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Objective Beyond static assessment, functional techniques are increasingly applied in magnetic resonance imaging (MRI) studies. Stress MRI techniques bring together MRI and mechanical loading to study knee joint and tissue functionality, yet prototypical axial compressive loading devices are bulky and complex to operate. This study aimed to design and validate an MRI-compatible pressure-controlled varus–valgus loading device that applies loading along the joint line. Methods Following the device’s thorough validation, we demonstrated proof of concept by subjecting a structurally intact human cadaveric knee joint to serial imaging in unloaded and loaded configurations, i.e. to varus and valgus loading at 7.5 kPa (= 73.5 N), 15 kPa (= 147.1 N), and 22.5 kPa (= 220.6 N). Following clinical standard (PDw fs) and high-resolution 3D water-selective cartilage (WATSc) sequences, we performed manual segmentations and computations of morphometric cartilage measures. We used CT and radiography (to quantify joint space widths) and histology and biomechanics (to assess tissue quality) as references. Results We found (sub)regional decreases in cartilage volume, thickness, and mean joint space widths reflective of areal pressurization of the medial and lateral femorotibial compartments. Discussion Once substantiated by larger sample sizes, varus–valgus loading may provide a powerful alternative stress MRI technique.

Background: To compare the effect of Adalimumab (ADA) plus Methotrexate (MTX) versus MTX monotherapy in patients with therapy naïve early rheumatoid arthritis (eRA) on cartilage quality measured by glycosaminoglycan (GAG) content in cartilage using gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC). Methods: Prospective double-blinded, randomized clinical trial of cartilage integrity in finger joints of eRA patients according to American College of Rheumatology/ European League Against Rheumatism. Patients were examined therapy-naïve, 12 and 24 weeks after initiation of Adalimumab+MTX or placebo+MTX with 3T-MRI, recording dGEMRIC values of metacarpophalangeal joints of index and middle finger. Results: The study was prematurely terminated due to theoretical safety concerns regarding gadolinium deposition in the brain after MR contrast agent application. Instead of 30 planned patients, 10 patients could be included in the Adalimumab group (ADA+MTX: 6 females, 44.9y, range: 19-65), four in the control group (Placebo+MTX: 2 females, 46.7y, range: 24-64). Between treatment groups, cartilage composition did not change significantly (ADA+MTX: dGEMRIC mean change 85.8ms, range -156.2–346.5ms; Placebo+MTX: mean change-30.75ms, range-273.0–131.0ms; W=27, p=0.37). Neverthless a significant increase of the dGEMRIC values over time was observed in the Adalimumab group (median change 75.88 ms p=0.0117), but not in the placebo group (median change 9.50, p=0.878).Conclusions: In patients with eRA, Adalimumab+MTX leads to a significant dGEMRIC improvement, indicating a possible reduction of cartilage damage in the finger joints. The level of significance for the difference of change in cartilage quality between groups, was not met, potentially due to lower than expected number of patients which could be recruited. Trial registration: The cartilage in early Rheumatoid Arthritis (CAR-ERA)-Study was approved by the local ethics committee of the Heinrich-Heine University of Duesseldorf (reference number: MO-LKP-719) and was registered at clinicaltrials.gov under the number NCT02150473 / CAR-ERA 2013-004604-19 (EudraCT Number).

Cartilage functionality is determined by tissue structure and composition. If altered, cartilage is predisposed to premature degeneration. This pathomimetical study of early osteoarthritis evaluated the dose-dependant effects of collagenase-induced collagen disintegration and proteoglycan depletion on cartilage functionality as assessed by serial T1, T1ρ, T2, and T2* mapping under loading. 30 human femoral osteochondral samples underwent imaging on a clinical 3.0 T MRI scanner (Achieva, Philips) in the unloaded reference configuration (δ0) and under pressure-controlled quasi-static indentation loading to 15.1 N (δ1) and to 28.6 N (δ2). Imaging was performed before and after exposure to low (LC, 0.5 mg/mL; n = 10) or high concentration (HC, 1.5 mg/mL; n = 10) of collagenase. Untreated samples served as controls (n = 10). Loading responses were determined for the entire sample and the directly loaded (i.e. sub-pistonal) and bilaterally adjacent (i.e. peri‑pistonal) regions, referenced histologically, quantified as relative changes, and analysed using adequate parametric and non-parametric statistical tests. Dose-dependant surface disintegration and tissue loss were reflected by distinctly different pre- and post-exposure response-to-loading patterns. While T1 generally decreased with loading, regardless of collagenase exposure, T1ρ increased significantly after HC exposure (p = 0.008). Loading-induced decreases in T2 were significant after LC exposure (p = 0.006), while changes in T2* were ambiguous. In conclusion, aberrant loading-induced changes in T2 and T1ρ reflect moderate and severe matrix changes, respectively, and indicate the close interrelatedness of matrix changes and functionality in cartilage.

Biomechanical Magnetic Resonance Imaging (MRI) of articular cartilage, i.e. its imaging under loading, is a promising diagnostic tool to assess the tissue's functionality in health and disease. This study aimed to assess the response to static and dynamic loading of histologically intact cartilage samples by functional MRI and pressure-controlled in-situ loading. To this end, 47 cartilage samples were obtained from the medial femoral condyles of total knee arthroplasties (from 24 patients), prepared to standard thickness, and placed in a standard knee joint in a pressure-controlled whole knee-joint compressive loading device. Cartilage samples' responses to static (i.e. constant), dynamic (i.e. alternating), and no loading, i.e. free-swelling conditions, were assessed before (δ0), and after 30 min (δ1) and 60 min (δ2) of loading using serial T1ρ maps acquired on a 3.0T clinical MRI scanner (Achieva, Philips). Alongside texture features, relative changes in T1ρ (Δ1, Δ2) were determined for the upper and lower sample halves and the entire sample, analyzed using appropriate statistical tests, and referenced to histological (Mankin scoring) and biomechanical reference measures (tangent stiffness). Histological, biomechanical, and T1ρ sample characteristics at δ0 were relatively homogenous in all samples. In response to loading, relative increases in T1ρ were strong and significant after dynamic loading (Δ1 = 10.3 ± 17.0%, Δ2 = 21.6 ± 21.8%, p = 0.002), while relative increases in T1ρ after static loading and in controls were moderate and not significant. Generally, texture features did not demonstrate clear loading-related associations underlying the spatial relationships of T1ρ. When realizing the clinical translation, this in-situ study suggests that serial T1ρ mapping is best combined with dynamic loading to assess cartilage functionality in humans based on advanced MRI techniques.

Background: Using high-field MRI to differ morphologically between OA and RA. Objectives: To evaluate the value of morphological and biochemical, contrast-agent free high-field (3 Tesla) MRI of the radiocarpal cartilage to differ between osteoarthritis (OA) and rheumatoid arthritis (RA). Methods: The group consisted of 47 subjects, who were examined during the period from October 2016 to December 2017. The clinical dominant hand of 11 patients suffering from early rheumatoid arthritis (RA) (German ArthroMark cohort, O 52.8years; min: 32; max 74), seropositive (ACPA and/or RF), disease duration Results: Morphological sequences demonstrated significantly higher cartilage damage in RA and OA compared to healthy controls (DESS: p = 0.01, p = 0.0004; TrueFISP: p = 0.02, p = 0.0001), while there was no significant difference between RA and OA patients. With biochemical MRI using T2* imaging, patients with OA showed higher cartilage integrity compared to patients with RA (p = 0.01). Conclusion: Morphological and biochemical MRI of radiocarpal cartilage could be helpful to differentiate between RA and OA patients. Both, RA and OA, are associated with cartilage damage measured by morphological MRI of the hand. Hence, OA was associated with more loss of cartilage integrity compared to RA using biochemical MRI, whereby only early RA patients were analyzed in this first evaluation. Non-contrast-agent morphological and biochemical MRI could be a non-invasive tool to investigate cartilage integrity in RA and OA patients and could help to differ disease pattern in the future. Acknowledgement: We would like to thank Erika Radisch for the assistance in receiving the MRI scans. Disclosure of Interests: Philipp Sewerin: None declared, Lino Sawicki: None declared, Christoph Schleich: None declared, Daniel Abrar: None declared, Matthias Schneider Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Speakers bureau: Chugai, Stefan Vordenbaumen: None declared, Benedikt Ostendorf: None declared

The aim of the study was to investigate biochemical cartilage composition under methotrexate (MTX) therapy and to intra-individually assess the impact of inflammation severity on cartilage composition by using dGEMRIC MRI in patients with early rheumatoid arthritis (eRA).dGEMRIC of MCP joints of the index and middle finger of 28 patients from the AthroMark cohort were examined prior to MTX-therapy as well as after 3 and 6 month. OMERACT RA MRI score and clinical parameters (CRP and DAS28) were registered at any time point. Each patient's second and third MCP joints were dichotomised into the joint with more severe synovitis versus the joint with less severe synovitis according to the RAMRIS synovitis subscore.MCP joints with more severe synovitis ('bad joints') demonstrated significantly lower dGEMRIC values compared to MCP joints with less severe synovitis ('good joints') at time-points 0 and 3 months (p=0.002; p=0.019, respectively). After 6 months of MTX therapy no significant difference of dGEMRIC index was found between good and bad joint (p=0.086).Under MTX therapy, biochemical cartilage integrity remains stable; no further cartilage destruction occurred if patients were treated early in the course of the disease. In addition, six months of MTX therapy triggered an alignment of dGEMRIC index of MCP joints with initially severe synovitis and less severe synovitis in an intra-individual assessment. This underlines the importance of an early treatment in eRA to reduce further cartilage damage of the inflamed joints.