Direct observation of cerebrospinal fluid bulk flow in the brain

Cerebrospinal fluid (CSF) serves a~vital~role~in~normal brain function.~Its~adequate~flow and~exchange~with interstitial fluid~through perivascular spaces (PVS)~has been shown to be important in the clearance of toxic metabolites like amyloid-$\beta $,~and~its~disturbance~can~cause severe neurological diseases. It has long been suspected that bulk flow may transport CSF, but limitations in imaging techniques have~prevented direct observation of such flows in the PVS.~In this talk, we describe a novel approach using~high speed two~photon laser scanning microscopy which has allowed for~the first ever direct observation of~CSF flow~in the PVS of a mouse brain.~By performing~particle tracking velocimetry, we quantify the CSF bulk flow speeds and PVS geometry.~This technique enables future studies of CSF flow disturbances on a new scale and~will pave the way for evaluating the role of these fluxes in neurodegenerative disease.~