Powerful magnetic resonance imaging provides markers to assess MS damage

Dr Scott Kolbe, senior author on the paper analysing
the association between nerve damage and gait
impairment in MS patients.

Findings published in the journal, Brain Communications, have revealed that patients with Multiple Sclerosis (MS) who had gait and lower limb motor control impairments also had corresponding axonal (parts of nerve cells) loss in major tracts in the brain which control sensing and movement response. 

Damage that occurs in MS (e.g. inflammation, demyelination and injury and loss of axons) results in upper and lower motor impairments in the majority of patients with symptoms including problems with balance and walking, muscle weakness and spasticity. These impairments have a considerable impact on their daily living and quality of life, in particular on their employment and study. 

Diffusion Tensor Imaging (DTI), an imaging technique that has been widely used previously to look at the damage that occurs in MS, is insufficient to model the axonal loss. Axons are the parts of neurons, or nerve cells, which allow the cells to pass on signals.

A multinational team of researchers and clinicians from the Department of Anatomy and Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam in the Netherlands, the Department of Radiology at Guy’s and St Thomas’ NHS Foundation Trust in London in the UK, the Department of Medicine and Radiology and Neurology at the University of Melbourne, the Royal Melbourne Hospital and the Department of Neuroscience, Monash University studied this issue using more advanced diffusion imaging with ultra-high field 7 Tesla MRI and signal modelling techniques, which provides greater sensitivity to measure the damage that can occur subtly with time.

The study team, led by Dr Scott Kolbe, Senior Research Fellow, Head of Clinical Imaging (Kolbe research group) and Deputy Director of the iBRAIN group in Monash University's Central Clinical School, used biomechanical techniques with 3D video tracking assessments to assess gait and control impairment in the patients, which could be matched with imaging using powerful (ultra-high field 7 Tesla) MRI. They found the imaging was sufficiently detailed for them to assess axonal damage.

The researchers also found regional loss of fibre cross-section in major white matter sensorimotor tracts in the brains of patients with MS who had minimal clinical disability compared to healthy subjects using ultra-high field 7 Tesla MRI. This was despite relatively few focal lesions being present in these tracts. 

As these impairments may lead to permanent disability, it is important for clinicians to measure the structural damage that occurs in the central nervous system (e.g. the brain and spinal cord) for patient monitoring to understand the effectiveness of a prescribed treatment and to look at the progression of motor impairments with time due to multiple sclerosis being a life-long disease. 

Dr Kolbe said, "Being able to identify patients who are at greatest risk of progressive sensorimotor decline, by knowing the extent of the damage that occurs before progression of the disease can allow for more aggressive therapeutic intervention to improve their quality of life."

The study showed that advanced diffusion 7 Tesla MRI can provide a marker for use in:

• Monitoring axonal loss or atrophy of brain tissue in people living with MS (i.e. in real-time or in vivo)
• As an endpoint in clinical trials to assess the effectiveness of neuroprotective drug treatments
• Being a complementary tool for validating tests of function to study the effects of disease.

Dr Myrte Strik

Dr Myrte Strik, a Melbourne Brain Centre Imaging Unit Research Fellow at the University of Melbourne and first author of the study, said that the combination of the high quality 7 Tesla MRI data and the extensive gait assessments made this project unique and powerful. "It provides the opportunity to assess subtle changes in lower limb disabilities and the underlying microstructural and functional changes in the brain in detail in early stage MS," she said.

Dr Scott Kolbe commented, "We were particularly interested in finding an in vivo marker that sensitively captured the axonal loss that occurs in patients with MS, before clinical progression of the disease as there is an urgent need not just for monitoring but also to use as an endpoint for trials for neuroprotective agents." 

The team look forward to extending these findings to bigger groups of patients to confirm the findings and working with organisations in the MS community who can advocate for:

• Advanced imaging techniques to become an established tool in clinical practice 
• Better treatments for those at risk of more severe motor impairments using this powerful combination approach

The study was funded by a Melbourne Neuroscience Institute Interdisciplinary Seed Grant (through The University of Melbourne). Dr Myrte Strik also received a Melbourne International Research Scholarship. 

Find out more

If you would like to hear more about the potential capabilities of the ultra-high field 7 Tesla diffusion MRI for clinical research, Dr Myrte Strik and Associate Professor Bradford Moffat, Director of the Melbourne Brain Centre Imaging Unit at the University of Melbourne node of the National Imaging Facility will be presenting at the Department of Neuroscience Translational Research Seminar Series on Monday 16 August (12:30 - 1:30pm, lunch provided at 12noon).

Reference: 

Strik M, Cofré Lizama LE, Shanahan CJ, van der Walt A, Boonstra FMC, Glarin R, Kilpatrick TJ, Geurts JJG, Cleary JO, Schoonheim MM, Galea MP, Kolbe SC. Axonal loss in major sensorimotor tracts is associated with impaired motor performance in minimally disabled multiple sclerosis patients. Brain Communications, Volume 3, Issue 2, 2021, fcab032, https://doi.org/10.1093/braincomms/fcab032