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 i...
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BMC
2024-10-01
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| Series: | Fluids and Barriers of the CNS |
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| Online Access: | https://doi.org/10.1186/s12987-024-00582-0 |
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| author | Lars Willas Dreyer Anders Eklund Marie E. Rognes Jan Malm Sara Qvarlander Karen-Helene Støverud Kent-Andre Mardal Vegard Vinje |
| author_facet | Lars Willas Dreyer Anders Eklund Marie E. Rognes Jan Malm Sara Qvarlander Karen-Helene Støverud Kent-Andre Mardal Vegard Vinje |
| author_sort | Lars Willas Dreyer |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e26d5ad6452b443394cb844469d76bdc |
| institution | OA Journals |
| issn | 2045-8118 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
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| series | Fluids and Barriers of the CNS |
| spelling | doaj-art-e26d5ad6452b443394cb844469d76bdc2025-08-20T02:17:53ZengBMCFluids and Barriers of the CNS2045-81182024-10-0121112210.1186/s12987-024-00582-0Modeling CSF circulation and the glymphatic system during infusion using subject specific intracranial pressures and brain geometriesLars Willas Dreyer0Anders Eklund1Marie E. Rognes2Jan Malm3Sara Qvarlander4Karen-Helene Støverud5Kent-Andre Mardal6Vegard Vinje7Department of Scientific Computing and Numerical Analysis, Simula Research LaboratoryDepartment of Diagnostics and Intervention, Biomedical engineering and radiation physics, Umeå UniversityDepartment of Scientific Computing and Numerical Analysis, Simula Research LaboratoryDepartment of Clinical Sciences, Umeå UniversityDepartment of Diagnostics and Intervention, Biomedical engineering and radiation physics, Umeå UniversityDepartment of Diagnostics and Intervention, Biomedical engineering and radiation physics, Umeå UniversityDepartment of Scientific Computing and Numerical Analysis, Simula Research LaboratoryDepartment of Scientific Computing and Numerical Analysis, Simula Research LaboratoryAbstract 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.https://doi.org/10.1186/s12987-024-00582-0Infusion testCSF circulationGlymphatic pathwayCSF dynamicsIntracranial pressureParavascular flow |
| spellingShingle | Lars Willas Dreyer Anders Eklund Marie E. Rognes Jan Malm Sara Qvarlander Karen-Helene Støverud Kent-Andre Mardal Vegard Vinje Modeling CSF circulation and the glymphatic system during infusion using subject specific intracranial pressures and brain geometries Fluids and Barriers of the CNS Infusion test CSF circulation Glymphatic pathway CSF dynamics Intracranial pressure Paravascular flow |
| title | Modeling CSF circulation and the glymphatic system during infusion using subject specific intracranial pressures and brain geometries |
| title_full | Modeling CSF circulation and the glymphatic system during infusion using subject specific intracranial pressures and brain geometries |
| title_fullStr | Modeling CSF circulation and the glymphatic system during infusion using subject specific intracranial pressures and brain geometries |
| title_full_unstemmed | Modeling CSF circulation and the glymphatic system during infusion using subject specific intracranial pressures and brain geometries |
| title_short | Modeling CSF circulation and the glymphatic system during infusion using subject specific intracranial pressures and brain geometries |
| title_sort | modeling csf circulation and the glymphatic system during infusion using subject specific intracranial pressures and brain geometries |
| topic | Infusion test CSF circulation Glymphatic pathway CSF dynamics Intracranial pressure Paravascular flow |
| url | https://doi.org/10.1186/s12987-024-00582-0 |
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