Microbubble-enhanced cavitation for noninvasive ultrasound surgery

Experiments were conducted to explore the potential of stabilized microbubbles for aiding tissue ablation during ultrasound therapy. Surgically exteriorized canine kidneys were irradiated in situ using single exposures of focused ultrasound. In each experiment, up to eight separate exposures were placed in the left kidney. The right kidney was then similarly exposed, but while an ultrasound contrast agent was continually infused. Kidneys were sectioned and examined for gross observable tissue damage. Tissue damage was produced more frequently, by lower intensity and shorter duration exposures, in kidneys irradiated with the contrast agent present. Using 250-ms exposures, the minimum intensity that produced damage was lower in kidneys with microbubbles than those without (controls) in 10 of 11 (91%) animals. In a separate study using ∼3200 W/cm² exposures, the minimum duration that produced damage was shorter after microbubbles were introduced in 11 of 12 (92%) animals. With microbubbles, gross observable tissue damage was produced with exposure intensity ≥∼800 W/cm² and exposure duration ≥10 μs. The overall intensity and duration tissue damage thresholds were reduced by ∼2x and ∼100x, respectively. Results indicate that acoustic cavitation is a primary damage mechanism. Lowering in vivo tissue damage thresholds with stabilized microbubbles acting as cavitation nuclei may make acoustic cavitation a more predictable, and thus practical, mechanism for noninvasive ultrasound surgery.