Detection of axonal degeneration in a mouse model of Huntington's disease: comparison between diffusion tensor imaging and anomalous diffusion metrics

MAGMA. 2019 Aug;32(4):461-471. doi: 10.1007/s10334-019-00742-6. Epub 2019 Feb 15.


Objective: The goal of this work is to study the changes in white matter integrity in R6/2, a well-established animal model of Huntington's disease (HD) that are captured by ex vivo diffusion imaging (DTI) using a high field MRI (17.6 T).

Materials and methods: DTI and continuous time random walk (CTRW) models were used to fit changes in the diffusion-weighted signal intensity in the corpus callosum of controls and in R6/2 mice.

Results: A significant 13% decrease in fractional anisotropy, a 7% increase in axial diffusion, and a 33% increase in radial diffusion were observed between R6/2 and control mice. No change was observed in the CTRW beta parameter, but a significant decrease in the alpha parameter (- 21%) was measured. Histological analysis of the corpus callosum showed a decrease in axonal organization, myelin alterations, and astrogliosis. Electron microscopy studies demonstrated ultrastructural changes in degenerating axons, such as an increase in tortuosity in the R6/2 mice.

Conclusions: DTI and CTRW diffusion models display quantitative changes associated with the microstructural alterations observed in the corpus callosum of the R6/2 mice. The observed increase in the diffusivity and decrease in the alpha CTRW parameter providing support for the use of these diffusion models for non-invasive detection of white matter alterations in HD.

Keywords: Anomalous diffusion; Diffusion tensor imaging; Huntington disease; Magnetic resonance imaging; Mice.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anisotropy
  • Axons*
  • Corpus Callosum / diagnostic imaging
  • Diffusion Tensor Imaging*
  • Female
  • Huntington Disease / diagnostic imaging*
  • Magnetic Resonance Imaging*
  • Male
  • Mice
  • Microscopy, Fluorescence
  • Myelin Sheath
  • White Matter / diagnostic imaging