Longitudinal Multiparametric Quantitative MRI Evaluation of Acute and Chronic Multiple Sclerosis Paramagnetic Rim Lesions

Ahmed M Elkady; Colm Elliott; Dumitru Fetco; David Araujo; Zahra Karimaghaloo; Marco Ganzetti; David Clayton; Licinio Craveiro; Agne Kazlauskaite; Sridar Narayanan; Douglas L Arnold; David A Rudko

doi:10.1002/jmri.29583

Longitudinal Multiparametric Quantitative MRI Evaluation of Acute and Chronic Multiple Sclerosis Paramagnetic Rim Lesions

J Magn Reson Imaging. 2024 Sep 6. doi: 10.1002/jmri.29583. Online ahead of print.

Authors

Ahmed M Elkady^{1

2

3}, Colm Elliott³, Dumitru Fetco^{1

2

3}, David Araujo^{1

3}, Zahra Karimaghaloo³, Marco Ganzetti⁴, David Clayton⁵, Licinio Craveiro⁴, Agne Kazlauskaite⁴, Sridar Narayanan^{1

2

3}, Douglas L Arnold^{1

2

3}, David A Rudko^{1

2

6}

Affiliations

¹ McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada.
² Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
³ NeuroRx Research, Montreal, Quebec, Canada.
⁴ F. Hoffmann-La Roche Ltd, Basel, Switzerland.
⁵ Genentech Inc., San Francisco, California, USA.
⁶ Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada.

PMID: 39239775
DOI: 10.1002/jmri.29583

Abstract

Background: Multiple sclerosis (MS) paramagnetic rim lesions (PRLs) are markers of chronic active biology and exhibit complex iron and myelin changes that may complicate quantification when using conventional MRI approaches.

Purpose: To conduct a multiparametric MRI analysis of PRLs.

Study type: Retrospective/longitudinal.

Subjects: Ninety-five progressive MS subjects with at least one persistent PRL who were enrolled in the CONSONANCE trial.

Field strength/sequence: 3-T/Susceptibility-weighted, T1-weighted, T2-weighted, and fluid-attenuated inversion recovery.

Assessment: Acute/chronic PRLs and non-PRLs were measured at screening, 24, 48, and 96 weeks using quantitative magnetic susceptibility (QS), R2*, and standardized T1w/T2w ratio (sT1w/T2w). PRL analyses were performed for whole lesion, core, and rim. The correlations between PRL core and rim sT1w/T2w, QS, and R2* were assessed.

Statistical tests: Linear mixed models. A P-value <0.05 was considered significant.

Results: There was a significant decrease in sT1w/T2w (-0.24 ± -5.3 × 10^-3) and R2* (-3.6 ± 2.2 Hz) but a significant increase in QS (+21 ± 1.3 ppb) using whole-lesion analysis of chronic PRLs compared to non-PRLs at screening. Tissue damage accumulated at the 96-week time point was more evident in acute/chronic PRLs compared to acute/chronic non-PRLs (ΔsT1w/T2w = -0.21/-0.24 ± 0.033/0.0053; ΔR2* = -4.4/-3.6 ± 1.4/2.2 Hz). New, acute PRL sT1w/T2w significantly increased in lesion core (+4.3 × 10^-3 ± 1.2 × 10^-4) and rim (+5.6 × 10^-3 ± 1.2 × 10^-4) 24 weeks post lesion inception, suggestive of partial recovery. Chronic PRLs, contrastingly, showed significant decreases in sT1w/T2w over the initial 24 weeks for both core (-2.1 × 10^-4 ± 2.0 × 10^-5) and rim (-2.4 × 10^-4 ± 2.0 × 10^-5), indicative of irreversible tissue damage. Significant positive correlations between PRL core and rim sT1w/T2w (R² = 0.53), R2* (R² = 0.69) and QS (R² = 0.52) were observed.

Data conclusion: Multiparametric assessment of PRLs has the potential to be a valuable tool for assessing complex iron and myelin changes in chronic active PRLs of progressive MS patients.

Level of evidence: 2 TECHNICAL EFFICACY: Stage 3.

Keywords: R2* mapping; T1w/T2w; iron; myelin; paramagnetic rim lesions; quantitative susceptibility mapping.

Abstract

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