Reliability of Central Vein Sign Imaging With 3T FLAIR* in a Multicenter Study

Background and Purpose: The central vein sign (CVS) is a diagnostic imaging biomarker for multiple sclerosis (MS). FLAIR* is a combined MRI contrast that provides high conspicuity for CVS at 3 Tesla (3T), enabling its sensitive and accurate detection in clinical settings. This study evaluated whether CVS conspicuity of 3T FLAIR* is reliable across imaging sites and MRI vendors and whether gadolinium (Gd) contrast increases CVS conspicuity. Methods: A cross-sectional, multicenter study recruited adults referred for possible diagnosis of MS at 10 sites. FLAIR* contrast was generated using high-resolution T2*-weighted (acquired pre- and post-injection of Gd) and T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) brain images at 3T from two MRI vendors. Lesions and veins were segmented to compute lesion-to-vein contrast-to-noise ratio (CNRlesion-to-vein), a quantitative measure of CVS conspicuity. CNRlesion-to-vein measures for pre- and post-Gd FLAIR* were compared across sites and vendors. Results: Eighty-seven participants from nine sites were included in the analysis. There was no significant difference in mean CNRlesion-to-vein between sites for pre-Gd (p-value = 0.07) or post-Gd (p-value = 0.27) FLAIR*. There were also no significant differences between vendors for pre-Gd (p-value = 0.10) or post-Gd (p-value = 0.31) FLAIR*. Patient-level pairwise differences in CNRlesion-to-vein between pre-Gd and post-Gd FLAIR* revealed a significant increase for post-Gd FLAIR* (p-value < 0.001). Conclusions: CVS conspicuity on 3T FLAIR* is consistent across imaging sites and MRI vendors. Moreover, Gd-based contrast agent significantly improved CVS conspicuity on 3T FLAIR*. These findings support the implementation of FLAIR* in clinical settings for MS.