Characterizing axonal myelination within the healthy population: a tract-by-tract mapping of effects of age and gender on the fiber g-ratio

Abstract

The g-ratio, equal to the ratio of the inner-to-outer diameter of a myelinated axon, is associated with the speed of conduction, and thus reflects axonal function and integrity. It is now possible to estimate an “aggregate” g-ratio in vivo using MRI. The aim of this study was to assess the variation of the MRI-derived fiber g-ratio in the brain of healthy individuals, and to characterize its variation across the lifespan. Thirty-eight healthy participants, aged between 20 and 76, were recruited. Whole-brain g-ratio maps were computed and analyzed voxel-wise. Median tract g-ratio values were also extracted. No significant effect of gender was found, whereas age was found to be significantly associated with the g-ratio within the white matter. The tract-specific analysis showed this relationship to follow a nearly-linear increase, although the slope appears to slow down slightly after the 6th decade of life. The most likely interpretation is a subtle but consistent reduction in myelin throughout adulthood, with the density of axons beginning to decrease between the 4th and 5th decade.

Evolution of white matter tract microstructure across the life span

“…In-line with (Cercignani et al, 2016;Mohammadi et al, 2015), this calibration was conducted using a healthy g-ratio value of 0.7 in the splenium of a subset of young adults. In-line with (Cercignani et al, 2016;Mohammadi et al, 2015), this calibration was conducted using a healthy g-ratio value of 0.7 in the splenium of a subset of young adults.…”

“…We estimated the normalization factor, α, by following the previous literature (Cercignani et al, 2016;Mancini et al, 2017;Mohammadi et al, 2015). We estimated the normalization factor, α, by following the previous literature (Cercignani et al, 2016;Mancini et al, 2017;Mohammadi et al, 2015).…”

“…One such quantitative magnetic resonance imaging (qMRI) methodology-multiparameter mapping (MPM; Weiskopf et al, 2013), provides estimates for the magnetization transfer (MT) and relaxation rates R1 and R2*, each providing a level of sensitivity to local myelination and/or iron deposi- Draganski et al, 2011), particularly in later life after myelination has matured to a peak density before reversing in trend and declining with age (Li et al, 2014;Yeatman et al, 2014). Preliminary investigations of g-ratio change across the life span in small imaging cohorts (n = 38-92) have reported linear increases with age in the deep WM (Cercignani et al, 2016), with little age-related change observed across the mid-sagittal portion of the corpus callosum (Berman, West, Does, Yeatman, & Mezer, 2017). Preliminary investigations of g-ratio change across the life span in small imaging cohorts (n = 38-92) have reported linear increases with age in the deep WM (Cercignani et al, 2016), with little age-related change observed across the mid-sagittal portion of the corpus callosum (Berman, West, Does, Yeatman, & Mezer, 2017).…”

Analysis of White Matter Damage in Patients with Multiple Sclerosis via a Novel In Vivo MR Method for Measuring Myelin, Axons, and G-Ratio

“…34 MR studies evaluating g-ratio have mostly been based on magnetization transfer imaging. 12,15,18 However, quantitative magnetization transfer imaging requires approximately 30 minutes for acquisition, and it is still unrealistic for routine use in a clinical setting. Quantitative magnetization transfer imaging first measures macromolecular pool size, and a coefficient for regressing it to MVF should be determined in each protocol.…”

“…G-ratio has a limited dynamic range in healthy WM 13 and depends on age [15][16][17] and region. 15,18 Stikov et al 12 developed a model that estimates "aggregate" g-ratio in a voxel via MR imaging. This model assumes that the g-ratios of all axons in a voxel are the same.…”