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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.


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.

SUBMITTER: Gatto RG 

PROVIDER: S-EPMC7837609 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Gatto Rodolfo G RG   Gatto Rodolfo G RG   Ye Allen Q AQ   Colon-Perez Luis L   Mareci Thomas H TH   Lysakowski Anna A   Price Steven D SD   Brady Scott T ST   Karaman Muge M   Morfini Gerardo G   Magin Richard L RL  

Magma (New York, N.Y.) 20190215 4


<h4>Objective</h4>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).<h4>Materials and methods</h4>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.<h4>Results</h4>A significant 13% decrease in fractiona  ...[more]

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