ASAS MRImagine - ASAS MRI Working group for MRI Lesion Definitions

Background: There has been no systematic update of MRI lesion definitions in the sacroiliac joint and spine in the past decade. In that time there have been substantial advances in our understanding of the scope of lesions evident in these locations, the relationship between inflammatory and structural lesions, and their sensitivity and specificity for axial spondyloarthritis. Consequently, an update of lesion definitions was considered desirable by ASAS. There has been no systematic assessment of inflammatory and structural lesions on MRI scans of patients recruited to the ASAS Classification project. It was considered desirable to apply the updated lesion definitions for the purposes of evaluating their relative frequency according to diagnostic category and reliability of their detection in the scans from the ASAS cohort. There have been substantial concerns with the validity of the ASAS definition of a positive MRI for sacroiliitis according to the 2-slice definition for bone marrow edema in the SIJ proposed in 2009. The 2016 update mainly focuses on bone marrow edema considered highly suggestive of axSpA and is therefore an entirely subjective definition. Moreover, there has been no proposal for an ASAS definition of a positive MRI for structural lesions in the SIJ.

Aim:

  1. To update lesion descriptions and definitions for MRI lesions in the sacroiliac joint and spine of patients with axial spondyloarthritis.
  2. To describe the spectrum of ASAS-defined MRI lesions in the sacroiliac joints and spine according to diagnostic category in patients recruited to the ASAS classification cohort and the reliability of their detection.
  3. To identify quantitative definitions of an ASAS positive MRI for inflammatory and structural lesions in the sacroiliac joint using the scans from patients recruited to the ASAS classification cohort.


Methodology:

  1. The literature pertaining to these MRI lesion definitions was discussed at three meetings of the group. 25 investigators (20 rheumatologists, 5 radiologists) determined which definitions should be retained or required revision, and which required a new definition. Lesion definitions were assessed in a multi-reader validation exercise using 278 MRI scans from the ASAS classification cohort by global assessment (lesion present/absent) and detailed scoring (inflammation and structural). Reliability of detection of lesions was analysed using kappa statistics and the intraclass correlation coefficient (ICC).
  2. The ASAS MRI group assessed MRIs from the ASAS Classification Cohort in two reading exercises where (A) 169 cases and 7 central readers; (B) 107 cases and central readers. We calculated sensitivity/specificity for the number of SI joint quadrants or slices with bone marrow oedema (BME), erosion, fat lesion, where a majority of central readers had high confidence there was a definite active or structural lesion. Cut-offs with ≥95% specificity were analysed for their predictive utility for follow-up rheumatologist diagnosis of axSpA by calculating positive/negative predictive values (PPVs/NPVs) and selecting cut-offs with PPV≥95%.
  3. After review of the existing literature on all possible types of spinal MRI pathologies in axSpA, the group (12 rheumatologists and two radiologists) consented on the required revisions of lesion definitions compared with the existing nomenclature of 2012. In a second step, using 62 MRI scans from the ASAS classification cohort, the proposed definitions were validated in a multireader campaign by global (absent/ present) and detailed (inflammation and structural) lesion assessment at the vertebral corner (VC), vertebral endplate, facet joints, transverse processes, lateral and posterior elements. Intraclass correlation coefficient (ICC) was used for analysis.


Results:

  1. No revisions were made to the current ASAS definition of a positive SIJ MRI or definitions for subchondral inflammation and sclerosis. The following definitions were revised: capsulitis, enthesitis, fat lesion and erosion. New definitions were developed for joint space enhancement, joint space fluid, fat metaplasia in an erosion cavity, ankylosis and bone bud. The most frequently detected structural lesion, erosion, was detected almost as reliably as subchondral inflammation (κappa/ICC:0.61/0.54 and 0.60/0.83). Fat metaplasia in an erosion cavity and ankylosis were also reliably detected despite their low frequency (κappa/ ICC:0.50/0.37 and 0.58/0.97).
  2. Structural lesions, especially erosions, were as frequent as active lesions (≈40%), the majority of patients in the ASAS classification cohort having both types of lesions. The ASAS definitions for active MRI lesion typical of axSpA and erosion were comparatively discriminatory between axSpA and non-axSpA. Local reader overcall for active MRI lesions was about 30% but this had a minor impact on the number of patients (6.4%) classified as axSpA. Substitution of radiography with MRI structural lesions also had little impact on classification status (1.4%).
  3. Active or structural lesions typical of axSpA on MRI had PPVs≥95% for clinical diagnosis of axSpA. Cut-offs that best reflected a definite active lesion typical of axSpA were either ≥4 SI joint quadrants with BME at any location or at the same location in ≥3 consecutive slices. For definite structural lesion, the optimal cut-offs were any one of ≥3 SI joint quadrants with erosion or ≥5 with fat lesions, erosion at the same location for ≥2 consecutive slices, fat lesions at the same location for ≥3 consecutive slices, or presence of a deep (i.e. >1 cm depth) fat lesion.
  4. For the spine, revisions were made for both inflammatory (bone marrow oedema, BMO) and structural (fat, erosion, bone spur and ankylosis) lesions, including localization (central vs lateral), extension (VC vs vertebral endplate) and extent (minimum number of slices needed), while new definitions were suggested for the type of lesion based on lesion maturity (VC monomorphic vs dimorphic). The most reliably assessed lesions were VC fat lesion and VC monomorphic BMO (ICC (mean of all 36 reader pairs/overall 9 readers): 0.91/0.92; 0.70/0.67, respectively.


Conclusions:

  1. The ASAS-MRI WG concluded that several definitions required revision and some new definitions were necessary. Multi-reader validation demonstrated substantial reliability for the most frequently detected lesions and comparable reliability between active and structural lesions.
  2. Despite substantial discrepancy between central and local readers in interpretation of both types of MRI lesion, this had a minor impact on the numbers of patients classified as axSpA supporting the robustness of the ASAS criteria for differences in assessment of imaging.
  3. The ASAS MRI group has proposed cut-offs for definite active and structural lesions typical of axSpA that have high PPVs for a long-term clinical diagnosis of axSpA for application in disease classification and clinical research.
  4. The lesion definitions for spinal MRI lesions compatible with SpA were updated by consensus and validated by a group of experienced readers. The lesions with the highest frequency and best reliability were fat and monomorphic inflammatory lesions at the VC.

 

Timelines of the project: 2017- ongoing

Project Team

PI: Walter P. Maksymowych and Xenofon Baraliakos

Working group:

Walter P Maksymowych (Edmonton, Canada), Robert GW Lambert (Edmonton, Canada), Mikkel Østergaard (Copenhagen, Denmark), Susanne Juhl Pedersen (Copenhagen, Denmark), Pedro M Machado (London, United Kingdom), Ulrich Weber (Zurich, Switzerland),  Alexander N Bennett (London, United Kingdom), Juergen Braun (Herne, Germany), Ruben Burgos-Vargas (Mexico City, Mexico), Manouk de Hooge (Ghent, Belgium), Atul A Deodhar (Portland, USA), Iris Eshed (Tel Aviv, Israel), Anne Grethe Jurik (Aarhus, Denmark), Kay-Geert Armin Hermann (Berlin, Germany), Robert BM Landewé (Amsterdam, the Netherlands), Helena Marzo-Ortega (Leeds, United Kingdom), Victoria Navarro-Compán (Madrid, Spain), Denis Poddubnyy (Berlin, Germany), Monique Reijnierse (Leiden, the Netherlands), Martin Rudwaleit (Berlin, Germany), Joachim Sieper (Berlin, Germany), Filip E Van den Bosch (Ghent, Belgium), Désirée van der Heijde (Leiden, the Netherlands), Irene E van der Horst-Bruinsma (Amsterdam, the Netherlands), Stephanie Wichuk (Edmonton, Canada), Xenofon Baraliakos (Herne, Germany)

 

Publications

  1. Maksymowych WP, Lambert RG, Østergaard M, Pedersen SJ, Machado P, Weber U, Bennett A, Braun J, Burgos-Vargas R, de Hooge M, Deodhar A, Eshed I, Jurik A, Armin Hermann KG, Landewé RB, Marzo-Ortega H, Navarro-Compán V, Poddubnyy D, Reijnierse M, Rudwaleit M, Sieper J, Van den Bosch F, van der Heijde D, van der Horst-Bruinsma I, Wichuk S, Baraliakos X. MRI lesions in the sacroiliac joints of patients with spondyloarthritis: an update of definitions and validation by the ASAS MRI working group. Ann Rheum Dis 78(11): 1550-1558, 2019
  2. Maksymowych WP, Lambert RG, Baraliakos X, Weber U, Machado PM, Pedersen SJ, de Hooge M, Sieper J, Wichuk S, Poddubnyy D, Rudwaleit M, van der Heijde D, Landewe R, Eshed I, Ostergaard M. Data-Driven Definitions for Active and Structural MRI Lesions in the Sacroiliac Joint in Spondyloarthritis and their Predictive Utility. Rheumatology (Oxford) 60(10): 4778-4789, 2021
  3. Maksymowych WP, Pedersen SJ, Weber U, Baraliakos X, Machado PM, Eshed I, de Hooge M, Sieper J, Wichuk S, Rudwaleit M, van der Heijde D, Landewe RBM, Poddubnyy D, Ostergaard M, Lambert RGW. Central reader evaluation of MRI scans of the sacroiliac joints from the ASAS classification cohort: discrepancies with local readers and impact on the performance of the ASAS criteria. Ann Rheum Dis 79(7): 935-942, 2020
  4. Baraliakos X, Østergaard M, Lambert RGW, Eshed I, Machado PM, Pedersen SJ, Weber U, de Hooge M, Sieper J, Poddubnyy D, Rudwaleit M, van der Heijde D, Landewé RBM, Maksymowych WP. MRI lesions of the spine in patients with axial spondyloarthritis: An update of lesion definitions and validation by the ASAS MRI working group. Ann Rheum Dis 81(9); 1243-1251, 2022