Shear-Wave Elastography of the Achilles tendon: reliability analysis and impact of parameters modulating elasticity values.

PURPOSE: Shear wave elastography (SWE) has seen many advancements in Achilles tendon evaluation in recent years, yet standardization of this technique is still problematic due to the lack of knowledge regarding the optimal way to perform the examination. The purpose of this study was to evaluate the effects of ankle position, probe frequency and physical effort on the shear modulus of the Achilles tendon, but also to determine the intra and inter-observer reliability of the technique. METHODS: 37 healthy volunteers were included; SWE protocol was performed by two examiners. We analyzed the shear modulus of the tendon with the ankle in neutral, maximum dorsiflexion and maximum plantar flexion using two different high frequency probes. Afterwards, the subjects performed a brief physical exercise and SWE measurements were repeated. RESULTS: The L18-5 probe showed the highest ICC values (ICC = 0.798, 95% CI 0.660-0.880, p < 0.001) when positioned at 2 cm from the calcaneal insertion with the ankle in a neutral state. Conversely, utilizing the same L18-5 probe at 1 cm from the insertion during maximum plantar flexion of the ankle resulted in the lowest ICC (ICC = 0.422, 95% CI 0.032-0.655, p = 0.019). Significant variations in elasticity values were noted among different ankle positions and probe types, while no significant changes in elasticity were observed post-physical exercise. CONCLUSION: Ankle position and probe frequency are factors that influence elasticity values of the Achilles tendon. An ankle position between 10 and 20 degrees of plantar flexion is the most suitable for SWE evaluation. However, more research focusing on Achilles tendon SWE is essential due to the challenges encountered in standardizing this region.

Assessing forefoot bursitis in rheumatoid arthritis: a comprehensive approach with ultrasound, MRI, and baropodometry.

AIM: In rheumatoid arthritis (RA), forefoot bursitis is prevalent, with limited studies comparing ultrasonography (US) and Magnetic Resonance Imaging (MRI). This study aims to evaluate these bursae, providing a comparative analysis of US and MRI, and explore associations with demographic, disease-related factors, pain, clinical examination, and baropodometryin RA patients. MATERIAL AND METHODS: Participants with RA were recruited from the day-hospital clinic. The forefeet were assessed clinically, and the selected foot was examined by US and MRI to evaluate intermetatarsal (IMB) and submetatarsal bursitis (SMB). Baropodometry assessed plantar pressures and contact surfaces. RESULTS: Thirty-five RA patients were enrolled, 85.7% females, mean age 59.2 (11.3) years, mean body mass index (BMI) 26.5 (5.7) kg/m2, median disease duration of 36.0 (16.5-114.0) months, and 34.3% with painful forefoot. A total of 140 intermetatarsal and 175 submetatarsal spaces were evaluated. Agreement between US and MRI was high (PA=97.14%, k=0.801, p<0.001), and interobserver reliability for both modalities was excellent (US: PA=98.73%, k=0.888, p<0.001; MRI: PA=98.41%, k=0.900, p<0.001). IMB was negatively associated with disease duration (the only independent predictor) and linked to clinical signs like the opening toes sign and hammer toe deformity. SMB showed an association with BMI and erosions. Baropodometric analysis indicated no significant differences in plantar pressures for IMB, and larger contact surfaces in SMB regions. CONCLUSIONS: US and MRI are valuable tools for forefoot bursitis evaluation. IMB is associated with disease duration (negative association), the opening toes sign, and hammer toe deformity, while SMB correlates with BMI, erosions, and foot architectural deformity. Baropodometry revealed larger contact surfaces in regions with SMB.

Factors influencing the Shear Wave Elastography evaluation of the patellar tendon.

AIM: There is no clear standardization for tendon Shear Wave Elastography (SWE), and data regarding the factors that influence the correctness of evaluation are scarce. We aimed to determine the intra- and interobserver agreement in patellar tendon SWE, and to establish the influence of various factors on elasticity values. MATERIALS AND METHODS: We recruited 37 healthy volunteers; SWE of the patellar tendon was performed by two examiners. The following factors were analyzed: probe frequency, degree of joint flexion, size of region of interest (ROI), distance of the color box from the probe footprint, utilization of coupling gel as standoff, and the effect of physical exercise on elastic modulus values. RESULTS: Highest overall interobserver [k=0.767, 95%CI (0.717-0.799), p<0.001] and intraobserver agreement [k=0.920 (0.909-0.929) for examiner 1, k=0.891 (0.875-0.905) for examiner 2] was obtained with the knee in the neutral position, using the L18-5 probe. With the knee flexed at 30º and 45º, the elasticity values were higher compared to the neutral position (p<0.001). With the probe immersed in 0.25 and 0.50 cm coupling gel, the median values were lower compared to the probe placed on the skin (p=0.001, p=0.018). The ROI dimensions and the placement of the SWE box at the level of the skin or at 0.5 cm below skin did not significantly influence the elastic modulus. After physical exercise, the elasticity values decreased in the proximal and middle portion of the tendon (p=0.002, p<0.001). CONCLUSION: The best results obtained in patellar tendon SWE were with the knee in neutral position, in the proximal or middle tendon, after 10 minutes of relaxation and with the probe placed directly on the skin with minimal pressure. The size and position of ROI do not significantly influence the examination.

Diagnostic role of CXCL13 biomarker in primary Sjogren's syndrome patients with parotid non-Hodgkin's lymphoma complication / Papel diagnóstico del biomarcador CXCL13 en pacientes con síndrome de Sjogren primario con complicación de linfoma no Hodgkin parotídeo

Introduction Serum biomarkers are important predictive factors for development of parotid non-Hodgkin's lymphoma (NHL) complication in primary Sjogren's syndrome (pSS) patients. The aim was to evaluate the diagnostic accuracy of serum CXCL13 chemokine in pSS patients with parotid NHL complication. Material and methods Serum CXCL13 chemokine was assessed in 33 patients with pSS [7 with parotid NHL complication (pSS+NHL subgroup) and 26 without NHL (pSS-NHL subgroup)] and 30 healthy subjects. Results The serum CXCL13 levels in pSS+NHL subgroup [175.2 (107.9–220.4) pg/ml] were significantly higher comparing to the healthy subjects group (p=0.018) and the pSS-NHL subgroup (p=0.048). A cut-off value of 123.45pg/ml (Se=71.4%, Sp=80.8%, AUROC=0.747) was established for parotid lymphoma diagnosis. Conclusion The serum CXCL13 biomarker could be considered a valuable tool for the diagnosis of parotid NHL complication in pSS patients (AU)

Introducción Los biomarcadores séricos son factores predictivos importantes para el desarrollo de complicaciones del linfoma no Hodgkin (LNH) parotídeo en pacientes con síndrome de Sjogren primario (SSp). El objetivo fue evaluar la precisión diagnóstica de la quimiocina sérica CXCL13 en pacientes con SSp con complicación del LNH parotídeo. Material y métodos Se evaluó la quimiocina sérica CXCL13 en 33 pacientes con SSp [7 con complicación de LNH parotídeo (subgrupo SSp+LNH) y 26 sin LNH (subgrupo SSp-LNH)] y 30 sujetos sanos. Resultados Los niveles séricos de CXCL13 en el subgrupo pSS+NHL [175,2 (107,9-220,4) pg/ml] fueron significativamente más altos en comparación con el grupo de sujetos sanos (p=0,018) y el subgrupo pSS-NHL (p=0,048). Se estableció un valor de corte de 123,45 pg/ml (Se=71,4%, Sp=80,8%, AUROC=0,747) para el diagnóstico de linfoma de parótida. Conclusión El biomarcador sérico CXCL13 podría considerarse una herramienta valiosa para el diagnóstico de la complicación del LNH parotídeo en pacientes con SSp (AU)

Diagnostic role of CXCL13 biomarker in primary Sjogren's syndrome patients with parotid non-Hodgkin's lymphoma complication.

INTRODUCTION: Serum biomarkers are important predictive factors for development of parotid non-Hodgkin's lymphoma (NHL) complication in primary Sjogren's syndrome (pSS) patients. The aim was to evaluate the diagnostic accuracy of serum CXCL13 chemokine in pSS patients with parotid NHL complication. MATERIAL AND METHODS: Serum CXCL13 chemokine was assessed in 33 patients with pSS [7 with parotid NHL complication (pSS+NHL subgroup) and 26 without NHL (pSS-NHL subgroup)] and 30 healthy subjects. RESULTS: The serum CXCL13 levels in pSS+NHL subgroup [175.2 (107.9-220.4) pg/ml] were significantly higher comparing to the healthy subjects group (p=0.018) and the pSS-NHL subgroup (p=0.048). A cut-off value of 123.45pg/ml (Se=71.4%, Sp=80.8%, AUROC=0.747) was established for parotid lymphoma diagnosis. CONCLUSION: The serum CXCL13 biomarker could be considered a valuable tool for the diagnosis of parotid NHL complication in pSS patients.

Radiomic Features Associated with Lymphoma Development in the Parotid Glands of Patients with Primary Sjögren's Syndrome.

Non-Hodgkin Lymphoma (NHL) represents a severe complication and the main cause of morbidity in patients with primary Sjögren's syndrome (pSS). This study aimed to assess the role of textural analysis (TA) in revealing lymphoma-associated imaging parameters in the parotid gland (PG) parenchyma of patients with pSS. This retrospective study included a total of 36 patients (54.93 ± 13.34 years old; 91.6% females) diagnosed with pSS according to the American College of Rheumatology and the European League Against Rheumatism criteria (24 subjects with pSS and no lymphomatous proliferation; 12 subjects with pSS and NHL development in the PG, confirmed by the histopathological analysis). All subjects underwent MR scanning between January 2018 and October 2022. The coronal STIR PROPELLER sequence was employed to segment PG and perform TA using the MaZda5 software. A total of 65 PGs underwent segmentation and texture feature extraction (48 PGs were included in the pSS control group, and 17 PGs were included in the pSS NHL group). Following parameter reduction techniques, univariate analysis, multivariate regression, and receiver operating characteristics (ROC) analysis, the following TA parameters proved to be independently associated with NHL development in pSS: CH4S6_Sum_Variance and CV4S6_Inverse_Difference_Moment, with an area under ROC of 0.800 and 0.875, respectively. The radiomic model (resulting by combining the two previously independent TA features), presented 94.12% sensitivity and 85.42% specificity in differentiating between the two studied groups, reaching the highest area under ROC of 0.931 for the chosen cutoff value of 1.556. This study suggests the potential role of radiomics in revealing new imaging biomarkers that might serve as useful predictors for lymphoma development in patients with pSS. Further research on multicentric cohorts is warranted to confirm the obtained results and the added benefit of TA in risk stratification for patients with pSS.

The Diagnostic Value of MRI-Based Radiomic Analysis of Lacrimal Glands in Patients with Sjögren's Syndrome.

This study aimed to assess the effectiveness of MRI-based texture features of the lacrimal glands (LG) in augmenting the imaging differentiation between primary Sjögren's Syndrome (pSS) affected LG and healthy LG, as well as to emphasize the possible importance of radiomics in pSS early-imaging diagnosis. The MRI examinations of 23 patients diagnosed with pSS and 23 healthy controls were retrospectively included. Texture features of both LG were extracted from a coronal post-contrast T1-weighted sequence, using a dedicated software. The ability of texture features to discriminate between healthy and pSS lacrimal glands was performed through univariate, multivariate, and receiver operating characteristics analysis. Two quantitative textural analysis features, RunLengthNonUniformityNormalized (RLNonUN) and Maximum2DDiameterColumn (Max2DDC), were independent predictors of pSS-affected glands (p < 0.001). Their combined ability was able to identify pSS LG with 91.67% sensitivity and 83.33% specificity. MRI-based texture features have the potential to function as quantitative additional criteria that could increase the diagnostic accuracy of pSS-affected LG.

Do ankle, hindfoot, and heel ultrasound findings predict the symptomatology and quality of life in rheumatoid arthritis patients?

Objectives: To evaluate the ankle, hindfoot, and heel changes (determined by physical examination, ultrasound and baropodometry) in patients with rheumatoid arthritis, to compare the findings with healthy subjects, and to analyze if these findings are associated with ankle pain and could affect the quality of life. Methods: We enrolled 35 rheumatoid arthritis patients and 35 healthy controls, and evaluated their ankles (tibiotalar joints, tendons), hindfeet (talonavicular, subtalar joints) and heels using clinical examination, DAS28-CRP, RAPID3 for the evaluation of functional status, quality of life in rheumatoid arthritis questionnaire, ultrasound, and baropodometry. Results: The ultrasound inter-observer agreement was good for the subtalar joint, and very good for the other structures. Flat foot was identified in 50% of feet in rheumatoid arthritis patients, with 83.8% having concomitant hindfoot valgus and less subtalar joint synovitis visible from the lateral approach (32.4% vs 55.6%, p = 0.041). The body mass index, RAPID3 and subtalar synovitis were independent predictors for the symptomatic ankle (all p <0.05). Midfoot and heel plantar pressures were higher in rheumatoid arthritis patients compared to healthy controls, but when subtalar synovitis was present, the pressures decreased (avoidance of heel support). Poor quality of life in rheumatoid arthritis patients was independently predicted by DAS28-CRP, RAPID3, disease stage, hindfoot valgus, tibiotalar and subtalar synovitis, tendon pathology, Achilles tendon enthesophytes, calcaneal erosions, plantar fasciitis, and perifasciitis (all p <0.05). Conclusion: The quality of life of rheumatoid arthritis patients is significantly affected by ankle and hindfoot pathology (inflammatory modifications, but also degenerative findings and deformities). Ultrasound scanning is an important tool in the evaluation of inflammatory and degenerative lesions in these regions, and their early detection might contribute to a better therapeutic management in these patients.Objectives: To evaluate the ankle, hindfoot, and heel changes (determined by physical examination, ultrasound and baropodometry) in patients with rheumatoid arthritis, to compare the findings with healthy subjects, and to analyze if these findings are associated with ankle pain and could affect the quality of life. Methods: We enrolled 35 rheumatoid arthritis patients and 35 healthy controls, and evaluated their ankles (tibiotalar joints, tendons), hindfeet (talonavicular, subtalar joints) and heels using clinical examination, DAS28-CRP, RAPID3 for the evaluation of functional status, quality of life in rheumatoid arthritis questionnaire, ultrasound, and baropodometry. Results: The ultrasound inter-observer agreement was good for the subtalar joint, and very good for the other structures. Flat foot was identified in 50% of feet in rheumatoid arthritis patients, with 83.8% having concomitant hindfoot valgus and less subtalar joint synovitis visible from the lateral approach (32.4% vs 55.6%, p = 0.041). The body mass index, RAPID3 and subtalar synovitis were independent predictors for the symptomatic ankle (all p <0.05). Midfoot and heel plantar pressures were higher in rheumatoid arthritis patients compared to healthy controls, but when subtalar synovitis was present, the pressures decreased (avoidance of heel support). Poor quality of life in rheumatoid arthritis patients was independently predicted by DAS28-CRP, RAPID3, disease stage, hindfoot valgus, tibiotalar and subtalar synovitis, tendon pathology, Achilles tendon enthesophytes, calcaneal erosions, plantar fasciitis, and perifasciitis (all p <0.05). Conclusion: The quality of life of rheumatoid arthritis patients is significantly affected by ankle and hindfoot pathology (inflammatory modifications, but also degenerative findings and deformities). Ultrasound scanning is an important tool in the evaluation of inflammatory and degenerative lesions in these regions, and their early detection might contribute to a better therapeutic management in these patients.

Combining surface-enhanced Raman scattering (SERS) of saliva and two-dimensional shear wave elastography (2D-SWE) of the parotid glands in the diagnosis of Sjögren's syndrome.

In this study, we combine the molecular structural information gained by SERS of saliva samples with the morphological data given by two-dimensional shear wave elastography (2D-SWE) (SuperSonic Imagine, Aixplorer) of parotid glands in the case of n = 31 patients with Sjögren's syndrome (SjS) and n = 22 controls, with the aim to discriminate between the two groups. The overall classification accuracy yielded by a hybrid principal component analysis-linear discriminant analysis (PCA-LDA) model based on both SERS and elastography (81%) was superior to that yielded by SERS spectra alone (75%) and elastography data alone (71%). This preliminary study is the first report on the use of 2D-SWE of parotid glands for the diagnosis of SjS as well as the first to describe the diagnosis of SjS based on the SERS spectra of dried saliva samples, the results suggesting that the strategy of combining the two methods could improve the diagnosis of SjS.

Shear wave elastography as a new method to identify parotid lymphoma in primary Sjögren Syndrome patients: an observational study.

Parotid non-Hodgkin lymphoma (NHL) in primary Sjögren syndrome (pSS) has no specific biomarker for diagnosis. Salivary glands ultrasound (US) is largely used, but its contribution in detecting parotid NHL has not been established. The aim of our study was to determine the added value of bidimensional shear wave elastography (2D-SWE) in pSS diagnosis and to determine its accuracy in identifying parotid NHL. Grey-scale US (GSUS) and 2D-SWE of salivary glands were performed in 35 patients with pSS and 35 healthy controls. The GSUS scores were calculated and the mean of three SWE consecutive measurements was used to appreciate the gland stiffness. SWE increase the diagnostic rate at a cut-off of 6.45 kPa (from 88.6 to 94.2%, p < 0.001) only if applied in patients with insufficient GSUS criteria for pSS diagnosis. The parotid glands with NHL (8 patients, all mucosa-associated lymphoid tissue type) had hyperechoic bands in more than half of the glandular parenchyma (in 68.75% of the glands), large hypoechoic area > 20 mm (all glands), traced gland area over 5 cm2 (all glands), parotid US score greater than 13 (in 68.75% of the glands), and high stiffness (elasticity modulus 13.9 ± 4.08 vs 6.32 ± 2.24) (all p < 0.001). These findings give high sensitivity (92.3%), specificity (100%), and positive (100%) and negative predictive values (98.3%) for NHL identification. The rest of GSUS findings did not correlate with the classic risk factors for lymphoma development (all p > 0.05). 2D-SWE had added value for pSS diagnosis in cases where GSUS aspect is normal or nonspecific. The higher stiffness of parotid NHL can be used for early diagnosis, biopsy guidance, and, possible, for treatment monitoring.

Reasons for discordances between ultrasonography and magnetic resonance imaging in the evaluation of the ankle, hindfoot and heel of the patients with rheumatoid arthritis.

AIM: To compare the ultrasonography (US) performance with magnetic resonance imaging (MRI) in identifying pathology in ankles, hindfeet and heels of rheumatoid arthritis (RA) patients and to evaluate the reasons for discordances between the two imaging methods. MATERIAL AND METHODS: RA patients were enrolled and evaluated using the Clinical Disease Activity Index (CDAI) and the Disease Activity Score 28 with C-reactive Protein (DAS28-CRP). The ankle (tibiotalar joint, tendons), hindfoot (talonavicular, subtalar joints) and heel of the most symptomatic or dominant foot (for the asymptomatic patient)were evaluated by two pairs of examiners using US and contrast-enhanced MRI. RESULTS: Totally, 105 joints, 245 tendons and 35 heels in 35 patients [mean age 59.2±11.25 years old, median disease duration 36 (16.5-114), mean CDAI 19.87±12.7] were evaluated. The interobserver agreements between the two sonographers, and the two radiologists were good and very good (k=0.624-0.940). The overall agreement between US and MRI was very good for subcalcaneal panniculitis (k=0.928, p<0.001), moderate for synovitis (k=0.463, p<0.001) and tenosynovitis (k=0.514, p<0.001), fair for osteophytes (k=0.260, p=0.004), and poor for erosions (k=0.063, p=0.308) and heel's structures. MRI found more erosions, synovitis, osteophytes,tenosynovitis and retrocalcaneal bursitis, but US found more enthesophytes and plantar fasciitis. Many of the discordancesbetween the two imaging techniques have explanations related to the technique itself or definition of the pathologic findings. CONCLUSIONS: US is comparable to MRI for the evaluation of ankle, hindfoot and heel in RA patients and discordances in theinterpretation of the pathological findings/normal structures must be carefully analyzed.

Multimodal ultrasound investigation (grey scale, Doppler and 2D-SWE) of salivary and lacrimal glands in healthy people and patients with diabetes mellitus and/or obesity, with or without sialosis.

AIM: To evaluate the ultrasound (US) modifications [grey scale, Doppler, 2D-share wave elastography (2D-SWE)] ofsalivary (parotid and submandibular) and lacrimal glands in healthy people and patients with diabetes mellitus and/or obesity, with or without sialosis. MATERIAL AND METHODS: We evaluated 170 patients (1020 glands, 1700 grey scale and Doppler images), split in two groups (group 1- healthy people, group 2- obese and/or diabetes patients, with or without sialosis). For each patient we assessed the parotid, submandibular and lacrimal glands in grey scale US (echogenicity, homogeneity, glandular contour, posterior border, lymph nodes), color Doppler US and 2D-SWE. All images were analyzed by two examiners blinded to each other or to patients. RESULTS: The interobserver agreement was strong or moderate for all parameters. In group 2, the salivary glands had increased echogenicity, homogeneous aspect and invisible posterior border (all p<0.001). There was no significant variation of elasticity modulus in the groups analyzed (5.46±1.57 vs 5.67±1.81 in parotid, 8.63±1.84 vs 8.55±1.94 in submandibular and 9.47±2.1 vs 9.53±2.23 in lacrimal glands, all p>0.05) or according to the body mass index (BMI), sex, patient age, the aspect in grey scale/Doppler US or the presence of sialosis (all p>0.05). CONCLUSION: The main US differences between healthy people and patients with diabetes mellitus and/or obesity are suggested by the echogenicity, homogeneity, posterior border and the size of glandular area. No significant differences of elasticity modulus were found between the analyzed groups or related to BMI, sex, patient age or other grey scale/Doppler US items analyzed.

SERS-based liquid biopsy of saliva and serum from patients with Sjögren's syndrome.

In this preliminary study, we employed surface-enhanced Raman scattering (SERS) of saliva and serum samples for diagnosing Sjogren's syndrome (SjS), a systemic autoimmune disease characterized by dryness of the mouth and eyes. The saliva and serum samples from n = 29 patients with SjS and n = 21 controls were deproteinized with methanol and then the SERS spectra were acquired using silver nanoparticles synthesized by reduction with hydroxylamine hydrochloride. In the case of both saliva and serum, the SERS spectra were dominated by similar bands attributed to purine metabolites such as uric acid, xanthine, and hypoxanthine. Principal component analysis-linear discriminant analysis (PCA-LDA) models built from SERS spectra of saliva and serum yielded an overall classification accuracy of 94% and 98%, respectively. These results suggest that the SERS analysis of saliva and serum is able to capture the complex biochemical perturbations that accompany the onset of SjS, a strategy which could be translated in the future into a novel point-of-care diagnosis method. Graphical abstract.

The relevance of ultrasound examination of the foot and ankle in patients with rheumatoid arthritis - a review of the literature.

Rheumatoid arthritis (RA) is an inflammatory disease characterized by symmetrical involvement of the joints and tendons, especially of the hands and wrists, but also of the feet and ankles from the very beginning of the disease. For the patient, the foot and ankle involvement is equally important as the other joints, since it affects the functionality of the feet and the quality of life of the patients. It is already known that subclinical involvement of the ankles and feet occurs even in patients that are considered in clinical remission, thus they do not need for changes of therapy, but still might benefit from it. In spite of this, theclinicians do not give enough care to the ankle and foot in RA patients, especially if asymptomatic, resulting future deformities, joint damage and feet disability. In order to show the importance of the feet and ankles in RA patients and to demonstrate the indispensable role of ultrasonography (US) for that purpose, at the same time displaying the US abnormalities that should draw our attention, we performed this review of the literature.