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

Fiber-specific white matter (WM) changes are promising neuroimaging markers to evaluate upper motor neuron damage in amyotrophic lateral sclerosis (ALS) patients. However,to our knowledge, no studies have specifically applied fixel-based analysis (FBA) to investigate fiber-specific WM changes in King’s stage 1 ALS patients in vivo.” 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. According to the new "Gold Coast" criteria and the King’s clinical staging system, we defined ALS patients at King’s stage 1 as ALS-ES patients, which corresponds to the earliest symptomatic phase . 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. 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. Our findings suggest that FBA metrics can provide valuable and complementary fixel-level information regarding the early WM degenerative process in ALS.