家兔肝纤维化模型的建立及三维全肝动态磁共振灌注成像对纤维化分期的量化价值

目的 探索家兔肝纤维化模型的建立方法,评价三维全肝动态磁共振灌注成像对肝纤维化分期量化研究的可行性及价值. 方法分别用5%CCl4油溶液和纯CCl4,按0.1 ml/kg剂量每周1次腹腔注射,并于6、8、10、12周分组行磁共振灌注成像检查,量化分析门静脉和肝实质的峰值时刻、达峰时间、信号上升最大斜率和最大相对信号增加率的变化规律并与病理结果对照.不同浓度CCl4造模对比采用卡方检验;实验组灌注参数的多组问比较采用单因素方差分析,组间两两比较采用最小显著差法. 结果 5%CCl4h浓度组和纯CCl4组成模率分别为40%和75%,两组家兔死亡率差异有统计学意义(χ2=5.013,P<0.05).31只家兔均顺利完成磁共振灌注成像检查,肝脏灌注的基线平稳,均得到了较满意的时间-信号强度曲线.随着肝纤维化程度的加重,门静脉和肝实质的峰值时刻南SO期的(22.62±1.80)s和(29.04±0.60)s上升至S4期的(39.84±0.44)s和(45.44±1.95)s;达峰时间由(11.06±0.92)S和(13.19±1.06)S上升至(25.57±0.36)S和(28.81±2.92)s;信号上升最大斜率由(322.49±88.13)/s和(191.79±60.00)/s下降至(147.97±40.83)/s和(70.20±10.59)/s;最大相对信号增加率由4.47%±0.63%和2.69%±0.36%下降至2.54%±0.30%0和1.20%0±0.16%,S0～S2期与S3、S4期差异均有统计学意义(P值均<0.01).结论 按0.1 ml/kg剂量纯CCl4每周1次腹腔注射,家兔肝纤维化成模率高.高质量的三维全肝动态磁共振灌注成像,能够对肝纤维化程度进行量化评估.

Establishment of liver fibrosis in rabbit model and quantitative study on hepatic perfusion with dynamic whole-liver 3D MR imaging

Objectives To investigate the ideal approach in creating rabbit model of hepatic fibrosis and to evaluate the feasibility and value of dynamic whole-liver 3D magnetic resonance (MR) perfusion-weighted imaging (PWI) in the quantitative study on the staging of hepatic fibrosis. Methods Rabbit model of hepatic fibrosis was created by intraperitoneal injection of 5% and 100% carbon tetrachloride (0.1ml/kg,once a week) respectively. MR perfusion weighted imaging was performed at the 6th, 8th, 10th and 12th week since injection. The time of peak (TOP), the time to peak (TIP), the maximum slope of increase(MSI) and the maximal relative signal increase (MRSI) of portal vein and hepatic parenchyma were analyzed quantitatively, and were compared with pathological results. Comparison of different concentrations of CCl4 was analyzed using chi-square test. Inter-group comparison of perfusion parameters was analyzed using one-way ANOVA P<0.05 was regarded as statistically significant. Results 40% of the rabbits treated with 5% carbon tetrachloride developed hepatic fibrosis, while 75% of the rabbits treated with 100% carbon tetrachioride developed hepatic fibrosis; the mortality rate is significantly different between these two groups (χ2 = 5.013.P<0.05). PWI examination was successfully achieved in 31 rabbits, liver perfusion baseline was stable, and good TIC curve was obtained. With the progress of hepatic fibrosis, TOP and TIP of portal vein and hepatic parenchyma were increased, and MSI and MRSI were decreased. There were significant differences among stage of S0-S2 ,S3 and S4. Conclusions The method (100% carbon tctrachloride intraperitoneal injection, 0.1 ml/kg, once a week) has high success rate of creating rabbit model of hepatic fibrosis. The stage of hepatic fibrosis could be evaluated quantitatively with dynamic whole-liver 3D MR perfusion-weighted imaging.