Enhanced histotripsy induced by hundreds of microsecond pulses and dual-frequency second harmonic superimposition: A preliminary study

A novel hundred-microsecond histotripsy treatment method is proposed. This method utilizes the confocal dual-frequency of second harmonic superimposition control approach. A custom-designed transducer consisting of two confocal spherical-annular element arrays is used. The frequencies of the transducer are 1.1 and 2.2 MHz, and the peak negative pressures are 5 MPa and 12 MPa with shock wave. Due to the dual-frequency superimposition, inertial cavitation threshold can be significantly decreased and inertial cavitation activity can be enhanced. By controlling the ratio of the dual-frequency acoustic power, the superimposition of two frequency pressures results in nine split foci along a beam axis within the confocal region, and the maximal peak intensity of the split foci can reach approximately twice the sum of the two frequency intensities, indicating strong wave interference. Experiments were conducted on BSA gel phantoms and on porcine liver tissues ex vivo. Target tissue could be mechanically disintegrated into long-tear-shape lesion with smooth borders. Lesion inception time, boiling bubble emergence time, and first stage treatment time were decreased to nearly 1/6, 1/7, and 1/2 of the single-frequency monofocal mode. The boiling bubbles occurred frequently at multiple foci in each lesion formation, beneficiating shorten the treatment time. The inertial-cavitation-energy waveform revealed that the energetic inertial cavitation activity dominated the entire histotripsy treatment and the occurrence of boiling activity significantly increased the filtered-PCD signal amplitude in the frequency-domain. These results demonstrated that the hundred-microsecond dual-frequency of second harmonic superimposition had potential value being used in improvement of histotripsy treatment efficiency.