Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study

Abstract

Background: The “central vein sign” (CVS), a linear hypointensity on T2*-weighted imaging corresponding to a central vein/venule, is associated with multiple sclerosis (MS) lesions. The effect of lesion-size exclusion criteria on MS diagnostic accuracy has not been extensively studied. Objective: Investigate the optimal lesion-size exclusion criteria for CVS use in MS diagnosis. Methods: Cross-sectional study of 163 MS and 51 non-MS, and radiological/histopathological correlation of 5 MS and 1 control autopsy cases. The effects of lesion-size exclusion on MS diagnosis using the CVS, and intralesional vein detection on histopathology were evaluated. Results: CVS+ lesions were larger compared to CVS− lesions, with effect modification by MS diagnosis (mean difference +7.7 mm3, p = 0.004). CVS percentage-based criteria with no lesion-size exclusion showed the highest diagnostic accuracy in differentiating MS cases. However, a simple count of three or more CVS+ lesions greater than 3.5 mm is highly accurate and can be rapidly implemented (sensitivity 93%; specificity 88%). On magnetic resonance imaging (MRI)-histopathological correlation, the CVS had high specificity for identifying intralesional veins (0/7 false positives). Conclusion: Lesion-size measures add important information when using CVS+ lesion counts for MS diagnosis. The CVS is a specific biomarker corresponding to intralesional veins on histopathology.

Paramagnetic rim lesions and the central vein sign: Characterizing multiple sclerosis imaging markers

“…The CVS is a promising diagnostic marker of MS lesions; however, previous 3T studies have also reported an association between the CVS and increased lesion size and tissue injury. [11][12][13] We report no significant associations between the CVS and lesion size or myelin integrity in our study using a small number of CVS-negative lesions. At 3T, the number of lesions with central veins is underestimated compared to 7T, 7,34 which corresponds more closely to findings from histopathology.…”

“…At 3T, the number of lesions with central veins is underestimated compared to 7T, 7,34 which corresponds more closely to findings from histopathology. 12 At 7T, more veins are visible but also more lesions are excluded due to multiple veins being detected potentially resulting in contradictory findings across different field strengths. Moreover, our cohort of patients was younger compared to the other studies (over 40 years of age) [11][12][13] and, therefore, less likely to be affected by age-related white matter changes (lesions without the CVS).…”

“…12 At 7T, more veins are visible but also more lesions are excluded due to multiple veins being detected potentially resulting in contradictory findings across different field strengths. Moreover, our cohort of patients was younger compared to the other studies (over 40 years of age) [11][12][13] and, therefore, less likely to be affected by age-related white matter changes (lesions without the CVS). Overall, our findings support the role of the CVS as a common feature of MS lesions, not associated with lesion size or extent of demyelination.…”

“…10 Previous studies using 3T MRI, which underestimates the CVS in MS compared to 7T, have also shown that lesions with a central vein tend to be larger and have higher levels of tissue injury than those without. [11][12][13] Studies combining ultra-high field MRI and advanced imaging methods to better characterize both PRLs and the CVS, particularly in patients at the earliest stages of MS prior to the initiation of diseasemodifying therapy (DMT), are lacking. In this study, we aimed to:…”

“…At 7T, 100% diagnostic sensitivity and specificity have been reported when using a 40% threshold of lesions with the CVS to differentiate between MS and mimicking disorders 10 . Previous studies using 3T MRI, which underestimates the CVS in MS compared to 7T, have also shown that lesions with a central vein tend to be larger and have higher levels of tissue injury than those without 11–13 …”