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Modeling CSF circulation and the glymphatic system during infusion using subject specific intracranial pressures and brain geometries

Abstract

Background Infusion testing is an established method for assessing CSF resistance in patients with idiopathic normal pressure hydrocephalus (iNPH). To what extent the increased resistance is related to the glymphatic system is an open question. Here we introduce a computational model that includes the glymphatic system and enables us to determine the importance of (1) brain geometry, (2) intracranial pressure, and (3) physiological parameters on the outcome of and response to an infusion test. Methods We implemented a seven-compartment multiple network porous medium model with subject specific geometries from MR images using the finite element library FEniCS. The model consists of the arterial, capillary and venous blood vessels, their corresponding perivascular spaces, and the extracellular space (ECS). Both subject specific brain geometries and subject specific infusion tests were used in the modeling of both healthy adults and iNPH patients. Furthermore, we performed a systematic study of the effect of variations in model parameters. Results Both the iNPH group and the control group reached a similar steady state solution when subject specific geometries under identical boundary conditions was used in simulation. The difference in terms of average fluid pressure and velocity between the iNPH and control groups, was found to be less than 6% during all stages of infusion in all compartments. With subject specific boundary conditions, the largest computed difference was a 75% greater fluid speed in the arterial perivascular space (PVS) in the iNPH group compared to the control group. Changes to material parameters changed fluid speeds by several orders of magnitude in some scenarios. A considerable amount of the CSF pass through the glymphatic pathway in our models during infusion, i.e., 28% and 38% in the healthy and iNPH patients, respectively. Conclusions Using computational models, we have found the relative importance of subject specific geometries to be less important than individual differences in resistance as measured with infusion tests and model parameters such as permeability, in determining the computed pressure and flow during infusion. Model parameters are uncertain, but certain variations have large impact on the simulation results. The computations resulted in a considerable amount of the infused volume passing through the brain either through the perivascular spaces or the extracellular space.
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Category

Academic article

Language

English

Author(s)

  • Lars Willas Dreyer
  • Anders Eklund
  • Marie Elisabeth Rognes
  • Jan Malm
  • Sara Qvarlander
  • Karen-Helene Støverud
  • Kent-Andre Mardal
  • Vegard Vinje

Affiliation

  • SINTEF Digital / Health Research
  • Umeå University
  • BI Norwegian Business School
  • University of Oslo
  • Expert Analytics
  • Simula Research Laboratory

Date

15.10.2024

Year

2024

Published in

Fluids and Barriers of the CNS

Volume

21

Issue

1

View this publication at Norwegian Research Information Repository