Inducing Biomechanical Heterogeneity in Brain Tumor Modeling by MR Elastography: Effects on Tumor Growth, Vascular Density and Delivery of Therapeutics

SIMPLE SUMMARY: Biomechanical forces aggravate brain tumor progression. In this study, magnetic resonance elastography (MRE) is employed to extract tissue biomechanical properties from five glioblastoma patients and a healthy subject, and data are incorporated in a mathematical model that simulates tumor growth. Mathematical modeling enables further understanding of glioblastoma development and allows patient-specific predictions for tumor vascularity and delivery of drugs. Incorporating MRE data results in a more realistic intratumoral distribution of mechanical stress and anisotropic tumor growth and a better description of subsequent events that are closely related to the development of stresses, including heterogeneity of the tumor vasculature and intrapatient variations in tumor perfusion and delivery of drugs. ABSTRACT: The purpose of this study is to develop a methodology that incorporates a more accurate assessment of tissue mechanical properties compared to current mathematical modeling by use of biomechanical data from magnetic resonance elastography. The elastography data were derived from five glioblastoma patients and a healthy subject and used in a model that simulates tumor growth, vascular changes due to mechanical stresses and delivery of therapeutic agents. The model investigates the effect of tumor-specific biomechanical properties on tumor anisotropic growth, vascular density heterogeneity and chemotherapy delivery. The results showed that including elastography data provides a more realistic distribution of the mechanical stresses in the tumor and induces anisotropic tumor growth. Solid stress distribution differs among patients, which, in turn, induces a distinct functional vascular density distribution—owing to the compression of tumor vessels—and intratumoral drug distribution for each patient. In conclusion, incorporating elastography data results in a more accurate calculation of intratumoral mechanical stresses and enables a better mathematical description of subsequent events, such as the heterogeneous development of the tumor vasculature and intrapatient variations in tumor perfusion and delivery of drugs.