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Cited by 11Advanced Neuroimaging Techniques and ApplicationsMultiple Sclerosis Research StudiesAdvanced MRI Techniques and Applications

Diffusivity in the core of chronic multiple sclerosis lesions

Open access
Klistorner, Alexander, Wang, Chenyu, Yiannikas, Con, Parratt, John, Barton, Joshua, You, Yuyi, Graham, Stuart L., Barnett, Michael H.·2018·PLOS ONE
DOI 10.1371/journal.pone.0194142PMC PMC5918637
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Abstract

BACKGROUND: Diffusion tensor imaging (DTI) has been suggested as a potential biomarker of disease progression, neurodegeneration and de/remyelination in MS. However, the pathological substrates that underpin alterations in brain diffusivity are not yet fully delineated. We propose that in highly cohesive fiber tracts: 1) a relative increase in parallel (axial) diffusivity (AD) may serve as a measure of increased extra-cellular space (ESC) within the core of chronic MS lesions and, as a result, may provide an estimate of the degree of tissue destruction, and 2) the contribution of the increased extra-cellular water to perpendicular (radial) diffusivity (RD) can be eliminated to provide a more accurate assessment of membranal (myelin) loss. OBJECTIVE: The purpose of this study was to isolate the contribution of extra-cellular water and demyelination to observed DTI indices in the core of chronic MS lesions, using the OR as an anatomically cohesive tract. METHOD: Pre- and post-gadolinium (Gd) enhanced T1, T2 and DTI images were acquired from 75 consecutive RRMS patients. In addition, 25 age and gender matched normal controls were imaged using an identical MRI protocol (excluding Gd). The optic radiation (OR) was identified in individual patients using probabilistic tractography. The T2 lesions were segmented and intersected with the OR. Average eigenvalues were calculated within the core of OR lesions mask. The proportion of extra-cellular space (ECS) within the lesional core was calculated based on relative increase of AD, which was then used to normalise the perpendicular eigenvalues to eliminate the effect of the expanded ECS. In addition, modelling was implemented to simulate potential effect of various factors on lesional anisotropy. RESULTS: Of 75 patients, 41 (55%) demonstrated sizable T2 lesion volume within the ORs. All lesional eigenvalues were significantly higher compared to NAWM and controls. There was a strong correlation between AD and RD within the core of OR lesions, which was, however, not seen in OR NAWM of MS patients or normal controls. In addition, lesional anisotropy (FA) was predominantly driven by the perpendicular diffusivity, while in NAWM and in OR of normal controls all eigenvectors contributed to variation in FA. Estimated volume of ECS component constituted significant proportion of OR lesional volume and correlated significantly with lesional T1 hypointensity. While perpendicular diffusivity dropped significantly following normalisation, it still remained higher compared with diffusivity in OR NAWM. The "residual" perpendicular diffusivity also showed a substantial reduction of inter-subject variability. Both observed and modelled diffusion data suggested anisotropic nature of water diffusion in ESC. In addition, the simulation procedure offered a possible explanation for the discrepancy in relationship between eigenvalues and anisotropy in lesional tissue and NAWM. CONCLUSION: This paper presents a potential technique for more reliably quantifying the effects of neurodegeneration (tissue loss) versus demyelination in OR MS lesions. This may provide a simple and effective way for applying single tract diffusion analysis in MS clinical trials, with particular relevance to pro-remyelinating and neuroprotective therapeutics.

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  • In highly coherent fiber tracts, ΔAD within chronic MS lesions reflects axonal loss, while ΔRD is related to both axonal loss and demyelination in survived axons.

    “Our previous work suggests that, in highly coherent fiber tracts, ΔAD within chronic MS lesions reflects axonal loss, while ΔRD is related to both axonal loss and demyelination in survived axons [24].”

    From Differentiating axonal loss and demyelination in chronic MS lesions: A novel approach using single streamline diffusivity analysis (2021) · cites this paper as [24]

  • The maximum AD and RD values in chronic MS lesions within highly coherent fiber tracts indicate some degree of diffusion restriction and residual anisotropy even in severely damaged white matter, attributed to lesional gliosis and axonal tortuosity.

    “We previously reported that in chronic MS lesions situated within highly coherent fiber tracts the maximum AD and RD values do not exceed 2.5 μm2/ms and 1.7 μm2/ms respectively [24], indicating some degree of diffusion restriction and residual anisotropy even in severely damaged white matter, which was attributed to lesional gliosis and axonal tortuosity [8–10, 25].”

    From Differentiating axonal loss and demyelination in chronic MS lesions: A novel approach using single streamline diffusivity analysis (2021) · cites this paper as [24]

  • In chronic MS lesions situated within highly coherent fiber tracts, the maximum AD and RD values do not exceed 2.5 μm2/ms and 1.7 μm2/ms respectively.

    “We previously reported that in chronic MS lesions situated within highly coherent fiber tracts the maximum AD and RD values do not exceed 2.5 μm2/ms and 1.7 μm2/ms respectively [24], indicating some degree of diffusion restriction and residual anisotropy even in severely damaged white matter, which was attributed to lesional gliosis and axonal tortuosity [8–10, 25].”

    From Differentiating axonal loss and demyelination in chronic MS lesions: A novel approach using single streamline diffusivity analysis (2021) · cites this paper as [24]

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Sorted by citations

Authors
Klistorner, A., Wang, C., Yiannikas, C., Parratt, J., Barton, J., You, Y., Graham, S. L., & Barnett, M. H.
Affiliations
  • The University of Sydney (AU)
  • Royal North Shore Hospital (AU)
  • Macquarie University (AU)
Corresponding author
  • Klistorner, Alexander
  • Wang, Chenyu
  • Yiannikas, Con
  • Parratt, John
  • Barton, Joshua
  • You, Yuyi
  • Graham, Stuart L.
  • Barnett, Michael H.
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2018-04-25
Volume
13
Issue
4
Pages
e0194142
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0194142
PMC
PMC5918637
OpenAlex
W2801797891
Cited by
11
References
10
Citations by year
2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1
FWCI
0.86
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Multiple Sclerosis Society
  • Novartis Pharmaceuticals Corporation
  • Sydney Medical School Foundation
  • National Health and Medical Research Council
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
multiple sclerosis, optic radiation, demyelination, axial diffusivity, radial diffusivity, fractional anisotropy, gadolinium enhancement, T1 hypointensity, disease progression biomarkers, relapsing-remitting multiple sclerosis, white matter lesions, diffusion modeling
MeSH terms
Algorithms, Computer Simulation, Female, Humans, Image Processing, Computer-Assisted, Male, Multiple Sclerosis, Biomarkers, Diffusion Tensor Imaging

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