Quantitative in vivo measurements of cerebrospinal fluid flow through perivascular spaces in the brain

Recent discoveries have uncovered a novel route for the flow of cerebrospinal fluid (CSF) through the brain which is important for the removal of protein waste, such as amyloid-β. Characterizing this flow and the mechanisms which reduce it may offer new insight into the development of neurodegenerative diseases, such as Alzheimer’s disease, which are correlated with accumulation of protein waste. CSF enters the brain along perivascular spaces (PVSs) — annular tunnels around arteries — and arterial pulsations are hypothesized to drive these flows, but this has never been quantitatively shown. We perform experiments to measure PVS flows by injecting microspheres into the CSF of living mice, imaging PVSs using two-photon microscopy, and performing particle tracking velocimetry. We also perform line scans to measure arterial pulsations. These measurements offer the first quantitative evidence demonstrating that CSF is driven through PVSs by arterial pulsations. Furthermore, by increasing blood pressure, we observe changes in the arterial pulsations and a net reduction in the CSF flow speed. Our results offer one potential causal mechanism which may contribute to reduced protein waste clearance and development of neurodegenerative diseases.