During which phase of the cardiac cycle is freshly actively formed cerebrospinal fluid released into the brain ventricles: systole or diastole?

Abstract The timing of freshly actively formed cerebrospinal fluid (FAF CSF) release into the cerebral ventricles during the cardiac cycle remains uncertain despite extensive imaging and experimental studies. By analyzing phase-contrast MRI data from healthy individuals, developing a simplified mathematical model of CSF volume changes per cardiac cycle, and re-evaluating prior aqueductal cannulation experiments in cats, we demonstrate that the observed net caudal CSF flow of approximately 6 µL per cardiac cycle can be explained by FAF CSF release confined exclusively to either systole or diastole. In contrast, continuous release throughout the entire cardiac cycle would lead to progressive CSF volume accumulation of 6 µL per cycle, which is incompatible with steady-state conditions. Experimental observations in cats showed no net CSF outflow when an open aqueductal cannula prevented diastolic negative pressure according to Pascal's law, supporting a passive diastolic release mechanism rather than an active systolic release that would require additional energy to overcome elevated intraventricular pressure. This passive diastolic process operates through a "push-and-refill" mechanism, where old CSF is expelled during systole due to increased intraventricular pressure and FAF CSF is released into the ventricles during diastole due to relative negative pressure (suction). The clinical function of external ventricular drainage (EVD) further corroborates this mechanism: when the EVD is set to a positive pressure value relative to the reference point, no relative negative pressure is created during diastole and drainage stops, whereas negative pressure settings result in continuous CSF release. These findings indicate that FAF CSF release most consistently occurs during diastole as a passive, pressure-driven process. This diastolic refill mechanism refines current concepts of CSF physiology and provides a biophysical basis for understanding both normal CSF dynamics and clinical CSF diversion techniques such as EVD. Keywords: CSF flow MRI, Cerebrospinal fluid dynamics, Choroid plexus, Cardiac cycle, EVD CSF drainage