Cedars-Sinai Medical Center
Neurology

Author Of 3 Presentations

Biomarkers and Bioinformatics Poster Presentation

P0083 - Gadolinium improves detection of central vein lesions in MS using 3T FLAIR*. (ID 1404)

Abstract

Background

The central vein sign (CVS) is a proposed MRI diagnostic biomarker for multiple sclerosis (MS). Use of gadolinium (Gd) in the CVS literature has been inconsistent, and it is unknown whether Gd improves detection of CVS when using FLAIR*.

Objectives

To determine if, and to what extent, gadolinium injection improves detection of CVS lesions when using FLAIR* imaging.

Methods

A cross-sectional multicenter study recruited adults clinically and/or radiologically suspected of having MS. High-isotropic-resolution, T2*-weighted segmented echo-planar imaging (T2*-EPI) was acquired pre- and post-injection of Gd-based contrast agent at 3T; pre-Gd 3D FLAIR images were also acquired. T2*-EPI and FLAIR images were processed on the QMENTA platform to generate FLAIR* images. FLAIR* pre-Gd and post-Gd scans from this substudy of 30 patients at 5 sites were analyzed. FLAIR images were used to create T2 lesion masks. Subsequently, FLAIR* images were evaluated in a random order. Lesions were categorized as CVS+, CVS-, or excluded based on the North American Imaging in MS (NAIMS) Criteria by two trained raters blinded to clinical data and Gd use. The proportion of CVS+ lesions was calculated for each scan, and differences in CVS detection based on Gd use were assessed by a Wilcoxon rank-sum test. Diagnostic performance was compared against McDonald 2017 Criteria.

Results

The mean participant age was 45 years (SD: 12); 23 (77%) were women. 14 (47%) met McDonald 2017 Criteria for MS, while 16 (53%) did not (“non-MS”). A total of 487 CVS+ lesions and 976 CVS- lesions were evaluated. The percentage of CVS+ lesions post-Gd in the MS group (median 67% [IQR 30%]) was higher than pre-Gd (41% [47%], p<0.001). There was no apparent difference in percentage of CVS+ lesion in the non-MS group (post-Gd: 10% [23%]; pre-Gd: 5% [29%]; p=0.1). In the MS group, 12/14 (86%) had ≥40% CVS+ lesions on post-Gd imaging, whereas only 8/14 (57%) exceeded that threshold on pre-Gd imaging. When evaluating CVS performance using the 40% CVS+ threshold, the sensitivity and specificity of the CVS post-Gd for MS were 86% and 81%, respectively, compared to 54% and 86% pre-Gd.

Conclusions

The detection of the CVS using FLAIR* at 3T is improved when Gd is used. Based on these results, a multicenter prospective CVS diagnostic study, sponsored by NINDS and NAIMS, will use Gd in the study protocol. Future clinical use of the CVS should balance the increased costs and potential risks of Gd use with the risks of misdiagnosis due to missing CVS on non-contrast imaging.

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Biomarkers and Bioinformatics Poster Presentation

P0135 - Preventing multiple sclerosis misdiagnosis using the “central vein sign”: A real-world study (ID 500)

Speakers
Presentation Number
P0135
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Misdiagnosis of multiple sclerosis (MS) is common and often occurs due to misattribution of non-MS magnetic resonance imaging (MRI) lesions to MS demyelination. A recently developed MRI biomarker, the central vein sign (CVS), has demonstrated high specificity for MS lesions and may thus help prevent misdiagnosis.

Objectives

We explored the potential “real world” value of CVS in preventing MS misdiagnosis by comparing CVS in patients with MS and patients previously misdiagnosed with MS by standard clinical practice and established diagnostic tools.

Methods

30 patients (15 with MS and 15 misdiagnosed with MS) were prospectively recruited to undergo 3T brain MRI. T2-weighted fluid-attenuated inversion recovery (FLAIR) and T2*-weighted segmented echo-planar-imaging (T2*-EPI) were acquired to generate FLAIR* images, then analyzed by two independent raters blinded to clinical information. The percentage of lesions with CVS was calculated for each patient.

Results

The number of brain lesions per patient did not significantly differ between the two groups. The number of lesions with CVS, however, did differ, with a mean of 0.93 lesions (range 0-6) in the misdiagnosed group versus 6.3 (range 0-15) in the MS group. A CVS lesion threshold of 29% or higher resulted in high adjusted sensitivity of 0.79 (95% CI: 0.68-0.95) and specificity of 0.88 (95% CI: 0.68-0.95) for MS and correctly identified 87% of patients previously misdiagnosed with MS. Interrater reliability for CVS was excellent with a Cohen’s kappa coefficient of 0.86.

Conclusions

Our study found that CVS differentiated with high sensitivity and specificity patients with MS from patients who were previously misdiagnosed with MS after undergoing routine clinical evaluation. We believe that our findings further support the incorporation of CVS in the diagnostic approach to MS to increase accuracy and reduce misdiagnosis.

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Imaging Poster Presentation

P0542 - Assessment of central vein sign conspicuity in multicenter 3T FLAIR* imaging (ID 985)

Abstract

Background

The central vein sign (CVS) is a proposed diagnostic biomarker for MS that can be identified using FLAIR*. The robustness of 3T FLAIR*, with and without the injection of gadolinium contrast agent (Gd), for imaging the CVS in a multicenter setting has not yet been demonstrated.

Objectives

To assess the conspicuity of the CVS on 3T FLAIR* imaging acquired across different sites with and without the injection of Gd.

Methods

A cross-sectional multicenter study recruited adults with a clinical and/or radiological suspicion of having MS from 10 sites within the North American Imaging in MS (NAIMS) Cooperative. High-isotropic-resolution T2*-weighted segmented echo-planar imaging (T2*-EPI) was acquired at 3T, pre- and post-injection of Gd, along with 3D FLAIR on different scanner brands and models. T2*-EPI and FLAIR images were processed on an online imaging platform (QMENTA) to generate FLAIR* images. To objectively assess the conspicuity of the CVS inside MS lesions, lesions and veins were segmented automatically and used to compute lesion-to-vein contrast-to-noise ratio (CNR) measures. ANOVA was used to compare CNR values across sites with post-hoc Tukey Honest Significant Difference testing. Multiple testing between sites was considered by controlling the false discovery rate. One-sided paired t-testing was used to compare the overall lesion-to-vein CNR values between pre- and post-Gd FLAIR*.

Results

Seventy-eight patients from nine sites were included in the analysis; one site was excluded due to low enrollment. The overall mean(coefficient of variation, CV) lesion-to-vein CNR values across the nine sites were 0.35(14%) and 0.37(12%) for pre- and post-Gd FLAIR*, respectively. Excluding an additional site that used an unharmonized FLAIR acquisition, the resulting mean(CV) CNR values were 0.36(12%) for pre-Gd and 0.37(11%) for post-Gd FLAIR*. Across most sites, there was a significant improvement in lesion-to-vein CNR measures for post-Gd compared to pre-Gd FLAIR* [mean difference = 0.011, p < 0.001, 95% CI: (0.008,0.015)].

Conclusions

Lesion-to-vein CNR measures across sites are in line with values first published for 3T FLAIR* and demonstrate the robustness of 3T FLAIR* for imaging the CVS in a multicenter setting. Moreover, there was an increase in vein conspicuity with improvement in CNR on post-Gd FLAIR*. Based on these results, a prospective multicenter NAIMS CVS diagnostic study, sponsored by NINDS, will use 3T FLAIR* imaging with Gd in the study protocol.

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