Abstract
Traditionally, cerebrospinal fluid (CSF) is believed to exit the brain via arachnoid villi, being absorbed into the superior sagittal sinus (SSS), with a net flow towards these exit sites driven by constant CSF turnover. However, measuring these velocities non-invasively in humans is challenging due to their slow nature and the presence of relatively large confounding factors such as physiological CSF pulsations (heartbeat and respiration) and head motion. This study presents a novel magnetic resonance imaging (MRI) method designed to measure the net velocity of CSF whilst accounting for confounding effects, which is called CSF displacement encoding with stimulated echoes (CSF-DENSE). By applying a similar model as used to study sea-level rise, different motion components of CSF were successfully disentangled. Simulations, along with phantom and in vivo experiments, demonstrate the ability of CSF-DENSE combined with time series analysis using unobserved components modeling to detect ultraslow velocities of approximately 1 μm/s, even in the presence of confounding motions that are an order of magnitude larger. Based on CSF flow measurements in the aqueduct, the expected net velocity in the subarachnoid space (SAS) towards the SSS was estimated to be 4.22 ± 0.14 µm/s. However, no significant net velocity toward the SSS was observed (v = -0.18±0.15 µm/s, with positive velocity directed towards the SSS). This questions whether outflow via the SAS towards the SSS is the main exit route of CSF, thereby challenging the classical view of CSF outflow. These findings suggest the need to reconsider traditional models of CSF outflow pathways, with potential implications for understanding and treating neurological disorders. Clinical trial number: Not applicable.