scholarly journals Exploratory MRI measures after intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis

2019 ◽  
Vol 5 (2) ◽  
pp. 205521731985603 ◽  
Author(s):  
Jenny Feng ◽  
Erik Offerman ◽  
Jian Lin ◽  
Elizabeth Fisher ◽  
Sarah M Planchon ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Diffusion Tensor ◽  
Phase 1 ◽  
Lesion Volume ◽  
Open Label ◽  
Mesenchymal Stem Cell Transplantation ◽  
Post Transplant ◽  
Normal Appearing White Matter ◽  
Motor Tracts ◽  
Clinical Measures

Background Mesenchymal stem cells (MSC) have immunomodulatory and neuro-protective properties and are being studied for treatment of multiple sclerosis (MS). Tractography-based diffusion tensor imaging (DTI), cortical thickness (Cth) and T2 lesion volume (T2LV) can provide insight into treatment effects. Objective The objective of this study was to analyse the effects of MSC transplantation in MS on exploratory MRI measures. Methods MRIs were obtained from 24 MS patients from a phase 1 open-label study of autologous MSC transplantation. DTI metrics were obtained in lesions and normal-appearing white matter motor tracts (NAWM). T2LV and Cth were derived. Longitudinal evolution of MRI outcomes were modelled using linear mixed effects. Pearson’s correlation was calculated between MRI and clinical measures. Results Lesional radial diffusivity (RD) and axial diffusivity (AD) decreased pre-transplant and showed no changes post-transplant. There were mixed trends in NAWM RD and AD pre/post-transplant. Transplantation stabilized T2LV growth. NAWM RD and AD correlated with Cth, T2LV and with leg and arm function but not with cognition. Lesional DTI demonstrated similar but less robust correlations. Conclusions Microstructural tissue integrity is altered in MS. DTI changes pre-transplant may be influenced by concomitant lesion accrual. Contributor to DTI stabilization post-transplant is multifactorial. DTI of major motor tracts correlated well with clinical measures, highlighting its sensitivity to clinically meaningful changes.

Wallerian and trans-synaptic degeneration contribute to optic radiation damage in multiple sclerosis: a diffusion tensor MRI study

2013 ◽  
Vol 19 (12) ◽  
pp. 1610-1617 ◽  
Author(s):  
Maria A Rocca ◽  
Sarlota Mesaros ◽  
Paolo Preziosa ◽  
Elisabetta Pagani ◽  
Tatjana Stosic-Opincal ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optic Nerve ◽  
Optic Neuritis ◽  
Diffusion Tensor ◽  
Lesion Volume ◽  
Optic Radiation ◽  
Focal Lesions ◽  
Normal Appearing White Matter ◽  
Topographical Distribution ◽  
Synaptic Degeneration

Background: Optic radiation (OR) damage occurs in multiple sclerosis (MS). Objectives: The purpose of this study was to explore the contribution of local and distant mechanisms associated with OR damage in MS. Methods: Diffusion tensor (DT) magnetic resonance imaging (MRI) tractography probability maps of the ORs were derived from 102 MS patients and 11 controls. Between-group differences of OR normal-appearing white matter (NAWM) damage and topographical distribution of OR damage were assessed using quantitative and voxel-wise analyses, considering the influence of previous optic neuritis (ON+) and T2 OR lesions (T2 OR+). Results: OR NAWM diffusivity abnormalities were more severe in ON+ patients vs patients without previous optic neuritis (ON–) and T2 OR+ vs T2 OR– patients. Damage to the anterior portions of the ORs was more severe in ON+ vs ON– patients. Compared to controls and T2 OR– patients, T2 OR+ patients experienced a more distributed pattern of DT MRI abnormalities along the ORs, with an increased axial diffusivity limited to the anterior portions of the ORs. In T2 OR+ group, ON+ vs ON– patients showed DT MRI abnormalities in the middle portion of the ORs, in correspondence with focal lesions. OR damage correlated with OR T2 lesion volume, visual dysfunction and optic nerve atrophy. Conclusions: Both trans-synaptic degeneration secondary to optic nerve damage and Wallerian degeneration due to local T2 lesions contribute to OR damage in MS.

Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter

2004 ◽  
Vol 10 (2) ◽  
pp. 188-196 ◽  
Author(s):  
Emmanuelle Cassol ◽  
Jean-Philippe Ranjeva ◽  
Danielle Ibarrola ◽  
Claude Mékies ◽  
Claude Manelfe ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Diffusion Tensor ◽  
Lesion Load ◽  
Normal Appearing White Matter ◽  
Relapsing Remitting ◽  
One Year ◽  
Diffusion Tensor Imaging Dti

Our objectives were to determine the reproducibility of diffusion tensor imaging (DTI) in volunteers and to evaluate the ability of the method to monitor longitudinal changes occurring in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS). DTI was performed three-mo nthly for one year in seven MS patients: three relapsing-remitting (RRMS), three secondary progressive (SPMS) and one relapsing SP. They were selected with a limited cerebral lesion load. Seven age- and sex-matched controls also underwent monthly examinations for three months. Diffusivity and anisotropy were quantified over the segmented whole supratentorial white matter, with the indices of trace (Tr) and fractional anisotropy (FA). Results obtained in volunteers show the reproducibility of the method. Patients had higher trace and lower anisotropy than matched controls (P B-0.0001). O ver the follow-up, both Tr and FA indicated a recovery after the acute phase in RRMS and a progressive shift towards abnormal values in SPMS. A lthough this result is not statistically significant, it suggests that DTI is sensitive to microscopic changes occurring in tissue of normal appearance in conventional images and could be useful for monitoring the course of the disease, even though it was unable to clearly distinguish between the various physiopathological processes involved.

A 24-month advanced magnetic resonance imaging study of multiple sclerosis patients treated with alemtuzumab

2018 ◽  
Vol 25 (6) ◽  
pp. 811-818 ◽  
Author(s):  
Irene M Vavasour ◽  
Roger Tam ◽  
David KB Li ◽  
Cornelia Laule ◽  
Carolyn Taylor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Cortical Thickness ◽  
Diffusion Tensor ◽  
Imaging Study ◽  
Water Fraction ◽  
Normal Appearing White Matter ◽  
Brain Parenchymal Fraction ◽  
Brain Parenchymal ◽  
Multiple Sclerosis Patients

Background: Tissue damage in both multiple sclerosis (MS) lesions and normal-appearing white matter (NAWM) are important contributors to disability and progression. Specific aspects of MS pathology can be measured using advanced imaging. Alemtuzumab is a humanised monoclonal antibody targeting CD52 developed for MS treatment. Objective: To investigate changes over 2 years of advanced magnetic resonance (MR) metrics in lesions and NAWM of MS patients treated with alemtuzumab. Methods: A total of 42 relapsing–remitting alemtuzumab-treated MS subjects were scanned for 2 years at 3 T. T1 relaxation, T2 relaxation, diffusion tensor, MR spectroscopy and volumetric sequences were performed. Mean T1 and myelin water fraction (MWF) were determined for stable lesions, new lesions and NAWM. Fractional anisotropy was calculated for the corpus callosum (CC) and N-acetylaspartate (NAA) concentration was determined from a large NAWM voxel. Brain parenchymal fraction (BPF), cortical thickness and CC area were also calculated. Results: No change in any MR measurement was found in lesions or NAWM over 24 months. BPF, cortical thickness and CC area all showed decreases in the first year followed by stability in the second year. Conclusion: Advanced MR biomarkers of myelin (MWF) and neuron/axons (NAA) show no change in NAWM over 24 months in alemtuzumab-treated MS participants.

scholarly journals Evaluation of white matter in patients with multiple sclerosis through diffusion tensor magnetic resonance imaging

2007 ◽  
Vol 65 (3a) ◽  
pp. 561-564 ◽  
Author(s):  
Rachel E. Maia de Andrade ◽  
Emerson L. Gasparetto ◽  
Luiz Celso Hygino Cruz Jr. ◽  
Fabiana Brito Ferreira ◽  
Roberto Cortês Domingues ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetic Resonance ◽  
Mr Imaging ◽  
Diffusion Tensor ◽  
Statistical Treatment ◽  
Control Group ◽  
Normal Appearing White Matter ◽  
Significant Difference ◽  
Normal White Matter

OBJECTIVE: To study the white matter of patients with multiple sclerosis (MS) with diffusion tensor magnetic resonance (MR) imaging (DTI). METHOD: Forty patients with clinical-laboratorial diagnosis of relapsing-remitting MS and 40 age- and sex-matched controls, who underwent conventional and functional (DTI) MR imaging, were included in the study. The DTI sequences resulted in maps of fractional anisotropy (FA) and regions of interest were placed on the plaques, peri-plaque regions, normal-appearing white matter (NAWM) around the plaques, contralateral normal white matter (CNWM) and normal white matter of the controls (WMC). The FA values were compared and the statistical treatment was performed with the Mann-Whitney U test. RESULTS: The mean FA in plaques was 0.268, in peri-plaque regions 0.365, in NAWM 0.509, in CNWM 0.552 and in WMC 0.573. Statistical significant differences in FA values were observed in plaques, peri-plaque regions and in NAWM around the plaques when compared to the white matter in the control group. There was no significant difference between the FA values of the CNWM of patients with MS and normal white matter of controls. CONCLUSION: Patients with MS show difference in the FA values of the plaques, peri-plaques and NAWM around the plaques when compared to the normal white matter of controls. As a result, DTI may be considered more efficient than conventional MR imaging for the study of patients with MS.

Diffusion tensor magnetic resonance imaging in very early onset pediatric multiple sclerosis

2015 ◽  
Vol 22 (5) ◽  
pp. 620-627 ◽  
Author(s):  
MA Rocca ◽  
M Sonkin ◽  
M Copetti ◽  
E Pagani ◽  
DL Arnold ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Structural Integrity ◽  
Linear Models ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Lesion Volume ◽  
Resonance Imaging ◽  
The Impact

Objectives: Active myelination during childhood may influence the impact of multiple sclerosis (MS) on brain structural integrity. We studied normal-appearing white matter (NAWM) in children with MS onset before age 12 years using diffusion tensor (DT) magnetic resonance imaging (MRI). Methods: DT MRI scans were obtained from 22 MS children with their first attack before age 12 years, and 31 healthy controls from two referral centers. Using probabilistic tractography, brain tissue integrity within interhemispheric, intrahemispheric, and projection tracts was compared between patients and site-matched controls. The impact of disease and age at MRI on tract NAWM fractional anisotropy (FA) and mean diffusivity (MD) values was evaluated using linear models. Results: Compared to controls, pediatric MS patients had reduced FA and increased MD of the bilateral superior longitudinal fasciculus and corpus callosum (CC), without center-by-group interaction. CC NAWM average FA was correlated with brain T2 lesion volume. In controls, the majority of the tracts analyzed showed a significant increase of FA and decrease of MD with age. Such a linear correlation was lost in patients. Conclusions: In very young pediatric MS patients, DT MRI abnormalities affect brain WM tracts differentially, and are only partially correlated with focal WM lesions. Impaired maturation of WM tracts with age may be an additional factor contributing to these findings.

Fatigue in multiple sclerosis: The contribution of occult white matter damage

2016 ◽  
Vol 22 (13) ◽  
pp. 1676-1684 ◽  
Author(s):  
Alvino Bisecco ◽  
Giuseppina Caiazzo ◽  
Alessandro d’Ambrosio ◽  
Rosaria Sacco ◽  
Simona Bonavita ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Diffusion Tensor ◽  
Cerebral Peduncle ◽  
Superior Longitudinal Fasciculus ◽  
Normal Appearing White Matter ◽  
External Capsule ◽  
Mri Protocol ◽  
Fatigue Severity ◽  
Magnetic Resonance Imaging Mri

Background: A functional cortico-subcortical disconnection has been recognized in fatigued multiple sclerosis (MS) patients. Normal appearing white matter (NAWM) damage might contribute to the abovementioned disconnectivity. Objectives: To assess the relationship between fatigue and microstructural NAWM damage in relapsing-remitting (RR) MS. Methods: Sixty RRMS patients and 29 healthy controls (HC) underwent a magnetic resonance imaging (MRI) protocol including diffusion tensor imaging (DTI). Patients with a mean Fatigue Severity Scale (FSS) score ⩾ 4 were considered fatigued (fatigued MS (F-MS)). Tract-based spatial statistics were applied for voxel-wise analysis of DTI indices. A correlation analysis was performed between FSS score and DTI indices in the entire MS group. Results: Thirty MS patients were F-MS. Compared to HC, F-MS patients showed a more extensive NAWM damage than not fatigued MS (NF-MS) patients, with additional damage in the following tracts: frontal and occipital juxtacortical fibers, external capsule, uncinate fasciculus, forceps minor, superior longitudinal fasciculus, cingulum, and pons. No differences were found between F-MS and NF-MS patients. Fatigue severity correlated to DTI abnormalities of corona radiata, cingulum, corpus callosum, forceps minor, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamus and anterior thalamic radiation, cerebral peduncle, and midbrain. Conclusions: Fatigue is associated to a widespread microstructural NAWM damage, particularly in associative tracts connected to frontal lobes.

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