• Nicola Toschi, Silvia De Santis, Tobias Granberg, Russell Ouellette, Constantina A Treaba, Elena Herranz, and Caterina Mainero.
• Athinoula A. Martinos Center for Biomedical Imaging and Harvard Medical School, Boston, MA, USA; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy. Electronic address: toschi@med.uniroma2.it.
• Neuroscience. 2019 Apr 1; 403: 27-34.

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. This article is part of a Special Issue entitled: SI: MRI and Neuroinflammation.Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

25 keywords...

hide…