Demyelination increases radial diffusivity in corpus callosum of mouse brain
Abstract
Myelin damage, as seen in multiple sclerosis (MS) and other demyelinating diseases, impairs axonal conduction and can also be associated with axonal degeneration. Accurate assessments of these conditions may be highly beneficial in evaluating and selecting therapeutic strategies for patient management. Recently, an analytical approach examining diffusion tensor imaging (DTI) derived parameters has been proposed to assess the extent of axonal damage, demyelination, or both. The current study uses the well-characterized cuprizone model of experimental demyelination and remyelination of corpus callosum in mouse brain to evaluate the ability of DTI parameters to detect the progression of myelin degeneration and regeneration. Our results demonstrate that the extent of increased radial diffusivity reflects the severity of demyelination in corpus callosum of mouse brain affected by cuprizone treatment. Subsequently, radial diffusivity decreases with the progression of remyelination. Furthermore, radial diffusivity changes were specific to the time course of changes in myelin integrity as distinct from axonal injury, which was detected by betaAPP immunostaining and shown to be most extensive prior to demyelination. Radial diffusivity offers a specific assessment of demyelination and remyelination, as distinct from acute axonal damage.
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Decreased axial diffusivity in 5xFAD;APOE4 mice suggests axonal injury or degeneration.
“Because axial diffusivity reflects axonal integrity, the decreased values in 5xFAD;APOE4 mice suggest axonal injury or degeneration. 52”
From Apolipoprotein ε4 exacerbates white matter impairment in a mouse model of Aβ amyloidosis by decreasing actively myelinating oligodendrocytes (2025) · cites this paper as [52]
Increased radial diffusivity in 5xFAD;APOE4 mice suggests myelin loss.
“Because radial diffusivity reflects a magnitude of water diffusion perpendicular to axonal fibers, our data suggest that 5xFAD;APOE4 mice had myelin loss. 52”
From Apolipoprotein ε4 exacerbates white matter impairment in a mouse model of Aβ amyloidosis by decreasing actively myelinating oligodendrocytes (2025) · cites this paper as [52]
Demyelination and neuroinflammation together may drive microstructural disorganization.
“Conversely, negative correlations of MBP with radial diffusivity (Figure S4B) and isotropic volume fraction (Figure S4C), as well as the positive correlation between IBA1 and radial diffusivity (Figure S4F), highlight that demyelination and neuroinflammation together may drive microstructural disorganization. 52”
From Apolipoprotein ε4 exacerbates white matter impairment in a mouse model of Aβ amyloidosis by decreasing actively myelinating oligodendrocytes (2025) · cites this paper as [52]
Myelin loss may loosen axonal sheaths, enhancing perpendicular diffusion of water, leading to lower fractional anisotropy.
“Mechanistically, myelin loss may loosen axonal sheaths, enhancing perpendicular diffusion of water, leading to 52 lower fractional anisotropy.”
From Apolipoprotein ε4 exacerbates white matter impairment in a mouse model of Aβ amyloidosis by decreasing actively myelinating oligodendrocytes (2025) · cites this paper as [52]
Axial diffusivity (AD) has been linked to axonal pathology.
“While axial diffusivity (AD) has been linked to axonal pathology, radial diffusivity (RD) has been suggested as a surrogate biomarker associated with the level of white matter myelination [1–3].”
From Differentiating axonal loss and demyelination in chronic MS lesions: A novel approach using single streamline diffusivity analysis (2021) · cites this paper as [1]
Radial diffusivity (RD) has been suggested as a surrogate biomarker associated with the level of white matter myelination.
“While axial diffusivity (AD) has been linked to axonal pathology, radial diffusivity (RD) has been suggested as a surrogate biomarker associated with the level of white matter myelination [1–3].”
From Differentiating axonal loss and demyelination in chronic MS lesions: A novel approach using single streamline diffusivity analysis (2021) · cites this paper as [1]
Greater radial diffusivity indicates more severe demyelination or dysmyelination.
“with greater RD indicating more severe of either of the former (Song et al., 2005; Wozniak and Lim 2006)”
From Substance abuse and white matter: Findings, limitations, and future of diffusion tensor imaging research (2019) · cites this paper as Song et al., 2005
Increases in axial diffusivity may indicate axonal degradation, whereas decreases in axial diffusivity are often linked to healthy brain maturation.
“AD increases potentially indicate axonal degradation (Song et al., 2005), while AD decreases are often associated with healthy brain maturation (Tamnes et al., 2010).”
From Substance abuse and white matter: Findings, limitations, and future of diffusion tensor imaging research (2019) · cites this paper as Song et al., 2005
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- Authors
- Song, S.-K., Yoshino, J., Le, T. Q., Lin, S.-J., Sun, S.-W., Cross, A. H., & Armstrong, R. C.
- Affiliations
- Washington University in St. Louis (US)
- Uniformed Services University of the Health Sciences (US)
- Corresponding author
- Song, Sheng-Kwei
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 26
- Issue
- 1
- Pages
- 132-140
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W2025047388
- Cited by
- 1,658
- References
- 35
- Citations by year
- 2026: 36 · 2025: 50 · 2024: 46 · 2023: 54 · 2022: 75 · 2021: 87 · 2020: 98 · 2019: 114 · 2018: 90 · 2017: 100 · 2016: 107 · 2015: 98 · 2014: 122 · 2013: 109 · 2012: 105
- FWCI
- 27.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Washington (R24-CA83060)
- National Multiple Sclerosis Society (CA 1012-A-13, RG 3376-A-2/1)
- Alzheimer’s Disease Research Center, University of Washington
- National Institutes of Health (NS39293, AG05681)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- demyelination, radial diffusivity, corpus callosum, cuprizone, remyelination, diffusion tensor imaging, axonal injury, myelin integrity, multiple sclerosis, mouse model
- MeSH terms
- Algorithms, Amidines, Animals, Axons, Brain, Brain Chemistry, Chelating Agents, Corpus Callosum, Cuprizone, Demyelinating Diseases, Histocytochemistry, Image Interpretation, Computer-Assisted, Male, Mice, Inbred C57BL, Myelin Sheath, Periodic Acid-Schiff Reaction, Amyloid beta-Peptides, Tissue Fixation, Diffusion Magnetic Resonance Imaging, Mice
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