A multi-shell multi-tissue diffusion study of brain connectivity in early multiple sclerosis

Mult Scler. 2020 Jun;26(7):774-785. doi: 10.1177/1352458519845105. Epub 2019 May 10.


Background: The potential of multi-shell diffusion imaging to produce accurate brain connectivity metrics able to unravel key pathophysiological processes in multiple sclerosis (MS) has scarcely been investigated.

Objective: To test, in patients with a clinically isolated syndrome (CIS), whether multi-shell imaging-derived connectivity metrics can differentiate patients from controls, correlate with clinical measures, and perform better than metrics obtained with conventional single-shell protocols.

Methods: Nineteen patients within 3 months from the CIS and 12 healthy controls underwent anatomical and 53-direction multi-shell diffusion-weighted 3T images. Patients were cognitively assessed. Voxel-wise fibre orientation distribution functions were estimated and used to obtain network metrics. These were also calculated using a conventional single-shell diffusion protocol. Through linear regression, we obtained effect sizes and standardised regression coefficients.

Results: Patients had lower mean nodal strength (p = 0.003) and greater network modularity than controls (p = 0.045). Greater modularity was associated with worse cognitive performance in patients, even after accounting for lesion load (p = 0.002). Multi-shell-derived metrics outperformed single-shell-derived ones.

Conclusion: Connectivity-based nodal strength and network modularity are abnormal in the CIS. Furthermore, the increased network modularity observed in patients, indicating microstructural damage, is clinically relevant. Connectivity analyses based on multi-shell imaging can detect potentially relevant network changes in early MS.

Keywords: Diffusion-weighted imaging; clinically isolated syndrome; multi-shell acquisitions; multi-shell multi-tissue constrained spherical deconvolution; multiple sclerosis; tractography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cognitive Dysfunction / diagnostic imaging*
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / pathology
  • Diffusion Tensor Imaging / methods*
  • Female
  • Gray Matter / diagnostic imaging*
  • Gray Matter / pathology
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / diagnostic imaging*
  • Multiple Sclerosis / pathology
  • Nerve Net / diagnostic imaging*
  • Nerve Net / pathology
  • Retrospective Studies
  • White Matter / diagnostic imaging*
  • White Matter / pathology