PurposeTo assess the region-specific atrophy of precentral gyrus (PrCG) and its correlation to clinical function score in amyotrophic lateral sclerosis (ALS). Materials and MethodsTwenty-eight patients with sporadic ALS and 28 healthy controls underwent high-resolution 3D T1-BRAVO magnetic resonance imaging at 3T. The bilateral PrCG segmentations were automatically obtained from a validated segmentation pipeline based on diffeomorphic multi-atlas likelihood fusion. Patients with ALS were further subclassified into early-stage (ALS-e, n=22) and late-stage (ALS-l, n=6) groups, with 12 months as a disease duration cutoff. Vertex-based shape analysis was performed to quantify the region-specific abnormalities of PrCG in ALS subgroups as compared to controls. In addition, we tested the statistical association between altered PrCG morphometry and clinical disability in ALS as evaluated by the revised ALS Functional Rating Scale (ALSFRS-r). ResultsCompared to controls, vertex-wise analysis showed that both ALS-e and ALS-l had significant atrophy of the dorsal-lateral part of PrCG (P<0.05, uncorrected). Importantly, atrophy in ALS-e was not as widespread as that in ALS-l; while atrophy in ALS-e was mostly confined to the dorsal-lateral region (P<0.05, uncorrected, surface areas exhibiting significant difference at a level of P=0.05: left 613.88mm(2), right 937.80mm(2)), atrophy in ALS-l occurred at the dorsal-medial and ventral region as well (P<0.05, uncorrected, surface areas exhibiting significant difference at a level of P=0.05: left 1465.98mm(2), right 1253.89mm(2)). Partial correlation analysis showed that the significant surface area atrophy of PrCG in ALS, especially that of the dorsal-lateral portion, was found to link tightly with ALSFRS-r (P<0.05, uncorrected, surface areas exhibiting significant correlation: left 723.08mm(2), right 474.24mm(2)). ConclusionOur findings suggest that an altered PrCG morphometry, especially atrophy of the surface area in the dorsal-lateral portion, may be associated with the dysfunction that characterizes ALS. This study is an initial attempt to apply a validated statistical shape analysis pipeline to cortical gray matter structure like PrCG. Level of Evidence: 1 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2018;47:115-122.