Water diffusion is elevated in widespread regions of normal-appearing white matter in multiple sclerosis and correlates with diffusion in focal lesions

2001 ◽  
Vol 7 (2) ◽  
pp. 83-89 ◽  
Author(s):  
D J Werring ◽  
C A Clark ◽  
A G Droogan ◽  
G J Barker ◽  
D H Miller ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Corpus Callosum ◽  
Diffusion Imaging ◽  
Water Diffusion ◽  
Focal Lesions ◽  
Anatomical Distribution ◽  
Normal Appearing White Matter ◽  
Apparent Diffusion ◽  
The Brain

Pathological changes in the normal-appearing white matter in multiple sclerosis are well recognised, but their relationship to pathology in focal lesions is not well understood. Magnetic resonance diffusion imaging is sensitive to abnormalities in the integrity, size and geometry of water spaces in brain tissue. This study investigated the anatomical distribution of normal-appearing white matter diffusion abnormalities and their relationship to diffusion in focal lesions in multiple sclerosis (MS). The average apparent diffusion coefficient (ADCav) was measured by three-axis echoplanar diffusion imaging in normal-appearing white matter regions and lesions throughout the brain in 40 patients, and in white matter in 14 matched controls. The correlation between the ADCav in normal-appearing white matter and lesions was determined. In controls and patients, diffusion was highest in the corpus callosum. Patients had a higher mean ADCav than controls in widespread regions including the corpus callosum, cerebellar, temporal and occipital normal-appearing white matter. Mean normal-appearing white matter ADCav correlated strongly with mean lesion ADCav (r=0.67, P < 0.001). This study demonstrates that water diffusion is elevated in widespread areas of normal-appearing white matter in MS, and is correlated with diffusion in lesions. These findings suggest that the pathogenetic mechanisms causing tissue damage in lesions and normal-appearing white matter are at least partly linked.

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.

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.

scholarly journals Magnetization transfer and adiabatic T1ρ MRI reveal abnormalities in normal-appearing white matter of subjects with multiple sclerosis

2013 ◽  
Vol 20 (8) ◽  
pp. 1066-1073 ◽  
Author(s):  
Silvia Mangia ◽  
Adam F Carpenter ◽  
Andy E Tyan ◽  
Lynn E Eberly ◽  
Michael Garwood ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetization Transfer ◽  
Magnetic Resonance Images ◽  
Relaxation Methods ◽  
Normal Appearing White Matter ◽  
Relaxation Parameters ◽  
Relapsing Remitting ◽  
Cortical Gray Matter ◽  
The Brain

Background: Diffuse abnormalities are known to occur within the brain tissue of multiple sclerosis (MS) patients that is “normal appearing” on T1-weighted and T2-weighted magnetic resonance images. Objectives: With the goal of exploring the sensitivity of novel MRI parameters to detect such abnormalities, we implemented an inversion-prepared magnetization transfer (MT) protocol and adiabatic T1ρ and T2ρ rotating frame relaxation methods. Methods: Nine relapsing–remitting MS patients and seven healthy controls were recruited. Relaxation parameters were measured in a single slice just above the lateral ventricles and approximately parallel to the AC-PC line. Results: The MT ratio of regions encompassing the normal-appearing white matter (NAWM) was different in MS patients as compared with controls ( p = 0.043); however, the T1 measured during off-resonance irradiation (T1sat) was substantially more sensitive than the MT ratio for detecting differences between groups ( p = 0.0006). Adiabatic T1ρ was significantly prolonged in the NAWM of MS patents as compared to controls (by 6%, p = 0.026), while no differences were found among groups for T2ρ. No differences among groups were observed in the cortical gray matter for any relaxation parameter. Conclusions: The results suggest degenerative processes occurring in the NAWM of MS, likely not accompanied by significant abnormalities in iron content.

scholarly journals A Quantitative Study of Water Diffusion in Multiple Sclerosis Lesions and Normal-Appearing White Matter Using Echo-Planar Imaging

2000 ◽  
Vol 57 (7) ◽  
pp. 1017 ◽  
Author(s):  
Massimo Filippi ◽  
Giuseppe Iannucci ◽  
Mara Cercignani ◽  
Maria Assunta Rocca ◽  
Arianna Pratesi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Quantitative Study ◽  
Echo Planar Imaging ◽  
Water Diffusion ◽  
Planar Imaging ◽  
Normal Appearing White Matter ◽  
Echo Planar

scholarly journals Analysis of normal-appearing white matter of multiple sclerosis by tensor-based two-compartment model of water diffusion

2015 ◽  
Vol 25 (6) ◽  
pp. 1701-1707 ◽  
Author(s):  
Yasuhiko Tachibana ◽  
Takayuki Obata ◽  
Mariko Yoshida ◽  
Masaaki Hori ◽  
Koji Kamagata ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Compartment Model ◽  
Water Diffusion ◽  
Normal Appearing White Matter ◽  
Two Compartment Model

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.

Non-invasive quantification of inflammation, axonal and myelin injury in multiple sclerosis

Brain ◽  
2020 ◽  
Author(s):  
Simona Schiavi ◽  
Maria Petracca ◽  
Peng Sun ◽  
Lazar Fleysher ◽  
Sirio Cocozza ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Black Holes ◽  
White Matter ◽  
Corpus Callosum ◽  
Fractional Anisotropy ◽  
White Matter Lesions ◽  
Healthy Controls ◽  
Normal Appearing White Matter ◽  
Relapsing Remitting ◽  
Spectrum Imaging

Abstract The aim of this study was to determine the feasibility of diffusion basis spectrum imaging in multiple sclerosis at 7 T and to investigate the pathological substrates of tissue damage in lesions and normal-appearing white matter. To this end, 43 patients with multiple sclerosis (24 relapsing-remitting, 19 progressive), and 21 healthy control subjects were enrolled. White matter lesions were classified in T1-isointense, T1-hypointense and black holes. Mean values of diffusion basis spectrum imaging metrics (fibres, restricted and non-restricted fractions, axial and radial diffusivities and fractional anisotropy) were measured from whole brain white matter lesions and from both lesions and normal appearing white matter of the corpus callosum. Significant differences were found between T1-isointense and black holes (P ranging from 0.005 to &lt;0.001) and between lesions’ centre and rim (P &lt; 0.001) for all the metrics. When comparing the three subject groups in terms of metrics derived from corpus callosum normal appearing white matter and T2-hyperintense lesions, a significant difference was found between healthy controls and relapsing-remitting patients for all metrics except restricted fraction and fractional anisotropy; between healthy controls and progressive patients for all metrics except restricted fraction and between relapsing-remitting and progressive multiple sclerosis patients for all metrics except fibres and restricted fractions (P ranging from 0.05 to &lt;0.001 for all). Significant associations were found between corpus callosum normal-appearing white matter fibres fraction/non-restricted fraction and the Symbol Digit Modality Test (respectively, r = 0.35, P = 0.043; r = −0.35, P = 0.046), and between black holes radial diffusivity and Expanded Disability Status Score (r = 0.59, P = 0.002). We showed the feasibility of diffusion basis spectrum imaging metrics at 7 T, confirmed the role of the derived metrics in the characterization of lesions and normal appearing white matter tissue in different stages of the disease and demonstrated their clinical relevance. Thus, suggesting that diffusion basis spectrum imaging is a promising tool to investigate multiple sclerosis pathophysiology, monitor disease progression and treatment response.

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