Transcranial histotripsy therapy: a feasibility study

This study investigates the feasibility of performing noninvasive histotripsy therapy through an intact human skull cap. The ablation precision of the therapy using extremely short pulses was also evaluated. A 500-kHz 32-element focused hemispherical array was fabricated in-house; it can generate high instantaneous peak rarefactional pressures (p-) at the focus (theoretically over 100 MPa in free field) with pulses <;2 cycles. The skull cap significantly decreased the p- value to approximately 14% of free-field conditions. With timing corrections applied to 32 elements, focal pressure was restored to approximately 28% of free field, allowing consistent cavitation initiation at the focus at an estimated p- of 29 to 30 MPa. Lesions were created in agarose tissue phantoms and ex vivo canine liver using PRFs of 1, 10, and 100 Hz, with a total of 500 histotripsy pulses applied. Main lesions as small as 0.7 × 1.6 mm (±0.1 × 0.1 mm) in the phantoms and 0.5 × 1.2 mm in tissue samples were generated transcranially. Results showed that treatments at lower PRF yielded lesions with more confined ablation and sharper boundaries. The capability of generating small, precise transcranial lesions could be potentially useful for noninvasive brain therapy applications at low frequencies.