15 Jul 24. Small pilot study grant awarded by TENOVUS

£17,548 has been awarded by TENOVUS Scotland for a small pilot study grant conducted by Dr Rozanna Meijboom, Professor Adam Waldman and Dr Michael Thrippleton.

The main goal of this study is to:

1. set up an advanced quantitative spinal cord MRI protocol for measuring neurodegeneration and demyelination in multiple sclerosis 
2. establish normative measures for the cervical spinal cord for comparison with MS-related cervical spinal cord atrophy

The scientific summary for the grant is provided below:

Multiple sclerosis (MS) is an incurable neuroinflammatory and neurodegenerative disease of the brain and spinal cord that poses a significant health burden in Scotland. Accurate non-invasive in vivo magnetic resonance imaging

(MRI) biomarkers of disease progression, particularly neurodegeneration, are essential for improved treatment of MS. Despite brain-independent disease progression and contribution to disability, spinal cord neurodegeneration remains poorly understood. Macroscopic (area, atrophy) and microstructural (axon, myelin) data indicate spinal cord degeneration associations with disability, but generally restricted to cervical levels and unexplored in early MS. Further research is required to establish MRI biomarkers of whole spinal cord neurodegeneration in early MS.

Using existing longitudinal MRI data from FutureMS (N=324) and UK Biobank (N=1000), cervical spinal cord cross-sectional area will be compared in early MS and healthy volunteers. Atrophy in patients and normative measures will establish robust novel data on upper spinal cord neurodegeneration in early MS. Additionally, a comprehensive, dedicated quantitative spinal cord MRI protocol will be validated (N=15) and implemented, through established collaboration with National Institutes of Health (NIH, US). The protocol will include high-resolution, multi-contrast T1 and T2-weighted structural imaging, with diffusion MRI (dMRI) and magnetisation transfer saturation (MTsat) MRI for measures of axonal and myelin integrity, respectively. Existing processing and analysis pipelines will be used to generate measures of atrophy, and myelin and axonal integrity.

Spinal cord measurements from brain MRI in early MS and healthy subjects, and a comprehensive whole-spinal cord protocol, will provide critical pilot data, evidence of feasibility and technical capabilities to support substantive funding applications for a study assessing the relationship between whole spinal cord neurodegeneration, and clinical trajectory in early MS. The ultimate aim is to translate precision spinal cord imaging metrics for clinical stratification and for novel neurodegeneration-targeted therapeutic trial platforms.

Keywords:

• Multiple sclerosis
• FutureMS
• UK Biobank
• diffusion MRI