The use of MRI to measure brain tissue loss in people with MS

Dr Heidi Beadnall

Dr Heidi Beadnall

The University of Sydney, NSW

| Better treatments | Neurobiology | Scholarship | 2014 | Investigator Led Research |
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Summary

Loss of brain tissue (atrophy) occurs faster in people with MS than in the normal adult population. In research studies, brain atrophy, correlates well with physical and cognitive disability in people with MS. Although brain atrophy appears to be an excellent marker of disease progression in MS, and therefore a potential measure of the effectiveness of MS treatments, quantitative assessments of brain volume have not, as yet moved out of the research arena and been incorporated into clinical neurology practice.

Clinical relapses and the presence or absence of new lesions on magnetic resonance imaging (MRI) scans currently help clinicians determine a treatment trajectory in MS. However, loss of brain volume appears to be a more sensitive marker of disease progression. A deeper understanding of how brain atrophy correlates with clinical measures will assist with prognosis, guide therapeutic decisions, and allow clinicians to monitor responses to specific treatments. This will be especially relevant to new therapies under development, which aim to promote repair mechanisms in the brain in progressive MS.

This project will investigate if brain MRI scans over time, are useful in clinical practice. Dr Beadnall aims to determine if she can identify and overcome any technical, logistical, and clinical barriers to the introduction of quantitative MRI into clinical practice. The MRI data will be correlated with clinical data (including patient-centred outcomes) collected using a novel, cost- and time-effective tablet-based tool that will be developed and validated by this work. Dr Beadnall will also examine whether the MRI measurements are useful in monitoring patients given specific MS treatments in a real-world setting.

Project Outcomes

Using three different MRI brain volume measuring techniques, Dr Beadnall has measured the brains of 63 patients with MS, including two patients with clinically isolated syndrome (CIS). To be accepted into clinical practice quantitative MRIs need to be easy, reliable, consistent and correlated with other clinical measurements. For this reason, two of the techniques she investigated were fully automated. Dr Beadnall’s studies suggest that automated MRI techniques can reproducibly measure brain volume, bringing the routine use of MRI for MS diagnosis one step closer to the clinic. To extend these findings, Dr Beadnall is currently investigating if reporting changes in brain volume loss to treating clinicians changes their management of MS.

Dr Beadnall has collect other data from 150 people with MS to determine if these measuring techniques can be applied to previously collected and stored MRIs. A further 30 patients have been recruited to compare other quantitative MRI techniques, and another 102 patients for studies in changes in these scans over a time period of approximately 12 months. She is currently performing data analyses and plans to write these data up for publication.

To determine how this information would be used in the clinic, and if there would be any barriers for introducing the brain atrophy measures into routine practice, Dr Beadnall has developed questionnaires for radiologists, radiographers, and neurologists. These questionnaires are awaiting ethics approval before being sent to clinicians.

Further studies looking at whether these MRI techniques can sensitively measure the impact of specific treatments on brain volume are underway with the TACIMS (Thalamic Atrophy and Cognition In Multiple Sclerosis) and the CortiMuS study (Cortical structure and function in Multiple Sclerosis). The importance of these studies is that the loss of brain volume appears to be one of the most sensitive markers of disease progression, so including routine MRI into clinical practice would allow more accurate detection of therapy response.

Dr Beadnall has recruited all the patients and healthy controls for the TACIMS study. Testing is ongoing, but data from the 12 month follow-up has been collected and analysed for publication. The CortiMuS study is still recruiting patients and healthy controls, with the help of MS Research Australia and other neurologists. The follow-up and assessments of the data are ongoing. Preliminary results indicate that some drug treatments reduce brain volume loss and Dr Beadnall is currently trying to link clinical outcomes with brain volume measures.

Dr Beadnall has also been involved with the development of a tablet-based tool (TaDiMuS – Tablet-based Data capture in Multiple Sclerosis) which collects patient continence information at MS clinics. The system allows patients to answer questions regarding continence issues and generates an automatic referral to the MS continence nurse should the patient’s symptoms require it. This data has been published and is already having an impact on continence management in some MS clinics, leading to improved continence management in these people with MS.

Dr Beadnall plans to submit her PhD thesis next year and during this scholarship she presented her work at many national and international conferences and meetings. Some commercial and academic collaborations have also arisen as a result of this work, ensuring that Australian MS researchers are at the forefront of worldwide research into MS.

Publications

  • Beadnall HN, Gill AJ, Riminton S, Barnett MH. Virus-related Merkel Cell Carcinoma Complicating Fingolimod Treatment for Multiple Sclerosis. Neurology 2016;87(24):2595-2597.
  • Hardy TA, Wang C, Beadnall HN, Lagopoulos J, Barnett Y, Klistorner A, Barnett MH. Wallerian Degeneration in the Corticospinal Tract Following Tumefactive Demyelination: Conventional and Advanced Magnetic Resonance Imaging. Can J Neurol Sci 2016;0:1-2. Published Online First: 15 July 2016. doi:10.1017/cjn-2016-253.
  • Wang C, Beadnall HN, Hatton SN, Bader G, Tomic D, Silva DG, Barnett MH. Automated brain volumetrics in multiple sclerosis: a step closer to clinical application. J Neurol Neurosurg Psychiatry 2016;87(7):754-757. Published Online First: 12 April 2016. doi:10.1136/jnnp-2015-312304.
  • Beadnall HN, Kuppanda K, O’Connell A, Hardy T, Reddel S, Barnett MH. Tablet-based screening improves continence management in multiple sclerosis. Ann Clin Transl Neurol 2015;2(6):679-687. Published Online First: 1 May 2015. doi:1002/acn3.205
  • Hardy TA, Beadnall HN, Sutton IJ, Mohamed A, Jonker BP, Buckland ME, Barnett MH. Baló's concentric sclerosis and tumefactive demyelination: A shared immunopathogenesis? J Neurol Sci2015;348(1-2):279-281. Published Online First: 25 November 2014. doi:10.1016/j.jns.2014.11.024
  • Several more in preparation.

Updated: 02 June 2017

Updated: 04 January, 2014

Investigator

  • Dr Heidi Beadnall, Brain and Mind Centre, The University of Sydney, NSW

Supervisor

Grant Awarded

  • Postgraduate Scholarship

Total Funding

  • $108,000

Duration

  • 3 years over 2014 - 2016

Funding Partner

  • MS Angels Melbourne
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The use of MRI to measure brain tissue loss in people with MS