Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis

项目总结/摘要 多发性硬化症（MS）的诊断目前是基于空间传播的证明（ 中枢神经系统内不同解剖位置的病变发展）和 时间（随着时间的推移出现或出现新的CNS病变）。没有简单的实验室测试可用 MRI的进步导致了更敏感的诊断标准，并促进了早期诊断。 诊断.尽管诊断敏感性有所提高，但许多患者仍然存在延迟诊断。 诊断. DMT的早期治疗可以防止复发和随后的残疾积累， 诊断延误可能会造成严重的终身后果。此外，研究表明， 诊断标准的验证在具有典型症状的个体中进行 （临床孤立综合征），降低了特异性，使标准对约50%的 被转诊诊断为MS且具有非典型或非经典症状的患者。的问题 误诊是显著的，因为大约20%的患者在先前诊断的情况下被转诊到MS中心 MS被误诊。有助于区分MS病变的一个特征是 MRI上的中央静脉征（CVS）。CVS标准已制定使用CVS的存在，在特定的 对单个MRI研究进行分级。CVS被提议作为诊断生物标志物， MS诊断的灵敏度，同时保留诊断特异性-所有这些都在一个易于使用的诊断测试中 可以应用于典型和非典型疾病表现的患者。T2的组合- 加权FLAIR和T2* 加权segEPI成像，我们为此应用提出的方法，已被 显示出对于中心静脉的检测特别敏感。MS中央静脉征（CAVS-MS） 一项研究试图回答中央静脉征（CVS）是否可以作为一种敏感和特异的诊断方法。 该研究将调查参与者的混合人群中的CVS， 典型和非典型临床表现，包括无神经系统症状的放射学表现。 该研究将招募200名具有典型临床表现的患者和200名具有非典型临床表现的参与者。 向MS中心进行诊断转诊并将随访研究受试者的演示文稿（共400例） 长达24个月，以确定中央静脉征诊断MS的特异性和敏感性 使用McDonald 2017年2年作为诊断的金标准。这个多中心的首要目标是 建议允许将CVS -一种易于测量的放射性生物标志物-纳入 MS的诊断标准，从而促进更早和更准确的诊断。定义CVS标准， 典型和非典型MS表现的模式，以及确定诊断的准确性和速度，将 为MS的公共卫生干预提供信息。

PROJECT SUMMARY/ ABSTRACT The diagnosis of multiple sclerosis (MS) is currently based on demonstration of dissemination in space (the development of lesions in distinct anatomical locations within the central nervous system) and dissemination in time (development or appearance of new CNS lesions over time). There is no simple laboratory test available for a diagnosis of MS. Advances in MRI have led to more sensitive diagnostic criteria and facilitated earlier diagnosis. Despite some improvements in diagnostic sensitivity, many patients continue to have a delay in diagnosis. Early treatment with DMT prevents relapses and subsequent accumulation of disability — so diagnostic delay can have severe and life-long consequences. In addition, studies that have informed revisions and validation of the diagnostic criteria were conducted in individuals presenting with typical syndromes (clinically isolated syndrome), diminishing specificity and making the criteria uninformative for the ~50% of patients who are referred for a diagnosis of MS with atypical or non-classical symptoms. The problem of misdiagnosis is significant as approximately 20% of patients referred to an MS center with a previous diagnosis of MS have been found to be misdiagnosed. One feature that helps differentiate MS lesions is the presence of the Central Vein Sign (CVS) on MRI. CVS criteria have been formulated using the presence of CVS in specific lesions to grade an individual MRI study. The CVS is proposed as a diagnostic biomarker with improved sensitivity for a diagnosis of MS, while retaining diagnostic specificity — all in an-easy-to use diagnostic test that can be applied in patients with both typical and atypical disease presentation. A combination of T2- weighted FLAIR and T2*-weighted segEPI imaging, the methodology we propose for this application, has been shown to be particularly sensitive for the detection of central veins. The CentrAl Vein Sign in MS (CAVS-MS) study seeks to answer whether the central vein sign (CVS) can be used as a sensitive and specific diagnostic marker for a diagnosis of MS. The study will investigate the CVS in a mixed population of participants with typical and atypical clinical presentations including radiological presentations without neurological symptoms. The study will enroll 200 patients with typical clinical presentations and 200 participants with atypical presentations (total 400) who present to an MS center for a diagnostic referral and will follow study participants for up to 24 months to determine the specificity and sensitivity of the central vein sign for a diagnosis of MS using McDonald 2017 at 2 years as the gold standard for diagnosis. The overarching goal of this multi-center proposal is to allow incorporation of the CVS — an easy-to-measure radiological biomarker — into the diagnostic criteria for MS, thereby facilitating earlier and more accurate diagnosis. Defining CVS criteria and patterns in typical and atypical MS presentations, as well as determining accuracy and speed of diagnosis, will inform public health interventions in MS.