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.
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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.
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Experiments were performed under protocols approved by the Animal Care Committee at the University of illinois in Chicago.
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Gatto, R.G., Ye, A.Q., Colon-Perez, L. et al. Detection of axonal degeneration in a mouse model of Huntington’s disease: comparison between diffusion tensor imaging and anomalous diffusion metrics. Magn Reson Mater Phy 32, 461–471 (2019). https://doi.org/10.1007/s10334-019-00742-6
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DOI: https://doi.org/10.1007/s10334-019-00742-6