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. 2022 Mar 29:14:11795735221084842.
doi: 10.1177/11795735221084842. eCollection 2022.

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

Victoria A Levasseur  1 , Biao Xiang  2 , Amber Salter  3 , Dmitriy A Yablonskiy  1 , Anne H Cross  2
Affiliations

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

Victoria A Levasseur et al. J Cent Nerv Syst Dis. .

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.

Objective: We aimed to determine if CVS positive lesions were specific to MS subtype, if CVS can be detected consistently among readers using the GEPCI method, and if there were differences in tissue damage in lesions with vs without CVS.

Subjects and methods: Thirty relapsing-remitting MS (RRMS) subjects and 38 primary and secondary progressive MS (PMS) subjects were scanned with GEPCI protocol at 3T. 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, and mean lesion volume, R2t*-based tissue damage score (TDS) of individual lesions and tissue damage load (TDL) were measured for CVS+, CVS-, and confluent lesions. Spearman correlations were made between MRI and clinical data. One-way ANCOVA with age and sex as covariates was used to compare measurements of CVS+ vs CVS- lesions in each individual.

Results: 398 of 548 lesions meeting inclusion criteria showed CVS. Most patients had ≥40% CVS+ lesions. CVS+ lesions were present in similar proportion among MS subtypes. Interobserver agreement was high for CVS detection. CVS+ and confluent lesions had higher average and total volumes vs CVS- lesions. CVS+ and confluent lesions had more tissue damage than CVS- lesions based on TDL and mean TDS.

Conclusion: CVS occurred in RRMS and PMS in similar proportions. CVS+ lesions had greater tissue damage and larger size than CVS- lesions.

Keywords: central vein sign; gradient echo plural contrast imaging; progressive MS; relapsing remitting multiple sclerosis.

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Conflict of interest statement

Declaration of Competing Interests: Victoria A. Levasseur has nothing to disclose in relation to this study. Biao Xiang has nothing to disclose in relation to this study. Amber Salter has nothing to disclose in relation to this study. Dmitriy Yablonskiy has nothing to disclose in relation to this study. Anne H. Cross is funded by the Manny and Rosenthal – Dr. John L. Trotter MS Center Chair of Barnes Jewish Hospital foundation and the Leon and Harriet Felman Fund for Human MS Research. She has also received consulting and/or speaking fees from Biogen, Celgene, EMD Serono, Genentech/Roche, Greenwich Biosciences, Janssen Pharmaceuticals, Novartis, and Race to Erase MS, all outside the submitted work.

Figures

Figure 1.
Figure 1.
T2*-SWI images (0.5 x 0.5 x 1 mm3 resolution) of the brain of a person with RRMS demonstrate co-localization of WM lesion with central vein, highlighted in axial, coronal, and sagittal planes (A-C).
Figure 2.
Figure 2.
R2t* map (A) and color-coded R2t*-based tissue damage score (TDS) map superimposed on the GEPCI-T1w image (B) show two periventricular lesions of a person with PMS. TDS map shows the heterogeneity of damage in the two lesions. Gray-scale bar represents R2t* (in 1/s); color bar represents TDS (unitless parameter changes between 0 and 1). Higher TDS represents lower R2t*, indicating more severe tissue damage.
Figure 3.
Figure 3.
Correlation analysis of independent lesion volume (mm3) measures by two investigators, R2 = 0.96.
Figure 4.
Figure 4.
One-way ANCOVA with age and sex as covariates comparing total lesion volume (A-C) and mean lesion volume (D-F) of lesions with and without CVS and confluent lesions in all subjects (n = 68) and separately in PMS and RRMS subgroups. Lesions with CVS (CVS+, green dots) had significantly higher lesion volumes compared to lesions without CVS (CVS-, red dots) in the entire MS group (p < .001) and in each subtype (p < .001) (A-C). Lesions with CVS had significantly higher mean lesion volumes compared to lesions without CVS in the entire MS group (p < .001) (D), PMS (p < .001) (E) and RRMS (p < .01) (F). Note: if a patient did not have CVS- lesions (n = 6), the CVS- lesion volume was assigned as 0. The lines connecting each dot represent data from the same subject. *** p < .001, ** p < .01, * p < .05. All listed p values are after multiple comparison correction using false discovery rate.
Figure 5.
Figure 5.
One-way ANCOVA with age and sex as covariates comparing tissue damage load (TDL) (A-C) and mean tissue damage score (TDS) (D-F) of lesions with and without CVS and confluent lesions in all subjects (n = 68), PMS, and RRMS patients. Lesions with CVS (green dots) and confluent lesions (blue dots) had significantly higher TDL and mean TDS compared to lesions without CVS (red dots) in the MS group (p < .01) (A, D) and the RRMS subtype (p < .01) (C, F). Note: if a patient did not have CVS- lesions (n = 6), the CVS- lesion volume was assigned as 0. The lines connecting each dot represent data from the same subject. *** p < .001, ** p < .01, * p < .05, n.s. p ≥ .05. All listed p values are after multiple comparison correction using false discovery rate.
Figure 6.
Figure 6.
Distribution of proportion of lesions with CVS by MS subtype. There was no significant difference of CVS% between MS subtypes (p = .085). Boxes represent the interquartile ranges; the horizontal lines within the boxes indicate median values.
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