Abstract: Background　Hepatic fibrosis is a precancerous lesion of cirrhosis and hepatocellular carcinoma.Early treatment can delay the progress of fibrosis.At present，the main diagnostic methods of liver fibrosis include liver biopsy and serological markers，but each method has its own defects.Objective　To evaluate the accuracy of acoustic radiation force impulse imaging（ARFI） in the determination of liver fibrosis severity in a rabbit model of liver fibrosis.Methods　This experiment was conducted between April and October 2015.A total of 44 healthy New Zealand rabbits were selected and randomly divided into 2 groups，36 for the experimental group，and 8 for control group.The experimental group were subcutaneously injected with CCl4 with the initial dose of 0.3ml/kg，0.4ml/kg from the 4th week，and 0.5ml/kg from the fifth week，which was also the maintenance dose till the end of 16-week intervention.The control group received the same amount of normal saline.At the 4th，6th，8th，10th，12th，14th，16th weeks of intervention，3-6 rabbits in the experimental group were randomly selected to be examined by ARFI technology in vitro and in vivo liver tissue to obtain the stiffness parameters of transverse shear wave velocity（SWV，SWV1），respectively.After each examination，the rabbits were killed by air embolization，and.liver tissues were sampled.H&E and Masson's trichrome staining were used to determine the pathological stage of liver fibrosis.The diagnostic efficiency of the ARFI in liver fibrosis stages was evaluated according to the area under the curve（AUC） of the receiver operating characteristic curve（ROC）．Results　By the 16th week of intervention，the rabbit liver fibrosis models were successfully established at different stages.Pathological examination showed that the control group had normal results and there was no fibrosis.In the experimental group，rabbit models were successfully established in all cases except 4 deaths（6 in stage F1，10 in stage F2，8 in stage F3 and 8 in stage F4）．The rate of successful models was 88.9%（32/36）．The SWV and SWV1 of the control group were less than those of the rabbits with stage F1-F4 fibrosis in the experimental group（P<0.05）．In the experimental group，the SWV and SWV1 successively increased with the severity of liver fibrosis（P<0.05）．SWV1 was greater than SWV either in rabbits of the control group or in rabbits with stage F1-F4 fibrosis in the experimental group（P<0.05）．The AUC of SWV for the diagnosis of stage ≥F2，≥F3，F4 liver fibrosis were 0.901，0.939，0.945，respectively（P<0.001）．When the cut-off points of SWV were selected as 2.21m/s，2.29 m/s，2.36 m/s，the sensitivity were 80.8%，87.5%，87.5% and the specificity were 83.3%，87.5%，79.3%，respectively.The AUC of SWV1 in diagnosing stage ≥F2，≥F3，F4 liver fibrosis were 0.901，0.901，0.958，respectively（P<0.001）．When the cut-off points of SWV1 were selected as 2.58 m/s，2.92 m/s，3.26 m/s，the sensitivity were 80.8%，81.3%，87.5%，and the specificity were 83.3%，87.5%，95.8%，respectively.Conclusion　 ARFI may be used as an effective tool for the evaluation of liver fibrosis severity in rabbits.The AUC of ARFI parameters，SWV and SWV1，in the determination of liver fibrosis in rabbits was larger than 0.9，indicating high accuracy，so they may be used for the evaluation of liver fibrosis severity.

Key words: Liver cirrhosis；Models, animal；Rabbits；Elasticity imaging techniques；Diagnosis

摘要： 背景　肝纤维化是肝硬化、肝细胞癌的前期病变，早期治疗可以延缓肝纤维化的进展速度。目前肝纤维化程度的诊断方法主要有肝穿刺活检术、血清学标志物等，但各诊断方法又各有其缺陷。目的　通过建立兔肝纤维化模型，探讨应用声脉冲辐射力弹性成像（ARFI）技术评估兔肝纤维化程度的诊断价值。方法　2015年4—10月选用健康新西兰大白兔44只，随机选取36只为实验组，8只为对照组。实验组给予皮下注射四氯化碳（CCl4）16周建立兔肝纤维化模型，起始剂量为0.3 ml/kg，剂量递增，第4周剂量为0.4 ml/kg，第5周后剂量为0.5 ml/kg；对照组给予相同剂量0.9%氯化钠溶液。分别于造模第4、6、8、10、12、14、16周随机选取实验组3~6只，对照组1~2只，应用ARFI检查活体、离体兔肝横向剪切波速度（SWV、SWV1）。每次检查完成后采用空气栓塞法处死兔并取兔肝组织先行苏木素-伊红（HE）染色，而后行Masson 染色，确定兔肝纤维化病理分期，采用受试者工作特征曲线（ROC曲线）及ROC曲线下面积（AUC）评价ARFI评估肝纤维化分级的诊断价值。结果　至造模第16周时，成功建立各分期的兔肝纤维化模型。病理检查结果示：对照组兔肝脏病理学检查均正常，无纤维化；实验组36只兔最终死亡4只，造模成功32只（肝纤维化分期为F1期6只、F2期10只、F3期8只、F4期8只），造模成功率为88.9%（32/36）。实验组F1~F4期的SWV、SWV1大于对照组，实验组F2~F4期的SWV、SWV1大于实验组F1期，实验组F3~F4期的SWV、SWV1大于实验组F2期，实验组F4期SWV1大于实验组F3期（P<0.05）；对照组及实验组F1~F4期SWV1均大于SWV（P<0.05）。通过ROC曲线分析，SWV诊断肝纤维化≥F2期、≥F3期、F4期的AUC分别为0.901、0.939、0.945（P均<0.001），截断值分别为2.21、2.29、2.36 m/s，灵敏度分别为80.8%、87.5%、87.5%，特异度分别为83.3%、87.5%、79.3%；SWV1诊断肝纤维化≥F2期、≥F3期、F4期的AUC分别为0.901、0.901、0.958（P均<0.001），截断值分别为2.58、2.92、3.26 m/s，灵敏度分别为80.8%、81.3%、87.5%，特异度分别为83.3%、87.5%、95.8%。结论　采用ARFI检查的SWV、SWV1可用于评估肝纤维化程度，SWV、SWV1诊断兔肝纤维化程度各期的AUC均大于0.9，具有较好的诊断效能。

关键词: 肝硬化；模型, 动物；兔；弹性成像技术；诊断