Differentiate aquaporin-4 antibody negative neuromyelitis optica spectrum disorders from multiple sclerosis by multimodal advanced MRI techniques

Background: It is clinically essential to distinguish aquaporin-4 antibody (AQP4-Ab) negative neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) because of different therapeutic strategies. Since clinical and lesion features may not allow the distinction, we aimed to identify advanced imaging features that could improve the distinction between two disorders. Methods: Multimodal imaging measures included fractional anisotropy, mean, axial, radial diffusivity (MD, AD, RD) and kurtosis (MK, AK, RK) from diffusion kurtosis imaging; functional connectivity strength (FCS) and density, regional homogeneity, amplitude of low frequency fluctuations from resting -state functional MRI; gray matter volume from structural MRI; and cerebral blood flow from arterial spin labeling imaging. Voxel-wise comparisons were performed to identify inter -group differences in imaging measures, and the performance of differentiating these two disorders was estimated by receiver operating characteristic curves. Results: Compared to MS, patients with AQP4-Ab negative NMOSD showed decreased MD and AD but increased MK and AK in white matter regions; and reduced FCS in the occipital cortex ( P < 0.05, FWE corrected). The joint -use of these five imaging measures distinguished the two disorders with an accuracy of 94% ( P < 0.001, 95% CI = 0.84 -0.98). Other imaging measures showed no significant differences between the two patient groups. Conclusions: The study showed less white matter damage and a more severe functional disconnection of the occipital cortex in patients with AQP4-Ab negative NMOSD compared to MS. The combined use of diffusion and functional connectivity could facilitate a better distinction between NMO and MS with seronegative AQP4-Ab in clinical management.