Spatial Gradient of Microstructural Changes in Normal-Appearing White Matter in Tracts Affected by White Matter Hyperintensities in Older Age

Background and Purpose: White matter hyperintensities (WMH) are commonly seen on structural MRI of older adults and are a manifestation of underlying and adjacent tissue damage. WMH may contribute to cortical disconnection and cognitive dysfunction, but it is unclear how WMH affect intersecting or nearby white matter tract integrity. This study investigated the effects of WMH on tract microstructure by determining the spatial distribution of water diffusion characteristics in white matter tract areas adjacent to both intersecting and nearby WMH. Methods: We used diffusion and structural MRI data from 52 representative participants from the Lothian Birth Cohort 1936 (72.2 ± 0.7 years) including a range of WMH burden. We segmented WMH, reconstructed 18 main white mater tracts using automated quantitative tractography and identified intersections between tracts and WMH. We measured mean diffusivity (MD) and fractional anisotropy (FA) in tract tissue at 2 mm incremental distances from tract-intersecting and non-intersecting (nearby) WMH. Results: We observed a spatial gradient of FA and MD abnormalities for most white matter tracts which diminished with a similar distance pattern for tract-intersecting and nearby WMH. Overall, FA was higher, while MD was lower around nearby WMH compared with tract-intersecting WMH. However, for some tracts, FA was lower in areas immediately surrounding nearby WMH, although with faster normalization than in FA values surrounding tract-intersecting WMH. Conclusion: WMH have similar effects on tract infrastructure, whether they be intersecting or nearby. However, the observed differences in tract water diffusion properties around WMH suggest that degenerative processes in small vessel disease may propagate further along the tract for intersecting WMH, while in some areas of the brain there is a larger and more localized accumulation of axonal damage in tract tissue nearby a non-connected WMH. Longitudinal studies should address differential effects of intersecting vs. nearby WMH progression and how they contribute to cognitive aging.