scholarly journals Cortical axonal loss is associated with both gray matter demyelination and white matter tract pathology in progressive multiple sclerosis: Evidence from a combined MRI-histopathology study

2020 ◽  
pp. 135245852091897 ◽  
Author(s):  
Svenja Kiljan ◽  
Paolo Preziosa ◽  
Laura E Jonkman ◽  
Wilma DJ van de Berg ◽  
Jos Twisk ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
White Matter Lesions ◽  
Progressive Multiple Sclerosis ◽  
Axonal Loss ◽  
Normal Appearing White Matter ◽  
Axonal Density ◽  
Neuroaxonal Degeneration

Background: Neuroaxonal degeneration is one of the hallmarks of clinical deterioration in progressive multiple sclerosis (PMS). Objective: To elucidate the association between neuroaxonal degeneration and both local cortical and connected white matter (WM) tract pathology in PMS. Methods: Post-mortem in situ 3T magnetic resonance imaging (MRI) and cortical tissue blocks were collected from 16 PMS donors and 10 controls. Cortical neuroaxonal, myelin, and microglia densities were quantified histopathologically. From diffusion tensor MRI, fractional anisotropy, axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were quantified in normal-appearing white matter (NAWM) and white matter lesions (WML) of WM tracts connected to dissected cortical regions. Between-group differences and within-group associations were investigated through linear mixed models. Results: The PMS donors displayed significant axonal loss in both demyelinated and normal-appearing (NA) cortices ( p < 0.001 and p = 0.02) compared with controls. In PMS, cortical axonal density was associated with WML MD and AD ( p = 0.003; p = 0.02, respectively), and NAWM MD and AD ( p = 0.04; p = 0.049, respectively). NAWM AD and WML AD explained 12.6% and 22.6%, respectively, of axonal density variance in NA cortex. Additional axonal loss in demyelinated cortex was associated with cortical demyelination severity ( p = 0.002), explaining 34.4% of axonal loss variance. Conclusion: Reduced integrity of connected WM tracts and cortical demyelination both contribute to cortical axonal loss in PMS.

Diffusion tensor imaging abnormalities in depressed multiple sclerosis patients

2009 ◽  
Vol 16 (2) ◽  
pp. 189-196 ◽  
Author(s):  
A. Feinstein ◽  
P. O'Connor ◽  
N. Akbar ◽  
L. Moradzadeh ◽  
CJM Scott ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Magnetic Resonance ◽  
Grey Matter ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Resonance Imaging ◽  
Normal Appearing White Matter

Depression is common in patients with multiple sclerosis, but to date no studies have explored diffusion tensor imaging indices associated with mood change. This study aimed to determine cerebral correlates of depression in multiple sclerosis patients using diffusion tensor imaging. Sixty-two subjects with multiple sclerosis were assessed for depression with the Beck Depression Inventory (BDI-II). All subjects underwent magnetic resonance imaging. Whole brain and regional volumes were calculated for lesions (hyper/hypointense) and normal-appearing white and grey matter. Fractional anisotropy and mean diffusivity were calculated for each brain region. Magnetic resonance imaging comparisons were undertaken between depressed (Beck Depression Inventory ≥19) and non-depressed subjects. Depressed subjects (n = 30) had a higher hypointense lesion volume in the right medial inferior frontal region, a smaller normal-appearing white matter volume in the left superior frontal region, and lower fractional anisotropy and higher mean diffusivity in the left anterior temporal normal-appearing white matter and normal-appearing grey matter regions, respectively. Depressed subjects also had higher mean diffusivity in right inferior frontal hyperintense lesions. Magnetic resonance imaging variables contributed to 43% of the depression variance. We conclude that the presence of more marked diffusion tensor imaging abnormalities in the normal-appearing white matter and normal-appearing grey matter of depressed subjects highlights the importance of more subtle measures of structural brain change in the pathogenesis of depression.

scholarly journals Discrimination of epileptogenic lesions and perilesional white matter using diffusion tensor magnetic resonance imaging

2018 ◽  
Vol 32 (1) ◽  
pp. 10-16
Author(s):  
Alexander Rau ◽  
Elias Kellner ◽  
Niels A Foit ◽  
Niklas Lützen ◽  
Dieter H Heiland ◽  
...  
Keyword(s):  
White Matter ◽  
Fractional Anisotropy ◽  
Diffusion Tensor ◽  
Focal Cortical Dysplasia ◽  
Mean Diffusivity ◽  
Area Under The Curve ◽  
P Value ◽  
Radial Diffusivity ◽  
Normal Appearing White Matter ◽  
Diffusion Parameters

The aim of this study was to evaluate whether ganglioglioma (GGL), dysembryoplastic neuroepithelial tumour (DNET) and FCD (focal cortical dysplasia) are distinguishable through diffusion tensor imaging. Additionally, it was investigated whether the diffusion measures differed in the perilesional (pNAWM) and in the contralateral normal appearing white matter (cNAWM). Six GGLs, eight DNETs and seven FCDs were included in this study. Quantitative diffusion measures, that is, axial, radial and mean diffusivity and fractional anisotropy, were determined in the lesion identified on isotropic T2 or FLAIR-weighted images and in pNAWM and cNAWM, respectively. DNET differed from FCD in mean diffusivity, and GGL from FCD in radial diffusivity. Both types of glioneuronal tumours were different from pNAWM in fractional anisotropy and radial diffusivity. For identifying the tumour edges, threshold values for tumour-free tissue were investigated with receiver operating characteristic analyses: tumour could be separated from pNAWM at a threshold ≤ 0.32 (fractional anisotropy) or ≥ 0.56 (radial diffusivity) *10–3 mm2/s (area under the curve 0.995 and 0.990 respectively). While diffusion parameters of FCDs differed from cNAWM (radial diffusivity (*10–3 mm/s2): 0.74 ± 0.19 vs. 0.43 ± 0.05; corrected p-value < 0.001), the pNAWM could not be differentiated from the FCD.

scholarly journals Expression of disease‐related mi RNA s in white‐matter lesions of progressive multiple sclerosis brains

2019 ◽  
Vol 6 (5) ◽  
pp. 854-862 ◽  
Author(s):  
Ajai Tripathi ◽  
Christina Volsko ◽  
Ushasi Datta ◽  
Keren Regev ◽  
Ranjan Dutta
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
White Matter Lesions ◽  
Progressive Multiple Sclerosis

In vivo gradients of thalamic damage in paediatric multiple sclerosis: a window into pathology

Brain ◽  
2020 ◽  
Author(s):  
Ermelinda De Meo ◽  
Loredana Storelli ◽  
Lucia Moiola ◽  
Angelo Ghezzi ◽  
Pierangelo Veggiotti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetic Resonance ◽  
Fractional Anisotropy ◽  
Mean Diffusivity ◽  
White Matter Lesions ◽  
Healthy Controls ◽  
Paediatric Multiple Sclerosis ◽  
Multiple Sclerosis Patients

Abstract The thalamus represents one of the first structures affected by neurodegenerative processes in multiple sclerosis. A greater thalamic volume reduction over time, on its CSF side, has been described in paediatric multiple sclerosis patients. However, its determinants and the underlying pathological changes, likely occurring before this phenomenon becomes measurable, have never been explored. Using a multiparametric magnetic resonance approach, we quantified, in vivo, the different processes that can involve the thalamus in terms of focal lesions, microstructural damage and atrophy in paediatric multiple sclerosis patients and their distribution according to the distance from CSF/thalamus interface and thalamus/white matter interface. In 70 paediatric multiple sclerosis patients and 26 age- and sex-matched healthy controls, we tested for differences in thalamic volume and quantitative MRI metrics—including fractional anisotropy, mean diffusivity and T1/T2-weighted ratio—in the whole thalamus and in thalamic white matter, globally and within concentric bands originating from CSF/thalamus interface. In paediatric multiple sclerosis patients, the relationship of thalamic abnormalities with cortical thickness and white matter lesions was also investigated. Compared to healthy controls, patients had significantly increased fractional anisotropy in whole thalamus (f2 = 0.145; P = 0.03), reduced fractional anisotropy (f2 = 0.219; P = 0.006) and increased mean diffusivity (f2 = 0.178; P = 0.009) in thalamic white matter and a trend towards a reduced thalamic volume (f2 = 0.027; P = 0.058). By segmenting the whole thalamus and thalamic white matter into concentric bands, in paediatric multiple sclerosis we detected significant fractional anisotropy abnormalities in bands nearest to CSF (f2 = 0.208; P = 0.002) and in those closest to white matter (f2 range = 0.183–0.369; P range = 0.010–0.046), while we found significant mean diffusivity (f2 range = 0.101–0.369; P range = 0.018–0.042) and T1/T2-weighted ratio (f2 = 0.773; P = 0.001) abnormalities in thalamic bands closest to CSF. The increase in fractional anisotropy and decrease in mean diffusivity detected at the CSF/thalamus interface correlated with cortical thickness reduction (r range = −0.27–0.34; P range = 0.004–0.028), whereas the increase in fractional anisotropy detected at the thalamus/white matter interface correlated with white matter lesion volumes (r range = 0.24–0.27; P range = 0.006–0.050). Globally, our results support the hypothesis of heterogeneous pathological processes, including retrograde degeneration from white matter lesions and CSF-mediated damage, leading to thalamic microstructural abnormalities, likely preceding macroscopic tissue loss. Assessing thalamic microstructural changes using a multiparametric magnetic resonance approach may represent a target to monitor the efficacy of neuroprotective strategies early in the disease course.

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.

scholarly journals Hypoperfusion of the Cerebral White Matter in Multiple Sclerosis: Possible Mechanisms and Pathophysiological Significance

2008 ◽  
Vol 28 (10) ◽  
pp. 1645-1651 ◽  
Author(s):  
Jacques De Keyser ◽  
Christel Steen ◽  
Jop P Mostert ◽  
Marcus W Koch
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Adrenergic Receptors ◽  
Perfusion Magnetic Resonance Imaging ◽  
Cerebral White Matter ◽  
Perivascular Spaces ◽  
Axonal Loss ◽  
Normal Appearing White Matter ◽  
Demyelinating Lesions ◽  
The Central Nervous System

Multiple sclerosis (MS) is a disease of the central nervous system characterized by patchy areas of demyelination, inflammation, axonal loss and gliosis, and a diffuse axonal degeneration throughout the so-called normal-appearing white matter (NAWM). A number of recent studies using perfusion magnetic resonance imaging in both relapsing and progressive forms of MS have shown a decreased perfusion of the NAWM, which does not appear to be secondary to axonal loss. The reduced perfusion of the NAWM in MS might be caused by a widespread astrocyte dysfunction, possibly related to a deficiency in astrocytic β2-adrenergic receptors and a reduced formation of cAMP, resulting in a reduced uptake of K+ at the nodes of Ranvier and a reduced release of K+ in the perivascular spaces. Pathologic and imaging studies suggest that ischemic changes might be involved in the development of a subtype of focal demyelinating lesions (type III lesions), and there appears to exist a relationship between decreased white matter perfusion and cognitive dysfunction in patients with MS.

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