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 in | Journal of magnetic resonance imaging Vol. 61; no. 4; pp. 1812 - 1828 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken, USA
John Wiley & Sons, Inc
01.04.2025
Wiley Subscription Services, Inc |
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Online Access | Get full text |
ISSN | 1053-1807 1522-2586 1522-2586 |
DOI | 10.1002/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 |
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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 – name: 5 Genentech Inc. San Francisco California USA – name: 3 NeuroRx Research Montreal Quebec Canada – name: 1 McConnell Brain Imaging Centre Montreal Neurological Institute and Hospital Montreal Quebec Canada – name: 2 Department of Neurology and Neurosurgery McGill University Montreal Quebec Canada – name: 6 Department of Biomedical Engineering McGill University Montreal Quebec Canada |
Author_xml | – sequence: 1 givenname: Ahmed M. orcidid: 0000-0002-6793-3396 surname: Elkady fullname: Elkady, Ahmed M. organization: NeuroRx Research – sequence: 2 givenname: Colm surname: Elliott fullname: Elliott, Colm organization: NeuroRx Research – sequence: 3 givenname: Dumitru surname: Fetco fullname: Fetco, Dumitru organization: NeuroRx Research – sequence: 4 givenname: David surname: Araujo fullname: Araujo, David organization: NeuroRx Research – sequence: 5 givenname: Zahra surname: Karimaghaloo fullname: Karimaghaloo, Zahra organization: NeuroRx Research – sequence: 6 givenname: Marco surname: Ganzetti fullname: Ganzetti, Marco organization: F. Hoffmann‐La Roche Ltd – sequence: 7 givenname: David surname: Clayton fullname: Clayton, David organization: Genentech Inc – sequence: 8 givenname: Licinio surname: Craveiro fullname: Craveiro, Licinio organization: F. Hoffmann‐La Roche Ltd – sequence: 9 givenname: Agne surname: Kazlauskaite fullname: Kazlauskaite, Agne organization: F. Hoffmann‐La Roche Ltd – sequence: 10 givenname: Sridar surname: Narayanan fullname: Narayanan, Sridar organization: NeuroRx Research – sequence: 11 givenname: Douglas L. surname: Arnold fullname: Arnold, Douglas L. organization: NeuroRx Research – sequence: 12 givenname: David A. surname: Rudko fullname: Rudko, David A. email: david.rudko@mcgill.ca organization: McGill University |
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 https://www.proquest.com/docview/3101236981 https://pubmed.ncbi.nlm.nih.gov/PMC11896925 |
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