Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Feb 16;9(1):20552173221147620.
doi: 10.1177/20552173221147620. eCollection 2023 Jan-Mar.

Axonal and myelin changes and their inter-relationship in the optic radiations in people with multiple sclerosis

Eva A Krijnen  1   2 , Chanon Ngamsombat  3   4 , Ilena C George  2 , Fang F Yu  5 , Qiuyun Fan  6   7 , Qiyuan Tian  3 , Susie Y Huang  3 , Eric C Klawiter  2
Affiliations

Axonal and myelin changes and their inter-relationship in the optic radiations in people with multiple sclerosis

Eva A Krijnen et al. Mult Scler J Exp Transl Clin. .

Abstract

Background: The imaging g-ratio, estimated from axonal volume fraction (AVF) and myelin volume fraction (MVF), is a novel biomarker of microstructural tissue integrity in multiple sclerosis (MS).

Objective: To assess axonal and myelin changes and their inter-relationship as measured by g-ratio in the optic radiations (OR) in people with MS (pwMS) with and without previous optic neuritis (ON) compared to healthy controls (HC).

Methods: Thirty pwMS and 17 HCs were scanned on a 3Tesla Connectom scanner. AVF and MVF, derived from a multi-shell diffusion protocol and macromolecular tissue volume, respectively, were measured in normal-appearing white matter (NAWM) and lesions within the OR and used to calculate imaging g-ratio.

Results: OR AVF and MVF were decreased in pwMS compared to HC, and in OR lesions compared to NAWM, whereas the g-ratio was not different. Compared to pwMS with previous ON, AVF and g-ratio tended to be higher in pwMS without prior ON. AVF and MVF, particularly in NAWM, were positively correlated with retinal thickness, which was more pronounced in pwMS with prior ON.

Conclusion: Axonal measures reflect microstructural tissue damage in the OR, particularly in the setting of remote ON, and correlate with established metrics of visual health in MS.

Keywords: Optic neuritis; diffusion magnetic resonance imaging; diffusion tractography; multiple sclerosis; optical coherence tomography; white matter.

PubMed Disclaimer

Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: I.C.G. became employed by Biogen following her contributions to this research. S.Y.H. has received consulting fees and research grants from Siemens Healthineers. E.C.K. has received consulting fees from Banner Life Sciences, Galen/Atlantica, Genentech, Greenwich Biosciences and OM1, and research funds from Abbvie, Biogen, and Genentech. Other authors report no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Volume rendered results of the thresholded tractography results of the optic radiation in a representative multiple sclerosis (MS) patient (red).
Figure 2.
Figure 2.
Representation of NAWM (light blue; second image) and lesional (red; second image) OR on axial FLAIR image and maps of corresponding MVF (third image), AVF (fourth image), and g-ratio (fifth image). Solid arrows indicate lesions. Dotted arrows indicate NAWM.
Figure 3.
Figure 3.
Differences in MR metrics in the optic radiations between pwMS and HC. AVF, MVF, and g-ratio are reported as median values with interquartile range and minimum and maximum values for both pwMS and HC. Open circles in the MVF plot denote outliers. Differences between pwMS and HC surviving Bonferroni correction are marked with an asterisk (*); others are denoted as ns.
Figure 4.
Figure 4.
Differences in MR metrics in the optic radiations between lesions and NAWM. AVF, MVF, and g-ratio are reported as median values with interquartile range and minimum and maximum for both NAWM and lesions. Open circles in the AVF and MVF plots denote outliers. Differences between NAWM and lesions surviving Bonferroni correction are marked with an asterisk (*); others are denoted as ns.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Stikov N, Campbell JS, Stroh T, et al. In vivo histology of the myelin g-ratio with magnetic resonance imaging. Research support, non-U.S. Gov't. NeuroImage 2015; 118: 397–405. - PubMed
    1. Yu F, Fan Q, Tian Q, et al. Imaging G-ratio in multiple sclerosis using high-gradient diffusion MRI and macromolecular tissue volume. AJNR Am J Neuroradiol 2019; 40: 1871–1877. - PMC - PubMed
    1. Hagiwara A, Hori M, Yokoyama K, et al. Analysis of white matter damage in patients with multiple sclerosis via a novel in vivo MR method for measuring myelin, axons, and G-ratio. AJNR Am J Neuroradiol 2017; 38: 1934–1940. - PMC - PubMed
    1. Frohman EM, Frohman TC, Zee DSet al. et al. The neuro-ophthalmology of multiple sclerosis. Lancet Neurol 2005; 4: 111–121. - PubMed
    1. Graves JS, Oertel FC, Van der Walt A, et al. Leveraging visual outcome measures to advance therapy development in neuroimmunologic disorders. Neurol Neuroimmunol Neuroinflamm 2021; 9: e1126. - PMC - PubMed

LinkOut - more resources