title: Simulation of tumor induced angiogenesis using an analytical adaptive modeling including dynamic sprouting and blood flow modeling.
abstract: In this paper, an adaptive model for tumor induced angiogenesis is developed that integrates generation and diffusion of a growth factor originated from hypoxic cells, adaptive sprouting from a parent vessel, blood flow and structural adaptation. The proposed adaptive sprout spacing model (ASS) determines position, time and number of sprouts which are activated from a parent vessel and also the developed vascular network is modified by a novel sprout branching prediction algorithm. This algorithm couples local vascular endothelial growth factor (VEGF) concentrations, stresses due to the blood flow and stochastic branching to the structural reactions of each vessel segment in response to mechanical and biochemical stimuli. The results provide predictions for the time-dependent development of the network structure, including the position and diameters of each segment and the resulting distributions of blood flow and VEGF. Considering time delays between sprout progressions and number of sprouts activated at different time durations provides information about micro-vessel density in the network. Resulting insights could be useful for motivating experimental investigations of vascular pattern in tumor induced angiogenesis and development of therapies targeting angiogenesis.
authors.affiliation: Department of Electrical Engineering, Ferdowsi University of Mashhad, Mashhad, Iran; Center of Excellence on Soft Computing and Intelligent Information Processing, Mashhad, Iran. Electronic address: n.naghavi@um.ac.ir.
authors.forename: Nadia
authors.initials: N
authors.lastname: Naghavi
authors.affiliation: Department of Electrical Engineering, Ferdowsi University of Mashhad, Mashhad, Iran.
authors.forename: Farideh S
authors.initials: FS
authors.lastname: Hosseini
authors.affiliation: Department of Mechanical Engineering, Ferdowsi University of Mashhad, Mashhad, Iran; Micro/Nano-fluidics and MEMS/NEMS Laboratory, Ferdowsi University of Mashhad, Mashhad, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sardarabadi
authors.affiliation: Department of Mechanical Engineering, Ferdowsi University of Mashhad, Mashhad, Iran; Center of Excellence on Soft Computing and Intelligent Information Processing, Mashhad, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Kalani
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001783:Blood Flow Velocity; D003198:Computer Simulation; D006801:Humans; D055806:Microvessels / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008955:Models, Cardiovascular; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism; D009389:Neovascularization, Pathologic; D012039:Regional Blood Flow; D013269:Stochastic Processes; D013997:Time Factors; D000072258:Tumor Hypoxia; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A
keywords: Blood flow; Feedback inhibition; Sprout spacing; Time adaptive vessel branching; Tumor angiogenesis