ArticleBMC medicine2026
Impairment of brain short association fibers across clinical stages in amyotrophic lateral sclerosis: a new biomarker mirroring disease progression.
Article in BMC medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundA quantitative biomarker for clinical staging is essential for amyotrophic lateral sclerosis (ALS) stratification. This study evaluated microstructural impairment in brain short association fibers (SAFs) across ALS stages via neurite orientation dispersion and density imaging (NODDI) and assessed correlations with disease severity.
methodsDiffusion-weighted imaging data were collected from 87 ALS patients (categorized into four groups King's stages) and 37 healthy controls. Whole-brain SAF mapping was performed via a spherical deconvolution-driven probabilistic tractography approach. Diffusion tensor imaging (DTI) and NODDI parameters (neurite density index, NDI; orientation dispersion index, ODI; isotropic volume fraction, ISO) were estimated for each SAF.
resultsSeven SAFs connecting the left postcentral-precentral gyrus, left precentral-precentral gyrus, right postcentral-precentral gyrus, right paracentral-posterior cingulate gyrus, left paracentral-posterior cingulate gyrus, left precentral-superior parietal gyrus, and left precentral-superior frontal gyrus exhibited significant NDI differences across the five groups. Additionally, one fiber connecting the left medial orbitofrontal-rostral anterior cingulate gyrus demonstrated an ISO difference [false discovery rate (FDR)-corrected p < 0.05]. Progressive trends of NDI reduction and ISO increase were observed at higher ALS stages. No intergroup differences were found in the ODI or DTI parameters. The NDI values of these seven SAFs were positively correlated with disease severity scores (FDR-corrected p < 0.05). Combining NDI and ISO revealed moderate classification potential for ALS (area under the curve = 0.780).
conclusionsNeurite injury in SAFs involving primary motor and extramotor areas worsened alongside clinical staging and motor disability in ALS. NODDI provides quantitative SAF-related biomarkers for assessing ALS disease severity.
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