MRI Assessment of Cerebral White Matter Microvascular Hemodynamics Across the Adult Lifespan

Abstract

Background: Changes in cerebral hemodynamics with aging are important for understanding age-related variation in neuronal health. While many prior studies have focused on gray matter, less is known regarding white matter due in part to measurement challenges related to the lower vascular density in white matter.

Purpose: To investigate the impact of age and sex on white matter hemodynamics in a Human Connectome Project in Aging (HCP-A) cohort using tract-based spatial statistics (TBSS).

Study type: Retrospective cross-sectional.

Population: Six hundred seventy-eight typically aging individuals (381 female), aged 36-100 years.

Field strength/sequence: Multi-delay pseudo-continuous arterial spin labeling (ASL) and diffusion-weighted pulsed-gradient spin-echo echo planar imaging sequences at 3.0 T.

Assessment: A skeleton of mean fractional anisotropy (FA) was produced using TBSS. This skeleton was used to project ASL-derived cerebral blood flow (CBF) and arterial transit time (ATT) measures onto white matter tracts.

Statistical tests: General linear models were applied to white matter FA, CBF, and ATT maps, while covarying for age and sex. Threshold-free cluster enhancement multiple comparisons correction was performed for the effects of age and sex, thresholded at P_FWE < 0.05. CBF, ATT, and FA were compared between sex for each tract using analysis of covariance, with multiple comparisons correction for the number of tracts at P_FDR < 0.05.

Results: Significantly lower white matter CBF and significantly prolonged white matter ATTs were associated with older age. These effects were widespread across tracts for ATT. Significant (P_FDR < 0.05) sex differences in ATT were observed across all tracts, and significant sex differences in CBF were observed in all tracts except the bilateral uncinate fasciculus. Females demonstrated significantly higher CBF compared to males across the lifespan. Few tracts demonstrated significant sex differences in FA.

Data conclusion: This study identified significant sex- and age-associated differences in white matter hemodynamics across tracts.

Evidence level: 3 TECHNICAL EFFICACY: Stage 3.

Keywords: arterial spin labeling; arterial transit time; cerebral perfusion; fractional anisotropy; typical aging; white matter.