A Feasibility Study Of CT Perfusion And DCE-MRI Parameters In Evaluating The Anti-angiogenic Effect Of Rabbit VX2 Liver Cancer Treated With Sorafenib

Part one Comparison of two kinds transplantation methods for rabbitn VX2 liver cancer model.Objective:Comparison of tumor mass embedding method and tumor cell suspension method to establish rabbit VX2 liver cancer model.Method:36 healthy New Zealand white rabbits, weighing 3.2±0.5kg, the male or the female, were divided randomly two groups. One group were established rabbit VX2 liver cancer model with tumor mass puncture embedding method and the other one were with tumor cell suspension method.14 days after the operation, MRI T1 and T2 scanning were performed to observe the liver cancers respectively. Two rabbit each group were killed randomly to observe the tumors generally, then the liver and cancer specimen were made into paraffin blacks to carry out HE staining.Result:1 With tumor mass puncture embedding method, 14 rabbit VX2 liver cancer models were established successfully. 7days after the operation, 2rabbits were dead unexpected. 14 days after the operation,2 rabbits failed to establish liver cancer model. Modeling success rate of 77.7%.The other group with tumor mass puncture embedding method, 13 rabbit VX2 liver cancer models were established successfully. 7days after the operation, 3 rabbits were dead unexpected. 14 days after the operation, 2 rabbits failed to establish liver cancer model. Modeling success rate of 72.2%.2 rabbit cancer specimen generally looked as an fish-like gray nodule,unclear with the boundary of the liver. HE staining showed the VX2 tumor cells were heteromorphic highly, the nucleus was large and deep-coloring,fusiformis or irregular in shape. Also the VX2 tumor cells arranged indisorder.Conclusion:There was no significantly difference in the two method to establish the VX2 liver cancer model, but tumor in the tumor mass puncture embedding look regular in shape. The tumor mass puncture embedding method is more suitable for our experiment.Part two A experimental study of CT perfusion in evaluating the anti-angiogenic effect of Sorafenib for liver VX2 cancer in rabbitObjective: With volume CT perfusion parameters change, we tried to quantize evaluating the response of sorafenib treatment for liver VX2 cancer in different time points.Method:7 days after the operation, 30 rabbit models with liver VX2 cancer were chose through MRI scanning and divided randomly into two groups（each group of 15）:the experimental group was oral gavage with sorafenib and the control group was oral gavage with the same amount of 5%glucose. The rabbits were performed by Dual-source CT perfusion before treatment and on the 7th, 14 th days after treatment. Compare the CT perfusion parameters in the three time points: blood volume（BV）, blood flow（BF）,arterial liver perfusion（ALP）, portal liver perfusion（PVP）, hepatic perfusion index（HPI）. After the last examination, rabbits were sacrificed to perform HE staining and VEGF 、 MVD immunohistochemistry observation. Correlation between CT perfusion parameters and immunohistochemistry results were measured.Result:1 There was significantly difference in BV, BF, ALP values between the two groups（P<0.05）. But there was no significantly difference in PVP, HPI values between the two groups（P>0.05）. The BF value of the VX2 liver cancer in experimental group was（54.92±11.93） ml/100ml/min before treatment,（26±6.44） ml/100ml/min 7days after treatment and（28.89±12.87）ml/100ml/min 14 days after treatment. The BF value in control group was（56.43±10.54） ml/100ml/min before treatment,（62.32±18.20） ml/100ml/min7 days after treatment and（46.46±14.51） ml/100ml/min 14 days after treatment.The BV value of the VX2 liver cancer in experimental group was（9.23±0.52） ml/100 ml before treatment,（5.03±2.56） ml/100 ml 7days after treatment and（4.39±2.32） ml/100 ml 14days after treatment. The BV value in control group was（8.94±1.22） ml/100 ml before treatment,（9.94±1.66）ml/100 ml 7days after treatment and（10.13±2.10） ml/100 ml 14days after treatment.The ALP value of the VX2 liver cancer in experimental group was（51.83±5.21） ml/100ml/min before treatment,（31.45±3.38） ml/100ml/min7 days after treatment and（27.98±3.13） ml/100ml/min 14 days after treatment.The ALP value in control group was（51.17±2.57） ml/100ml/min before treatment,（48.48±9.52） ml/100ml/min 7days after treatment and（58.41±7.39）ml/100ml/min 14 days after treatment.2 here was no significantly difference 7days after treatment, the maximum diameter increased 0.23±0.06 cm and 0.31±0.09 cm in the experiment and control group. But There was significantly difference 14 days after treatment, the maximum diameter increased 0.43±0.21 cm and1.48±0.56 cm in the experiment and control group.3 There was significantly difference in MVD, VEGF values between the two groups（P<0.05）. There were positive correlation between ALP values and MVD、VEGF results respectively（r=0.614 and r=0.57）.Conclusion:CT perfusion parameters could early be used to quantize evaluating the response of sorafenib treatment for rabbit VX2 liver cancer.There were positive correlation between CT perfusion parameters value ALP and immunohistochemistry results.Part three Evaluating DCE-MRI Parameters in predicting the anti-angiogenic effect of rabbit VX2 liver cancer treated by Sorafenib in A experimental studyObjective:To evaluate DCE-MRI perfusion parameters early monitor the therapeutic effect of sorafenib for the liver VX2 cancer. the correlation between the perfusion parameters and immunohistochemistry parameterswould be analyzed.Method:30 rabbit models were the same ones in Part Two. DCE-MRI was performed 1h after CT perfusion in three different time points. The DCE-MRI parameters were recorded in three time points: microvascular permeability transfer constant(K_trans) 、 microvascular permeability reflux constant(K_ep) 、 Ve 、 Vp. Correlation test between DCE-MRI parameters and immunohistochemistry counting（VEGF、MVD） was perfor med.Results:1 The K_trans and K_ep had statistical difference between the two groups（P<0.05）, but the Ve and Vp had no statistical difference between the two groups（P>0.05）. The K_trans values of the VX2 liver cancer in experimental group were（0.34±0.12） min^-1 before treatment,（0.23±0.04） min^-1 7days after treatment and（0.13±0.03） min^-1 14 days after treatment. The K_trans value in control group were（0.35±0.06） min^-1 before treatment,（0.36±0.07） min^-17 days after treatment and（0.42±0.09） min^-1 14 days after treatment.The K_ep values of the VX2 liver cancer in experimental group were（2.32±1.14） min^-1 before treatment,（1.70±0.96） min^-1 7days after treatment and（1.05±0.71） min^-1 14 days after treatment. The K_ep values in control group were（3.02±2.11） min^-1 before treatment,（2.70±0.70） min^-1 7days after treatment and（1.47±0.69） min^-1 14 days after treatment.2 There was no significantly difference 7days after treatment, the maximum diameter increased 0.23±0.06 cm and 0.31±0.09 cm in the experiment and control group. But There was significantly difference 14 days after treatment, the maximum diameter increased 0.43±0.21 cm and1.48±0.56 cm in the experiment and control group.3 The VEGF and MVD had statistical difference between the two groups（P<0.05）. K_trans correlating well with MVD 、 VEGF, that had statistical difference, and the r values were 0.792 and 0.651 respectively.Conclusion:DCE-MRI parameters cloud be used to predict hemodynamic changes of the liver cancer before and after treatment. There were positive correlation between DCE-MRI parameters value K_trans andimmunohistochemistry results.