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 ◽  
Water Diffusion ◽  
Focal Lesions ◽  
Normal Appearing White Matter

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 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

Progressive change in primary progressive multiple sclerosis normal-appearing white matter: a serial diffusion magnetic resonance imaging study

2004 ◽  
Vol 10 (2) ◽  
pp. 182-187 ◽  
Author(s):  
Klaus Schmierer ◽  
Daniel R Altmann ◽  
Nadja Kassim ◽  
Hagen Kitzler ◽  
Christian M Kerskens ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetic Resonance ◽  
Healthy Subjects ◽  
Progressive Multiple Sclerosis ◽  
Water Diffusion ◽  
Primary Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Normal Appearing White Matter

In spite of marked disability, patients with primary progressive multiple sclerosis (PPMS) display smaller lesion volumes on conventional magnetic resonance imaging (MRI) compared with other forms of multiple sclerosis (MS). Hence, damage to the normal-appear ing brain tissue (NA BT) may play an important role in explaining the patho genesis of disability in PPMS. Diffusion-weighted MRI (DW-MRI) probes water diffusion in vivo that can be altered by patho logic changes. Using DW-MRI we investigated diffusion in the NA BT of 15 patients with PPMS over one year. The average apparent diffusion coefficient (A DC av) was measured in 10 regions of interest located in the normal- appearing thalamus and the normal-appearing white matter (NAWM). Six healthy subjects served as a reference. In contrast to healthy subjects, patients with PPMS showed an increment within 12 months of the A DC av in NAWM which was associated with an increase of the T2- and T1-lesion volumes. The A DC av in frontal NAWM was associated with disability as measured by the MS Functio nal C omposite Measure. Serial DW-MRI depicts progressive changes in the NAWM of patients with PPMS. O ur preliminary findings suggest that the processes causing structural damage in NAWM and lesions in patients with PPMS are partially linked and that changes of water diffusion in NAWM depicted by DW-MRI are clinically relevant.

scholarly journals Automated Separation of Diffusely Abnormal White Matter from Focal White Matter Lesions on MRI in Multiple Sclerosis

2019 ◽  
Author(s):  
Josefina Maranzano ◽  
Mahsa Dadar ◽  
Douglas L. Arnold ◽  
D. Louis Collins ◽  
Sridar Narayanan
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Immune Cell ◽  
Magnetization Transfer ◽  
White Matter Lesions ◽  
Rank Test ◽  
Normalization Factor ◽  
Focal Lesions ◽  
Normal Appearing White Matter ◽  
The Mean

ABSTRACTBackgroundPrevious histopathology and MRI studies have addressed the differences between focal white matter lesions (FWML) and diffusely abnormal white matter (DAWM) in multiple sclerosis (MS). These two categories of white matter T2-weighted (T2w) hyperintensity show different degrees of demyelination, axonal loss and immune cell density on histopathology, potentially offering distinct correlations with symptoms.Objectives1) To automate the separation of FWML and DAWM using T2w MRI intensity thresholds and to investigate their differences in magnetization transfer ratios (MTR), which are sensitive to myelin content; 2) to correlate MTR values in FWML and DAWM with normalized signal intensity values on fluid attenuated inversion recovery (FLAIR), T2w, and T1-weighted (T1w) contrasts, as well as with the ratio of T2w/T1w normalized values, in order to determine whether these normalized intensities can be used as myelin-sensitive markers when MTR is not available.MethodsUsing similar 3T MRI protocols, 2 MS cohorts of 20 participants each were scanned in 2 centers, including: 3D T1w (MP2RAGE), 3D FLAIR, 2D T2w, and 3D magnetization-transfer (MT) contrasts. We used the first dataset to develop an automated technique to separate FWML from DAWM and the second one to validate the automation of the technique. We applied the automatic thresholds to both datasets and assessed the overlap of the manual and the automated masks using Dice kappa. We also assessed differences in mean MTR values between NAWM, DAWM and FWML, using manually and automatically derived masks in both datasets. Finally, we used the mean intensity of manually-traced areas of NAWM on T2w images as the normalization factor for each MRI contrast, and compared these with the normalized-intensity values obtained using automated NAWM (A-NAWM) masks as the normalization factor. Paired t-tests assessed the MTR differences across tissue types. Wilcoxon Signed Rank test and paired t-tests assessed FWML and DAWM differences in manual and automated derived volumes. Pearson correlations assessed the relationship between MTR and normalized intensity values in the manual and automated derived masks.ResultsThe mean Dice-kappa values for dataset 1 were: 0.8 for DAWM masks and 0.7 for FWML masks. In dataset 2, mean dice-kappa values were: 0.8 for DAWM and 0.8 for FWML. Also, manual and automated DAWM and FWML volumes were not significantly different in both datasets. MTR values (expressed as mean and standard deviation, arbitrary units) were significantly lower in manually derived FWML compared with DAWM in both datasets: 1) FWML: 37.1 ± 3.2 vs DAWM: 43.3 ± 2.1; t=13.2; p<0.0001, and 2) FWML: 32.5 ± 3.9 vs DAWM: 38.8 ± 1.7; t=9.8; p<0.0001. Similar results were obtained using the automatic derived masks in both datasets: 1) FWML: 35.8 ± 2.8 vs DAWM: 43.1 ± 1.6; t=15.3; p<0.0001, and 2) FWML: 31.3 ± 3.1 vs DAWM: 38.1 ± 1.5; t=12.8; p<0.0001. MTR was also significantly lower in manually derived DAWM masks compared with normal appearing white matter (NAWM) in both datasets: 1) NAWM: 46.7 ± 1.3; t=10.1; p<0.0001, and 2) NAWM: 39.3 ± 0.8; t=3.1; p=0.003. Similar results were obtained using the automatic derived masks in both datasets: 1) NAWM: 46.3 ± 1.1; t=13.7; p<0.0001, and 2) NAWM: 39.9 ± 1.1; t=9.6; p<0.0001.In both datasets, manually derived FWML and DAWM MTR values showed significant correlations with normalized FLAIR (r=−0.35 to −0.67; p=0.06 to <0.0001), T2w (r=−0.60 to −0.72; p=0.003 to <0.0001), T1w/T2w (r=0.63 to 0.77; p=0.002 to <0.0001), and T1w (r=0.77 to 0.92; p<0.0001) intensities. Finally, normalized intensity values obtained using automatic derived masks were significantly correlated with the manually derived values in both datasets.ConclusionsThe separation of FWML and DAWM on MRI scans of MS patients using automated intensity thresholds on T2w images is feasible. MTR values are significantly lower in FWML than DAWM, and DAWM values are significantly lower than NAWM, reflecting potentially greater demyelination within focal lesions. Normalized intensity values of different MRI contrasts exhibit a significant correlation with MTR values in both tissues of interest and could be used as a proxy to assess demyelination when MTR images are not available.

NODDI discloses early changes in the normal appearing white matter in paediatric multiple sclerosis

2021 ◽  
Vol 429 ◽  
pp. 118881
Author(s):  
Monica Margoni ◽  
Umberto Villani ◽  
Silvia Franciotta ◽  
Martina Rubin ◽  
Margherita Nosadini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Normal Appearing White Matter ◽  
Paediatric Multiple Sclerosis

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.

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