Comparison of central FLAIR hypointensity and central vein sign on FLAIR* in a diagnostic cohort

BACKGROUND: The central vein sign (CVS) is a neuroimaging biomarker in multiple sclerosis (MS) with high diagnostic specificity. CVS is best detected with high-quality susceptibility-sensitive MRI sequences. For concurrent detection of lesions and veins, FLAIR* was developed as a post-processing method to provide contrast for T2 hyperintense lesions (FLAIR) and paramagnetic hypointense veins (T2*-weighted). Occasionally, CVS-like features have been noted on FLAIR, but the reliability of this finding is unknown. OBJECTIVE: To compare the central FLAIR hypointensity to FLAIR* CVS. METHODS: Scans from the CentrAl Vein Sign in MS (CAVS-MS) pilot study were included for the analysis. A blinded rater assessed all lesions for CVS on 3-tesla post-contrast FLAIR*. A second blinded rater assessed the same lesions for central hypointensity on FLAIR images alone. Counts were compared between methods. The same approach was applied for a subset with available non-contrast FLAIR* lesion ratings. RESULTS: With post-contrast FLAIR* CVS as the standard (n= 92; 1737 lesions), central FLAIR hypointensity demonstrated concordance of 64%, with sensitivity of 34% (95% CI, 30-37%) and specificity of 83% (95% CI, 81-85%). With non-contrast FLAIR* CVS as the standard (n= 38; 768 lesions), FLAIR demonstrated sensitivity of 40% (95% CI, 33-47%) and specificity of 85% (95% CI, 82-88%). Select 6 (≥6 central hypointense lesions) FLAIR was 59% accurate for a diagnosis of MS, with a lower specificity (63% vs. 90%, p= 0.008) in comparison to post-contrast FLAIR*. CONCLUSIONS: Assessment of CVS on FLAIR alone is unreliable and requires susceptibility-sensitive sequences to be clinically useful.