The role of the microvascular network structure on diffusion and consumption of anticancer drugs

We investigate the impact of microvascular geometry on the transport of drugs in solid tumors, focusing on the diffusion and consumption phenomena. We embrace recent advances in the asymptotic homogenization literature starting from a double Darcy—double advection-diffusion-reaction system of partial differential equations that is obtained exploiting the sharp length separation between the intercapillary distance and the average tumor size. The geometric information on the microvascular network is encoded into effective hydraulic conductivities and diffusivities, which are numerically computed by solving periodic cell problems on appropriate microscale representative cells. The coefficients are then injected into the macroscale equations, and these are solved for an isolated, vascularized spherical tumor. We consider the effect of vascular tortuosity on the transport of anticancer molecules, focusing on Vinblastine and Doxorubicin dynamics, which are considered as a tracer and as a highly interacting molecule, respectively. The computational model is able to quantify the treatment performance through the analysis of the interstitial drug concentration and the quantity of drug metabolized in the tumor. Our results show that both drug advection and diffusion are dramatically impaired by increasing geometrical complexity of the microvasculature, leading to nonoptimal absorption and delivery of therapeutic agents. However, this effect apparently has a minor role whenever the dynamics are mostly driven by metabolic reactions in the tumor interstitium, eg, for highly interacting molecules. In the latter case, anticancer therapies that aim at regularizing the microvasculature might not play a major role, and different strategies are to be developed

On the validity of the Carman-Kozeny equation in random fibrous media

The transverse permeability for creeping flow through unidirectional random arrays of fibers/cylinders has been studied numerically using the finite element method (FEM). A modified Carman-Kozeny (CK) relation is presented which takes into account the tortuosity (flow path) and the lubrication effect of the narrow channels. The proposed relation is valid in a wide range of porosities compared to the classical CK equation. The proposed general relationship for the permeability can be utilized for composite manufacturing and also for validation of advanced coarse models for particle-fluid interactions

A review of the state of art in applying Biot theory to acoustic propagation through the bone

Understanding the propagation of acoustic waves through a liquid-perfused porous solid framework such as cancellous bone is an important pre-requisite to improve the diagnosis of osteoporosis by ultrasound. In order to elucidate the propagation dependence upon the material and structural properties of cancellous bone, several theoretical models have been considered to date, with Biot-based models demonstrating the greatest potential. This paper describes the fundamental basis of these models and reviews their performance

Predictions of angle dependent tortuosity and elasticity effects on sound propagation in cancellous bone

The anisotropic pore structure and elasticity of cancellous bone cause wave speeds and attenuation in cancellous bone to vary with angle. Previously published predictions of the variation in wave speed with angle are reviewed. Predictions that allow tortuosity to be angle dependent but assume isotropic elasticity compare well with available data on wave speeds at large angles but less well for small angles near the normal to the trabeculae. Claims for predictions that only include angle-dependence in elasticity are found to be misleading. Audio-frequency data obtained at audio-frequencies in air-filled bone replicas are used to derive an empirical expression for the angle-and porosity-dependence of tortuosity. Predictions that allow for either angle dependent tortuosity or angle dependent elasticity or both are compared with existing data for all angles and porosities