Free Water MRI of White Matter in Wilson's Disease.

Background: Diffusion tensor imaging (DTI) is susceptible to partial volume effects from free water, which can be corrected by using bi-tensor free water imaging (FWI). This approach may improve the evaluation of microstructural changes associated with Wilson's disease (WD).

Purpose: To investigate microstructural changes in white matter of WD using DTI and FWI.

Study type: Prospective.

Subjects: Nineteen neurological WD (7 female, 31.68 ± 7.89 years), 10 hepatic WD (3 female, 29.67 ± 13.37 years), and 25 healthy controls (13 female, 29.5 ± 7.7 years).

Field strength/sequence: 3-T, spin-echo echo-planar imaging diffusion-weighted imaging, T1-weighted, T2-weighted, fluid-attenuated inversion recovery.

Assessment: Various diffusion metrics, including mean diffusivity (MD), radial diffusivity (RD), fractional anisotropy (FA), axial diffusivity (AD), free water, and free water-corrected metrics (MD_T, RD_T, FA_T, and AD_T) were estimated and compared across entire white matter skeleton among neurological WD, hepatic WD, and controls. Voxel-wise tract-based spatial statistics and region of interest (ROI) analysis based on white matter atlas were performed. Additionally, partial correlation analysis was conducted to assess the relationship between FWI indices in ROIs and clinical indicators.

Statistical tests: One-way analysis of variance, family-wise error correction for multiple comparisons, and Bonferroni correction for post hoc comparisons. A P-value <0.05, corrected for multiple comparisons, was considered statistically significant.

Results: Our study found significantly lower FA and higher MD, AD, and RD across most of white matter skeleton in neurological WD. Decreased FA_T and increased MD_T, AD_T, and RD_T were observed only in limited white matter areas compared to DTI indices. Additionally, a significant relationship was found between Unified WD Rating Scale neurological subscale of neurological WD and free water (r = 0.613) in middle cerebellar peduncle, AD_T (r = -0.555) in superior cerebellar peduncle, RD_T (r = 0.655), and FA_T (r = -0.660) in posterior limb in internal capsule.

Data conclusion: FWI may allow a more precise evaluation of microstructural changes in WD than conventional DTI, with FWI metrics potentially correlating with clinical severity scores of WD patients.

Level of evidence: 2 TECHNICAL EFFICACY: Stage 2.