Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study.

OBJECTIVES: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.

'Double target' ultrasound monitoring of biologic therapy in psoriatic arthritis.

OBJECTIVES: We aimed to 1) evaluate by power Doppler (PD) ultrasound (US) the response to therapy of the most inflamed joint and enthesis (target sites) in psoriatic arthritis (PsA) patients starting a biologic disease-modifying anti-rheumatic drug (bDMARD); and 2) to investigate the correlation between the US response and clinical data. METHODS: Consecutive PsA patients with US synovitis and US 'active' enthesitis, starting a bDMARD, were included. The joint with the highest OMERACT-EULAR-US composite score and the enthesis with the highest PD grade (targets) were identified at baseline. The US examination and clinical assessment were performed at 0, 3 and 6 months. The response of OMERACT-EULAR-US synovitis composite score was defined as reaching a grade = 0 at follow-up examination; synovial and entheseal PD responses were defined as a PD=0 and/or a reduction of ≥2 PD grades at follow-up examination. RESULTS: Thirty patients were included. Synovitis composite score, synovial PD and entheseal PD showed significant responses at 3 and 6 months compared to baseline (p<0.01). Synovial PD responses were higher than entheseal PD responses at 3 months (71.4% vs 40.0%, p=0.01) and 6 months (77.8% vs. 46.7%, p=0.02). US synovitis responses were correlated with DAPSA (p<0.01) and MDA responses (p=0.01 for composite score, p=0.02 for PD). CONCLUSIONS: US was found sensitive for monitoring treatment response in PsA patients starting a biologic drug. Entheseal PD was less responsive than synovial PD, suggesting that enthesitis may represent a 'difficult-to-treat' domain in PsA.

Diagnosis of calcium pyrophosphate crystal deposition disease by ultrasonography: how many and which sites should be scanned?

OBJECTIVE: To develop the optimal US scanning protocol for the diagnosis of CPPD disease. METHODS: In this cross-sectional study, consecutive patients with a crystal-proven diagnosis of CPPD disease, and age-, sex-matched disease controls and with a negative synovial fluid analysis were prospectively enrolled in two Italian Institutions. Four rheumatologists, blinded to patients' clinical details, performed US examinations using a standardised scanning protocol including 20 joints (shoulders, elbows, wrists, metacarpophalangeal joints from 2nd to 5th fingers, hips, knees, ankles). CPPD was identified as presence/absence, according to the OMERACT definitions. Reduced US scanning protocols were developed by selecting the most informative joints to be imaged by US using the LASSO technique. Patients were randomly divided into training and validation sets. Their diagnostic accuracy was tested comparing the area under the ROC curves. RESULTS: 204 participants were enrolled: 102 with CPPD disease and 102 disease controls [age (mean±standard deviation) 71.3 ± 12.0 vs 71.1 ± 13.5 years, female: 62.8% vs 57.8%].The median number of joints with US evidence of CPPD was 5 (IQR: 4-7) and 0 (IQR: 0-1) in patients with CPPD disease and controls, respectively (p< 0 01).The detection of CPPD in ≥ 2 joints using a reduced scanning protocol (bilateral assessment of knees, wrists, and hips) showed a sensitivity of 96.7% (95%CI: 82.8-99.9) and a specificity of 100 (95%CI: 88.8-100.0) for the diagnosis of CPPD disease and had good feasibility [(mean±standard deviation) 12.5 ± 5.3 min]. CONCLUSION: Bilateral US assessment of knees, wrists, and hips had excellent accuracy and good feasibility for the diagnosis of CPPD disease.

Multimodal ultrasound muscle assessment in patients with rheumatic diseases: a patient-based reliability study.

Objectives: The aim was to explore the inter-reliability of a newly developed US scanning protocol (multimodal US) for the assessment of different aspects of sarcopenia-related muscle involvement, including muscle mass, muscle quality and muscle stiffness [using point shear-wave elastography (SWE)], in patients with rheumatic and musculoskeletal diseases (RMDs). Methods: Quadriceps muscle mass (i.e. muscle thickness), muscle quality (i.e. muscle echogenicity evaluated with both a visual semi-quantitative scale and a dedicated software package for image analysis, ImageJ) and point SWE measurements were obtained by two rheumatologists (blinded to each other's evaluation) in consecutive RMD patients without previous/current myositis or neuromuscular disorders.Inter-reliability was assessed using the intraclass correlation coefficient (ICC) for continuous variables and Cohen's kappa (κ) for categorical variables. Results: A total of 45 RMD patients were enrolled [mean age 54.5 (16.0) years, male-to-female ratio 1:1.5, mean BMI 24.6 (4.6) kg/m2], 10 with PsA, 7 RA, 5 AS, 5 PMR, 4 SLE, 4 gout, 4 OA, 3 FM and 3 SSc. The grade of inter-rater reliability was excellent for muscle mass [ICC = 0.969 (0.953 < ICC < 0.979)]. Regarding muscle echogenicity, the agreement was substantial/almost perfect using the visual semi-quantitative scale (weighted linear = 0.793, weighted squared = 0.878) and excellent using ImageJ analysis [ICC = 0.916 (0.876 < ICC < 0.944)]. Finally, a good agreement was obtained for point SWE measurements [ICC = 0.76 (0.712 < ICC < 0.8)]. Conclusion: Multimodal US is a novel and reliable tool for the evaluation of different aspects of muscle involvement (muscle mass, muscle quality and muscle stiffness) in RMD patients.

Doppler Signal and Bone Erosions at the Enthesis Are Independently Associated With Ultrasound Joint Erosive Damage in Psoriatic Arthritis.

OBJECTIVE: To explore the association of the Outcome Measures in Rheumatology ultrasound (US) entheseal abnormalities with the presence of US joint bone erosions in psoriatic arthritis (PsA). METHODS: Consecutive patients with PsA were included in this cross-sectional study. Demographic and clinical variables were collected. A bilateral US assessment was carried out at the following entheses: plantar fascia, and the quadriceps, patellar (proximal and distal), and Achilles tendons. The following US entheseal abnormalities were registered: hypoechogenicity, thickening, Doppler signal < 2 mm from the bony cortex, calcification/enthesophyte, and bone erosion. The presence of US joint bone erosions was investigated at the second and fifth metacarpophalangeal joints, ulnar head, and fifth metatarsophalangeal (MTP) joint, bilaterally, as well as at the level of the most inflamed joint on physical examination. Multiple linear regression analysis was performed to identify clinical and/or US variables associated with US-detected joint bone erosions. RESULTS: A total of 104 patients with PsA were enrolled. At least 1 joint bone erosion was found in 47 of 104 patients (45.2%). Bone erosions were most frequently detected at the fifth MTP joint level (42/208 joints [20.2 %] in 32/104 patients [30.8%]). In the multivariate model, only a power Doppler (PD) signal at the enthesis (P < 0.001, standardized ß = 0.51), bone erosions at the enthesis (P = 0.02, standardized ß = 0.20), PsA disease duration (P = 0.04, standardized ß = 0.17), and greyscale joint synovitis (P = 0.03, standardized ß = 0.42) were associated with US-detected joint bone erosions. CONCLUSION: PD signal and bone erosions at the enthesis represent sonographic biomarkers of a more severe subset of PsA in terms of US-detected joint erosive damage.

Development of a convolutional neural network for the identification and the measurement of the median nerve on ultrasound images acquired at carpal tunnel level.

BACKGROUND: Deep learning applied to ultrasound (US) can provide a feedback to the sonographer about the correct identification of scanned tissues and allows for faster and standardized measurements. The most frequently adopted parameter for US diagnosis of carpal tunnel syndrome is the increasing of the cross-sectional area (CSA) of the median nerve. Our aim was to develop a deep learning algorithm, relying on convolutional neural networks (CNNs), for the localization and segmentation of the median nerve and the automatic measurement of its CSA on US images acquired at the proximal inlet of the carpal tunnel. METHODS: Consecutive patients with rheumatic and musculoskeletal disorders were recruited. Transverse US images were acquired at the carpal tunnel inlet, and the CSA was manually measured. Anatomical variants were registered. The dataset consisted of 246 images (157 for training, 40 for validation, and 49 for testing) from 103 patients each associated with manual annotations of the nerve boundary. A Mask R-CNN, state-of-the-art CNN for image semantic segmentation, was trained on this dataset to accurately localize and segment the median nerve section. To evaluate the performances on the testing set, precision (Prec), recall (Rec), mean average precision (mAP), and Dice similarity coefficient (DSC) were computed. A sub-analysis excluding anatomical variants was performed. The CSA was automatically measured by the algorithm. RESULTS: The algorithm correctly identified the median nerve in 41/49 images (83.7%) and in 41/43 images (95.3%) excluding anatomical variants. The following metrics were obtained (with and without anatomical variants, respectively): Prec 0.86 ± 0.33 and 0.96 ± 0.18, Rec 0.88 ± 0.33 and 0.98 ± 0.15, mAP 0.88 ± 0.33 and 0.98 ± 0.15, and DSC 0.86 ± 0.19 and 0.88 ± 0.19. The agreement between the algorithm and the sonographer CSA measurements was excellent [ICC 0.97 (0.94-0.98)]. CONCLUSIONS: The developed algorithm has shown excellent performances, especially if excluding anatomical variants. Future research should aim at expanding the US image dataset including a wider spectrum of normal anatomy and pathology. This deep learning approach has shown very high potentiality for a fully automatic support for US assessment of carpal tunnel syndrome.

Reliability assessment of ultrasound muscle echogenicity in patients with rheumatic diseases: Results of a multicenter international web-based study.

Objectives: To investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases. Methods: Forty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0-3) and a continuous quantitative measurement ("VAS echogenicity," 0-100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall's Tau and Pearson's Rho coefficients. Results: The semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57-0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68-0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. "VAS echogenicity" showed a high reliability both in the inter-observer [ICC = 0.80 (0.75-0.85)] and intra-observer [ICC = 0.88 (0.88-0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and "VAS echogenicity" [ICC = 0.52 (0.50-0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively). Conclusion: The results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases.