Wesley Richerson, PhD

ABSTRACT Background Sickle cell anemia (SCA) patients upregulate cerebral blood flow to compensate for decreased arterial oxygen content. Such hyperemic conditions can manifest as venous hyperintense signal on arterial spin labeling (ASL) MRI, which may reflect faster capillary blood transit, altered oxygen extraction fraction (OEF), and infarct risk. Purpose To implement multi-delay ASL to quantify cerebral arterial arrival time (AAT), arterial transit time (ATT) to tissue, and venous arrival time (VAT) and to test whether reductions in these parameters are present in SCA and relate to condition severity. Study Type Prospective, cross-sectional. Subjects Adults with SCA (n = 40; age = 28.1 ± 7.1 years; sex = 47.5% female) and nonanemic controls (n = 24; age = 30.6 ± 6.6 years; sex = 37.5% male). Field Strength/Sequence 3 T 3D T1-weighted, 3D T2-FLuid-Attenuated-Inversion-Recovery, 2D T2-relaxation-under-spin-tagging (TRUST), 3D pseudo-Continuous ASL (pCASL) Gradient-And-Spin-Echo, and 2D multi-delay (delay range = 200–3200 ms) Pulsed ASL (PASL). Assessment Multi-delay PASL was used to quantify AAT, gray matter ATT, VAT, and labeled venous blood volume. Venous hyperintensities and OEF were quantified from 3D pCASL and TRUST, respectively. Infarcts and vasculopathy were assessed from radiological review. Statistical Tests AAT, gray matter ATT, VAT, and labeled venous blood volume were evaluated using a Wilcoxon rank-sum test; ANOVA assessed relationships with venous hyperintense signal. Continuous variable relationships were assessed using Spearman rank-correlation (significance: two-sided p < 0.05). Results Venous labeled blood volume was significantly increased in SCA (median = 0.015 mL; IQR = 0.0087–0.023 mL) versus control (median = 0.0047 mL; IQR = 0.0032–0.0092 mL) participants, whereas VAT was significantly reduced in SCA (median = 2.53 s; IQR = 2.23–2.72 s) versus control (median = 2.75 s; IQR = 2.63–2.80 s) participants. AAT, gray matter ATT, and VAT values were not significantly related to OEF (AAT: p = 0.38; gray matter ATT: p = 0.24; VAT: p = 0.48) or prior infarct (AAT: p = 0.99; gray matter ATT: p = 0.88; VAT: p = 0.98). AAT and gray matter ATT, but not VAT (p = 0.153), were directly related to hemoglobin. Conclusion SCA patients had elevated labeled venous blood volume and shorter VAT. Differential relationships between blood transit and hemoglobin across vascular compartments provides support for venous blood kinetics not representing a simple sequela of anemia severity. Evidence Level 2. Technical Stage of Development 2.