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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. MaginEmail author
Research Article
  • 102 Downloads

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.

Keywords

Magnetic resonance imaging Diffusion tensor imaging Anomalous diffusion Huntington disease Mice 

Notes

Acknowledgements

This work was support provided by grants from the National Center for Advancing Translational Science grant (NCATS TLTR000049 to AY), NIH DC02058 (to AL), CHDI (#A-11872; to GM and SB), NIH R21NS096642 (to GM). A portion of this work was performed in the McKnight Brain Institute at the National High Magnetic Field Laboratory’s AMRIS Facility, which is supported by National Science Foundation Cooperative Agreement no. DMR-1157490 and the State of Florida. In addition, we would like to thank Mr. Dan Plant for his input and assistance in the design and experimental set up for this project, as well as Dr. Carson Ingo for his assistance in fitting the data to the Mittag–Leffler function.

Compliance with ethical standards

Conflict of interest

Authors of this manuscript have no conflicts of interest to report.

Ethical approval

Experiments were performed under protocols approved by the Animal Care Committee at the University of illinois in Chicago.

Statement on the welfare of animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

10334_2019_742_MOESM1_ESM.pdf (1.4 mb)
Supplementary material 1 (PDF 1421 kb)

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Copyright information

© European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) 2019

Authors and Affiliations

  • Rodolfo G. Gatto
    • 1
    • 2
  • Allen Q. Ye
    • 2
  • Luis Colon-Perez
    • 3
    • 4
  • Thomas H. Mareci
    • 4
  • Anna Lysakowski
    • 1
  • Steven D. Price
    • 1
  • Scott T. Brady
    • 1
  • Muge Karaman
    • 2
    • 5
  • Gerardo Morfini
    • 1
  • Richard L. Magin
    • 2
    Email author
  1. 1.Department of Anatomy and Cell BiologyUniversity of Illinois at ChicagoChicagoUSA
  2. 2.Department of BioengineeringUniversity of Illinois at ChicagoChicagoUSA
  3. 3.Department of Neurology and BehaviorUniversity of California at IrvineIrvineUSA
  4. 4.Department of Biochemistry and Molecular BiologyUniversity of FloridaGainesvilleUSA
  5. 5.Center for MR ResearchUniversity of Illinois at ChicagoChicagoUSA

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