Image-guided subject-specific modeling of glymphatic transport and amyloid deposition.

The glymphatic system is a brain-wide system of perivascular networks that facilitate exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF) to remove waste products from the brain. A greater understanding of the mechanisms for glymphatic transport may provide insight into how amyloid beta ( A β ) and tau agglomerates, key biomarkers for Alzheimer's disease and other neurodegenerative diseases, accumulate and drive disease progression. In this study, we develop an image-guided computational model to describe glymphatic transport and A β deposition throughout the brain. A β transport and deposition are modeled using an advection-diffusion equation coupled with an irreversible amyloid accumulation (damage) model. We use immersed isogeometric analysis, stabilized using the streamline upwind Petrov-Galerkin (SUPG) method, where the transport model is constructed using parameters inferred from brain imaging data resulting in a subject-specific model that accounts for anatomical geometry and heterogeneous material properties. Both short-term (30-min) and long-term (12-month) 3D simulations of soluble amyloid transport within a mouse brain model were constructed from diffusion weighted magnetic resonance imaging (DW-MRI) data. In addition to matching short-term patterns of tracer deposition, we found that transport parameters such as CSF flow velocity play a large role in amyloid plaque deposition. The computational tools developed in this work will facilitate investigation of various hypotheses related to glymphatic transport and fundamentally advance our understanding of its role in neurodegeneration, which is crucial for the development of preventive and therapeutic interventions.
Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.