Figure 1
A schematic illustration of the present multi-scale computational model. The subcellular scale is the primary scale of the model, containing biochemical agents, including ECM (fibronectin gradient-induced haptotaxis for sprouting), matrix metalloproteinases, and VEGF gradient-induced chemotaxis. At the cellular scale, it consists of EC phenotypes, including tip cell migration. At the tissue level, this model also incorporates microvessel growth and remodeling, which is affected by mechanobiological and biochemical signals from wall shear stress with accurate hemodynamics and hemorheology. (a) Hypoxic tumor cells that have been deprived of oxygen, release some chemical agents (i.e., VEGF) which result in the formation of new microvessels from pre-existing vessels. Capillary networks induced by tumor angiogenesis play as a source for release of nutrients, therapeutic agents, as well as FDG molecules, which are injected into the patient’s bloodstream, (b) Extracellular FDG molecules can transport from tumor tissue to intracellular space and vice versa by GLUTs through L3 and L4 constant rate, respectively. Subsequently, each absorbed FDG molecule may phosphorylate by hexokinase enzymes to phosphorylated FDG via L5 constant rate. This process releases two high-energy gamma-rays in opposite directions, which can pass through the tissue, and (c) PET machine can detect these high-energy rays and hence via computer processing of the series of images taken in different angels the clinicians can detect the tumor tissue status for their further clinical decision-making process. (d) According to the FDG transport processes, a multi-compartment model is used in the spatiotemporal modeling of FDG transport. It should be mentioned that Microsoft Office PowerPoint 365 was used to create this figure.
