Optimal heat transport induced by magnetic nanoparticle delivery in vascularised tumours.

ABSTRACT

We describe a novel mathematical model for blood flow, delivery of nanoparticles, and heat transport in vascularised tumour tissue. The model, which is derived via the asymptotic homogenisation technique, provides a link between the macroscale behaviour of the system and its underlying, tortuous micro-structure, as parametrised in Penta and Ambrosi (2015). It consists of a double Darcy's law, coupled with a double advection-diffusion-reaction system describing heat transport, and an advection-diffusion-reaction equation for transport and adhesion of particles. Particles are assumed sufficiently large and do not extravasate to the tumour interstitial space but blood and heat can be exchanged between the two compartments. Numerical simulations of the model are performed using a finite element method to investigate cancer hyperthermia induced by the application of magnetic field applied to injected iron oxide nanoparticles. Since tumour microvasculature is more tortuous than that of healthy tissue and thus suboptimal in terms of fluid and drug transport, we study the influence of the vessels' geometry on tumour temperature. Effective and safe hyperthermia treatment requires tumour temperature within certain target range, generally estimated between 42 °C and 46 °C, for a certain target duration, typically 0.5h to 2h. As temperature is difficult to measure in situ, we use our model to determine the ranges of tortuosity of the microvessels, magnetic intensity, injection time, wall shear stress rate, and concentration of nanoparticles required to achieve given target conditions.