Objective:We sought to determine lesion sites and spatial lesion patterns in spontaneous anterior interosseous nerve syndrome (AINS) with high-resolution magnetic resonance neurography (MRN).Methods:In 20 patients with AINS and 20 age- and sex-matched controls, MRN of median nerve fascicles was performed at 3T with large longitudinal anatomical coverage (upper arm/elbow/forearm): 135 contiguous axial slices (T2-weighted: echo time/repetition time 52/7,020 ms, time of acquisition: 15 minutes 48 seconds, in-plane resolution: 0.25 × 0.25 mm). Lesion classification was performed by visual inspection and by quantitative analysis of normalized T2 signal after segmentation of median nerve voxels.Results:In all patients and no controls, T2 lesions of individual fascicles were observed within upper arm median nerve trunk and strictly followed a somatotopic/internal topography: affected were those motor fascicles that will form the anterior interosseous nerve further distally while other fascicles were spared. Predominant lesion focus was at a mean distance of 14.6 ± 5.4 cm proximal to the humeroradial joint. Discriminative power of quantitative T2 signal analysis and of qualitative lesion rating was high, with 100% sensitivity and 100% specificity (p < 0.0001). Fascicular T2 lesion patterns were rated as multifocal (n = 17), monofocal (n = 2), or indeterminate (n = 1) by 2 independent observers with strong agreement (kappa = 0.83).Conclusion:It has been difficult to prove the existence of fascicular/partial nerve lesions in spontaneous neuropathies using clinical and electrophysiologic findings. With MRN, fascicular lesions with strict somatotopic organization were observed in upper arm median nerve trunks of patients with AINS. Our data strongly support that AINS in the majority of cases is not a surgically treatable entrapment neuropathy but a multifocal mononeuropathy selectively involving, within the main trunk of the median nerve, the motor fascicles that continue distally to form the anterior interosseous nerve.