Thalamic lesions in multiple sclerosis by 7T MRI: Clinical implications and relationship to cortical pathology

Objective: Pathology in both cortex and deep gray matter contribute to disability in multiple sclerosis (MS). We used the increased signal-to-noise ratio of 7-tesla (7T) MRI to visualize small lesions within the thalamus and to relate this to clinical information and cortical lesions. Methods: We obtained 7T MRI scans on 34 MS cases and 15 healthy volunteers. Thalamic lesion number and volume were related to demographic data, clinical disability measures, and lesions in cortical gray matter. Results: Thalamic lesions were found in 24/34 of MS cases. Two lesion subtypes were noted: discrete, ovoid lesions, and more diffuse lesional areas lining the periventricular surface. The number of thalamic lesions was greater in progressive MS compared to relapsing–remitting (mean ±SD, 10.7 ±0.7 vs. 3.0 ±0.7, respectively, p < 0.001). Thalamic lesion burden (count and volume) correlated with EDSS score and measures of cortical lesion burden, but not with white matter lesion burden or white matter volume. Conclusions: Using 7T MRI allows identification of thalamic lesions in MS, which are associated with disability, progressive disease, and cortical lesions. Thalamic lesion analysis may be a simpler, more rapid estimate of overall gray matter lesion burden in MS.

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Heterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: Insights from 7 T imaging

Multiple Sclerosis Journal ◽

10.1177/1352458517726382 ◽

2017 ◽

Vol 24 (11) ◽

pp. 1433-1444 ◽

Cited By ~ 17

Author(s):

Céline Louapre ◽

Sindhuja T Govindarajan ◽

Costanza Giannì ◽

Nancy Madigan ◽

Jacob A Sloane ◽

...

Keyword(s):

Multiple Sclerosis ◽

Progressive Multiple Sclerosis ◽

Lesion Volume ◽

Thalamic Lesion ◽

Cortical Lesions ◽

Focal Lesions ◽

Thalamic Degeneration ◽

Relapsing Remitting ◽

Thalamic Lesions ◽

Magnetic Resonance Imaging Mri

Background: Thalamic degeneration impacts multiple sclerosis (MS) prognosis. Objective: To investigate heterogeneous thalamic pathology, its correlation with white matter (WM), cortical lesions and thickness, and as function of distance from cerebrospinal fluid (CSF). Methods: In 41 MS subjects and 17 controls, using 3 and 7 T imaging, we tested for (1) differences in thalamic volume and quantitative T2* (q-T2*) (2) globally and (3) within concentric bands originating from the CSF/thalamus interface; (4) the relation between thalamic, cortical, and WM metrics; and (5) the contribution of magnetic resonance imaging (MRI) metrics to clinical scores. We also assessed MS thalamic lesion distribution as a function of distance from CSF. Results: Thalamic lesions were mainly located next to the ventricles. Thalamic volume was decreased in MS versus controls ( p < 10−2); global q-T2* was longer in secondary progressive multiple sclerosis (SPMS) only ( p < 10−2), indicating myelin and/or iron loss. Thalamic atrophy and longer q-T2* correlated with WM lesion volume ( p < 0.01). In relapsing-remitting MS, q-T2* thalamic abnormalities were located next to the WM ( p < 0.01 (uncorrected), p = 0.09 (corrected)), while they were homogeneously distributed in SPMS. Cortical MRI metrics were the strongest predictors of clinical outcome. Conclusion: Heterogeneous pathological processes affect the thalamus in MS. While focal lesions are likely mainly driven by CSF-mediated factors, overall thalamic degeneration develops in association with WM lesions.

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Profiles of cortical inflammation in multiple sclerosis by 11C-PBR28 MR-PET and 7 Tesla imaging

Multiple Sclerosis Journal ◽

10.1177/1352458519867320 ◽

2019 ◽

Vol 26 (12) ◽

pp. 1497-1509 ◽

Cited By ~ 8

Author(s):

Elena Herranz ◽

Céline Louapre ◽

Constantina Andrada Treaba ◽

Sindhuja T Govindarajan ◽

Russell Ouellette ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Burden ◽

Relative Difference ◽

Tracer Uptake ◽

Microglia Activation ◽

Inactive Disease ◽

7 Tesla ◽

Cortical Lesion ◽

Cortical Lesions ◽

Cortical Areas

Background: Neuroinflammation with microglia activation is thought to be closely related to cortical multiple sclerosis (MS) lesion pathogenesis. Objective: Using 11C-PBR28 and 7 Tesla (7T) imaging, we assessed in 9 relapsing–remitting multiple sclerosis (RRMS) and 10 secondary progressive multiple sclerosis (SPMS) patients the following: (1) microglia activation in lesioned and normal-appearing cortex, (2) cortical lesion inflammatory profiles, and (3) the relationship between neuroinflammation and cortical integrity. Methods: Mean 11C-PBR28 uptake was measured in focal cortical lesions, cortical areas with 7T quantitative T2* (q-T2*) abnormalities, and normal-appearing cortex. The relative difference in cortical 11C-PBR28 uptake between patients and 14 controls was used to classify cortical lesions as either active or inactive. Disease burden was investigated according to cortical lesion inflammatory profiles. The relation between q-T2* and 11C-PBR28 uptake along the cortex was assessed. Results: 11C-PBR28 uptake was abnormally high in cortical lesions in RRMS and SPMS; in SPMS, tracer uptake was significantly increased also in normal-appearing cortex. 11C-PBR28 uptake and q-T2* correlated positively in many cortical areas, negatively in some regions. Patients with high cortical lesion inflammation had worse clinical outcome and higher intracortical lesion burden than patients with low inflammation. Conclusion: 11C-PBR28 and 7T imaging reveal distinct profiles of cortical inflammation in MS, which are related to disease burden.

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Quantitative 7-Tesla Imaging of Cortical Myelin Changes in Early Multiple Sclerosis

Frontiers in Neurology ◽

10.3389/fneur.2021.714820 ◽

2021 ◽

Vol 12 ◽

Author(s):

Valeria Barletta ◽

Elena Herranz ◽

Constantina A. Treaba ◽

Ambica Mehndiratta ◽

Russell Ouellette ◽

...

Keyword(s):

Multiple Sclerosis ◽

Quantitative Mri ◽

7 Tesla ◽

Cortical Lesion ◽

Healthy Controls ◽

Cortical Lesions ◽

Lesion Analysis ◽

Cortical Map ◽

The Brain

Cortical demyelination occurs early in multiple sclerosis (MS) and relates to disease outcome. The brain cortex has endogenous propensity for remyelination as proven from histopathology study. In this study, we aimed at characterizing cortical microstructural abnormalities related to myelin content by applying a novel quantitative MRI technique in early MS. A combined myelin estimation (CME) cortical map was obtained from quantitative 7-Tesla (7T) T2* and T1 acquisitions in 25 patients with early MS and 19 healthy volunteers. Cortical lesions in MS patients were classified based on their myelin content by comparison with CME values in healthy controls as demyelinated, partially demyelinated, or non-demyelinated. At follow-up, we registered changes in cortical lesions as increased, decreased, or stable CME. Vertex-wise analysis compared cortical CME in the normal-appearing cortex in 25 MS patients vs. 19 healthy controls at baseline and investigated longitudinal changes at 1 year in 10 MS patients. Measurements from the neurite orientation dispersion and density imaging (NODDI) diffusion model were obtained to account for cortical neurite/dendrite loss at baseline and follow-up. Finally, CME maps were correlated with clinical metrics. CME was overall low in cortical lesions (p = 0.03) and several normal-appearing cortical areas (p < 0.05) in the absence of NODDI abnormalities. Individual cortical lesion analysis revealed, however, heterogeneous CME patterns from extensive to partial or absent demyelination. At follow-up, CME overall decreased in cortical lesions and non-lesioned cortex, with few areas showing an increase (p < 0.05). Cortical CME maps correlated with processing speed in several areas across the cortex. In conclusion, CME allows detection of cortical microstructural changes related to coexisting demyelination and remyelination since the early phases of MS, and shows to be more sensitive than NODDI and relates to cognitive performance.

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Correlation of cortical lesions of multiple sclerosis at double inversion recovery with cognition screening scores

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-021-00285-5 ◽

2021 ◽

Vol 57 (1) ◽

Author(s):

Sally Mohamed Shaaban ◽

Azza Elmongui Elmongui ◽

Ahmed Abdel Khalek Abdel Razek ◽

Tamer Mohamed Belal

Keyword(s):

Multiple Sclerosis ◽

Gray Matter ◽

Inverse Correlation ◽

Inversion Recovery ◽

Double Inversion Recovery ◽

Cortical Lesion ◽

Cortical Lesions ◽

Lesion Load ◽

Significant Inverse Correlation ◽

Lesion Number

Abstract Background Multiple sclerosis is a chronic inflammatory disease affecting both white and gray matters of the central nervous system. It has been approved that the degree of gray matter involvement is closely associated with the degree of physical disability and the extent of cognitive impairment. Thus, it is necessary to incorporate widely available simple methods for neurocognitive evaluation and gray matter detection in the periodic assessment of MS patients that will influence treatment decisions. Objectives To assess the correlation of cortical lesions of multiple sclerosis (MS) at double inversion recovery (DIR) with cognition screening scores Methods This study was conducted on 30 patients with MS with an average age of 31.3±13.6 years. All of them underwent MRI and clinical assessment with the calculation of Expanded Disability Status Scale (EDSS), Montreal Cognitive Assessment (MoCA), and Symbol Digit Modality Test (SDMT) scores. The image analysis was performed by 2 reviewers for cortical lesion number, shape, and subtypes, and total lesion load. Results Both MoCA and SDMT scales had a significant inverse correlation with cortical lesions number (r=− 0.68, − 0.72) respectively and total lesion load (r=− 0.53, − 0.65) respectively. Besides, there was a significant inverse correlation between the MoCA test, varied cortical subtypes: leukocortical, juxtacortical, and intracortical subtypes (r = − 0.63, − 0.56, − 0.52) respectively, and different cortical lesion shapes: oval, wedge, and curvilinear shaped (r = − 0.62, − 0.69, − 0.49) respectively. As well, the SDMT scale showed a significant inverse correlation with varied cortical subtypes: intracortical, leukocortical, and juxtacortical subtypes (r = − 0.63, − 0.61, − 0.57) respectively, and different cortical lesion shapes: oval, curvilinear, and wedge shaped (r = − 0.61, − 0.59, − 0.46) respectively. Interestingly, there was an excellent inter-observer correlation of cortical lesion number (r = 0.96), total lesion load (r = 0.95), subtypes of cortical lesion (r = 0.94), and cortical lesion shapes (r = 0.77). Conclusion We concluded that DIR can detect cortical lesions of MS, and MRI findings were well-correlated with cognitive dysfunction in these patients.

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Characterization of thalamic lesions and their correlates in multiple sclerosis by ultra-high-field MRI

Multiple Sclerosis Journal ◽

10.1177/1352458520932804 ◽

2020 ◽

pp. 135245852093280

Author(s):

Ambica Mehndiratta ◽

Constantina A Treaba ◽

Valeria Barletta ◽

Elena Herranz ◽

Russell Ouellette ◽

...

Keyword(s):

Multiple Sclerosis ◽

Great Majority ◽

7 Tesla ◽

Lesion Volume ◽

Thalamic Lesion ◽

Information Processing Speed ◽

Neurological Disability ◽

Thalamic Lesions ◽

Clinical Measures

Background: Thalamic pathology is a marker for neurodegeneration and multiple sclerosis (MS) disease progression. Objective: To characterize (1) the morphology of thalamic lesions, (2) their relation to cortical and white matter (WM) lesions, and (3) clinical measures, and to assess (4) the imaging correlates of thalamic atrophy. Methods: A total of 90 MS patients and 44 healthy controls underwent acquisition of 7 Tesla images for lesion segmentation and 3 Tesla scans for atrophy evaluation. Thalamic lesions were classified according to the shape and the presence of a central venule. Regression analysis identified the predictors of (1) thalamic atrophy, (2) neurological disability, and (3) information processing speed. Results: Thalamic lesions were mostly ovoid than periventricular, and for the great majority (78%) displayed a central venule. Lesion volume in the thalamus, cortex, and WM did not correlate with each other. Thalamic atrophy was only associated with WM lesion volume ( p = 0.002); subpial and WM lesion volumes were associated with neurological disability ( p = 0.016; p < 0.001); and WM and thalamic lesion volumes were related with cognitive impairment ( p < 0.001; p = 0.03). Conclusion: Thalamic lesions are unrelated to those in the cortex and WM, suggesting that they may not share common pathogenic mechanisms and do not contribute to thalamic atrophy. Combined WM, subpial, and thalamic lesion volumes at 7 Tesla contribute to the disease severity.

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Cortical lesion load correlates with diffuse injury of multiple sclerosis normal appearing white matter

Multiple Sclerosis Journal ◽

10.1177/1352458513496344 ◽

2013 ◽

Vol 20 (2) ◽

pp. 227-233 ◽

Cited By ~ 13

Author(s):

Niraj Mistry ◽

Rasha Abdel-Fahim ◽

Olivier Mougin ◽

Christopher Tench ◽

Penny Gowland ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Cortical Lesion ◽

Cortical Lesions ◽

Magnetisation Transfer ◽

Magnetisation Transfer Ratio ◽

Lesion Load ◽

Transfer Ratio ◽

Normal Appearing White Matter ◽

Axon Loss

Background:Degeneration of central nervous system normal appearing white matter (NAWM) underlies disability and progression in multiple sclerosis (MS). Axon loss typifies NAWM degeneration.Objective:The objective of this paper is to assess correlation between cortical lesion load and magnetisation transfer ratio (MTR) of the NAWM in MS. This was in order to test the hypothesis that cortical lesions cause NAWM degeneration.Methods:Nineteen patients with MS underwent 7 Tesla magnetisation-prepared-rapid-acquisition-gradient-echo (MPRAGE), and magnetisation transfer ratio (MTR) brain magnetic resonance imaging (MRI). Cortical lesions were identified using MPRAGE and MTR images of cortical ribbons. White matter lesions (WMLs) were segmented using MPRAGE images. WML maps were subtracted from white matter volumes to produce NAWM masks. Pearson correlation was calculated for NAWM MTR vs cortical lesion load, and WML volumes.Results:Cortical lesion volumes and counts all had significant correlation with NAWM mean MTR. The strongest correlation was with cortical lesion volumes obtained using MTR images ( r = −0.6874, p = 0.0006). WML volume had no significant correlation with NAWM mean MTR ( r = −0.08706, p = 0.3615).Conclusion:Our findings are consistent with the hypothesis that cortical lesions cause NAWM degeneration. This implicates cortical lesions in the pathogenesis of NAWM axon loss, which underpins long-term disability and progression in MS.

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Faculty Opinions recommendation of Detecting cortical lesions in multiple sclerosis at 7 T using white matter signal attenuation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717297805.792652807 ◽

2012 ◽

Author(s):

Nancy Richert ◽

Francesca Bagnato

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Cortical Lesions ◽

Signal Attenuation

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Modeling the Relationship among Gray Matter Atrophy, Abnormalities in Connecting White Matter, and Cognitive Performance in Early Multiple Sclerosis

American Journal of Neuroradiology ◽

10.3174/ajnr.a4165 ◽

2014 ◽

Vol 36 (4) ◽

pp. 702-709 ◽

Cited By ~ 14

Author(s):

A.F. Kuceyeski ◽

W. Vargas ◽

M. Dayan ◽

E. Monohan ◽

C. Blackwell ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Cognitive Performance ◽

Gray Matter ◽

Gray Matter Atrophy ◽

The Relationship

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Association of Age at Onset With Gray Matter Volume and White Matter Microstructural Abnormalities in People With Multiple Sclerosis

Neurology ◽

10.1212/wnl.0000000000012869 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012869

Author(s):

Raffaello Bonacchi ◽

Alessandro Meani ◽

Elisabetta Pagani ◽

Olga Marchesi ◽

Andrea Falini ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Gray Matter ◽

Linear Models ◽

Gray Matter Volume ◽

Age At Onset ◽

Healthy Controls ◽

Compensatory Mechanisms ◽

Cross Sectional ◽

Matter Volume

Objective:To investigate whether age at onset influences brain gray matter volume (GMV) and white matter (WM) microstructural abnormalities in adult multiple sclerosis (MS) patients, given its influence on clinical phenotype and disease course.Method:In this hypothesis-driven cross-sectional study, we enrolled 67 pediatric-onset MS (POMS) patients and 143 sex- and disease duration (DD)-matched randomly-selected adult-onset MS (AOMS) patients, together with 208 healthy controls. All subjects underwent neurological evaluation and 3T MRI acquisition. MRI variables were standardized based on healthy controls, to remove effects of age and sex. Associations with DD in POMS and AOMS patients were studied with linear models. Time to reach clinical and MRI milestones was assessed with product-limit approach.Results:At DD=1 year, GMV and WM fractional anisotropy (FA) were abnormal in AOMS but not in POMS patients. Significant interaction of age at onset (POMS vs AOMS) into the association with DD was found for GMV and WM FA. The crossing point of regression lines in POMS and AOMS patients was at 20 years of DD for GMV and 14 for WM FA. For POMS and AOMS patients, median DD was 29 and 19 years to reach Expanded Disability Status Scale=3 (p<0.001), 31 and 26 years to reach abnormal Paced Auditory Serial Addition Task-3 (p=0.01), 24 and 18 years to reach abnormal GMV (p=0.04), and 19 and 17 years to reach abnormal WM FA (p=0.36).Conclusions:Younger patients are initially resilient to MS-related damage. Then, compensatory mechanisms start failing with loss of WM integrity, followed by GM atrophy and finally disability.

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