured blood flow was correlated with TCD-measured blood flow velocity in middle cerebral artery ( ), although the trend was not statistically significant ( ). These results are consistent with those of several previous studies using traditional neuroimaging techniques, suggesting that DCS may be a promising low-cost tool for assessment of tissue-level CBF in pediatric SCD.
Highlights
Sickle cell disease (SCD) is a genetic blood disorder affecting nearly 300,000 neonates worldwide per year.[1]
Our results suggest that in children with SCD, the alterations in cerebral blood flow appear to be substantial enough to significantly reduce the effects of extracerebral layers such that we are able to observe expected CBF trends seen by other “gold standard” modalities, i.e., (1) the diffuse correlation spectroscopy (DCS) measured blood flow index (BFI) is increased in children with SCD compared to healthy controls and (2) within SCD subjects, BFI is inversely correlated with arterial hemoglobin concentration
Our results suggest that DCS is qualitatively sensitive to the known increases in CBF associated with SCD and to the relationship of CBF to anemia and other associated hematological factors
Summary
Sickle cell disease (SCD) is a genetic blood disorder affecting nearly 300,000 neonates worldwide per year.[1]. While patients with sickle cell trait who inherit one HbS gene and one HbA gene are typically asymptomatic, individuals who inherit HbS genes from both parents suffer from sickle cell anemia that can cause serious acute and chronic complications in multiple organs.[2]. The cerebral effects of SCD are substantial. By age 15, ∼2% of pediatric SCD patients experience an overt stroke accompanied by obvious neurological symptoms, and ∼40% of patients will develop silent infarctions.[3] These silent infarcts accumulate occultly, but they can be seen by MRI and are associated with cognitive impairments and increased risk of overt stroke.[3,4,5,6] compared with age-matched controls, children with SCD have significantly diminished IQ, increased incidence of attention deficits, and impaired executive skills and visuospatial memory.[3,7,8,9]
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