1. Role of MRI in Assessment and Diagnosis of Axial Spondyloarthritis Lebanese Society of Rheumatology 2009 Nov 07 Ulrich Weber MD, Rheumatology Balgrist University Hospital, Zurich, Switzerland

2. Disclosure Nothing to disclose No advisory board memberships Funding of the project Whole Body MRI in SpA Walter L. and Johanna Wolf Foundation, Zurich, Switzerland Foundation for Scientific Research at the University of Zurich, Switzerland

3. Ankylosing Spondylitis Axial Disease

4. Ankylosing Spondylitis Nonaxial Disease Uveitis Dactylitis Anterior chest wall inflammation Coxitis

5. Objectives Role of MRI in early diagnosis of axial SpA Whole body MRI – a promising MRI variant Emerging roles of MRI in axial SpA

6. Early diagnosis 28y f, fall from horse 15 mo ago, persist. LBP

8. 22y f with left groin pain Femoroacetabular impingement?

9. Ankylosing Spondylitis Delayed diagnosis Germany 1999 8.8 years Switzerland 2005-20085.7 years Feldtkeller E et al. Rheumatol Int 2003;23:61 SCQM AS; Zollikofer A. Medical thesis (unpublished data)

10. SpA - The challenge of early diagnosis Early SpA No validated diagnostic criteria Plain radiography Equivocal findings in early SpA Definite lesions are seen after ~10 years Rudwaleit M et al. Arthritis Rheum 2005;52:1000 Mau W et al. J Rheumatol 1988;15:1109

11. Radiographic SIJ classification grade 1/2 grade 2grade 3 grade 4 Van der Linden S et al. Arthritis Rheum 1984;27:361

12. Radiographic SIJ classification Moderate sensitivity and specificity Scoring of SIJ by 23 radiologists and 100 rheumatologists Sensitivity 84 % / 80 % Specificity 71 % / 75 % After training unchanged Sensitivity83 % / 79 % Specificity80 % / 76 % Van Tubergen A et al. Ann Rheum Dis 2003;62:519

13. Modified New York classification criteria low back pain >3 months‘ duration improved by exercise and not relieved by rest limited lumbar spinal motion in both the sagittal and frontal planes decreased chest expansion (rel. to normal values for sex and age) bilateral radiographic sacroiliitis grade 2–4 unilateral radiographic sacroiliitis grade 3–4 Positive: 1 of 2 radiographic AND ≥1 of 3 clinical criteria Van der Linden S et al. Arthritis Rheum 1984;27:361

14. ASAS classification criteria for axial SpA Sacroiliitis on imaging X-ray or MRI plus ≥1/11 clinical features IBP; Arthritis; Enthesitis (heel); Uveitis; Dactylitis; Ps/CD/UC; HLAB27; Response to NSAIDs; FH SpA; CRP Sensitivity 66% Specificity 97% „Imaging arm“ HLA B27 plus ≥2/10 clinical features IBP; Arthritis; Enthesitis (heel); Uveitis; Dactylitis; Ps/CD/UC; Response to NSAIDs; FH SpA; CRP Sensitivity 83% Specificity 84% „Clinical arm“ n = 649 pat; LBP >3 mon; symptom onset <45 J; rheumatology practices Rudwaleit M et al. Ann Rheum Dis 2009;68:777

15. ASAS classification criteria for axial SpA MRI equivalent to plain X-ray however: What is a positive MRI? in the spine? in the SIJ?

16. Diagnostic utility of spinal MRI lesions Romanus Lesion (RL) = Spondylitis angularis ≥3 RL: positive LR 12 1 ≥2 RL: positive LR 12 2 1 Bennett AN et al. Arthritis Rheum 2009;60:1331 2 Weber U et al. Arthritis Rheum 2009;61:900 3 Jaeschke R et al. JAMA 1994;271:703 Clinical relevance LR+: 3 5-10 moderate >10 high

17. SpA ? „Romanus-Lesion“ in 26% of healthy volunteers Weber U et al. Arthritis Rheum 2009;61:900

18. Diagnostic utility of chronic spinal MRI lesions Fatty Romanus Lesion >0 FRL: positive LR 5 >5 FRL: positive LR 13 Bennett AN et al. Ann Rheum Dis 2009; published online 9 Aug T1 STIR

19. Diagnostic utility of SIJ MRI lesions ASAS/OMERACT consensual approach Active inflammatory SIJ lesions required Subchondral or periarticular bone marrow edema (BME) highly suggestive of sacroiliitis BME score ≥2 on a single SIJ slice and/or ≥1 lesion on 2 consecutive slices 1 slice sufficient require 2 slices Rudwaleit M et al. Ann Rheum Dis 2009;68:1520

20. What about structural lesions? Symptom duration 24 months; normal pelvic X-ray T1 STIR Erosions

21. Diagnostic utility of SIJ MRI lesions MORPHO Study 4 abstracts EULAR 2009 Copenhagen 5 abstracts ACR 2009 Philadelphia

22. Objectives of MORPHO program To assess the diagnostic utility of SIJ MRI by - MRI sequences used in routine practice - comparison with appropriate controls To assess the relative contribution of T1 (structural lesions) versus STIR (acute lesions) to assess diagnostic utility To define a „positive“ MRI for SpA using a data driven approach

23. MORPHO Methodology 187 subjects / patients All ≤45 years old All patients with inflammatory back pain ≤10 years duration Subjects –59 asymptomatic healthy volunteers (HV) –26 patients with non-specific back pain (NSBP) –77 patients with SpA (met modified NY criteria) –25 patients with inflammatory back pain (did not meet modified NY criteria)

24. MORPHO Methodology STIR Bone Marrow Oedema Erosion T1 Ankylosis T1 Fatty Infiltration T1

25. MORPHO results Mean Sens, Spec and LR+/- for 5 readers Comparison groups SensitivitySpecificityPos. Likeli- hood ratio Neg. Likeli- hood ratio AS vs NSBP+HC 0.89 (0.82-0.97)0.97 (0.94-0.99)44 (16-73)0.11 (0.03-0.18) IBP vs NSBP+HC 0.50 (0.48-0.52)0.97 (0.94-0.99)26 (9-43)0.51 (0.49-0.54) AS: Ankylosing spondylitis IBP: Inflammatory back pain = Preradiographic SpA NSPB: Non-specific back pain HC: Healthy controls

26. Diagnostic utility of SIJ MRI lesions MORPHO proposal BME score ≥2 on a single SIJ slice and/or ≥1 on 2 consecutive slices (ASAS proposal) OR Erosion score ≥2 on a single SIJ slice or ≥2 on 2 consecutive slices OR BME score ≥1 AND Erosion score ≥1 on any slice

27. IBP patients: Comparison of diagnostic utility ASAS versus MORPHO proposal ReaderSensitivitySpecificityPos. Likelihood ratioNeg. Likelihood ratio Any 20.640.885.40.4 ReaderSensitivitySpecificityPos. Likelihood ratioNeg. Likelihood ratio Any 20.840.887.10.2 ASAS proposal MORPHO proposal NB: 13/25 (52%) IBP patients diagnosed as SpA by ≥2 readers according to overall assessment of MRI

28. SpA ? Bone marrow edema-like lesion STIRT1 35y old healthy volunteer

29. SpA ? Fat deposition STIRT1 Healthy volunteer

30. SpA ? Erosion- and BME-like lesion STIRT1 Healthy volunteer

31. Inflammatory back pain and SpA MRI – the key for early diagnosis Suspicion based on clinical grounds (IBP / additional clinical SpA features) Plain X-ray of the pelvis Radiographic („late stage“) SpA MRI (conventional or whole body) Preradiographic („early“) SpA Heuft-Dorenbosch L et al. Ann Rheum Dis 2006;65:804

32. Objectives Role of MRI in early diagnosis of axial SpA Whole body MRI – a promising MRI variant Emerging roles of MRI in axial SpA

33. WB MRI – a recently introduced imaging modality Multichannel technology Parallel imaging Whole body multicoil system Spatial resolution WB = CON MRI Moving table platform No patient or coil repositioning Fusion of the images by a dedicated software

34. WB MRI in AS Practical issues Examination time 30 minutes including patient positioning Reporting time 15 minutes for a trained reader Costs about 1.5 times the expense for CON MRI (in billing systems based on the amount of time needed for a particular exam) Additional imaging of lower extremities potential objective measure for enthesitis additional examination time of 20 minutes

35. WB MRI – introduced for systemic screening in oncology and angiology Systemic arterial occlusive disease Nael K et al. AJR 2007;188:529-39 Oncological screening and staging Schaefer JF et al. Eur Radiol 2006;16:2000-15

36. Validation Whole body MRI versus Conventional MRI in SpA: SIJ and spine Weber U et al. Ann Rheum Dis 2009;published online 7 May Weber U et al. Arthritis Rheum 2009;61:893

37. MRI lesions in early SpA 21y m, HLA B27+, IBP 14 months, ESR 55

38. Early diagnosis in monozygotic twin 23y m, dactylitis, right buttock pain for 4 mo August 2007 September 2008 Diagnosis 4 months after symptom onset Weber U et al. J Rheumatol 2008;35:1464

39. Spinal MRI lesions

40. Anterior chest wall inflammation

41. WB MRI in clinical practice Coxitis 30 yrs old male, disease duration 7 yrs; no hip pain

42. WB MRI in clinical practice Inflammatory versus mechanical back pain 57 yrs old male, HLA B27+, disease duration 32 yrs, fusion th/l spine Increasing th/l back pain for 3 yrs, intense night pain no response to conventional and alternative therapy Pseudarthrosis T10/11 after transspinal fracture Weber U, Maksymowych WP. Skelet Radiol 2008;37:487-90

43. Objectives Role of MRI in early diagnosis of axial SpA Whole body MRI – a promising MRI variant Emerging roles of MRI in axial SpA

44. Inflammatory MRI spinal lesions Predictive for new syndesmophytes Prospective observational cohort, follow-up after 24 months by plain X-ray and MRI New syndesmophytes developed significantly more frequently in vertebral corners with inflammation (14.3%) than in those without inflammation (2.9%) seen on baseline MRI (p<0.003) Maksymowych WP et al. Arthritis Rheum 2009;60:93 Baraliakos X et al. Arthritis Res Ther 2008;10:R104

45. Guiding TNFa-inhibitor treatment in early SpA (symptom duration 3mo-3y) Percentage of ASAS partial remission Early SpA (MRI)55.6% 1 Established SpA (Xray)22.4% 2 1 Barkham N et al. Arthritis Rheum 2009;60:946 2 Van der Heijde D et al. Arthritis Rheum 2005;52:582

46. Monitoring response to TNFa-inhibitors 2006 2009

47. Disease activity MRI versus clinical/laboratory parameters No correlation of MRI activity parameters with clinical and laboratory activity in various study designs (cross-sectional, cohort and interventional studies) MRI may reflect other aspects of disease activity than the ones expressed by clinical and laboratory parameters Puhakka KB et al. Rheumatology 2004;43:234 Maksymowych WP et al. Arthritis Rheum 2007;57:501 Lambert RG et al. Arthritis Rheum 2007;56:4005 Weber U et al. Arthritis Rheum 2009;61:893

48. Roles of MRI in axial SpA Summary Confirmation of SpA diagnosis suspected on clinical grounds (preradiographic stage) Diagnostic MRI thresholds both for SIJ and spine needed Emerging role for guiding treatment and predicting disease course

49. Acknowledgement Radiology Balgrist Juerg Hodler Marco Zanetti Christian Pfirrmann Rheumatology Balgrist Rudolf Kissling Walter Maksymowych, Edmonton Robert Lambert, Edmonton Anne Grethe Jurik, Aarhus Anna Zejden, Aarhus Mikkel Ostergaard, Copenhagen Susanne Pedersen, Copenhagen Asim Khan, Cleveland Kaspar Rufibach, Zurich Rahel Kubik, Baden Stefan Duewell, Frauenfeld

50. Discussion White-browed Robin (pair)

51. % vertebral corners developing syndesmophytes after 2 years Inflammatory MRI spinal lesions Predictive for new syndesmophytes Courtesy: Dr Walter Maksymowych, Edmonton