The Use of the Central Vein Sign in the Diagnosis of Multiple Sclerosis: A Systematic Review and Meta-analysis

Abstract

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.

Central vein sign: A putative diagnostic marker for multiple sclerosis

“…Based on a meta-analysis evaluating 35 studies, the 40% positive CVS criterion appears to be the optimal threshold to discriminate MS from its mimickers. 18,24 However, integration of the CVS into clinical practice still requires the adoption of standardized criteria that would have to be tested in longitudinal multicentric studies. CVS use is first limited by the additional SWI scanning time (roughly five minutes) that should be included in the already long MRI MS protocol.…”

“…However, the meta-analysis of Castellaro et al demonstrated that the use of FLAIR* showed no significant differences in the pooled proportion of CVS presence. 24 It is also important to note the high value of 3D high-resolution echo-planar imaging (EPI). 25 Indeed, when compared with other susceptibility images, these optimized 3D-T2* images achieved the best performance in differentiating MS from mimicking disorders.…”

“…Castellaro et al (Diagnostics 2020) demonstrated that compared to 1.5T magnets, 3T magnets might be sufficient for detecting the CVS. 24 This reduced sensitivity of lower field-strength magnets could be compensated by obtaining susceptibility-based MR sequences during or immediately after the administration of gadolinium-based contrast agents. Indeed, evidence suggested that using gadolinum-based contrast agents enhanced central vein detection by increasing the paramagnetic effect of the veins and thereby facilitating their visualization.…”

Central Vein Sign Profile of Newly Developing Lesions in Multiple Sclerosis

“… 9 , 10 The CVS has been proposed as a radiologic biomarker and is seen with high frequency in MS lesions, 11 , 12 such that it can effectively differentiate MS from other etiologies associated with nonspecific white matter lesions. 13 , 14 However, whereas the CVS has shown promise in aiding the initial diagnosis of MS based on the evaluation of established lesions, the CVS characteristics of newly appearing T2/FLAIR or Gd+ lesions in MS have not been comprehensively described. In this study, we sought to (1) investigate CVS characteristics of newly developing lesions in MS cases and HCs followed longitudinally; (2) study their relationship with clinical and radiologic measures of disease burden; and (3) describe the frequency of associated DMT changes seen retrospectively in this cohort.…”

Stronger Microstructural Damage Revealed in Multiple Sclerosis Lesions with Central Vein Sign by Quantitative Gradient Echo MRI

“…7 It has been proposed that having more than 40% lesions with CVS or three or more lesions with CVS is specific for MS. 8 Other studies have proposed varying CVS thresholds and absolute lesion number, with similar degrees of specificity. 7,9 Advanced post-processing techniques, such as T2* and FLAIR* improve discernment of CVS. 10,11,12 In this study we used a gradient echo plural contrast imaging (GEPCI) technique that is based on a multi-echo gradient echo MR sequence and post processing algorithms, to generate images and quantitative maps with different biological contrasts.…”