Stronger Microstructural Damage Revealed in Multiple Sclerosis Lesions with Central Vein Sign by Quantitative Gradient Echo MRI

Abstract

Background: Multiple sclerosis (MS) lesions typically form around a central vein that can be visualized with FLAIR* MRI, creating the central vein sign (CVS) which may reflect lesion pathophysiology. Herein we used Gradient Echo Plural Contrast Imaging (GEPCI) MRI to simultaneously visualize CVS and measure tissue damage in MS lesions. We examined CVS in relation to tissue integrity in white matter (WM) lesions and among MS subtypes. Subjects and Methods: Thirty relapsing remitting MS (RRMS) subjects and 38 progressive MS (PMS) subjects were scanned with GEPCI protocol. GEPCI T2*SWI images were generated to visualize CVS. Two investigators independently evaluated WM lesions for CVS and measured lesion volumes. To estimate tissue damage severity, total lesion volume, mean lesion volume, R2t* based tissue damage score (TDS) of individual lesions and tissue damage load (TDL) were measured for CVS positive, CVS negative , and confluent lesions. Spearman correlations were made between MRI and clinical data. A paired t-test was used to compare measurements of CVS positive versus CVS negative lesions in each individual. Results: 398 of 548 lesions meeting inclusion criteria showed CVS. Most patients had > 40% CVS positive lesions. CVS positive lesions were present in similar proportion among MS subtypes. Interobserver agreement was high for CVS detection. CVS positive and confluent lesions had higher average and total volumes versus CVS negative lesions. CVS positive and confluent lesions had more tissue damage than CVS negative lesions based on TDL and mean TDS. Conclusion: CVS occurred in RRMS and PMS in similar proportions. CVS positive lesions had greater tissue damage and larger size than CVS negative lesions.