Quantitative evaluation of normal cerebrospinal fluid flow in the Sylvian aqueduct and perivascular spaces of the middle cerebral artery and circle of Willis via 2D phase-contrast MR imaging

Recently, it was proposed that CSF flow constitutes a critical part of the glymphatic system, playing a critical role in various brain abnormalities from Alzheimers disease to hydrocephalus. Thus, measurement of CSF flow has been increasingly used for diagnostic and clinical monitoring purposes. Phase-contrast MRI has been used to determine CSF flow. However, CSF flow in the periarterial spaces of the circle of Willis and the middle cerebral artery which are important conduits remain unexplored. We employed phase-contrast MRI to explore CSF flow along the perivascular spaces of the circle of Willis and the middle cerebral artery to establish baseline parameters of CSF and compare them with the Sylvian aqueduct. To analyze CSF flow in the perivascular space, we developed a new, semi-automated method for outlining the perivascular space and extracting CSF flow parameters. The twenty-four healthy participants were recruited to achieve an even distribution by age (mean: 40 {+/-} 11) and gender (13 males). We validated our routine for CSF flow measurements by comparing CSF flow in the Sylvian aqueduct (0.00700 mL/s) with the range of literature values, 0.0049-0.0432 mL/s. For all CSF parameters, the circle of Willis and middle cerebral artery were differed from the Sylvian aqueduct. For most CSF flow parameters, the 95% confidence intervals of the circle of Willis and middle cerebral artery overlap. The linear mixed models and general linear mixed models for flow indicate strong effects of the conduits. CSF velocity in these conduits were lower 0.159 cm/s and 0.198 cm/s respectively than in the Sylvian aqueduct. Overall, differences in CSF flow parameters between sex and age groups were negligible. In this study, we have validated our routine and established baseline values of CSF flow along the circle of Willis and the middle cerebral artery as well as highlighted the limited influence of sex and/or age.