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

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...

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Bibliographic Details
Published in:PloS one Vol. 16; no. 1; p. e0244766
Main Authors: Klistorner, Samuel, Barnett, Michael H., Wasserthal, Jakob, Yiannikas, Con, Barton, Joshua, Parratt, John, You, Yuyi, Graham, Stuart L., Klistorner, Alexander
Format: Journal Article
Language:English
Published: United States Public Library of Science 06.01.2021
Public Library of Science (PLoS)
Subjects:
Adult
Alzheimer's disease
Axons - metabolism
Axons - pathology
Biology and Life Sciences
Brain research
Care and treatment
Chronic Disease
Clinical trials
Degeneration
Demyelination
Development and progression
Diffusion Magnetic Resonance Imaging
Diffusivity
Female
Health sciences
Humans
Lesions
Male
Medical research
Medicine and Health Sciences
Methods
Middle Aged
Multiple sclerosis
Multiple Sclerosis - pathology
Nerve Fibers, Myelinated - pathology
Nervous system
Neuroprotection
Recurrence
Research and Analysis Methods
Scleroderma
White Matter - diagnostic imaging
White Matter - pathology
Australia
Sydney New South Wales Australia
New South Wales Australia
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary: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.
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Competing Interests: Study was partially funded by Novartis. This funds was used exclusively for MRI data acquisition. None of the authors were employed or recieved consultancy from commercial entity or participated in patents, products development or marketing. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0244766