IEEE Trans Biomed Eng. 2022 Sep;69(9):2723-2732. doi: 10.1109/TBME.2022.3150781. Epub 2022 Aug 19.
Focused ultrasound (FUS) combined with microbubble-mediated blood-brain barrier (BBB) opening (FUS-BBBO) is not only a promising technique for clinical applications but also a powerful tool for preclinical research. However, existing FUS devices for preclinical research are expensive, bulky, and lack the precision needed for small animal research, which limits the broad adoption of this promising technique by the research community. Our objective was to design and fabricate an affordable, easy-to-use, high-precision FUS device for small animal research.
We designed and fabricated in-house mini-FUS transducers (∼$80 each in material cost) with three frequencies (1.5, 3.0, and 6.0 MHz) and integrated them with a stereotactic frame for precise mouse brain targeting using established stereotactic procedures. The BBB opening volume by FUS at different acoustic pressures (0.20-0.57 MPa) was quantified using T1-weighted contrast-enhanced magnetic resonance imaging of gadolinium leakage and fluorescence imaging of Evans blue extravasation.
The targeting accuracy of the device as measured by the offset between the desired target location and the centroid of BBBO was 0.63 ± 0.19 mm. The spatial precision of the device in targeting individual brain structures was improved by the use of higher frequency FUS transducers. The BBB opening volume had high linear correlations with the cavitation index (defined by the ratio between acoustic pressure and frequency) and mechanical index (defined by the ratio between acoustic pressure and the square root of frequency). The correlation coefficient of the cavitation index was slightly higher than that of the mechanical index.
This study demonstrated that spatially accurate and precise BBB opening was achievable using an affordable and easy-to-use FUS device. The BBB opening volume was tunable by modulating the cavitation index. This device is expected to decrease the barriers to the adoption of the FUS-BBBO technique by the broad research community.
聚焦超声（FUS）联合微泡介导的血脑屏障（BBB）开放（FUS-BBBO）不仅是一种有前途的临床应用技术，也是一种强大的临床前研究工具。然而，现有的临床前研究用 FUS 设备昂贵、体积庞大，且缺乏小动物研究所需的精度，这限制了该有前途的技术在研究界的广泛采用。我们的目标是设计和制造一种经济实惠、易于使用、高精度的小动物研究用 FUS 设备。
我们自主设计和制造了成本约为 80 美元的迷你 FUS 换能器（每个换能器的材料成本约为 80 美元），具有三个频率（1.5、3.0 和 6.0 MHz），并将其与立体定位框架集成，以便使用既定的立体定位程序精确靶向小鼠大脑。通过 T1 加权对比增强磁共振成像测量钆泄漏和 Evans 蓝外渗荧光成像来量化 FUS 在不同声压（0.20-0.57 MPa）下的 BBB 开放体积。
该设备的靶向准确性通过所需目标位置与 BBB 开放中心点之间的偏移来衡量，偏移为 0.63 ± 0.19 mm。通过使用更高频率的 FUS 换能器，提高了该设备靶向单个脑结构的空间精度。BBB 开放体积与空化指数（通过声压与频率的比值定义）和机械指数（通过声压与频率平方根的比值定义）具有高度线性相关性。空化指数的相关系数略高于机械指数。
本研究表明，使用经济实惠且易于使用的 FUS 设备可实现空间精确且精确的 BBB 开放。通过调节空化指数可以调节 BBB 开放体积。该设备有望降低 FUS-BBBO 技术在广大研究界的采用障碍。
