Abstract WP243: Choroid Plexus Perfusion in Sickle Cell Disease: an Imaging Biomarker of Brain Health?

Introduction: Cerebrovascular complications are a major cause of disability in sickle cell disease (SCD); the increased risk of strokes and silent cerebral infarcts begins in early childhood and continues lifelong. An emerging marker of glial and possibly ischemic stress is the choroid plexus (ChP) activity. As the primary cerebrospinal fluid (CSF) producing structure and most proximal component of the neurofluid circuit, CSF produced by the ChP partly circulates along perivascular spaces, and the compliance of these conduits may inform, via feedback loops, the ChP activity. We tested the hypothesis that ChP perfusion, relative to gray matter perfusion, is reduced in SCD due to increased microvascular pulsatility from anemia, is lowest in patients with prior infarcts, and may represent a novel marker of cerebral health in SCD. Methods: Patients with SCD, aged 18-45 years and age-matched healthy controls underwent 3T MRI and MRA with standard anatomical protocols for infarct and vasculopathy assessment, along with arterial spin labeling MRI for cortical and ChP perfusion assessment. ChP in the atria of the lateral ventricles was segmented using a recently-validated deep learning method; the ratio of cortical gray matter to ChP perfusion was compared between SCD and control participants using linear regression analysis, adjusting for age and sex. Results: 118 participants, comprised of SCD (n=59, mean age=29.0±7.9 yrs) and age-matched non-anemic controls (n=59, mean age=30.6±7.8 yrs) were enrolled and completed imaging ( Table) . Consistent with the study hypothesis, total gray matter perfusion was elevated (p<0.001) in SCD (61.8±23.0 ml/100g/min) vs. controls (46.5±10.9 ml/100g/min) ( Fig. 1 ), but a relative uncoupling of ChP to gray matter perfusion was observed, with the ratio reduced (p<0.001) in SCD (0.63±0.16) vs. controls (0.77±0.16) ( Fig. 2 ). Within the SCD participants, a trend (p=0.066) for a further reduction in participants with (n=29; ratio=0.60±0.17) vs. without (n=30; ratio=0.66±0.14) infarct history was found. Conclusions: The ChP to gray matter perfusion ratio is significantly reduced (p<0.001) in SCD vs. controls. Given associations between neurofluid circulation and microvascular health, the ChP to gray matter perfusion ratio may serve as a non-invasive marker of vascular brain health; this metric is being investigated in ongoing work focused on infarct progression and treatment response.