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Voxelized simulation of cerebral oxygen perfusion elucidates hypoxia in aged mouse cortex
- Source :
- PLoS Computational Biology, Vol 17, Iss 1, p e1008584 (2021), PLoS Computational Biology
- Publication Year :
- 2021
- Publisher :
- Public Library of Science (PLoS), 2021.
-
Abstract
- Departures of normal blood flow and metabolite distribution from the cerebral microvasculature into neuronal tissue have been implicated with age-related neurodegeneration. Mathematical models informed by spatially and temporally distributed neuroimage data are becoming instrumental for reconstructing a coherent picture of normal and pathological oxygen delivery throughout the brain. Unfortunately, current mathematical models of cerebral blood flow and oxygen exchange become excessively large in size. They further suffer from boundary effects due to incomplete or physiologically inaccurate computational domains, numerical instabilities due to enormous length scale differences, and convergence problems associated with condition number deterioration at fine mesh resolutions. Our proposed simple finite volume discretization scheme for blood and oxygen microperfusion simulations does not require expensive mesh generation leading to the critical benefit that it drastically reduces matrix size and bandwidth of the coupled oxygen transfer problem. The compact problem formulation yields rapid and stable convergence. Moreover, boundary effects can effectively be suppressed by generating very large replica of the cortical microcirculation in silico using an image-based cerebrovascular network synthesis algorithm, so that boundaries of the perfusion simulations are far removed from the regions of interest. Massive simulations over sizeable portions of the cortex with feature resolution down to the micron scale become tractable with even modest computer resources. The feasibility and accuracy of the novel method is demonstrated and validated with in vivo oxygen perfusion data in cohorts of young and aged mice. Our oxygen exchange simulations quantify steep gradients near penetrating blood vessels and point towards pathological changes that might cause neurodegeneration in aged brains. This research aims to explain mechanistic interactions between anatomical structures and how they might change in diseases or with age. Rigorous quantification of age-related changes is of significant interest because it might aide in the search for imaging biomarkers for dementia and Alzheimer’s disease.<br />Author summary Brain function critically depends on the maintenance of physiological blood supply and metabolism in the cortex. Disturbances to adequate perfusion have been linked to age-related neurodegeneration. However, the precise correlation between age-related hemodynamic changes and the resulting decline in oxygen delivery is not well understood and has not been quantified. Therefore, we introduce a new compact, and therefore highly scalable, computational method for predicting the physiological relationship between hemodynamics and cortical oxygen perfusion for large sections of the cortical microcirculation. We demonstrate the novel mesh generation-free (MGF), multi-scale simulation approach through realistic in vivo case studies of cortical microperfusion in the mouse brain. We further validate mechanistic correlations and a quantitative relationship between blood flow and brain oxygenation using experimental data from cohorts of young, middle aged and old mouse brains. Our computational approach overcomes size and performance limitations of previous unstructured meshing techniques to enable the prediction of oxygen tension with a spatial resolution of least two orders of magnitude higher than previously possible. Our simulation results support the hypothesis that structural changes in the microvasculature induce hypoxic pockets in the aged brain that are absent in the healthy, young mouse.
- Subjects :
- 0301 basic medicine
Aging
Pulmonology
Physiology
Computer science
Biochemistry
Mice
0302 clinical medicine
Blood Flow
Cortex (anatomy)
Image Processing, Computer-Assisted
Medicine and Health Sciences
Biology (General)
Hypoxia
Cerebral Cortex
Microscopy, Confocal
Ecology
Mathematical model
Physics
Simulation and Modeling
Neurodegeneration
Models, Cardiovascular
Hematology
Oxygen Metabolism
Body Fluids
Chemistry
Blood
medicine.anatomical_structure
Hematocrit
Computational Theory and Mathematics
Cerebral blood flow
Mesh generation
Cerebrovascular Circulation
Modeling and Simulation
Physical Sciences
Anatomy
medicine.symptom
Perfusion
Algorithms
Research Article
Chemical Elements
QH301-705.5
Research and Analysis Methods
Microcirculation
03 medical and health sciences
Cellular and Molecular Neuroscience
Medical Hypoxia
Genetics
medicine
Animals
Computer Simulation
Mass Transfer
Molecular Biology
Ecology, Evolution, Behavior and Systematics
Computational Biology
Biology and Life Sciences
Hypoxia (medical)
medicine.disease
Oxygen
Blood Counts
Metabolism
030104 developmental biology
Cardiovascular Anatomy
Blood Vessels
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 15537358
- Volume :
- 17
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- PLoS Computational Biology
- Accession number :
- edsair.doi.dedup.....b48065aae2b51131ee6c8b3c77aa2a7d