Effect of GBCA Use on Detection and Diagnostic Performance of the Central Vein Sign: Evaluation Using a 3-T FLAIR* Sequence in Patients With Suspected Multiple Sclerosis

Abstract

<b>BACKGROUND.</b> The central vein sign (CVS) is a proposed MRI biomarker of multiple sclerosis (MS). The impact of gadolinium-based contrast agent (GBCA) administration on CVS evaluation remains poorly investigated. <b>OBJECTIVE.</b> The purpose of this study was to assess the effect of GBCA use on CVS detection and on the diagnostic performance of the CVS for MS using a 3-T FLAIR* sequence. <b>METHODS.</b> This study was a secondary analysis of data from the pilot study for the prospective multicenter Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS), which recruited adults with suspected MS from April 2018 to February 2020. Participants underwent 3-T brain MRI including FLAIR and precontrast and post-contrast echo-planar imaging T2*-weighted acquisitions. Postprocessing was used to generate combined FLAIR and T2*-weighted images (hereafter, FLAIR*). MS diagnoses were established using the 2017 McDonald criteria. Thirty participants (23 women, seven men; mean age, 45 years) were randomly selected from the CAVS-MS pilot study cohort. White matter lesions (WMLs) were marked using FLAIR* images. A single observer, blinded to clinical data and GBCA use, reviewed marked WMLs on FLAIR* images for the presence of the CVS. <b>RESULTS.</b> Thirteen of 30 participants had MS. Across participants, on precontrast FLAIR* imaging, 218 CVS-positive and 517 CVS-negative WMLs were identified; on post-contrast FLAIR* imaging, 269 CVS-positive and 459 CVS-negative WMLs were identified. The fraction of WMLs that were CVS-positive on precontrast and postcontrast images was 48% and 58% in participants with MS and 7% and 10% in participants without MS, respectively. The median patient-level CVS-positivity rate on precontrast and postcontrast images was 43% and 67% for participants with MS and 4% and 8% for participants without MS, respectively. In a binomial model adjusting for MS diagnoses, GBCA use was associated with an increased likelihood of at least one CVS-positive WML (odds ratio, 1.6; <i>p</i> < .001). At a 40% CVS-positivity threshold, the sensitivity of the CVS for MS increased from 62% on precontrast images to 92% on postcontrast images (<i>p</i> = .046). Specificity was not significantly different between precontrast (88%) and postcontrast (82%) images (<i>p</i> = .32). <b>CONCLUSION.</b> GBCA use increased CVS detection on FLAIR* images, thereby increasing the sensitivity of the CVS for MS diagnoses. <b>CLINICAL IMPACT.</b> The postcontrast FLAIR* sequence should be considered for CVS evaluation in future investigational trials and clinical practice.