Thermal-sensitive acoustic droplets for dual-mode ultrasound imaging and drug delivery

Mild hyperthermia (40-43 °C) could assist with acoustic droplet vaporization (ADV) via focused ultrasound heating and enable ultrasound thermal imaging to monitor the heating position. We explored the possibility of predicting the treatment position of ADV using thermal-sensitive droplets (TSDs) and ultrasound thermal imaging. The TSDs were created with an encapsulated mixture of C₅F₁₂ and C₆F₁₄ that could be vaporized by ultrasound under mild hyperthermia. The ultrasound imaging-guided high-intensity focused ultrasound system was used to collect ultrasound images, heat tumors, and vaporize the TSDs. The overlap between the location of heating and ADV-induced bubble formation was used to evaluate the accuracy of predicting the treatment position. The optimal fabrication of TSDs (1.21 ± 0.19 μm, volume ratio of C₅F₁₂:C₆F₁₄ = 7:3) increased ADV efficiency by 33 ± 11% at 41 °C under an acoustic pressure of 8.6 MPa. The accuracy of ADV region prediction by ultrasound thermal imaging was 87.2 ± 3.5% for the in vitro study and 83.2 ± 8.6% for the in vivo study. The similarity among the location of bubble enhancement and distribution of 41 °C areas demonstrated the credibility of our estimates. Therefore, in this study, we validated the feasibility of applying TSDs and ultrasound thermal imaging to predict the in vivo treatment position of ADV.