(30 Lines) The BRAIN initiative (RFA-EB-19-002) has called for the development of entirely new or next-generation noninvasive human brain imaging tools and methods that will lead to transformative advances in our understanding of the human brain. Functional MRI (fMRI) at ultrahigh fields has made tremendous improvements in spatiotemporal resolution, allowing brain function to be studied on the level of cortical layers and columns. However, fMRI is generally considered to have a low sensitivity and strong tissue background for detection of function. Positron emission tomography provides powerful metabolic imaging through radioactive tracers but suffers low spatial resolution, as is diffuse optical tomography despite its advantages in speed, cost, and portability. Ultrasound-only imaging cannot image adult human brains because the ultrasonic waves are attenuated and aberrated twice by the skull due to the round-trip propagation. To address these issues, we propose to develop 3D photoacoustic computed tomography (PACT) for fast and ultrafast large-scale neural activity imaging in human brains. PACT is especially well suited for detecting hemodynamic changes related to neural activities. It offers comparable spatial resolution but can be made much faster than fMRI. It is directly sensitive to both oxy- and deoxy-hemoglobin linearly with a low tissue background. Other potential benefits of PACT over fMRI include open imaging platforms, minimal site requirements, quiet and bedside operation, magnet-free environment, and low system maintenance. In the last two decades, we have developed photoacoustic technology at multiple spatial scales ranging from microscopic (subcellular and cellular) to macroscopic (whole rodent, whole human breast, ex vivo adult human skull, and preliminary single-channel 2D and 64-channel 3D in vivo adult human brain) imaging. We have revealed hemodynamic response in the rodent brain to whisker or electrical stimulation and mapped the resting- state functional connectivity of the rat brain in the deep thalamic region. We have also developed sophisticated numerical methods for simulating photoacoustic wave propagation in heterogeneous media and developed frameworks for image reconstruction in acoustically heterogeneous media. Further, we have successfully demonstrated ex vivo PACT through adult human skulls and acquired preliminary images of human heads in vivo. We propose to translate these advances in PACT to human brain imaging through two specific aims:
Aim 1 : Develop massively parallel high-speed 3D PACT for in vivo fast and ultrafast functional human brain imaging.
Aim 2 : Validate functional PACT in adult humans in vivo by comparing with ultrahigh-field 7 T fMRI.
(Three Sentences) Despite the success of the existing human brain imaging technologies, next-generation imaging tools are strongly desired. We propose to develop fast and ultrafast 3D photoacoustic computed tomography for high- resolution brain activity imaging based on the state-of-the-art technologies. This new modality has the advantages of high imaging speed, high spatial definition, high sensitivity, low background, rich signal contrast, open and magnet-free imaging, bedside and quiet operation, and low maintenance cost.
