Fixel-based analysis to detect early fiber-specific white matter alterations in sporadic patients with amyotrophic lateral sclerosis

Background: Fiber-specific white matter (WM) changes are promising neuroimaging markers to evaluate upper motor neuron damage in amyotrophic lateral sclerosis (ALS) patients. However, no available studies have explored fiber-specific WM changes in vivo in early-stage ALS patients to date. Purpose: To fill this gap in the literature, we performed a retrospective analysis to identify early fiber-specific WM alterations in a large group of sporadic early-stage ALS (ALS-ES) patients and their correlation with clinical data. Materials and Methods: According to the new "Gold Coast" criteria and an important conceptual framework of presymptomatic ALS, using the well-validated King’s clinical staging system, we defined ALS patients at King’s stage 1 as ALS-ES patients. In this study, 64 newly diagnosed ALS-ES patients and 80 demographic-matched healthy controls (HCs) were included. Then, a novel diffusion-weighted imaging-based approach, fixel-based analysis (FBA), was performed to explore fiber-specific WM alterations in ALS-ES patients and HCs. Three FBA metrics, fiber density (FD), fiber-bundle cross-section (FC), and fiber density and cross-section (FDC), were analysed. Results: Compared with HCs, ALS-ES patients had significantly decreased FD values and FDC values mainly in the bilateral corticospinal tract (CST) and corpus callosum (CC) regions. Compared with HCs, in ALS-ES patients, the FC values were significantly decreased mainly in the bilateral CST regions, while were significantly increased in the CC regions. Moreover, FDC values significantly correlated with motor deficits in ALS-ES patients. Conclusions: Our findings suggest that FBA metrics can provide more valuable information regarding the early WM degenerative process in ALS.