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Cited by 42Advanced Neuroimaging Techniques and ApplicationsGenetic Neurodegenerative DiseasesAdvanced MRI Techniques and Applications

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

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Gatto, Rodolfo G., Ye, Allen Q., Colon-Perez, Luis, Mareci, Thomas H., Lysakowski, Anna, Price, Steven D., Brady, Scott T., Karaman, Muge +2 more·2019·Magnetic Resonance Materials in Physics, Biology and Medicine
DOI 10.1007/s10334-019-00742-6PMC PMC7837609
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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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  • Previous studies on 3×Tg-AD mice have reported significant volumetric decreases and WM microstructural abnormalities in the corpus callosum and internal capsule compared with controls.

    “Previous studies on 3×Tg-AD mice have reported significant volumetric decreases (Kong et al., 2018) and WM microstructural abnormalities (Praet et al., 2018; Gatto et al., 2019; Bergamino et al., 2023) in the CC and internal capsule compared with controls.”

    From Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain (2026) · cites this paper as Gatto et al., 2019

    The Results and Discussion report white-matter microstructural abnormalities in the corpus callosum compared with controls. But the mice studied were R6/2 Huntington’s disease mice, not 3×Tg-AD mice, and these passages do not report abnormalities in the internal capsule. The volumetric-decrease portion of the citing sentence is attributed to Kong et al., not to this source. (LLM, conf=0.88)

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Authors
Gatto, R. G., Ye, A. Q., Colon-Perez, L., Mareci, T. H., Lysakowski, A., Price, S. D., Brady, S. T., Karaman, M., Morfini, G., & Magin, R. L.
Affiliations
  • University of Illinois Chicago (US)
  • University of Florida (US)
Corresponding author
Magin, Richard L.
ORCID
Venue
Magnetic Resonance Materials in Physics, Biology and Medicine
Publisher
Springer Science and Business Media LLC
Published
2019-02-15
Volume
32
Issue
4
Pages
461-471
ISSN
  • 0968-5243 (ISSN-L)
  • 1352-8661
DOI
10.1007/s10334-019-00742-6
PMC
PMC7837609
OpenAlex
W2912762199
Cited by
42
References
3
Citations by year
2026: 1 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 11 · 2020: 9 · 2019: 4 · 2018: 1
FWCI
4.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Magnetic Resonance Materials in Physics Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Center for Advancing Translational Science (NCATS TLTR000049)
  • National Institutes of Health (NIH DC02058, NIH R21NS096642, CHDI #A-11872)
  • Chicago Biomedical Consortium (Award #085740)
  • National Science Foundation (DMR-1157490)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Keywords
Huntington's disease, R6/2 mice, axonal degeneration, white matter integrity, diffusion tensor imaging, anomalous diffusion, continuous time random walk, fractional anisotropy, corpus callosum, astrocyte activation, axon ultrastructure, high-field MRI
MeSH terms
Animals, Axons, Corpus Callosum, Female, Huntington Disease, Magnetic Resonance Imaging, Male, Microscopy, Fluorescence, Myelin Sheath, Anisotropy, Mice, Diffusion Tensor Imaging, White Matter

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