A computational model of glioma reveals opposing, stiffness-sensitive effects of leaky vasculature and tumor growth on tissue mechanical stress and porosity

• Main Authors: Ewing, J.R (Author), Rey, J.A (Author), Sarntinoranont, M. (Author)
• Format: Article
• Language: English
• Published: Springer Science and Business Media Deutschland GmbH 2021
• Subjects: animal; Animals; Antiangiogenesis; antiangiogenic therapy; Article; biological model; Biphasic theory; brain; Brain; Brain Neoplasms; brain tissue; brain tumor; cancer infiltration; cancer radiotherapy; comparative study; compression; compressive strength; Compressive Strength; Compressive stress; Computation theory; Computational methods; Computational model; computer model; computer simulation; Computer Simulation; Deformation; Effective stiffness; extracellular fluid; Extracellular Fluid; finite element analysis; glioma; Glioma; human; Humans; hydraulic conductivity; Hydraulic conductivity; in vivo study; Interstitial fluid pressures; lymph; Lymph; lymphatic system; mathematical model; Mechanical interactions; Mechanical model; mechanical stress; Mechanical stress; mechanics; Microenvironments; Models, Biological; Models, Theoretical; pathophysiology; physiology; Poroelasticity; porosity; Porosity; Porous media; pressure; Pressure; rigidity; simulation; Stiffness; Stress, Mechanical; tensile strength; Tensile Strength; theoretical model; Tissue deformations; Tissue engineering; tissue pressure; tumor growth; tumor microenvironment; Tumor Microenvironment; tumor vascularization; Tumors; Unique features
• Online Access: View Fulltext in Publisher

 A biphasic computational model of a growing, vascularized glioma within brain tissue was developed to account for unique features of gliomas, including soft surrounding brain tissue, their low stiffness relative to brain tissue, and a lack of draining lymphatics. This model is the first to couple nonlinear tissue deformation with porosity and tissue hydraulic conductivity to study the mechanical interaction of leaky vasculature and solid growth in an embedded glioma. The present model showed that leaky vasculature and elevated interstitial fluid pressure produce tensile stress within the tumor in opposition to the compressive stress produced by tumor growth. This tensile effect was more pronounced in softer tissue and resulted in a compressive stress concentration at the tumor rim that increased when tumor was softer than host. Aside from generating solid stress, fluid pressure-driven tissue deformation decreased the effective stiffness of the tumor while growth increased it, potentially leading to elevated stiffness in the tumor rim. A novel prediction of reduced porosity at the tumor rim was corroborated by direct comparison with estimates from our in vivo imaging studies. Antiangiogenic and radiation therapy were simulated by varying vascular leakiness and tissue hydraulic conductivity. These led to greater solid compression and interstitial pressure in the tumor, respectively, the former of which may promote tumor infiltration of the host. Our findings suggest that vascular leakiness has an important influence on in vivo solid stress, stiffness, and porosity fields in gliomas given their unique mechanical microenvironment. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.