Abstract

Angiogenesis plays an essential role in many pathological processes such as tumor growth, wound healing, and keloid development. Low oxygen level is the main driving stimulus for angiogenesis. In an animal tissue, the oxygen level is mainly determined by three effects-the oxygen delivery through blood flow in a refined vessel network, the oxygen diffusion from blood to tissue, and the oxygen consumption in cells. Evaluation of the oxygen field is usually the bottleneck in large scale modeling and simulation of angiogenesis and related physiological processes. In this work, a fast numerical method is developed for the simulation of oxygen supply in tissue with a large-scale complex vessel network. This method employs an implicit finite-difference scheme to compute the oxygen field. By virtue of an oxygen source distribution technique from vessel center lines to mesh points and a corresponding post-processing technique that eliminate the local numerical error induced by source distribution, square mesh with relatively large mesh sizes can be applied while sufficient numerical accuracy is maintained. The new method has computational complexity which is slightly higher than linear with respect to the number of mesh points and has a convergence order which is slightly lower than second order with respect to the mesh size. With this new method, accurate evaluation of the oxygen field in a fully vascularized tissue on the scale of centimeter becomes possible.

Highlights

  • Oxygen plays a key role in animal metabolism

  • Poor microcirculation structure results in local tissue hypoxia, which leads to the production of growth factors for angiogenesis, such as vascular endothelial growth factor (VEGF) [4, 5]

  • We develop a fast numerical method to evaluate the coupled system for oxygen delivery in tissue, with particular attention paid to the large-scale complex blood vessel network structures

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Summary

Introduction

Oxygen plays a key role in animal metabolism. Oxygen supply to tissue is mainly achieved by the circulation system of animals. In order to improve the efficiency of their microcirculation structure, animals have developed different physiological processes to modify the geometry and topology of vessel networks, including blood vessel adaptation and angiogenesis [1,2,3]. In these physiological processes, the oxygen level is the key driving stimulus. We develop a fast numerical method to evaluate the coupled system for oxygen delivery in tissue, with particular attention paid to the large-scale complex blood vessel network structures. Due to the advantages of this new method, we can accurately evaluate the oxygen field of a three dimensional fully vascularized tissue on the scale of centimeter within 20h

Modeling
Oxygen diffusion in tissue
Blood flow and blood pressure
Oxygen flux in vessels
Oxygen exchange on vessel walls
Model simplification
Numerical method
Nonlinear iteration
Dt ðPOnþ1
PDE solver
Post-processing
Da 4 dP þ qnkþ1hkðdðxk À xÞ À d ðxk À xÞÞ: ð17Þ
Parameters for simulation
Blood vessel network structures
Numerical solution for the cobweb vessel network
Numerical solution for the 2D refined vessel network
Numerical solution for the 3D refined vessel network
Model validation
Convergence analysis and efficiency analysis
Conclusions and discussions
B Peskin’s numerical δ-function
C Localization of δPk
D Detail error analysis for single vessel
Findings
E Inflow and outflow conditions

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