Association of retinal atrophy with cortical lesions and leptomeningeal enhancement in multiple sclerosis on 7T MRI

2021 ◽  
pp. 135245852110233
Author(s):  
Ryan Mizell ◽  
Hegang Chen ◽  
Jeffrey Lambe ◽  
Shiv Saidha ◽  
Daniel M Harrison
Keyword(s):  
Multiple Sclerosis ◽  
7 Tesla ◽  
Retinal Layer ◽  
Inner Plexiform Layer ◽  
Cortical Lesions ◽  
Post Contrast ◽  
Leptomeningeal Enhancement ◽  
Retinal Layers ◽  
Meningeal Inflammation ◽  
Retinal Atrophy

Background: Retinal atrophy in multiple sclerosis (MS) as measured by optical coherence tomography (OCT) correlates with demyelinating lesions and brain atrophy, but its relationship with cortical lesions (CLs) and meningeal inflammation is not well known. Objectives: To evaluate the relationship of retinal layer atrophy with leptomeningeal enhancement (LME) and CLs in MS as visualized on 7 Tesla (7T) magnetic resonance imaging (MRI). Methods: Forty participants with MS underwent 7T MRI of the brain and OCT. Partial correlation and mixed-effects regression evaluated relationships between MRI and OCT findings. Results: All participants had CLs and 32 (80%) participants had LME on post-contrast MRI. Ganglion cell/inner plexiform layer (GCIPL) thickness correlated with total CL volume ( r =−0.45, p < 0.01). Participants with LME at baseline had thinner macular retinal nerve fiber layer (mRNFL; p = 0.01) and GCIPL ( p < 0.01). Atrophy in various retinal layers was faster in those with certain patterns of LME. For example, mRNFL declined –1.113 (–1.974, –0.252) μm/year faster in those with spread/fill-pattern LME foci at baseline compared with those without ( p = 0.01). Conclusion: This study associates MRI findings of LME and cortical pathology with thinning of retinal layers as measured by OCT, suggesting a common link between meningeal inflammation, CLs, and retinal atrophy in MS.

scholarly journals No association between cortical lesions and leptomeningeal enhancement on 7-Tesla MRI in multiple sclerosis

2019 ◽  
Vol 26 (2) ◽  
pp. 165-176 ◽  
Author(s):  
Mehrnaz Ighani ◽  
Samuel Jonas ◽  
Izlem Izbudak ◽  
Seongjin Choi ◽  
Alfonso Lema-Dopico ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cortical Thickness ◽  
7 Tesla ◽  
Focal Lesion ◽  
Cortical Lesions ◽  
Leptomeningeal Enhancement ◽  
Meningeal Inflammation ◽  
Cortical Gray Matter ◽  
Inflammatory Processes ◽  
Magnetic Resonance Imaging Mri

Background: Autopsy data suggest a causative link between meningeal inflammation and cortical lesions (CLs) in multiple sclerosis (MS). Objective: To use leptomeningeal enhancement (LME) and CLs on 7-Tesla (7T) magnetic resonance imaging (MRI) to investigate associations between meningeal inflammation and cortical pathology. Methods: Forty-one participants with MS underwent 7T MRI of the brain. CLs and foci of LME were quantified. Results: All MS participants had CLs; 27 (65.8%) had >1 focus of LME. Except for hippocampal CL count (ρ = 0.32 with spread/fill-sulcal pattern LME, p = 0.042), no significant correlations were seen between LME and CLs. Mean cortical thickness correlated with the number of LME foci (ρ = –0.43, p = 0.005). Participants with relapsing–remitting multiple sclerosis (RRMS) showed no correlation with neocortical CLs, but significant correlations were seen between LME and hippocampal lesion count (ρ = 0.39, p = 0.030), normalized cortical gray matter (GM) volume (ρ = –0.49, p = 0.005), and mean cortical thickness (ρ = –0.59, p < 0.001). Conclusion: This study supports a relationship between LME and cortical GM atrophy but does not support an association of LME and neocortical CLs. This may indicate that meningeal inflammation is involved with neurodegenerative inflammatory processes, rather than focal lesion development.

scholarly journals Retinal atrophy in relation to visual functioning and vision-related quality of life in patients with multiple sclerosis

2017 ◽  
Vol 24 (6) ◽  
pp. 767-776 ◽  
Author(s):  
Lisanne J Balk ◽  
Danko Coric ◽  
Jenny A Nij Bijvank ◽  
Joep Killestein ◽  
Bernard MJ Uitdehaag ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Visual Acuity ◽  
Optic Neuritis ◽  
Retinal Layer ◽  
Inner Plexiform Layer ◽  
Visual Functioning ◽  
Retinal Atrophy ◽  
Related Quality

Background: Inner retinal layer atrophy in patients with multiple sclerosis (MS) has been validated as a structural imaging biomarker for neurodegeneration. Objective: To determine how retinal layer thickness relates to high-contrast visual acuity (HCVA), low-contrast visual acuity (LCVA) and vision-related quality of life (QoL) and to investigate the effect of previous episodes on MS-associated optic neuritis (MSON). Methods: Spectral-domain optical coherence tomography (SD-OCT) was performed in 267 patients with MS. Images were segmented for the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion cell inner plexiform layer (GCIPL). Ophthalmological evaluations included history of MSON, HCVA, LCVA, and vision-related QoL. Results: Independent of MSON, HCVA and LCVA were significantly associated with pRNFL and GCIPL thicknesses. Vision-related QoL was positively associated with pRNFL (β = 0.92, p = 0.06) and GCIPL (β = 0.93, p = 0.02) thicknesses. These associations were independent of MSON. Not only binocular but also monocular atrophy of the inner retinal layers was associated with lower vision-related QoL. Conclusion: This study showed that retinal atrophy has a significant impact on visual functioning in patients with MS. OCT may therefore provide useful insight to patients with visual dysfunction, and our findings support including OCT and vision-related QoL measures into optic neuritis treatment trials.

scholarly journals Serum neurofilament levels reflect outer retinal layer changes in multiple sclerosis

2021 ◽  
Vol 14 ◽  
pp. 175628642110034
Author(s):  
Caspar B. Seitz ◽  
Falk Steffen ◽  
Muthuraman Muthuraman ◽  
Timo Uphaus ◽  
Julia Krämer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optic Neuritis ◽  
Previous History ◽  
Supervised Machine Learning ◽  
Support Vector ◽  
Retinal Layer ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Retinal Layers ◽  
History Of

Background: Serum neurofilament light chain (sNfL) and distinct intra-retinal layers are both promising biomarkers of neuro-axonal injury in multiple sclerosis (MS). We aimed to unravel the association of both markers in early MS, having identified that neurofilament has a distinct immunohistochemical expression pattern among intra-retinal layers. Methods: Three-dimensional (3D) spectral domain macular optical coherence tomography scans and sNfL levels were investigated in 156 early MS patients (female/male: 109/47, mean age: 33.3 ± 9.5 years, mean disease duration: 2.0 ± 3.3 years). Out of the whole cohort, 110 patients had no history of optic neuritis (NHON) and 46 patients had a previous history of optic neuritis (HON). In addition, a subgroup of patients ( n = 38) was studied longitudinally over 2 years. Support vector machine analysis was applied to test a regression model for significant changes. Results: In our cohort, HON patients had a thinner outer plexiform layer (OPL) volume compared to NHON patients ( B = −0.016, SE = 0.006, p = 0.013). Higher sNfL levels were significantly associated with thinner OPL volumes in HON patients ( B = −6.734, SE = 2.514, p = 0.011). This finding was corroborated in the longitudinal subanalysis by the association of higher sNfL levels with OPL atrophy ( B = 5.974, SE = 2.420, p = 0.019). sNfL levels were 75.7% accurate at predicting OPL volume in the supervised machine learning. Conclusions: In summary, sNfL levels were a good predictor of future outer retinal thinning in MS. Changes within the neurofilament-rich OPL could be considered as an additional retinal marker linked to MS neurodegeneration.

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

2019 ◽  
Vol 26 (12) ◽  
pp. 1497-1509 ◽  
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.

A clinically feasible 7-Tesla protocol for the identification of cortical lesions in Multiple Sclerosis

2020 ◽  
Vol 30 (8) ◽  
pp. 4586-4594 ◽  
Author(s):  
Sirio Cocozza ◽  
Mirco Cosottini ◽  
Alessio Signori ◽  
Lazar Fleysher ◽  
Mohamed Mounir El Mendili ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
7 Tesla ◽  
Cortical Lesions

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

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 &lt; 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 &lt; 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.

scholarly journals Association of body mass index with longitudinal rates of retinal atrophy in multiple sclerosis

2020 ◽  
Vol 26 (7) ◽  
pp. 843-854
Author(s):  
Angeliki G Filippatou ◽  
Jeffrey Lambe ◽  
Elias S Sotirchos ◽  
Kathryn C Fitzgerald ◽  
Andrew Aston ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Body Mass Index ◽  
Body Mass ◽  
Plexiform Layer ◽  
Normal Weight ◽  
Uncontrolled Hypertension ◽  
Inner Plexiform Layer ◽  
Atrophy Rate ◽  
Spectral Domain Oct ◽  
Retinal Atrophy

Background: Studies evaluating associations between body mass index (BMI) and optical coherence tomography (OCT) measures in multiple sclerosis (MS) are lacking. Objective: To assess whether elevated BMI is associated with accelerated retinal atrophy. Methods: In this observational study, 513 MS patients were followed with serial spectral-domain OCT for a median of 4.4 years. Participants were categorized as normal weight (BMI: 18.5–24.9 kg/m2), overweight (BMI: 25–29.9 kg/m2), and obese (BMI: ⩾30 kg/m2). Participants with diabetes mellitus or uncontrolled hypertension and eyes with optic neuritis (ON) ⩽6 months prior to baseline OCT or during follow-up were excluded. Statistical analyses were performed with mixed-effects linear regression. Results: Obese patients ( n = 146) exhibited accelerated rates of ganglion cell + inner plexiform layer (GCIPL) atrophy relative to normal weight patients ( n = 214; –0.57%/year (95% confidence interval (CI): –0.65% to –0.48%) versus –0.42%/year (95% CI: –0.49% to –0.35%); p = 0.012). GCIPL atrophy rate did not differ between overweight ( n = 153) and normal weight patients (–0.47%/year vs –0.42%/year; p = 0.41). Each 1 kg/m2 higher BMI was associated with accelerated GCIPL (–0.011%/year; 95% CI: –0.019% to –0.004%; p = 0.003) atrophy. Multivariable analyses accounting for age, sex, race, MS subtype, and ON history did not alter the above findings. Conclusions: Elevated BMI, in the absence of overt metabolic comorbidities, may be associated with accelerated GCIPL atrophy. Obesity, a modifiable risk factor, may be associated with accelerated neurodegeneration in MS.

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