In vivo detection of damage in multiple sclerosis cortex and cortical lesions using NODDI

Objective To characterise in vivo the microstructural abnormalities of multiple sclerosis (MS) normal-appearing (NA) cortex and cortical lesions (CLs) and their relations with clinical phenotypes and disability using neurite orientation dispersion and density imaging (NODDI). Methods One hundred and seventy-two patients with MS (101 relapsing-remitting multiple sclerosis (RRMS), 71 progressive multiple sclerosis (PMS)) and 62 healthy controls (HCs) underwent a brain 3T MRI. Brain cortex and CLs were segmented from three-dimensional T1-weighted and double inversion recovery sequences. Using NODDI on diffusion-weighted sequence, intracellular volume fraction (ICV_f) and Orientation Dispersion Index (ODI) were assessed in NA cortex and CLs with default or optimised parallel diffusivity for the cortex (D//=1.7 or 1.2 mu m(2)/ms, respectively). Results The NA cortex of patients with MS had significantly lower ICV_f versus HCs' cortex with both D// values (false discovery rate (FDR)-p <0.001). CLs showed significantly decreased ICV_f and ODI versus NA cortex of both HCs and patients with MS with both D// values (FDR-p <= 0.008). Patients with PMS versus RRMS had significantly decreased NA cortex ICV_f and ODI (FDR-p=0.050 and FDR-p=0.032) with only D//=1.7 mu m(2)/ms. No CL microstructural differences were found between MS clinical phenotypes. MS NA cortex ICV_f and ODI were significantly correlated with disease duration, clinical disability, lesion burden and global and regional brain atrophy (r from -0.51 to 0.71, FDR-p from <0.001 to 0.045). Conclusions A significant neurite loss occurs in MS NA cortex. CLs show a further neurite density reduction and a reduced ODI suggesting a simplification of neurite complexity. NODDI is relevant to investigate in vivo the heterogeneous pathology affecting the MS cortex.

Automated summary

This study characterized microstructural abnormalities in multiple sclerosis (MS) cortex using neurite orientation dispersion and density imaging (NODDI). Results showed significant neurite loss in MS normal-appearing (NA) cortex and further neurite density reduction in cortical lesions (CLs), indicating a simplification of neurite complexity. NODDI is relevant for investigating the heterogeneous pathology of the MS cortex in vivo.