A Quantitative Understanding of Glymphatic Transport and Amyloid Deposition Using Image-Based Subject-Specific Modelling
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The glymphatic system is a brain-wide network of perivascular pathways that facilitates waste clearance by enabling solute exchange between cerebrospinal fluid (CSF) and interstitial fluid (ISF). Dysfunction of this system can lead to the accumulation of amyloid beta (Aβ) and tau proteins, key hallmarks of Alzheimer’s and other neurodegenerative diseases. A mechanistic understanding of glymphatic transport and deposition of these biomarkers is essential for developing strategies to prevent or slow disease progression. In this work, we developed an image-based, subject-specific computational framework, tightly integrated with experimental data, to enable quantitative analysis of glymphatic transport and protein deposition throughout the brain. Amyloid transport and deposition are modelled using an unsteady advection–diffusion equation of soluble amyloid, coupled with an irreversible amyloid plaque accumulation model to account for fibrilized amyloid formation [1]. Simulations are performed using immersed isogeometric analysis, stabilized with the streamline upwind Petrov-Galerkin (SUPG) method. Model parameters are inferred directly from brain imaging data, yielding subject-specific representations that capture anatomical geometry and heterogeneous material properties. The diffusive field and brain geometry are extracted from diffusion-weighted magnetic resonance imaging (MRI), while the advective field is reconstructed by solving an inverse velocity estimation problem informed by contrast-enhanced MRI data acquired via tracer injection into the CSF through the cisterna magna. Short- and long-term simulations of soluble Aβ transport and plaque deposition are performed in mouse brain models and analysed. This image-informed computational framework provides a robust tool for predicting brain-wide glymphatic transport, facilitating hypothesis testing and advancing subject-specific prevention and treatment strategies for neurodegenerative disease.
