A simple, clinically usable whole-body MRI system of joint assessment in adolescents and young people with juvenile idiopathic arthritis.

OBJECTIVES: To introduce and evaluate a simple method for assessing joint inflammation and structural damage on whole-body MRI (WBMRI) in juvenile idiopathic arthritis (JIA), which is usable in clinical practice. METHODS: The proposed system utilises post-contrast Dixon WBMRI scans. Joints are assessed for synovitis (grade 0-2) and structural damage (present/absent) at 81 sites. The synovitis grading is based on features including above-normal intensity synovial enhancement, synovial hypertrophy, joint effusion, subarticular bone marrow oedema and peri-articular soft tissue oedema.This system was evaluated in a prospective study of 60 young people (47 patients with JIA and 13 controls with non-inflammatory musculoskeletal pain) who underwent a WBMRI. Three readers (blinded to diagnosis) independently reviewed all images and re-reviewed 20 individual scans. The intra- and inter-reader overall agreement (OA) and the intra- and inter-reader Gwet's agreement coefficients 2 (GAC2) were measured for the detection of a) participants with ≥1 joint with inflammation or structural damage and b) joint inflammation or structural damage for each joint. RESULTS: The inter-reader OA for detecting patients with ≥1 joint with inflammation, defined as grade 2 synovitis (G2), and ≥1 joint with structural damage were 80% and 73%, respectively. The intra-reader OA for readers 1-3 were 80-90% and 75-90% respectively. The inter-reader OA and GAC2 for joint inflammation (G2) at each joint were both ≥85% for all joints but were lower if grade 1 synovitis was included as positive. CONCLUSION: The intra- and inter-reader agreements of this WBMRI assessment system are adequate for assessing objective joint inflammation and damage in JIA.

Detection of inflammation by whole-body MRI in young people with juvenile idiopathic arthritis.

OBJECTIVES: To assess the frequency of joint inflammation detected by whole-body MRI (WBMRI) in young people (YP) with JIA and controls, and to determine the relationship between WBMRI-detected inflammation and clinical findings. METHODS: YP aged 14-24 years, with JIA (patients) or arthralgia without JIA (controls), recruited from one centre, underwent a WBMRI scan after formal clinical assessment. Consensus between at least two of the three independent radiologists was required to define inflammation and damage on WBMRI, according to predefined criteria. YP with JIA were deemed clinically active as per accepted definitions. The proportions of YP with positive WBMRI scans for joint inflammation (≥1 inflamed joint) as well as serum biomarkers were compared between active vs inactive JIA patients and controls. RESULTS: Forty-seven YP with JIA (25 active and 22 inactive patients) and 13 controls were included. WBMRI detected joint inflammation in 60% (28/47) patients with JIA vs 15% (2/13) controls (difference: 44%, 95% CI 20%, 68%). More active than inactive JIA patients had WBMRI-detected inflammation [76% (19/25) vs 41% (9/22), difference: 35% (95% CI 9%, 62%)], and this was associated with a specific biomarker signature. WBMRI identified inflammation in ≥ 1 clinically inactive joint in 23/47 (49%) patients (14/25 active vs 9/22 inactive JIA patients). CONCLUSIONS: WBMRI's validity in joint assessment was demonstrated by the higher frequency of inflammation in JIA patients vs controls, and in active vs inactive JIA patients. WBMRI found unsuspected joint inflammation in 49% YP with JIA, which needs further investigation of potential clinical implications.

A multiparametric alternative to short inversion-time inversion recovery for imaging inflammation: T2water and fat fraction measurement using chemical shift-encoded turbo spin-echo MRI.

PURPOSE: Short-inversion-time inversion-recovery MRI is used widely for imaging bone and soft-tissue inflammation in rheumatic inflammatory diseases, but there is no widely available quantitative equivalent of this sequence. This limits our ability to objectively assess inflammation and distinguish it from other processes. To address this, we investigate the use of the widely available Dixon turbo spin echo (TSE Dixon) sequence as a practical approach to simultaneous water-specific T2 (T2water ) and fat fraction (FF) measurement. METHODS: We use a series of TSE Dixon acquisitions with varying effective TEs (TEeff ) to quantify T2water and FF. The validity of this approach is assessed in a series of phantom and in vivo experiments, with reference values provided by Carr-Purcell-Meiboom-Gill acquisitions, MRS, and phantoms. The effect of inflammation on parameter values is evaluated in patients with spondyloarthritis. RESULTS: The T2water estimates obtained from TSE Dixon were accurate compared with the reference values from Carr-Purcell-Meiboom-Gill and spectroscopy in both fat-free environments and in the presence of fat. FF measurements with T2water correction from TSE Dixon were accurate from 0% to 60% FF and were not confounded by T2water variations. In vivo imaging produced good quality images that were artifact free, produced plausible T2 values, separating and quantifying the effect of inflammation on T2water and FF. CONCLUSION: The T2water and FF measurements based on TSE Dixon with effective TE increments are accurate over a range of T2 and FF values and could provide a widely available quantitative alternative to the short-inversion-time inversion-recovery sequence for imaging inflamed tissue.

Biomarkers Associated with Organ-Specific Involvement in Juvenile Systemic Lupus Erythematosus.

Juvenile systemic lupus erythematosus (JSLE) is characterised by onset before 18 years of age and more severe disease phenotype, increased morbidity and mortality compared to adult-onset SLE. Management strategies in JSLE rely heavily on evidence derived from adult-onset SLE studies; therefore, identifying biomarkers associated with the disease pathogenesis and reflecting particularities of JSLE clinical phenotype holds promise for better patient management and improved outcomes. This narrative review summarises the evidence related to various traditional and novel biomarkers that have shown a promising role in identifying and predicting specific organ involvement in JSLE and appraises the evidence regarding their clinical utility, focusing in particular on renal biomarkers, while also emphasising the research into cardiovascular, haematological, neurological, skin and joint disease-related JSLE biomarkers, as well as genetic biomarkers with potential clinical applications.

The role of whole-body MRI in musculoskeletal inflammation detection and treatment response evaluation in inflammatory arthritis across age: A systematic review.

OBJECTIVE: To evaluate the relation between whole-body MRI (WBMRI) outcomes and disease activity measures, including clinical examination, composite scores, and other imaging outcomes, and the ability of WBMRI to detect treatment response in patients with inflammatory arthritis (IA) across age. METHODS: Human studies published as full text or abstract in the PubMed and MEDLINE and Cochrane databases from inception to 11th April 2021 were systematically and independently searched by two reviewers. Studies including patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), spondyloarthritis (SpA), juvenile idiopathic arthritis (JIA) or unclassified inflammatory arthritis (UA) who underwent WBMRI and which reported on disease outcomes were included. RESULTS: Nineteen full-text studies were eligible for inclusion: 2 interventional, 7 retrospective and 10 prospective observational studies, comprising 540 participants (SpA 38.7%, RA 24.8%, JIA 17.8%, PsA 11.5%, healthy controls 5.9%, UA 1.3%). Abstracts of 6 conference papers were reported separately. Five studies in PsA and SpA and 4 in RA measured the frequency of WBMRI-detected and clinically-detected synovitis, and all found the former to be more frequent. Less enthesitis was detected by WBMRI than clinical examination in 5/8 studies. After biologic treatment, the WBMRI inflammation scores declined in 3 studies in SpA and 2 in RA, whilst in 3 studies the results were equivocal. CONCLUSION: The ability of WBMRI to assess disease activity and treatment response in IA was adequate overall. Further studies are needed to corroborate WBMRI findings with IA outcomes and investigate the clinical value of subclinical inflammation.

Biomarkers of Response to Biologic Therapy in Juvenile Idiopathic Arthritis.

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthritis of childhood, characterized by various clinical phenotypes associated with variable prognosis. Significant progress has been achieved with the use of biologic treatments, which specifically block pro-inflammatory molecules involved in the disease pathogenesis. The most commonly used biologics in JIA are monoclonal antibodies and recombinant proteins targeting interleukins 1 (IL-1) and 6 (IL-6), and tumor necrosis factor α (TNF-α). Several biomarkers have been investigated in JIA. Aims: To assess the level of evidence available regarding the role of biomarkers in JIA related to guiding clinical and therapeutic decisions, providing disease prognostic information, facilitating disease activity monitoring and assessing biologic treatment response in JIA, as well as propose new strategies for biologic therapy-related biomarker use in JIA. Methods: We searched PubMed for relevant literature using predefined key words corresponding to several categories of biomarkers to assess their role in predicting and assessing biologic treatment response and clinical remission in JIA. Results: We reviewed serological, cellular, genetic, transcriptomic and imaging biomarkers, to identify candidates that are both well-established and widely used, as well as newly investigated in JIA on biologic therapy. We evaluated their role in management of JIA as well as identified the unmet needs for new biomarker discovery and better clinical applications. Conclusion: Although there are no ideal biomarkers in JIA, we identified serological biomarkers with potential clinical utility. We propose strategies of combining biomarkers of response to biologics in JIA, as well as routine implementation of clinically acceptable imaging biomarkers for improved disease assessment performance.