MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis
Elizabeth N. York, Sarah‐Jane Martin, Rozanna Meijboom, Michael J. Thrippleton, Mark E. Bastin, Edwin Carter, James Overell, Peter Connick, Siddharthan Chandran, Adam Waldman, David Hunt, Amit Akula, Javier Carod Artal, Sergio E. Baranzini, F Barret, Mark E. Bastin, Christine L. Batchelor, Emily Beswick, Fraser Brown, Siddharthan Chandran, Jessie Chang, Yingdi Chen, Shuna Colville, Peter Connick, Denise Cranley, Rachel Dakin, Baljean Dhillon, Elizabeth Elliot, James K. Finlayson, Peter Foley, Stella A. Glasmacher, Angus Grossart, Haane Haagenrud, Katarzyna Hafezi, Emily Harrison, Adil Harroud, Sara Hathorn, Tracey Hopkins, David Hunt, Aidan Hutchinson, Kiran Jayprakash, M Karthiga S Justin, Agniete Kampaite, Patrick K. A. Kearns, Gwen Kennedy, Michaela Kleynhans, Julian Ng Kee Kwong, Juan Larraz, Kathryn Love, Dawn Lyle, James MacDonald, Niall MacDougall, Lesley Macfarlane, Beverly MacLennan, Alan Maclean, Margaret Ann Macleod, Nicola MacLeod, Don Mahad, Sarah J. Martin, Lynn McMahon, Ian L. Megson, Rozanna Meijboom, Daisy Mollison, Mary Monaghan, Lee Murphy, Katy Murray, Judith Newton, J O’Riordan, David J. Perry, Suzanne Quigley, Adam Scotson, Amy Stenson, Michael J. Thrippleton, Maria Valdéz Hernandez, Adam Waldman, Christine Weaver, Stewart Webb, Belinda Weller, Anna Williams, Stewart Wiseman, Charis Wong, Michael L. Wong, Elizabeth N. York
Abstract
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 and neurite orientation dispersion and density imaging diffusion data. We found significantly higher g-ratios within cerebral white matter lesions (suggesting myelin loss) compared with normal-appearing white matter (0.61 versus 0.57, difference 0.036, 95% CI: 0.029–0.043, 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.