Axon morphology is modulated by the local environment and impacts the noninvasive investigation of its structure-function relationship

Mariam Andersson, Hans Martin Kjer, Jonathan Rafael-Patino, Alexandra Pacureanu, Bente Pakkenberg, Jean Philippe Thiran, Maurice Ptito, Martin Bech, Anders Bjorholm Dahl, Vedrana Andersen Dahl, Tim B. Dyrby

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Abstract

Axonal conduction velocity, which ensures efficient function of the brain network, is related to axon diameter. Noninvasive, in vivo axon diameter estimates can be made with diffusion magnetic resonance imaging, but the technique requires three-dimensional (3D) validation. Here, high-resolution, 3D synchrotron X-ray nano-holotomography images of white matter samples from the corpus callosum of a monkey brain reveal that blood vessels, cells, and vacuoles affect axonal diameter and trajectory. Within single axons, we find that the variation in diameter and conduction velocity correlates with the mean diameter, contesting the value of precise diameter determination in larger axons. These complex 3D axon morphologies drive previously reported 2D trends in axon diameter and g-ratio. Furthermore, we find that these morphologies bias the estimates of axon diameter with diffusion magnetic resonance imaging and, ultimately, impact the investigation and formulation of the axon structure-function relationship.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number52
Pages (from-to)33649-33659
ISSN0027-8424
DOIs
Publication statusPublished - 29 Dec 2020

Keywords

  • Axon morphology
  • Brain
  • Conduction velocity
  • MRI
  • Myelination

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