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MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643503/ https://www.ncbi.nlm.nih.gov/pubmed/34877533 http://dx.doi.org/10.1093/braincomms/fcab249 |
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author | York, Elizabeth N Martin, Sarah-Jane Meijboom, Rozanna Thrippleton, Michael J Bastin, Mark E Carter, Edwin Overell, James Connick, Peter Chandran, Siddharthan Waldman, Adam D Hunt, David P J |
author_facet | York, Elizabeth N Martin, Sarah-Jane Meijboom, Rozanna Thrippleton, Michael J Bastin, Mark E Carter, Edwin Overell, James Connick, Peter Chandran, Siddharthan Waldman, Adam D Hunt, David P J |
author_sort | York, Elizabeth N |
collection | PubMed |
description | 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 r(s)= 0.38, P < 0.001) and g-ratio (r(s)= 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. |
format | Online Article Text |
id | pubmed-8643503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-86435032021-12-06 MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis York, Elizabeth N Martin, Sarah-Jane Meijboom, Rozanna Thrippleton, Michael J Bastin, Mark E Carter, Edwin Overell, James Connick, Peter Chandran, Siddharthan Waldman, Adam D Hunt, David P J Brain Commun Original Article 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 r(s)= 0.38, P < 0.001) and g-ratio (r(s)= 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. Oxford University Press 2021-11-03 /pmc/articles/PMC8643503/ /pubmed/34877533 http://dx.doi.org/10.1093/braincomms/fcab249 Text en © The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article York, Elizabeth N Martin, Sarah-Jane Meijboom, Rozanna Thrippleton, Michael J Bastin, Mark E Carter, Edwin Overell, James Connick, Peter Chandran, Siddharthan Waldman, Adam D Hunt, David P J MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis |
title | MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis |
title_full | MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis |
title_fullStr | MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis |
title_full_unstemmed | MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis |
title_short | MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis |
title_sort | mri-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643503/ https://www.ncbi.nlm.nih.gov/pubmed/34877533 http://dx.doi.org/10.1093/braincomms/fcab249 |
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