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Evidence for progressive microstructural damage in early multiple sclerosis by multi-shell diffusion magnetic resonance imaging

AuthorsToschi, Nicola; Santis, Silvia de; Granberg, Tobias; Ouellette, Russell; Treaba, Constantina A.; Herranz, Elena; Mainero, Caterina
KeywordsMultiple sclerosis
Multi-shell diffusion MRI
Axonal pathology
Normal-appearing white matter
Longitudinal disease progression
Issue Date1-Apr-2019
CitationNeuroscience 403: 27-34 (2019)
AbstractIn multiple sclerosis (MS), it would be of clinical value to be able to track the progression of axonal pathology, especially before the manifestation of clinical disability. However, non-invasive evaluation of short-term longitudinal progression of white matter integrity is challenging. This study aims at assessing longitudinal changes in the restricted (i.e. intracellular) diffusion signal fraction (FR) in early-stage MS by using ultra-high gradient strength multi-shell diffusion magnetic resonance imaging. In 11 early MS subjects (disease duration ≤ 5 years), FR was obtained at two timepoints (one year apart) through the Composite Hindered and Restricted Model of Diffusion, along with conventional Diffusion Tensor Imaging metrics. At follow-up, no statistically significant change was detected in clinical variables, while all imaging metrics showed statistically significant longitudinal changes (p < 0.01, corrected for multiple comparisons) in widespread regions in normal-appearing white matter (NAWM). The most extensive longitudinal changes were observed in FR, including areas known to include a large fraction of crossing fibers. Furthermore, FR was also the only metric showing significant longitudinal changes in lesions that were present at both time points (p = 0.007), with no significant differences found for conventional diffusion metrics. Finally, FR was the only diffusion metric (as compared to Diffusion Tensor Imaging) that revealed pre-lesional changes already present at baseline. Taken together, our data provide evidence for progressive microstructural damage in the NAWM of early MS cases detectable already at 1-year follow-up. Our study highlights the value of multi-shell diffusion imaging for sensitive tracking of disease evolution in MS before any clinical changes are observed.
DescriptionThis article is part of a Special Issue entitled: SI: MRI and Neuroinflammation.
Publisher version (URL)https://doi.org/10.1016/j.neuroscience.2019.01.022
Appears in Collections:(IN) Artículos
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