High intensity focused ultrasound (HIFU) has been used for treatment of various kinds of cancer. Extracorporeal HIFU has been used for liver and pancreas cancers, although there are several limitations for treatment. One of the limitations is the complication of skin burns. Another one is attenuation of the HIFU power by the subcutaneous tissue and ribs. Yet another is that the HIFU ablation area is so small that it takes a long time to ablate a tumor, for example, the approximate time required for ablation of a tumor of 5 cm in size might be several hours. Therefore, an enhancer is necessary to increase the ablation size and decrease the required power for the desired HIFU ablation effect.
Microbubble ultrasound contrast agents are known to enhance HIFU effects. The enhancement effects of microbubbles are divided into two categories; cavitation and non-cavitation effects. The cavitation effect is divided into thermal and non-thermal effects. Commercially available ultrasound contrast agents act as cavitation nuclei resulting in non-thermal effects of cavitation when the microbubble is present in the tissue exposed to HIFU energy.
The size of hyper-echoic changes after HIFU treatment in the liver followed by intravenous administration of microbubbles is increased 5 times more than without microbubbles. The threshold of HIFU power for echogenic changes, and cavitation induced area, can be lowered using pre-administration of microbubbles.
Sonazoid microbubbles accumulate in the liver after intravenous administration because they are phagocytosed by Kupffer cells. The stable accumulation lasts long enough for them to be useful to enhance HIFU therapy in the liver.
It is expected that HIFU treatment will become safer and more widely indicated using microbubble contrast agents.