Perfluorobutane phase shift nanoemulsion enables cavitation-mediated nonthermal ablation of brain tumors in rat

Ultrasound nonthermal ablation is an emerging noninvasive technology for transcranial ablation. Nonthermal ablation has been achieved previously through inertial cavitation of ultrasound contrast agents (UCA). However, it is possible to generate unwanted damage in pre-focal regions due to the presence of UCA throughout the beam path. We propose to use perfluorobutane phase shift nanoemulsions (PFB-PSNE) instead of MBs to limit cavitation-mediated damage to the focal region. PFB-PSNE consist of a lipid shell and a liquid perfluorobutane core which can be vaporized and nucleate inertial cavitation using ultrasound. In this study, we demonstrated PFB-PSNE facilitated ablation in rat brain tumor. Four Fischer rats were implanted with F98 glioma in the caudate putamen. Two rats were sonicated with PFB-PSNE, and the other two served as controls. The tumors were sonicated 8 days after tumor implantation, and the animals were sacrificed at day 13 to harvest the brains. The tumor growth was evaluated with magnetic resonance imaging and histology. Localized microhemorrhage and ischemia was observed in the targeted tumors. We did not observe effects in the beam path. In summary, this work demonstrates the feasibility of using activated PFB-PSNE to produce localized cavitation sources that result in controlled damage in a glioma model.Ultrasound nonthermal ablation is an emerging noninvasive technology for transcranial ablation. Nonthermal ablation has been achieved previously through inertial cavitation of ultrasound contrast agents (UCA). However, it is possible to generate unwanted damage in pre-focal regions due to the presence of UCA throughout the beam path. We propose to use perfluorobutane phase shift nanoemulsions (PFB-PSNE) instead of MBs to limit cavitation-mediated damage to the focal region. PFB-PSNE consist of a lipid shell and a liquid perfluorobutane core which can be vaporized and nucleate inertial cavitation using ultrasound. In this study, we demonstrated PFB-PSNE facilitated ablation in rat brain tumor. Four Fischer rats were implanted with F98 glioma in the caudate putamen. Two rats were sonicated with PFB-PSNE, and the other two served as controls. The tumors were sonicated 8 days after tumor implantation, and the animals were sacrificed at day 13 to harvest the brains. The tumor growth was evaluated with magnetic...