scholarly journals Periventricular magnetisation transfer ratio abnormalities in multiple sclerosis improve after alemtuzumab

2019 ◽  
Vol 26 (9) ◽  
pp. 1093-1101
Author(s):  
J William L Brown ◽  
Ferran Prados Carrasco ◽  
Arman Eshaghi ◽  
Carole H Sudre ◽  
Tom Button ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
White Matter Lesions ◽  
Magnetisation Transfer ◽  
Magnetisation Transfer Ratio ◽  
Brain Volumes ◽  
Transfer Ratio ◽  
Lesion Number ◽  
Brain Parenchymal Fraction ◽  
Brain Parenchymal

Background: In multiple sclerosis (MS), disease effects on magnetisation transfer ratio (MTR) increase towards the ventricles. This periventricular gradient is evident shortly after first symptoms and is independent of white matter lesions. Objective: To explore if alemtuzumab, a peripherally acting disease-modifying treatment, modifies the gradient’s evolution, and whether baseline gradients predict on-treatment relapses. Methods: Thirty-four people with relapsing-remitting MS underwent annual magnetic resonance imaging (MRI) scanning (19 receiving alemtuzumab (four scans each), 15 untreated (three scans each)). The normal-appearing white matter was segmented into concentric bands. Gradients were measured over the three bands nearest the ventricles. Mixed-effects models adjusted for age, gender, relapse rate, lesion number and brain parenchymal fraction compared the groups’ baseline gradients and evolution. Results: Untreated, the mean MTR gradient increased (+0.030 pu/band/year) but decreased following alemtuzumab (−0.045 pu/band/year, p = 0.037). Within the alemtuzumab group, there were no significant differences in baseline lesion number ( p = 0.568) nor brain parenchymal fraction ( p = 0.187) between those who relapsed within 4 years ( n = 4) and those who did not ( n = 15). However, the baseline gradient was significantly different ( p = 0.020). Conclusion: Untreated, abnormal periventricular gradients worsen with time, but appear reversible with peripheral immunotherapy. Baseline gradients – but not lesion loads or brain volumes – may predict on-treatment relapses. Larger confirmatory studies are required.

Cortical lesion load correlates with diffuse injury of multiple sclerosis normal appearing white matter

2013 ◽  
Vol 20 (2) ◽  
pp. 227-233 ◽  
Author(s):  
Niraj Mistry ◽  
Rasha Abdel-Fahim ◽  
Olivier Mougin ◽  
Christopher Tench ◽  
Penny Gowland ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Cortical Lesion ◽  
Cortical Lesions ◽  
Magnetisation Transfer ◽  
Magnetisation Transfer Ratio ◽  
Lesion Load ◽  
Transfer Ratio ◽  
Normal Appearing White Matter ◽  
Axon Loss

Background:Degeneration of central nervous system normal appearing white matter (NAWM) underlies disability and progression in multiple sclerosis (MS). Axon loss typifies NAWM degeneration.Objective:The objective of this paper is to assess correlation between cortical lesion load and magnetisation transfer ratio (MTR) of the NAWM in MS. This was in order to test the hypothesis that cortical lesions cause NAWM degeneration.Methods:Nineteen patients with MS underwent 7 Tesla magnetisation-prepared-rapid-acquisition-gradient-echo (MPRAGE), and magnetisation transfer ratio (MTR) brain magnetic resonance imaging (MRI). Cortical lesions were identified using MPRAGE and MTR images of cortical ribbons. White matter lesions (WMLs) were segmented using MPRAGE images. WML maps were subtracted from white matter volumes to produce NAWM masks. Pearson correlation was calculated for NAWM MTR vs cortical lesion load, and WML volumes.Results:Cortical lesion volumes and counts all had significant correlation with NAWM mean MTR. The strongest correlation was with cortical lesion volumes obtained using MTR images ( r = −0.6874, p = 0.0006). WML volume had no significant correlation with NAWM mean MTR ( r = −0.08706, p = 0.3615).Conclusion:Our findings are consistent with the hypothesis that cortical lesions cause NAWM degeneration. This implicates cortical lesions in the pathogenesis of NAWM axon loss, which underpins long-term disability and progression in MS.

Investigation of outer cortical magnetisation transfer ratio abnormalities in multiple sclerosis clinical subgroups

2014 ◽  
Vol 20 (10) ◽  
pp. 1322-1330 ◽  
Author(s):  
Rebecca S Samson ◽  
Manuel J Cardoso ◽  
Nils Muhlert ◽  
Varun Sethi ◽  
Claudia AM Wheeler-Kingshott ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Three Dimensional ◽  
Neuronal Loss ◽  
Magnetisation Transfer ◽  
Magnetisation Transfer Ratio ◽  
Outer Cortex ◽  
Transfer Ratio ◽  
Relapsing Remitting ◽  
Healthy Control

Background: Pathological abnormalities including demyelination and neuronal loss are reported in the outer cortex in multiple sclerosis (MS). Objective: We investigated for in vivo evidence of outer cortical abnormalities by measuring the magnetisation transfer ratio (MTR) in MS patients of different subgroups. Methods: Forty-four relapsing–remitting (RR) (mean age 41.9 years, median Expanded Disability Status Scale (EDSS) 2.0), 25 secondary progressive (SP) (54.1 years, EDSS 6.5) and 19 primary progressive (PP) (53.1 years, EDSS 6.0) MS patients and 35 healthy control subjects (mean age 39.2 years) were studied. Three-dimensional (3D) 1×1×1mm3 T1-weighted images and MTR data were acquired. The cortex was segmented, then subdivided into outer and inner bands, and MTR values were calculated for each band. Results: In a pairwise analysis, mean outer cortical MTR was lower than mean inner cortical MTR in all MS groups and controls ( p<0.001). Compared with controls, outer cortical MTR was decreased in SPMS ( p<0.001) and RRMS ( p<0.01), but not PPMS. Outer cortical MTR was lower in SPMS than PPMS ( p<0.01) and RRMS ( p<0.01). Conclusions: Lower outer than inner cortical MTR in healthy controls may reflect differences in myelin content. The lowest outer cortical MTR was seen in SPMS and is consistent with more extensive outer cortical (including subpial) pathology, such as demyelination and neuronal loss, as observed in post-mortem studies of SPMS patients.

scholarly journals Tractography in the presence of white matter lesions in multiple sclerosis

2019 ◽  
Author(s):  
Ilona Lipp ◽  
Greg D Parker ◽  
Emma Tallantyre ◽  
Alex Goodall ◽  
Steluta Grama ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Fibre Orientation ◽  
White Matter Lesions ◽  
Radial Diffusivity ◽  
White Matter Tracts ◽  
Transfer Ratio ◽  
Microstructural Parameters ◽  
Probability Map ◽  
Tracking Algorithms

AbstractAccurate anatomical localisation of specific white matter tracts and the quantification of their tractspecific microstructural damage in multiple sclerosis (MS) can contribute to a better understanding of symptomatology, disease progression and intervention effects. Diffusion MRI-based tractography is being used increasingly to segment white matter tracts as regions-of-interest for subsequent quantitative analysis. Since MS lesions can interrupt the tractography algorithms tract reconstruction, clinical studies frequently resort to atlas-based approaches, which are convenient but ignorant to individual variability in tract size and shape. Here, we revisit the problem of individual tractography in MS, comparing tractography algorithms using: (i) The diffusion tensor framework; (ii) constrained spherical deconvoution (CSD); and (iii) damped Richardson-Lucy (dRL) deconvolution. Firstly, using simulated and in vivo data from 29 MS patients and 19 healthy controls, we show that the three tracking algorithms respond differentially to MS pathology. While the tensor-based approach is unable to deal with crossing fibres, CSD produces spurious stream-lines, in particular in tissue with high fibre loss and low diffusion anisotropy. With dRL, streamlines are increasingly interrupted in pathological tissue. Secondly, we demonstrate that despite the effects of lesion on the fibre orientation reconstruction algorithms, fibre tracking algorithms are still able to segment tracts that pass areas with high prevalence of lesions. Combining dRL-based tractography with an automated tract segmentation tool on data from 131 MS patients, the corticospinal tracts and arcuate fasciculi were successfully reconstructed in more than 90% of individuals. Comparing tractspecific microstructural parameters (fractional anisotropy, radial diffusivity and magnetisation transfer ratio) in individually segmented tracts to those from a tract probability map, we showed that there is no systematic disease-related bias in the individually reconstructed tracts, suggesting that lesions and otherwise damaged parts are not systematically omitted during tractography. Thirdly, we demonstrate modest anatomical correspondence between the individual and tract probability-based approach, with a spatial overlap between 35 and 55%. Correlations between tract-averaged microstructural parameters in individually segmented tracts and the probability-map approach ranged between r = .52 (p < .001) for radial diffusivity in the right cortico-spinal tract and r = .97 (p < .001) for magnetization transfer ratio in the arcuate fasciculi. Our results show that MS white matter lesions impact fibre orientation reconstructions but this does not appear to hinder the ability to anatomically localise white matter tracts in MS. Individual tract segmentation in MS is feasible on a large scale and could prove a powerful tool for investigating diagnostic and prognostic markers.

Magnetisation transfer ratio measurement in the cervical spinal cord: a preliminary study in multiple sclerosis

1997 ◽  
Vol 39 (6) ◽  
pp. 441-445 ◽  
Author(s):  
N. C. Silver ◽  
G. J. Barker ◽  
N. A. Losseff ◽  
M. L. Gawne-Cain ◽  
D. G. MacManus ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Cervical Spinal Cord ◽  
Magnetisation Transfer ◽  
Magnetisation Transfer Ratio ◽  
Ratio Measurement ◽  
Transfer Ratio ◽  
Preliminary Study
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