MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis

York, E. N. et al. (2021) MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis. Brain Communications, 3(4), fcab249. (doi: 10.1093/braincomms/fcab249) (PMID:34877533) (PMCID:PMC8643503)

Abstract

Myelin loss is associated with axonal damage in established multiple sclerosis. This relationship is challenging to study in vivo in early disease. Here, we ask whether myelin loss is associated with axonal damage at diagnosis, by combining non-invasive neuroimaging and blood biomarkers. We performed quantitative microstructural MRI and single molecule ELISA plasma neurofilament measurement in 73 patients with newly diagnosed, immunotherapy naïve relapsing-remitting multiple sclerosis. Myelin integrity was evaluated using aggregate g-ratios, derived from magnetization transfer saturation (MTsat) and neurite orientation dispersion and density imaging (NODDI) diffusion data. We found significantly higher g-ratios within cerebral white matter lesions (suggesting myelin loss) compared with normal-appearing white matter (0.61 vs 0.57, difference 0.036, 95% CI 0.029 to 0.043, p < 0.001). Lesion volume (Spearman’s rho rs= 0.38, p < 0.001) and g-ratio (rs= 0.24 p < 0.05) correlated independently with plasma neurofilament. In patients with substantial lesion load (n = 38), those with higher g-ratio (defined as greater than median) were more likely to have abnormally elevated plasma neurofilament than those with normal g-ratio (defined as less than median) (11/23 [48%] versus 2/15 [13%] p < 0.05). These data suggest that, even at multiple sclerosis diagnosis, reduced myelin integrity is associated with axonal damage. MRI-derived g-ratio may provide useful additional information regarding lesion severity, and help to identify individuals with a high degree of axonal damage at disease onset. York, Martin et al. simultaneously measured g-ratio and plasma neurofilament in 73 relapsing-remitting multiple sclerosis patients at diagnosis using advanced MRI and single molecule ELISA. They demonstrate that g-ratio of cerebral white matter lesions varies at diagnosis, and show that high g-ratio of lesions is associated with elevated plasma neurofilament.

• Item Type: Articles
• Additional Information: D.P.J.H. is supported by a Wellcome Trust Senior Research Fellowship (215621/Z/19/Z) and the Medical Research Foundation. S.-J.M. is supported by the Anne Rowling Clinic and Glasgow Multiple Sclerosis Clinical Research Facility. E.N.Y. is supported by a Chief Scientist Office Scottish PhD Research & Innovation Network Traineeships Motor Neuron Disease/Multiple Sclerosis Studentship. Additional funding for authors came from the NHS Lothian Research and Development Office (M.J.T.). The University 3 T MRI Research scanner in RIE is funded by the Wellcome Trust (104916/Z/14/Z), Dunhill Trust (R380R/1114), Edinburgh and Lothians Health Foundation (2012/17), Muir Maxwell Research Fund, Edinburgh Imaging and University of Edinburgh. We acknowledge support and funding from the MS Society UK Centre of Excellence and the Anne Rowling Clinic.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Overell, Dr James and Martin, Dr Sarah-Jane
• Authors: York, E. N., Martin, S.-J., Meijboom, R., Thrippleton, M. J., Bastin, M. E., Carter, E., Overell, J., Connick, P., Chandran, S., Waldman, A. D., Hunt, D. P. J., Akula, A., Artal, J. C., Baranzini, S., Barret, F., Bastin, M., Batchelor, C., Beswick, E., Brown, F., Chandran, S., Chang, J., Chen, Y., Colville, S., Connick, P., Cranley, D., Dakin, R., Dhillon, B., Elliot, E., Finlayson, J., Foley, P., Glasmacher, S., Grossart, A., Haagenrud, H., Hafezi, K., Harrison, E., Harroud, A., Hathorn, S., Hopkins, T., Hunt, D., Hutchinson, A., Jayprakash, K., Justin, M., Kampaite, A., Kearns, P., Kennedy, G., Kleynhans, M., Kwong, J. N. K., Larraz, J., Love, K., Lyle, D., MacDonald, J., MacDougall, N., Macfarlane, L., Maclennan, B., Maclean, A., MacLeod, M. A., Macleod, N., Mahad, D., Martin, S. J., McMahon, L., Megson, I., Meijboom, R., Mollison, D., Monaghan, M., Murphy, L., Murray, K., Newton, J., O’Riordan, J., Perry, D., Quigley, S., Scotson, A., Stenson, A., Thrippleton, M., Hernandez, M. V., Waldman, A., Weaver, C., Webb, S., Weller, B., Williams, A., Wiseman, S., Wong, C., Wong, M., and York, E.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Brain Communications
• Publisher: Oxford University Press
• ISSN: 2632-1297
• ISSN (Online): 2632-1297
• Published Online: 03 November 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Brain Communications 3(4): fcab249
• Publisher Policy: Reproduced under a Creative Commons License