Lin Yi, McMahon Dallan, Jones Ryan M, Hynynen Kullervo
IEEE Trans Biomed Eng. 2025 Feb;72(2):630-644. doi: 10.1109/TBME.2024.3466550. Epub 2025 Jan 21.
Focused ultrasound (FUS) combined with circulating microbubbles (MBs) can be employed for non-invasive, localized agent delivery across the blood-brain barrier (BBB). Previous work has demonstrated the feasibility of clinical-scale transmit-receive phased arrays for performing transcranial therapies under MB imaging feedback.
This study aimed to design, construct, and evaluate a dual-mode phased array for MB-mediated FUS brain therapy in small animals.
A 256-element sparse hemispherical array (100 mm diameter) was fabricated by installing 128 PZT cylinder transmitters (f = 1.16 MHz) and 128 broadband PVDF receivers within a 3D-printed scaffold.
The transmit array's focal size at the geometric focus was 0.8 mm × 0.8 mm × 1.7 mm, with a 31 mm/27 mm (lateral/axial) steering range. The receive array's point spread function was 0.6 mm × 0.6 mm × 1.5 mm (1.16 MHz source) at the geometric focus, and sources were localized up to 30 mm/16 mm (lateral/axial) from geometric focus. The array was able to spatially map MB cloud activity in 3D throughout a vessel-mimicking phantom at sub-, ultra-, and second-harmonic frequencies. Preliminary in-vivo work demonstrated its ability to induce localized BBB permeability changes under 3D sub-harmonic MB imaging feedback in a mouse model.
Small form factor transmit-receive phased arrays enable acoustic imaging-controlled FUS and MB-mediated brain therapies with high targeting precision required for rodent studies.
Dual-mode phased arrays dedicated for small animal use will facilitate high-throughput studies of FUS-mediated BBB permeability enhancement to explore novel therapeutic strategies for future clinical application.
聚焦超声（FUS）联合循环微泡（MBs）可用于无创、局部性的跨血脑屏障（BBB）药物递送。先前的研究已经证明了临床规模的发射-接收相控阵在微泡成像反馈下进行经颅治疗的可行性。
本研究旨在设计、构建并评估一种用于小动物MB介导的FUS脑治疗的双模相控阵。
通过在3D打印支架内安装128个PZT圆柱发射器（f = 1.16 MHz）和128个宽带PVDF接收器，制作了一个256阵元的稀疏半球形阵列（直径100 mm）。
发射阵列在几何焦点处的焦斑尺寸为0.8 mm×0.8 mm×1.7 mm，横向/轴向转向范围为31 mm/27 mm。接收阵列在几何焦点处的点扩散函数为0.6 mm×0.6 mm×1.5 mm（1.16 MHz源），源定位范围可达距几何焦点30 mm/16 mm（横向/轴向）。该阵列能够在亚谐波、超谐波和二次谐波频率下，在整个模拟血管体模中对MB云活动进行三维空间映射。初步的体内研究表明，在小鼠模型中，该阵列能够在三维亚谐波MB成像反馈下诱导局部BBB通透性变化。
小型化的发射-接收相控阵能够实现声学成像控制的FUS和MB介导的脑治疗，具有啮齿类动物研究所需的高靶向精度。
专门用于小动物的双模相控阵将有助于高通量研究FUS介导的BBB通透性增强，以探索未来临床应用的新型治疗策略。
