# Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis

> **NIH NIH U01** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $1,782,272

## Abstract

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 presentation...

## Key facts

- **NIH application ID:** 10168677
- **Project number:** 5U01NS116776-02
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** DANIEL ONTANEDA
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,782,272
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168677

## Citation

> US National Institutes of Health, RePORTER application 10168677, Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (5U01NS116776-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10168677. Licensed CC0.

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