Non-lesional white matter changes in pediatric multiple sclerosis and monophasic demyelinating disorders

2012 ◽  
Vol 18 (12) ◽  
pp. 1754-1759 ◽  
Author(s):  
JM Tillema ◽  
J Leach ◽  
I Pirko
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Demyelinating Disease ◽  
Diffusion Tensor ◽  
Internal Capsule ◽  
Acute Disseminated Encephalomyelitis ◽  
Childhood Onset ◽  
Normal Appearing White Matter ◽  
Automated Method ◽  
Demyelinating Disorders

Objective: To analyze diffusion tensor imaging (DTI) derived metrics between patients with childhood onset multiple sclerosis (MS), monophasic demyelinating illnesses, and healthy controls. Background: Monophasic demyelinating illnesses can be indistinguishable clinically and radiologically, utilizing standard MRI studies. DTI studies in adults implicate the involvement of normal-appearing white matter (NAWM) in MS. Methods: Subjects with DTI studies (15 directions, 1.5 Tesla (GE), 3x3x3 mm, interpolated to 1.5x1.5x3 mm) were retrospectively identified. We studied three groups: childhood onset MS ( n=18), monophasic illness (eight with acute disseminated encephalomyelitis (ADEM), seven with clinically isolated syndrome (CIS)) and age-matched controls. DTI had been obtained within one month of symptom onset for patients with ADEM and within a median of 20 months for the MS group. DTI measures were determined using a semi-automated method from standardized regions of interest (ROI) containing central fibers of the corpus callosum genu and internal capsule. Results: The MS group had significantly lower fractional anisotropy (FA) values compared to controls ( p<0.001), with increased radial diffusivity (RD) and decreased axial diffusivity (AD). In the monophasic group FA was smaller than the controls ( p=0.01) with increased RD and no difference in AD. Conclusions: This retrospective analysis provides evidence that NAWM is affected in pediatric MS and monophasic demyelinating disease, with a potentially novel pattern demonstrating reduced AD in pediatric MS. Further larger scale confirmatory studies are needed to address whether the demonstrated DTI changes could be used as a biomarker in pediatric patients presenting with an initial demyelinating event.

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.

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.

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.

scholarly journals Investigating Microstructural Changes in White Matter in Multiple Sclerosis: A Systematic Review and Meta-Analysis of Neurite Orientation Dispersion and Density Imaging

2021 ◽  
Vol 11 (9) ◽  
pp. 1151
Author(s):  
Abdulmajeed Alotaibi ◽  
Anna Podlasek ◽  
Amjad AlTokhis ◽  
Ali Aldhebaib ◽  
Rob A. Dineen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
White Matter ◽  
Diffusion Tensor ◽  
Meta Analysis ◽  
Random Effect ◽  
Microstructural Changes ◽  
Neurite Density ◽  
Normal Appearing White Matter ◽  
Significant Difference

Multiple sclerosis (MS) is characterised by widespread damage of the central nervous system that includes alterations in normal-appearing white matter (NAWM) and demyelinating white matter (WM) lesions. Neurite orientation dispersion and density imaging (NODDI) has been proposed to provide a precise characterisation of WM microstructures. NODDI maps can be calculated for the Neurite Density Index (NDI) and Orientation Dispersion Index (ODI), which estimate orientation dispersion and neurite density. Although NODDI has not been widely applied in MS, this technique is promising in investigating the complexity of MS pathology, as it is more specific than diffusion tensor imaging (DTI) in capturing microstructural alterations. We conducted a meta-analysis of studies using NODDI metrics to assess brain microstructural changes and neuroaxonal pathology in WM lesions and NAWM in patients with MS. Three reviewers conducted a literature search of four electronic databases. We performed a random-effect meta-analysis and the extent of between-study heterogeneity was assessed with the I2 statistic. Funnel plots and Egger’s tests were used to assess publication bias. We identified seven studies analysing 374 participants (202 MS and 172 controls). The NDI in WM lesions and NAWM were significantly reduced compared to healthy WM and the standardised mean difference of each was −3.08 (95%CI −4.22 to (−1.95), p ≤ 0.00001, I2 = 88%) and −0.70 (95%CI −0.99 to (−0.40), p ≤ 0.00001, I2 = 35%), respectively. There was no statistically significant difference of the ODI in MS WM lesions and NAWM compared to healthy controls. This systematic review and meta-analysis confirmed that the NDI is significantly reduced in MS lesions and NAWM than in WM from healthy participants, corresponding to reduced intracellular signal fraction, which may reflect underlying damage or loss of neurites.

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.

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