A systematic comparison of cavitation regimes and histotripsy efficiency across pulse duration and repetition rate in a fibrous tissue mimicking phantom

Histotripsy is a focused ultrasound technique that mechanically liquefies tissue through cavitation bubble activity and has shown promise for noninvasive tumor ablation. However, treating fibrous, mechanically robust tissues remains challenging, and the influence of pulse parameters on cavitation dynamics and treatment efficiency in these tissues is not well understood. Here, we systematically investigated the combined effects of pulse duration and pulse repetition frequency (PRF) on cavitation behavior and lesion formation in a fibrous tissue-mimicking double-network hydrogel. Pulse duration and PRF were varied over four orders of magnitude while maintaining a constant 1% duty cycle. High-speed photographic imaging, shear wave elastography (SWE), B-mode ultrasound, and open-top light-sheet (OTLS) microscopy were used to relate cavitation behavior to phantom damage and liquefaction. Short-pulse, high-PRF exposures (1–10 cycles) produced larger bubble cloud areas, higher frame-to-frame correlation, and greater spatial persistence, whereas longer-pulse, low-PRF exposures (≥ 100 cycles) produced more localized cavitation and contiguous lesion formation. Among the tested parameters, 1,000 -cycle pulses at 10 Hz yielded the highest volumetric liquefaction rates. In contrast, short-pulse, high-PRF conditions generated substantial total damage but little to no fully liquefied volume. These findings show that pulse duration and PRF strongly govern histotripsy outcomes in fibrous tissues