Validating a MRI measure for axonal degeneration in MS - MS Research Australia

Validating a MRI measure for axonal degeneration in MS

Ms Sanuji Gajamange

University of Melbourne, VIC

| Better treatments | Neurobiology | Scholarship | 2015 | Investigator Led Research |
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Summary

The course and severity of MS is highly variable between individuals, and is mainly dependent on the degree of neurodegeneration in the brain. There is a real need to identify accurate biological markers of neurodegeneration that may be used to predict the risk or rate of progression of MS. Accurate prediction will ensure patients receive the appropriate treatments to slow or halt the progression of the disease. Biomarkers of neurodegeneration are also needed so that we can measure in clinical trials whether experimental new treatments are working to slow or stop progression.

Advanced MRI techniques such as diffusion imaging are a growing area of research that holds great potential for predicting long-term clinical outcome. Ms Sanuji Gajamange under the supervision Dr Scott Kolbe at the University of Melbourne will aim to test a new type of imaging technique called Apparent Fibre Density (AFD). This technique is very sensitive in identifying neurodegeneration. This technique has been used in other disorders such as Motor Neurone Disease, but has not been used before in people with MS.

Ms Gajamange with study the brains of people with MS to determine whether changes in brain structure or function are linked to decline in vision or other clinical measures of disease progression. This information will help clinicians to provide appropriate treatments and to predict illness course in people with MS in real-time.

Progress to Date

Ms Gajamange has investigated the AFD technique in 17 people with optic neuritis, a common precursor of MS, and 14 healthy controls. The AFD technique measures specific features of nerve fibres which gives an indication of the nerve’s integrity. Data gathered using this technique indicates that people with optic neuritis have higher levels of neurodegeneration than healthy controls. Whilst this is expected, all new techniques require validation to confirm that they can detect known changes. Therefore this study has shown that the AFD technique is likely to be useful to detect neurodegeneration in MS.

Further experimental work carried out in collaboration with the Florey Institute of Neuroscience and Mental Health, showed that inflammation and scarring in people with MS can affect the results of this technique. However, Ms Gajamange has now successfully developed ways to overcome these challenges.

Ms Gajamange used this AFD technique to examine the levels of nerve cell intergrity in people with clinically isolated syndrome (CIS – a first episode of neurological symptoms that may precede a diagnosis of definite MS). The aim of this study was to determine whether subtle changes in neurodegeneration can be detected prior to the onset of MS. The results showed, that early changes can be detected, and possibly suggest that early cognitive decline, can be explained by physical changes in the brain.

Following this success Ms Gajamange, completed a further study looking at people with clinically definite MS at two different time points using this AFD brain imaging technique. She hopes to identify early markers of disease that could better predict those at risk of developing MS, so that treatment can be started earlier minimising the impact of MS.

On the basis of her new AFD brain imaging technique, Ms Gajamange has now attracted industry funding to undertake a larger longitudinal study to track people with MS over time using the technique. This research has been presented at a number of international and Australian scientific conferences.

Publications

  • S Gajamange, D Raffelt, T Dhollander, E Lui, A van der Walt, T Kilpatrick, J Fielding, A Connelly, S Kolbe. Fibre-specific white matter changes in multiple sclerosis patients with optic neuritis” NeuroImage Clinical 2018 17:60-68
  • Sanuji Gajamange, Annie Shelton, Owen White, Thijs Dhollander, Alan Connelly, Joanne Fielding, Scott Kolbe. Neural correlates of cognitive dysfunction in clinically isolated syndromes. In preparation

Updated: 20 April 2018

Updated: 04 January, 2015

Investigator

  • Ms Sanuji Gajamange, University of Melbourne, VIC

Supervisor

Grant Awarded

  • Postgraduate Scholarship

Total Funding

  • $99,000

Duration

  • 3 years over 2015 - 2017

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