Utilization of longitudinal ultrasound measurements to quantify changes in knee joint synovial vascularity in a rabbit model of rheumatoid arthritis

2020 ◽  
Author(s):  
Hui Liu ◽  
Chao Huang ◽  
Shuqiang Chen ◽  
Qing Zheng ◽  
Yuhong Ye ◽  
...  

Abstract Objective: This study of rabbits with ovalbumin-induced arthritis (OIA), a model of rheumatoid arthritis (RA), examined the time course of changes in synovial neovascularization based on imaging from power Doppler ultrasound (PDUS) and contrast-enhanced ultrasound (CEUS).Methods: 25 male New Zealand rabbits were in the OIA group and 5 were in the control group. Both rear knee joints of all rabbits were examined using conventional US and CEUS over 16 weeks. The knee synovia of OIA rabbits were sampled by US-guided biopsy, and the expression of CD31 and VEGF were determined by immunohistochemistry. The correlation of microvessel density (CD31 positivity) and VEGF at different times was analyzed using multimodal US.Results: OIA rabbits had increased synovial expression of CD31 and VEGF from week 6 to 12 (P<0.01). During the early stage of CEUS enhancement, dot enhancement was more common on weeks 6 and 8, and strip enhancement was more common on weeks 12 and 16 (P<0.05). There were significant positive correlations of synovial CD31 and VEGF expression with PDI grade, CEUS grade, and peak intensity (PI) (P<0.05 for all).Conclusions: OIA rabbits mimicked early-stage RA at 4 to 8 weeks, middle-stage RA at 8 to 12 weeks, and late-stage RA at 12 to 16 weeks. PDI, CEUS, and PI, especially when combined with CD31 expression, accurately characterized the extent of synovial vascularization. Increased vascular morphology based on CEUS may have value for the early diagnosis of RA.

2019 ◽  
Vol 47 (11) ◽  
pp. 5740-5751 ◽  
Author(s):  
Hui Liu ◽  
Chao Huang ◽  
Shuqiang Chen ◽  
Qing Zheng ◽  
Yuhong Ye ◽  
...  

Objective This study aimed to examine the associations between contrast-enhanced ultrasound (CEUS) imaging and synovial hypervascularity and synovitis score in a rabbit model of antigen-induced arthritis (AIA), compared with power Doppler ultrasound (PDUS). Methods We investigated 50 knee joints in 25 AIA rabbits (AIA group), and 10 knee joints in five sham-injected rabbits (control group). PDUS and CEUS images were evaluated at the 8th week. Ultrasound-guided synovial biopsies were targeted in the area with hypervascularity, and synovial microvessel density (MVD) was evaluated by immunohistochemical staining of CD31. Results The PDUS score was significantly higher in the AIA group (2.61 ± 0.78) compared with the control group (0.50 ± 0.53). CEUS in the AIA group revealed a fast-in/slow-out pattern of contrast enhancement. MVD revealed by CD31+ vessel count and the synovitis score were significantly higher in the AIA group compared with the control group. In the AIA group, CEUS findings showed a better correlation with MVD revealed by CD31+ and synovitis score than PDUS findings. Conclusion CEUS is superior to PDUS for estimating synovial hypervascularity and hyperplasia in experimental rheumatoid arthritis.


2018 ◽  
Vol 45 (04) ◽  
pp. 341-347
Author(s):  
Zahraa Ibrahim Selim ◽  
Eman H El-Hakeim ◽  
Eman Ahmed Hamed Omran ◽  
Naglaa K. Idriss ◽  
Marwa A. Gaber ◽  
...  

Abstract Introduction Rheumatoid arthritis (RA) is an autoimmune disease that affects multiple joints causing joint destruction. KIAA1199 is a novel angiogenic biomarker derived from fibroblast-like synoviocytes (FLS) it has a role in acceleration and proliferation of FLS and activation of angiogenic signaling pathways leading to erosion of cartilage and bone. Musculoskeletal ultrasound (MUSU) and Power Doppler (PDUS) directly visualizing the synovial membrane vessels, which is important in providing very early information on the changes in synovitis activity during the course of the inflammatory joint disease Objective To assess the serum level of angiogenic biomarker KIAA1199 in RA patients and its correlation with MSUS, PDUS findings, and the disease activity Patients and methods: Fifty RA patients and 40 healthy control persons age and sex-matched were recruited in this study, KIAA1199 was assessed in the serum of patients and controls, MSUS and PDUS were done for the wrist, elbow, and knee joints for all RA patients Results Serum KIAA1199 level was significantly higher among RA patients 4.36±1.22 ng/dl compared to control group 2.87±0.51 ng/dl (p<0.001). There was a highly significant correlation between KIAA1199 level and DAS28 (p=0.004), and there was a significant correlation between the PDUS with KIAA1199 level and DAS28 (p=0.001, 0.002 respectively) in wrist joints Conclusion KIAA1199 is a new pathway that enhancing cell proliferation and angiogenesis. Serum KIAA1199 level may be a useful biomarker for RA activity, and therapeutic target in RA. PDUS correlates significantly with clinical findings and novel angiogenic biomarker in RA patients.


2021 ◽  
pp. 153537022110271
Author(s):  
Yuanyuan Jia ◽  
Liuqin Xie ◽  
Zhenglong Tang ◽  
Dongxiang Wang ◽  
Yun Hu ◽  
...  

After high fractures of the mandibular condyle, the insufficient blood supply to the condyle often leads to poor bone and cartilage repair ability and poor clinical outcome. Parathyroid hormone (PTH) can promote the bone formation and mineralization of mandibular fracture, but its effects on cartilage healing after the free reduction and internal fixation of high fractures of the mandibular condyle are unknown. In this study, a rabbit model of free reduction and internal fixation of high fractures of the mandibular condyle was established, and the effects and mechanisms of PTH on condylar cartilage healing were explored. Forty-eight specific-pathogen-free (SPF) grade rabbits were randomly divided into two groups. In the experimental group, PTH was injected subcutaneously at 20 µg/kg (PTH (1–34)) every other day, and in the control group, PTH was replaced with 1 ml saline. The healing cartilages were assessed at postoperative days 7, 14, 21, and 28. Observation of gross specimens, hematoxylin eosin staining and Safranin O/fast green staining found that every-other-day subcutaneous injection of PTH at 20 µg/kg promoted healing of condylar cartilage and subchondral osteogenesis in the fracture site. Immunohistochemistry and polymerase chain reaction showed that PTH significantly upregulated the chondrogenic genes Sox9 and Col2a1 in the cartilage fracture site within 7–21 postoperative days in the experimental group than those in the control group, while it downregulated the cartilage inflammation gene matrix metalloproteinase-13 and chondrocyte terminal differentiation gene ColX. In summary, exogenous PTH can stimulate the formation of cartilage matrix by triggering Sox9 expression at the early stage of cartilage healing, and it provides a potential therapeutic protocol for high fractures of the mandibular condyle.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 985.1-985
Author(s):  
K. Triantafyllias ◽  
S. Liverakos ◽  
C. Noack ◽  
A. Schwarting

Background:Valid assessment of disease activity leads to improvement of long-term outcomes in patients with inflammatory arthritis (1). Optical spectral transmission (OST) is a modern diagnostic tool able to assess the blood-specific absorption of light transmitted through a tissue, promising quantification of inflammation in the finger and wrist joints of patients with rheumatoid arthritis (RA) (commercial device: HandScan – Demcon/Hemics, The Netherlands) (2). Even though an increasing number of studies have evaluated diagnostic value of this new technology in RA patients (2,3), no data exist regarding psoriatic arthritis (PsA).Objectives:To examine for the first time the diagnostic value of OST in detecting inflammation in patients with PsA and to evaluate its relationship with disease activity markers and various epidemiological and anthropometric patient characteristics.Methods:OST-Measurements were performed in a group of PsA patients and a group of healthy controls. The difference between OST in the two groups was statistically examined and relationships of OST with clinical (tender / swollen joint counts, disease activity on a visual analogue scale) and serological disease activity markers were evaluated. Moreover, joint ultrasound (US) examinations were performed in a subgroup of PsA patients and OST associations with a Power Doppler- and a Grey Scale-US score were examined. Finally, relationships of OST with various anthropometric and epidemiologic parameters (BMI, hand-size, gender, age) were assessed.Results:We recruited 49 PsA patients [65.3% female; mean age 53.3 years (± 11.8 SD)] and 114 control subjects [77.2% female; mean age 46 years (± 12.8 SD)]. OST was statistically significantly higher in the patient group, compared to the control group [14.95 (12.04 - 17.18, IQR) vs. 10.31 (7.84 – 13.79, IQR); p<0.001]. OST correlated moderately-strongly with both examined US scores (Power Doppler-score: r = 0.5; p = 0.026 and Grey Scale-score: r = 0.52; p = 0.028). Moreover, OST showed a moderate, statistically significant association with C-reactive protein (CRP) (r = 0,298; p = 0,037). Finally, males had significantly higher OST values than females and OST associated moderately-weakly with body mass index (BMI) in the control group (rho = 0.24; p< 0.001).Conclusion:This is the first report of a possible diagnostic value of OST in patients with PsA. OST correlated with ultrasound and serological activity markers and may thus prove to be a useful tool of disease activity assessment, next to well established diagnostic modalities, such as the joint US. Correlations of OST with patient characteristics implicate the need to take also anthropometric and epidemiological patient characteristics into account when interprenting OST results in order to avoid confounding.References:[1]Katchamart W, et al. Systematic monitoring of disease activity using an outcome measure improves outcomes in rheumatoid arthritis. J Rheumatol 2010;37:1411–1415.[2]Triantafyllias, et al. Diagnostic value of optical spectral transmission in rheumatoid arthritis: associations with clinical characteristics and comparison with joint ultrasonography. J Rheumatol 2020 1;47(9):1314-1322.[3]Onna M Van, et al. Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique. Ann Rheum Dis 2016;75:511–518.Disclosure of Interests:Konstantinos Triantafyllias Speakers bureau: Pfizer, Novartis, Janssen, Chugai, Stefanie Liverakos: None declared, Claudia Noack: None declared, Andreas Schwarting: None declared


2015 ◽  
Vol 24 (3) ◽  
pp. 132-140
Author(s):  
Maria-Magdalena Tamas ◽  
◽  
Nicolae Rednic ◽  
Simon Siao-Pin ◽  
Simona Rednic ◽  
...  

The diagnosis of rheumatoid arthritis (RA) is, most often, challenging, due to the variety of clinical features and to the absence of gold standard tests for diagnosing this disease. Early diagnosis as well as the identification of poor prognostic markers will lead to an early, appropriate treatment that will prevent the evolution towards a severe disease, offering the chance for a complete remission. Ultrasonography (US), used as an extension of clinical examination, helps in the early classification of the disease. Power Doppler is important for quantification of synovial inflammation, both at diagnosis and during therapy monitoring, but has limits in detecting blood flow in small vessels. Ultrasound contrast-agents improve visualization of vascularity and allow a better characterization and quantification of synovial pannus inflammation. We aim to discuss the role of contrast-enhanced ultrasonography (CEUS) in the diagnosis and follow-up of early RA.


VASA ◽  
2012 ◽  
Vol 41 (5) ◽  
pp. 353-359 ◽  
Author(s):  
Ahmad ◽  
Garg ◽  
Dhar ◽  
Srivastava ◽  
Biswas ◽  
...  

Background: Atherosclerosis is emerging as an important complication of rheumatoid arthritis (RA), with coronary artery disease being projected as the major cause of mortality in these patients.This study was undertaken to evaluate the presence of subclinical atherosclerosis and to identify the risk factors of atherosclerosis in patients with RA. Patients and methods: All consecutive in- and out-patients of rheumatoid arthritis (n = 100) irrespective of the disease duration were included in the study. A group of 100 age and sex matched controls were also studied. Increased carotid intima media thickness (beyond the 75th percentile for age and sex), presence of plaques, ankle brachial pressure index and QT dispersion were deemed as non-invasive measures of atherosclerotic burden. Results: Fifty patients (50.0 %) with RA had evidence of subclinical atherosclerosis as compared to the control group (n = 11, 11 %); plaques were observed in 26 patients. Eighteen (36 %) of these developed this evidence within 1 - 5 years of disease onset. Low HDL levels among the conventional risk factors and advanced patient age, longer disease duration, greater number of involved joint areas, steroid use and indices of inflammation in particular in RA, were associated with subclinical atherosclerosis. Sustained inflammation was observed throughout the sub-group with atherosclerosis irrespective of the disease duration. Conclusions: RA is a pro-atherogenic state with the process of atherosclerosis initiated in the early stage of the disease. Besides the traditional risk factors, sustained inflammation contributes to atherogenesis.


2015 ◽  
Vol 51 (2) ◽  
pp. 97-104
Author(s):  
Agnieszka Gala-Błądzińska ◽  
Agnieszka Żyłka ◽  
Katarzyna Rybak ◽  
Paulina Dumnicka ◽  
Marek Kuźniewski ◽  
...  

The aim of the study was to assess the usefulness of measuring concentrations of NGAL in first morning urine and calculating NGAL/creatinine ratio (uNGAL/uCr) among patients with early stage diabetic kidney disease (DKD) in course of type 2 diabetes (DMt2) and to assess the correlations between these markers and routine biochemical and blood count parameters. Material and Methods: The studied group consisted of 55 patients with DKD in course of DMt2 and 22 controls without diabetes; the study included patients with estimated glomerular filtration rate >60ml/min/1,73m2 without overt proteinuria. NGAL was measured with chemiluminescence microparticle immunoassay (CMIA) with ARCHITECT analyzer (Abbott Diagnostics). Results: Studied group had higher values of uNGAL/uCr than controls (median 21.3 vs. 12.2 μg/g; p=0.014). Among studied group, women presented higher uNGAL/uCr comparing to men (38.6 vs. 11.7 μg/g; p=0.001). Both in patients and controls, uNGAL concentrations were positively correlated with urine creatinine. In studied group, we observed positive correlations of uNGAL and uNGAL/uCr with urine albumin and albumin/creatinine retaio (UACR); in control group, only the correlation between uNGAL and albuminuria was statistically significant. Additionally, in studied group, positive correlations were observed between uNGAL and uNGAL/uCr and serum cholesterol, LDL-cholesterol and triglycerides concentrations. In multiple regression, albuminuria and LDL-cholesterol significantly predicted uNGAL and UACR and triglycerides significantly predicted uNGAL/uCr in the studied group. Conclusions: The obtained results confirm the usefulness of measuring uNGAL and calculating uNGAL/uCr as early markers of kidney dysfunction in patients with DMt2. The results of the study should be confirmed in larger group of patients.


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