Exploring Tissue Permeability of Brain Tumours in Different Grades: Insights from Pore-scale Fluid Dynamics Analysis

Interstitial fluid (ISF) flow is identified as an essential physiological process that plays an important role in the development and progression of brain tumours. However, the relationship between the permeability of the tumour tissue, a complex porous medium, and the interstitial fluid flow around the tumour cells at the microscale is not well understood. To shed light on this issue, and in the absence of experimental techniques that can provide direct measurements, we develop a computational model to predict the tissue permeability of brain tumours in different grades by analysing the ISF flow at the pore scale. The 3-D geometrical models of tissue extracellular spaces are digitally reconstructed for each grade tumour based on their morphological properties measured from microscopic images. The predictive accuracy of the framework is validated by experimental results reported in the literature. Our results indicate that high-grade brain tumours are less permeable despite their higher porosity, whereas necrotic areas of glioblastoma are more permeable than the viable tumour areas. This implies that tissue permeability is primarily governed by both tissue porosity and the deposition of hyaluronic acid (HA), a key component of the extracellular matrix, while the HA deposition can have a greater effect than macro-level porosity. Parametric studies show that tissue permeability falls exponentially with increasing HA concentration in all grades of brain tumours, and this can be captured using an empirically derived relationship in a quantitative manner. These findings provide an improved understanding of the hydraulic properties of brain tumours and their intrinsic links to tumour microstructure. This work can be used to reveal the intratumoural physiochemical processes that rely on fluid flow and offer a powerful tool to tune textured and porous biomaterials for desired transport properties.