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.

Quantitative magnetic resonance imaging (qMRI) aims to quantify tissue parameters by eliminating instrumental bias. We describe qMRI theory, simulations, and software designed to estimate proton density (PD), the apparent local concentration of water protons in the living human brain. First, we show that, in the absence of noise, multichannel coil data contain enough information to separate PD and coil sensitivity, a limiting instrumental bias. Second, we show that, in the presence of noise, regularization by a constraint on the relationship between T1 and PD produces accurate coil sensitivity and PD maps. The ability to measure PD quantitatively has applications in the analysis of in-vivo human brain tissue and enables multisite comparisons between individuals and across instruments.

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ObjectiveWe combined diffusion MRI (dMRI) with quantitative T1 (qT1) relaxometry in a sample of school-aged children born preterm and full term to determine whether reduced fractional anisotropy (FA) within the corpus callosum of the preterm group could be explained by a reduction in myelin content, as indexed by R1 (1/T1) from qT1 scans.Methods8-year-old children born preterm (n = 29; GA 22–32 weeks) and full term (n = 24) underwent dMRI and qT1 scans. Four subdivisions of the corpus callosum were segmented in individual native space according to cortical projection zones (occipital, temporal, motor and anterior-frontal). Fractional anisotropy (FA) and R1 were quantified along the tract trajectory of each subdivision and compared across two birth groups.ResultsCompared to controls, preterm children demonstrated significantly decreased FA in 3 of 4 analyzed corpus callosum subdivisions (temporal, motor, and anterior frontal segments) and decreased R1 in only 2 of 4 corpus callosum subdivisions (temporal and motor segments). FA and RD were significantly associated with R1 within temporal but not anterior frontal subdivisions of the corpus callosum in the term group; RD correlated with R1 in the anterior subdivision in the preterm group only.ConclusionsMyelin content, as indexed by R1, drives some but not all of the differences in white matter between preterm and term born children. Other factors, such as axonal diameter and directional coherence, likely contributed to FA differences in the anterior frontal segment of the corpus callosum that were not well explained by R1.