scholarly journals LesionQuant for Assessment of MRI in Multiple Sclerosis—A Promising Supplement to the Visual Scan Inspection

2020 ◽  
Vol 11 ◽  
Author(s):  
Synne Brune ◽  
Einar A. Høgestøl ◽  
Vanja Cengija ◽  
Pål Berg-Hansen ◽  
Piotr Sowa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Atrophy ◽  
Significant Positive Correlation ◽  
Brain Mri ◽  
Lesion Volume ◽  
Radiological Evaluation ◽  
Lesion Count ◽  
Whole Brain ◽  
Positive Correlation ◽  
Time Points

Background and Goals: Multiple sclerosis (MS) is a central nervous system inflammatory disease where magnetic resonance imaging (MRI) is an important tool for diagnosis and disease monitoring. Quantitative measurements of lesion volume, lesion count, distribution of lesions, and brain atrophy have a potentially significant value for evaluating disease progression. We hypothesize that utilizing software designed for evaluating MRI data in MS will provide more accurate and detailed analyses compared to the visual neuro-radiological evaluation.Methods: A group of 56 MS patients (mean age 35 years, 70% females and 96% relapsing-remitting MS) was examined with brain MRI one and 5 years after diagnosis. The T1 and FLAIR brain MRI sequences for all patients were analyzed using the LesionQuant (LQ) software. These data were compared with data from structured visual evaluations of the MRI scans performed by neuro-radiologists, including assessments of atrophy, and lesion count. The data from LQ were also compared with data from other validated research methods for brain segmentation, including assessments of whole brain volume and lesion volume. Correlations with clinical tests like the timed 25-foot walk test (T25FT) were performed to explore additional value of LQ analyses.Results: Lesion count assessments by LQ and by the neuro-radiologist were significantly correlated one year (cor = 0.92, p = 2.2 × 10−16) and 5 years (cor = 0.84, p = 2.7 × 10−16) after diagnosis. Analyzes of the intra- and interrater variability also correlated significantly (cor = 0.96, p < 0.001, cor = 0.97, p < 0.001). Significant positive correlation was found between lesion volume measured by LQ and by the software Cascade (cor = 0.7, p < 0.001. LQ detected a reduction in whole brain percentile >10 in 10 patients across the time-points, whereas the neuro-radiologist assessment identified six of these. The neuro-radiologist additionally identified five patients with increased atrophy in the follow-up period, all of them displayed decreasing low whole brain percentiles (median 11, range 8–28) in the LQ analysis. Significant positive correlation was identified between lesion volume measured by LQ and test performance on the T25FT both at 1 and 5 years after diagnosis.Conclusion: For the number of MS lesions at both time-points, we demonstrated strong correlations between the assessments done by LQ and the neuro-radiologist. Lesion volume evaluated with LQ correlated with T25FT performance. LQ-analyses classified more patients to have brain atrophy than the visual neuro-radiological evaluation. In conclusion, LQ seems like a promising supplement to the evaluation performed by neuro-radiologists, providing an automated tool for evaluating lesions in MS patients and also detecting early signs of atrophy in both a longitudinal and cross-sectional setting.

scholarly journals LesionQuant for assessment of MRI in multiple sclerosis - a promising supplement to the visual scan inspection

2020 ◽  
Author(s):  
Synne Brune ◽  
Einar A. Høgestøl ◽  
Vanja Cengija ◽  
Pål Berg-Hansen ◽  
Piotr Sowa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Atrophy ◽  
Brain Mri ◽  
Lesion Volume ◽  
Radiological Evaluation ◽  
Lesion Count ◽  
Cross Sectional ◽  
Whole Brain ◽  
Time Points ◽  
One Year

AbstractBackground and goalsMultiple sclerosis (MS) is a central nervous system inflammatory disease where magnetic resonance imaging (MRI) is an important tool for diagnosis and disease monitoring. Quantitative measurements of lesion volume, lesion count, distribution of lesions and brain atrophy have a potentially significant value for evaluating disease progression. We hypothesize that utilizing software designed for evaluating MRI data in MS will provide more accurate and detailed analyses compared to the visual neuro-radiological evaluation.MethodsA group of 56 MS patients (mean age 35 years, 70% females and 96% relapsing-remitting MS) was examined with brain MRI one and five years after diagnosis. The T1 and FLAIR brain MRI sequences for all patients were analysed using the LesionQuant(LQ) software. These data were compared with data from structured visual evaluations of the MRI scans performed by a neuro-radiologist, including assessments of atrophy and lesion count. Correlations with clinical tests like the timed 25-foot walk test (T25FT) were performed to explore additional value of LQ analyses.ResultsLesion count assessments by LQ and by the neuro-radiologist were significantly correlated one year (cor=0.92, p=2.2×10−16) and five years (cor=0.84, p=2.7×10−16) after diagnosis. LQ detected a reduction in whole brain percentile >10 in 10 patients across the time-points, whereas the neuro-radiologist assessment identified six of these. The neuro-radiologist additionally identified five patients with increased atrophy in the follow-up period, all of them displayed decreasing low whole brain percentiles (median 11, range 8-28) in the LQ analysis. Significant positive correlation was identified between lesion volume measured by LQ and test performance on the T25FT both at one year and five years after diagnosis.ConclusionFor the number of MS lesions at both time-points, we demonstrated strong correlations between the assessments done by LQ and the neuro-radiologist. Lesion volume evaluated with LQ correlated with T25FT performance. LQ-analyses were more sensitive in capturing brain atrophy than the visual neuro-radiological evaluation. In conclusion, LQ seems like a promising supplement to the evaluation performed by neuro-radiologists, providing an automated tool for evaluating lesions and brain volume in MS patients in both a longitudinal and cross-sectional setting.

Brain atrophy in multiple sclerosis: impact of lesions and of damage of whole brain tissue

2002 ◽  
Vol 8 (5) ◽  
pp. 410-414 ◽  
Author(s):  
N F Kalkers ◽  
H Vrenken ◽  
B MJ Uitdehaag ◽  
C H Polman ◽  
F Barkhof
Keyword(s):  
Multiple Sclerosis ◽  
Brain Tissue ◽  
Brain Atrophy ◽  
Brain Volume ◽  
Peak Height ◽  
Tissue Loss ◽  
Magnetization Transfer Ratio ◽  
Lesion Volume ◽  
Intracranial Volume ◽  
Whole Brain

Introduction: In multiple sclerosis (MS), brain atrophy measurement on magnetic resonance imaging (MRI) reflects overall tissue loss, especially demyelination and axonal loss. We studied which factor contributes most to the development of brain atrophy: extent and severity of lesions or damage of whole brain tissue (WBT). Methods: Eighty-six patients with MS [32 primary progressive (PP), 32 secondary progressive (SP)] and 22 relapsing-remitting (RR) were studied. MRI included T1- and T2-weighted imaging to obtain hypointense T1 lesion volume (T1LV) and two brain volume measurements: 1) the parenchymal fraction (PF; whole brain parenchymal volume/intracranial volume) as a marker of overall brain volume, and 2) the ventricular fraction (VF; ventricular volume/intracranial volume) as a marker of central atrophy. From magnetization transfer ratio (MTR) histograms, the relative peak height (rHp) was derived as an index of damage of WBT (a lower peak height reflects damage of WBT). Results: Multiple linear regression analysis revealed that damage of WBT explains most of the variance of PF (standardized coefficient b=0.59, p <0.001 for WBT and b= −0.19, p <0.05 for T1LV). These findings are independent of disease phase; even in RR patients, damage of WBT plays a dominant role in explaining the variance in overall brain volume. By contrast, the variance in VF is explained by both T1LV and damage of WBT (standardized coefficient b =0.43, p<0.001 for T1LV and b = −0.38, p <0.001 for WBT). Conclusion: This study shows that overall brain volume (PF) is best explained by damage of WBT, supporting the significance of nonfocal pathology in MS in producing tissue loss. Central atrophy (VF) is determined by both lesion volume and damage of WBT. Our results underline the importance of nonfocal pathology even in the early (RR) phase of the disease.

scholarly journals Assessing Neurofilaments as Biomarkers of Neuroprotection in Progressive Multiple Sclerosis

2022 ◽  
Vol 9 (2) ◽  
pp. e1130
Author(s):  
Thomas E. Williams ◽  
Katherine P. Holdsworth ◽  
Jennifer M. Nicholas ◽  
Arman Eshaghi ◽  
Theodora Katsanouli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Effect ◽  
Brain Atrophy ◽  
Progressive Multiple Sclerosis ◽  
High Dose ◽  
Lesion Volume ◽  
Phase 2 ◽  
Whole Brain ◽  
Simvastatin Treatment ◽  
Link Type

Background and ObjectivesImproved biomarkers of neuroprotective treatment are needed in progressive multiple sclerosis (PMS) to facilitate more efficient phase 2 trial design. The MS-STAT randomized controlled trial supported the neuroprotective potential of high-dose simvastatin in secondary progressive MS (SPMS). Here, we analyze serum from the MS-STAT trial to assess the extent to which neurofilament light (NfL) and neurofilament heavy (NfH), both promising biomarkers of neuroaxonal injury, may act as biomarkers of simvastatin treatment in SPMS.MethodsThe MS-STAT trial randomized patients to 80 mg simvastatin or placebo. Serum was analyzed for NfL and NfH using Simoa technology. We used linear mixed models to investigate the treatment effects of simvastatin compared with placebo on NfL and NfH. Additional models examined the relationships between neurofilaments and MRI and clinical measures of disease severity.ResultsA total of 140 patients with SPMS were included. There was no evidence for a simvastatin treatment effect on NfL or NfH: compared with placebo, NfL was 1.2% lower (95% CI 10.6% lower to 9.2% higher; p = 0.820) and NfH was 0.4% lower (95% CI 18.4% lower to 21.6% higher; p = 0.969) in the simvastatin treatment group. Secondary analyses suggested that higher NfL was associated with greater subsequent whole brain atrophy, higher T2 lesion volume, and more new/enlarging T2 lesions in the previous 12 months, as well as greater physical disability. There were no significant associations between NfH and MRI or clinical variables.DiscussionWe found no evidence of a simvastatin treatment effect on serum neurofilaments. While confirmation of the neuroprotective benefits of simvastatin is awaited from the ongoing phase 3 study (NCT03387670), our results suggest that treatments capable of slowing the rate of whole brain atrophy in SPMS, such as simvastatin, may act via mechanisms largely independent of neuroaxonal injury, as quantified by NfL. This has important implications for the design of future phase 2 clinical trials in PMS.Trial Registration InformationMS-STAT: NCT00647348.Classification of EvidenceThis study provides class I evidence that simvastatin treatment does not have a large impact on either serum NfL or NfH, as quantified in this study, in SPMS.

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.

A Comparison Between the Sensitivities of 3-mm and 5-mm Thick Serial Brain MRI for Detecting Lesion Volume Changes in Patients with Multiple Sclerosis

1998 ◽  
Vol 8 (3) ◽  
pp. 144-147 ◽  
Author(s):  
Marco Rovaris ◽  
Maria Assunta Rocca ◽  
Ruggero Capra ◽  
Francesca Prandini ◽  
Vittorio Martinelli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Mri ◽  
Lesion Volume ◽  
Volume Changes ◽  
Serial Brain

Preferential spinal cord volume loss in primary progressive multiple sclerosis

2018 ◽  
Vol 25 (7) ◽  
pp. 947-957 ◽  
Author(s):  
Charidimos Tsagkas ◽  
Stefano Magon ◽  
Laura Gaetano ◽  
Simon Pezold ◽  
Yvonne Naegelin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Clinical Outcomes ◽  
Brain Mri ◽  
Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Over Time ◽  
Spinal Cord Volume

Background: Little is known on longer term changes of spinal cord volume (SCV) in primary progressive multiple sclerosis (PPMS). Objective: Longitudinal evaluation of SCV loss in PPMS and its correlation to clinical outcomes, compared to relapse-onset multiple sclerosis (MS) subtypes. Methods: A total of 60 MS age-, sex- and disease duration-matched patients (12 PPMS, each 24 relapsing-remitting (RRMS) and secondary progressive MS (SPMS)) were analysed annually over 6 years of follow-up. The upper cervical SCV was measured on 3D T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images using a semi-automatic software (CORDIAL), along with the total brain volume (TBV), brain T2 lesion volume (T2LV) and Expanded Disability Status Scale (EDSS). Results: PPMS showed faster SCV loss over time than RRMS ( p < 0.01) and by trend ( p = 0.066) compared with SPMS. In contrast to relapse-onset MS, in PPMS SCV loss progressed independent of TBV and T2LV changes. Moreover, in PPMS, SCV was the only magnetic resonance imaging (MRI) measurement associated with EDSS increase over time ( p < 0.01), as opposed to RRMS and SPMS. Conclusion: SCV loss is a strong predictor of clinical outcomes in PPMS and has shown to be faster and independent of brain MRI metrics compared to relapse-onset MS.

Whole-brain atrophy in multiple sclerosis measured by two segmentation processes from various MRI sequences

2003 ◽  
Vol 216 (1) ◽  
pp. 169-177 ◽  
Author(s):  
M.A. Horsfield ◽  
M. Rovaris ◽  
M.A. Rocca ◽  
P. Rossi ◽  
R.H.B. Benedict ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Atrophy ◽  
Whole Brain ◽  
Mri Sequences

Brain atrophy evolution and lesion load accrual in multiple sclerosis: a 2-year follow-up study

2008 ◽  
Vol 15 (2) ◽  
pp. 204-211 ◽  
Author(s):  
G Tedeschi ◽  
D Dinacci ◽  
M Comerci ◽  
L Lavorgna ◽  
G Savettieri ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Disease Progression ◽  
Gray Matter ◽  
Brain Atrophy ◽  
Disease Duration ◽  
Lesion Load ◽  
Whole Brain ◽  
Gray Matter Atrophy

Background To investigate in a large cohort of patients with multiple sclerosis (MS), lesion load and atrophy evolution, and the relationship between clinical and magnetic resonance imaging (MRI) correlates of disease progression. Methods Two hundred and sixty-seven patients with MS were studied at baseline and two years later using the same MRI protocol. Abnormal white matter fraction, normal appearing white matter fraction, global white matter fraction, gray matter fraction and whole brain fraction, T2-hyperintense, and T1-hypointense lesions were measured at both time points. Results The majority of patients were clinically stable, whereas MRI-derived brain tissue fractions were significantly different after 2 years. The correlation between MRI data at baseline and their variation during the follow-up showed that lower basal gray matter atrophy was significantly related with higher progression of gray matter atrophy during follow-up. The correlation between MRI parameters and disease duration showed that gray matter atrophy rate decreased with increasing disease duration, whereas the rate of white matter atrophy had a constant pattern. Lower basal gray matter atrophy was associated with increased probability of developing gray matter atrophy at follow-up, whereas gray matter atrophy progression over 2 years and new T2 lesion load were risk factors for whole brain atrophy progression. Conclusions In MS, brain atrophy occurs even after a relatively short period of time and in patients with limited progression of disability. Short-term brain atrophy progression rates differ across tissue compartments, as gray matter atrophy results more pronounced than white matter atrophy and appears to be a early phenomenon in the MS-related disease progression.

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