Inflammation in the brain known as “smouldering inflammation” plays a crucial role in the progression of multiple sclerosis (MS). Unlike the shorter bursts of “acute” inflammation sometimes associated with MS relapses, smouldering inflammation is a slow and persistent process that contributes significantly to nerve damage and disability in people with MS. Current treatments mainly target the acute episodes but do not effectively address this chronic, underlying inflammation.
During this fellowship, Dr Samuel Klistorner and the team are developing and refining brain scanning to detect and monitor smouldering inflammation. By using advanced magnetic resonance imaging (MRI) methods, they are tracking the subtle changes in areas of damage in the brain (lesions) over time. This will help with understanding how these lesions expand and contribute to the overall progression of MS.
The research will also explore the potential of combining MRI with other diagnostic tools measuring the visual system (visual evoked potentials (VEP) and optical coherence tomography (OCT)), to create a combined measure for smouldering inflammation. This would allow for more precise and early detection of disease progression, allowing better monitoring and more effective treatment plans for people with MS.
Significant progress has been made in developing new ways to detect and measure ongoing (“smouldering”) inflammation in MS.
A key focus has been a technique developed by Dr Klistorner’s team that measures slow expansion of chronic lesions. The team’s previous work has shown this is strongly linked to brain volume loss and worsening disability.
The fellowship is also investigating how this measure relates to other imaging approaches, including specialised MRI markers and PET imaging, which can directly detect active immune processes in the brain.
The first study investigated whether a particular MRI feature could reliably indicate smouldering inflammation and predict disease severity and progression. However, it revealed an unexpected finding – that this feature may occur early in lesion formation rather than being a marker of chronic inflammation. This work drew on data from multiple centres across Australia, Germany, and the UK and was published in 2025.
The second study used PET imaging to assess brain immune cell (microglia) activity and how this relates to disease progression. This analysis is in the final stages, with a manuscript in preparation for publication in a scientific journal.
The fellowship has also established a strong international research network, with collaborations across multiple countries. The findings have also been presented at major national and international conferences including the MS Australia Progress in MS Research Conference and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress.
In the final year, the focus will shift to studying the visual system as another way to detect smouldering inflammation. Ultimately, the goal is to combine MRI, PET, and visual system measures into a single tool to support more precise monitoring of MS progression in both clinical practice and clinical trials.
Klistorner S, Usnich T, Clarke MA, Pareto D, Rovira À, Paul F, Barnett M, Klistorner A. The presence of a paramagnetic phase rim in multiple sclerosis is linked to lesion age: An exploratory study. Mult Scler J Exp Transl Clin. 2025; 11(3):20552173251378788. doi: 10.1177/20552173251378788.
Updated 31 March 2026
$225,000
2025
3 years
Current project
