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 $0.4\,\,\text {mm} \times {0.4}\,\,\text {mm} \times {2.6}$ 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 ( ${p}_{\text {no corrs}} = {24}\,\,\pm \,\, {4}$ % ${p}_{\text {water}}$ ); however, phase corrections restored partial focal quality ( ${p}_{\text {skull corrs}} = {31} \pm {3}$ % $p_{\text {water}}$ ). 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.

中文翻译：

---

高频相控阵系统，经颅超声在小动物中的传递。

现有的用于在小动物中应用经颅聚焦超声（FUS）的系统产生的焦点体积相对于可用于审讯的大脑结构的大小而言要大。高超声频率的使用可以提高靶向特异性。但是，啮齿动物颅盖在兆赫兹频率下引起的像差会严重扭曲单元素聚焦换能器产生的声场。在这里，我们介绍小型动物经颅FUS输送的高频相控阵系统的设计，制造和表征。通过将球面弯曲的PZT-5H碗（直径= 25 mm，曲率半径= 20 mm，基频= 3.3 MHz）微加工成具有相等表面积的64个独立元件，来构造换能器阵列。离体带有和不带有水听器辅助相差校正的大鼠黄盖。进行了大视野声场模拟，以研究潜在的光栅波瓣形成。以阵列的几何焦点作为目标时获得的聚焦光束大小为 $ 0.4 \，\，\文本{mm} \倍{0.4} \，\，\文本{mm} \倍{2.6} $ 毫米在水中。该阵列可以在直径为4.5 mm，高度为6 mm的圆柱体上电子引导FUS光束，而不会引入光栅波瓣。插入大鼠黄skull会导致声场的严重失真（ $ {p} _ {\ text {no corrs}} = {24} \，\，\ pm \，\，{4} $ ％ $ {p} _ {\ text {water}} $ ）; 但是，相位校正可以恢复部分焦距质量（ $ {p} _ {\ text {skull corrs}} = {31} \ pm {3} $ ％ $ p _ {\ text {water}} $ ）。使用相位校正，该阵列能够产生高达〜2.0 MPa的跨大鼠颅骨峰值负聚焦压力，足以在该频率下微泡介导的血脑屏障通透性。