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

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 Retros...

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Published inJournal of magnetic resonance imaging Vol. 61; no. 4; pp. 1812 - 1828
Main Authors Elkady, Ahmed M., Elliott, Colm, Fetco, Dumitru, Araujo, David, Karimaghaloo, Zahra, Ganzetti, Marco, Clayton, David, Craveiro, Licinio, Kazlauskaite, Agne, Narayanan, Sridar, Arnold, Douglas L., Rudko, David A.
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.04.2025
Wiley Subscription Services, Inc
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Online AccessGet full text
ISSN1053-1807
1522-2586
1522-2586
DOI10.1002/jmri.29583

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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
AbstractList BackgroundMultiple 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.PurposeTo conduct a multiparametric MRI analysis of PRLs.Study TypeRetrospective/longitudinal.SubjectsNinety‐five progressive MS subjects with at least one persistent PRL who were enrolled in the CONSONANCE trial.Field Strength/Sequence3‐T/Susceptibility‐weighted, T1‐weighted, T2‐weighted, and fluid‐attenuated inversion recovery.AssessmentAcute/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 TestsLinear mixed models. A P‐value <0.05 was considered significant.ResultsThere 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 ConclusionMultiparametric 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 Evidence2Technical EfficacyStage 3
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. To conduct a multiparametric MRI analysis of PRLs. Retrospective/longitudinal. Ninety-five progressive MS subjects with at least one persistent PRL who were enrolled in the CONSONANCE trial. 3-T/Susceptibility-weighted, T1-weighted, T2-weighted, and fluid-attenuated inversion recovery. 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. Linear mixed models. A P-value <0.05 was considered significant. There was a significant decrease in sT1w/T2w (-0.24 ± -5.3 × 10 ) 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  ± 1.2 × 10 ) and rim (+5.6 × 10  ± 1.2 × 10 ) 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  ± 2.0 × 10 ) and rim (-2.4 × 10  ± 2.0 × 10 ), indicative of irreversible tissue damage. Significant positive correlations between PRL core and rim sT1w/T2w (R  = 0.53), R2* (R  = 0.69) and QS (R  = 0.52) were observed. 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. 2 TECHNICAL EFFICACY: Stage 3.
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.BACKGROUNDMultiple 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.To conduct a multiparametric MRI analysis of PRLs.PURPOSETo conduct a multiparametric MRI analysis of PRLs.Retrospective/longitudinal.STUDY TYPERetrospective/longitudinal.Ninety-five progressive MS subjects with at least one persistent PRL who were enrolled in the CONSONANCE trial.SUBJECTSNinety-five progressive MS subjects with at least one persistent PRL who were enrolled in the CONSONANCE trial.3-T/Susceptibility-weighted, T1-weighted, T2-weighted, and fluid-attenuated inversion recovery.FIELD STRENGTH/SEQUENCE3-T/Susceptibility-weighted, T1-weighted, T2-weighted, and fluid-attenuated inversion recovery.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.ASSESSMENTAcute/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.Linear mixed models. A P-value <0.05 was considered significant.STATISTICAL TESTSLinear mixed models. A P-value <0.05 was considered significant.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.RESULTSThere 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.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.DATA CONCLUSIONMultiparametric 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.2 TECHNICAL EFFICACY: Stage 3.LEVEL OF EVIDENCE2 TECHNICAL EFFICACY: Stage 3.
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
Author Elliott, Colm
Craveiro, Licinio
Arnold, Douglas L.
Fetco, Dumitru
Elkady, Ahmed M.
Clayton, David
Kazlauskaite, Agne
Narayanan, Sridar
Rudko, David A.
Araujo, David
Karimaghaloo, Zahra
Ganzetti, Marco
AuthorAffiliation 2 Department of Neurology and Neurosurgery McGill University Montreal Quebec Canada
4 F. Hoffmann‐La Roche Ltd Basel Switzerland
3 NeuroRx Research Montreal Quebec Canada
1 McConnell Brain Imaging Centre Montreal Neurological Institute and Hospital Montreal Quebec Canada
5 Genentech Inc. San Francisco California USA
6 Department of Biomedical Engineering McGill University Montreal Quebec Canada
AuthorAffiliation_xml – name: 4 F. Hoffmann‐La Roche Ltd Basel Switzerland
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/39239775$$D View this record in MEDLINE/PubMed
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CitedBy_id crossref_primary_10_1002_jmri_29585
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Keywords myelin
T1w/T2w
iron
quantitative susceptibility mapping
R2 mapping
paramagnetic rim lesions
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Snippet Background Multiple sclerosis (MS) paramagnetic rim lesions (PRLs) are markers of chronic active biology and exhibit complex iron and myelin changes that may...
Multiple sclerosis (MS) paramagnetic rim lesions (PRLs) are markers of chronic active biology and exhibit complex iron and myelin changes that may complicate...
BackgroundMultiple sclerosis (MS) paramagnetic rim lesions (PRLs) are markers of chronic active biology and exhibit complex iron and myelin changes that may...
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SubjectTerms Acute Disease
Adult
Bioaccumulation
Brain - diagnostic imaging
Chronic Disease
Damage accumulation
Female
Field strength
Humans
Image Processing, Computer-Assisted
Iron
Lesions
Longitudinal Studies
Magnetic permeability
Magnetic resonance imaging
Magnetic Resonance Imaging - methods
Magnetic susceptibility
Male
Middle Aged
Multiparametric Magnetic Resonance Imaging - methods
Multiple sclerosis
Multiple Sclerosis - diagnostic imaging
Myelin
paramagnetic rim lesions
quantitative susceptibility mapping
R2 mapping
Recovery
Retrospective Studies
Statistical analysis
Statistical models
Statistical tests
T1w/T2w
Title Longitudinal Multiparametric Quantitative MRI Evaluation of Acute and Chronic Multiple Sclerosis Paramagnetic Rim Lesions
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fjmri.29583
https://www.ncbi.nlm.nih.gov/pubmed/39239775
https://www.proquest.com/docview/3176111886
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https://pubmed.ncbi.nlm.nih.gov/PMC11896925
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