Multimodal MRI Assessment of CSF Dynamics

Yukai (Kai) Zou, Ph.D.

Yukai.Zou@uhs.nhs.uk

Southampton General Hospital

02/10/2026

Mayflower Park

Works set to start on Mayflower Park revetment repairs

Cerebrospinal Fluids (CSF)

Neurons are not the only cells in the CNS.
Choroid plexus secretes the cerebrospinal fluid (CSF)
Brain clears metabolites of transmitters into CSF, also through the choroid plexus
Adult CNS ventricular system is developed from the neural tube lumen. Each endbrain vesicle contains a lateral ventricle, which communicates through an interventricular foramen with the third ventricle in the inter-brain vesicle’s center. The third ventricle continues into the midbrain’s cerebral aqueduct, which becomes the hindbrain’s fourth ventricle and then the spinal cord’s central canal. The ventricular system later contains CSF in older embryos and adults, much of CSF is elaborated by specialised, highly vascular regions of choroid plexus in the roof of the lateral, third, and fourth ventricles
Functions:
Mechanical protection
Metabolic waste clearance
Maintain Homeostasis
Regulation of intracranial pressure
Functional disturbance often manifest before structural abnormalities.

Pathological Mechanisms in Alzheimer’s disease

CSF Assessment: A Multimodal MRI Approach

Enlarged PVS Segmentation

Parenchymal CSF

Compartmental Solute Exchange

Water Transport

PC-MRI

Bulk CSF Flow

Physiological Coupling

Optimising CSF Dynamics Assessment Post Endoscopic Third Ventriculostomy: Integrating Phase-Contrast MRI and fMRI

Hydrocephalus

Abnormal accumulation of CSF
- Elevate intracranial pressure
- Cause brain injury

Endoscopic Third Ventriculostomy (ETV)

Create a small opening in the floor of the third ventricle
- New drainage pathway via the basal cisterns
- Restore CSF circulation

Phase Contrast MRI (PC-MRI)

Chiari Malformation

PC-MRI: Post-ETV Assessment

VENC=6

Physiological CSF Dynamics in fMRI

Aim & Hypothesis

To assess the feasibility of characterising post-ETV CSF dynamics by integrating PC-MRI and fMRI.

We hypothesise that fMRI signals within the basal cisterns are coupled to respiration and capture physiological CSF dynamics.

MRI Acquisition

Data were acquired from a healthy volunteer using a 3 T Siemens Magnetom Vida
- 64-channel head coil
- Sequences:

Cardiac and respiratory signals were recorded using the MR peripheral pulse unit and chest belt

PC-MRI: Acquisition and CSF Flow Quantification

fMRI: Acquisition

fMRI: Preprocessing

Slice-timing correction
Coregistration to T1
Single-voxel time series
1. Cerebellum (negative control)
2. The fourth ventricle
3. Inferior to the interpeduncular cistern (i-IPC)

fMRI: Time Series

fMRI: Time Series Analysis

Power spectrum analysis to assess CSF fluctuations for:
1. Low-frequency oscillation, e.g. vasomotion (0.01 to 0.1 Hz)
2. Respiratory oscillation (0.2 to 0.4 Hz)
3. Cardiac pulsation (1 to 1.7 Hz)

fMRI: Time Series Analysis

fMRI: Time Series Analysis (cont.)

Detrended and band-pass filtered to isolate respiratory oscillations (RO, 0.2 to 0.4Hz).

Coupling strength to respiration assessed with the derivative of the chest-belt signal: \[\frac{d}{dt}\mathrm{RO_{chest}\text{, with a lag range of 10 seconds}}\]
Maximal cross-correlation coefficients (MCCCs) and corresponding delays were calculated.

fMRI: Time Series Analysis (cont.)

Discussion

fMRI provides complementary information to PC‑MRI
- Capture physiological CSF dynamics
- Don’t require setting velocity encoding
- Short increment to the total time
- Suitable for clinical workflows

By integrating PC-MRI and fMRI, this pilot study demonstrates the feasibility of a multimodal MRI protocol for post ETV assessment of CSF dynamics, enabling a non-invasive evaluation of both the CSF patency and physiological dynamics for hydrocephalus patients.

Future Work

MR Physics
- Validation in hydrocephalus patients
- Optimise slice positioning and signal sensitivity
- Minimise aliasing of physiological signals

Interdisciplinary Research
- Interthalamic adhesion
- Intracranial pulsatility
- CSF and plasma biomarkers
- Glymphatic function
- Sleep regulation and cognition

References

Teunissen et al. Blood-based biomarkers for Alzheimer’s disease: towards clinical implementation. Lancet Neurol. 2022; 21(1):66-77.
Huang et al. Alzheimer’s Disease Neuroimaging Initiative. Development and validation of a perivascular space segmentation method in multi-center datasets. Neuroimage. 2024; 298:120803.
Keil et al. Glymphatic dysfunction in Alzheimer’s disease: A critical appraisal. Science. 2025; 389(6756):eadv8269.
Bognár et al. MRI Diffusion Tensor Image Analysis Along the Perivascular Space: Effects of Mean Tract Orientation Divergence. J Magn Reson Imaging. 2026; 64(3):815-829.
Agarwal et al. Current Understanding of the Anatomy, Physiology, and Magnetic Resonance Imaging of Neurofluids: Update From the 2022 “ISMRM Imaging Neurofluids Study Group” Workshop in Rome. J Magn Reson Imaging. 2024; 59(2):431-449.
Yadav et al. Endoscopic Third Ventriculostomy - A Review. Neurol India. 2021; 69(Suppl):S502-S513.
Fultz et al. Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science. 2019; 366(6465):628-631.
Yang et al. Coupling between cerebrovascular oscillations and CSF flow fluctuations during wakefulness: An fMRI study. J Cereb Blood Flow Metab. 2022; 42(6):1091-1103.
Nair et al. Human CSF movement influenced by vascular low frequency oscillations and respiration. Front Physiol. 2022; 13:940140.
Nair et al. Amplitude fluctuations of cerebrovascular oscillations and CSF movement desynchronize during NREM3 sleep. J Cereb Blood Flow Metab. 2025; 45(10):1980-1992.
Dagum et al. The glymphatic system clears amyloid beta and tau from brain to plasma in humans. Nat Commun. 2026; 17(1):715.

Acknowledgements

UHS Medical Physics Department
UHS Radiology Department
Dr Angela Darekar
Dr Robert Marchbanks
Dr Yunjie Tong
Dr Ho-Ching Yang
Rory Heard
Emmanuel Ogunsakin
Study Volunteers

Learn more about
MRI research at Southampton

https://www.southampton.ac.uk/research/groups/southampton-imaging-radiology-research-group-sirrg