IEEE Trans Ultrason Ferroelectr Freq Control. 2021 Jan;68(1):127-135. doi: 10.1109/TUFFC.2020.3012868. Epub 2020 Dec 23.
Existing systems for applying transcranial focused ultrasound (FUS) in small animals produce large focal volumes relative to the size of cerebral structures available for interrogation. The use of high ultrasonic frequencies can improve targeting specificity; however, the aberrations induced by rodent calvaria at megahertz frequencies severely distort the acoustic fields produced by single-element focused transducers. Here, we present the design, fabrication, and characterization of a high-frequency phased array system for transcranial FUS delivery in small animals. A transducer array was constructed by micromachining a spherically curved PZT-5H bowl (diameter = 25 mm, radius of curvature = 20 mm, fundamental frequency = 3.3 MHz) into 64 independent elements of equal surface area. The acoustic field generated by the phased array was measured at various target locations using a calibrated fiber-optic hydrophone, both in free-field conditions as well as through ex vivo rat skullcaps with and without hydrophone-assisted phase aberration corrections. Large field-of-view acoustic field simulations were carried out to investigate potential grating lobe formation. The focal beam size obtained when targeting the array's geometric focus was [Formula: see text] mm in water. The array can steer the FUS beam electronically over cylindrical volumes of 4.5 mm in diameter and 6 mm in height without introducing grating lobes. Insertion of a rat skullcap resulted in substantial distortion of the acoustic field ( [Formula: see text]% [Formula: see text]); however, phase corrections restored partial focal quality ( [Formula: see text]% [Formula: see text]). Using phase corrections, the array is capable of generating a trans-rat skull peak negative focal pressure of up to ~2.0 MPa, which is sufficient for microbubble-mediated blood-brain barrier permeabilization at this frequency.
现有的用于小动物的经颅聚焦超声（FUS）应用系统相对于可用于询问的脑结构的大小产生了较大的焦点体积。使用高超声频率可以提高靶向特异性；然而，在兆赫兹频率下，啮齿动物颅骨引起的像差严重扭曲了单元件聚焦换能器产生的声场。在这里，我们提出了一种用于小动物经颅 FUS 传递的高频相控阵系统的设计、制造和特性。通过微机械加工一个球形弯曲的 PZT-5H 碗（直径= 25mm，曲率半径= 20mm，基频= 3.3MHz），将一个换能器阵列构建成 64 个相等表面积的独立元件。在自由场条件下以及在具有和不具有水听器辅助相位像差校正的离体大鼠颅骨盖下，使用校准的光纤水听器测量了相控阵产生的声场在各种目标位置处的声压。进行了大视场声场模拟，以研究潜在的栅瓣形成。当以阵列的几何焦点为目标时，在水中获得的焦点束大小为[公式：见文本]mm。该阵列可以在不引入栅瓣的情况下，通过电子方式引导 FUS 波束在直径为 4.5mm、高度为 6mm 的圆柱体内。插入大鼠颅骨盖会导致声场的严重失真（[公式：见文本]%[公式：见文本]）；然而，相位校正恢复了部分焦点质量（[公式：见文本]%[公式：见文本]）。使用相位校正，该阵列能够在大鼠颅骨下产生高达约 2.0MPa 的跨大鼠颅骨的负焦点压力，这足以在该频率下实现微泡介导的血脑屏障通透性。
