Neurite Orientation Dispersion and Density Imaging for Assessing Acute Inflammation and Lesion Evolution in MS

Abstract

BACKGROUND AND PURPOSE: MR imaging is essential for MS diagnosis and management, yet it has limitations in assessing axonal damage and remyelination. Gadolinium-based contrast agents add value by pinpointing acute inflammation and blood-brain barrier leakage, but with drawbacks in safety and cost. Neurite orientation dispersion and density imaging (NODDI) assesses microstructural features of neurites contributing to diffusion imaging signals. This approach may resolve the components of MS pathology, overcoming conventional MR imaging limitations. MATERIALS AND METHODS: Twenty-one subjects with MS underwent serial enhanced MRIs (12.6 6 9 months apart) including NODDI, whose key metrics are the neurite density and orientation dispersion index. Twenty-one age-and sex-matched healthy controls underwent unenhanced MR imaging with the same protocol. Fifty-eight gadolinium-enhancing and non-gadolinium-enhancing lesions were semiautomatically segmented at baseline and follow-up. Normal-appearing WM masks were generated by subtracting lesions and dirty-appearing WM from the whole WM. RESULTS: The orientation dispersion index was higher in gadolinium-enhancing compared with non-gadolinium-enhancing lesions; logistic regression indicated discrimination, with an area under the curve of 0.73. At follow-up, in the 58 previously enhancing lesions, we identified 2 subgroups based on the neurite density index change across time: Type 1 lesions showed increased neurite density values, whereas type 2 lesions showed decreased values. Type 1 lesions showed greater reduction in size with time compared with type 2 lesions. CONCLUSIONS: NODDI is a promising tool with the potential to detect acute MS inflammation. The observed heterogeneity among lesions may correspond to gradients in severity and clinical recovery after the acute phase. ABBREVIATIONS: AD ¼ axial diffusivity; DAWM ¼ dirty-appearing white matter; FA ¼ fractional anisotropy; FU ¼ follow-up; GEL ¼ gadolinium-enhancing lesion; HC ¼ healthy control; MD ¼ mean diffusivity; NAWM ¼ normal-appearing white matter; NDI ¼ neurite density index; NGEL ¼ non-gadolinium-enhancing lesion; NODDI ¼ neurite orientation dispersion and density Imaging; nODI ¼ normalized orientation dispersion index; ODI ¼ orientation dispersion index; RD ¼ radial diffusivity; VEC ¼ extra-neurite compartment C onventional MR imaging is essential for MS diagnosis and management, specifically for demonstrating WM lesion dissemination in space (involvement of .1 CNS region) and time (across time accumulation). 1 Conventional MR imaging, however, lacks specificity in characterizing MS WM lesions after the acute phase; all lesions show a similar radiologic appearance on T2WI, irrespective of the degree of inflammation, axonal loss, gliosis,

Investigating Microstructural Changes in White Matter in Multiple Sclerosis: A Systematic Review and Meta-Analysis of Neurite Orientation Dispersion and Density Imaging

“…12 studies remained for the eligibility assessment; 5 studies were excluded based on the reasons shown on the PRISMA diagram ( Figure 1 ). A total of 7 studies investigating the brain microstructure in patients with MS using NODDI were included and met the inclusion/exclusion criteria for this meta-analysis [ 20 , 23 , 24 , 25 , 26 , 27 , 29 ]. A total of 202 patients with MS (mean age of 40.1 years) and 172 healthy controls (mean age of 35.1 years) were included.…”

“…A total of 202 patients with MS (mean age of 40.1 years) and 172 healthy controls (mean age of 35.1 years) were included. The mean MS duration of all the studies was 8.3 years; however, two studies did not report disease duration [ 26 , 29 ]. There was no significant difference in the age and sex distribution between MS patients and healthy controls, with the caveat that one study did not provide information relating to the sex of participants [ 25 ].…”

“…Seven studies reported on the NDI and on the NAWM among 202 MS patients and 172 healthy controls [ 20 , 23 , 24 , 25 , 26 , 27 , 29 ]. The standardised mean difference was −0.70 (95% CI −0.99 to (−0.40)), p ≤ 0.00001 ( Figure 4 ).…”

“…Although NODDI has not been widely applied in MS, this technique is promising in investigating the complexity of MS pathology, as it is more specific than DTI in detecting microstructural alterations [ 20 , 22 , 23 , 24 , 25 ]. Recent studies found that DTI and myelin-sensitive imaging are less sensitive than NODDI to neurite density and changes in NAWM and WM lesions in patients with MS [ 23 , 24 , 26 ]. In addition, changes in NODDI parameters in specific brain WM [ 22 , 23 ], such as the internal capsule and corpus callosum in which long-tract axons are found [ 27 ], are associated with disability [ 22 , 23 ].…”

“…In addition, changes in NODDI parameters in specific brain WM [ 22 , 23 ], such as the internal capsule and corpus callosum in which long-tract axons are found [ 27 ], are associated with disability [ 22 , 23 ]. However, some other studies have unexpectedly reported increased fibre coherence (as shown by the low ODI) in WM lesions and NAWM compared to healthy WM, which suggests careful interpretation in the presence of severe axonal loss (as indicated by low NDI) [ 20 , 24 , 25 , 26 ]. Unfortunately, longitudinal studies, which may help clarify the relationship between disease activity/progression and NODDI-detected WM changes, are absent in the literature.…”