超声造影定量分析大鼠肝急性移植物抗宿主病的实验研究  

Contrast-enhanced ultrasonography quantitative analysis for diagnosis of hepatic acute graft-versus-host disease in rats:an experimental study

作　　者：刘逸群[1] 朱家安[1] 熊钰 辛雨薇 曲琳琳 杨力[1] 李文雪 田辉[1] Liu Yiqun;Zhu Jia'an;Xiong Yu;Xin Yuwei;Qu Linlin;Yang Li;Li Wenxue;Tian Hui(Peking University People's Hospital,Beijing 100044,China)

机构地区：[1]北京大学人民医院超声医学科,100044

出　　处：《中华医学超声杂志（电子版）》2024年第1期75-81,共7页Chinese Journal of Medical Ultrasound(Electronic Edition)

基　　金：多模态超声成像技术在造血干细胞移植后肝窦阻塞综合症早期诊断预警研究,北京大学人民医院院内基础培育项目(RDJP2022-64)。

摘　　要：目的探讨超声造影技术定量参数在评价肝急性移植物抗宿主病(aGVHD)中的诊断价值。方法健康雌性Wistar大鼠42只,随机选取6只作为对照组,余36只作为移植受体,10只Fischer 344大鼠作为供体,进行骨髓移植,以建立aGVHD模型。术后每周随机抽取6只大鼠,进行临床观察并评分;进行超声造影检查观察肝实质血流灌注情况并脱机分析时间-强度曲线(TIC),得出峰值强度(PI)、达峰时间(TTP)、平均渡越时间(MTT)超声造影定量指标。检查结束后处死大鼠取肝标本进行病理诊断并评分。采用H检验比较对照组、未发生aGVHD组(nGVHD组)及aGVHD组间临床评分、超声造影各参数的差异,分析aGVHD组不同病程[依据病理严重程度分为:轻度组(病理2级)、中度组(病理3级)和重度组(病理4级)]超声造影定量参数的变化情况。采用Spearman检验分析临床评分、TIC参数与病理评分的相关性。将临床评分、超声造影定量参数纳入二元Logistic回归分析得出整体预测参数,绘制受试者操作特征(ROC)曲线,并采用Delong检验与临床评分和超声造影参数对肝aGVHD的诊断效能进行比较。结果aGVHD组大鼠(24只)的PI降低、TTP及MTT增高,与对照组和nGVHD组相比差异均具有统计学意义(P均<0.05)。重度组MTT高于轻度组[(135.21±27.71)s vs(84.37±25.26)s],差异具有统计学意义(P=0.020)。PI、MTT与病理评分有高度相关性(r=-0.790、0.733,P均<0.001),TTP与病理学评分呈中度相关性(r=0.489,P=0.001)。临床评分、超声造影参数、整体参数诊断aGVHD的ROC曲线下面积(AUC)分别为0.698、0.885、0.910,根据ROC曲线分析,其敏感度分别为79.2%、87.5%、91.7%,特异度分别为75.0%、83.3%、83.3%。超声造影参数和整体预测参数的诊断效能高于临床评分(Z=2.290,P=0.022;Z=2.412,P=0.016)。结论超声造影定量参数为肝aGVHD的诊断提供形态学依据,有望成为评估肝aGVHD影像学新方法。Objective To investigate the diagnostic value of real-time contrast-enhanced ultrasound(CEUS)quantitative parameters for assessment of liver graft‐versus‐host disease(aGVHD).Methods A total of 42 Wistar rats were included in the present study.Six rats were randomly selected as controls,and the remaining 36 rats were used as recipients.Ten Fischer 344 rats were included as donors.Bone marrow transplantation was performed to establish an aGVHD model.Six rats were randomly selected every week after surgery.Clinical scoring and ultrasonic examination were performed to obtain time-intensity curve(TIC)parameters[peak intensity(PI),time to peak(PPT),and mean transit time(MTT)].Specimens were collected at the end of the examination and subjected to pathological diagnosis and scoring.The differences of clinical scores and TIC parameters among the control group,the group without aGVHD(nGVHD),and the aGVHD group were compared by the Kruskal-Wallis H test.According to the severity of pathology,rats in the aGVHD group were divided into mild(pathology level 2),moderate(pathology level 3),and severe(pathology level 4)groups.TIC parameters among different stage of aGVHD were analyzed.The correlation of clinical scores and TIC parameters with pathological scores was calculated by the Spearman test.Each TIC parameter and clinical scores were included in the binary Logistic regression analysis to obtain the joint prediction parameters,which were compared with the clinical indicators with regard to the diagnosis of liver aGVHD.Then,the receiver operating characteristic(ROC)curve was plotted.Clinical scores and contrast-enhanced ultrasound parameters in the diagnosis of liver aGVHD were compared by the Delong test.Results Compared with the other two groups,PI was decreased,and TTP and MTT were increased in the aGVHD group(n=24;P<0.05).MTT had good ability to distinguish mild and severe aGVHD[(135.21±27.71)s vs(84.37±25.26)s].There was a high correlation between PT and MTT and pathological scores(r=-0.790 and 0.733,respectively)

关 键 词：肝 移植物抗宿主病 超声造影 动物模型 

分 类 号：R445.1[医药卫生—影像医学与核医学] R575[医药卫生—诊断学]