Surface-in pathology in multiple sclerosis: a new view on pathogenesis?

Brain ◽  
2021 ◽  
Author(s):  
Matteo Pardini ◽  
J William L Brown ◽  
Roberta Magliozzi ◽  
Richard Reynolds ◽  
Declan T Chard
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Grey Matter ◽  
Magnetization Transfer ◽  
Neuronal Loss ◽  
Magnetization Transfer Ratio ◽  
Supporting Evidence ◽  
Transfer Ratio ◽  
Meningeal Inflammation

Abstract While multiple sclerosis can affect any part of the CNS, it does not do so evenly. In white matter it has long been recognized that lesions tend to occur around the ventricles, and grey matter lesions mainly accrue in the outermost (subpial) cortex. In cortical grey matter, neuronal loss is greater in the outermost layers. This cortical gradient has been replicated in vivo with magnetization transfer ratio and similar gradients in grey and white matter magnetization transfer ratio are seen around the ventricles, with the most severe abnormalities abutting the ventricular surface. The cause of these gradients remains uncertain, though soluble factors released from meningeal inflammation into the CSF has the most supporting evidence. In this Update, we review this ‘surface-in’ spatial distribution of multiple sclerosis abnormalities and consider the implications for understanding pathogenic mechanisms and treatments designed to slow or stop them.

scholarly journals Magnetization transfer ratio abnormalities reflect clinically relevant grey matter damage in multiple sclerosis

2009 ◽  
Vol 15 (6) ◽  
pp. 668-677 ◽  
Author(s):  
LK Fisniku ◽  
DR Altmann ◽  
M Cercignani ◽  
DJ Tozer ◽  
DT Chard ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Grey Matter ◽  
Magnetization Transfer ◽  
Magnetization Transfer Ratio ◽  
Expanded Disability Status Scale ◽  
Transfer Ratio ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

Background In multiple sclerosis, grey matter (GM) damage appears more clinically relevant than either white matter damage or lesion load. Objective We investigated if normal-appearing white matter (NAWM) and grey matter tissue changes assessed by magnetization transfer ratio were associated with long-term disability. Methods Sixty-nine people were assessed 20 years after presentation with a clinically isolated syndrome (CIS) [28 still CIS, 31 relapsing-remitting multiple sclerosis, 10 secondary progressive multiple sclerosis], along with 19 healthy subjects. Mean magnetization transfer ratio, peak height (PH) and peak location of the normalized magnetization transfer ratio histograms were determined in NAWM and grey matter, as well as, white matter and GM Fraction (GMF) and T2-weighted lesion load. Results Median expanded disability status scale for multiple sclerosis patients was 2.5 (range 1–8). GM-PH, and less so, NAWM mean and peak location, were lower in multiple sclerosis patients ( P = 0.009) versus controls, relapsing-remitting multiple sclerosis versus CIS ( P = 0.008) and secondary progressive multiple sclerosis versus relapsing-remitting multiple sclerosis ( P = 0.002). GM-PH (as well as GMF) correlated with expanded disability status scale ( rs = −0.49; P = 0.001) and multiple sclerosis functional score ( rs = 0.51; P = 0.001). GM-PH independently predicted disability with similar strength to the associations of GMF with clinical measures. Conclusion Grey matter damage was related to long-term disability in multiple sclerosis cohort with a relatively low median expanded disability status scale. Markers of intrinsic grey matter damage (magnetization transfer ratio) and tissue loss offer clinically relevant information in multiple sclerosis.

Characterization of white matter damage in animal models of multiple sclerosis by magnetization transfer ratio and quantitative mapping of the apparent bound proton fraction f*

2009 ◽  
Vol 15 (1) ◽  
pp. 16-27 ◽  
Author(s):  
M Rausch ◽  
PS Tofts ◽  
P Lervik ◽  
AR Walmsley ◽  
A Mir ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Animal Models ◽  
Tissue Damage ◽  
Magnetization Transfer ◽  
Transverse Relaxation Time ◽  
Magnetization Transfer Ratio ◽  
White Matter Damage ◽  
Transfer Ratio ◽  
Quantitative Mapping

Quantitative magnetization transfer magnetic resonance imaging (qMT-MRI) can be used to improve detection of white matter tissue damage in multiple sclerosis (MS) and animal models thereof. To study the correlation between MT parameters and tissue damage, the magnetization transfer ratio (MTR), the parameter f* (closely related to the bound proton fraction) and the bound proton transverse relaxation time T2B of lesions in a model of focal experimental autoimmune encephalomyelitis (EAE) were measured on a 7T animal scanner and data were compared with histological markers indicative for demyelination, axonal density, and tissue damage. A clear spatial correspondence was observed between reduced values of MTR and demyelination in this animal model. We observed two different levels of MTR and f* reduction for these lesions. One was characterized by a pronounced demyelination and the other corresponded to a more severe loss of the cellular matrix. Changes in f* were generally more pronounced than those of MTR in areas of demyelination. Moreover, a reduction of f* was already observed for tissue where MTR was virtually normal. No changes in T2B were observed for the lesions. We conclude that MTR and qMT mapping are efficient and reliable readouts for studying demyelination in animal models of MS, and that the analysis of regional f* might be even superior to the analysis of MTR values. Therefore, quantitative mapping of f* from human brains might also improve the detection of white matter damage in MS.

Voxel-based analysis of grey matter magnetization transfer ratio maps in early relapsing remitting multiple sclerosis

2007 ◽  
Vol 13 (4) ◽  
pp. 483-489 ◽  
Author(s):  
B. Audoin ◽  
G. Davies ◽  
W. Rashid ◽  
L. Fisniku ◽  
A.J. Thompson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Grey Matter ◽  
Morphological Changes ◽  
Magnetization Transfer ◽  
Histogram Analysis ◽  
Magnetization Transfer Ratio ◽  
Transfer Ratio ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Previous studies using magnetization transfer ratio (MTR) histogram analysis have demonstrated the existence of global grey matter (GM) abnormalities in patients with early relapsing-remitting multiple sclerosis (RRMS). However, MTR histogram analysis does not provide any information on the localization of the morphological changes within the GM. The aim of this study was to investigate the localization of GM injury in early RRMS, performing voxel-based analysis of GM MTR maps. Statistical mapping analysis of GM MTR maps was performed in a group of 38 patients with early RRMS and 45 healthy controls. Between-group comparisons (P<0.05, corrected for multiple comparisons) demonstrated significant GM MTR decrease in patients located in the bilateral lenticular nuclei, the bilateral insula, the left posterior cingulate cortex, and the right orbitofrontal cortex. To limit the potential confounding effect of regional GM atrophy, the percentages of GM were assessed in the regions showing significant MTR decrease, and no GM atrophy was evidenced in these regions. This study demonstrates that several GM regions are commonly affected in patients with early RRMS. Predominant involvement of these structures may be partly related to their vulnerability to anterograde or retrograde degeneration from transected axons in the white matter and/or to the predominant localization of GM demyelinating lesions in such regions. Multiple Sclerosis 2007; 13: 483-489. http://msj.sagepub.com

scholarly journals Magnetization transfer ratio measures in normal-appearing white matter show periventricular gradient abnormalities in multiple sclerosis

Brain ◽  
2015 ◽  
Vol 138 (5) ◽  
pp. 1239-1246 ◽  
Author(s):  
Zheng Liu ◽  
Matteo Pardini ◽  
Özgür Yaldizli ◽  
Varun Sethi ◽  
Nils Muhlert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetization Transfer ◽  
Magnetization Transfer Ratio ◽  
Transfer Ratio ◽  
Normal Appearing White Matter

scholarly journals Prevalence of Grey Matter Pathology in Early Multiple Sclerosis Assessed by Magnetization Transfer Ratio Imaging

PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e24969 ◽  
Author(s):  
Lydie Crespy ◽  
Wafaa Zaaraoui ◽  
Mathias Lemaire ◽  
Audrey Rico ◽  
Anthony Faivre ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Grey Matter ◽  
Magnetization Transfer ◽  
Magnetization Transfer Ratio ◽  
Transfer Ratio ◽  
Ratio Imaging

Long-Term Magnetization Transfer Ratio Evolution in Multiple Sclerosis White Matter Lesions

2017 ◽  
Vol 28 (2) ◽  
pp. 191-198 ◽  
Author(s):  
Yufan Zheng ◽  
Jar-Chi Lee ◽  
Richard Rudick ◽  
Elizabeth Fisher
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetization Transfer ◽  
White Matter Lesions ◽  
Magnetization Transfer Ratio ◽  
Transfer Ratio
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