In vivo histology of the myelin g-ratio with magnetic resonance imaging

Neuroimage. 2015 Sep:118:397-405. doi: 10.1016/j.neuroimage.2015.05.023. Epub 2015 May 21.

Abstract

The myelin g-ratio, defined as the ratio between the inner and the outer diameter of the myelin sheath, is a fundamental property of white matter that can be computed from a simple formula relating the myelin volume fraction to the fiber volume fraction or the axon volume fraction. In this paper, a unique combination of magnetization transfer, diffusion imaging and histology is presented, providing a novel method for in vivo magnetic resonance imaging of the axon volume fraction and the myelin g-ratio. Our method was demonstrated in the corpus callosum of one cynomolgus macaque, and applied to obtain full-brain g-ratio maps in one healthy human subject and one multiple sclerosis patient. In the macaque, the g-ratio was relatively constant across the corpus callosum, as measured by both MRI and electron microscopy. In the human subjects, the g-ratio in multiple sclerosis lesions was higher than in normal appearing white matter, which was in turn higher than in healthy white matter. Measuring the g-ratio brings us one step closer to fully characterizing white matter non-invasively, making it possible to perform in vivo histology of the human brain during development, aging, disease and treatment.

Keywords: Diffusion; Histology; Magnetization transfer; Myelin g-ratio; Quantitative MRI; White matter microstructure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Axons / ultrastructure*
  • Brain / ultrastructure*
  • Corpus Callosum / ultrastructure
  • Diffusion Magnetic Resonance Imaging / methods*
  • Humans
  • Macaca fascicularis
  • Magnetic Phenomena
  • Male
  • Mice, Neurologic Mutants
  • Multiple Sclerosis / pathology
  • Myelin Sheath / ultrastructure*