Photoacoustic Imaging of Evoked Cortical and Subcortical Responses in Small Animal Brain

Abstract

Photoacoustic imaging is an emerging, non-invasive biomedical imaging modality, offering a unique blend of high spatial resolution and deep tissue penetration with endogenous contrast agent. This dissertation presents a comprehensive exploration of advanced photoacoustic imaging techniques in neuroscience, focusing on utilizing photoacoustic computed tomography (PACT) and photoacoustic microscopy (PAM) to study hemodynamic responses in the brain for various mouse models and non-human primates (NHPs). First, a label-free PACT system was developed for imaging mouse brains. This system was employed to monitor hemodynamic responses in the primary visual cortex (V1) during retinal photostimulation. The findings demonstrated the system's sensitivity in detecting differences in response between wild-type mice, rod/cone-degenerate mice, and melanopsin-knockout mice, showing its potential in providing detailed insights into brain activities. Furthermore, the research demonstrated the ability of the PACT system to image not just cortical but also subcortical responses. A total of five visually related brain regions at different depths and coronal planes were simultaneously observed. This demonstrates the versatility and depth of imaging capability in the PACT system. Second, the application of photoacoustic imaging to NHP models, specifically squirrel monkeys, marked a significant advancement in the research. Photoacoustic imaging techniques, both PACT and PAM, were utilized to detect cortical and subcortical responses to peripheral electrical and mechanical stimulation. The research revealed significant hemodynamic changes in the somatosensory and motor cortices during stimulation. A deep fully connected neural network was trained and proven to considerably enhance the image quality. This application of photoacoustic imaging in NHPs, which are closer analogs to human brain physiology, established its efficacy in mapping brain functions. Finally, the dissertation explores the capability of capacitive micromachined ultrasonic transducer (CMUT) arrays in capturing visual-evoked hemodynamic responses in the mouse brain. Demonstrating the comparable performance between CMUT and traditional piezoelectric arrays, this research paves the way for the development of more compact and efficient imaging systems for small animal studies. A wearable imaging device setting was also demonstrated using a catheter ultrasound array. In conclusion, this dissertation demonstrates significant advancements in photoacoustic imaging for brain research. The collective findings highlight the potential of photoacoustic imaging in overcoming the limitations of traditional neuroimaging modalities, offering non-invasive, label-free detection, high spatial resolution, and the ability to image deep brain structures. This work contributes significantly to the field of neuroscience, offering new insights and methodologies for studying brain functions in small animal models and potentially in clinical settings.