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 (1) Our unpublished ongoing work has shown for the first time that PACT has imaged through the entire mouse brain, with abundant vessels resolved (see the images in the Aim 4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.

Revealing how our brain works is challenging but potentially rewarding: 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 at single- neuron resolution. The proposed high-frequency photoacoustic computed tomography technology has the potential to meet this goal.