|Table of Contents|

Dynamic evaluation of inflammation activity in rheumatoid arthritis rabbits using contrast-enhanced ultrasound



Research Field:
Publishing date:



Dynamic evaluation of inflammation activity in rheumatoid arthritis rabbits using contrast-enhanced ultrasound


WU Changjie WANG Yahui HUA Xing GUO Yanli TENG Yongliang LIU Xueting

Department of Ultrasonography, First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038; Department of Pathology, First Affiliated Hospital, Jilin University, Changchun, Jilin Province, 130000; 3Dalian Sanatorium of Shenyang Military Command, Dalian, Liaoning Province, 116000, China


rheumatoid arthritis contrast-enhanced ultrasound inflammation activity ultrasound examination

R364.5; R445.1; R593.22

Objective    To evaluate the value of contrast-enhanced ultrasound (CEUS) in the dynamic detection of inflammation activity in rabbit model of rheumatoid arthritis (RA). Methods   A total of 24 rabbits (both sexes, 6 months old, weighing 3.0~3.5 kg) were used to establish RA model via ovalbumin sensitization in 48 knee joints. The rabbits were divided into 4 groups, that is, control (pre-modeling), M1 (1 week post induction), M4 (4 weeks post induction) and M8 (8 weeks post induction) groups, with 12 knees in each group. Ultrasound examination including grey scale ultrasonography and power Doppler imaging (PDI) was performed in both femorotibial joints of each rabbit to measure the synovial thickness and semi-quantitatively score (0~3). CEUS was subsequently performed to evaluate the enhancement of synovium. Time-intensity curve (TIC) was drawn with automatic fitting, and the data including peak intensity (PI), peak time (PT), area under curve (AUC) and half time of descending (T1/2) were determined automatically. All the rats were killed, and the synovial tissues were collected for pathological examination. The synovial vascular bed area index was calculated in each group, and the results were compared. The correlations between ultrasonic data and pathologic data were analyzed. Results    Ultrasonographic results showed that the thickness of femorotibial synovium was increased with modeling time, with significant differences among groups (P<0.01). There was a significant difference in PDI score between the M4 and M8 groups (P<0.05). A positive correlation was found between synovial thickness and pathologic score (r=0.887, P<0.01). Positive rate of CEUS was higher than that of PDI in both the M4 and M8 groups (8/12 vs 3/12, 12/12 vs 10/12). Among the TIC data, the values of PI and AUC in the synovial tissues were lower than those of surrounding fat tissues (P<0.01). There were positive correlations of the PI value, AUC value and PDI score of the synovial tissue with synovial vascular bed area index (r1=0.664, P<0.01; r2=0.711, P<0.01; r3=0.483, P<0.05). Conclusion    Grey scale ultrasonography can reflect the pathological changes of synovitis. CEUS is more sensitive than PDI in reflecting the formation of early angiogenesis in the synovium, and is valuable in the early dynamic detection of inflammation activity in RA.


[1]ELSHABRAWY H A,CHEN Z,VOLIN M V,et al. The pathogenic role of angiogenesis in rheumatoid arthritis[J]. Angiogenesis,2015,18(4):433-448.DOI:10.1007/s1045601594772.
[2]华兴. 肌骨超声的应用现状与发展趋势[J]. 第三军医大学学报,2015,37(20):2005-2010.DOI:10.16016/j.10005404.201507183.
HUA X. Application status and development tendency of musculoskeletal ultrasound[J]. J Third Mil Med Univ,2015, 37(20): 2005-2010. DOI:10.16016/j.10005404.201507183.
[3]华兴,邹庆华,方勇飞,等. 小关节超声整体评分系统在类风湿关节炎疗效评价中的应用[J]. 临床超声医学杂志,2016,18(8): 512-516.DOI:10.16245/j.cnki.issn10086978.2016.08.004.
HUA X,ZOU Q H,FANG Y F,et al. Value of therapeutic effect evaluation on rheumatoid arthritis for small joints by ultrasonic global scoring system[J].J Clin Ultrasound Med, 2016,18(8):512-516. DOI:10.16245/j.cnki.issn10086978.2016.08.004.
[4]LIU P, WANG X, ZHOU S, et al. Effects of a novel ultrasound contrast agent with long persistence on right ventricular pressure: Comparison with SonoVue[J]. Ultrasonics,2011, 51(2):210-214.DOI:10.1016/j.ultras.2010.07.008.
[5]DUMONDE D C, GLYNN L E. The production of arthritis in rabbits by an immunological reaction to fibrin[J]. Br J Exp Pathol, 1962,43: 373-383.
[6]SZKUDLAREK M, COURTPAYEN M,JACOBSEN S,et al.Interobserver agreement in ultrasonography of the finger and toe joints in rheumatoid arthritis[J]. Arthritis Rheum,2003,48(4): 955-962. DOI: 10.1002/art.10877.
[7]AOKI S,MITSUI T. Histological features of rheumatoid arthritis patients having antibodies to enterobacterial common antigens: correlation of antibody levels with semiquantitative histologic scores and laboratory markers[J]. Clin Exp Rheumatol,2005,23(1): 13-18.
[8]FIRESTEIN G S,MCINNES I B. Immunopathogenesis of rheumatoid arthritis[J]. Immunity,2017,46(2): 183-196. DOI: 10.1016/j.immuni.2017.02.006.
[9]KIM S J. Angiogenesis in rheumatoid arthritis is fostered directly by tolllike receptor 5 ligation and indirectly through interleukin17 induction[J]. Arthritis Rheum, 2013,65(8): 20242-20236. DOI: 10.1002/art.37992.
[10]SU C M,HUANG C Y,TANG C H. Characteristics of resistin in rheumatoid arthritis angiogenesis[J]. Biomark Med,2016,10(6): 651-660. DOI: 10.2217/bmm.15.125.
[11]SMITH M D, WEEDON H, PAPANGELIS V, et al.Apoptosis in the rheumatoid arthritis synovial membrane:modulation by diseasemodifying antirheumatic drug treatment[J]. Rheumatology(Oxford), 2010,49(5): 862-875. DOI: 10.1093/rheumatology/kep467.
[12]FREESTON J E,COATES L C,MOVERLEY A R,et al.Is there subclinical synovitis in early psoriatic arthritis? A clinical comparison with grayscale and power Doppler ultrasound[J]. Arthritis Care Res (Hoboken), 2014, 66(3): 432-439. DOI: 10.1002/acr.22158.
[13]BROWN A K. Using ultrasonography to facilitate best practice in diagnosis and management of RA[J]. Nat Rev Rheumatol, 2009,5(12): 698-706. DOI: 10.1038/nrrheum.2009.227.
[14]GORAI M,OGASAWARA M,MATSUKI Y, et al. Weighting with the Lansbury articular index improves the correlation of ultrasound score with serum matrix metalloproteinase3 level in rheumatoid arthritis patients[J]. Mod Rheumatol,2014,24(6): 915-919. DOI: 10.3109/14397595.2014.888794.
[15]JO P C,JANG H J,BURNS P N,et al.Integration of contrastenhanced US into a multimodality approach to imaging of nodules in a cirrhotic liver: how I do it[J]. Radiology,2017,282(2): 317-331. DOI: 10.1148/radiol.2016151732.


Last Update: 2018-06-14