全肝CT灌注成像对经导管动脉化疗栓塞术联合阿帕替尼治疗兔VX2肝肿瘤效果的评价

目的：探讨全肝CT灌注成像评估兔VX2肝肿瘤经导管动脉化疗栓塞术(transcatheter arterial chemoembolization，TACE)联合阿帕替尼治疗效果的价值。方法：建立36只兔VX2肝肿瘤模型，随机分为4组，每组9只。A组行TACE(0.4 mg栓塞微粒球)，B组单纯口饲强服阿帕替尼50 mg/(kg.d)，C组行TACE(0.4 mg栓塞微粒球)+口饲强服阿帕替尼50 mg/(kg.d)，D组使用相同剂量的生理盐水行肝动脉灌注。4组均于治疗前和治疗7，14 d后行CT灌注成像(CT perfusion imaging，CTPI)获取灌注参数，包括血流量(blood flow，BF)、血容量(blood volume，BV)、肝动脉分数(hepatic arterial fracture，HAF)、平均通过时间(mean transit time，MTT)及毛细血管表面通透性(permeability surface，PS)。各组于第1次灌注扫描后分别处死1只兔，治疗14 d后行最后一次灌注扫描后处死剩余8只兔。取肿瘤边缘区组织行免疫组织化学染色，对比各组肿瘤边缘区CT灌注参数。比较各组治疗前及治疗7 d后肿瘤边缘区CT灌注参数的变化，采用多组间方差分析比较各组的肿瘤边缘区微血管密度(microvessel density，MVD)值，对各组灌注参数与MVD值行相关性分析。结果：治疗前4组间肿瘤边缘区CT灌注参数BF，BV，MTT，HAF，PS差异无统计学意义(P>0.05)。与治疗前相比，治疗后A，B，C组BF，HAF，PS明显降低(P<0.05)，D组稍增高。治疗14 d后MVD值分别为A组80.1±16.4，B组50.2±11.2，C组27.4±9.7，D组68.7±12.7，C组MVD值较其他3组显著降低(P<0.01)。除A组外，其余各组兔VX2肝肿瘤边缘区CTPI参数BF，HAF，PS与MVD均呈正相关；BV，MTT与MVD无明显相关性；A组MVD与各CTPI参数无明显相关性。结论：全肝CT灌注可定量评估兔VX2肝肿瘤TACE治疗前后肝血流动力学变化，可替代MVD评价肿瘤血供生成，TACE联合口服阿帕替尼能够有效抑制肿瘤血管生长。

Evaluation of total liver perfusion imaging of CT for efficacy of transcatheter arterial chemoembolization combined with apatinib on rabbit VX2 liver tumors

Objective: To investigate the value of the total liver CT perfusion imaging in the evaluation of rabbit VX2 liver tumors treated with TACE and apatinib.Methods: Thirty-six rabbit VX2 liver cancer models were established and randomly divided into 4 groups. Group A: simple TACE group; Group B: simple oral administration of apatinib mesylate; Group C: TACE + oral apatinib mesylate; Group D: control group, administration of saline. CT perfusion imaging (CTPI) was performed before treatment and on the 7 and 14 days after the treatment to acquire perfusion parameters including blood flow (BF), blood volume (BV), MTT (mean transit time), surface permeability (PS), and hepatic artery fraction (HAF). One tumor rabbit was sacrificed in each group after the first perfusion scan, and the remaining tumor rabbits were sacrificed after the last perfusion scan on the 14th day of the treatment. The borders of the tumors were stained immunohistochemically, and microvascular density (MVD) was measured by anti-CD34. The differences of perfusion parameters were compared to evaluate the liver hemodynamic changes, and statistical repeated measurement variance analysist correlation analysis were performed.Results: There were no significant differences in CTPI parameters of BF, BV, MTT, HAF and PS between the 4 groups before treatment (P>0.05). After the treatment, HB, HAF and PS were decreased significantly in Group A, B, and C and slightly increased in the Group D. The value of MVD after 14 d treatment was 80.1±16.4 in Group A, 50.2±11.2 in Group B, 27.4±9.7 in Group C, 68.7±12.7 in Group D, respectively. The value of MVD in the Group C were significantly lower than that in Group A, B, and D. It showed positive correlation between BF, HAF, PS and MVD in Group B, C, and D, and there was no significant correlation between BV, MTT and MVD. It showed no significant correlation between MVD and each CTPI parameter in Group A.Conclusion: Total liver CT perfusion can quantitatively evaluate the blood perfusion information of rabbit liver VX2 tumor after TACE. TACE combined with oral apatinib can effectively inhibit tumor growth and improve the therapeutic effect of VX2 tumor.