Developing MRI bio-makers of neurodegeneration

Dr Scott Kolbe

Florey Neurosciences Institute

| Better treatments | Neurobiology | Scholarship | 2007 | Investigator Led Research |
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Summary

People with MS often experience visual dysfunction resulting from damage to neurons in the optic nerve, the connection between the eye and the brain. Many people with MS often regain full vision but many continue to experience problems with vision mirroring MS disease progression. Despite the development of new treatments, there are currently no rapid methods by which to test their efficacy.

Scott Kolbe is developing techniques to measure damage to the visual system in the brain. The outcome will increase our understanding of how degeneration in the nervous system causes disability in MS, and develop a testing platform for neuroprotective and regenerative therapies.

Novel treatments, which act to protect neurons and regenerate myelin, have been developed in animal models but there are currently no established techniques by which to test their efficacy in preclinical human trials, thus large-scale clinical trials cannot proceed. Overcoming this hurdle requires both the development of new imaging technologies for assessing neuronal injury in MS.

Scott and several other international research groups have begun to develop novel MRI techniques that can potentially fulfill this role and apply them to the study of optic neuritis. Studying optic neuritis specifically has several advantages: it is common and often occurs early in the disease course, it is localised to the optic nerve, and it results in a stereotypical relapse/remission.

Project Outcomes

Developing optic nerve MRI techniques is challenging because of the nerve’s is small and highly mobile. Despite this Scott has developed an optic nerve imaging sequence called diffusion tensor imaging (DTI) which is sensitive to damage to the microstructure of the optic nerve in patients with a history of optic neuritis. Scott has also found that DTI-indicated optic nerve damage in those patients was associated with loss of optic nerve function. Scott did not, however, observe any association between optic nerve injury and loss of visual acuity, the principal clinical measure of visual function.

To further investigate the lack of association between optic nerve injury and clinical visual impairment, Scott has studied patients with a history of optic neuritis and extant loss of visual acuity. Scott found that optic nerve injury did not differentiate patients with severe visual impairment from those with mild impairment. In fact, many patients with severe optic nerve injury had near-normal visual acuity.

These results suggest that visual recovery following optic neuritis could be strongly influenced by neuroplasticity, the brains inherent ability to change in response to injury to maintain function. Scott will be further investigating the role of neuroplasticity in mediating visual recovery in future research studies.

Publications

  1. S.C. Kolbe. C.E. Bajraszewski, C.M. Chapman, T.Nguyen, P.J. Mitchell, M. Paine, L.A. Johnston, H. Butzkueven, T.J. Kilpatrick and G.F. Egan. 2009 “Diffusion Tensor Imaging Detects Axonal Pathology in the Optic Radiations after Optic Neuritis” Brain. (Under Review)
  2. S Kolbe, C Chapman, T Nguyen, C Bajraszewski, P Mitchell, L Johnston, H Butzkueven, M Paine, T Kilpatrick and G Egan. 2009 “Optic nerve diffusion changes and atrophy jointly predict visual dysfunction after optic neuritis.” NeuroImage. 45: 679-86
  3. Johnston LA, Kolbe SC, Mareels IMY and Egan GF. 2008. "Voxelwise regularisation of high angular resolution diffusion imaging data." IEEE Transactions of the 30th Annual Engineering in Medicine and Biology Conference.

Conference Abstracts

  1. S.C. Kolbe, C.E. Bajraszewski, C. M. Chapman, T. Nguyen, L.A. Johnston, P.J. Mitchell, H. Butzkueven, M. Paine, T.J. Kilpatrick and G.F. Egan. 2009 “Optic radiation abnormalities after optic neuritis” 17th Scientific Meeting for the International Society for Magnetic Resonance in Medicine, Honolulu, USA.
  2. S.C. Kolbe, L.A. Johnston, T.J. Kilpatrick and G.F. Egan. 2009 “Advanced MR brain imaging techniques for investigating white matter injury” New Horizons in Human Brain Imaging (A Focus on the Pacific Rim), Waikoloa, Hawaii, USA.
  3. S.C. Kolbe, C. M. Chapman, T. Nguyen, C.E. Bajraszewski, P.J. Mitchell, L.A. Johnston, H. Butzkueven, M. Paine, T.J. Kilpatrick and G.F. Egan. 2008 “Optic nerve volume and diffusivity jointly predict multifocal visual evoked potential amplitude after optic neuritis” World Congress on Treatment and Research in Multiple Sclerosis, Montreal, Canada.
  4. S.C. Kolbe, C.E. Bajraszewski, C. M. Chapman, P.J. Mitchell, L.A. Johnston, H. Butzkueven, T.J. Kilpatrick and G.F. Egan. 2008 “Reduced diffusion anisotropy in optic radiation correlates with optic nerve atrophy after optic neuritis” World Congress on Treatment and Research in Multiple Sclerosis, Montreal, Canada.
  5. CE Bajraszewski, SC Kolbe, CA Chapman, PJ Mitchell, H Butzkueven, TJ Kilpatrick, GF Egan. 2008. “Diffusion tensor analysis of optic radiation changes after optic neuritis.” Organisation for Human Brain Mapping Meeting, Melbourne, Australia.
  6. LA Johnston, SC Kolbe, I Mareels and GF Egan. 2008. “Regularisation of high angular resolution diffusion imaging data.” Organisation for Human Brain Mapping Meeting, Melbourne, Australia.
  7. CE Bajraszewski, SC Kolbe, CA Chapman, PJ Mitchell, H Butzkueven, TJ Kilpatrick, GF Egan. 2008. “Diffusion tensor analysis of optic radiation changes after optic neuritis.” Australian Neuroscience Society Conference, Hobart, Australia.
  8. Kolbe, S.C., Chapman, C., Butzkueven, H., Kilpatrick, T.J. and Egan G.F. 2007 “Quantitative diffusion tensor imaging of the human optic nerve after severe unilateral optic neuritis.” 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Prague, Czech Republic.
  9. SC Kolbe, C Chapman, H Butzkueven, MR Ditchfield, TJ Kilpatrick, and GF Egan. 2007. “Quantitative MR Imaging of the Human Optic Nerve in Optic Neuritis.” IBRO International Congress of Neuroscience, Melbourne Australia.
  10. T Kilpatrick, H Butzkueven, P Mitchell, S Kolbe, Q Yang, Q Wu, H Wang and G Egan. 2006. “Development of optic nerve diffusion weighted magnetic resonance imaging for translational research.” 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Madrid, Spain.

Updated: 04 January, 2007

Investigator

Grant Awarded

  • Scholarship

Total Funding

  • $66,380

Duration

  • 3 years

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Developing MRI bio-makers of neurodegeneration