Dataset Information

Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study.

ABSTRACT:

Background

The "central vein sign" (CVS), a linear hypointensity on T2*-weighted imaging corresponding to a central vein/venule, is associated with multiple sclerosis (MS) lesions. The effect of lesion-size exclusion criteria on MS diagnostic accuracy has not been extensively studied.

Objective

Investigate the optimal lesion-size exclusion criteria for CVS use in MS diagnosis.

Methods

Cross-sectional study of 163 MS and 51 non-MS, and radiological/histopathological correlation of 5 MS and 1 control autopsy cases. The effects of lesion-size exclusion on MS diagnosis using the CVS, and intralesional vein detection on histopathology were evaluated.

Results

CVS+ lesions were larger compared to CVS- lesions, with effect modification by MS diagnosis (mean difference +7.7 mm³, p = 0.004). CVS percentage-based criteria with no lesion-size exclusion showed the highest diagnostic accuracy in differentiating MS cases. However, a simple count of three or more CVS+ lesions greater than 3.5 mm is highly accurate and can be rapidly implemented (sensitivity 93%; specificity 88%). On magnetic resonance imaging (MRI)-histopathological correlation, the CVS had high specificity for identifying intralesional veins (0/7 false positives).

Conclusion

Lesion-size measures add important information when using CVS+ lesion counts for MS diagnosis. The CVS is a specific biomarker corresponding to intralesional veins on histopathology.

SUBMITTER: Al-Louzi O

PROVIDER: S-EPMC9489648 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study.

Al-Louzi Omar O Manukyan Sargis S Donadieu Maxime M Absinta Martina M Letchuman Vijay V Calabresi Brent B Desai Parth P Beck Erin S ES Roy Snehashis S Ohayon Joan J Pham Dzung L DL Thomas Anish A Jacobson Steven S Cortese Irene I Auluck Pavan K PK Nair Govind G Sati Pascal P Reich Daniel S DS

Multiple sclerosis (Houndmills, Basingstoke, England) 20220608 12

<h4>Background</h4>The "central vein sign" (CVS), a linear hypointensity on T2*-weighted imaging corresponding to a central vein/venule, is associated with multiple sclerosis (MS) lesions. The effect of lesion-size exclusion criteria on MS diagnostic accuracy has not been extensively studied.<h4>Objective</h4>Investigate the optimal lesion-size exclusion criteria for CVS use in MS diagnosis.<h4>Methods</h4>Cross-sectional study of 163 MS and 51 non-MS, and radiological/histopathological correlat ...[more]

PMID: 35674284

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Project description:Quantitative MRI (qMRI) probes the microstructural properties of the central nervous system (CNS) by providing biophysical measures of tissue characteristics. In this work, we aimed to (i) identify qMRI measures that distinguish histological lesion types in postmortem multiple sclerosis (MS) brains, especially the remyelinated ones; and to (ii) investigate the relationship between those measures and quantitative histological markers of myelin, axons, and astrocytes in the same experimental setting. Three fixed MS whole brains were imaged with qMRI at 3T to obtain magnetization transfer ratio (MTR), myelin water fraction (MWF), quantitative T1 (qT1), quantitative susceptibility mapping (QSM), fractional anisotropy (FA) and radial diffusivity (RD) maps. The identification of lesion types (active, inactive, chronic active, or remyelinated) and quantification of tissue components were performed using histological staining methods as well as immunohistochemistry and immunofluorescence. Pairwise logistic and LASSO regression models were used to identify the best qMRI discriminators of lesion types. The association between qMRI and quantitative histological measures was performed using Spearman's correlations and linear mixed-effect models. We identified a total of 65 lesions. MTR and MWF best predicted the chance of a lesion to be remyelinated, whereas RD and QSM were useful in the discrimination of active lesions. The measurement of microstructural properties through qMRI did not show any difference between chronic active and inactive lesions. MWF and RD were associated with myelin content in both lesions and normal-appearing white matter (NAWM), FA was the measure most associated with axon content in both locations, while MWF was associated with astrocyte immunoreactivity only in lesions. Moreover, we provided evidence of extensive astrogliosis in remyelinated lesions. Our study provides new information on the discriminative power of qMRI in differentiating MS lesions -especially remyelinated ones- as well as on the relative association between multiple qMRI measures and myelin, axon and astrocytes.

Project description:Background: The central vein sign (CVS) is a radiological feature proposed as a multiple sclerosis (MS) imaging biomarker able to accurately differentiate MS from other white matter diseases of the central nervous system. In this work, we evaluated the pooled proportion of the CVS in brain MS lesions and to estimate the diagnostic performance of CVS to perform a diagnosis of MS and propose an optimal cut-off value. Methods: A systematic search was performed on publicly available databases (PUBMED/MEDLINE and Web of Science) up to 24 August 2020. Analysis of the proportion of white matter MS lesions with a central vein was performed using bivariate random-effect models. A meta-regression analysis was performed and the impact of using particular sequences (such as 3D echo-planar imaging) and post-processing techniques (such as FLAIR*) was investigated. Pooled sensibility and specificity were estimated using bivariate models and meta-regression was performed to address heterogeneity. Inclusion and publication bias were assessed using asymmetry tests and a funnel plot. A hierarchical summary receiver operating curve (HSROC) was used to estimate the summary accuracy in diagnostic performance. The Youden index was employed to estimate the optimal cut-off value using individual patient data. Results: The pooled proportion of lesions showing a CVS in the MS population was 73%. The use of the CVS showed a remarkable diagnostic performance in MS cases, providing a pooled specificity of 92% and a sensitivity of 95%. The optimal cut-off value obtained from the individual patient data pooled together was 40% with excellent accuracy calculated by the area under the ROC (0.946). The 3D-EPI sequences showed both a higher pooled proportion compared to other sequences and explained heterogeneity in the meta-regression analysis of diagnostic performances. The 1.5 Tesla (T) scanners showed a lower (58%) proportion of MS lesions with a CVS compared to both 3T (74%) and 7T (82%). Conclusions: The meta-analysis we have performed shows that the use of the CVS in differentiating MS from other mimicking diseases is encouraged; moreover, the use of dedicated sequences such as 3D-EPI and the high MRI field is beneficial.

Project description:ImportanceMultiple sclerosis (MS) misdiagnosis remains an important issue in clinical practice.ObjectiveTo quantify the performance of cortical lesions (CLs) and central vein sign (CVS) in distinguishing MS from other conditions showing brain lesions on magnetic resonance imaging (MRI).Design, setting, and participantsThis was a retrospective, cross-sectional multicenter study, with clinical and MRI data acquired between January 2010 and May 2020. Centralized MRI analysis was conducted between July 2020 and December 2022 by 2 raters blinded to participants' diagnosis. Participants were recruited from 14 European centers and from a multicenter pan-European cohort. Eligible participants had a diagnosis of MS, clinically isolated syndrome (CIS), or non-MS conditions; availability of a brain 3-T MRI scan with at least 1 sequence suitable for CL and CVS assessment; presence of T2-hyperintense white matter lesions (WMLs). A total of 1051 individuals were included with either MS/CIS (n = 599; 386 [64.4%] female; mean [SD] age, 41.5 [12.3] years) or non-MS conditions (including other neuroinflammatory disorders, cerebrovascular disease, migraine, and incidental WMLs in healthy control individuals; n = 452; 302 [66.8%] female; mean [SD] age, 49.2 [14.5] years). Five individuals were excluded due to missing clinical or demographic information (n = 3) or unclear diagnosis (n = 2).ExposuresMS/CIS vs non-MS conditions.Main outcomes and measuresArea under the receiver operating characteristic curves (AUCs) were used to explore the diagnostic performance of CLs and the CVS in isolation and in combination; sensitivity, specificity, and accuracy were calculated for various cutoffs. The diagnostic importance of CLs and CVS compared to conventional MRI features (ie, presence of infratentorial, periventricular, and juxtacortical WMLs) was ranked with a random forest model.ResultsThe presence of CLs and the previously proposed 40% CVS rule had a sensitivity, specificity, and accuracy for MS of 59.0% (95% CI, 55.1-62.8), 93.6% (95% CI, 91.4-95.6), and 73.9% (95% CI, 71.6-76.3) and 78.7% (95% CI, 75.5-82.0), 86.0% (95% CI, 82.1-89.5), and 81.5% (95% CI, 78.9-83.7), respectively. The diagnostic performance of the CVS (AUC, 0.89 [95% CI, 0.86-0.91]) was superior to that of CLs (AUC, 0.77 [95% CI, 0.75-0.80]; P < .001), and was increased when combining the 2 imaging markers (AUC, 0.92 [95% CI, 0.90-0.94]; P = .04); in the random forest model, both CVS and CLs outperformed the presence of infratentorial, periventricular, and juxtacortical WMLs in supporting MS differential diagnosis.Conclusions and relevanceThe findings in this study suggest that CVS and CLs may be valuable tools to increase the accuracy of MS diagnosis.

Project description:ImportanceThe central vein sign has been proposed as a specific imaging biomarker for distinguishing between multiple sclerosis (MS) and not MS, mainly based on findings from ultrahigh-field magnetic resonance imaging (MRI) studies. The diagnostic value of the central vein sign in a multicenter setting with a variety of clinical 3 tesla (T) MRI protocols, however, remains unknown.ObjectiveTo evaluate the sensitivity and specificity of various central vein sign lesion criteria for differentiating MS from non-MS conditions using 3T brain MRI with various commonly used pulse sequences.Design, setting, and participantsThis large multicenter, cross-sectional study enrolled participants (n = 648) of ongoing observational studies and patients included in neuroimaging research databases of 8 neuroimaging centers in Europe. Patient enrollment and MRI data collection were performed between January 1, 2010, and November 30, 2016. Data analysis was conducted between January 1, 2016, and April 30, 2018. Investigators were blinded to participant diagnosis by a novel blinding procedure.Main outcomes and measuresOccurrence of central vein sign was detected on 3T T2*-weighted or susceptibility-weighted imaging. Sensitivity and specificity were assessed for these MRI sequences and for different central vein sign lesion criteria, which were defined by the proportion of lesions with central vein sign or by absolute numbers of lesions with central vein sign.ResultsA total of 606 participants were included in the study after exclusion of 42 participants. Among the 606 participants, 413 (68.2%) were women. Patients with clinically isolated syndrome and relapsing-remitting MS (RRMS) included 235 women (66.6%) and had a median (range) age of 37 (14.7-61.4) years, a median (range) disease duration of 2 (0-33) years, and a median (range) Expanded Disability Status Scale score of 1.5 (0-6.5). Patients without MS included 178 women (70.4%) and had a median (range) age of 54 (18-83) years. A total of 4447 lesions were analyzed in a total of 487 patients: 690 lesions in 98 participants with clinically isolated syndrome, 2815 lesions in 225 participants with RRMS, 54 lesions in 13 participants with neuromyelitis optica spectrum disorder, 54 lesions in 14 participants with systemic lupus erythematosus, 121 lesions in 29 participants with migraine or cluster headache, 240 lesions in 20 participants with diabetes, and 473 lesions in 88 participants with other types of small-vessel disease. The sensitivity was 68.1% and specificity was 82.9% for distinguishing MS from not MS using a 35% central vein sign proportion threshold. The 3 central vein sign lesion criteria had a sensitivity of 61.9% and specificity of 89.0%. Sensitivity was higher when an optimized T2*-weighted sequence was used.Conclusions and relevanceIn this study, use of the central vein sign at 3T MRI yielded a high specificity and a moderate sensitivity in differentiating MS from not MS; international, multicenter studies may be needed to ascertain whether the central vein sign-based criteria can accurately detect MS.

Project description:The central vein sign (CVS), a central linear hypointensity within lesions on T2*-weighted imaging, has been established as a sensitive and specific biomarker for the diagnosis of multiple sclerosis (MS). However, the CVS has not yet been comprehensively studied in newly developing MS lesions. We aimed to identify the CVS profiles of new white matter lesions in patients with MS followed over time and investigate demographic and clinical risk factors associated with new CVS+ or CVS- lesion development. In this retrospective longitudinal cohort study, adults from the NIH MS Natural History Study were considered for inclusion. Participants with new T2 or enhancing lesions were identified through review of the radiology report and/or longitudinal subtraction imaging. Each new lesion was evaluated for the CVS. Clinical characteristics were identified through chart review. A total of 153 adults (95 relapsing-remitting MS, 27 secondary progressive MS, 16 primary progressive MS, 5 clinically isolated syndrome, and 10 healthy; 67% female) were included. Of this cohort, 96 had at least 1 new T2 or contrast-enhancing lesion during median 3.1 years (Q1-Q3: 0.7-6.3) of follow-up; lesions eligible for CVS evaluation were found in 62 (65%). Of 233 new CVS-eligible lesions, 159 (68%) were CVS+, with 30 (48%) individuals having only CVS+, 12 (19%) only CVS-, and 20 (32%) both CVS+ and CVS- lesions. In gadolinium-enhancing (Gd+) lesions, the CVS+ percentage increased from 102/152 (67%) at the first time point where the lesion was observed, to 92/114 (82%) after a median follow-up of 2.8 years. Younger age (OR = 0.5 per 10-year increase, 95% CI = 0.3-0.8) and higher CVS+ percentage at baseline (OR = 1.4 per 10% increase, 95% CI = 1.1-1.9) were associated with increased likelihood of new CVS+ lesion development. In a cohort of adults with MS followed over a median duration of 3 years, most newly developing T2 or enhancing lesions were CVS+ (68%), and nearly half (48%) developed new CVS+ lesions only. Importantly, the effects of edema and T2 signal changes can obscure small veins in Gd+ lesions; therefore, caution and follow-up is necessary when determining their CVS status. Clinical trial registration number NCT00001248. This study provides Class III evidence that younger age and higher CVS+ percentage at baseline are associated with new CVS+ lesion development.

Dataset Information

Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study.

Background

Objective

Methods

Results

Conclusion

Publications

Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study.

Similar Datasets

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