MRI Technique Shows Early Changes in Normal-Appearing White Matter in Pediatric MS

4. Diagnostic Challenges
4. Diagnostic Challenges
Using neurite orientation dispersion and density imaging, researchers investigated the presence of early microstructural damage and its link with physical disability and white matter lesion volume within tracts in pediatric patients with multiple sclerosis.

Neurite orientation dispersion and density imaging (NODDI) reveals an association between normal-appearing white matter (NAWM) orientation dispersion index and within tract white matter lesion volume in pediatric patients with multiple sclerosis (MS), according to study results published in the Journal of Neurology, Neurosurgery and Psychiatry. This suggests the presence of early fiber disorganization in the NAWM.

NODDI, a multicompartment model of diffusion MRI, can better capture brain microstructural complexity in vivo, according to the researchers. It’s able to provide neurite density index (a measure of neuritis), volume, and orientation dispersion index. This can help gauge neurite orientation variability, which may be beneficial for determining the relationship between inflammation and neurodegeneration in MS.

The objective of the current study was to investigate the presence of early microstructural damage and its link to physical disability and white matter lesion volume within tracts using NODDI in pediatric patients with MS.

The study population included 19 patients with relapsing-remitting pediatric MS who were either treatment naïve (n=8) or undergoing treatment with natalizumab and 12 age- and sex-matched patients without history of neurological dysfunction, who participated as healthy control individuals.

The researchers conducted 3T whole-brain MRI scans to obtain sagittal three-dimensional (3D0 T1-weighted turbo field echo and sagittal 3D fluid-attenuated inversion recovery (FLAIR) scans, which identified overall and tract-specific T2-hyperintension lesions volume and lesion mask. The researchers administered neurological evaluations within 1 week of the MRI scan.

They found that patients with pedMS had significantly lower neurite density in the corpus collosum (P =.029; P =.175 corrected) and PTR (P =.001, P =.011 corrected) compared with their healthy peers. Within the corpus collosum’s normal-appearing white matter, lower neurite density index was linked with elevated orientation dispersion. Both measures were associated with greater lesion volume (r=−0.585, P =.008 and r=0.440, P =.047, respectively).

The orientation dispersion index in the NAWM in the corticospinal tract and the posterior thalamic radiation were linked with lesion volume (r=0.564, P =.011; r=0.514, P =.024, respectively).

Neurite density index and Expanded Disability Status Scale scores (EDSS) were not linked. The researchers said that that lack of association might signify that in early MS, inflammation and demyelination promote the disability.

Study limitations included a small sample size and the study’s exploratory nature.

“Our findings are particularly relevant since the clinical onset of [pediatric] pedMS is most likely very close to its biological onset, and further provide in vivo evidence supporting the hypothesis that inflammatory-triggered neurodegeneration affects MS brain since the biological onset of the disease,” the researchers concluded.

Disclosure: This research was supported by Biogen. Some study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Margoni M, Villani U, Finos L, et al. Neurite orientation dispersion and density imaging discloses early changes in the normal-appearing white matter in pediatric multiple sclerosis. J Neurol Neurosurg Psychiatry. Published online July 16, 2021. doi: 10.1136/jnnp-2021-326355.