Lattice boltzmann based simulation of blood vessel normalization in tumors

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Tumor blood vessels grow in a chaotic manner. This compromises the delivery of chemo therapeutics. Normalization of tumor blood vessels has shown to be a promising way to improve the efficiency of subsequently administered chemotherapeutics. The predominant effects of anti-VEGF therapies are decreased vessel leakiness hydraulic conductivity), decreased vessel diameters and pruning of the immature vessel network. It is thought that each of these can influence the functionality of the vessel network. Unfortunately, anti-VEGF therapies affect vessel structure and leakiness. These changes are dynamic and overlapping in time, and it has been difficult to identify a consistent and predictable normalization during which drug delivery is optimal. This is largely due to the non-linearity in the system, and the inability to distinguish the effects of decreased vessel leakiness from those due to structural network changes in clinical trials or animal studies.To address this problem, we will develop mathematical model to decouple vascular leakiness and network structural changes. This will allow determination of how each factor influences flow patterns, oxygen distribution, and drug delivery during anti-angiogenic therapy. An understanding of how hydraulic conductivity and network architecture act to enhance delivery of chemotherapeutics, will allow rational use of existing drugs, or the design of new ones, to improve chemotherapy.For the simulation of the vascular remodeling process we propose a lattice Boltzmann based simulation. This simulation should be able to solve the full hemodynamic of the vessel network on an actual 3D network. Further it has to be able to calculate the oxygen distribution in of the system based the distribution of red blood cells. From this the distribution of growth factors (i.e. VEGF) can be calculated which then enables an local remodeling of the vessel structure based on the local shear stress and VEGF concentration.