Use of a microbubble agent to increase the effects of high intensity focused ultrasound on liver tissue

In order to find out whether high intensity focused ultrasound (HIFU) might be useful against hepatocellular carcinoma, we analyzed the effect of a microbubble agent (Levovist) on the temperature rise and tissue necrosis induced by HIFU. Rabbits were given 7 ml Levovist (300 mg/ml) or saline intravenously. Up to six areas per rabbit liver were exposed to HIFU for 60 s (2.18 MHz, I_SPTA=400 W/cm²). The volume of the tissue coagulated by HIFU was measured 10 min after the start of HIFU. HIFU-induced lesions were larger in the animals given Levovist: (mm³, Levovist versus saline) 371±104 versus 166±71 (P<0.001). Temperatures in the animals given Levovist were also higher 60 s after the start of exposure: (°C, Levovist versus saline) 20.3±3.5 versus 13.2±3.8 (P<0.001). The amount of damage differed greatly, but the pathological changes caused by HIFU with Levovist were the same as those caused by HIFU with saline. Hemorrhagic areas and implosion cysts were seen, and many cells had been disrupted or destroyed. Microbubble agents developed for diagnostic uses could also be used in anticancer therapy.