CAREER: Transcranial Optical Imaging of Neural and Cerebrospinal Fluid Dynamics in Freely Behaving Animals

Healthy brains depend on neural activity and cerebrospinal fluid (CSF) flow. Problems in CSF flow have been linked to aging and brain diseases such as Alzheimer’s disease. However, little is known about how CSF flow and brain activity interact with each other. Current imaging methods cannot measure these two processes together in freely moving animals. This CAREER project will develop a new miniature imaging system that can monitor both brain activity and cerebrospinal fluid movement through an intact skull. The outcome of the project will advance understanding of how brain activity, behavior, and CSF flow are linked in health and disease. This project will also benefit society through STEM education activities aimed at strengthening the biophotonics workforce. These activities include learning experiences for high school students in North Dakota, hands-on training for undergraduate and graduate students, and public outreach to raise awareness of brain health and optical technology. Overall, the project will develop new imaging technologies and deep learning frameworks to better understand the brain. This CAREER project will develop a compact imaging platform to measure neural activity and CSF dynamics in freely behaving animals. The platform will combine light-field fluorescence imaging and optical coherence tomography into a single system. This system will be capable of recording neural calcium activity, CSF transport, and structural information from the brain. Unlike existing approaches that require head fixation, the platform is designed to support minimally invasive imaging during natural behaviors. The platform will provide structural information needed to distinguish CSF signals in different brain regions. An anatomy-informed deep learning model will be integrated for image reconstruction. This system will study how brain state and behavior influence neural activity and CSF dynamics in mouse models of Alzheimer’s disease. The new imaging approach will advance understanding of brain clearance, aging, and neurodegenerative disease. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2543272 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Bo Liang | Institution: University of North Dakota Main Campus, GRAND FORKS, ND | Award Amount: $576,649 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2543272 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2543272.html