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

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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.