Treatment envelope of transcranial histotripsy: challenges and strategies to maximize the treatment location profile.

A 750 kHz, 360-element ultrasound array has been built for transcranial histotripsy applications. This study aims to evaluate its performance to determine whether this array is adequate for treating a wide range of brain locations through a human skull. Treatment location profiles in 2 excised human skulls were experimentally characterized based on passive cavitation mapping. Full-wave acoustic simulations were performed in 8 human skulls to analyze the ultrasound propagation at shallow targets in skulls with different properties. Results showed that histotripsy successfully generated cavitation from deep to shallow targets within 5 mm from the skull surface in the skull with high SDR and small thickness, whereas in the skull with low SDR and large thickness, the treatment envelope was limited up to 16 mm from the skull surface. Simulation results demonstrated that the treatment envelope was highly dependent on the skull acoustic properties. Pre-focal pressure hotspots were observed in both simulation and experiments when targeting near the skull. For each skull, the acoustic pressure loss increases significantly for shallow targets compared to central targets due to high attenuation, large incident angles, and pre-focal pressure hotspots. Strategies including array design optimization, pose optimization, and amplitude correction, are proposed to broaden the treatment envelope. This study identifies the capabilities and limitations of the 360-element transcranial histotripsy array and suggests strategies for designing the next-generation transcranial histotripsy array to expand the treatment location profile for a future clinical trial.