Microvessel Chaste: An Open Library for Spatial Modeling of Vascularized Tissues

Abstract

Spatial models of vascularized tissues are widely used in computational physiology. We introduce a software library for composing multiscale, multiphysics models for applications including tumor growth, angiogenesis, osteogenesis, coronary perfusion, and oxygen delivery. Composition of such models is time consuming, with many researchers writing custom software. Recent advances in imaging have produced detailed three-dimensional (3D) datasets of vascularized tissues at the scale of individual cells. To fully exploit such data there is an increasing need for software that allows user-friendly composition of efficient, 3D models of vascularized tissues, and comparison of predictions with in vivo or in vitro experiments and alternative computational formulations. Microvessel Chaste can be used to build simulations of vessel growth and adaptation in response to mechanical and chemical stimuli; intra- and extravascular transport of nutrients, growth factors and drugs; and cell proliferation in complex 3D geometries. In addition, it can be used to develop custom software for integrating modeling with experimental data processing workflows, facilitated by a comprehensive Python interface to solvers implemented in C++. This article links to two reproducible example problems, showing how the library can be used to build simulations of tumor growth and angiogenesis with realistic vessel networks.

Figure 1

Given here is a schematic showing the components used in the Microvessel Chaste library, and how they can be used to generate custom simulation software. Shaded components are not currently used in the library. To see this figure in color, go online.

Figure 2

(a) A 3D intravital image of a tumor microvessel network (red) is obtained and a skeleton extracted as described in Grogan et al. (22). A cylindrical region of interest with diameter 1.2 mm is extracted for the example simulation. (b) A tumor growth simulation using the extracted microvessel network and Microvessel Chaste is given. The predicted evolution of the tumor over 25 h is shown, including blood pressure in growing vessels, VEGF concentrations in the extravascular space, and discrete cells. To see this figure in color, go online.

Figure 3

(a) Given here are images from a cornea micropocket experiment showing microvessels (dark red) at 3–5 days postpellet implantation (26). (b) Shown here is application of the Microvessel Chaste library in modeling a similar experiment. To see this figure in color, go online.