Estimation of Oxygen Distribution in RIF-1 Tumors by Diffusion Model-Based Interpretation of Pimonidazole Hypoxia and Eppendorf Measurements

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Abstract
Pogue, B. W., O'Hara, J. A., Wilmot, C. M., Paulsen, K. D. and Swartz, H. M. Estimation of Oxygen Distribution in RIF-1 Tumors by Diffusion Model-Based Interpretation of Pimonidazole Hypoxia and Eppendorf Measurements.Numerical simulations of oxygen diffusion from the capillaries in tumor tissue were used to predict the capillary oxygen supply within and near hypoxic regions of the RIF-1 tumor. A finite element method to simulate the oxygen distribution from a histology section is presented, along with a method to iteratively estimate capillary oxygen concentrations. Pathological structural data for these simulations came from sections of the tumor stained with hematoxylin and eosin and were used to define the capillary positions and shapes, while overlapping regions of low oxygen concentration were defined by the hypoxia marker pimonidazole. These simulations were used to calculate spatial maps of the oxygen concentration and were tested for their ability to reproduce Eppendorf pO2 histograms from the same tumor line. This simulation study predicted that capillary oxygen concentrations ranged from zero to above 20 μM, with a dominant peak in the hypoxic regions showing 78% of capillaries with less than 1 μM oxygen concentration, compared to only 12% in the non-hypoxic regions. The results were not highly sensitive to the metabolic oxygen consumption rate, within the range of 2 to 16 μM/s. This numerical method for oxygen capillary simulation is readily adaptable to histology sections and provides a method to examine the heterogeneity of oxygen within the capillaries and throughout the tumor tissue section being examined.