Photoacoustic computed tomography monitors cerebrospinal fluid dynamics and glymphatic function

Abstract

Abstract Cerebrospinal fluid (CSF) continuously circulates through the brain and surrounding tissues to remove metabolic waste, a process that becomes less efficient with ageing and in neurodegenerative disease. Visualizing this drainage in living animals has been difficult because existing imaging tools either lack depth, require radioactive tracers, or are too slow to capture dynamic flow. Here, we show that whole-body photoacoustic computed tomography (PACT) enables three-dimensional, real-time tracking of CSF transport in mice using indocyanine green. We visualize CSF movement from the spinal canal into the brain, quantify its efflux under different anesthesia conditions, and detect impaired clearance in a mouse model of Alzheimer’s disease. Compared with healthy animals, diseased mice retain the tracer in the brain for several days, indicating reduced waste removal. These results establish PACT as a non-invasive platform for measuring CSF and glymphatic function in vivo, providing a way to study how brain fluid transport is altered in ageing and neurological disorders.