MR弹性成像与超声实时剪切波弹性成像评估兔肝纤维化的对比研究

Noninvasive assessment of liver fibrosis staging with MR elastography versus ultrasound real-time shear wave elastography in a rabbit model

目的:比较MR弹性成像(MRE)与超声实时剪切波弹性成像(SWE)评估兔肝纤维化的价值。方法:2020年3月至11月间选取200只健康新西兰大白兔采用随机数表法随机分为对照组(40只)和肝纤维化组(160只)。将四氯化碳(CCl 4)与橄榄油体积比为1∶1配成50%的CCl 4油溶液,肝纤维化组实验兔皮下注射50%CCl 4油溶液。第1~3周每周注射1次,剂量为0.1 ml/kg;第4~6周每周注射1次,剂量为0.2 ml/kg;第7~16周每周注射2次,剂量为0.1 ml/kg。对照组实验兔皮下注射等剂量生理盐水。肝纤维化组及对照组在第4、8、12、16周末采用随机数表法分别随机选取40、10只进行MRE和SWE检查,分别获得肝脏弹性硬度值(LS),记为LS_(MRE)、LS_(SWE)。检查结束后处死实验兔取肝组织进行病理学Scheuer纤维化分期,分为F0~F4组。采用单因素方差分析评价不同肝纤维化分期间LS_(MRE)、LS_(SWE)的差异;LS值与病理分期的相关性分析采用Spearman法;采用受试者操作特征曲线评价LS_(MRE)、LS_(SWE)诊断肝纤维化分期的效能,曲线下面积(AUC)的比较采用Z检验。结果:共162只实验兔纳入研究,其中F0期38只、F1期33只、F2期35只、F3期31只、F4期25只。不同肝纤维化分期间LS_(MRE)、LS_(SWE)总体差异均有统计学意义(F=295.29、102.40,P均<0.001)。LS_(MRE)、LS_(SWE)与肝纤维化分期均呈正相关(r=0.93、0.81,P均<0.001)。LS_(MRE)诊断肝纤维化分期≥F1、≥F2、≥F3、≥F4期的AUC分别为0.955、0.967、0.996、0.980,LS_(SWE)的AUC分别为0.856、0.880、0.974、0.953。LS_(MRE)诊断肝纤维化分期≥F1、≥F2的AUC高于LS_(SWE)(Z=2.93、3.29,P=0.003、0.001),诊断≥F3、≥F4的AUC差异无统计学意义(Z=1.58、1.68,P=0.115、0.093)。结论:MRE及SWE技术均能较为准确地预测实验兔肝纤维化分期,MRE诊断早期肝纤维化的效能优于SWE。

Objective To explore the value of MR elastography(MRE)and shear wave elastography(SWE)for staging liver fibrosis in a rabbit model.Methods From March to November 2020,200 healthy New Zealand white rabbits were randomly divided into control group(n=40)and liver fibrosis group(n=160)by random number table method.The volume ratio of CCl4 and olive oil was 1∶1 to prepare 50%CCl4 oil solution,and the experimental rabbits in the liver fibrosis group were subcutaneously injected with 50%CCl4 olive oil solution.It was injected once a week at the dose of 0.1 ml/kg in the first to third weeks,once a week at the dose of 0.2 ml/kg in the 4th to 6th weeks.The dose of 0.1 ml/kg was injected twice a week from week 7 to 16.The control group were subcutaneously injected with an equal dose of normal saline.At the end of the 4th,8th,12th,and 16th week,40 and 10 animals in the liver fibrosis group and the control group were randomly selected by random number table method for MRE and SWE,respectively,to obtain the liver elastic stiffness(LS),which were recorded as LS_(MRE) and LS_(SWE).After the examination,the experimental rabbits were sacrificed and liver tissue of rabbits were taken for histopathological Scheuer staging,and they were divided into F0-F4 groups.One-way ANOVA was used to evaluate the differences of LS_(MRE) and LS_(SWE) in different stages of liver fibrosis.Spearman correlation was used to analyze the correlation between LS and pathological stages.The receiver operating characteristic curve was used to evaluate the efficacy of LS_(MRE) and LS_(SWE) in diagnosing liver fibrosis staging,and the area under the curve(AUC)was compared using the Z test.Results Totally 162 rabbits were included,which covered F0(n=38),F1(n=33),F2(n=35),F3(n=31)and F4(n=25).Significant differences of LS_(MRE) and LS_(SWE) values were found among different stages of liver fibrosis(F=295.29,102.40,both P<0.001).LS_(MRE),LS_(SWE) were both positively correlated with liver fibrosis stage(r=0.93,0.81,both P<0.001).The AUC of LS_(MRE) for diagnosing liver fibrosis stages≥F1,≥F2,≥F3,and≥F4 were 0.955,0.967,0.996,and 0.980,respectively;the AUC of LS_(SWE) were 0.856,0.880,0.974,and 0.953,respectively.The AUC of liver fibrosis stage≥F1,≥F2 for LS_(MRE) value were greater than LS_(SWE) value(Z=2.93,3.29,P=0.003,0.001),and the AUC of≥F3,≥F4 had no significant differences(Z=1.58,1.68,P=0.115,0.093).Conclusion Both MRE and SWE can accurately predict the stage of liver fibrosis in experimental rabbits,and MRE is better than SWE in diagnosing early liver fibrosis.