Effect of periodic shifting of relative phase in second-harmonic superimposition on inducing cavitation in vitro and in vivo

We reported that ultrasound exposure with second-harmonic superimposition (SHS) efficiently induced cavitational effects both in vitro and in vivo. This time we investigated the effect of periodical shifting of the relative phase on the cavitation induction by using SHS. In an aqueous solution, subharmonic emission intensity, a measure of cavitation intensity, obtained by using SH phase shifting with a shift pitch not larger than 1/2 π and a shift interval time not shorter than 30 ms was as much as that obtained with the optimum fixed SH phase. When exposed to tumor tissues subcutaneously implanted in mice, SH phase shifting with a shifting period larger than 10 ms was effective to suppress tumor growth, which roughly agree with in vitro results. This result may be important for the application of SHS to in vivo treatment in which it is difficult to maintain the relative phase in a target tissue constant because of movements and biophysical changes.