Evaluating g-ratio weighted changes in the corpus callosum as a function of age and sex

Abstract

Recent years have seen a growing interest in relating MRI measurements to the structural-biophysical properties of white matter fibers. The fiber g-ratio, defined as the ratio between the inner and outer radii of the axon myelin sheath, is an important structural property of white matter, affecting signal conduction. Recently proposed modeling methods that use a combination of quantitative-MRI signals, enable a measurement of the fiber g-ratio in vivo. Here we use an MRI-based g-ratio estimation to observe the variance of the g-ratio within the corpus callosum, and evaluate sex and age related differences. To estimate the g-ratio we used a model (Stikov et al., 2011; Duval et al., 2017) based on two different WM microstructure parameters: the relative amounts of myelin (myelin volume fraction, MVF) and fibers (fiber volume fraction, FVF) in a voxel. We derived the FVF from the fractional anisotropy (FA), and estimated the MVF by using the lipid and macromolecular tissue volume (MTV), calculated from the proton density (Mezer et al., 2013). In comparison to other methods of estimating the MVF, MTV represents a stable parameter with a straightforward route of acquisition. To establish our model, we first compared histological MVF measurements (West et al., 2016) with the MRI derived MTV. We then implemented our model on a large database of 92 subjects (44 males), aged 7 to 81, in order to evaluate age and sex related changes within the corpus callosum. Our results show that the MTV provides a good estimation of MVF for calculating g-ratio, and produced values from the corpus callosum that correspond to those found in animals ex vivo and are close to the theoretical optimum, as well as to published in vivo data. Our results demonstrate that the MTV derived g-ratio provides a simple and reliable in vivo g-ratio-weighted (GR*) measurement in humans. In agreement with theoretical predictions, and unlike other tissue parameters measured with MRI, the g-ratio estimations were found to be relatively stable with age, and we found no support for a significant sexual dimorphism with age.

Evolution of white matter tract microstructure across the life span

“…levels have tract specific values in the range 0.67-0.76, consistent with previous findings in younger adults(20-40 years;Cercignani et al, 2016). PD-based estimates of the g-ratio do not require calibration(Berman et al, 2017;Duval et al, 2017) and differences arising from such a comparison might highlight changes in macromolecular content with age.Our findings suggest that the largest investments in myelination for a given axonal caliber occur in the anterior callosal fibers (forceps minor) while conversely the lowest myelination investments occur in Projection and callosal fiber trajectories for FA, MD, ICVF, and ODI. A comparison between the g-ratio aging trajectories shown here and those calculated from myelin volume fraction obtained from PD estimates would be of high interest.…”

“…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).…”

Four in vivo g‐ratio‐weighted imaging methods: Comparability and repeatability at the group level

“…The difference between MVF imaging markers was particularly strong in the corticospinal tract. While both imaging markers have been previously used as proxy for myelin density (MT [Mohammadi et al, ], MTV [Duval et al, ]), there is only direct comparison with ex vivo histology gold standard for MTV [Berman et al, ].…”

Evaluating arcuate fasciculus laterality measurements across dataset and tractography pipelines

“…We also used mrQ to calculate two additional quantitative brain maps: the lipid and macromolecular tissue volume (MTV) map (Mezer et al, , ), which uses the proton density signal to determine the amount of nonwater per voxel; and the water‐surface interaction rate (SIR) map, which estimates the spin‐lattice relaxation rate normalized by nonwater tissue volume and reflects differences in tissue composition (Mezer et al, ). Finally, we used mrQ to synthesize a bias‐free T1‐weighted image from the qMRI data (Berman, West, Does, Yeatman, & Mezer, ; Gomez et al, ; Yeatman, Wandell, & Mezer, ).…”

“…Since different readout schemes produce different geometrical artifacts, we used ANTs to warp the nondiffusion quantitative maps into the diffusion space. (For further discussion and examples, see Berman et al, ; Yeatman, Wandell, & Mezer, ). Finally, the tract profile for each metric was calculated by performing a weighted averaging of the corresponding points, such that points closer to the core count more than points farther away.…”