Salient Central Lesion Volume: A Standardized Novel Fully Automated Proxy for Brain FLAIR Lesion Volume in Multiple Sclerosis

2019 ◽  
Vol 29 (5) ◽  
pp. 615-623 ◽  
Author(s):  
Michael G. Dwyer ◽  
Niels Bergsland ◽  
Deepa P. Ramasamy ◽  
Bianca Weinstock‐Guttman ◽  
Michael H. Barnett ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Lesion Volume ◽  
Central Lesion

scholarly journals Changes in Cerebrospinal Fluid Balance of TNF and TNF Receptors in Naïve Multiple Sclerosis Patients: Early Involvement in Compartmentalised Intrathecal Inflammation

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1712
Author(s):  
Roberta Magliozzi ◽  
Francesco Pezzini ◽  
Mairi Pucci ◽  
Stefania Rossi ◽  
Francesco Facchiano ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cell ◽  
Protein Pattern ◽  
Fold Change ◽  
Cortical Lesion ◽  
Control Group ◽  
Lesion Volume ◽  
Mri Features ◽  
Csf Levels ◽  
Multiple Sclerosis Patients

An imbalance of TNF signalling in the inflammatory milieu generated by meningeal immune cell infiltrates in the subarachnoid space in multiple sclerosis (MS), and its animal model may lead to increased cortical pathology. In order to explore whether this feature may be present from the early stages of MS and may be associated with the clinical outcome, the protein levels of TNF, sTNF-R1 and sTNF-R2 were assayed in CSF collected from 122 treatment-naïve MS patients and 36 subjects with other neurological conditions at diagnosis. Potential correlations with other CSF cytokines/chemokines and with clinical and imaging parameters at diagnosis (T0) and after 2 years of follow-up (T24) were evaluated. Significantly increased levels of TNF (fold change: 7.739; p < 0.001), sTNF-R1 (fold change: 1.693; p < 0.001) and sTNF-R2 (fold change: 2.189; p < 0.001) were detected in CSF of MS patients compared to the control group at T0. Increased TNF levels in CSF were significantly (p < 0.01) associated with increased EDSS change (r = 0.43), relapses (r = 0.48) and the appearance of white matter lesions (r = 0.49). CSF levels of TNFR1 were associated with cortical lesion volume (r = 0.41) at T0, as well as with new cortical lesions (r = 0.56), whilst no correlation could be found between TNFR2 levels in CSF and clinical or MRI features. Combined correlation and pathway analysis (ingenuity) of the CSF protein pattern associated with TNF expression (encompassing elevated levels of BAFF, IFN-γ, IL-1β, IL-10, IL-8, IL-16, CCL21, haptoglobin and fibrinogen) showed a particular relationship to the interaction between innate and adaptive immune response. The CSF sTNF-R1-associated pattern (encompassing high levels of CXCL13, TWEAK, LIGHT, IL-35, osteopontin, pentraxin-3, sCD163 and chitinase-3-L1) was mainly related to altered T cell and B cell signalling. Finally, the CSF TNFR2-associated pattern (encompassing high CSF levels of IFN-β, IFN-λ2, sIL-6Rα) was linked to Th cell differentiation and regulatory cytokine signalling. In conclusion, dysregulation of TNF and TNF-R1/2 pathways associates with specific clinical/MRI profiles and can be identified at a very early stage in MS patients, at the time of diagnosis, contributing to the prediction of the disease outcome.

Serum amyloid A level correlates with T2 lesion volume and cortical volume in patients with multiple sclerosis

2021 ◽  
Vol 351 ◽  
pp. 577466
Author(s):  
Hiroaki Yokote ◽  
Shuta Toru ◽  
Yoichiro Nishida ◽  
Takaaki Hattori ◽  
Nobuo Sanjo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Lesion Volume ◽  
Cortical Volume ◽  
Amyloid A

T1 hypointense lesion load in secondary progressive multiple sclerosis: a comparison of pre versus post contrast loads and of manual versus semi automated threshold techniques for lesion segmentation

1998 ◽  
Vol 4 (5) ◽  
pp. 408-412 ◽  
Author(s):  
J I O'Riordan ◽  
M Gawne Cain ◽  
A Coles ◽  
L Wang ◽  
D AS Compston ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Strong Correlation ◽  
Measurement Techniques ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Mri Findings ◽  
Lesion Load ◽  
Post Contrast ◽  
Secondary Progressive

Magnetic resonance imaging (MRI) is increasingly being used as a monitoring tool for disease activity in therapeutic trials in multiple sclerosis. There is, however, only a limited relationship between MRI findings and clinical outcome measurements. It has been suggested that hypointense lesion load on T1 weighted imaging has a better correlation with disability than the more conventional T2 hyper intense lesion load. This study was undertaken to (i) evaluate different measurement techniques used to quantify T1 hypointense lesion load, and (ii) to compare lesion load as measured using different parameters and disability. Twenty-five patients with secondary progressive multiple sclerosis, mean age of 40 years (23-57), mean EDSS 5.7 (4-7) were analysed. T2 lesion load on FSE correlated well with both the hypointense lesion load on T1 pre-gadolinium (r=0.8, P50.0001) and T1 post-gadolinium (r=0.8, P50.0001) but less so with the enhancing lesion load (r=0.4, P50.05). There was a very strong correlation with T1 hypo-intense lesion volume pre and post gadolinium (r=0.96, P50.001). However, the EDSS was not correlated with the T2 lesion load (r=70.27, P=0.2), T1 pre-gadolinium load (r=70.3, P=0.1), T1 post gadolinium load (r=70.4, P=0.7) and enhancing lesion load (r=70.28, P=0.2), or with the degree of hypointensity of T1 weighted images determined using the threshold technique. There is a strong correlation between T1 hypointense lesion volume both pre and post gadolinium and also between T1 and T2 lesion volumes.

scholarly journals Learning ability correlates with brain atrophy and disability progression in RRMS

2018 ◽  
Vol 90 (1) ◽  
pp. 38-43 ◽  
Author(s):  
Maria Pia Sormani ◽  
Nicola De Stefano ◽  
Gavin Giovannoni ◽  
Dawn Langdon ◽  
Daniela Piani-Meier ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Volume ◽  
Practice Effect ◽  
Wilcoxon Test ◽  
Learning Ability ◽  
Lesion Volume ◽  
Volume Loss ◽  
Disability Progression ◽  
Brain Volume Loss ◽  
Quartile Group

ObjectiveTo assess the prognostic value of practice effect on Paced Auditory Serial Addition Test (PASAT) in multiple sclerosis.MethodsWe compared screening (day −14) and baseline (day 0) PASAT scores of 1009 patients from the FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) trial. We grouped patients into high and low learners if their PASAT score change was above or below the median change in their screening PASAT quartile group. We used Wilcoxon test to compare baseline disease characteristics between high and low learners, and multiple regression models to assess the respective impact of learning ability, baseline normalised brain volume and treatment on brain volume loss and 6-month confirmed disability progression over 2 years.ResultsThe mean PASAT score at screening was 45.38, increasing on average by 3.18 from day −14 to day 0. High learners were younger (p=0.003), had lower Expanded Disability Status Scale score (p=0.031), higher brain volume (p<0.001) and lower T2 lesion volume (p=0.009) at baseline. Learning status was not significantly associated with disability progression (HR=0.953, p=0.779), when adjusting for baseline normalised brain volume, screening PASAT score and treatment arm. However, the effect of fingolimod on disability progression was more pronounced in high learners (HR=0.396, p<0.001) than in low learners (HR=0.798, p=0.351; p for interaction=0.05). Brain volume loss at month 24 tended to be higher in low learners (0.17%, p=0.058), after adjusting for the same covariates.ConclusionsShort-term practice effects on PASAT are related to brain volume, disease severity and age and have clinically meaningful prognostic implications. High learners benefited more from fingolimod treatment.

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

2017 ◽  
Vol 24 (11) ◽  
pp. 1433-1444 ◽  
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.

scholarly journals Using dual-calibrated functional MRI to map brain oxygen supply and consumption in multiple sclerosis

2021 ◽  
Author(s):  
Hannah L Chandler ◽  
Rachael C Stickland ◽  
Michael Germuska ◽  
Eleonora Patitucci ◽  
Catherine Foster ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Oxygen Consumption ◽  
Healthy Volunteers ◽  
Oxygen Supply ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Group Differences ◽  
Lesion Volume ◽  
Brain Physiology ◽  
Significant Difference

Evidence suggests that cerebrovascular function and oxygen consumption are altered in multiple sclerosis (MS). Here, we quantified the vascular and oxygen metabolic MRI burden in patients with MS (PwMS) and assessed the relationship between these MRI measures of and metrics of damage and disability. In PwMS and in matched healthy volunteers, we applied a newly developed dual-calibrated fMRI method of acquisition and analysis to map grey matter (GM) cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen consumption (CMRO2) and effective oxygen diffusivity of the capillary network (DC). We also quantified physical and cognitive function in PwMS and controls. There was no significant difference in GM volume between 22 PwMS and 20 healthy controls (p=0.302). Significant differences in CBF (PwMS vs. controls: 44.91 +/- 6.10 vs. 48.90 +/- 5.87 ml/100g/min, p=0.010), CMRO2 (117.69 +/- 17.31 vs. 136.49 +/- 14.48 μmol/100g/min p<0.001) and DC (2.70 +/- 0.51 vs. 3.18 +/- 0.41 μmol/100g/mmHg/min, p=0.002) were observed in the PwMS. No significant between-group differences were observed for OEF (PwMS vs. controls: 0.38 +/- 0.09 vs. 0.39 +/- 0.02, p=0.358). Regional analysis showed widespread reductions in CMRO2 and DC for PwMS compared to healthy volunteers. There was a significant correlation between physiological measures and T2 lesion volume, but no association with current clinical disability. Our findings demonstrate concurrent reductions in oxygen supply and consumption in the absence of an alteration in oxygen extraction that may be indicative of a reduced demand for oxygen (O2), an impaired transfer of O2 from capillaries to mitochondria, and/or a reduced ability to utilise O2 that is available at the mitochondria. With no between-group differences in GM volume, our results suggest that changes in brain physiology may precede MRI-detectable GM loss and thus may be one of the pathological drivers of neurodegeneration and disease progression.

scholarly journals Evaluation of cerebellar function scores in relation to cerebellar axonal loss in multiple sclerosis

2020 ◽  
Author(s):  
F. Boonstra ◽  
S. Gajamange ◽  
G. Noffs ◽  
T. Perera ◽  
M. Strik ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Diffusion Mri ◽  
Lesion Volume ◽  
Axonal Loss ◽  
Cerebellar Dysfunction ◽  
Clinical Assessments ◽  
Cerebellar Function ◽  
Cerebellar Damage ◽  
Primary Driver ◽  
And Diffusion

AbstractBackgroundCerebellar damage is common in people with multiple sclerosis (pwMS) and is associated with worse progression and relapse recovery. Studies into the importance of the cerebellum in pwMS are hampered by limited understanding of cerebellar damage and its relation to cerebellar function in pwMS.ObjectiveExamine axonal loss, as a primary driver of progressive neurological decline, in the cerebellum using advanced diffusion MRI and compare axonal loss with cerebellar dysfunction in pwMSMethodsWe recruited 55 pwMS and 14 healthy controls. Clinical assessments included scale for the assessment and rating of ataxia (SARA), and Bain tremor ratings. Subjects underwent FLAIR, T1-weighted and diffusion MRI. Cerebellar grey and white matter and lesion volume were calculated. Cerebellar axonal loss was examined with fibre-specific markers. Fibre density and cross-section (FDC) accounts for microscopic and macroscopic changes in a fibre bundle.ResultsLoss of cerebellar FDC was associated with increased SARA (r=-0.42, p<0.01) and tremor severity (rho=-0.35, p=0.01). Cerebellar lesion volume correlated with SARA (r=0.49, p<0.01) and tremor severity (rho=0.41, p=0.01).ConclusionFibre-specific measures of cerebellar pathology could provide a functionally relevant marker of cerebellar damage in MS. Future trials using fibre-specific markers are needed to further characterize cerebellar pathology in pwMS and understand its significance in disease progression.

scholarly journals Epigallocatechin Gallate in Relapsing-Remitting Multiple Sclerosis

2021 ◽  
Vol 8 (3) ◽  
pp. e981
Author(s):  
Judith Bellmann-Strobl ◽  
Friedemann Paul ◽  
Jens Wuerfel ◽  
Jan Dörr ◽  
Carmen Infante-Duarte ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Primary Outcome ◽  
Brain Mri ◽  
Trial Registration ◽  
Lesion Volume ◽  
Volume Number ◽  
Egcg Treatment ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo assess the safety and efficacy of epigallocatechin-3-gallate (EGCG) add-on to glatiramer acetate (GA) in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsWe enrolled patients with RRMS (aged 18–60 years, Expanded Disability Status Scale [EDSS] score 0–6.5), receiving stable GA treatment in a multicenter, prospective, double-blind, phase II, randomized controlled trial. Participants received up to 800 mg oral EGCG daily over a period of 18 months. The primary outcome was the proportion of patients without new hyperintense lesions on T2-weighted (T2w) brain MRI within 18 months. Secondary end points included additional MRI and clinical parameters. Immunologic effects of EGCG were investigated in exploratory experiments.ResultsA total of 122 patients on GA were randomly assigned to EGCG treatment (n = 62) or placebo (n = 60). We could not demonstrate a difference between groups after 18 months for the primary outcome or other radiologic (T2w lesion volume, T1w hypointense lesion number or volume, number of cumulative contrast-enhancing lesions, percent brain volume change), or clinical (EDSS, MS functional composite, and annualized relapse rate) parameter. EGCG treatment did not affect immune response to GA. Pharmacologic analysis revealed wide ranging EGCG plasma levels. The treatment was well tolerated with a similar incidence of mostly mild adverse events similar in both groups.ConclusionIn RRMS, oral EGCG add-on to GA was not superior to placebo in influencing MRI and clinical disease activity over 18 months. The treatment was safe at a daily dosage up to 800 mg EGCG. It did not influence immune parameters, despite indication of EGCG being bioavailable in patients.Classification of EvidenceThis study provides Class II evidence that for patients with RRMS, EGCG added to GA did not significantly affect the development of new hyperintense lesions on T2-weighted brain MRI.Trial Registration InformationClinical trial registration number: NCT00525668.

scholarly journals Applying Deep Learning to Accelerated Clinical Brain Magnetic Resonance Imaging for Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Ashika Mani ◽  
Tales Santini ◽  
Radhika Puppala ◽  
Megan Dahl ◽  
Shruthi Venkatesh ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Deep Learning ◽  
Magnetic Resonance ◽  
Image Quality ◽  
Repeated Measures ◽  
Financial Burden ◽  
Brain Magnetic Resonance Imaging ◽  
Lesion Volume ◽  
Patient Reported

Background: Magnetic resonance (MR) scans are routine clinical procedures for monitoring people with multiple sclerosis (PwMS). Patient discomfort, timely scheduling, and financial burden motivate the need to accelerate MR scan time. We examined the clinical application of a deep learning (DL) model in restoring the image quality of accelerated routine clinical brain MR scans for PwMS.Methods: We acquired fast 3D T1w BRAVO and fast 3D T2w FLAIR MRI sequences (half the phase encodes and half the number of slices) in parallel to conventional parameters. Using a subset of the scans, we trained a DL model to generate images from fast scans with quality similar to the conventional scans and then applied the model to the remaining scans. We calculated clinically relevant T1w volumetrics (normalized whole brain, thalamic, gray matter, and white matter volume) for all scans and T2 lesion volume in a sub-analysis. We performed paired t-tests comparing conventional, fast, and fast with DL for these volumetrics, and fit repeated measures mixed-effects models to test for differences in correlations between volumetrics and clinically relevant patient-reported outcomes (PRO).Results: We found statistically significant but small differences between conventional and fast scans with DL for all T1w volumetrics. There was no difference in the extent to which the key T1w volumetrics correlated with clinically relevant PROs of MS symptom burden and neurological disability.Conclusion: A deep learning model that improves the image quality of the accelerated routine clinical brain MR scans has the potential to inform clinically relevant outcomes in MS.

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