低频率高强度聚焦超声(HIFU)致兔VX2肌肉肿瘤血管栓塞的实验研究

Embolism Caused by Low-frequency High-intensity Focused Ultrasound in VX2 Muscle Tumor Vessels

目的:探讨低频率(0.4MHZ)高强度聚焦超声(high-intensity focused ultrasound,HIFU)辐照对兔VX2肌肉肿瘤血管的作用效应及其对实验性肿瘤局部生长的影响。方法:将VX2瘤块接种于56只新西兰大白兔股外侧肌内制成动物肿瘤模型,采用随机数字表法将其分为对照组(A组)、实验组(B、C、D组)4组,分别给予HIFU假照和声强为1194、1592、1990W/cm2的HIFU辐照,随之于HIFU辐照后3、7天行二维超声测量肿瘤大小,并计算肿瘤增长率;彩色多普勒血流显像(color Doppler flow imaging,CDFI)及病理学检查,以观察肿瘤血供及肿瘤组织病理学改变。结果:HIFU辐照后3天,D组增长率为13.4%±6%,明显低于A、B、C3组(P<0.05),而A、B、C组间增长率无差异(P>0.05),CDFI见D组肿瘤组织内血流信号较辐照前减少,A、B、C组无变化,病理学检查见肿瘤间质部分血管内血栓形成;HIFU辐照后7天,C、D组增长率分别为41.9%±15%和25.8%±6%,明显低于A、B组(P<0.05),CDFI见C、D组肿瘤组织内血流信号较辐照前明显减少,病理学检查可见C组部分血管肿胀、淤血;D组大部分血管栓塞和周围肿瘤组织坏死。结论:频率为0.4MHZ的HIFU,焦域声强为1990W/cm2时,可于HIFU辐照后早期(3天内)诱导兔VX2肌肉肿瘤血管内血栓形成,使肿瘤营养血供减少,从而促进肿瘤组织坏死,延缓肿瘤增长。

Objective： To investigate the effect of low-frequency （0.4 MHz） high-intensity focused ultrasound （HIFU） on the vessels of rabbit VX2 muscle tumor and the growth of tumor. Methods： The VX2 tumor mass was transplanted into the vastus lateralis of 56 New Zealand white rabbits. Using a random digits table, we divided the rabbits into a control group （Group A） and 3 experimental groups （Groups B, C, and D）. The experimental groups received low-frequency HIFU with a sound energy density of 1194, 1592, and 1990 W/cm^2 in the B, C, and D groups, respectively. Tumor size was measured at 3 and 7 days after low-frequency HIFU, and the tumor growth rate was calculated. We employed color Doppler flow imaging （CDFI） to observe the blood supply of tumors. The tumor tissue was examined pathologically after the animals were sacrificed. Results： At 3 days after low-frequency HIFU, the growth rate of the D group was 13.4±6%, lower than that in the A, B, and C groups （P〈0.05）. No statistically significant difference was found in the growth rate among the A, B, and C groups （P〉0.05）. CDFI showed that the D group had less tumor blood flow after low-frequency HIFU. No changes were observed in the tumor blood flow in the A, B, and C groups. In all groups, pathological examination showed thrombosis in blood vessels in the interstitial tissues. At 7 days, the tumor growth rate in the C and D groups was 41.9±15% and 25.8±6%, respectively, both values lower than those in the A and B groups （P〈0.05）. CDFI showed that the C and D groups had less tumor blood flow after low-frequency HICU. Engorgement and congestion were observed in the C group. Most blood vessels of the D group were embolized and had necrosis of tissues surrounding the tumor. Conclusion： HIFU at a frequency of 0.4 MHZ and with a sound energy density of 1990 W/cm^2 can cause thrombosis in the vessels of rabbit VX2 muscle tumors. Interrupting tumor blood supply in such a manner can promote tumor necrosis and delay tumor growth.