Optimization of pulsed focused ultrasound exposures for hyperthermia applications

Hyperthermic temperatures, with potential applications in drug/gene delivery and chemo/radio sensitization, may be generated in biological tissues by applying focused ultrasound (FUS) in pulsed mode. Here, a strategy for optimizing FUS exposures for hyperthermia applications is proposed based on theoretical simulations and in vitro experiments. Initial simulations were carried out for tissue-mimicking phantoms, and subsequent thermocouple measurements allowed for validation of the simulation results. Advanced simulations were then conducted for an ectopic, murine xenograft tumor model. The ultrasound exposure parameters investigated in this study included acoustic power (3-5 W), duty cycle (DC) (10%-50%), and pulse repetition frequency (PRF) (1-5 Hz), as well as effects of tissue perfusion. The thermocouple measurements agreed well with simulation outcomes, where differences between the two never exceeded 1.9%. Based on a desired temperature range of 39-44 °C, optimal tumor coverage (40.8% of the total tumor volume) by a single FUS exposure at 1 MHz was achieved with 4 W acoustic power, 50% DC, and 5 Hz PRF. Results of this study demonstrate the utility of a proposed strategy for optimizing pulsed-FUS induced hyperthermia. These strategies can help reduce the requirement for empirical animal experimentation, and facilitate the translation of pulsed-FUS applications to the clinic.