A time-dependent diffusion MRI signature of axon caliber variations and beading

Commun Biol. 2020 Jul 7;3(1):354. doi: 10.1038/s42003-020-1050-x.

Abstract

MRI provides a unique non-invasive window into the brain, yet is limited to millimeter resolution, orders of magnitude coarser than cell dimensions. Here, we show that diffusion MRI is sensitive to the micrometer-scale variations in axon caliber or pathological beading, by identifying a signature power-law diffusion time-dependence of the along-fiber diffusion coefficient. We observe this signature in human brain white matter and identify its origins by Monte Carlo simulations in realistic substrates from 3-dimensional electron microscopy of mouse corpus callosum. Simulations reveal that the time-dependence originates from axon caliber variation, rather than from mitochondria or axonal undulations. We report a decreased amplitude of time-dependence in multiple sclerosis lesions, illustrating the potential sensitivity of our method to axonal beading in a plethora of neurodegenerative disorders. This specificity to microstructure offers an exciting possibility of bridging across scales to image cellular-level pathology with a clinically feasible MRI technique.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Axons / ultrastructure*
  • Corpus Callosum / ultrastructure
  • Diffusion Magnetic Resonance Imaging* / methods
  • Diffusion Tensor Imaging / methods
  • Female
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / ultrastructure
  • Models, Theoretical
  • Monte Carlo Method
  • Time Factors
  • White Matter / ultrastructure