Neurite orientation dispersion and density imaging (NODDI) can detect brain microstructural and metabolic alterations after the first demyelinating event in MS [1]. There was increased axonal dispersion in normal-appearing white matter (NAWM), particularly in the corpus callosum, as well as reduced axonal density and total sodium accumulation, suggesting that this structure can be affected at an early stage.

The goal of the presented study was to demonstrate that a multi-parametric quantitative MRI approach can detect clinically relevant alterations in the brain of early patients not captured by conventional MRI. This was done by using NODDI, which can measure the neurite density index (NDI) and the orientation dispersion index (ODI) in the brain NAWM, white matter lesions, and grey matter. NDI is a marker of neuronal and axonal density, while ODI reflects the crossing or fanning of axons. Furthermore, 23Na MRI was applied to measure total sodium concentration (TSC), reflecting neuro-axonal metabolic dysfunction and loss.

Participants were 42 patients with clinically isolated syndrome (CIS) or MS within 3 months from the first demyelinating event, plus 16 healthy controls. Brain and spinal cord structural scans were done, as well as brain NODDI. Of these, 32 patients and 13 healthy controls also underwent brain 23Na MRI.

In NAWM, including the corpus callosum, ODI was higher in patients compared with controls; NDI was lower, TSC was higher. In grey matter, ODI in the frontal, parietal, and temporal cortex of patients was lower compared with controls; NDI in the parietal, temporal, and occipital cortex was also lower; while TSC in the limbic and frontal cortex was higher. Brain volumes did not differ between patients and controls. Higher ODI in the corpus callosum of patients was associated with worse performance on timed walk test (B=0.01, P=0.009, R2=0.017), independent of brain and lesion volumes. Higher TSC in the left frontal middle gyrus was associated with higher disability on the Expanded Disability Status Scale (EDSS; r=0.5, P=0.005). No associations between the study parameters and T2 lesion volume load was found, but a lower NDI in the corpus callosum was associated with a lower NDI in the T2 hyperintense lesion (B=0.51, P<0.0001).

The authors speculate that higher ODI in the NAWM could reflect inflammation and early fibre disorganization. Higher ODI, lower NDI, and higher TCS in the corpus callosum could reflect early neurodegeneration; morphological and metabolic alterations in this structure may contribute to disability in MS. In this cohort, brain volume was neither altered nor related to disability, so ODI and NDI may be very sensitive at detecting clinically relevant pathology in very early MS.

  1. Collorone S. MSVIRTUAL2020, Abstract LB01.04.