Modern Technology in Multi-Shell Diffusion MRI Reveals Diffuse White Matter Changes in Young Adults With Relapsing-Remitting Multiple Sclerosis

Abstract

ObjectiveTo characterize microstructural white matter changes related to relapsing-remitting multiple sclerosis using advanced diffusion MRI modeling and tractography. The association between imaging data and patient’s cognitive performance, fatigue severity and depressive symptoms is also explored.MethodsIn this cross-sectional study, 24 relapsing-remitting multiple sclerosis patients and 11 healthy controls were compared using high angular resolution diffusion imaging (HARDI). The imaging method includes a multi-shell scheme, free water correction to obtain tissue-specific measurements, probabilistic tracking algorithm robust to crossing fibers and white matter lesions, automatic streamlines and bundle dissection and tract-profiling with tractometry. The neuropsychological evaluation included the Symbol Digit Modalities Test, Paced Auditory Serial Addition Test, Modified Fatigue Impact Scale and Beck Depression Inventory-II.ResultsBundle-wise analysis by tractometry revealed a difference between patients and controls for 11 of the 14 preselected white matter bundles. In patients, free water corrected fractional anisotropy was significantly reduced while radial and mean diffusivities were increased, consistent with diffuse demyelination. The fornix and left inferior fronto-occipital fasciculus exhibited a higher free water fraction. Eight bundles showed an increase in total apparent fiber density and four bundles had a higher number of fiber orientations, suggesting axonal swelling and increased organization complexity, respectively. In the association study, depressive symptoms were associated with diffusion abnormalities in the right superior longitudinal fasciculus.ConclusionTissue-specific diffusion measures showed abnormalities along multiple cerebral white matter bundles in patients with relapsing-remitting multiple sclerosis. The proposed methodology combines free-water imaging, advanced bundle dissection and tractometry, which is a novel approach to investigate cerebral pathology in multiple sclerosis. It opens a new window of use for HARDI-derived measures and free water corrected diffusion measures. Advanced diffusion MRI provides a better insight into cerebral white matter changes in relapsing-remitting multiple sclerosis, namely diffuse demyelination, edema and increased fiber density and complexity.

High-frequency longitudinal white matter diffusion- & myelin-based MRI database: reliability and variability

“…Regarding the bundles, our results suggest that all bundles that show high consistency, whether extracted on whole or along the bundles, are involved in different pathologies, aging or development. This is particularly the case for AF, ILF, IFOF, CST, UF and CG which have very good consistency per se (Dice score) (Atkinson-Clement et al, 2017; Beaudoin et al, 2021; Bergamino et al, 2020; Coelho et al, 2021). A more moderate observation can be made regarding some parts of the corpus callosum, which showed more variable consistency of data.…”

“…Other techniques like magnetization transfer imaging (MTI, M. Kim & Cercignani, 2014; Wolff & Balaban, 1989) are also increasingly used to examine changes in the myelin content of WM. Key measures of WM microstructure derived from these models are sensitive to changes in a healthy population (Alexander, 2017; Beck et al, 2021; Boukadi et al, 2019; Honnedevasthana Arun et al, 2021; Koshiyama et al, 2020; Munsch et al, 2021; Uddin et al, 2019) or in pathological conditions (Beaudoin et al, 2021; Brown et al, 2017; Granziera et al, 2021; Laule & Moore, 2018; Lu et al, 2021; Rahmanzadeh et al, s. d.; Schneider et al, 2017). In addition, studies have also shown the effect of a treatment or therapeutic intervention on WM measures in clinical trials (Arnold et al, 2022; Gurevich et al, 2018; Roy et al, 2021; Vavasour et al, 2019).…”

Brain connectivity changes underlying depression and fatigue in relapsing-remitting multiple sclerosis: a systematic review

“…Fifteen studies were identified that evaluated the relationship between fatigue and dMRI measures, all of which used DTI and one used HARDI [139]. Seven out of fifteen studies did not report any significant findings (Table 1) [66, 105, 108, 110, 138, 139, 150] and 8/15 found significant associations (Tables 1 and 3).…”

“…Five studies were identified that assessed associations between structural connectivity measures and depression in pwRRMS, four of which used DTI [29, 98, 136, 138] and one used HARDI [139] (Tables 1 and 3), but only three found statistically significant relationships between structural connectivity and depression in pwRRMS [29, 136, 139].…”

“…Eight studies assessed both fatigue and depression [132][133][134][135][138][139][140][141]. All but one [139] examined the associations between depression or fatigue and structural MR measures, but only one paper observed overlapping changes. Specifically, Lazzarotto et al reported significant correlations between BDI scores and lower volume of the right cerebellar vermis crus I, and between FSS score and reduced volume of cerebellar lobule right V, but other than cerebellum involvement for both, no other overlapping brain areas were found [135].…”