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Cited by 10Advanced Neuroimaging Techniques and ApplicationsMultiple Sclerosis Research StudiesAdvanced MRI Techniques and Applications

Differentiating axonal loss and demyelination in chronic MS lesions: A novel approach using single streamline diffusivity analysis

Open access
Klistorner, Samuel, Barnett, Michael H., Wasserthal, Jakob, Yiannikas, Con, Barton, Joshua, Parratt, John, You, Yuyi, Graham, Stuart L. +1 more·2021·PLOS ONE
DOI 10.1371/journal.pone.0244766PMC PMC7787472
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Abstract

We describe a new single-streamline based approach to analyse diffusivity within chronic MS lesions. We used the proposed method to examine diffusivity profiles in 30 patients with relapsing multiple sclerosis and observed a significant increase of both RD and AD within the lesion core (0.38+/-0.09 μm 2/ms and 0.30+/-0.12 μm 2/ms respectively, p<0.0001 for both) that gradually and symmetrically diminished away from the lesion. T1-hypointensity derived axonal loss correlated highly with ΔAD (r = 0.82, p<0.0001), but moderately with ΔRD (r = 0.60, p<0.0001). Furthermore, the trendline of the ΔAD vs axonal loss intersected both axes at zero indicating close agreement between two measures in assessing the degree of axonal loss. Conversely, the trendline of the ΔRD function demonstrated a high positive value at the zero level of axonal loss, suggesting that even lesions with preserved axonal content exhibit a significant increase of RD. There was also a significant negative correlation between the level of preferential RD increase (ΔRD-ΔAD) in the lesion core and the degree of axonal damage (r = -0.62, p<0.001), indicating that ΔRD dominates in cases with milder axonal loss. Modelling diffusivity changes in the core of chronic MS lesions based on the direct proportionality of ΔAD with axonal loss and the proposed dual nature of ΔRD yielded results that were strikingly similar to the experimental data. Evaluation of lesions in a sizable cohort of MS patients using the proposed method supports the use of ΔAD as a marker of axonal loss; and the notion that demyelination and axonal loss independently contribute to the increase of RD in chronic MS lesions. The work highlights the importance of selecting appropriate patient cohorts for clinical trials of pro-remyelinating and neuroprotective therapeutics.

AI snapshot

Written from the paper’s full text.

TL;DR

The paper describes a single-streamline diffusivity analysis for chronic MS lesions and applies it to 30 RRMS patients, finding that ΔAD tracks T1-hypointensity-derived axonal loss while ΔRD reflects both demyelination and axonal loss. Modelling supports ΔAD as an axonal-loss marker and a dual origin of RD increase.

Key findings

  • In 30 RRMS patients with 314 lesions, the lesion core showed increased ΔRD (0.38±0.09 μm²/ms) and ΔAD (0.30±0.12 μm²/ms) versus matched non-lesional fibers (p<0.0001 for both), diminishing symmetrically away from the lesion.
  • T1-hypointensity-derived axonal loss in the core averaged 36.1±11.6% (range 22–66%); ΔAD correlated highly with axonal loss (r=0.82, p<0.0001), while ΔRD correlated moderately (r=0.60, p<0.0001). The ΔAD trendline intersected both axes at zero, whereas the ΔRD trendline had a residual value of 0.20 μm²/ms at zero axonal loss.
  • Preferential RD increase (ΔRD−ΔAD) negatively correlated with axonal loss (r=−0.62, p<0.001), indicating ΔRD dominates in milder axonal loss; modelling based on direct ΔAD proportionality and dual-nature ΔRD yielded results similar to experimental data.
  • In the rim, axonal loss was 21.2±6.0% (range 13–34%), with ΔAD r=0.73 (p<0.0001), ΔRD r=0.39 (p=0.026), and residual ΔRD of 0.15 μm²/ms at zero axonal loss.

Methods

  • Single-streamline approach: each lesional streamline was limited to 5 mm on each side of the lesion and matched to at least 5 adjacent non-lesional streamlines of similar length and orientation from the same tract; ΔAD and ΔRD were computed voxel-by-voxel and averaged into patient-specific Personalized Lesional Diffusivity profiles.
  • Thirty consecutive RRMS patients (McDonald 2010 criteria) underwent 3T MRI with T1, FLAIR, and diffusion-weighted imaging; lesions >100 mm³ were analyzed, Gd-enhancing lesions were excluded, and TractSeg identified 72 tracts with 2000 streamlines per tract. T1 hypointensity normalized by NAWM was used to estimate axonal loss.
  • Statistical analysis used Pearson correlation, Student t-test, Shapiro-Wilk test, and SPSS 22.0, with p<0.05 considered significant.

Limitations

  • Stated: voxel-based analysis may be more suited for cross-sectional tissue-loss measurement, especially with severe axonal loss; partial voluming from DTI resampling is possible; remyelination monitoring is limited to lesions with relatively preserved axons because when neurodegeneration exceeds 30–40%, ΔRD is mainly driven by axonal loss; and centrally located voxels in large lesions are less likely to be included due to constraints on non-lesional fiber selection.
  • Stated: the single-fiber method is biased toward voxels with better axonal preservation—only 33% of lesional voxels contained a streamline, analyzed voxels had less T1 hypointensity (592 vs 751 units, p<0.001), and the proportion of analyzed voxels negatively correlated with lesion T1 hypointensity (r=−0.53, p=0.002).
  • Evident from the text: axonal loss was inferred from T1 hypointensity rather than direct histopathology, so the reference measure is an imaging proxy.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0244766

Cites

27 of 27 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

14 of 22 cited sources checked · 9 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    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].”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [1] S.-K. Song, 2005, Demyelination increases radial diffusivity in corpus callosum of mouse brain, Neuroimage source
    • cites [2] E. C. Klawiter, 2011, Radial diffusivity predicts demyelination in ex vivo multiple sclerosis spinal cords, Neuroimage source
    • cites [3] V. a Janve, 2013, The radial diffusivity and magnetization transfer pool size ratio are sensitive markers for demyelination in a rat model of type III multiple sclerosis (MS) lesions, Neuroimage source
  • Premisecitation

    T1 hypointensity reflects the severity of axonal loss in MS lesions.

    “Previous studies have demonstrated that the degree of hypointensity on T1-weighted MR images (T1 hypointensity) reflects the severity of axonal loss in MS lesions [22, 23].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [22] A. A. A. van Walderveen, 1998, Histopathologic correlate of hypointense lesions on Tl-weighted spin-echo lesions in multiple sclerosis MRI, Neurology source
    • cites [23] P. a Brex, 2000, Lesion heterogeneity in multiple sclerosis: a study of the relations between appearances on T1 weighted images, T1 relaxation times, and metabolite concentrations, J. Neurol. Neurosurg. Psychiatry source

      The Results and Discussion (pages not provided) report lower tNAA in hypointense T1 lesions and an inverse correlation between tNAA and T1 relaxation time. But the paper treats tNAA as a surrogate for axonal density or function and says its reduction *may* reflect more extensive axonal damage; it does not establish that the degree of hypointensity directly measures the severity of axonal loss. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Premisecitation

    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].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [24] A. Klistorner, 2018, Diffusivity in the core of chronic multiple sclerosis lesions, PLoS One source
  • Premisecitation

    Voxel-based analysis utilising DTI models does not adequately estimate orientationally-sensitive diffusivity measures such as axial and radial diffusivity (AD and RD).

    “Therefore, apart from the limited area of white matter occupied by coherent fiber tracts, voxel-based analysis utilising DTI models does not adequately estimate orientationally-sensitive diffusivity measures, such as axial and radial diffusivity (AD and RD) [12, 13].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [12] S. Taipel, 2014, Fractional Anisotropy Changes in Alzheimer’s Disease Depend on the Underlying Fiber Tract Architecture: A Multiparametric DTI Study using Joint Independent Component Analysis, J. Alzheimer’s Dis. source
    • cites [13] C. A. M. Wheeler-Kingshott, 2009, About ‘Axial’ and ‘Radial’ Diffusivities, Mag Res Med source

      The Abstract and Discussion (page not available in our copy) explain that axial and radial diffusivity measures can be misleading in crossing-fiber and other complex regions when the principal eigenvector changes direction. The claim overstates this as a general failure of voxel-based DTI outside coherent tracts: the paper recommends checking eigenvector alignment to identify where comparisons are unreliable, rather than ruling out adequate estimation everywhere else. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Premisecitation

    The majority of white matter voxels are characterized by extensive crossing, kissing, bending or fanning of fibers.

    “The majority of white matter voxels are characterized by extensive crossing, kissing, bending or fanning of fibers [11].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [11] B. Jeurissen, 2013, Investigating the Prevalence of Complex Fiber Configurations in White Matter Tissue with Diffusion Magnetic Resonance Imaging, Hum. Brain Map source

      The In Vivo Estimation of Fiber Orientations section reports multiple orientations in about 90% of white-matter voxels using CSD and complex configurations in 63% using bedpostx, supporting the claim that a majority have complex fiber organization. The paper discusses bending and fanning, but these measurements do not establish how many voxels have each listed configuration, including kissing fibers, or that the configurations are extensive. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Classified as probably not a substantial claim. 8
  • May combine two claims. 11

  • Classified as probably not a substantial claim.

    Premisecitation

    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].”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [1] S.-K. Song, 2005, Demyelination increases radial diffusivity in corpus callosum of mouse brain, Neuroimage source
    • cites [2] E. C. Klawiter, 2011, Radial diffusivity predicts demyelination in ex vivo multiple sclerosis spinal cords, Neuroimage source
    • cites [3] V. a Janve, 2013, The radial diffusivity and magnetization transfer pool size ratio are sensitive markers for demyelination in a rat model of type III multiple sclerosis (MS) lesions, Neuroimage source

  • May combine two claims.

    Premisecitation

    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].”
    Quote in the paperSubstantial claim2 of 5 sources checked
    • cites [24] A. Klistorner, 2018, Diffusivity in the core of chronic multiple sclerosis lesions, PLoS One source
    • cites [8] H. Zhang, 2012, NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain, Neuroimage source
    • cites [9] Y. Assaf, 2004, New Modeling and Experimental Framework to Characterize Hindered and Restricted Water Diffusion in source
    • cites [10] E. Panagiotaki, 2012, Compartment models of the diffusion MR signal in brain white matter: A taxonomy and comparison, Neuroimage source
    • cites [25] M. D. Budde, 2011, The contribution of gliosis to diffusion tensor anisotropy and tractography following traumatic brain injury: validation in the rat using Fourier analysis of stained tissue sections, Brain source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    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].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [24] A. Klistorner, 2018, Diffusivity in the core of chronic multiple sclerosis lesions, PLoS One source

  • Classified as probably not a substantial claim.

    Premisecitation

    We recently reported an elevation of AD in the distal part of the lesional fibers in highly coherent fiber tracts (optic radiation).

    “We recently reported an elevation of AD in the distal part of the lesional fibers in highly coherent fiber tracts (optic radiation) [17].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [17] A. Klistorner, 2015, Decoding diffusivity in multiple sclerosis: Analysis of optic radiation lesional and non-lesional white matter, PLoS One source

  • May combine two claims.

    Findingown data

    In the model, the increase in RD is larger at low levels of axonal loss, and ΔRD and ΔAD become equal as axonal degeneration advances.

    “Fig 7b demonstrates the predicted slopes of ΔRD and ΔAD vs axonal loss. While the increase in RD is larger at low levels of axonal loss, ΔRD and ΔAD become equal as axonal degeneration advances.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Increase in radial diffusivity can be modelled as a sum of demyelination-related ΔRDdem and axonal loss-related ΔRDax changes.
    • The authors state this as an assumption: Axonal loss-related ΔRDax can be calculated as a replacement of lost axonal tissue by extra-cellular water.

  • May combine two claims.

    Findingown data

    Inside the lesion (core and rim), averaged ΔRD is larger than ΔAD; in the extra-lesional part, ΔAD dominates.

    “While inside the lesion (both in the core and in the rim) averaged ΔRD was larger than ΔAD, this relationship was reversed in the extra-lesional part of PLD profile, where ΔAD dominated.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Our analysis revealed a substantial increase of both AD and RD in the lesion core, which diminished towards the lesion rim.

    “Our analysis revealed a substantial increase of both AD and RD in the lesion core, which diminished towards the lesion rim.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Considerable variability of the increase of lesional diffusivity was observed between patients, although the magnitude of ΔRD was typically larger.

    “Considerable variability of the increase of lesional diffusivity was observed between patients, although the magnitude of ΔRD was typically larger.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    ΔRD dominates in cases with milder axonal loss (where majority of axons still survive but remain demyelinated), but ΔAD and ΔRD approach parity as axonal damage advances.

    “The result, shown in Fig 6, demonstrates significant negative correlation between the level of preferential RD increase and the degree of (T1 hypointensity-derived) axonal destruction (r = -0.62, p<0.001), indicating that ΔRD dominates in cases with milder axonal loss (where majority of axons still survive, but remain demyelinated), but ΔAD and ΔRD approach parity as axonal damage advances.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The contribution of demyelination to ΔRD is expected to decrease proportionally with attrition of demyelinated axons as axonal loss progresses.

    “However, since the number of (demyelinated) axons decline as axonal loss progresses the contribution of demyelination to ΔRD is also expected to decrease proportionally with attrition of demyelinated axons.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Study design and conductnone given

    The current single fiber-based approach substantially minimizes the effect of crossing fibers.

    “Since the current approach substantially minimizes the effect of crossing fibers, we hypothesized that diffusion modelling within coherent fiber tracts can be extended to lesions involving any region of the brain.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Voxels with better axonal preservation have a higher chance of containing tractography streamlines and are preferentially selected for single fiber-based analysis.

    “indicating that voxels with better axonal preservation have higher chance of containing tractography streamlines and, therefore, are preferentially selected for single fiber-based analysis.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Study design and conductnone given

    The proposed approach was designed to minimise the impact of crossing fibers on the inter-voxel variability of orientation-selective diffusivity measures and to eliminate the confounding effect of irregular MS lesion morphology, thereby improving the detection of pathology-specific DTI changes in MS lesions.

    “The proposed approach was designed to minimise the impact of crossing fibers on the inter-voxel variability of orientation-selective diffusivity measures and to eliminate the confounding effect of irregular MS lesion morphology, thereby improving the detection of pathology-specific DTI changes in MS lesions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Differences from the lesion core are likely related to less severe axonal loss and a variable degree of remyelination between patients, both characteristic features of the lesion edge.

    “Differences from the lesion core are likely be related to less severe axonal loss and a variable degree of remyelination between patients, both characteristic features of the lesion edge.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    Another limitation is potential partial voluming effect caused by resampling of DTI images.

    “Another limitation is related to potential partial voluming effect caused by resampling of DTI images.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The effect of demyelination dominates in cases of mild axonal destruction (where majority of axons still survive, but remain demyelinated), while neurodegeneration is a primary cause of RD increase in more destructive lesions.

    “While the effect of demyelination dominates in cases of mild axonal destruction (where majority of axons still survive, but remain demyelinated), neurodegeneration is a primary cause of RD increase in more destructive lesions.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The proposed approach is beneficial for longitudinal analysis of changes affecting survived axons (such as remyelination).

    “While the proposed approach is beneficial for longitudinal analysis of changes affecting survived axons (such as remyelination), voxel-based analysis may be more suited for measurement of tissue loss in cross-sectional comparison studies, especially when axonal loss is severe.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Remyelination-induced change of diffusivity can only occur in survived (existing) axons.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    This limitation is probably applicable to all diffusion-based studies of remyelination.

    “This limitation is probably applicable to all diffusion-based studies of remyelination.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Remyelination-induced change of diffusivity can only occur in survived (existing) axons.
18 of 18

  • The authors state this as an assumption.

    Normal-appearing white matter (NAWM) represents intact brain tissue with no axonal loss.

    “Based on assumptions that NAWM represents intact (i.e. no axonal loss) brain tissue”

  • The authors state this as an assumption.

    Cerebrospinal fluid (CSF) characterises brain tissue totally devoid of axons.

    “while CSF characterises brain tissue totally devoid of axons”

  • The authors state this as an assumption.

    The intensity of T1 signal is inversely proportional to the degree of axonal loss.

    “and the intensity of T1 signal is inversely proportional to the degree of axonal loss”

  • The authors state this as an assumption.

    ΔAD is directly proportional to axonal loss.

    “Modelling diffusivity changes in the core of chronic MS lesions based on the direct proportionality of ΔAD with axonal loss and the proposed dual nature of ΔRD yielded results that were strikingly similar to the experimental data.”

  • The paper relies on this without support.

    MS lesions are rarely confined within a single coherent fiber tract.

    “However, MS lesions are rarely confined within a single (coherent) fiber tract.”

  • The paper relies on this without support.

    Multiple crossing tracts frequently traverse individual lesions in different directions.

    “Rather, multiple crossing tracts frequently traverse individual lesions (or part thereof) in different directions”

  • The paper relies on this without support.

    DTI's practical application, including use in clinical trials, is limited by inherent dependency on fiber coherency and complexity of the underlying brain structure.

    “While DTI was suggested as a potential in-vivo biomarker of axonal loss and demyelination in MS more than a decade ago, its practical application, including use in clinical trials, is limited by inherent dependency on fiber coherency and complexity of the underlying brain structure.”

  • The paper relies on this without support.

    T1-hypointensity is linked to the degree of axonal destruction.

    “Since T1-hypointensity is linked to the degree of axonal destruction, it is reasonable to assume that ΔAD derived using the single fiber-based approach is also strongly associated with axonal loss in MS lesions.”

  • The authors state this as an assumption.

    In hypothetical lesions with fully preserved axons, the increase of RD is entirely driven by demyelination.

    “Assuming that in hypothetical lesions with fully preserved axons, the increase of RD is entirely driven by demyelination, the intersection of the ΔRD trendline with the zero value of the (horizontal) axonal loss axis (Fig 5b) was used to identify the value of demyelination-related increase of RD (ΔRDdem), which was equal to 0.2 μm2/ms.”

  • The authors state this as an assumption.

    Increase in radial diffusivity can be modelled as a sum of demyelination-related ΔRDdem and axonal loss-related ΔRDax changes.

    “Increase in radial diffusivity was modelled as a sum of demyelination-related ΔRDdem and axonal loss-related ΔRDax changes:”

  • The authors state this as an assumption.

    Axonal loss-related ΔRDax can be calculated as a replacement of lost axonal tissue by extra-cellular water.

    “Axonal loss-related ΔRDax was calculated as a replacement of lost axonal tissue by extra-cellular water: Where:”

  • The authors state this as an assumption.

    The increase in axial diffusivity (ΔAD) in chronic MS lesions can be estimated based on replacement of lost axonal tissue by extra-cellular water.

    “Based on replacement of lost axonal tissue by extra-cellular water, we previously estimated the increase in axial diffusivity (ΔAD) in chronic MS lesions [24].”

  • The paper relies on this without support.

    Remyelination-induced change of diffusivity can only occur in survived (existing) axons.

    “This is particularly applicable to measurement of remyelination in MS lesions, where remyelination-induced change of diffusivity can only occur in survived (existing) axons.”
13 of 13

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • T1-intensity reduction is described in the opposite direction to its reported values

    Minor

    The stated reduction is 592 units in analysed voxels and 751 units in the rest of the lesion, so it is less prominent-not more prominent-in analysed voxels. The later statement that analysed voxels have greater T1 signal agrees with the numbers, not with the stated direction.

  • RD model parameter is labeled as an AD average

    Minor

    The modelling definitions assign different values to what both descriptions call average AD in non-lesional fibers. The 0.59 parameter is named RDnormal tissue, contradicting its description as AD.

  • A negative correlation is reported with a positive coefficient

    Minor

    A correlation coefficient of 0.85 denotes a positive relationship, contrary to the sentence's description of a strong negative relationship.

3 of 3

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Authors
Klistorner, S., Barnett, M. H., Wasserthal, J., Yiannikas, C., Barton, J., Parratt, J., You, Y., Graham, S. L., & Klistorner, A.
Affiliations
  • The University of Sydney (AU)
  • German Cancer Research Center (DE)
  • Royal North Shore Hospital (AU)
  • Macquarie University (AU)
Corresponding author
Klistorner, Alexander
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2021-01-06
Volume
16
Issue
1
Pages
e0244766
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0244766
PMC
PMC7787472
OpenAlex
W3119276788
Semantic Scholar
49bbeed860b14dc7e17a11ed6c17738282b386aa
Cited by
10
References
26
Citations by year
2024: 1 · 2022: 4 · 2021: 5
FWCI
1.22
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Multiple Sclerosis Society
  • Multiple Sclerosis Society
  • Sydney Eye Hospital Foundation
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, axonal loss, demyelination, axial diffusivity, radial diffusivity, T1 hypointensity, neuroprotection, remyelination
MeSH terms
Adult, Axons, Chronic Disease, Female, Humans, Male, Middle Aged, Multiple Sclerosis, Nerve Fibers, Myelinated, Recurrence, Diffusion Magnetic Resonance Imaging, White Matter

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