| Objective: 1) To explore biological characteristics of VX2 liver tumor which were build through tumor tissue block implantation and dynamiclly monitored by normal CT and MRI in order to select the proper timing of VX2 liver tumor model which appropriate for the radiofrequency ablation; 2) To evaluate the relationship of function images including CT perfusion image and MRI diffusion weighted image with proliferation and apoptosis of VX2 tumor cells by comparison with the function image parameters and proliferating cell nuclear antigen index and apoptosis index; 3) To detect imaging-pathologic correlation of VX2 liver tumors after radiofrequency ablation (RFA) and analysis morphologic patterns and exact sites of local tumor progression (LTP) by dynamic enhanced CT in rabbit VX2 liver tumor after RFA. Methods:Twenty-nige New Zealand rabbits, including two tumor breading rabbits, nine rabbits in control group and eighteen rabbits in study group. Rabbits in study group were performed the open abdominal VX2 tissue block implantation while rabbits in control group were performed the open abdominal gelatin sponge implantation. All rabbits underwent CT and MRI scan after implantation 7,14 and 21 days. The morphologic features of liver tumors were observed and the volume of VX2 liver tumors were measured by soft wares in advanced workstation and then calculated the tumor doubling time in volume. Each time after exam, six rabbits in study group and three rabbit in control group were selected and sacrificed to observe liver and tumors. The tissue specimen were selected corresponding to images, and then routine paraffin embedding, section, hematoxylineosin dye, pan cytokeratin (CK) immunohistochemical staining, proliferating cell nuclear antigen (PCNA) immuno-histochemical staining and in situ apoptosis staining. Images were compared with grass morphology and pathological findings. Thirty New Zealand rabbits were implanted in liver with VX2 tumor tissue block. After implantation 14 days, thirty New Zealand white rabbits with single VX2 hepatic tumor were randomly divided into study group (n=9) and control group (n=21) to perform RFA guided by CT single time.Ablated areas included the entire tumor and about 10 mm peripheral margin of normal hepatic parenchyma in control group, while ablated areas included the entire tumor and less than 5 mm peripheral normal margin at least in one side surrounding the tumor in study group. Three phases enhanced CT scan was performed in 3,7 and 14 day after radiofrequency ablation respectively. Each time after CT scan, 3 rabbits in control group and 7 rabbits in study group were selected randomly and scarified. CT images were compared with grass morphology and pathological findings. Results:Twenty-seven rabbits were all alive still to the end of experiment. After implantation 7 days,6 VX2 liver tumors in 6 rabbits were found in T2WI and enhanced CT images while 3 lesion were found by T1WI images, which were quasi-circle lesion with average diameter was (0.57±0.14) cm. After implantation 14 days,6 tumors were found T1WI, T2WI and CT images in 6 rabbits, and tumors were still quasi-circle shape with average diameter was (1.48±0.28) cm. After implantation 21 days,9 tumors were found T1WI, T2WI and CT images in 6 rabbits, and tumors were irregular shape with lobular in CT and MRI images, and average diameter was (2.28±0.32) cm. After implantation 7,14 and 21 days, the average tumor volume measured by CT volume rendering softer ware were (0.181±0.089) ml, (1.527±0.207) ml and (8.836±1.397) ml, respectively. Based on formula, the VX2 tumors doubling time in volume were (2.6283±0.4202) day. The PCNA index in periphery of tumor tissue were higher than periphery hepatic tissue and normal tissue in control group (F=174.275, 121.999,158.785, respectively, P<0.001). the apoptosis index were high in tumor tissue than normal tissue in control group (t=38.144,19.047 and 20.655, respectively, P<0.001). The correlation analysis showed that apoptosis index were correlative with ADC value, Spearman related coefficient were -0.351, P<0.05. The blood flow and blood volume of periphery of tumor tissue were different in different implantation time (F=3.94, P=0.42 and F=3.878,P=0.044) and were related with PCNA index (r=0.486, P=0.041and r=0.546, P=0.019). The DTV of tumor were negative related with PCNA index (r=-0.585, P=0.046) 30 New Zealand rabbits were all made single VX2 hepatic tumor with average diameter 15.0mm, and 29 rabbits were successfully performed radiofrequency ablation, while 4 rabbits were died after RFA.25 lesions of local tumor progression in 18 rabbits were found in study group, including 13 extrazonal peripheral nodules,9 extrazonal crescentic lesions,1 intralzonal peripheral nodule and 2 intrazonal crescentic lesions, while no viable tumor cells were founding ablative margin in control group. Most local tumor progression were found around the transverse diameter of ablation zone (17/25), followed by proximal (6/25) and distal (2/25) (P=0.11). Conclusion:Tissue block abdominal implantation was a simple ways to build VX2 hepatic tumor model which had high tumor formation rate. The growth of VX2 hepatic tumors were rapid with tumor volume doubling time in (2.6283±0.4202) day, which suggested that 3 day were proper image follow-up interval. BF and BV were correlated with tumor PCNA index. ADC value was not correlated with tumor cell apoptosis. Excessive proliferation and apoptosis were both contributed to the development of VX2 liver tumors. After RFA, Local tumor progression of hepatic VX2 tumors had some particular morphology, and extranzonal local tumor progression was the most common pattern. Local tumor progression related to the insufficient ablative margin.
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