Sonodynamic treatment by inducing microbubble reaction

It was found that the ultrasonic intensity threshold for producing focal tissue damage through inducing cavitation can be significantly reduced by superimposing the second harmonic onto the fundamental. The threshold in murine liver tissue was reduced by orders of magnitude especially in combination with administration of erythrosin or its derivative. Such an effect was obtained at a second-harmonic phase emphasizing the peak rarefaction, but second-harmonic superimposition was significantly less effective at a phase emphasizing the peak pressure. The intensity threshold for cavitationally producing focal tissue damage was also reduced by administration of Albunex by orders of magnitude, but second-harmonic superimposition was not effective in combination with Albunex. These are consistent with a hypothesis that second-harmonic superimposition enhances cavitational effects through accelerating microbubble growth rather than collapse. Experimental murine tumors were treated employing second-harmonic superimposition in combination with administration of a Sonochemically active gallium-porphyrin complex. The tumor growth was significantly suppressed through second-harmonic superimposition while single frequency insonation at either one of the two frequencies showed no significant or only a very slight effect.