In vitro and in vivo enhancement of sonodynamically active cavitation by second-harmonic superimposition

Acoustic cavitation, the primary mechanism of sonochemical effects, is known to be induced more easily by standing waves than by progressive waves. It has been found that acoustic cavitation can be an order of magnitude enhanced by superimposing the second harmonic on the fundamental. Significant synergistic effects between the fundamental and the second harmonic were observed in both in vitro and in vivo experiments employing a progressive wave field. Second-harmonic superimposition induces in vitro sonochemical reaction as well as fractional harmonic emission at a relatively low ultrasonic intensity even in a progressive wave field. The effect of second-harmonic superimposition was also investigated using exteriorized mouse livers suspended in degassed saline. The intensity threshold for the production of focal tissue damage, paired with fractional harmonic emission was significantly lowered by second-harmonic superimposition especially when a sonodynamically active agent had been administered to the mouse. Insonation with second-harmonic superimposition in combination with such administration may have potential use for selective tumor treatment.