Photoacoustic computed tomography monitors cerebrospinal fluid dynamics and glymphatic function.

Area of Science:

• Neuroscience
• Biomedical Imaging
• Fluid Dynamics

Background:

• Cerebrospinal fluid (CSF) circulation removes metabolic waste, but efficiency declines with aging and neurodegenerative diseases.
• Current imaging methods for CSF drainage lack depth, require radioactive tracers, or are too slow for dynamic flow visualization.
• Developing non-invasive techniques to visualize CSF transport is crucial for understanding brain health and disease.

Purpose of the Study:

• To establish whole-body photoacoustic computed tomography (PACT) as a method for real-time, three-dimensional imaging of CSF transport in vivo.
• To quantify CSF efflux under varying physiological conditions, such as different anesthesia protocols.
• To assess CSF clearance dynamics in a mouse model of Alzheimer's disease (AD) and compare it to healthy controls.

Main Methods:

• Utilized whole-body photoacoustic computed tomography (PACT) for imaging.
• Employed indocyanine green as a non-radioactive tracer for CSF visualization.
• Tracked CSF movement from the spinal canal into the brain and quantified its efflux in live mice.
• Compared tracer retention in a mouse model of Alzheimer's disease with healthy control mice.

Main Results:

• PACT successfully visualized three-dimensional, real-time CSF transport in mice.
• Quantified CSF efflux rates under different anesthesia conditions.
• Demonstrated significantly impaired CSF clearance in a mouse model of Alzheimer's disease, with tracer retention for several days.
• Indicated reduced waste removal in diseased mice compared to healthy controls.

Conclusions:

• Whole-body PACT is a viable non-invasive platform for measuring CSF and glymphatic function in vivo.
• PACT enables the study of altered brain fluid transport in aging and neurological disorders.
• This technique offers a new tool for preclinical research in neurodegenerative diseases affecting waste clearance.