Measurement of CSF pulsation from EPI-based human fMRI

It is recently discovered that the glymphatic system and meningeal lymphatic system are the primary routes for the clearance of brain waste products. The CSF flow is part of these systems, facilitating the clearance procedure. Nonetheless, the relationship between CSF flow and brain functional activity has been underexplored. To investigate CSF dynamics and functional brain activity simultaneously, recent studies have proposed a CSF inflow index measured on edge slices (CSFedge) of echo-planar imaging (EPI) based functional magnetic resonance imaging (fMRI), however, it lacks the quantitative aspect of the CSF pulsation. We proposed a new method for quantifying CSF pulsation (CSFpulse) based on an interslice CSF pulsation model in the 4th ventricle of EPI-based fMRI. The proposed CSFpulse successfully detected the higher CSF flow during the resting state than the typical task states (visual and motor) (p<.05), which is consistent with previous studies based on phase contrast (PC) MRI and CSF volume MRI, while it was not detected in CSFedge based indices or baseline CSF signals in various regions of interest (ROIs). Moreover, CSFpulse demonstrated dynamic functional changes in CSF pulsation: it decreased during the activation-on blocks while it increased during the activation-off blocks. CSFpulse significantly correlated with stroke volume measured using PC MRI, a standard method for CSF pulsation quantification, under the same functional state, while CSFedge based indices or CSF ROIs showed no correlation with the PC MRI stroke volume. Lastly, the correlation of CSFpulse with global BOLD was weaker than that of CSFedge, suggesting that CSFpulse may reflect distinct CSF physiological information that is less affected by global BOLD effects. Based on these results, the proposed CSFpulse provides CSF pulsatility information more accurately in a quantitative manner than CSFedge based indices from the recent CSF studies or the conventional ROI-based analysis. In addition to the high correlation with PC MRI, CSFpulse is much faster than PC MRI and provides information of functional brain activations simultaneously, advantageous over PC MRI or CSF volume MRI. Accordingly, the suggested CSFpulse can be used for investigating intra-subject functional changes in BOLD and CSF pulsation simultaneously and inter-subject CSF pulsation variations based on conventional EPI-based fMRI, which warrants further investigation.