Abstract
Sickle cell disease (SCD) is a genetic blood disorder characterized by the production of abnormal hemoglobin known as hemoglobin S, which leads to reduced oxygen-carrying capacity of the blood. This reduced blood oxygenation can trigger cerebrovascular remodeling, leading to a higher risk of cerebrovascular disease and cognitive impairment. Despite growing evidence of the importance of cerebrovascular health in managing SCD, the lack of specific diagnostic tools makes this area an underutilized target in clinical care. In this cross-sectional study, we aimed to investigate the hemodynamic mechanisms of SCD through functional magnetic resonance imaging (fMRI) and their relationship with hematological parameters. In this pioneering study, we utilized the patterns of systemic low-frequency oscillations within the blood oxygen level-dependent fMRI signal to discern oxygen levels in the brain and characterize distinct blood flow patterns in patients with SCD. We formulated a unique model that revealed two blood flow patterns in SCD patients: firstly, an abnormal rapid flow pattern through arterio-venous shunting, where highly oxygenated blood reaches the superior sagittal sinus prematurely, circumventing most capillaries; secondly, a normal flow pattern, wherein normally oxygenated blood reaches the superior sagittal sinus after traversing through the capillaries. Our findings indicate that both flow patterns coexist in SCD patients, but in those with more severe blood abnormalities, the rapid flow pattern predominates. This study marks the first instance of employing fMRI to investigate the rich hemodynamic information in SCD patients. The results hold significant potential for the development of non-invasive hemodynamic biomarkers to gauge cerebrovascular health in SCD.