Pathologic correlates of the magnetization transfer ratio in multiple sclerosis

Neurology ◽  
2020 ◽  
Vol 95 (22) ◽  
pp. e2965-e2976
Author(s):  
Marcello Moccia ◽  
Steven van de Pavert ◽  
Arman Eshaghi ◽  
Lukas Haider ◽  
Jonas Pichat ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetization Transfer ◽  
Mixed Effects ◽  
Mitochondrial Damage ◽  
Regions Of Interest ◽  
Magnetization Transfer Ratio ◽  
Linear Mixed Effects ◽  
Interaction Terms ◽  
Damage Coefficient

ObjectiveTo identify pathologic correlates of magnetization transfer ratio (MTR) in multiple sclerosis (MS) in an MRI–pathology study.MethodsWe acquired MTR maps at 3T from 16 fixed MS brains and 4 controls, and immunostained 100 tissue blocks for neuronal neurofilaments, myelin (SMI94), tissue macrophages (CD68), microglia (IBA1), B-lymphocytes, T-lymphocytes, cytotoxic T-lymphocytes, astrocytes (glial fibrillary acidic protein), and mitochondrial damage (COX4, VDAC). We defined regions of interest in lesions, normal-appearing white matter (NAWM), and cortical normal-appearing gray matter (NAGM). Associations between MTR and immunostaining intensities were explored using linear mixed-effects models (with cassettes nested within patients) and interaction terms (for differences between regions of interest and between cases and controls); a multivariate linear mixed-effects model identified the best pathologic correlates of MTR.ResultsMTR was the lowest in white matter (WM) lesions (23.4 ± 9.4%) and the highest in NAWM (38.1 ± 8.7%). In MS brains, lower MTR was associated with lower immunostaining intensity for myelin (coefficient 0.31; 95% confidence interval [CI] 0.07–0.55), macrophages (coefficient 0.03; 95% CI 0.01–0.07), and astrocytes (coefficient 0.51; 95% CI 0.02–1.00), and with greater mitochondrial damage (coefficient 0.31; 95% CI 0.07–0.55). Based on interaction terms, MTR was more strongly associated with myelin in WM (coefficient 1.58; 95% CI 1.09–2.08) and gray matter (GM) lesions (coefficient 0.66; 95% CI 0.13–1.20), and with macrophages (coefficient 1.40; 95% CI 0.56–2.25), astrocytes (coefficient 2.66; 95% CI 1.31–4.01), and mitochondrial damage (coefficient −12.59; 95% CI −23.16 to −2.02) in MS brains than controls. In the multivariate model, myelin immunostaining intensity was the best correlate of MTR (coefficient 0.31; 95% CI 0.09–0.52; p = 0.004).ConclusionsMyelin was the strongest correlate of MTR, especially in WM and cortical GM lesions, but additional correlates should be kept in mind when designing and interpreting MTR observational and experimental studies in MS.

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.

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 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 The Prognostic Value of White-Matter Selective Double Inversion Recovery MRI Sequence in Multiple Sclerosis: An Exploratory Study

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 686
Author(s):  
Francesco Crescenzo ◽  
Damiano Marastoni ◽  
Anna Isabella Pisani ◽  
Agnese Tamanti ◽  
Caterina Dapor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetization Transfer ◽  
Inversion Recovery ◽  
Double Inversion Recovery ◽  
Magnetization Transfer Ratio ◽  
Tissue Properties ◽  
Relapsing Remitting ◽  
3.0 T

Using a white-matter selective double inversion recovery sequence (WM-DIR) that suppresses both grey matter (GM) and cerebrospinal fluid (CSF) signals, some white matter (WM) lesions appear surrounded by a dark rim. These dark rim lesions (DRLs) seem to be specific for multiple sclerosis (MS). They could be of great usefulness in clinical practice, proving to increase the MRI diagnostic criteria specificity. The aims of this study are the identification of DRLs on 1.5 T MRI, the exploration of the relationship between DRLs and disease course, the characterization of DRLs with respect to perilesional normal-appearing WM using magnetization transfer imaging, and the investigation of possible differences in the underlying tissue properties by assessing WM-DIR images obtained at 3.0 T MRI. DRLs are frequent in primary progressive MS (PPMS) patients. Amongst relapsing-remitting MS (RRMS) patients, DRLs are associated with a high risk of the disease worsening and secondary progressive MS (SPMS) conversion after 15 years. The mean magnetization transfer ratio (MTR) of DRLs is significantly different from the lesion without the dark rim, suggesting that DRLs correspond to more destructive lesions.

scholarly journals Quantitative MRI Demonstrates Abnormality of the Fornix and Cingulum in Multiple Sclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Stephanie B. Syc ◽  
Daniel M. Harrison ◽  
Shiv Saidha ◽  
Michaela Seigo ◽  
Peter A. Calabresi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Healthy Volunteers ◽  
Cognitive Dysfunction ◽  
Diffusion Tensor ◽  
Magnetization Transfer ◽  
Mean Diffusivity ◽  
Brain Structures ◽  
Quantitative Mri ◽  
Magnetization Transfer Ratio

Objective. To characterize MR signal changes associated with tissue damage in the fornix and cingulum in multiple sclerosis (MS) using quantitative MRI measures and to determine associations with cognitive dysfunction.Background. The fornix and cingulum are white-matter bundles that carry information related to cognition. While cognitive dysfunction is reported in 40–60% of MS patients, the neuroanatomical correlates of cognitive impairment remain incompletely understood.Methods. The cingulum, pillars of the fornix, and corticospinal tract were segmented by fiber tracking via diffusion tensor imaging. Average tract-specific fractional anisotropy (FA), mean diffusivity (MD), and magnetization transfer ratio (MTR) were compared in MS cases and healthy volunteers. Associations with clinical measures and neuropsychological tests were derived by multivariate linear regression.Results. Fornix FA (P=0.004) and MTR (P=0.005) were decreased, and fornix MD (P<0.001) and cingulum MD (P<0.001) increased, in MS cases (n=101) relative to healthy volunteers (n=16) after adjustment for age and sex. Lower fornix FA and MTR, and higher fornix MD andλ∥, were correlated with lower PASAT-3 scores, but not with slower 25FTW times. Lower PASAT-3 scores were associated with lower cingulum FA and higher MD andλ⊥.Conclusions. Cognitive dysfunction in MS may involve damage to a widespread network of brain structures, including white-matter pathways within the limbic system.

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

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.

Cervical cord magnetization transfer ratio and clinical changes over 18 months in patients with relapsing-remitting multiple sclerosis: a preliminary study

2006 ◽  
Vol 12 (5) ◽  
pp. 662-665 ◽  
Author(s):  
A Charil ◽  
D Caputo ◽  
R Cavarretta ◽  
M P Sormani ◽  
P Ferrante ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Magnetization Transfer ◽  
Small Sample ◽  
Cervical Cord ◽  
Magnetization Transfer Ratio ◽  
Short Term ◽  
Disease Evolution ◽  
Transfer Ratio ◽  
Relapsing Remitting

Background Magnetization transfer ratio (MTR) permits the quantitative estimation of cervical cord tissue damage in patients with multiple sclerosis (MS). Objective To determine whether a single time-point MTR scan of the cervical cord is associated with short-term disease evolution in patients with relapsing-remitting (RR) MS. Methods Using a 1.5-T magnetic resonance imaging (MRI) system with a tailored cervical cord phased array coil, fast short-tau inversion recovery (fast-STIR) and MTR scans were obtained from 14 untreated patients with RRMS at baseline. Cervical cord MTR histograms were derived. Over the 18- month follow-up period, relapse rate was measured and disability assessed by the Expanded Disability Status Scale (EDSS) score. Results Average cervical cord MTR was correlated with relapse rate ( r= -0.56, P = 0.037). A moderate correlation ( r values ranging from -0.33 to -0.36) between baseline cervical cord MTR metrics and EDSS changes over 18 months was also noted, albeit statistical significance was not reached ( P = 0.26 and 0.21, respectively) perhaps because of the relatively small sample size. Conclusions This study suggests that a ‘snapshot’ MT MRI assessment of the cervical cord may detect cervical cord tissue changes associated with short-term disease evolution in RRMS.

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