Size measurement of tissue debris particles generated from pulsed ultrasound cavitational therapy-histotripsy

Extensive mechanical tissue fractionation can be achieved using successive high intensity ultrasound pulses ("histotripsy"). Histotripsy has many potential medical applications where noninvasive tissue removal is desired (e.g., tumor ablation). There is a concern that debris generated by histotripsy-induced tissue fractionation might be an embolization hazard. The aim of this study is to measure the size distribution of these tissue debris particles. Histotripsy pulses were produced by a 513-element 1 MHz array transducer, an 18-element 750 kHz array transducer and a 788 kHz single element transducer. Peak negative pressures of 11 to 25 MPa, pulse durations of 3 to 50 cycles, pulse repetition frequencies of 100 Hz to 2 kHz were used. Tissue debris particles created by histotripsy were collected and measured with a particle sizing system. In the resulting samples, debris <6 microm in diameter constituted >99% of the total number of tissue particles. The largest particle generated by one of the parameter sets tested was 54 microm in diameter, which is smaller than the clinic filter size (100 microm) used to prevent embolization. The largest particles generated using other parameter sets were larger than 60 microm but the value could not be specified using our current setup. Exposures with shorter pulses produced lower percentages of large tissue debris (>30 microm) in comparison to longer pulses. These results suggest that the tissue debris particle size distribution is adjustable by altering acoustic parameters if necessary.