Heterogeneity of Cerebral White Matter Lesions and Clinical Correlates in Older Adults.

BACKGROUND AND PURPOSE: Cerebral white matter signal abnormalities (WMSAs) are a significant radiological marker associated with brain and vascular aging. However, understanding their clinical impact is limited because of their pathobiological heterogeneity. We determined whether use of robust reliable automated procedures can distinguish WMSA classes with different clinical consequences. METHODS: Data from generally healthy participants aged >50 years with moderate or greater WMSA were selected from the Human Connectome Project-Aging (n=130). WMSAs were segmented on T1 imaging. Features extracted from WMSA included total and regional volume, number of discontinuous clusters, size of noncontiguous lesion, contrast of lesion intensity relative to surrounding normal appearing tissue using a fully automated procedure. Hierarchical clustering was used to classify individuals into distinct classes of WMSA. Radiological and clinical variability was evaluated across the individual WMSA classes. RESULTS: Class I was characterized by multiple, small, lower-contrast lesions predominantly in the deep WM; class II by large, confluent lesions in the periventricular WM; and class III by higher-contrast lesions restricted to the juxtaventricular WM. Class II was associated with lower myelin content than the other 2 classes. Class II was more prevalent in older subjects and was associated with a higher prevalence of hypertension and lower physical activity levels. Poor sleep quality was associated with a greater risk of class I. CONCLUSIONS: We classified heterogeneous subsets of cerebral white matter lesions into distinct classes that have different clinical risk factors. This new method for identifying classes of WMSA will be important in understanding the underlying pathophysiology and in determining the impact on clinical outcomes.

Characterizing cerebral hemodynamics across the adult lifespan with arterial spin labeling MRI data from the Human Connectome Project-Aging.

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) has become a popular approach for studying cerebral hemodynamics in a range of disorders and has recently been included as part of the Human Connectome Project-Aging (HCP-A). Due to the high spatial resolution and multiple post-labeling delays, ASL data from HCP-A holds promise for localization of hemodynamic signals not only in gray matter but also in white matter. However, gleaning information about white matter hemodynamics with ASL is challenging due in part to longer blood arrival times in white matter compared to gray matter. In this work, we present an analytical approach for deriving measures of cerebral blood flow (CBF) and arterial transit times (ATT) from the ASL data from HCP-A and report on gray and white matter hemodynamics in a large cohort (n = 234) of typically aging adults (age 36-90 years). Pseudo-continuous ASL data were acquired with labeling duration = 1500 ms and five post-labeling delays = 200 ms, 700 ms, 1200, 1700 ms, and 2200 ms. ATT values were first calculated on a voxel-wise basis through normalized cross-correlation analysis of the acquired signal time course in that voxel and an expected time course based on an acquisition-specific Bloch simulation. CBF values were calculated using a two-compartment model and with age-appropriate blood water longitudinal relaxation times. Using this approach, we found that white matter CBF reduces (ρ = 0.39) and white matter ATT elongates (ρ = 0.42) with increasing age (p < 0.001). In addition, CBF is lower and ATTs are longer in white matter compared to gray matter across the adult lifespan (Wilcoxon signed-rank tests; p < 0.001). We also found sex differences with females exhibiting shorter white matter ATTs than males, independently of age (Wilcoxon rank-sum test; p < 0.001). Finally, we have shown that CBF and ATT values are spatially heterogeneous, with significant differences in cortical versus subcortical gray matter and juxtacortical versus periventricular white matter. These results serve as a characterization of normative physiology across the human lifespan against which hemodynamic impairment due to cerebrovascular or neurodegenerative diseases could be compared in future studies.