Quantifying Cerebrospinal Fluid Flow Dynamics in Alzheimer's Disease Using 4D Flow MRI

This project aims to advance our understanding of cerebrospinal fluid (CSF) flow dynamics in relation to aging and amyloid accumulation in the brain, using velocity-sensitive 4D-Flow magnetic resonance imaging (4D-Flow MRI), and establish neurofluid flow metrics relevant to Alzheimer’s disease (AD).

Alzheimer’s disease (AD) is characterized by the accumulation of misfolded proteins in the brain and dysfunctional clearance to cerebrospinal fluid (CSF), suggesting that altered CSF flow dynamics could play a role in the pathophysiology. However, such findings are primarily based on studies in animals. Here, we will use a velocity-sensitive brain imaging technique to study CSF flow dynamics in patients with or at risk for AD, aiming to advance our understand of altered neurofluid dynamics in AD and establish new flow imaging biomarkers of interest in aging and AD.

There is a growing interesting in non-invasive methods targeting human CSF dynamics. However, existing flow sensitive MRI methods are typically tailored towards blood flow, limiting investigation of human CSF flow dynamics in neurological and neurodegenerative disorders. This project will evaluate 4D-Flow MRI acquisition and reconstruction strategies targeting both fast and slow CSF flow dynamics, and provide protocols and analysis tools for community use. Using these tools, we will perform comprehensive evaluations of CSF flow dynamics in AD cohorts to establish critical knowledge on how CSF flow dynamics are related to aging, neurodegeneration and AD.

While better understanding of human CSF dynamics will not directly provide any direct curative treatment, knowledge gaps in the pathophysiology of AD that will be addressed in this project may guide future large prospective studies on neurofluid flow dynamics in AD. Specifically, exploring various CSF flow metrics and their association to amyloid accumulation may in turn give insights on how altered CSF dynamics could relate to CSF-mediated clearance, and provide further understanding of which neurofluid flow metrics that are worth pursuing in interventional studies and clinical trials, and in turn facilitate development of prevention and treatment strategies.