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

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

Ankylosing Spondylitis Axial Disease

Ankylosing Spondylitis Nonaxial Disease Uveitis Dactylitis Anterior chest wall inflammation Coxitis

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

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

22y f with left groin pain Femoroacetabular impingement?

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 Rheumatol Int 2003;23:61 SCQM AS; Zollikofer A. Medical thesis (unpublished data)

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

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 ( )0.97 ( )44 (16-73)0.11 ( ) IBP vs NSBP+HC 0.50 ( )0.97 ( )26 (9-43)0.51 ( ) AS: Ankylosing spondylitis IBP: Inflammatory back pain = Preradiographic SpA NSPB: Non-specific back pain HC: Healthy controls

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

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

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

SpA ? Fat deposition STIRT1 Healthy volunteer

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

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

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

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

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

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

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

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

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

Spinal MRI lesions

Anterior chest wall inflammation

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

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

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

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

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

Monitoring response to TNFa-inhibitors

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

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

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

Discussion White-browed Robin (pair)

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