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Cited by 2,582Advanced Neuroimaging Techniques and ApplicationsAdvanced MRI Techniques and ApplicationsMultiple Sclerosis Research Studies

Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water

Song, Sheng-Kwei, Sun, Shu-Wei, Ramsbottom, Michael J., Chang, Chen, Russell, John, Cross, Anne H.·2002·NeuroImage
DOI 10.1006/nimg.2002.1267
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Abstract

Myelin loss and axonal damage are both observed in white matter injuries. Each may have significant impact on the long-term disability of patients. Currently, there does not exist a noninvasive biological marker that enables differentiation between myelin and axonal injury. We describe herein the use of magnetic resonance diffusion tensor imaging (DTI) to quantify the effect of dysmyelination on water directional diffusivities in brains of shiverer mice in vivo. The principal diffusion eigenvalues of eight axonal fiber tracts that can be identified with certainty on DTI maps were measured. The water diffusivity perpendicular to axonal fiber tracts, lambda(perpendicular), was significantly higher in shiverer mice compared with age-matched controls, reflecting the lack of myelin and the increased freedom of cross-fiber diffusion in white matter. The water diffusivity parallel to axonal fiber tracts, lambda(parallel), was not different, which is consistent with the presence of intact axons. It is clear that dysmyelination alone does not impact lambda(parallel). The presence of intact axons in the setting of incomplete myelination was confirmed by electron microscopy. Although further validation is still needed, our finding suggests that changes in lambda(perpendicular) and lambda(parallel) may potentially be used to differentiate myelin loss versus axonal injury.

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Crossref · 10.1006/nimg.2002.1267

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  • DTI successfully detects axon and myelin injury through decreased axial diffusivity and increased radial diffusivity in animal models of CNS diseases and injuries.

    “Diffusion tensor imaging (DTI) successfully detects axon and myelin injury through decreased axial diffusivity (λ∥, parallel to white matter tract) and increased radial diffusivity (λ⊥, perpendicular to white matter tract) in animal models of central nervous system (CNS) diseases and injuries (Song et al., 2002, Kim et al., 2006, Sun et al., 2006, DeBoy et al., 2007).”

    From Quantifying white matter tract diffusion parameters in the presence of increased extra-fiber cellularity and vasogenic edema (2014) · cites this paper as Song et al., 2002

  • Recent studies using animal models suggested that measures of directional diffusivity other than FA may be able to distinguish between axonal degeneration (increased axial diffusivity; normal radial diffusivity) and loss of myelin per se, at least in early phase of myelin breakdown (increased radial diffusivity; normal axial diffusivity).

    “Recent studies using animal models suggested that measures of directional diffusivity other than FA may be able to distinguish between axonal degeneration (increased axial diffusivity; normal radial diffusivity) (Song et al., 2003) and loss of myelin per se, at least in the early phase of myelin breakdown (increased radial diffusivity; normal axial diffusivity) (Song et al., 2002).”

    From Diffusion tensor imaging of post mortem multiple sclerosis brain (2007) · cites this paper as Song et al., 2002

  • The reduction in AxD during acute axonal degeneration is transient and eventually increases relative to control subjects.

    “This reduction is transient, though and eventually increases relative to control subjects 56, 58.”

    From Amyloid-beta induced retrograde axonal degeneration in a mouse tauopathy model (2019) · cites this paper as [58]

  • RD is considered to be sensitive to the degree of myelination and thus was expected to provide a significant negative correlation with MBP.

    “This was unexpected for the scalar metric RD, which is considered to be sensitive to the degree of myelination and thus was expected to provide a significant negative correlation (Song et al., 2002; Sun et al., 2006a, 2006b).”

    From The role of myelination in measures of white matter integrity: Combination of diffusion tensor imaging and two-photon microscopy of CLARITY intact brains (2017) · cites this paper as Song et al., 2002

  • The association of RD to myelination has been previously studied in some of these same WM structures, such as the corpus collosum and anterior commissure, but many other WM structures analyzed here have not been examined previously.

    “The association of RD to myelination has been previously studied in some of these same WM structures, such as the corpus collosum and anterior commissure (Song et al., 2002), however, many other WM structures analyzed here have not been examined previously.”

    From The role of myelination in measures of white matter integrity: Combination of diffusion tensor imaging and two-photon microscopy of CLARITY intact brains (2017) · cites this paper as Song et al., 2002

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Authors
Song, S.-K., Sun, S.-W., Ramsbottom, M. J., Chang, C., Russell, J., & Cross, A. H.
Affiliations
  • Washington University in St. Louis (US)
  • Institute of Biomedical Sciences, Academia Sinica (TW)
Corresponding author
Song, Sheng-Kwei
ORCID
Venue
NeuroImage
Publisher
Elsevier BV
Published
2002-11
Volume
17
Issue
3
Pages
1429-1436
ISSN
1053-8119 (ISSN-L)
DOI
10.1006/nimg.2002.1267
OpenAlex
W2047152236
Cited by
2,582
References
40
Citations by year
2026: 44 · 2025: 70 · 2024: 78 · 2023: 85 · 2022: 111 · 2021: 129 · 2020: 113 · 2019: 184 · 2018: 140 · 2017: 152 · 2016: 178 · 2015: 199 · 2014: 197 · 2013: 194 · 2012: 160
FWCI
11.47
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • NeuroImage (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (R24CA083060, 1 R24 CA83060-01)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords
dysmyelination, demyelination, axonal injury, diffusion tensor imaging, shiverer mice, white matter injury, brain MRI biomarkers
MeSH terms
Animals, Brain, Brain Diseases, Diagnosis, Differential, Disease Models, Animal, Heterozygote, Homozygote, Humans, Image Processing, Computer-Assisted, Mice, Neurologic Mutants, Nerve Fibers, Myelinated, Hereditary Central Nervous System Demyelinating Diseases, Diffuse Axonal Injury, Diffusion Magnetic Resonance Imaging, Mice

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