Deep brain photoacoustic tomography at single-neuron resolution using arrays of photonic emitters and high-frequency ultrasound transducers

拟议的为期三年的研究项目的目标是开发高速、高空间- 分辨率，深穿透光声计算机断层扫描(PACT)，用于实时成像 小鼠脑内神经活动的活体研究。拟议的硬件成像系统将是 在PACT领域中是前所未有的，其体积速率和空间分辨率， 受益于使用有史以来数量最多的一对一映射的传感元件 数字化频道。与现有的高分辨率光学神经成像方式相比， 作为双光子显微镜，所提出的系统将提供更深的穿透，和更高的 小鼠全脑成像的体积成像速度。 由于两个事件，这样一个令人兴奋的项目的时机是完美的。(1)我们未出版的 正在进行的研究首次表明，PACT已经通过整个老鼠的大脑进行了成像， 大量血管溶解(见目标4部分中的图像)。(2)高频超声波 Shepard实验室可以大规模集成具有全方位灵敏度的传感器元件 完成三维(3D)声学检测(在目标3部分中讨论)。通过使用 史无前例的1536超声波换能器元件一对一映射到数据采集 通道，我们将在单个神经元分辨率和2 kHz体积速率下进行实时3D PACT， 这是以前从未实现过的。 具体目标包括： 1.研制具有光子发射体阵列的植入式光子探测器。 2.研制了PACT高频超声换能器阵列。 3.发展脑深部高频诱发电位。 4.使用PACT对小鼠脑内的神经活动进行活体成像。

The objective of the proposed three-year research project is to develop high-speed, high-spatial- resolution, deep-penetration photoacoustic computed tomography (PACT) for real-time imaging of neuro-activities in mouse brains in vivo. The proposed hardware imaging system will be unprecedented in the field of PACT in terms of its volumetric rate and spatial resolving power, which benefit from the use of the largest ever number of sensing elements with one-to-one mapped digitization channels. In comparison to existing high-resolution optical neuroimaging modalities such as two-photon microscopy, the proposed system will provide deeper penetration, and higher volumetric imaging speed for whole mouse brain imaging. The timing for such an exciting project is perfect because of two events. (1) Our unpublished ongoing work has shown for the first time that PACT has imaged through the entire mouse brain, with abundant vessels resolved (see the images in the Aim 4 section). (2) High-frequency ultrasonic transducer elements with omnidirectional sensitivity can be massively integrated by the Shepard lab to accomplish three-dimensional (3D) acoustic detection (discussed in the Aim 3 section). By using an unprecedented 1536 ultrasonic transducer elements one-to-one mapped to data acquisition channels, we will perform real-time 3D PACT at single neuron resolution and 2 kHz volumetric rate, which has never been achieved before. The specific aims include: 1. Develop implantable photonic probes with arrays of photonic emitters. 2. Develop high-frequency ultrasonic transducer arrays for PACT. 3. Develop deep brain high-frequency PACT. 4. Use PACT to image neuro-activities in mouse brains in vivo.