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MAGMA. 2019 Feb 15. doi: 10.1007/s10334-019-00742-6. [Epub ahead of print]

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

Author information

1
Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA.
2
Department of Bioengineering, University of Illinois at Chicago, 851 S Morgan St, 218 SEO (MC 063), Chicago, IL, 60607, USA.
3
Department of Neurology and Behavior, University of California at Irvine, Irvine, CA, USA.
4
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, USA.
5
Center for MR Research, University of Illinois at Chicago, Chicago, IL, USA.
6
Department of Bioengineering, University of Illinois at Chicago, 851 S Morgan St, 218 SEO (MC 063), Chicago, IL, 60607, USA. rmagin@uic.edu.

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:

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

PMID:
30771034
DOI:
10.1007/s10334-019-00742-6

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