Low cost and low energy 3D volumetric histotripsy using nanodroplet vaporization

Abstract

Low pressure histotripsy may facilitate current treatments that require extremely high pressures. Here, a new technology platform for low-cost and low-energy 3D volumetric ultrasound histotripsy using nanodroplets was developed. The two-step approach involves the vaporization of the nanodroplets into gaseous microbubbles via a 1D rotating imaging probe (center frequency of 3.5 MHz). This transducer is situated within a therapeutic transducer that operates at a center frequency of 105 kHz. The therapeutic transducer is used to implode the vaporized nanodroplets and trigger potent mechanical effects in the surrounding tissues. Rotating the imaging transducer creates a circular vaporized ND shape, that upon their implosion generates a round shape lesion. In comparison, an elongated lesion shape is formed when using a standard 1D imaging transducer for ND activation. Initial optimization experiments were performed in tissue-mimicking phantoms, and ex-vivo chicken liver samples. Next, nanodroplet-mediated histotripsy was tested in a breast cancer tumor model in mice. The results confirm the generation of significant lesions and tumor tissue debulking compared to all control groups. Our approach facilitate the creation of large volume mechanical damage in tissues and solid tumors.