White matter abnormalities in amyotrophic lateral sclerosis: a free water imaging study

Abstract

Objective To investigate white matter microstructural alterations in amyotrophic lateral sclerosis (ALS) using free-water-corrected diffusion tensor imaging (FW-DTI), compare its findings with those of conventional DTI, and examine the clinical correlations and preliminary diagnostic value of these metrics. Methods 44 ALS patients and 42 healthy controls underwent multi-b-value diffusion MRI. Conventional DTI metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AxD], radial diffusivity [RD]), free-water-corrected metrics (FW-FA, FW-MD, FW-AxD, FW-RD), and the free-water fraction (FWF) were calculated. Tract-based spatial statistics (TBSS) was used for voxelwise group comparisons. Correlations between clinical parameters, including disease progression rate (ΔFS) and the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score, and DTI metrics were examined. A diagnostic nomogram was constructed using logistic regression based on imaging markers that showed significant differences between groups. Results Conventional DTI identified white matter abnormalities in ALS-related regions, including corticospinal tract-related regions, the corpus callosum, and the cingulate gyrus. FW-DTI showed additional and partially distinct alterations, including changes in the fornix, bilateral superior corona radiata, anterior and posterior corona radiata, and the posterior limb of the internal capsule. The free-water fraction did not differ between groups. Correlation analysis revealed that ΔFS was negatively associated with FA in the left posterior limb of the internal capsule (r = −0.432), and the ALSFRS-R score was positively associated with FW-FA in the right anterior corona radiata (r = 0.389). A diagnostic nomogram combining FA in the right cerebral peduncle and FW-FA in the right anterior corona radiata showed preliminary discriminative performance (area under the curve [AUC] = 0.860). Conclusion FW-DTI may provide complementary model-derived information for characterizing ALS-related white matter alterations beyond conventional DTI. Specific regional metrics were associated with ΔFS and the ALSFRS-R score, and the preliminary diagnostic nomogram yielded an AUC of 0.860.