Diagnostic utility of candidate definitions for demonstrating axial spondyloarthritis on magnetic resonance imaging of the spine.

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Arthritis & Rheumatology DOI 10.1002/art.39001

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Diagnostic utility of candidate definitions for a positive MRI of the spine in patients with axial spondyloarthritis Ulrich Weber MD 1, 2) Zheng Zhao MD 3) Kaspar Rufibach PhD 4) Veronika Zubler MD 5) Robert G.W. Lambert MB, FRCPC 6) Stanley M. Chan MD, FRCSC 7) Mikkel Østergaard MD, PhD, DMSc 8) Susanne J. Pedersen MD, PhD 8) Walter P. Maksymowych MB, FRCPC 1) Institutions 1

) Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

[email protected] [email protected] 2

) Department of Rheumatology, Balgrist University Hospital, Zurich, Switzerland

[email protected] 3

) Department of Rheumatology, PLA General Hospital, Beijing, China

[email protected] This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/art.39001 © 2014 American College of Rheumatology Received: Jul 28, 2014; Revised: Nov 07, 2014; Accepted: Dec 11, 2014 This article is protected by copyright. All rights reserved.

Arthritis & Rheumatology

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) Rufibach rePROstat, Biostatistical Consulting and Training, Engelgasse 123, 4052

Basel, Switzerland Dr. Rufibach is founder and owner of Rufibach rePROstat and is an employee of F. Hoffmann-La Roche, Basel, Switzerland. [email protected] 5

) Department of Radiology, Balgrist University Hospital, Zurich, Switzerland

[email protected] 6

) Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton,

Alberta, Canada [email protected] 7

) Department of Ophthalmology, University of Alberta, Edmonton, Alberta, Canada

[email protected] 8

) Copenhagen Center for Arthritis Research, Center for Rheumatology and Spinal

Diseases, Glostrup Hospital, and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark [email protected] [email protected]

Correspondence Ulrich Weber MD Division of Rheumatology

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John Wiley & Sons This article is protected by copyright. All rights reserved.

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Department of Medicine University of Alberta 562 Heritage Medical Research Building Edmonton, Alberta T6G 2S2 Canada Tel +1 780 407 1964 Fax +1 780 407 6055 [email protected]

Manuscript type Full-length Article Word Count Full-length Article 2903 Abstract 250 4 Tables and 2 Figures Funding sources The Canadian Arthritis Society: National Research Initiative Award Alberta Innovates Health Solutions Walter L. and Johanna Wolf Foundation, Zurich, Switzerland Running head

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Diagnostic utility of spinal MRI in SpA Key words spondyloarthritis; magnetic resonance imaging; spinal MRI; non-radiographic axial spondyloarthritis; ankylosing spondylitis; diagnostic utility; sensitivity and specificity Competing interests The authors declare that they have no competing interests in relation to this article. There was no financial support or other benefits from commercial sources for the work reported on in the manuscript.

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ABSTRACT Objective: A recent consensus statement suggested ≥3 corner inflammatory (CIL) or several corner fatty lesions (CFL) as candidate criteria for a positive spine MRI in axial spondyloarthritis. We aimed to evaluate the diagnostic utility of these cut-offs in non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS). Methods: 130 consecutive back pain patients ≤50 years newly referred to 2 university clinics (cohorts A/B) were classified according to rheumatologist expert opinion based on clinical examination and pelvic radiographs as having nr-axSpA (n=50), AS (n=33), or non-specific back pain (NSBP) (n=47). Cohort A also had 20 age-matched healthy controls. Four blinded readers assessed spine MRIs using the standardized CanadaDenmark module. Readers recorded CIL and CFL in 23 discovertebral units. We tested the diagnostic utility (mean sensitivity/specificity over 4 readers) of cut-off values for spinal MRI lesions as proposed in the literature (≥2/≥3 CIL; ≥6 CFL), and for possible thresholds from ≥1 to ≥10 CIL and CFL, for nr-axSpA and AS patients in both cohorts. Results: None of the spinal thresholds ≥2/≥3 CIL and ≥6 CFL showed clinically relevant diagnostic utility (range for positive likelihood ratios 1.38-2.36) when comparing nr-axSpA versus NSBP patients. A threshold of ≥6 CIL had moderate to substantial diagnostic utility (positive likelihood ratio 13.26/6.74) in nr-axSpA, while ≥4 CIL showed small diagnostic utility (3.83/2.72) but specificities >0.90. Conclusions: No previously proposed candidate criteria for a positive spinal MRI showed clinically relevant diagnostic utility in nr-axSpA. These findings question definitions of a positive MRI in spondyloarthritis based on spine MRI alone.

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INTRODUCTION

A recent consensus statement based on a systematic literature review by the Assessment of SpondyloArthritis international Society (ASAS) and Outcome Measures in Rheumatology (OMERACT) working group suggested the presence of ≥3 corner inflammatory lesions (CIL) or of ≥6 corner fat lesions (CFL) (Figure 1) on ≥2 spinal magnetic resonance imaging (MRI) slices as candidate criteria for a positive MRI of the spine in axial spondyloarthritis (SpA) (1). The diagnostic utility of the proposed candidate criteria regarding the clinically relevant discrimination between non-radiographic axial SpA (nr-axSpA) and non-specific back pain (NSBP) patients is not known.

Several controlled studies explored spinal MRI lesions in patients with nraxSpA and ankylosing spondylitis (AS) (2-5). CIL were regarded as being the most characteristic lesion type for spinal involvement in SpA, while CFL lacked specificity (5) (Figure 2). Previous studies demonstrated that bone marrow edema (BME) in the postero-lateral spinal compartments had high specificity but lacked sensitivity (4, 6). Available candidate criteria for a positive MRI of the spine were developed based on evaluation of spinal MRI features alone. Data about the frequency of spinal involvement alone contrasting with normal findings on concomitant sacroiliac joint (SIJ) MRI is sparse and conflicting, and the few studies available show substantial methodological discrepancies. A study establishing classification standards for patients with axial SpA found isolated spine inflammation in the absence of SIJ inflammation in only 5.4% of 130 axial SpA patients having combined MRI examinations (7). There was no central reading, the evaluation was based on BME alone, and local 6


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readers had all patient-related clinical, laboratory and radiographic information available when assessing spine and SIJ MRI simultaneously. A secondary analysis of a randomized controlled trial indicated baseline involvement of spinal MRI alone without inflammation on SIJ MRI in 49% of nr-axSpA patients (8). Baseline data from another interventional trial using whole-body MRI in SpA patients (48.7% nr-axSpA and 51.3% AS patients) showed spinal BME alone in the absence of SIJ inflammation in 5.4% of all patients (9). We recently reported a positive spinal MRI in the absence of SIJ involvement in 15.8% and 19.4% of 2 nr-axSpA cohorts (10). The challenge when evaluating spinal MRI alone is illustrated by the fact that also 20.5%-28.6% of NSBP and healthy controls showed a positive spinal MRI with normal SIJ MRI findings.

The goal of our study based on assessment of spine MRI alone was to assess and compare the diagnostic utility of the lesion cut-offs for a positive spinal MRI as proposed in the literature (≥2/≥3 CIL and ≥6 CFL), and of all possible thresholds from ≥1 to ≥10 CIL and ≥1 to ≥10 CFL, for nr-axSpA and AS patients.

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PATIENTS AND METHODS

Subjects

The demographical and clinical characteristics of the study sample have been reported previously (10). MRI scans of the entire spine were obtained in 2 independent cohorts A/B of 130 consecutive adult patients aged ≤50 years with back pain newly referred to 2 university outpatient clinics from 2008 to 2011. Cohort A and B were recruited by different strategies. Cohort A (University of Zurich, Switzerland) comprised 42 back pain patients referred from rheumatology or primary care practices for evaluation of clinically suspected SpA. Twenty age-matched healthy controls, defined by the Nordic questionnaire (11) and by absence of clinical features indicative for SpA, were concomitantly recruited from hospital staff. Patients of cohort B (n=88; University of Alberta, Canada) presented with acute anterior uveitis (AAU) to a university ophthalmology department; all AAU patients who indicated past or present back pain for ≥3 months on a structured questionnaire were referred to rheumatology for assessment of SpA. Patients with previous or ongoing exposure to biologic therapy were excluded in both cohorts. The study protocols were approved by the local Ethics Review Boards, and written informed consent was obtained from patients and controls.

In both inception cohorts, clinician expert opinion by one local rheumatologist (UW/WPM for cohort A/B) was used to classify the back pain patients as having nraxSpA (n=19/31, for cohort A/B, respectively), AS (n=9/24) and NSBP (n=14/33). Clinician expert opinion was based on clinical assessment (including evaluation of inflammatory back pain according to Calin criteria (12)), structured questionnaires on 8


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SpA-related features (modified Outcome in Ankylosing Spondylitis International Study protocol (13) for cohort A and Spondyloarthritis Research Consortium of Canada protocol (14) for cohort B), pelvic radiographs and laboratory values (HLA-B27, CRP). Two readers at each site independently categorized pelvic radiographs according to the modified New York criteria (15). Disagreement between readers was resolved by consensus. MRI scans were not used for classification of the study subjects to avoid circular reasoning (16) since the diagnostic utility of various features on spinal MRI was the primary objective of this study.

Evaluation of spine MR images

The technical parameters for short tau inversion recovery (STIR) and T1 spin echo (T1SE) sequences of sagittal MR images of the entire spine have been presented previously (4, 6). The spinal MRI scans (1.5T Avanto, Siemens Medical Solutions, Erlangen, Germany, for both cohorts A and B) were read and scored independently by 4 blinded readers (1 radiologist: VZ; 3 rheumatologists: UW/WPM/ZZ). Two experienced MRI readers (WPM/UW) previously involved in developing the CanadaDenmark module and a corresponding reference image set (17-19) trained 2 additional readers (VZ/ZZ) over 3-6 months by using previous MRI study files and reference images for calibration. The images of each cohort were assessed separately in random order on electronic work stations in each reader’s institution. MRI scores were entered into a customized online data entry module featuring a schematic of 23 discovertebral units from C2/C3 to L5/S1. Spinal MRI scans were evaluated according to the Canada-Denmark module (17, 18). CIL and CFL in the spine were assessed according to standardized lesion

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definitions, that included anatomical location, and a reference image set (17-19). Presence/absence of CIL and CFL on ≥1 slice was recorded in the central sagittal slices of all 23 discovertebral units from C2/C3 to L5/S1. Central slices contain the spinal canal and are bordered by the pedicles, whereas lateral slices contain pedicles, facet joints, costovertebral and costotransverse joints, and enthesial soft tissue. Degenerative spinal lesions defined as loss of ≥50% of the normally expected disc height at this level recorded concordantly by ≥2 of 3 readers (UW/VZ/WPM) were assessed in the cervical (C2/C3-C7/T1) and lumbar (T12/L1-L5/S1) spine.

Statistical analysis

Data description. P-values for differences in demographic and clinical characteristics between cohort A and B were computed using Fisher’s exact test for nominal and Wilcoxon test for continuous variables. The frequency of MRI lesions on group level was described as median (interquartile range) according to 4 readers. On the individual subject level, we provide the mean percentage of subjects over 4 readers showing ≥1 to ≥10 CIL and ≥1 to ≥10 CFL, respectively, for all subjects together and stratified for age categories ≤30/>30 years. Inter-observer reproducibility of CIL and CFL was calculated by mean intraclass correlation coefficient ICC(3, 1) (range) for the 6 reader pairs for all study subjects and for SpA patients. Among the 6 reported ICC variants, the ICC(3, 1) approach considers the study readers to be a fixed sample and thus not representative of a larger population of raters (20-22). ICC values >0.4, >0.6, >0.8, and >0.9 were regarded as representing moderate, good, very good, and excellent reproducibility, respectively. 10


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Diagnostic utility of spinal MRI lesions. According to Lassere (23), diagnostic utility was determined by calculating mean sensitivity, specificity and positive/negative likelihood ratios over 4 readers for nr-axSpA and AS versus NSBP patients in both cohorts A and B. We calculated the diagnostic utility for CIL and CFL cut-off values proposed in the literature (≥2/≥3 CIL, ≥6 CFL), for all possible thresholds from ≥1 to ≥10 CIL and ≥1 to ≥10 CFL, respectively, and for combinations of CIL plus CFL that we regarded as potentially clinically relevant (≥2/≥3/≥4 CIL plus ≥2/≥3/≥4 CFL). According to Jaeschke (24), clinical utility was defined as substantial, moderate, small, and poor/rarely clinically relevant by values of positive/negative likelihood ratios of >10/5-10/0.1-0.2, >2-5/>0.2-0.5, and >1-2/>0.5-1. Gold standard for computing sensitivity, specificity, and corresponding diagnostic utility was rheumatologist expert opinion, which has served as gold standard to develop 3 classification criteria for SpA over the last 2 decades (7, 25, 26). We used R Core Team 2014, version 3.1.0, Vienna, Austria, for statistical analysis.

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RESULTS

Data description

Study subjects. Demographical and clinical characteristics of the 2 cohorts are shown in Table 1. Nr-axSpA patients in cohort A had a shorter symptom duration and higher disease activity. This heterogeneity attributable to different recruitment strategies to identify patients with nr-axSpA led us to analyse the 2 cohorts separately. The prevalence of HLA-B27 in patients with AAU in general is 50-60% (27) which explains the frequency of HLA-B27 of 55.6% in NSBP patients in cohort B.

Frequency of spinal MRI lesions. CIL were reported more frequently in cohort A consistent with a higher clinical disease activity, while CFL were more common in cohort B (Table 1). In nr-axSpA, the stratification by age groups ≤30/>30 years showed an increase both for CIL and CFL in the older age group of cohort A having short symptom duration, whereas an increase was seen only for CFL in cohort B with longstanding disease (Table 2). NSBP and healthy controls of cohort A showed no consistent change in frequency of CIL and CFL between the 2 age groups, while NSBP controls in cohort B had an increase in CIL and CFL in the older age group. Degenerative spinal lesions. In cohort A/B, only 1.6%/2.0% of all cervical and lumbar discovertebral units showed degenerative lesions, whereof 50%/52% were observed on level L5/S1. Due to this consistently small frequency of degenerative spinal lesions across both cohorts, possibly attributable to a median age of 31 and 36 years in the 2 cohorts, respectively, no adjustment for degenerative spinal lesions was performed.

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Reliability for detection of CIL and CFL

In cohorts A/B, the mean ICC(3, 1) (range) for 6 reader pairs and for all study subjects was 0.62 (0.48-0.75)/0.71 (0.66-0.83) for CIL, and 0.39 (0.27-0.63)/0.88 (0.85-0.95) for CFL, respectively. For the combined nr-axSpA and AS group, the mean ICC(3, 1) (range) for 6 reader pairs was 0.59 (0.47-0.68)/0.71 (0.65-0.83) for CIL, and 0.45 (0.32-0.66)/0.89 (0.87-0.95) for CFL, respectively.

Diagnostic utility of spinal lesions

None of the spinal thresholds of ≥2/≥3 CIL and ≥6 CFL proposed in the literature showed clinically relevant diagnostic utility in nr-axSpA versus NSBP patients in both cohorts (range for positive likelihood ratio 1.38-2.36) (Table 3). Limited diagnostic utility was seen in nr-axSpA patients at a threshold of ≥4 CIL (sensitivity 0.34/0.19, specificity 0.91/0.93 and positive likelihood ratio 3.83/2.72 for cohorts A/B). In AS patients, ≥3 CIL and ≥6 CFL (positive likelihood ratio 2.44/4.03 and 2.49/2.53 for cohort A/B, respectively) showed a small diagnostic utility (Table 4). A threshold of ≥6 CIL had moderate to substantial diagnostic utility in nr-axSpA and AS patients of both cohorts (positive likelihood ratio 13.26/6.74 and 29.56/14.67 for cohort A/B, respectively), at the cost of a drop in sensitivity compared to ≥2/≥3 CIL cut-offs as proposed in the literature. In nr-axSpA patients, a combination of ≥2/≥3 CIL plus ≥2/≥3/≥4 CFL resulted in a minimal and clinically irrelevant increase in diagnostic utility (range for positive likelihood ratio 2.58-2.95/1.57-2.34 for cohorts A/B) compared to ≥2/≥3 CIL alone (ranges 1.47-1.74/1.38-2.36). A combination of ≥4 CIL plus ≥2/≥3/≥4 CFL yielded a moderate to substantial diagnostic utility in nr-axSpA patients of cohort A (range

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for positive likelihood ratio 7.74-13.26), while in cohort B diagnostic utility was small (range 2.59-3.19).

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DISCUSSION

This standardized reading exercise of spinal MRI in 2 SpA inception cohorts by 4 readers showed several issues relevant towards diagnostic utility of spinal MRI alone in nr-axSpA. Diagnostic utility of all cut-off values for CIL and CFL as proposed in the literature (≥2/≥3 CIL or ≥6 CFL) were not clinically useful for differentiating nraxSpA from NSBP patients. Only a threshold of ≥6 CIL had moderate to substantial diagnostic utility in clinically suspected nr-axSpA, while a cut-off of ≥4 CIL showed small diagnostic utility but specificities >0.90. CFL proved to be less relevant for diagnostic utility. Sensitivity and specificity for the ≥6 CFL lesion cut-off proposed in the literature was only 0.26/0.40 and 0.82/0.81 for cohorts A/B, respectively, to differentiate between nr-axSpA and NSBP patients. The discrepancy reported for CIL thresholds in 2 previous studies with ≥3 CIL (3) versus ≥2 CIL (4) was attributable to different characteristics of patient and control groups. Patients in the retrospective study indicating a cut-off of ≥3 CIL (3) were older (mean age 52.5 years, only 48% under age 50 years) and had long mean symptom duration of 15.2 years. The heterogeneous control group consisted of patients with degenerative spine disease, spinal malignancy, tuberculosis, fracture or osteonecrosis, and had only few healthy controls. Patients in the prospective study concluding that diagnostic utility was optimal with a cut-off level of ≥2 CIL (4) were younger (median age 30.8 years) and showed a short median symptom duration of 10 months for nr-axSpA and of 8 years for AS. The primary study limitation was the control group consisting of age-matched healthy controls but lacking NSBP patients.

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CFL were less relevant towards developing candidate criteria for a positive spinal MRI because a much higher number of this lesion type was needed to reach a specificity close to 0.90. The present study analyzed 2 SpA inception cohorts separately because of significant differences in symptom duration and disease activity, which reflects the broad clinical spectrum of nr-axSpA patients presenting in daily routine. The impact of disease characteristics on diagnostic utility of MRI features challenges uniform definitions for a positive spinal MRI in disorders with a heterogeneous clinical spectrum as in SpA. All candidate criteria for defining a positive spine MRI proposed in previous reports (≥2/≥3 CIL and ≥6 CFL) failed to show a clinically relevant diagnostic utility for differentiating nr-axSpA from NSBP patients. Only a relatively high threshold of ≥6 CIL proved clinically useful to discriminate nr-axSpA from NSBP patients, but was limited by decreased sensitivity compared to the proposed thresholds of ≥2 or ≥3 CIL. We recently compared the diagnostic performance of global evaluation of SIJ MRI alone, spine MRI alone and SIJ plus spinal MRI combined which demonstrated a lack of specificity of spinal MRI changes, evident even when SIJ and spinal MRIs were simultaneously assessed (10). Spinal CIL and CFL were the main drivers towards misclassification of controls as having SpA. The limited diagnostic utility of spinal MRI lesion thresholds may be due to the fact, that studies were based on spinal MRI alone without taking into account concomitant lesions on SIJ MRI. Options to explore whether the specificity of spinal MRI features is indeed limited would be to analyze SpA subgroups with normal SIJ MRI, but having BME or fat infiltration on spine MRI, or SpA subgroups with an increase from low to high confidence in a diagnosis of SpA 16


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by combining SIJ with spine MRI. However, the small sample size of these 2 subgroups in our study (15.8%/24.2% and 6.6%/7.3% of nr-axSpA patients in cohort A/B) precluded a clinically meaningful analysis. A limitation inherent to imaging studies in nr-axSpA is the selection of the gold standard (28). To avoid conceptual circularity, MRI cannot be used simultaneously for classification purposes and for evaluating its diagnostic utility (16). Gold standard for classification of SpA was therefore physician expert opinion which is consistent with the gold standard used in several classification systems in SpA over the past 2 decades (Amor (25), European Spondylarthropathy Study Group (26), and ASAS (7) criteria). Our patients were also enrolled in standardized protocols to assess inflammatory back pain (12) and SpA-related clinical features (13, 14). An approach with physician expert opinion as gold standard for an MRI study in nr-axSpA implies the possibility of both false positive and false negative clinical assignments. Re-evaluation of the initial classification by longitudinal follow-up including serial pelvic radiographs may constitute an alternative gold standard. However, longitudinal studies are limited by patients lost to follow-up, particularly in disorders with slow progression such as SpA requiring a lengthy follow-up (29). In addition, some patients may never develop radiographic features (30) which perpetuates diagnostic uncertainty. A recent report highlighting an only moderate reproducibility of SIJ evaluation on pelvic radiographs by rheumatologist and radiologist readers (kappa value 0.54 for trained and 0.55 for trained versus less experienced readers, respectively) even put into question the role of radiographic sacroiliitis for diagnosing axial SpA (31). Strengths of this study are consistent results across two back pain inception cohorts despite differences in referral and clinical characteristics, an evaluation of MRI scans by readers from 3 interna17



tional sites inclusive of both radiologists and rheumatologists, and the inclusion of scans from healthy controls for further methodological rigor. Future studies following clinically suspected nr-axSpA patients with normal or equivocal SIJ scans would further help understand the role of spinal imaging in the diagnostic evaluation of patients with axial SpA. However, such cohorts are currently not available, and the current data provide the best possible evidence. In this controlled study, none of the candidate criteria for a positive spinal MRI as previously proposed in the literature (≥2/≥3 CIL and ≥6 CFL) had clinically relevant diagnostic utility in nr-axSpA. Only a threshold of ≥6 CIL had moderate to substantial diagnostic utility in clinically suspected nr-axSpA. These findings question definitions of a positive MRI in SpA based on spinal MRI alone without taking into account concomitant lesions on SIJ MRI.

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AUTHOR CONTRIBUTIONS

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Weber had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design: Weber, Rufibach, Lambert, Østergaard, Pedersen, Maksymowych Acquisition of data: Weber, Zhao, Zubler, Chan, Maksymowych Analysis and interpretation of data: Weber, Zhao, Rufibach, Zubler, Lambert, Chan, Østergaard, Pedersen, Maksymowych

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ACKNOWLEDGEMENTS

The authors thank the patients and the healthy volunteers for their participation; Tracey Clare, Clinical Research Manager, and Paul Filipow, Data Manager, Department of Radiology, University of Alberta, Edmonton, Canada for coordinating the Web-based MRI scoring module. Walter P. Maksymowych is a Medical Scientist of Alberta Innovates Health Solutions.

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REFERENCES

1. Hermann KGA, Baraliakos X, van der Heijde DMFM, Jurik AG, Landewé R, Marzo-Ortega H, et al. Descriptions of spinal MRI lesions and definition of a positive MRI of the spine in axial spondyloarthritis: a consensual approach by the ASAS/OMERACT MRI study group. Ann Rheum Dis 2012;71:1278-88. 2. Kim NR, Choi JY, Hong SH, Jun WS, Lee JW, Choi JA, et al. “MR corner sign”: value for predicting presence of ankylosing spondylitis. AJR 2008;191:124-8. 3. Bennett AN, Rehman A, Hensor EMA, Marzo-Ortega H, Emery P, McGonagle D. Evaluation of the diagnostic utility of spinal magnetic resonance imaging in axial spondylarthritis. Arthritis Rheum 2009;60:1331-41. 4. Weber U, Hodler J, Kubik RA, Rufibach K, Lambert RGW, Kissling RO, et al. Sensitivity and specificity of spinal inflammatory lesions assessed by wholebody magnetic resonance imaging in patients with ankylosing spondylitis or recent-onset inflammatory back pain. Arthritis Rheum (Arthritis Care Res) 2009;61:900-8. 5. Bennett AN, Rehman A, Hensor EMA, Marzo-Ortega H, Emery P, McGonagle D. The fatty Romanus lesion: a non-inflammatory spinal MRI lesion specific for axial spondyloarthropathy. Ann Rheum Dis 2010;69:891-4. 6. Rennie WJ, Dhillon SS, Conner-Spady B, Maksymowych WP, Lambert RGW. Magnetic resonance imaging assessment of spinal inflammation in ankylosing spondylitis: standard clinical protocols may omit inflammatory lesions in thoracic vertebrae. Arthritis Rheum (Arthritis Care Res) 2009;61:1187-93.

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7. Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009;68:777-83. 8. Van der Heijde D, Sieper J, Maksymowych WP, Brown MA, Lambert RGW, Rathmann SS, et al. Spinal inflammation in the absence of sacroiliac joint inflammation on magnetic resonance imaging in patients with active nonradiographic axial spondyloarthritis. Arthritis Rheum 2014;66:667-73. 9. Song IH, Hermann KG, Haibel H, Althoff CE, Listing J, Burmester GR, et al. Effects of etanercept versus sulfasalazine in early axial spondyloarthritis on active inflammatory lesions as detected by whole-body MRI (ESTHER): a 48week randomised controlled trial. Ann Rheum Dis 2011;70:590-6. 10. Weber U, Zubler V, Zhao Z, Lambert RGW, Chan SM, Pedersen SJ, et al. Does spinal MRI add incremental diagnostic value to MRI of the sacroiliac joints alone in patients with non-radiographic axial spondyloarthritis? Ann Rheum Dis online first 22 January 2014 10.1136/annrheumdis-2013-203887. 11. Kuorinka I, Jonsson B, Kilbom A, Vinterberg H, Biering-Sorensen F, Andersson G, et al. Standardised Nordic questionnaires for the analysis of musculoskeletal symptoms. Appl Ergon 1987;18:233-7. 12. Calin A, Porta J, Fries JF, Schurman DJ. Clinical history as a screening test for ankylosing spondylitis. JAMA 1977;237:2613-4. 13. Ciurea A, Scherer A, Exer P, Bernhard J, Dudler J, Beyeler B, et al. Tumor necrosis factor α inhibition in radiographic and nonradiographic axial

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spondyloarthritis: results from a large observational cohort. Arthritis Rheum 2013;65:3096-106. 14. Gladman DD, Rahman P, Cook RJ, Shen H, Zummer M, Thomson G, et al. The spondyloarthritis research consortium of Canada registry for spondyloarthritis. J Rheumatol 2011;38:1343-8. 15. Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27:361-8. 16. Landewé RBM. Magnetic resonance imaging in the diagnosis of ankylosing spondylitis: Be aware of gold standards and circularity [editorial]. J Rheumatol 2010;37:477-8. 17. Lambert RGW, Pedersen SJ, Maksymowych WP, Chiowchanwisawakit P, Østergaard M. Active inflammatory lesions detected by magnetic resonance imaging in the spine of patients with spondyloarthritis - definitions, assessment system, and reference image set. J Rheumatol 2009;36 (suppl 84):3-17. 18. Østergaard M, Maksymowych WP, Pedersen SJ, Chiowchanwisawakit P, Lambert RGW. Structural lesions detected by magnetic resonance imaging in the spine of patients with spondyloarthritis - definitions, assessment system, and reference image set. J Rheumatol 2009;36 (suppl 84):18-34. 19. https://www.carearthritis.com/Research_Collaborations.php 20. Shrout PE, Fleiss JL. Intraclass correlation: uses in assessing rater reliability. Psychol Bull 1979;86:420-8. 21. McGraw KO, Wong SP. Forming inferences about some intraclass correlation coefficients. Psychological Methods 1996;1:30-46. 23



22. Rousson V, Gasser T, Seifert B. Assessing intrarater, interrater and test-retest reliability of continuous measurements. Stat Med 2002;21:3431-46. 23. Lassere M. Are reporting standards of diagnostic test evaluation unrealistic? [editorial]. J Rheumatol 2010;37:220-2. 24. Jaeschke R, Guyatt GH, Sackett DL. Users’ guides to the medical literature. III. How to use an article about a diagnostic test. JAMA 1994;271:703-7. 25. Amor B, Dougados M, Mijiyawa M. Criteria for the classification of spondyloarthropathies [French]. Rev Rhum Mal Osteoartic 1990;57:85-9. 26. Dougados M, van der Linden S, Juhlin R, Huitfeldt B, Amor B, Calin A, et al. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum 1991;34:1218-27. 27. Martin TM, Rosenbaum JT. An update on the genetics of HLA B27-associated acute anterior uveitis [review]. Ocul Immunol Inflamm 2011;19:108-14. 28. Weber U, Maksymowych WP. Advances and challenges in spondyloarthritis imaging for diagnosis and assessment of disease [review]. Curr Rheumatol Rep 2013;15:345. 29. Mau W, Zeidler H, Mau R, Majewski A, Freyschmidt J, Stangel W, et al. Clinical features and prognosis of patients with possible ankylosing spondylitis. Results of a 10-year followup. J Rheumatol 1988;15:1109-14. 30. Aydin SZ, Maksymowych WP, Bennett AN, McGonagle D, Emery P, MarzoOrtega H. Validation of the ASAS criteria and definition of a positive MRI of the sacroiliac joint in an inception cohort of axial spondyloarthritis followed up for 8 years. Ann Rheum Dis 2012; 71:56-60. 24


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31. Van den Berg R, Lenczner G, Feydy A, van der Heijde D, Reijnierse M, Saraux A, et al. Agreement between clinical practice and trained central reading in reading of sacroiliac joints on plain pelvic radiographs. Arthritis Rheum 2014;66:2403-11.

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TABLES Table 1 Characteristics of 2 spondyloarthritis inception cohorts and frequency of spinal MRI lesions

Cohort Recruitment mode

A (n=62)

B (n=88)

Suspected axial SpA by practicing rheumatologists or primary care physician

AAU plus past or present back pain

Group Number of subjects

nr-axSpA

AS

NSBP

HC

nr-axSpA

AS

NSBP

19

9

14

20

31

24

33

Male:Female (% Male)

11:8 (57.9)

7:2 (77.8) 3:11 (21.4) 7:13 (35.0) 17:14 (54.8) 11:13 (45.8) 17:16 (51.5)

Age (years)

32.3 (14.4) *30.7 (11.4) 30.7 (14.1)

30.6 (6.5)

36.2 (12.1)

*41.5 (7.1)

33.6 (15.7)

NA *10.0 (14.0) *12.5 (13.5)

NA

Symptom duration (years)

*1.2 (2.2)

*4.0 (2.2)

NA

HLA B27 positive (%)

11 (57.9)

8 (88.9)

ND1

ND1

24 (80.0)2

21 (87.5)

10 (55.6)2

BASDAI (NRS)

4.4 (3.1)

5.4 (1.5)

NA

NA

3.5 (4.4)

2.0 (3.4)2

NA

BASFI (NRS)

*1.8 (3.9)

2.7 (1.5)

NA

NA

*0.8 (2.3)

0.6 (2.8)2

NA

CRP (mg/l)

4.0 (5.0)1

5.0 (8.5)1

ND1

ND1

2.7 (5.2)

8.0 (8.7)2

0.9 (0.9)2

CIL

2.0 (5.0)

6.5 (11.0)

1.0 (2.5)

0 (2.0)

0 (2.5)

2.0 (7.0)

0 (2.0)

CFL

3.0 (6.0)

4.0 (6.5)

2.0 (5.0)

2.0 (4.0)

4.0 (8.0)

5.0 (20.0)

1.0 (4.0)

Values are the median (IQR) unless otherwise indicated. Spine MRIs were assessed according to the CanDen module (17, 18). * p-value ≤0.05 (Fisher’s exact test) between cohort A and B; individual p-values for cohort A versus B: median age in AS 30.7 versus 41.5 years, p = 0.009; median symptom duration in nr-axSpA 1.2 versus 10.0 years, p 30 years

Cohort

A (n=62)

Group

B (n=88)

nr-axSpA

AS

NSBP

HC

nr-axSpA

AS

NSBP

All (≤30/>30 years)

100 (36.8/63.2)

100 (44.4/55.6)

100 (42.9/57.1)

100 (50.0/50.0)

100 (25.8/74.2)

100 (12.5/87.5)

100 (39.4/60.6)

CIL≥1

63.2 (17.9/89.6)

69.4 (56.3/80.0)

50.0 (62.5/40.6)

43.8 (40.0/47.5)

47.6 (56.3/44.6)

64.6 (58.3/65.5)

33.3 (17.3/43.8)

CIL≥2

52.6 (17.9/72.9)

66.7 (50.0/80.0)

35.7 (50.0/25.0)

33.8 (27.5/40.0)

35.5 (43.8/32.6)

55.2 (41.7/57.1)

25.8 (11.5/35.0)

CIL≥3

43.4 (14.3/60.4)

61.1 (50.0/70.0)

25.0 (29.2/21.9)

17.5 (12.5/22.5)

25.0 (25.0/25.0)

42.7 (16.7/46.4)

10.6 (3.8/15.0)

CIL≥4

34.2 (10.7/47.9)

58.3 (50.0/65.0)

8.9 (8.3/9.4)

12.5 (10.0/15.0)

18.5 (18.8/18.5)

41.7 (16.7/45.2)

6.8 (0/11.3)

CIL≥5

31.6 (10.7/43.8)

58.3 (50.0/65.0)

5.4 (8.3/3.1)

5.0 (2.5/7.5)

16.9 (15.6/17.4)

38.5 (16.7/41.7)

4.5 (0/7.5)

CIL≥6

23.7 (7.1/33.3)

52.8 (43.8/60.0)

1.8 (4.2/0)

5.0 (2.5/7.5)

15.3 (15.6/15.2)

33.3 (16.7/35.7)

2.3 (0/3.8)

CIL≥7

21.1 (7.1/29.2)

50.0 (43.8/55.0)

0 (0/0)

5.0 (2.5/7.5)

13.7 (15.6/13.0)

27.1 (0/31.0)

2.3 (0/3.8)

CIL≥8

14.5 (7.1/18.8)

41.7 (31.3/50.0)

0 (0/0)

5.0 (2.5/7.5)

10.5 (12.5/9.8)

22.9 (0/26.2)

1.5 (0/2.5)

CIL≥9

13.2 (7.1/16.7)

36.1 (31.3/40.0)

0 (0/0)

2.5 (0/5.0)

5.6 (9.4/4.3)

15.6 (0/17.9)

1.5 (0/2.5)

CIL≥10

9.2 (3.6/12.5)

33.3 (25.0/40.0)

0 (0/0)

2.5 (0/5.0)

5.6 (9.4/4.3)

11.5 (0/13.1)

1.5 (0/2.5)

CFL≥1

68.4 (50.0/79.2)

77.8 (81.3/75.0)

69.6 (70.8/68.8)

65.0 (62.5/67.5)

74.2 (37.5/87.0)

85.4 (58.3/89.3)

56.1 (21.2/78.8)

CFL≥2

61.8 (50.0/68.8)

75.0 (81.3/70.0)

58.9 (58.3/59.4)

53.8 (42.5/65.0)

66.1 (28.1/79.3)

81.3 (50.0/85.7)

46.2 (21.2/62.5)

CFL≥3

52.6 (32.1/64.6)

66.7 (62.5/70.0)

44.6 (45.8/43.8)

42.5 (30.0/55.0)

58.9 (21.9/71.7)

67.7 (25.0/73.8)

38.6 (13.5/55.0)

CFL≥4

40.8 (17.9/54.2)

52.8 (37.5/65.0)

35.7 (29.2/40.6)

31.3 (25.0/37.5)

54.0 (15.6/67.4)

63.5 (16.7/70.2)

30.3 (5.8/46.3)

CFL≥5

31.6 (14.3/41.7)

47.2 (37.5/55.0)

32.1 (25.0/37.5)

23.8 (22.5/25.0)

43.5 (9.4/55.4)

54.2 (8.3/60.7)

24.2 (5.8/36.3)

CFL≥6

26.3 (10.7/35.4)

44.4 (37.5/50.0)

17.9 (16.7/18.8)

17.5 (20.0/15.0)

39.5 (9.4/50.0)

47.9 (0/54.8)

18.9 (0/31.3)

CFL≥7

21.1 (3.6/31.3)

36.1 (37.5/35.0)

14.3 (12.5/15.6)

10.0 (12.5/7.5)

33.9 (9.4/42.4)

46.9 (0/53.6)

18.2 (0/30.0)

CFL≥8

13.2 (0/20.8)

36.1 (37.5/35.0)

14.3 (12.5/15.6)

8.8 (10.0/7.5)

28.2 (9.4/34.8)

45.8 (0/52.4)

14.4 (0/23.8)

CFL≥9

13.2 (0/20.8)

25.0 (31.3/20.0)

10.7 (12.5/9.4)

6.3 (7.5/5.0)

24.2 (6.3/30.4)

45.8 (0/52.4)

12.1 (0/20.0)

CFL≥10

11.8 (0/18.8)

19.4 (25.0/15.0)

10.7 (12.5/9.4)

3.8 (5.0/2.5)

21.0 (3.1/27.2)

44.8 (0/51.2)

9.8 (0/16.3)

Values are the mean percentage of subjects over 4 readers. Spine MRIs were assessed according to the CanDen module (17, 18). Abbreviations AS

Ankylosing spondylitis

CIL

Corner inflammatory lesion (in central spinal MRI slices)

CFL

Corner fatty lesion (in central spinal MRI slices)

HC

Healthy control

nr-axSpA Non-radiographic axial spondyloarthritis

28


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NSBP

Non-specific back pain

SpA

Spondyloarthritis

29



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Table 3 Diagnostic utility of candidate definitions for a positive spinal MRI observed in 2 cohorts A/B: Nr-axSpA versus NSBP patients

Diagnostic utility

Sensitivity Specificity Positive LR Negative LR

≥1 CIL

0.63/0.48 0.50/0.67

1.26/1.43

0.74/0.79

≥2 CIL*

0.53/0.35 0.64/0.74

1.47/1.38

0.74/0.87

≥3 CIL*

0.43/0.25 0.75/0.89

1.74/2.36

0.75/0.84

≥4 CIL

0.34/0.19 0.91/0.93

3.83/2.72

0.72/0.87

≥5 CIL

0.32/0.17 0.95/0.95

5.89/3.73

0.72/0.87

≥6 CIL

0.24/0.15 0.98/0.98 13.26/6.74

0.78/0.87

≥7 CIL

0.21/0.14 1.00/0.98

NC/6.03

0.79/0.88

≥8 CIL

0.14/0.10 1.00/0.98

NC/6.92

0.86/0.91

≥9 CIL

0.13/0.06 1.00/0.98

NC/3.73

0.87/0.96

≥10 CIL

0.09/0.06 1.00/0.98

NC/3.73

0.91/0.96

≥1 CFL

0.68/0.74 0.30/0.44

0.98/1.32

1.04/0.59

≥2 CFL

0.62/0.66 0.41/0.54

1.05/1.43

0.93/0.63

≥3 CFL

0.53/0.59 0.55/0.61

1.18/1.52

0.86/0.67

≥4 CFL

0.41/0.54 0.64/0.70

1.14/1.78

0.92/0.66

≥5 CFL

0.32/0.44 0.68/0.76

0.98/1.80

1.01/0.75

≥6 CFL*

0.26/0.40 0.82/0.81

1.47/2.09

0.90/0.75

≥7 CFL

0.21/0.34 0.86/0.82

1.47/1.86

0.92/0.81

≥8 CFL

0.13/0.28 0.86/0.86

0.92/1.96

1.01/0.84

≥9 CFL

0.13/0.24 0.89/0.88

1.23/2.00

0.97/0.86

≥10 CFL

0.12/0.21 0.89/0.90

1.11/2.13

0.99/0.88

≥2 CIL and ≥2 CFL

0.42/0.27 0.84/0.83

2.62/1.57

0.69/0.88


0.37/0.24 0.86/0.87

2.58/1.88

0.74/0.87


0.33/0.23 0.88/0.89

2.63/2.21

0.77/0.86


0.34/0.21 0.88/0.91

2.74/2.31

0.75/0.87

30


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0.30/0.19 0.89/0.91

2.82/2.04

0.78/0.90


0.26/0.18 0.91/0.92

2.95/2.34

0.81/0.89


0.28/0.17 0.96/0.95

7.74/3.19

0.75/0.88


0.24/0.15 0.98/0.95 13.26/2.74

0.78/0.90


0.21/0.14 0.98/0.95 11.79/2.59

0.80/0.91

Sensitivity, specificity and likelihood ratios are expressed as mean values over 4 readers. Gold standard for calculating sensitivity and specificity was rheumatologist expert opinion. *Cut-off values for a positive spinal MRI in SpA proposed in the literature. Abbreviations CIL


CFL


NC

Not calculable (sensitivity or specificity 1.0)

LR

Likelihood ratio

nr-axSpA

Non-radiographic axial spondyloarthritis

NSBP


31



Page 32 of 37

Table 4 Diagnostic utility of candidate definitions for a positive spinal MRI observed in 2 cohorts A/B: AS versus NSBP patients

Diagnostic utility

Sensitivity Specificity Positive LR Negative LR

≥1 CIL

0.69/0.65 0.50/0.67

1.39/1.94

0.61/0.53

≥2 CIL*

0.67/0.55 0.64/0.74

1.87/2.14

0.52/0.60

≥3 CIL*

0.61/0.43 0.75/0.89

2.44/4.03

0.52/0.64

≥4 CIL

0.58/0.42 0.91/0.93

6.53/6.11

0.46/0.63

≥5 CIL

0.58/0.39 0.95/0.95 10.89/8.48

0.44/0.64

≥6 CIL

0.53/0.33 0.98/0.98 29.56/14.67

0.48/0.68

≥7 CIL

0.50/0.27 1.00/0.98

NC/11.92

0.50/0.75

≥8 CIL

0.42/0.23 1.00/0.98

NC/15.13

0.58/0.78

≥9 CIL

0.36/0.16 1.00/0.98

NC/10.31

0.64/0.86

≥10 CIL

0.33/0.11 1.00/0.98

NC/7.56

0.67/0.90

≥1 CFL

0.78/0.85 0.30/0.44

1.12/1.52

0.73/0.33

≥2 CFL

0.75/0.81 0.41/0.54

1.27/1.76

0.61/0.35

≥3 CFL

0.67/0.71 0.55/0.61

1.49/1.83

0.60/0.48

≥4 CFL

0.53/0.64 0.64/0.70

1.48/2.10

0.73/0.52

≥5 CFL

0.47/0.54 0.68/0.76

1.47/2.23

0.78/0.61

≥6 CFL*

0.44/0.48 0.82/0.81

2.49/2.53

0.68/0.64

≥7 CFL

0.36/0.47 0.86/0.82

2.53/2.58

0.75/0.65

≥8 CFL

0.36/0.46 0.86/0.86

2.53/3.18

0.75/0.63

≥9 CFL

0.25/0.46 0.89/0.88

2.33/3.78

0.84/0.62

≥10 CFL

0.19/0.45 0.89/0.90

1.81/4.55

0.90/0.61


0.53/0.48 0.84/0.83

3.28/2.75

0.56/0.63


0.53/0.43 0.86/0.87

3.69/3.32

0.55/0.66


0.47/0.40 0.88/0.89

3.78/3.73

0.60/0.68


0.47/0.40 0.88/0.91

3.78/4.35

0.60/0.66


0.47/0.36 0.89/0.91

4.41/4.01

0.59/0.70

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0.42/0.34 0.91/0.92

4.67/4.54

0.64/0.71


0.44/0.39 0.96/0.95 12.44/7.27

0.58/0.65


0.44/0.35 0.98/0.95 24.89/6.68

0.57/0.68


0.42/0.33 0.98/0.95 23.33/6.29

0.59/0.70

Sensitivity, specificity and likelihood ratios are expressed as mean values over 4 readers. Gold standard for calculating sensitivity and specificity was rheumatologist expert opinion. *Cut-off values for a positive spinal MRI in SpA proposed in the literature. Abbreviations AS

Ankylosing spondylitis

CIL


CFL


NC

Not calculable (sensitivity or specificity 1.0)

LR

Likelihood ratio

NSBP


33



Page 34 of 37

FIGURE LEGENDS

Figure 1: Corner vertebral lesions in a patient with ankylosing spondylitis

Sagittal MR images of the lower spine performed at the time of initial diagnosis in a 38-year old HLA-B27 negative male patient with inflammatory back pain for years, acute phase reactants were normal. Pelvic radiography confirmed bilateral grade 2 sacroiliitis. Anterior/posterior corner inflammatory lesions (CIL) are seen on a mid-line sagittal STIR image of the T9, T11 and T12 vertebral bodies (arrows in 1A, left panel). These CIL are typical for spondyloarthritis in shape, distribution and in the absence of adjacent disc degeneration. Corner fat lesions (CFL) are seen on a parasagittal T1weighted spin echo image at the posterior corners of the T12, L1, L2, L3 and L5 vertebral bodies (arrows in 1B, right panel). These CFL are typical for spondyloarthritis in size, shape and distribution.

Figure 2: Vertebral fatty marrow lesions on MRI in two subjects with nonspecific back pain

Sagittal T1-weighted spin echo MR images of the lumbar spine in two subjects with non-specific back pain for more than 3 months. Fatty marrow infiltration is seen in the L2, L4 and L5 vertebral bodies in a 38-year old female patient (arrows in Figure 2A, left panel). No loss of disc signal was seen on T2-weighted images at any level and only minimal loss of height is present at the L4/5 disc consistent with either no or only minimal evidence of disc degeneration at any level. The corner fat lesions (CFL) in the L5 vertebral body have a similar configuration to CFL seen in spondyloarthritis. The more broad-based lesions in the L2 and L4 vertebrae may also be seen in both 34


Page 35 of 37


conditions. CFL are also clearly seen at L1, L2 and L3 in a 43-year old male patient (arrows in Figure 2B, right panel). There is more evidence of disc degeneration with some loss of disc height, disc bulging and osteophytosis but the CFL at the posteroinferior corner of L2 is bright and sharply circumscribed and this is commonly seen in both inflammatory and degenerative conditions.

35



Figure 1: Corner vertebral lesions in a patient with ankylosing spondylitis Sagittal MR images of the lower spine performed at the time of initial diagnosis in a 38-year old HLA-B27 negative male patient with inflammatory back pain for years, acute phase reactants were normal. Pelvic radiography confirmed bilateral grade 2 sacroiliitis. Anterior/posterior corner inflammatory lesions (CIL) are seen on a mid-line sagittal STIR image of the T9, T11 and T12 vertebral bodies (arrows in 1A, left panel). These CIL are typical for spondyloarthritis in shape, distribution and in the absence of adjacent disc degeneration. Corner fat lesions (CFL) are seen on a parasagittal T1-weighted spin echo image at the posterior corners of the T12, L1, L2, L3 and L5 vertebral bodies (arrows in 1B, right panel). These CFL are typical for spondyloarthritis in size, shape and distribution. 163x178mm (300 x 300 DPI)


Page 36 of 37

Page 37 of 37


Figure 2: Vertebral fatty marrow lesions on MRI in two subjects with non-specific back pain Sagittal T1-weighted spin echo MR images of the lumbar spine in two subjects with non-specific back pain for more than 3 months. Fatty marrow infiltration is seen in the L2, L4 and L5 vertebral bodies in a 38-year old female patient (arrows in Figure 2A, left panel). No loss of disc signal was seen on T2-weighted images at any level and only minimal loss of height is present at the L4/5 disc consistent with either no or only minimal evidence of disc degeneration at any level. The corner fat lesions (CFL) in the L5 vertebral body have a similar configuration to CFL seen in spondyloarthritis. The more broad-based lesions in the L2 and L4 vertebrae may also be seen in both conditions. CFL are also clearly seen at L1, L2 and L3 in a 43-year old male patient (arrows in Figure 2B, right panel). There is more evidence of disc degeneration with some loss of disc height, disc bulging and osteophytosis but the CFL at the posteroinferior corner of L2 is bright and sharply circumscribed and this is commonly seen in both inflammatory and degenerative conditions. 178x178mm (300 x 300 DPI)


Fat infiltration on magnetic resonance imaging of the sacroiliac joints has limited diagnostic utility in nonradiographic axial spondyloarthritis.

Guidelines for magnetic resonance imaging in axial spondyloarthritis: A Delphi study.

Does evaluation of the ligamentous compartment enhance diagnostic utility of sacroiliac joint MRI in axial spondyloarthritis?

Diagnostic magnetic resonance imaging of the breast.

Magnetic resonance imaging of vertebral erosion in spondyloarthritis.

Magnetic Resonance Imaging of the Axial Skeleton in Patients With Spondyloarthritis: Distribution Pattern of Inflammatory and Structural Lesions.

Physician provider type influences utilization and diagnostic utility of magnetic resonance imaging of the knee.

Utility of magnetic resonance spectroscopic imaging for human epilepsy.

Effectiveness of Adalimumab in Non-radiographic Axial Spondyloarthritis: Evaluation of Clinical and Magnetic Resonance Imaging Outcomes in a Monocentric Cohort.

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Diagnostic utility of magnetic resonance imaging and radiography in juvenile spondyloarthritis: evaluation of the sacroiliac joints in controls and affected subjects.

Epidural cavernous hemangioma of the spine: magnetic resonance imaging findings.

The utility of cardiac magnetic resonance imaging in Kounis syndrome.

Diagnostic and Prognostic Implications of Spine Magnetic Resonance Imaging at Diagnosis in Patients with Multiple Myeloma.

Magnetic Resonance Imaging and GeneXpert: A Rapid and Accurate Diagnostic Tool for the Management of Tuberculosis of the Spine.

Diagnostic accuracy of magnetic resonance imaging for subscapularis tendon tears using radial-slice magnetic resonance images.

Diagnostic Accuracy on Magnetic Resonance Imaging for the Diagnosis of Osteoarthritis of the Temporomandibular Joint.

Differential diagnosis of cardiomyopathies: Utility of cardiac magnetic resonance imaging.

Prevention of new osteitis on magnetic resonance imaging in patients with early axial spondyloarthritis during 3 years of continuous treatment with etanercept: data of the ESTHER trial.

Diagnostic Utility of Diffusion-weighted Magnetic Resonance Imaging in Differentiating Small Solid Renal Tumors (≤ 4 cm) at 3.0T Magnetic Resonance Imaging.

Magnetic resonance imaging of the head and spine: effective for the clinician or the patient?

Screening whole spine magnetic resonance imaging in multiple myeloma.

The Nonradiographic Axial Spondyloarthritis, the Radiographic Axial Spondyloarthritis, and Ankylosing Spondylitis: The Tangled Skein of Rheumatology.