Phase shift nanoemulsions facilitated transcranial high intensity focused ultrasound ablation
Embargo Date
2021-09-29
OA Version
Citation
Abstract
This thesis aims to investigate the feasibility of using perfluorobutane phase-shift nanoemulsions (PFB PSNE) to facilitate mechanical ablation and its potential as a treatment for brain tumors. PFB PSNE are cavitation nuclei that can be acoustically vaporized, a process which is termed acoustic droplet vaporization (ADV). The vaporized bubbles can be cavitated by ultrasound at different intensities leading to a range of bioeffects that can be exploited for different therapies, including blood-brain barrier disruption, thermal ablation, and mechanical ablation. In this thesis, the research was focused on mechanical ablation using PFB PSNE.
The thesis has been designed to test two major hypotheses: 1. PFB PSNE could significantly reduce the power and pressure needed to create lesions inside the brain through inertial cavitation while avoiding pre-focal damage. 2. PFB PSNE ablation can destroy a tumor at the targeted region, reducing tumor growth and prolonging survival.
A series of in vitro and in vivo experiments were designed to test these two central hypotheses. PFB PSNE were activated at acoustic pressure amplitudes of 1.5–2.5 MPa, and the vaporization/inertial cavitation threshold was identified from the acoustic emissions. The inertial cavitation of PFB PSNE resulted in hemorrhagic and ischemic damage in the brain, and these effects were evaluated using magnetic resonance imaging (MRI). In experiments with a clinically relevant setup comparing PFB PSNE with microbubbles (MBs), PFB PSNE-facilitated ablation improved the localization of the damage and avoided effects in the beam path typically observed with MB-nucleated cavitation. Further, PFB PSNE-facilitated ablation in a rat glioma model produced a higher percentage of tumor death (89.4% vs. 11.1% for PFB PSNE and MBs). PFB PSNE-facilitated ablation also prolonged the survival of glioma rats with a significant increase of median survival (27 vs. 25 days; p = 0.00126). Overall, these results demonstrate that PFB PSNE are cavitation nuclei, which are more effective and safer for brain tumor ablation via improved localization and reduced effects in the ultrasound beam path.