FAST HIGH-RESOLUTION DEEP PHOTOACOUSTIC TOMOGRAPHY OF ACTION POTENTIALS IN BRAINS

 描述(申请人提供)：揭示我们的大脑是如何工作的是一个巨大的挑战，但值得我们尽一切努力：它不仅将阐明科学上的深刻奥秘，还将为理解和治疗阿尔茨海默氏症和帕金森氏症等神经系统疾病提供关键。这项拟议的三年研究的目标是开发一种高速、高空间分辨率、深度穿透的光声计算机断层扫描(PACT)系统，用于实时成像小鼠大脑的动作电位。所提出的硬件成像系统在PACT领域的帧速率和空间分辨率方面将是史无前例的，并且在PACT中使用压敏吸收染料的提议也是新颖的。与现有的高分辨率光学神经成像手段如双光子显微镜相比，所提出的系统将为整个小鼠脑成像提供更深的渗透。由于最近发生的以下事件，这样一个令人兴奋的项目的时机是完美的。我们未发表的正在进行的工作首次表明：(1)PACT已达到类似X射线CT的图像质量(见Aim 2部分中的图像)，以及(2)一些电压敏感荧光染料提供出色的光声对比度(见Aim 1部分中的数据)。超声成像行业刚刚开始销售独立的多通道数据采集系统，而不捆绑到我们不需要的传统线阵超声系统，用户可以完全访问原始的RF数据。大规模并行(512个通道)数据采集可实现实时PACT。除了RFA，NIH项目主任Jonathan D.Pollock博士在3月份发表在《生物医学光学杂志》上的题为《NIH大脑计划所需的深度成像技术》的文章[1]敦促我们的团队提交这项拨款申请。具体目标包括：1.筛选细胞培养制剂中用于光声成像的电压敏感探针，优化检测参数。2.开发快速、高分辨率、深穿透的PACT系统。3.用PACT对小鼠脑内动作电位进行活体成像。

 DESCRIPTION (provided by applicant): Revealing how our brain works is a great challenge but yet worth our every effort: it will not only illuminate the profound mysteries in science but also provide the key to understanding and treating neurological diseases such as Alzheimer's and Parkinson's. The objective of the proposed three-year research is to develop a high- speed, high-spatial-resolution, deep-penetration photoacoustic computed tomography (PACT) system for real- time imaging of action potentials in mouse brains. The proposed hardware imaging system will be unprecedented in the field of PACT in terms of frame rate and spatial resolving power, and the proposed use of voltage-sensitive absorption dyes in PACT is also novel. In comparison to existing high-resolution optical neuroimaging modalities such as two-photon microscopy, the proposed system will provide deeper penetration for whole mouse brain imaging. The timing for such an exciting project is perfect due to the following recent events. Our unpublished ongoing works have shown for the first time that (1) PACT has reached x-ray CT like image quality (see images in the Aim 2 section) and (2) some of the voltage-sensitive fluorescent dyes provide excellent photoacoustic contrast (see data in the Aim 1 section). The ultrasound imaging industry has just started to sell standalone multi-channel data acquisition systems without bundling to a conventional linear-array ultrasonographic system that we do not need, and the users are given full access to the raw RF data. Massively parallel (512 channels) data acquisition enables real-time PACT. In addition to the RFA, the March publication in the Journal of Biomedical Optics by NIH Program Director, Dr. Jonathan D. Pollock, entitled "Deep imaging technology needed for NIH BRAIN initiative,"[1] urged our team to submit this grant application. The specific aims include 1. Screen voltage-sensitive probes for photoacoustic imaging in cell culture preparations and optimize detection parameters. 2. Develop a fast, high-resolution, deep-penetration PACT system. 3. Use PACT to image action potentials in mouse brains in vivo.