Fluid-attenuated inversion recovery magnetic resonance imaging textural features as 2 sensitive markers of white matter damage in midlife adults

Abstract

White matter hyperintensities (WMH) are common radiological findings in ageing and a typical manifestation of cerebral small vessel disease (SVD). WMH burden is evaluated by quantifying their volume, however, subtle changes in the white matter may not be captured by WMH volumetry. In this cross-sectional study we investigated whether MRI texture of both WMH and normal appearing white matter (NAWM) was associated with reaction time, WMH volume and dementia risk in a midlife cognitively normal population. Data from 183 cognitively healthy midlife adults from the PREVENT-Dementia study (mean age 51.9 ± 5.4; 70% females) were analysed. WMH were segmented from 3 Tesla fluid-attenuated inversion recovery (FLAIR) scans using a semi-automated approach. The FLAIR images were bias field corrected and textural features (intensity mean and standard deviation, contrast, energy, entropy, homogeneity) were calculated in WMH and NAWM based on generated textural maps. Textural features were analysed for associations with WMH volume, reaction time, and the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) dementia risk score using linear regression models adjusting for age and sex. The extent of NAWM surrounding the WMH demonstrating similar textural associations to WMH was further investigated by defining layers surrounding the WMH at increments of 0.86 mm thickness. Lower mean intensity within WMH was a significant predictor of longer reaction time (t = -3.77, p < 0.01). WMH volume was predicted by textural features within WMH and NAWM, albeit in opposite directions. WMH volume was not related to reaction time, although interaction analysis revealed that participants with high WMH burden and less homogeneous WMH texture demonstrated slower reaction time. A white matter area extending 2.5-3.5mm further from the WMH demonstrated similar associations. Higher CAIDE score was associated with a heterogeneous NAWM intensity pattern. Overall, greater homogeneity within WMH and a more heterogeneous NAWM intensity profile were connected to a higher WMH burden, while heterogeneous intensity was related to prolonged reaction time (WMH of larger volume) and dementia risk (NAWM). Our results suggest that the quantified textural measures extracted from widely used clinical scans, might capture underlying microstructural damage and might be more sensitive to early pathological changes compared to WMH volumetry.