Biomedical

AngioMT: A MATLAB based 2D image-to-physics tool to predict oxygen transport in vascularized microphysiological systems




  Peer Reviewed

Abstract

Microphysiological models (MPS) are increasingly getting recognized as in vitro preclinical systems of pathophysiology and drug discovery. However, there is also a growing need to adapt and advance MPS to include the physiological contributions of the capillary vascular dynamics, because they undergo angiogenesis or vasculogenesis to deliver soluble oxygen and nutrients to its organs. Currently, the process of formation of microvessels in MPS is measured arbitrarily, and vascularized MPS do not include oxygen measurements in their analysis. Sensing and measuring tissue oxygen delivery is extremely difficult because it requires access to opaque and deep tissue, and/or requires extensive integration of biosensors that makes such systems impractical to use in the real world. Here, a finite element method-based oxygen transport program, called AngioMT, is built in MATLAB. AngioMT processes the routinely acquired 2D confocal images of microvascular networks in vitro and solves physical equations of diffusion-reaction dominated oxygen transport phenomena. This user-friendly image-to-physics transition in AngioMT is an enabling tool of MPS analysis because unlike the averaged morphological measures of vessels, it provides information of the spatial transport of oxygen both within the microvessels and the surrounding tissue regions. Further, it solves the more complex higher order reaction mechanisms which also improve the physiological relevance of this tool when compared directly against in vivo measurements. Finally, the program is applied in a multicellular vascularized MPS by including the ability to define additional organ/tissue subtypes in complex co-cultured systems. Therefore, AngioMT serves as an analytical tool to enhance the predictive power and performance of MPS that incorporate microcirculation.

Key Questions

1. What is AngioMT and how does it work?

AngioMT is a MATLAB-based computational solver that predicts oxygen transport in vascularized microphysiological systems. It processes 2D confocal images of microvascular networks, segments them into distinct domains, and uses finite element methods to solve oxygen transport equations, providing spatial distribution of oxygen in vessels and surrounding tissues.

2. What are the advantages of AngioMT over existing methods?

AngioMT offers several advantages: it doesn't require contrast agents, can incorporate complex microvascular geometries and multi-tissue environments, allows for high-order reaction kinetics, and provides a user-friendly image-to-physics transition. It also calculates ancillary variables like flux vectors and area-averaged mass transport.

3. How does AngioMT compare to experimental measurements?

AngioMT's predictions showed good correlation with in vivo experimental measurements of oxygen distribution in rat mesenteric microvasculature. The correlation improved when non-linear enzymatic reaction kinetics were incorporated, demonstrating the software's ability to capture physiologically relevant oxygen transport phenomena.

4. What are the potential applications of AngioMT?

AngioMT can be used to evaluate vascular network performance in microphysiological systems, assess oxygen delivery in various tissue models, predict drug transport in vascularized tissues, and potentially aid in the design and optimization of organ-on-chip devices. It could also be valuable in studying diseases affecting microcirculation.

5. What are the current limitations of AngioMT?

AngioMT currently uses 2D images, which may not fully capture the complexity of 3D vascular networks. It also doesn't include convective flow contributions. While these limitations exist, the software still provides valuable insights and can be further developed to incorporate 3D analysis and additional transport phenomena in future versions.