Monitoring the perivascular cerebrospinal fluid dynamics of the glymphatic pathway using co-localized photoacoustic microscopy.

In vivo imaging plays an important role in investigating how the glymphatic system drains metabolic waste and pathological proteins from the central nervous system. However, the spatial resolutions and imaging specificities of the available preclinical imaging methods for the glymphatic system are insufficient, and they cannot simultaneously locate the cerebrovascular and glymphatic pathways to enable the monitoring of the perivascular cerebrospinal fluid dynamics. This Letter proposes an imaging strategy for the in vivo monitoring of cerebrospinal fluid flow using co-localized photoacoustic volumetric microscopy. Imaging results showed that the glymphatic pathway is one of the crucial pathways for the drainage of cerebrospinal fluid, and it mainly enters the brain parenchyma along periarterial routes. Continuous intravital imaging enables the monitoring of the cerebrospinal fluid flow as well as the drainage and clearance from the glymphatic system after the tracer has entered the cerebrospinal fluid. The technique can enhance understanding of the cerebrospinal fluid circulation and open up new insights into neurodegenerative brain diseases.