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This study aims to investigate the feasibility and potential of sparse random arrays driven by the particle swarm optimization (PSO) algorithm to generate multiple-focus patterns and a large scanning range without grating lobes, which extends the scanning range of focused ultrasound in the treatment of brain tumors, opening the blood-brain barrier, and neuromodulation. Operating at 1.1 MHz, a random spherical array with 200 square elements (sparseness 58%) and a sparse random array with 660 square elements (sparseness 41%) driven by PSO are employed to simulate different focus patterns. With the same radius of curvature and diameter of transducer and element size, the scanning range of the off-axis single focus of a random 200-element array is two times that of an ordinary array using symmetric arrangement. The focal volume of multiple-focus patterns of the random array is 18 times that of the single focus. The single focus of the sparse random array with 660 elements could steer up to ±23 mm in the radial direction, without grating lobes. The maximum distance between two foci in a multiple-focus "S"-shaped deflection is approximately 25 mm. Simulation results illustrate the capability of a focused beam steered in 3-D space. Multiple-focus patterns could significantly increase the focal volume and shorten the treatment time for large target volumes. Simulation results show the feasibility and potential of the method combining PSO with a sparse random array to generate flexible focus patterns that can adapt to different needs in different tissue treatments.

Objective. Histotripsy is a non-invasive focused ultrasound ablation method that can mechanically disintegrate tissues. This study aims to verify that ultrasound-guided histotripsy using millisecond-length two-stage ultrasound pulses combined with fundamental and second harmonic superposition can enhance treatment in rabbit kidneys in vivo. Approach. Rabbit kidneys (n = 10) were treated using a custom-designed 1.1/2.2 MHz two-element confocal-annular array, with lateral and axial full width at half-maximum pressure dimensions of approximately 1.0 and 6.0 mm. Two-stage ultrasound pulses were applied: stage 1 used 60–80 pulses with a pulse duration of 6 ms and a pulse repetition frequency of 10 Hz. Meanwhile, stage 2 consists of 2–4 periods, each period consists of a concentrated pulse train of localized high DC of 6% and an off-time of 3–5 s, with an average DC of 1%–1.5%. B-mode ultrasound imaging was used to guide and monitor the boiling and cavitation bubbles. Main results. Ultrasound-guided treatment was successful in all rabbits, and the ablation rate is about seven times that of single-frequency combined two-stage pulses, achieving enhanced histotripsy. The regular elliptical lesions with dimensions of 10.6 ± 0.8 mm × 3.9 ± 0.6 mm (axial × lateral) were generated, and a large-volume lesion was generated by multi-point treatment. The size of most lysates was about 2.5 μm. Histologically, lesions were completely homogenized and well demarcated between treated-untreated areas. There was no apparent damage to critical structures surrounding lesions. Nonlinear simulations revealed that it may be the interaction between shock front and the cavitation and boiling bubbles generated by the dual-frequency effect enhanced the treatment efficiency. Significance. The novel histotripsy could improve treatment efficiency and generate regular elliptical lesions with controllable shape and axial dimensions, which may be a useful tool in treating renal cell carcinoma.