Acoustic droplet vaporization for nonthermal ablation of brain tumors

Acoustic vaporization of perfluorobutane-based phase-shift nanoemulsions (PSNE) can be used to nucleate inertial cavitation (IC) in vivo. The acoustic pressure amplitude must exceed a threshold for vaporization of PFB-based nanoemulsions. Two focused ultrasound transducers with a center frequency of 837 kHz were oriented such that their focal volumes overlapped and the acoustic pressure amplitude was amplified. In this study, the dual transducer system was combined with circulating PSNE to nucleate IC in established brain tumors, leading to nonthermal ablation of the tumors. For comparison, microbubble ultrasound agents (UCA) were used as IC nuclei for ultrasound-mediated tumor ablation. The ablation volume was confined to focal volume when PSNE were used to nucleate IC, whereas pre-focal damage was observed when UCA were used as IC nuclei. Additionally, PSNE-nucleated IC ablated a larger percentage of the brain tumors on average than MB-nucleated IC (89.46.8% vs 11.17.7%, respectively). These results suggest that PFB-based PSNE may be used to significantly reduce the inertial cavitation threshold in the cerebrovasculature, and when combined with transcranial focused ultrasound, enable efficient focal intracranial nonthermal ablation.