CSF pulsations measured in Parkinson's disease patients using EPI-based fMRI data.

Introduction: Cerebrospinal fluid (CSF) flow is involved in brain waste clearance and may be impaired in neurodegenerative diseases such as Parkinson's disease. This study aims to investigate the relationship between the CSF pulsation and the development of dementia in Parkinson's disease (PD) patients using EPI-based fMRI. Methods: We measured CSF pulsation in the 4th ventricle of 17 healthy controls and 35 PD patients using a novel CSF pulsation index termed "CSFpulse" based on echo-planar imaging (EPI)-based fMRI. The PD patients were classified into a PD with dementia high-risk group (PDD-H, n = 19) and a low risk group (PDD-L, n = 16), depending on their development of dementia within 5 years after initial brain imaging. The size of the 4th ventricle was measured using intensity-based thresholding. Results: We found that CSF pulsation was significantly higher in PD patients than in healthy controls, and that PD patients with high risk of dementia (PDD-H) had the highest CSF pulsation. We also observed an enlargement of the 4th ventricle in PD patients compared to healthy controls. Conclusion: Our results suggest that CSF pulsation may be a potential biomarker for PD progression and cognitive decline, and that EPI-based fMRI can be a useful tool for studying CSF flow and brain function in PD.

Measurement of changes in cerebrospinal fluid pulsation after traumatic brain injury using echo-planar imaging-based functional MRI.

Traumatic brain injury (TBI) is a major public health concern worldwide, with a high incidence and a significant impact on morbidity and mortality. The alteration of cerebrospinal fluid (CSF) dynamics after TBI is a well-known phenomenon; however, the underlying mechanisms and their implications for cognitive function are not fully understood. In this study, we propose a new approach to studying the alteration of CSF dynamics in TBI patients. Our approach involves using conventional echo-planar imaging-based functional MRI with no additional scan, allowing for simultaneous assessment of functional CSF dynamics and blood oxygen level-dependent-based functional brain activities. We utilized two previously suggested indices of (i) CSFpulse, and (ii) correlation between global brain activity and CSF inflow. Using CSFpulse, we demonstrated a significant decrease in CSF pulsation following TBI (p < 0.05), which was consistent with previous studies. Furthermore, we confirmed that the decrease in CSF pulsation was most prominent in the early months after TBI, which could be explained by ependymal ciliary loss, intracranial pressure increment, or aquaporin-4 dysregulation. We also observed a decreasing trend in the correlation between global brain activity and CSF inflow in TBI patients (p < 0.05). Our findings suggest that the decreased CSF pulsation after TBI could lead to the accumulation of toxic substances in the brain and an adverse effect on brain function. Further longitudinal studies with larger sample sizes, TBI biomarker data, and various demographic information are needed to investigate the association between cognitive decline and CSF dynamics after TBI. Overall, this study sheds light on the potential role of altered CSF dynamics in TBI-induced neurologic symptoms and may contribute to the development of novel therapeutic interventions.

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.