Real-Time, Longitudinal, Functional Brain Imaging via 4D Smart Epidermal Photoacoustic Tomography

About This Grant

ABSTRACT Neurological studies greatly benefit from functional brain imaging to investigate brain activity and understand the underlying mechanisms of healthy and disordered behavior. Studying non-human primates (NHP) stands at the forefront of neurological research, offering unparalleled insights into complex brain activities and advanced cognitive and behavioral processes. Utilizing optical or ultrasound technologies, researchers have developed various brain imaging methods that are versatile for studying a range of awake and behaving applications. However, these tools have been restricted to only small animal models. Recently, photoacoustic tomography (PAT) has emerged as a promising non-invasive, label-free technique capable of mapping deep brain hemodynamic functions by acoustically probing the brain’s optical contrast. Yet, the efficacy of traditional photoacoustic imaging is compromised by the strong acoustic aberration induced by the NHP’s dense, curved, and thick skull. Furthermore, current PAT systems are ill-suited for awake NHP imaging, due to their unwieldy size and complex operation. In this proposal, we will transcend these limitations by developing a four-dimensional smart epidermal photoacoustic tomography (4D-SEPAT) technology, allowing for real-time, longitudinal, functional brain imaging in behaving NHPs. The proposed 4D-SEPAT technology will leverage state-of-the-art epidermal electronics, which combines soft ultrasound transducer array and high-precision shape mapping. Most importantly, the soft ultrasound transducer array, with integrated shape sensor and high-power laser source, can closely adapt to the contour of the NHP head, effectively mitigating the skull’s aberration effect. Powered by fast 3D image reconstruction, 4D-SEPAT will enable real-time transcranial brain imaging while maintaining its high sensitivity to hemodynamic functions. With full conformability to the head, 4D-SEPAT is insensitive to motion artifacts, can be longitudinally applied to behaving NHPs, and allow for deep-brain analysis of sensory and cognition. To achieve this objective, we will pursue the design, development, and validation of the proposed 4D- SEPAT system in Aim 1 and Aim 2, and demonstrate its imaging performance in awake rhesus macaques during visual-oculomotor behavior in Aim 3. Success of this 4D-SEPAT technology has the potential to revolutionize the way the brain is studied, diagnosed, and treated, by providing non-invasive, longitudinal, real-time mapping of deep brain functions.