Characterizing white matter hemodynamic markers of lesion burden and cognitive function using arterial spin labeling MRI

Abstract

AbstractBackgroundWhite matter lesions (WMLs) have been linked to cognitive decline in Alzheimer’s disease (AD), but physiological mechanisms associated with microvascular dysfunction in white matter remain incompletely understood. The purpose of this study was to investigate associations between arterial spin labeling (ASL) magnetic resonance imaging (MRI) markers of white matter hemodynamics and aging, cognitive function, and WML burden.Method Study design. Participants (n=234) provided written consent for this IRB‐approved cross‐sectional study as part of the Human Connectome Aging Project. Participants underwent a range of health and cognitive assessments, including the Montreal Cognitive Assessment (MoCA), and 3 Tesla MRI. Structural imaging. High‐resolution T1‐weighted images were acquired for co‐registration and were processed with FreeSurfer for calculation of white matter signal abnormalities as a measure of WML burden. Hemodynamic imaging. ASL data were acquired using a labeling duration=1500 ms and five equally spaced post‐labeling delays from 200‐2200 ms with spatial resolution=2.5x2.5x2.5 mm3. ASL images were corrected for distortion and for motion. Cerebral blood flow (CBF) and arterial transit time (ATT) were computed using a cross‐correlation approach and a two‐compartment model. Data analysis. Mean CBF and ATT values were calculated inside white matter masks derived using FreeSurfer for each subject and assessed as a function of age, WML burden, and MoCA score.ResultWe found an inverse association between white matter CBF and age (p<0.001) and a direct association between white matter ATT and age (p<0.001), where increasing age corresponded to lower CBF and longer ATT. After including age as a covariate, we found a trend for an inverse relationship between white matter CBF and WML burden (p=0.064), with lower CBF indicating higher WML burden (Figure 2). Lastly, we also found a trend for an inverse association between white matter ATT and MoCA score (p=0.097), with longer ATT indicating lower MoCA scores (Figure 3).ConclusionPreliminary results indicate that impaired hemodynamic properties (lower white matter CBF and longer white matter ATT) may be associated with elevated WML burden and poorer cognition. Further longitudinal studies are necessary to determine whether white matter hemodynamic may represent a prospective marker of WML burden and associated cognitive impairment.