Modeling the Effect of Hyperoxia on the Spin-Lattice Relaxation Rate R1 of Tissues

Inducing hyperoxia in tissues is common practice in several areas of research, including oxygen-enhanced MRI (OE-MRI), which attempts to use the resulting signal changes to detect regions of tumor hypoxia or pulmonary disease. The linear relationship between PO₂ and R1 has been reproduced in phantom solutions and body fluids such as vitreous fluid; however, in tissue and blood experiments, factors such as changes in deoxyhemoglobin levels can also affect the ΔR1.

This manuscript proposes a three-compartment model for estimating the hyperoxia-induced changes in R1 of tissues depending on B0, SO₂ , blood volume, hematocrit, oxygen extraction fraction, and changes in blood and tissue PO₂ . The model contains two blood compartments (arterial and venous) and a tissue compartment. This model has been designed to be easy for researchers to tailor to their tissue of interest by substituting their preferred model for tissue oxygen diffusion and consumption. A specific application of the model is demonstrated by calculating the resulting ΔR1 expected in healthy, hypoxic and necrotic tumor tissues. In addition, the effect of sex-based hematocrit differences on ΔR1 is assessed.

The ΔR1 values predicted by the model are consistent with reported literature OE-MRI results: with larger positive changes in the vascular periphery than hypoxic and necrotic regions. The observed sex-based differences in ΔR1 agree with findings by Kindvall et al. suggesting that differences in hematocrit levels may sometimes be a confounding factor in ΔR1.

This model can be used to estimate the expected tissue ΔR1 in oxygen-enhanced MRI experiments.