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 Our unpublished ongoing works have shown for the first time that (1) PACT has reached x-ray CT like image quality (see images in the Aim 2 section) and (2) some of the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.

PUBLIC HEALTH RELEVANCE: 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. There remains an important need for the development of high-speed, high-resolution technologies that can image deep into small animal brains. The proposed photoacoustic computed tomography (PACT) technology has the potential to meet this goal.