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Cerebral function is highly dependent on a continuous blood supply of oxygen and nutrient. Depending on its duration and intensity, any disruption of blood supply can lead to progressive neurodegeneration and cognitive decline. For instance, Alzheimer’s disease (AD) patients are subject to a chronic decrease of cerebral blood flow (CBF) which is believed to induce tissue hypoxia and further neurodegeneration. The physical mechanisms shaping the distribution of hypoxic regions are still poorly understood.
In this context, a theoretical framework based on the statistical distribution of quantities derived from intravascular blood flow and transport simulations has been developed [1]. Its main advantage is that it quantitatively relates transport dynamics to the network architecture and flow distributions. However, oxygen transport and consumption in the tissue is currently overlooked. Here, in order to subsequently enrich this theoretical framework, we develop a complete coupled model for extravascular and intravascular transport by generalizing to 3D the operator splitting approach introduced in 2D in [2] and by coupling it with an averaged 1D intravascular model with effective coefficients modeling dispersive effects and exchanges with surrounding tissues [3] (Fig. 1a). In the long term, we expect that the accurate modelling of tissue/vessel couplings should significantly affect the relationship between network topology and the distribution of hypoxic regions (Fig.1b).
By expressing the mean oxygen concentration at the vascular outlet as a function of the tissue metabolic rate of oxygen consumption (Fig. 1b), we compare the fully resolved model with the simplified first-order model of Goirand et al. (2021) [1]. This comparison allows us to investigate how capillary–tissue exchange processes—commonly referred to as matrix diffusion—interact with broadly distributed transit times to shape anomalous transport dynamics. We further assess the implications of these interactions for oxygen delivery and the formation of hypoxic regions in cerebral tissue.
| References | [1] Florian Goirand, Network-driven anomalous transport is a fundamental component of brain microvascular dysfunction, Nature Communications, 12 (2021) ; [2] David Pastor-Alonso, Modeling oxygen transport in the brain: An efficient coarse-grid approach to capture perivascular gradients in the parenchyma, PLOS Computational Biology, 20 (2024) ; [3] Maxime Berg, Modelling solute transport in the brain microcirculation: is it really well mixed inside the blood vessels?, JFM, 884 (2020) ; [4] Amy Smith, Brain capillary networks across species: a few simple organizational requirements are sufficient to reproduce both structure and function, Frontiers in Physiology, 10 (2019) |
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| Country | France |
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