Yao Xinya, Piao Xiangkun, Hong Shulong, Ji Chenyu, Wang Mingyu, Wei Yan, Xu Zhouyang, Pan Jia-Ji, Pei Yanbo, Cheng Bingbing
Translational Research in Ultrasound Theranostics Laboratory, School of Biomedical Engineering, ShanghaiTech University, Shanghai, China.
State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai, China.
Commun Eng. 2025 Jun 2;4(1):99. doi: 10.1038/s44172-025-00428-z.
Focused ultrasound-induced blood-brain barrier (BBB) opening enables targeted brain drug delivery. However, achieving simultaneous multi-target BBB opening across various depths and regions remains challenging and cost-prohibitive. Here we address these challenges by employing encoded acoustic holograms combined with a single-element plane-wave transducer to generate precise focused acoustic fields. The holograms designed using an iterative angular spectrum approach and fabricated via 3D printing produce single or multiple foci at different depths and regions, which are confirmed by simulations and hydrophone-based measurements. Beam steering capability is demonstrated and further validated in vivo. We design a hologram with less than 10% variation in amplitude across different foci and successfully achieve biplane multi-target ( ≥3) BBB opening in the bilateral hippocampus and medial septum of mice in a single sonication session with no adverse effects. This innovative acoustic holographic approach for simultaneous multi-target BBB opening is time-efficient and cost-effective, presenting broad potential applications in brain drug delivery and neuromodulation.
聚焦超声诱导的血脑屏障（BBB）开放能够实现靶向性脑内药物递送。然而，要在不同深度和区域同时实现多靶点血脑屏障开放仍然具有挑战性且成本高昂。在此，我们通过采用编码声全息图结合单元素平面波换能器来生成精确聚焦声场，解决了这些挑战。利用迭代角谱方法设计并通过3D打印制造的全息图，可在不同深度和区域产生单个或多个焦点，这已通过模拟和基于水听器的测量得到证实。在体内展示并进一步验证了光束转向能力。我们设计了一种在不同焦点处振幅变化小于10%的全息图，并在单次超声处理过程中成功地在小鼠双侧海马体和内侧隔区实现了双平面多靶点（≥3个）血脑屏障开放，且无不良影响。这种用于同时多靶点血脑屏障开放的创新声全息方法既省时又经济高效，在脑内药物递送和神经调节方面具有广泛的潜在应用。
