Rapid Histotripsy Treatment Using Protocol of Fundamental and Second Harmonic Superposition Combined with Hundred-Microsecond Ultrasound Pulses with Sector Array Approach: Initial Experiments

Abstract

In this study, we propose a strategy of using a 4-element sector array, fundamental and second harmonic pressure superposition, and waveform of hundred-microsecond pulses and two stages. Hopefully, the rapid histotripsy process can be achieved through increasing one-spot lesion volume, enhancing pressure from cavitation reflection and multi boiling bubbles. A custom-designed 4-element sector array operated at 1.2 and 2.4 MHz with 146 mm aperture, 100 mm geometric focal length. In our initial experiments, we used the one focus pattern with acoustic focus dimension of 0.7 mm by 3 mm (lateral by axial length) and the peak negative pressure of each frequency exceeding −10 MPa. The histotripsy waveform scheme of hundred-microsecond pulses and two stages was used: stage 1, pulses with a pulse duration (PD) of 350 μs and pulse repetition frequency (PRF) of 100 Hz; stage 2, same PD and PRF as those in stage 1 and 1 % duty factor. The experiments were implemented in gel-phantom with bovine serum albumin (BSA), ex vivo porcine kidneys, monitored via high speed camera or passive cavitation detection (PCD). As expected, the experiments achieved successfully the disintegrated lesions with typical dimension of 5.5 mm by 7.5 mm (lateral by axial length) in porcine kidneys. The slide of H&E stained shows the lesion region where tissue fractionates into acellular debris with sharp boundary. The filtered-PCD mean square waveform indicates the enhanced inertial cavitation energy. The selected images from high speed imaging show the cavitation cloud structure and cavitation-bubble-layer reflection effects toward to transducer in prefocal region. The large sized lesion with wider 5.5-mm lateral dimension generated in prefocal region can attribute to dual-frequency parallel beams with shock waves, strong cavitation-bubble-layer reflection effects, and the parallel boiling bubbles of two frequencies.