Validation and Standardization of Paramagnetic Rim Lesion (PRL) Identification in Multiple Sclerosis Across MAGNIMS Centers

NCT07705581 | Active Not Recruiting

• 1 other identifier: PRL MAGNIMS MS
• Study Type: observational
• Target: 1,402
• Locations: 11 countries
• Sites: 15

Brief Summary

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system. Paramagnetic rim lesions (PRLs) are a subtype of chronic active MS lesions showing an iron-laden inflammatory rim on susceptibility-sensitive MRI. PRLs mark a more aggressive disease course and have recently been incorporated, together with the central vein sign, into the updated diagnostic criteria for MS. Before PRLs can be used reliably in multicenter clinical practice and trials, the way they are identified must be shown to be consistent across different centers, raters, and scanners. This is a retrospective, multicenter, observational validation study. Using previously acquired 3-Tesla brain MRI scans from MS patients across 15 MAGNIMS centers, expert raters count PRLs according to the NAIMS consensus definitions. The study measures how consistently PRLs are identified between centers, raters, and scanners (inter-rater, inter-center, and inter-scanner agreement), using statistical methods such as the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Where systematic sources of disagreement are found, the PRL definitions are refined through a structured Delphi consensus process and re-tested on an independent set of scans. The goal is to standardize PRL identification and provide an evidence-based basis for consistent, reproducible PRL assessment to support future multicenter studies. No new patients are recruited and no new scans or biological samples are collected; only pre-existing, de-identified imaging and clinical data are used.

Conditions

Multiple Sclerosis

Keywords

Paramagnetic Rim Lesions; Chronic Active Lesions; Magnetic Resonance Imaging; Susceptibility-Weighted Imaging; Quantitative Susceptibility Mapping; Imaging Biomarker; Multiple Sclerosis; MAGNIMS

Outcome Measures

Primary Outcomes (1)

• Rated number of paramagnetic rim lesions (PRLs) per MRI scan and per rater

  Number of paramagnetic rim lesions (PRLs) identified on each pre-acquired 3T MRI scan by each rater, according to NAIMS-PRL criteria, to evaluate the consistency and reliability of PRL identification across MAGNIMS centers, raters, and scanners.

  Baseline

Secondary Outcomes (1)

• Correlation between PRL burden and clinical characteristics

  Baseline

Study Arms (1)

MS patients with pre-acquired 3T MRI scans

Retrospective cohort of adult patients with confirmed Multiple Sclerosis according to the revised 2017 McDonald Criteria, with pre-acquired 3T MRI scans fulfilling NAIMS-PRL criteria and corresponding demographic and clinical data available for research use. No new patient recruitment, MRI scans, or study-specific interventions will be performed. MRI data will be retrospectively assessed for paramagnetic rim lesions to evaluate the reliability and consistency of PRL identification across MAGNIMS centers, raters, and scanners.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with confirmed Multiple Sclerosis according to the revised 2017 McDonald Criteria, with previously acquired 3T MRI scans fulfilling NAIMS-PRL criteria and corresponding demographic and clinical data available for retrospective PRL assessment. No new patient recruitment, additional MRI scans, or study-specific interventions will be performed.

You may qualify if:

• Patients with confirmed diagnosis of Multiple Sclerosis (MS) according to the revised 2017 McDonald Criteria.
• Aged 18 years or older at the time of MRI scan.
• Previously acquired 3T MRI scans performed according to NAIMS-PRL criteria, including 3D-FLAIR, SWI, and post-Gd 2D/3D T1-weighted sequences.
• MRI resolution according to NAIMS criteria: submillimeter in-plane resolution ≤0.9 mm; 2D acquisition with slice thickness ≤3 mm; 3D acquisition with ≤2-mm isotropic or higher resolution.
• Patients must have already provided consent for research use of their MRI scans and corresponding clinical data.

You may not qualify if:

• MRI scans with artifacts, poor image quality, or other limitations preventing reliable PRL assessment.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (15)

Medical University Graz

Graz, 8036, Austria

Location

Medical University of Vienna

Vienna, 1090, Austria

Location

Charles University and General University Hospital

Prague, 128 00, Czechia

Location

Danish Research Centre for Magnetic Resonance

Copenhagen, 2650, Denmark

Location

University Medical Center Mainz

Homburg, 66424, Germany

Location

IRCCS San Raffaele

Milan, 20132, Italy

Location

University Hospital of Padua

Padova, 35128, Italy

Location

University of Verona

Verona, 37129, Italy

Location

Amsterdam UMC

Amsterdam, 1105, Netherlands

Location

Unknown Facility

Oslo, 0372, Norway

Location

Vall d'Hebron University Hospital

Barcelona, 08035, Spain

Location

Karolinska Neuroimmunology & Multiple Sclerosis (KNIMS) Centre

Stockholm, 171 77, Sweden

Location

University Hospital Basel

Basel, 4031, Switzerland

Location

UCL Institute of Neurology

London, WC1N 3BG, United Kingdom

Location

University of Oxford

Oxford, OX1 2JD, United Kingdom

Location

Related Publications (18)

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• Cagol A, Benkert P, Melie-Garcia L, Schaedelin SA, Leber S, Tsagkas C, Barakovic M, Galbusera R, Lu PJ, Weigel M, Ruberte E, Radue EW, Yaldizli O, Oechtering J, Lorscheider J, D'Souza M, Fischer-Barnicol B, Muller S, Achtnichts L, Vehoff J, Disanto G, Findling O, Chan A, Salmen A, Pot C, Bridel C, Zecca C, Derfuss T, Lieb JM, Remonda L, Wagner F, Vargas MI, Du Pasquier RA, Lalive PH, Pravata E, Weber J, Cattin PC, Absinta M, Gobbi C, Leppert D, Kappos L, Kuhle J, Granziera C. Association of Spinal Cord Atrophy and Brain Paramagnetic Rim Lesions With Progression Independent of Relapse Activity in People With MS. Neurology. 2024 Jan 9;102(1):e207768. doi: 10.1212/WNL.0000000000207768. Epub 2023 Dec 13.

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• Dal-Bianco A, Grabner G, Kronnerwetter C, Weber M, Kornek B, Kasprian G, Berger T, Leutmezer F, Rommer PS, Trattnig S, Lassmann H, Hametner S. Long-term evolution of multiple sclerosis iron rim lesions in 7 T MRI. Brain. 2021 Apr 12;144(3):833-847. doi: 10.1093/brain/awaa436.

  PMID: 33484118 BACKGROUND

• Dal-Bianco A, Grabner G, Kronnerwetter C, Weber M, Hoftberger R, Berger T, Auff E, Leutmezer F, Trattnig S, Lassmann H, Bagnato F, Hametner S. Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging. Acta Neuropathol. 2017 Jan;133(1):25-42. doi: 10.1007/s00401-016-1636-z. Epub 2016 Oct 27.

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• Absinta M, Sati P, Schindler M, Leibovitch EC, Ohayon J, Wu T, Meani A, Filippi M, Jacobson S, Cortese IC, Reich DS. Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions. J Clin Invest. 2016 Jul 1;126(7):2597-609. doi: 10.1172/JCI86198. Epub 2016 Jun 6.

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• Absinta M, Sati P, Masuzzo F, Nair G, Sethi V, Kolb H, Ohayon J, Wu T, Cortese ICM, Reich DS. Association of Chronic Active Multiple Sclerosis Lesions With Disability In Vivo. JAMA Neurol. 2019 Dec 1;76(12):1474-1483. doi: 10.1001/jamaneurol.2019.2399.

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• Calvi A, Clarke MA, Prados F, Chard D, Ciccarelli O, Alberich M, Pareto D, Rodriguez Barranco M, Sastre-Garriga J, Tur C, Rovira A, Barkhof F. Relationship between paramagnetic rim lesions and slowly expanding lesions in multiple sclerosis. Mult Scler. 2023 Mar;29(3):352-362. doi: 10.1177/13524585221141964. Epub 2022 Dec 14.

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• Reeves JA, Mohebbi M, Wicks T, Salman F, Bartnik A, Jakimovski D, Bergsland N, Schweser F, Weinstock-Guttman B, Dwyer MG, Zivadinov R. Paramagnetic rim lesions predict greater long-term relapse rates and clinical progression over 10 years. Mult Scler. 2024 Apr;30(4-5):535-545. doi: 10.1177/13524585241229956. Epub 2024 Feb 17.

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MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 7, 2026
• First Posted: July 15, 2026
• Study Start: January 1, 2017
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 15, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1); AU (2); NL (1); IT (3); DK (1); ES (1); SE (1); CH (1); NO (1); DE (1); GB (2)