Diffuse optical spectroscopies to assess cerebral hemodynamics in pediatric sickle cell disease

Project Summary Silent cerebral infarction is a serious consequence of sickle cell disease (SCD), affecting ~40% of patients by age 15. Although these injuries accumulate occultly, they are linked with cognitive deficits, diminished school performance, and increased risk of overt stroke. Our long-term goal is to develop a low-cost brain monitoring

tool that can screen for silent infarct risk in pediatric SCD to facilitate timely therapeutic intervention and that can optimize these interventions to mitigate adverse events. Silent infarcts in SCD are thought to arise from anemia- induced microvascular perfusion abnormalities and subsequent reduced cerebrovascular reserve that is

insufficient to meet tissue metabolic demands. Thus, quantification of abnormalities in microvascular cerebral blood flow, vascular reactivity, and/or oxygen extraction may be useful in identifying infarct risk. Indeed, recent MRI studies have shown that SCD children with silent infarcts have globally elevated oxygen extraction in both

white and grey matter compared to those without infarct. However, current modalities that quantify microvascular hemodynamic parameters (e.g., PET, MRI) are prohibitively expensive, have limited availability, and require anesthesia in children