Arterial pulsations and transmantle pressure synergetically drive glymphatic flow

Clearance of waste material from the brain by the glymphatic system results from net flow of cerebrospinal fluid (CSF) through perivascular spaces surrounding veins and arteries. In periarterial spaces, this bulk flow is directed from the cranial subarachnoid space towards the brain's interior. The precise pumping mechanism explaining this net inflow remains unclear. While in vivo experiments have shown that the pulsatile motion in periarterial spaces is synchronized with arterial pulsations, peristalsis alone has been deemed insufficient to explain bulk flow. In this study we examine an alternative mechanism based on the interaction between arterial pulsations and fluctuations in transmantle pressure. Previously studied using pressure data from a hydrocephalus patient, this mechanism is analyzed here in healthy subjects using in vivo flow measurements obtained via phase-contrast magnetic resonance imaging. Arterial pulsations are derived from flow-rate measurements of arterial blood entering the cranial cavity, while transmantle-pressure fluctuations are computed using measurements of CSF flow in the cerebral aqueduct. The two synchronized waveforms are integrated into a canonical multi-branch model of the periarterial spaces, yielding a closed-form expression for the bulk flow. The results confirm that the dynamic interactions between arterial pulsations and transmantle pressure are sufficient to generate a positive inflow along periarterial spaces.