The fiber 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) 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 to estimate 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 aggregate 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 g-ratio-weighted map robust to free water pool contamination from cerebrospinal fluid or veins. Potential applications include the study of early demyelination in multiple sclerosis, and the quantitative assessment of remyelination drugs.
Bibliographical noteFunding Information:
We would like to thank the participants of this study and M. Brun-Cosme-Bruny and M. De Leener for their help with the processing of the data. We also thank the anonymous reviewers for their valuable comments. This study was founded by the National Institutes of Health, the NIH Blueprint Initiative for Neuroscience Research Grant U01MH093765, the National Institutes of Health Grant P41EB015896, the MS Society of Canada [EGID 2370], the Canada Research Chair in Quantitative Magnetic Resonance Imaging (JCA), the Canadian Institute of Health Research [CIHR FDN-143263], the Fonds de Recherche du Québec - Santé , the Fonds de Recherche du Québec - Nature et Technologies [2015-PR-182754], the Natural Sciences and Engineering Research Council of Canada [435897-2013] [2016-06774] and the Quebec BioImaging Network.
© 2016 Elsevier Inc.
- Myelin mapping
- Spinal cord