Using microbubbles to increase the destruction of liver tumors by high-intensity focused ultrasound

为探讨高强度聚焦超声(HIFU)与微气泡剂联合治疗肝细胞癌的可行性。HIFU换能器直径40 mm，产生2.18 MHz连续波30s。空间峰值时间平均强度为600W/cm2。经二甲基亚硝胺(100ppm)诱导大鼠肝肿瘤形成。麻醉大鼠，剖腹手术后，静脉注射微泡剂Levovist或生理盐水。在HIFU照射后即刻，评估HIFU区域的超声图像。HIFU后肝组织平均高回声区体积为(mm~3，Levovist：355.3±180.7 vs.47.4±35.6，p&lt；0.001，n=13)，HIFU凝固肝组织体积为(mm~3，Levovist：275.3±120.0 vs.60.1±23.6p&lt；0.001，n=13)。显微镜下可见高强度聚焦超声照射区域内爆裂性包囊，许多癌细胞被破坏或完全破坏。一些肿瘤细胞因细胞膜或细胞核丢失而变形。结论：微气泡剂利沃司特通过增加高强度聚焦超声的作用，在抗癌治疗中也有直接作用。

We studied the possibility of using high-intensity focused ultrasound (HIFU) together with a microbubble agent to treat hepatocellular carcinoma.The transducer for HIFU was 40 mm in diameter ; it produced a continuous 2.18-MHz wave for 30 seconds.The spatial peak temporal average intensity was 600 W/cm2.Development of liver tumors in rats was induced by administration of Dimethylnitrosamin (100 ppm).Rats with liver tumors were anesthetized, underwent laparotomy, and were given the microbubble agent Levovist or saline intravenously.After 60 seconds of Levovist or saline injection, the liver was exposed to HIFU for 30 seconds. Immediately after HIFU exposure, ultrasound images of the HIFU area were evaluated. Then the liver was excised and the volume of coagulated tissue was measured.The mean volume of hyperechoic areas after HIFU were as follows (mm3, Levovist vs. saline : 355.3 ± 180.7 vs. 47.4 ± 35.6, p < 0.001, n=13).The volumes of liver tissue coagulated by HIFU were as follows (mm3, Levovist vs. saline : 275.3 ± 120.0 vs. 60.1 ± 23.6, p < 0.001, n=13).On microscopic examination of areas exposed to HIFU, implosion cysts were seen, and many cancer cells were found to have been disrupted or destroyed completely.Some tumor cells had been distorted by loss of cell membranes or nuclei.In conclusion, the microbubble agent Levovist, by increasing the effect of HIFU, could also have a direct role in anti-cancer therapy.