Multiple sclerosis pathology in the normal and abnormal appearing white matter of the corpus callosum by diffusion tensor imaging

2004 ◽  
Vol 10 (4) ◽  
pp. 392-397 ◽  
Author(s):  
Bernard D Coombs ◽  
Alan Best ◽  
Mark S Brown ◽  
David E Miller ◽  
John Corboy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Diffusion Coefficient ◽  
White Matter ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
Age And Gender ◽  
Secondary Degeneration ◽  
Quantitative Mr ◽  
Normal Appearing White Matter ◽  
And Gender

Lesions in the corpus callosum in multiple sclerosis (MS) include those that are hyperintense on T2-weighted images, which can be either focal (isolated) or connected, but there is evidence that the corpus callosum, similar to other white matter regions, contains normal appearing white matter (NAWM) which is abnormal based on quantitative MR methodologies. In this pilot study, diffusion tensor based measures were determined in corpus callosum from 10 patients with MS and 12 age and gender matched controls. T2-hyperintense lesions were carefully segmented out from normal appearing corpus callosum to minimize contamination of the NAWM fraction with these lesions. The orientationally averaged diffusion coefficient was increased and the fractional anisotropy reduced in the NAWM fraction of the MS patients. These results confirm prior studies which suggest that pathology in the NAWM occurs independent of focal MS lesions, and are not likely the result of sample contamination through or across slices. This injury to the NAWM may be the result of focal, microscopic T2-invisible lesions and/or secondary degeneration related to distant lesions whose related fibres cross the corpus callosum.

scholarly journals Comparison of Neurite Orientation Dispersion and Density Imaging and Two-Compartment Spherical Mean Technique Parameter Maps in Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel Johnson ◽  
Antonio Ricciardi ◽  
Wallace Brownlee ◽  
Baris Kanber ◽  
Ferran Prados ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Diffusion Mri ◽  
Volume Fraction ◽  
Diffusion Tensor ◽  
Healthy Controls ◽  
Age And Gender ◽  
Spherical Mean ◽  
White Matter Microstructure ◽  
And Gender

Background: Neurite orientation dispersion and density imaging (NODDI) and the spherical mean technique (SMT) are diffusion MRI methods providing metrics with sensitivity to similar characteristics of white matter microstructure. There has been limited comparison of changes in NODDI and SMT parameters due to multiple sclerosis (MS) pathology in clinical settings.Purpose: To compare group-wise differences between healthy controls and MS patients in NODDI and SMT metrics, investigating associations with disability and correlations with diffusion tensor imaging (DTI) metrics.Methods: Sixty three relapsing-remitting MS patients were compared to 28 healthy controls. NODDI and SMT metrics corresponding to intracellular volume fraction (vin), orientation dispersion (ODI and ODE), diffusivity (D) (SMT only) and isotropic volume fraction (viso) (NODDI only) were calculated from diffusion MRI data, alongside DTI metrics (fractional anisotropy, FA; axial/mean/radial diffusivity, AD/MD/RD). Correlations between all pairs of MRI metrics were calculated in normal-appearing white matter (NAWM). Associations with expanded disability status scale (EDSS), controlling for age and gender, were evaluated. Patient-control differences were assessed voxel-by-voxel in MNI space controlling for age and gender at the 5% significance level, correcting for multiple comparisons. Spatial overlap of areas showing significant differences were compared using Dice coefficients.Results: NODDI and SMT show significant associations with EDSS (standardised beta coefficient −0.34 in NAWM and −0.37 in lesions for NODDI vin; 0.38 and −0.31 for SMT ODE and vin in lesions; p < 0.05). Significant correlations in NAWM are observed between DTI and NODDI/SMT metrics. NODDI vin and SMT vin strongly correlated (r = 0.72, p < 0.05), likewise NODDI ODI and SMT ODE (r = −0.80, p < 0.05). All DTI, NODDI and SMT metrics detect widespread differences between patients and controls in NAWM (12.57% and 11.90% of MNI brain mask for SMT and NODDI vin, Dice overlap of 0.42).Data Conclusion: SMT and NODDI detect significant differences in white matter microstructure between MS patients and controls, concurring on the direction of these changes, providing consistent descriptors of tissue microstructure that correlate with disability and show alterations beyond focal damage. Our study suggests that NODDI and SMT may play a role in monitoring MS in clinical trials and practice.

scholarly journals A higher proportion of ermin-immunopositive oligodendrocytes in areas of remyelination

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256155
Author(s):  
Intakhar Ahmad ◽  
Stig Wergeland ◽  
Eystein Oveland ◽  
Lars Bø
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Corpus Callosum ◽  
Mouse Model ◽  
Grey Matter ◽  
Early Stage ◽  
Relative Proportion ◽  
Normal Appearing White Matter ◽  
The Brain

Incomplete remyelination is frequent in multiple sclerosis (MS)-lesions, but there is no established marker for recent remyelination. We investigated the role of the oligodendrocyte/myelin protein ermin in de- and remyelination in the cuprizone (CPZ) mouse model, and in MS. The density of ermin+ oligodendrocytes in the brain was significantly decreased after one week of CPZ exposure (p < 0.02). The relative proportion of ermin+ cells compared to cells positive for the late-stage oligodendrocyte marker Nogo-A increased at the onset of remyelination in the corpus callosum (p < 0.02). The density of ermin-positive cells increased in the corpus callosum during the CPZ-phase of extensive remyelination (p < 0.0001). In MS, the density of ermin+ cells was higher in remyelinated lesion areas compared to non-remyelinated areas both in white- (p < 0.0001) and grey matter (p < 0.0001) and compared to normal-appearing white matter (p < 0.001). Ermin immunopositive cells in MS-lesions were not immunopositive for the early-stage oligodendrocyte markers O4 and O1, but a subpopulation was immunopositive for Nogo-A. The data suggest a relatively higher proportion of ermin immunopositivity in oligodendrocytes compared to Nogo-A indicates recent or ongoing remyelination.

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.

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.

Magnetisation transfer of normal appearing white matter in primary progressive multiple sclerosis

1999 ◽  
Vol 5 (5) ◽  
pp. 313-316 ◽  
Author(s):  
S M Leary ◽  
N C Silver ◽  
V L Stevenson ◽  
G J Barker ◽  
D H Miller ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Corpus Callosum ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Magnetisation Transfer ◽  
Centrum Semiovale ◽  
Primary Progressive ◽  
Normal Appearing White Matter ◽  
Frontal White Matter

Patients with primary progressive multiple sclerosis may develop severe disability despite a paucity of lesions on conventional magnetic resonance imaging, raising the possibility that intrinsic changes in normal appearing white matter (NAWM) contribute to disability. This study has measured magnetisation transfer ratio (MTR), an index of tissue damage, of NAWM in 52 patients with primary progressive multiple sclerosis and 26 healthy controls. Absolute values of MTR were obtained from the genu of the corpus callosum and pons, and mean values were calculated from bilateral regions in the centrum semiovale, frontal white matter, parieto-occipital white matter and posterior limb of the internal capsule. The median MTR was lower in all regions in patients compared to controls. Median values (per cent units) were significantly lower in corpus callosum (39.73 vs 40.63; P=0.01), frontal white matter (39.11 vs 39.59; P=0.01) and centrum semiovale (37.21 vs 37.82; P50.05). This study has demonstrated small but widespread decreases in MTR in NAWM in primary progressive multiple sclerosis supporting the hypothesis that there are intrinsic changes in NAWM which may contribute to disability in this patient group.

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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