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

Rodolfo G. Gatto, Allen Q. Ye, Luis Colon-Perez, Thomas H. Mareci, Anna Lysakowski, Steven D. Price, Scott T. Brady, Muge Karaman, Gerardo Morfini, Richard L. Magin

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)461-471
Number of pages11
JournalMagnetic Resonance Materials in Physics, Biology and Medicine
Volume32
Issue number4
DOIs
StatePublished - 1 Aug 2019

Keywords

  • Anomalous diffusion
  • Diffusion tensor imaging
  • Huntington disease
  • Magnetic resonance imaging
  • Mice

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