Perilesional neurodegenerative injury in multiple sclerosis: Relation to focal lesions and impact on disability

Clarke, Mitch; Lakhani, Dhairya A.; Wen, Sijin; Gao, Si; Smith, Seth A.; Dortch, Richard D.; Xu, Junzhong; Bagnato, Francesca

doi:10.1016/j.msard.2021.102738

Cited by 11 publications

(13 citation statements)

References 45 publications

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“…The strong periventricular MD gradient observed within chronic MS lesions raises the possibility that the previously reported CSF-related abnormality in NAWM may be driven by lesional changes (for instance, by Wallerian degeneration of the fibers transected at the lesion rim as a result of slow-burning inflammation 15 ). Therefore, to investigate whether the MD gradient in NAWM declines with increasing distance from the lesion border, we examined diffusivity change in five consecutive perilesional rings (each 2 voxel thick) expanding into NAWM.…”

Section: Resultsmentioning

confidence: 98%

The expansion and severity of chronic MS lesions follows a periventricular gradient

Klistorner

Barnett

Graham

et al. 2021

Preprint

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Background and Objectives: Expansion of chronic lesions in MS patients and recently described CSF-related gradient of tissue damage are linked to microglial activation. The aim of the current study was to investigate whether lesion expansion is associated with proximity to ventricular CSF spaces. Methods: Pre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion tensor images were acquired from 36 RRMS patients. Lesional activity was analysed between baseline and 48 months at different distances from the CSF using successive 1-mm thick concentric rings radiating from the ventricles. Results: Voxel-based analysis of the rate of lesion expansion demonstrated a clear periventricular gradient decreasing away from the ventricles. This was particularly apparent when lesions of equal diameter were analysed. Periventricular lesional tissue showed higher degree of tissue distraction at baseline that significantly increased during follow-up in rings close to CSF. This longitudinal change was proportional to degree of lesion expansion. Lesion-wise analysis revealed a gradual, centrifugal decrease in the proportion of expanding lesions from the immediate periventricular zone. Discussion: Our data suggest that chronic white matter lesions in close proximity to the ventricles are more destructive, show a higher degree of expansion at the lesion border and accelerated tissue loss in the lesion core.

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Section: Resultsmentioning

confidence: 98%

The expansion and severity of chronic MS lesions follows a periventricular gradient

Klistorner

Barnett

Graham

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…However, some studies did not find significant NAWM MPF differences between patients and controls ( Bagnato et al, 2018 ; McKeithan et al, 2019 ), probably due to methodological distinctions in acquisition protocols. MPF provided new insights into lesion pathology in MS enabling studies of demyelination heterogeneity ( Levesque et al, 2005 ; Clarke et al, 2021 ) and temporal evolution ( Giacomini et al, 2009 ; Levesque et al, 2010a ). Post-mortem MPF and histology studies of MS ( Schmierer et al, 2007 ; Bagnato et al, 2018 ) confirmed good agreement between demyelination and a reduced MPF.…”

Section: Literature Reviewmentioning

confidence: 99%

“…Post-mortem MPF and histology studies of MS ( Schmierer et al, 2007 ; Bagnato et al, 2018 ) confirmed good agreement between demyelination and a reduced MPF. The majority of MS studies utilized multipoint techniques with either off-resonance saturation ( Sled and Pike, 2001 ; Yarnykh, 2002 ; Tozer et al, 2003 , 2005 ; Davies et al, 2003 , 2004 ; Levesque et al, 2005 ; Narayanan et al, 2006 ; Schmierer et al, 2007 ; Cercignani et al, 2009 ; Giacomini et al, 2009 ; Levesque et al, 2010a ; Spano et al, 2010 ) or selective inversion-recovery preparation ( Bagnato et al, 2018 , 2020 ; McKeithan et al, 2019 ; Clarke et al, 2021 ) to obtain MPF maps. The single-point method ( Yarnykh, 2012 ) extended the area of MPF applications to GM ( Yarnykh et al, 2015 , 2018a ) and demonstrated strong associations of GM MPF with MS disability scales and disease phenotype ( Yarnykh et al, 2015 ).…”

Section: Literature Reviewmentioning

confidence: 99%

Macromolecular Proton Fraction as a Myelin Biomarker: Principles, Validation, and Applications

2022

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Macromolecular proton fraction (MPF) is a quantitative MRI parameter describing the magnetization transfer (MT) effect and defined as a relative amount of protons bound to biological macromolecules with restricted molecular motion, which participate in magnetic cross-relaxation with water protons. MPF attracted significant interest during past decade as a biomarker of myelin. The purpose of this mini review is to provide a brief but comprehensive summary of MPF mapping methods, histological validation studies, and MPF applications in neuroscience. Technically, MPF maps can be obtained using a variety of quantitative MT methods. Some of them enable clinically reasonable scan time and resolution. Recent studies demonstrated the feasibility of MPF mapping using standard clinical MRI pulse sequences, thus substantially enhancing the method availability. A number of studies in animal models demonstrated strong correlations between MPF and histological markers of myelin with a minor influence of potential confounders. Histological studies validated the capability of MPF to monitor both demyelination and re-myelination. Clinical applications of MPF have been mainly focused on multiple sclerosis where this method provided new insights into both white and gray matter pathology. Besides, several studies used MPF to investigate myelin role in other neurological and psychiatric conditions. Another promising area of MPF applications is the brain development studies. MPF demonstrated the capabilities to quantitatively characterize the earliest stage of myelination during prenatal brain maturation and protracted myelin development in adolescence. In summary, MPF mapping provides a technically mature and comprehensively validated myelin imaging technology for various preclinical and clinical neuroscience applications.

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“…The strong periventricular MD gradient observed within chronic MS lesions raises the possibility that the previously reported CSF-related abnormality in NAWM may be driven by lesional changes (for instance, by Wallerian degeneration of the fibres transected at the lesion rim as a result of slow-burning inflammation). 17 Therefore, to investigate whether the MD gradient in NAWM declines with increasing distance from the lesion border, we examined diffusivity change in five consecutive perilesional bands (each 2 voxels thick) expanding into NAWM.…”

Section: Resultsmentioning

confidence: 99%

The expansion and severity of chronic MS lesions follows a periventricular gradient

et al. 2022

View full text Add to dashboard Cite

Background and Objectives: Expansion of chronic lesions in multiple sclerosis (MS) patients and recently described cerebrospinal fluid (CSF)-related gradient of tissue damage are linked to microglial activation. The aim of this study was to investigate whether lesion expansion is associated with proximity to ventricular CSF spaces. Methods: Pre- and post-gadolinium three-dimensional (3D)-T1, 3D FLAIR and diffusion tensor images were acquired from 36 relapsing-remitting MS (RRMS) patients. Lesional activity was analysed between baseline and 48 months at different distances from the CSF using successive 1 mm thick concentric bands radiating from the ventricles. Results: Voxel-based analysis of the rate of lesion expansion demonstrated a clear periventricular gradient decreasing away from the ventricles. This was particularly apparent when lesions of equal diameter were analysed. Periventricular lesional tissue showed higher degree of tissue destruction at baseline that significantly increased during follow-up in bands close to CSF. This longitudinal change was proportional to degree of lesion expansion. Lesion-wise analysis revealed a gradual, centrifugal decrease in the proportion of expanding lesions from the immediate periventricular zone. Discussion: Our data suggest that chronic white matter lesions in close proximity to the ventricles are more destructive, show a higher degree of expansion at the lesion border and accelerated tissue loss in the lesion core.

show abstract

Perilesional neurodegenerative injury in multiple sclerosis: Relation to focal lesions and impact on disability

Cited by 11 publications

References 45 publications

The expansion and severity of chronic MS lesions follows a periventricular gradient

The expansion and severity of chronic MS lesions follows a periventricular gradient

Macromolecular Proton Fraction as a Myelin Biomarker: Principles, Validation, and Applications

The expansion and severity of chronic MS lesions follows a periventricular gradient

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