Boiling histotripsy: A noninvasive method for mechanical tissue disintegration

Boiling histotripsy is an experimental noninvasive focused ultrasound therapy that applies shocked ms-length pulses to achieve mechanical disintegration of a targeted tissue. Localized delivery of high-amplitude shocks causes rapid heating, resulting in boiling of the tissue. The interaction of incident shocks with the boiling bubble results in tissue disruption and liquefaction without significant thermal injury. Simulations are utilized to design and characterize therapy sources, predicting focal waveforms, shock amplitudes, and boiling times. Transducers have been developed to generate focal shock amplitudes >70 MPa and achieve rapid boiling at depth in tissue. Therapy systems including ultrasound-guided single-element sources and clinical MRI-guided phased arrays have been successfully used to create ex vivo and in vivo lesions at ultrasound frequencies in the 1–3 MHz range. Histological and biochemical analyses show mechanical disruption of tissue architecture with minimal thermal effect, similar to cavitation-based histotripsy. Atomization as observed with acoustic fountains has been proposed as an underlying mechanism of tissue disintegration. This promising technology is being explored for several applications in tissue ablation, as well as new areas such as tissue engineering and biomarker detection. [Work supported by NIH 2T32DK007779-11A1, R01EB007643-05, 1K01EB015745, and NSBRI through NASA NCC 9-58.]