超声造影动态评价兔类风湿关节炎模型炎症活动性的价值
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摘要
目的探讨超声造影(contrast-enhanced ultrasound,CEUS)动态检测兔类风湿关节炎(rheumatoid arthritis,RA)模型炎症活动度的价值。方法 6月龄兔24只,雌雄不拘,体质量3~3.5 kg,以卵蛋白法建立膝关节RA模型,共48例,按建模时间分为建模前(对照组)、诱导1周(M1组)、诱导4周(M4组)和诱导8周(M8组),每组12例。对双膝股胫关节行高分辨二维超声与能量多普勒超声成像(power Doppler imaging,PDI),测量滑膜厚度,对PDI血流信号进行视觉半定量评分(0~3分)。随后行CEUS检查,观察滑膜增强情况,仪器自动拟合时间强度曲线(time-intensity curve,TIC),测量峰值强度(peak intensity,PI)、达峰时间(peak time,PT)、曲线下面积(area under curve,AUC)、峰值强度减半时间(T_(1/2))等数值。采集滑膜标本计算滑膜血管面积指数,比较组间各项指标的差异,并对超声指标与滑膜病理指标进行相关性分析。结果随着建模时间增长,超声测得兔股胫关节滑膜厚度逐渐增加,组间差异有统计学意义(P<0.01),M4组和M8组PDI评分差异有统计学意义(P<0.05)。滑膜厚度与滑膜炎病理评分呈正相关(r=0.887,P<0.01)。M4组与M8组中,CEUS阳性比例高于PDI(8/12 vs3/12;12/12 vs 10/12)。TIC参数中,滑膜PI值和AUC值均显著低于周边组织(P<0.01);PI值、AUC值及PDI评分与滑膜血管面积指数呈正相关(r_1=0.664,P<0.01;r_2=0.711,P<0.01;r_3=0.483,P<0.05)。结论灰阶超声检测滑膜厚度能反映滑膜炎病理改变的程度,CEUS较PDI能更敏感地反映滑膜炎新生血管的形成,能早期动态检测RA滑膜炎的活动性。
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 semiquantitatively 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( T_(1/2)) 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( r_1= 0. 664,P < 0. 01; r_2= 0. 711,P < 0. 01; r_3= 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.
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 semiquantitatively 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( T_(1/2)) 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( r_1= 0. 664,P < 0. 01; r_2= 0. 711,P < 0. 01; r_3= 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.
引文
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[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.
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[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 contrastenhanced 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.
[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 Sono Vue[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 contrastenhanced 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.