Sensitivity analysis of a multi‐physics model for the vascular microenvironment

The vascular microenvironment is the scale at which microvascular transport, interstitial tissue properties and cell metabolism interact. The vascular microenvironment has been widely studied by means of quantitative approaches, including multi‐physics mathematical models as it is a central system for the pathophysiology of many diseases, such as cancer. The microvascular architecture is a key factor for fluid balance and mass transfer in the vascular microenvironment, together with the physical parameters characterizing the vascular wall and the interstitial tissue. The scientific literature of this field has witnessed a long debate about which factor of this multifaceted system is the most relevant. The purpose of this work is to combine the interpretative power of an advanced multi‐physics model of the vascular microenvironment with state of the art and robust sensitivity analysis methods, in order to determine the factors that most significantly impact quantities of interest, related in particular to cancer treatment. We are particularly interested in comparing the factors related to the microvascular architecture with the ones affecting the physics of microvascular transport. Ultimately, this work will provide further insight into how the vascular microenvironment affects cancer therapies, such as chemotherapy, radiotherapy or immunotherapy. We perform sensitivity analysis of the geometric and physical factors that influence the microvascular environment showing that the microvascular architecture has a significant effect on oxygen transfer. Oxygen transfer is affected by complex interactions between physical and geometric parameters but overall, the group of physical parameters is more influential than the group of geometric parameters.