Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052, USA.
J Acoust Soc Am. 2011 Jul;130(1):599-609. doi: 10.1121/1.3598464.
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.
高热温度，具有药物/基因传递和化疗/放射增敏的潜在应用，可通过施加聚焦超声（FUS）在脉冲模式下在生物组织中产生。在这里，提出了一种基于理论模拟和体外实验优化 FUS 暴露用于热疗应用的策略。首先对组织模拟体模进行了初步模拟，随后的热电偶测量验证了模拟结果。然后对异位、鼠异种移植肿瘤模型进行了高级模拟。本研究中研究的超声暴露参数包括声功率（3-5 W）、占空比（DC）（10%-50%）和脉冲重复频率（PRF）（1-5 Hz），以及组织灌注的影响。热电偶测量与模拟结果吻合良好，两者之间的差异从未超过 1.9%。基于 39-44°C 的期望温度范围，在 1 MHz 时，通过单次 FUS 暴露以 4 W 声功率、50% DC 和 5 Hz PRF 实现了 40.8%的总肿瘤体积的最佳肿瘤覆盖。这项研究的结果证明了所提出的优化脉冲-FUS 诱导热疗策略的实用性。这些策略可以帮助减少对经验性动物实验的需求，并促进脉冲-FUS 应用向临床的转化。
