Large-Vessel Vasculopathy in Children With Sickle Cell Disease: A Magnetic Resonance Imaging Study of Infarct Topography and Focal Atrophy

Abstract

Background Large-vessel vasculopathy (LVV) increases stroke risk in pediatric sickle cell disease (SCD) beyond the baseline elevated stroke risk in this vulnerable population. The mechanisms underlying this added risk and its unique impact on the developing brain are not established. Methods We analyzed magnetic resonance imaging (MRI) and angiography (MRA) scans of 66 children with SCD and infarcts by infarct density heatmaps and Jacobian determinants, a metric utilized to delineate focal volume change, to investigate if infarct location, volume, frequency, and cerebral atrophy differed among hemispheres with and without LVV. Results Infarct density heatmaps demonstrated infarct “hot spots” within the deep white matter internal borderzone region in both LVV and non-LVV hemispheres, but with greater infarct density and larger infarct volumes in LVV hemispheres (2.2 mL vs 0.25 mL, p <0.001). Additional scattered cortical infarcts in the internal carotid artery territory occurred in LVV hemispheres, but were rare in non-LVV hemispheres. Jacobian determinants revealed greater atrophy in gray and white matter of the parietal lobes of LVV compared to non-LVV hemispheres. Conclusion LVV in SCD appears to increase ischemic vulnerability in the borderzone region, as demonstrated by the increased frequency and extent of infarction within deep white matter, and increase risk of focal atrophy. Scattered infarctions across the LVV-affected hemispheres suggest additional stroke etiologies of vasculopathy (i.e. thrombo-embolism) in addition to chronic hypoxia-ischemia.

Anemia predicts lower white matter volume and cognitive performance in sickle and non‐sickle cell anemia syndrome

“…Deformation Index was positively correlated with hemoglobin in the frontal, parietal and temporal lobes but not in the occipital lobe. This finding aligned with reported regional WM volume loss, silent stroke distribution, and decreased white matter integrity in SCD patients . More specifically, regions susceptible to anemia were generally restricted to the bilateral deep white matter of watershed regions, and the territory of the middle cerebral artery.…”

“…Additionally, acute anemic events has been identified as risk factors for children with, and without, SCD . Colocalized tissue atrophy, and elevated oxygen extraction, in deep‐white matter watershed regions, have been reported in children with SCD, even in the absence of white matter hyperintensities. We hypothesize that maintaining a high hemoglobin count in patients with hemoglobinopathies during school age years will help preserve white matter volumes, although a longitudinal study is necessary to confirm this hypothesis.…”

White matter has impaired resting oxygen delivery in sickle cell patients

“…It implies that WMHs are occurring in borderzone regions where perfusion is inherently decreased in anyone. Studies from Numaguchi, Baldeweg, Guilliams and Ford in SCD patients also support that conclusion. Our O 2 delivery T‐score maps agrees with the observations of Fields et al, who demonstrated increased O 2 extraction fraction in watershed areas .…”

Red cell exchange transfusions lower cerebral blood flow and oxygen extraction fraction in pediatric sickle cell anemia

“…45 We identified a region of increased OEF in the deep supraventricular white matter, corresponding to the internal borderzone, which we and others have demonstrated to be at highest risk of infarction in SCA. 46,47 We propose that in addition to flow-limiting pathologies, oxygen-limiting pathologies would further increase ischemic vulnerability of the internal borderzone (or watershed region), as signaled by high OEF. In children with SCA, CaO 2 -lowering stressors could be common SCA complications, such as worsening of anemia or hypoxemia during acute chest syndrome.…”