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Voxelized simulation of cerebral oxygen perfusion elucidates hypoxia in aged mouse cortex

Grant Hartung, Shoale Badr, Mohammad Reza Moeini Gharagozlo, Frédéric Lesage, David Kleinfeld, Ali Alaraj et Andreas Linninger

Article de revue (2021)

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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.

Sujet(s): 1900 Génie biomédical > 1900 Génie biomédical
2500 Génie électrique et électronique > 2500 Génie électrique et électronique
9000 Sciences de la santé > 9000 Sciences de la santé
Département: Département de génie électrique
Organismes subventionnaires: National Science Foundation, National Institute of Health, Neurological Disorders and Stroke, National Institute of Aging
Numéro de subvention: CBET‐1301198, NIH NINDS 1R21NS099896, NIH NIA 1R56AG066634-01
URL de PolyPublie: https://publications.polymtl.ca/9357/
Titre de la revue: PLOS Computational Biology (vol. 17, no 1)
Maison d'édition: PLOS
DOI: 10.1371/journal.pcbi.1008584
URL officielle: https://doi.org/10.1371/journal.pcbi.1008584
Date du dépôt: 15 nov. 2022 15:36
Dernière modification: 27 mars 2024 19:30
Citer en APA 7: Hartung, G., Badr, S., Moeini Gharagozlo, M. R., Lesage, F., Kleinfeld, D., Alaraj, A., & Linninger, A. (2021). Voxelized simulation of cerebral oxygen perfusion elucidates hypoxia in aged mouse cortex. PLOS Computational Biology, 17(1), e1008584 (28 pages). https://doi.org/10.1371/journal.pcbi.1008584

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