超声造影组织血流灌注参数评价肝癌抗血管生成治疗效果的实验研究

目的 探讨超声造影组织血流灌注参数在评价抗肿瘤血管生成治疗中的作用.方法 建立小鼠H22肝癌皮下移植瘤模型,随机分为治疗组和对照组,模型自建立次日起分别经腹腔注射0.5%羧甲基纤维素钠(对照组)和沙利度胺200 mg/kg(治疗组),每天1次,连续给药7 d.末次给药24 h后行超声造影检查,然后脱机采用时间强度曲线软件进行分析,获取曲线下面积(AUC)、峰值强度(Imax)、灌注指数(PI)、平均通过时间(mTT)、峰值时间(TTP)和拟合优度(GOF)等参数.超声检查完成后完整剥离肿瘤,免疫组化检测肿瘤CD34表达情况,计算微血管密度.结果 与对照组相比,沙利度胺治疗对小鼠体质量和肿瘤均有明显的抑制作用(P＜0.05).治疗组的AUC、PI和Imax和微血管密度均明显低于对照组(P＜0.05),mTT和TTP在两组间差异无统计学意义(P＞0.05).结论 超声造影定量分析组织血流灌注参数的改变可以有效评价抗肿瘤血管生成治疗的治疗效果.

Value of quantitatively analyzing tissue perfusion parameters of contrast enhanced ultrasound in the evaluation of antiangiogenic therapeutics effect in a mouse hepatoma model

Objective To evaluate the value of quantitatively analyzing tissue perfusion parameters of contrast-enhanced ultrasound in the evaluation of antiangiogenic therapeutics effect. Methods Kun-min mouse were subcutaneously implanted with H22 cells. Ten mouse were treated with thalidomide (200 mg/kg once daily) by intraperitoneal injection over 7 days,starting at day 2 post-implantation. Ten control mouse were treated with an equivalent volume of 0.5 CMC. Contrast-enhanced gray-scale ultrasound was performed on day 8 after bolus injection of SonoVue (0.1 ml) and the imaging was recorded on cine.Regions of interest within tumour were analyzed off-line with the software of SonoLiver to determine the area under the curve (AUC), maximum intensity (Imax), perfusion index (PI), mean transit time (mTT),time to peak (TTP) and quality of fit (QOF). Immediately after imaging, minces were euthanized and tumour tissue removed for fixation in a 10% formalin solution. Microvascular density (MVD) was measured after anti-CD34 staining. Results The body weight and the tumor volume of treated tumors were significant different (lower) than that of control tumors (P ＜0.05). Treatment with thalidomide resulted into a significant decrease in AUC,PI and Imax in comparison with control tumors ( P ＜0.05). There were no significant difference in mTT and TTP between control and treated tumours ( P ＞0.05). Treated tumours were associated with a significantly lower MVD as compared with control tumours( P ＜0.05). ConclusionsQuantitatively analyzing tissue perfusion parameters of contrast enhanced ultrasound shows promise for monitoring tumor response to antiangiogenic therapy.