High intensity focused ultrasound and microbubbles induce targeted mild hyperthermia suitable for enhanced drug delivery

Abstract

High intensity focused ultrasound (HIFU) can elevate the temperature leading to tissue ablation (>60 °C). Mild hyperthermia (39–45 °C) can enhance drug delivery such as in the activation of thermosensitive liposomes for chemotherapy and in radiotherapy. The addition of microbubbles during HIFU could greatly enhance the heating process and increase the treatment area while operating at lower intensities. Here, we present a parametric study of microbubble-enhanced mild hyperthermia with HIFU in ex vivo porcine liver. A 30-s treatment at 0.9 MHz, 372 000 cycles, 82% duty cycle was used, and at estimated non-derated (water) pressures of 0.63, 1.25, 2.50 and 3.75 MPa. The microbubbles were injected locally in the treatment area. The measured temperature rise was greater with microbubbles than without at low acoustic pressures (0.63 and 1.25 MPa). At higher pressures (2.50 and 3.75 MPa), the presence of microbubbles did not have an effect on the measured temperature rise possibly due to inertial cavitation. Our results agree with predictions from a numerical model that solves the coupled acoustic-bubble flow fields with a two-way coupled Euler–Lagrange model. Future work will utilize the numerical model and new measurements to optimize targeted mild hyperthermia before applying it to enhanced drug delivery.