Liu Hao-Li, Jan Chen-Kai, Chu Po-Chun, Hong Jhong-Cing, Lee Pei-Yun, Hsu Jyh-Duen, Lin Chung-Chih, Huang Chiung-Ying, Chen Pin-Yuan, Wei Kuo-Chen
IEEE Trans Biomed Eng. 2014 Apr;61(4):1350-60. doi: 10.1109/TBME.2014.2305723.
Focused ultrasound (FUS) in the presence of microbubbles can bring about transcranial and local opening of the blood-brain barrier (BBB) for potential noninvasive delivery of drugs to the brain. A phased-array ultrasound system is essential for FUS-BBB opening to enable electronic steering and correction of the focal beam which is distorted by cranial bone. Here, we demonstrate our prototype design of a 256-channel ultrasound phased-array system for large-region transcranial BBB opening in the brains of large animals. One of the unique features of this system is the capability of generating concurrent dual-frequency ultrasound signals from the driving system for potential enhancement of BBB opening. A wide range of signal frequencies can be generated (frequency = 0.2-1.2 MHz) with controllable driving burst patterns. Precise output power can be controlled for individual channels via 8-bit duty-cycle control of transistor-transistor logic signals and the 8-bit microcontroller-controlled buck converter power supply output voltage. The prototype system was found to be in compliance with the electromagnetic compatibility standard. Moreover, large animal experiments confirmed the phase switching effectiveness of this system, and induction of either a precise spot or large region of BBB opening through fast focal-beam switching. We also demonstrated the capability of dual-frequency exposure to potentially enhance the BBB-opening effect. This study contributes to the design of ultrasound phased arrays for future clinical applications, and provides a new direction toward optimizing FUS brain drug delivery.
在微泡存在的情况下，聚焦超声（FUS）可实现血脑屏障（BBB）的经颅和局部开放，从而有可能将药物无创递送至大脑。相控阵超声系统对于FUS诱导的BBB开放至关重要，它能实现电子控制和校正因颅骨而畸变的聚焦束。在此，我们展示了一款256通道超声相控阵系统的原型设计，用于在大型动物大脑中实现大面积经颅BBB开放。该系统的独特之处之一在于其驱动系统能够产生并发双频超声信号，从而有可能增强BBB开放效果。该系统能够产生宽范围的信号频率（频率 = 0.2 - 1.2 MHz），且驱动脉冲模式可控。通过对晶体管 - 晶体管逻辑信号进行8位占空比控制以及由8位微控制器控制的降压转换器电源输出电压，可对各个通道的精确输出功率进行控制。结果发现，该原型系统符合电磁兼容性标准。此外，大型动物实验证实了该系统的相位切换有效性，以及通过快速聚焦束切换诱导精确靶点或大面积BBB开放的能力。我们还展示了双频暴露有可能增强BBB开放效果的能力。本研究有助于未来临床应用的超声相控阵设计，并为优化FUS脑内药物递送提供了新方向。
