Ventimiglia, T. A. | Search bioRxiv

bioRxiv2026

Microvascular network organization and hemodynamic perfusion protect the brain against hypoxia

Mechanistic simulations of blood flow and oxygen exchange showed regions of cortical tissue tolerating substantial increase in local oxygen consumption (CMRO2) before reaching hypoxia (pO2<10 mmHg). The observed robustness in O2 supply was attributed to overcapacity in convective oxygen transport in the pial arterial network combined with a surplus in the number of capillary flow paths. Microcirculatory flux analysis suggests that network induced hemodynamic flow patterns impart intrinsic reserve to protect the brain against perfusion variances or metabolic demand surges during activation. Furthermore, oxygen transport in cortical tissue is characterized by two regimes: in the transport zone -- centered on penetrating arteriole trees composed of a single penetrating vessel connected to the post-arteriole capillary transition zone -- strong diffusion supports high oxygen tension with only modest contribution from capillaries. This regime transitions into the terminal/reactive zone where oxygenation is sensitive to capillary density and perfusion. Quasi-dynamic simulations also enabled reconstruction of the BOLD signal underlying functional imaging. Simulations at single micron resolution further show that age-related reductions in arterial saturation and systemic hematocrit were sufficient to induce hypoxic tissue pockets in the terminal zone at nominal perfusion (CBF) and metabolic activity (CMRO2), and neutrophil adhesion induced capillary flow stalling further exacerbates hypoxia.

bioengineering↗

bioRxiv2023

MESH-FREE HIGH-RESOLUTION SIMULATION OF CEREBROCORTICAL OXYGENSUPPLY WITH FAST FOURIER PRECONDITIONING

Oxygen transfer from blood vessels to cortical brain tissue is representative of a class of problems with mixed-domain character. Large-scale efficient computation of tissue oxygen concentration is dependent on the manner in which the tubular network of blood vessels is coupled to the tissue mesh. Models which explicitly resolve the interface between the tissue and vasculature with a contiguous mesh are prohibitively expensive for very dense cerebral microvasculature. We propose a mixed-domain mesh-free technique whereby a vascular anatomical network (VAN) represented as a thin directed graph serves for convection of blood oxygen, and the surrounding extravascular tissue is represented as a Cartesian grid of 3D voxels throughout which oxygen is transported by diffusion. We split the network and tissue meshes by the Schur complement method of domain decomposition to obtain a reduced set of system equations for the tissue oxygen concentration. The use of a Cartesian grid allows the corresponding matrix equation to be solved approximately with a fast Fourier transform based Poisson solver, which serves as an effective preconditioner for Krylov subspace iteration. The performance of this method enables the steady state simulation of cortical oxygen perfusion for anatomically accurate vascular networks down to single micron resolution without the need for supercomputers. Practitioner PointsO_LIWe present a novel mixed-domain framework for efficiently modeling O2 extraction kinetics in the brain. C_LIO_LIModel equations are generated by graph-theoretic methods for mixed domains. C_LIO_LIDual mesh domain decomposition with FFT preconditioning yields very fast simulation times for extremely high spatial resolution. C_LI

bioengineering↗