Enhancement of ultrasonic heating with microbubbles and their localization in target tissue

The bioeffect of ultrasound can be enhanced by orders of magnitude with microbubbles in a few ways. Enhancement of ultrasonic tissue absorption with a microbubble agent has been demonstrated both in theory and in an in vivo experiment. The ultrasonic power absorbed by a microbubble in its continuous wave response was numerically estimated. It has been predicted that the tissue ultrasonic absorption will be doubled when resonant microbubbles are delivered to the tissue at a concentration in the order of ten bubbles /mm3. An exteriorized murine kidney was exposed to focused ultrasound at 3.2 MHz. With an intravenous bolus administration of 0.2 ml/kg OptisonTM, the ultrasonically induced tissue temperature elevation was multiplied by up to five times. This effect will be useful for therapeutic ultrasound if microbubbles are selectively distributed in the target tissue by ultrasound pulses focused to the tissue. Tissue selective nano-droplets which can be phase-changed to microbubbles by ultrasonic stimulation will be a key to this approach.