CSF dynamics throughout the ventricular system using 4D flow MRI: associations to arterial pulsatility, ventricular volumes, and age

Abstract

Background: Cerebrospinal fluid (CSF) dynamics are increasingly studied in aging and neurological disorders. Models of CSF-mediated waste clearance suggest that altered CSF dynamics could play a role in the accumulation of toxic waste in the CNS, with implications for Alzheimer's disease and other proteinopathies. Therefore, approaches that enable quantitative and volumetric assessment of CSF flow velocities could be of value. In this study we demonstrate the feasibility of 4D flow MRI for simultaneous assessment of CSF dynamics throughout the ventricular system, and evaluate associations to arterial pulsatility, ventricular volumes, and age.

Methods: In a cognitively unimpaired cohort (N = 43; age 41-83 years), cardiac-resolved 4D flow MRI CSF velocities were obtained in the lateral ventricles (LV), foramens of Monro, third and fourth ventricles (V3 and V4), the cerebral aqueduct (CA) and the spinal canal (SC), using a velocity encoding (venc) of 5 cm/s. Cerebral blood flow pulsatility was also assessed with 4D flow (venc = 80 cm/s), and CSF volumes were obtained from T1- and T2-weighted MRI. Multiple linear regression was used to assess effects of age, ventricular volumes, and arterial pulsatility on CSF velocities.

Results: Cardiac-driven CSF dynamics were observed in all CSF spaces, with region-averaged velocity range and root-mean-square (RMS) velocity encompassing from very low in the LVs (RMS 0.25 ± 0.08; range 0.85 ± 0.28 mm/s) to relatively high in the CA (RMS 6.29 ± 2.87; range 18.6 ± 15.2 mm/s). In the regression models, CSF velocity was significantly related to age in 5/6 regions, to CSF space volume in 2/3 regions, and to arterial pulsatility in 3/6 regions. Group-averaged waveforms indicated distinct CSF flow propagation delays throughout CSF spaces, particularly between the SC and LVs.

Conclusions: Our findings show that 4D flow MRI enables assessment of CSF dynamics throughout the ventricular system, and captures independent effects of age, CSF space morphology, and arterial pulsatility on CSF motion.

Keywords: 4D flow MRI; Cardiac pulsatility; Cerebral blood flow; Cerebrospinal fluid; Flow dynamics; Magnetic resonance imaging.

Fig. 1

Velocity images from a 4D flow MRI scan of cerebrospinal fluid (CSF) shown in the sagittal plane (left) in the anterior-posterior (AP) and superior-inferior (SI) velocity directions at late diastolic phase of the cardiac cycle, indicating CSF inflow in the third ventricle (V3), the cerebral aqueduct (CA) and the spinal canal (SC). Velocity streamlines (right) were generated from the same 4D flow dataset using Ansys EnSight (2022R2) at the same cardiac cycle time frame as the left velocity images. Cardiac-resolved visualizations of the same dataset are provided in the supplementary material (Sup. Vid. 1; Sup. Vid. 2). Note that the streamline figure in the middle represents a 45-degree rotation of the right figure around the vertical (SI) axis. RL, right-left; V4, fourth ventricle; FMo, foramen of Monro; LV, lateral ventricle

Fig. 2

Cardiac-resolved CSF velocity waveforms in all CSF ROIs averaged over the entire cohort (N = 43), with shaded regions representing ± 1 standard deviation (SD). The individual velocity waveforms were defined as the first principal component (PC1) of the ROI-averaged x-, y-, and z-velocity components. Note that positive velocities indicate CSF inflow to the brain (in the SC-to-LV direction), and negative velocities indicate CSF outflow due to CSF being pushed out by the inflow of blood during the systolic phase of the cardiac cycle. The cohort-average heart rate was 66 ± 9.7 bpm

Fig. 3

Timing differences in inflow and outflow among CSF spaces, indicating that CSF outflow during the systolic phase of the cardiac cycle starts in the (SC), followed by the 4th ventricle (V4), then relatively concomitantly in the cerebral aqueduct (CA), 3rd ventricle (V3) and foramen of Monro (FMo), and finally in the lateral ventricles (LV) with an outflow delay difference of about 3 frames (~ 140 ms) from the SC. Note that negative PCA velocity here indicates CSF outflow (which occurs several times frames after the systolic onset), due to CSF being pushed out by the inflow of blood. The PC1 waveforms displayed here were averaged over the entire cohort (N = 43), with shaded regions reflecting ± 1 standard deviation, and z-scored to facilitate visualization on different velocity scales

Fig. 4

Group-averaged cerebral aqueduct (CA) CSF flow waveform after manual segmentations performed in GyroTools GTFlow, with patched region corresponding to ± 1 standard deviation (SD). The average stroke volume was 13.7 ± 11.6 µl per cardiac cycle from N = 43 participants