ORIGINAL RESEARCH article
Front. Neurol.
Sec. Applied Neuroimaging
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1590997
Association Between White Matter Hyperintensities and Gray Matter Volume in Cerebral Small Vessel Disease: Insights from Periventricular and Deep White Matter Lesions
Provisionally accepted
- 1Lishui Hospital of Traditional Chinese Medicine affiliated Zhejiang Chinese Medical University, Lishui, China
- 2Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, China
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Objective: To investigate the relationship between the severity of periventricular white matter hyperintensities (PWMH) and deep white matter hyperintensities (DWMH) and gray matter volume in CSVD patients.Methods: Clinical and imaging data from 125 CSVD patients, collected between April and December 2022, were analyzed. The severity of PWMH and DWMH was assessed using the Fazekas scale. 3D T1-weighted images were processed with FSL software to segment gray matter and intracranial volume. The normalized gray matter volume (GM_n) was computed as the proportional ratio of gray matter volume relative to total intracranial volume.Results: Group-level analysis revealed significant differences in GM_n were observed across various Fazekas scores for both DWMH (P = 0.041) and PWMH (P<0.001). Post hoc analysis with false discovery rate (FDR) correction showed that PWMH severity was associated with significantly lower GM_n in scores 2 and 3 compared to score 1 (FDR-adjusted P = 0.001 and 0.004, respectively), though no difference was observed between scores 2 and 3 (P > 0.05). For DWMH, no pairwise comparisons survived FDR correction, though a non-significant trend toward reduced GM_n was noted in score 3 versus scores 0-1 (FDR-adjusted P = 0.08). After multivariate analysis adjusting for vascular risk factors, PWMH severity was found to be independently associated with GM_n [P<0.05, β (95% CI): Age -0.212 (-0.412, -0.011), PWMH score -0.408 (-0.605, -0.210)], while DWMH severity showed no independent association with GM_n (P>0.05). Mediation analysis revealed PWMH significantly mediated 39.1% of the total effect of age on GM_n (indirect effect = -0.136; 95% CI: -0.265 to -0.053).PWMH, but not DWMH, is independently associated with gray matter volume and partially mediates the age-related decline in GM volume. These findings highlight the topographical and mechanistic heterogeneity of WMH subtypes and underscore PWMH as a potential imaging marker for early intervention in CSVD-related neurodegeneration.
Keywords: White matter hyperintensity, Periventricular white matter, Cerebral small vessel disease, gray matter, Atrophy
Received: 10 Mar 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 FENG, LEI, XU and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhihua Xu, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, Zhejiang Province, China
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