Quantitative Assessment of Cerebrospinal Fluid-Vascular Association in Alzheimer's Disease Using Phase-Contrast and 4D-Flow Magnetic Resonance Imaging

Summary

Phase-contrast magnetic resonance imaging (PC-MRI) and four-dimensional flow MRI (4D-Flow) reveal an altered association between cerebrospinal fluid (CSF) dynamics and cerebral vasculature in Alzheimer's disease, reflecting potential glymphatic alterations and offering a non-invasive, quantitative method for potential adjunctive biomarker and disease monitoring.

Abstract

From a neuropathological perspective, the most well-known pathological change in Alzheimer's disease (AD) to date is primarily tau protein hyperphosphorylation, which leads to the formation of intracellular neurofibrillary tangles (NFTs) and amyloid protein deposition—namely, the accumulation of amyloid protein (Aβ) and other protein aggregates outside cells, resulting in neurofibrillary tangles. The glymphatic system, driven by arterial pulsation, clears waste, including amyloid-β, via perivascular spaces (PVS). In AD, vascular dysfunction and slow-wave sleep speculation have been separately observed, and both are hypothesized to impair glymphatic clearance. However, causal links among these factors remain unproven, and the proposed self‑reinforcing cycle—where vascular failure may aggravate protein deposition and further vascular damage—is speculative. This study utilized two-dimensional cine phase-contrast MRI (PC-MRI) and four-dimensional flow MRI (4D-Flow) to quantify hydrodynamic parameters, including cerebrospinal fluid (CSF) flow in the cerebral aqueduct (CA) and blood flow in the internal carotid artery (ICA). Altered CSF-vascular association was observed in AD, suggesting possible glymphatic involvement. The integration of CSF and vascular flow metrics provides a promising biomarker framework for early AD detection and monitoring. PC-MRI and 4D-Flow reveal altered CSF-vascular association in Alzheimer’s disease, reflecting potential glymphatic alteration and offering a non-invasive, quantitative method for potential adjunctive biomarker and disease monitoring.

Introduction

Alzheimer's disease (AD) is the most common type of dementia—a progressive, irreversible neurological disorder characterized by memory loss and cognitive dysfunction^1,2. With its global incidence rising rapidly³, early detection and intervention have gained significant attention worldwide.

The precise etiology of AD remains unclear due to its complex pathophysiology. Key neuropathological features include intracellular neurofibrillary tangles from tau hyperphosphorylation and extracellular amyloid-β (Aβ) plaques¹. A....

Protocol

Participants
Participants were recruited from the Neurology Department of Ningde Municipal Hospital and Ningde Normal University between November 2022 and November 2023. Following the inclusion/exclusion criteria, 35 patients (16 AD, 19 MCI) and 25 healthy elderly controls (NC) were included. Informed consent was obtained from all participants and from the families of those with cognitive impairment. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Ningde Municipal Hospital (Approval No: 20200901).

Inclusion criteria were age between 50 ....

Results

Clinical baseline information and cognitive scores
The cohort comprised 16 AD, 19 MCI, and 25 NC participants. Groups were comparable in gender, weight, height, BMI, cardiovascular risk factors, and heart rate (p > 0.05), but differed in age (p = 0.026) and years of education (p = 0.033) (Table 1). As expected, MMSE and MoCA total and sub-scores differed significantly among groups (all p < 0.001), with AD < MCI < NC (Table 2

Discussion

By integrating 2D cine PC-MRI and 4D flow MRI, this study quantitatively evaluated alterations in CSF dynamics and cervical macrovascular hemodynamics across the AD spectrum, as well as their interplay. The principal findings can be summarized as follows: (1) Peak systolic and diastolic CSF flow velocities in the cerebral aqueduct were significantly reduced in patients with AD and MCI, and these reductions correlated with cognitive scores. (2) Maximum flow velocity and WSS in the LICA were significantly lower in the AD g.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
28-channel head-neck coil	GE Healthcare, Waukesha, WI, USA	Part of GE SIGNA Architect system; https://www.gehealthcare.com	Dedicated receive-only phased-array coil for combined head and neck imaging; employed for signal reception in all MRI sequences.
2D cine phase-contrast MRI sequence (Fast PC Cine Slice)	GE Healthcare, Waukesha, WI, USA	Part of GE SIGNA Architect software package	2D retrospectively gated phase-contrast sequence; used to quantify CSF flow velocity and stroke volume in the cerebral aqueduct. Parameters: Venc 12 cm/s, 20–30 phases/cardiac cycle, acquired perpendicular to the aqueduct.
4D flow MRI sequence (Sag 4D Flow)	GE Healthcare, Waukesha, WI, USA	Part of GE SIGNA Architect software package	Time-resolved 3D phase-contrast sequence; used to capture spatially resolved hemodynamic data in the cervical carotid arteries. Parameters: Venc 50 cm/s, 20–30 phases/cardiac cycle, 40–50 slices.
CVI42 post-processing workstation (version 5.14)	Circle Cardiovascular Imaging, Calgary, Canada	https://www.circlecvi.com/cvi42/	Dedicated cardiovascular and flow analysis software; used for vessel segmentation, ROI delineation, flow quantification (CSF and blood), and wall shear stress calculation. Version 5.14.
GE SIGNA Architect 3.0T MRI scanner	GE Healthcare, Waukesha, WI, USA	https://www.gehealthcare.com/products/magnetic-resonance-imaging/signa-architect	Whole-body 3.0T superconducting MRI system equipped with a 28-channel head-neck quadrature coil; used for all structural, 2D cine PC, and 4D flow acquisitions.
IBM SPSS Statistics (version 25)	IBM Corp., Armonk, NY, USA	SCR_002865; https://www.ibm.com/products/spss-statistics	Statistical analysis software; used for all descriptive statistics, group comparisons, correlations, regression analyses, and ROC curve analysis. Version 25.