Neurite orientation dispersion and density imaging discloses early changes in the normal-appearing white matter in paediatric multiple sclerosis

Paediatric multiple sclerosis (pedMS) brain is known to be impacted by heightened inflammation and axonal degeneration.1 Structural changes in the normal-appearing white matter (NAWM) of pedMS have been disclosed by diffusion tensor imaging, further emphasising that MRI visible white matter (WM) lesions do not capture the full extent of tissue damage in MS.2 Understanding of the complexity of early brain pathology in pedMS can help to better characterise the relationship between inflammation and neurodegeneration in MS. Neurite orientation dispersion and density imaging (NODDI), a multicompartment model of diffusion MRI, is a clinically feasible method for better capturing brain microstructural complexity in vivo.3 Specifically, NODDI provides quantitative measures including the neurite density index (NDI), considered a measure of neurites (ie, axons and dendrites) volume and orientation dispersion index (ODI), reflecting neurite orientation variability. In this exploratory study, we applied NODDI to investigate the presence of early microstructural damage in pedMS compared with a matched group of healthy controls (HC), and its correlation with physical disability and WM lesion volume (LV) within tracts. A list of the acronyms used throughout the manuscript is provided in online supplemental table 1). ### Supplementary data [jnnp-2021-326355supp001.pdf] ### Subjects Nineteen relapsing-remitting pedMS patients (aged ≤17 years) were prospectively enrolled in a single MS Centre between January 2019 and April 2021. Eight patients were treatment naive; the remaining patients were in stable treatment with natalizumab. The median number of infusions at the time of MRI scan was 12 (IQR, 6–20). Twelve HC, balanced by age and sex, with no previous history of neurological dysfunction and a normal neurological examination, were also evaluated (see the online Supplemental Methods for pedMS inclusion criteria). All subjects underwent a detailed neurological evaluation, including Expanded Disability Status Scale (EDSS) score, within 1 week from the MRI acquisition. ### MRI The following sequences were acquired during a 3T …