g-Ratio weighted imaging of the human spinal cord in vivo

Abstract

The myelin g-ratio is defined as the ratio of the inner to the outer diameter of the myelin sheath. This ratio provides a measure of the myelin thickness that complements axon morphology (diameter and density) with high specificity for assessment of demyelination in diseases such as multiple sclerosis. Previous work has shown that an aggregate g-ratio map can be computed using a formula that combines axon and myelin density measured with quantitative MRI. In this work, we computed g-ratio weighted maps in the cervical spinal cord of nine healthy subjects. We utilized the 300 mT/m gradients from the CONNECTOM scanner for estimating the fraction of restricted water (fr) with high accuracy using the CHARMED model. Myelin density was estimated using the lipid and macromolecular tissue volume (MTV) method, derived from normalized proton density (PD) mapping. The variability across spinal level, laterality and subject were assessed using a three-way ANOVA. The average g-ratio value obtained in the white matter was 0.76 +/− 0.03, consistent with previous histology work. Coefficients of variation of fr and MTV were respectively 4.3% and 13.7%. fr and myelin density were significantly different across spinal tracts (p = 3×10−7 and 0.004 respectively) and were positively correlated in the white matter (r = 0.42), suggesting shared microstructural information. The g-ratio did not show significant differences across tracts (p=0.6). This study suggests that fr and myelin density can be measured in vivo with high precision and that they can be combined to produce a map robust to free water pool contamination such as cerebrospinal fluid or veins and weighted by the myelin g-ratio. Potential applications include the study of early demyelination in multiple sclerosis and the quantitative assessment of remyelination drugs.

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.…”

Relevance of time‐dependence for clinically viable diffusion imaging of the spinal cord

“…Here, we considered myelinated axons, and therefore used specific values for a and b to describe the distributions of outer cylinders (axons including myelin) and inner cylinders (axons without myelin), assuming a ratio of unmyelinated/myelinated axon radius (i.e. g‐ratio) of 0.75 . In practice, for the outer cylinder radius distribution, we used: a = 3.01, b = 1.63 μ m for the substrate with large axons ( E [ R ] = 3.51 μ m; Var [ R ] = 4.07 μ m 2 ); a = 5.73 and b = 0.23 μ m for the substrate with small axons ( E [ R ] = 1.29 μ m; Var [ R ] = 0.29 μ m 2 ).…”

Design and Validation of Diffusion MRI Models of White Matter

“…For example, using WMTI, AWF has been shown to correlate with axon volume fraction but not with the g -ratio derived from EM, while D e,⊥ correlated with the g -ratio but not the with axon volume fraction (Jelescu et al, 2016b). Measures of axonal water fraction have also been combined with MRI measures of myelin content to estimate myelin g-ratio in vivo , which compared favorably to that derived from EM (Duval et al, 2017; Stikov et al, 2015). However, a strong correlation is not necessarily proof of parameter specificity.…”