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

Abstract

Purpose 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. Theory and Methods 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. Results 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. Conclusion This model can be used to estimate the expected tissue ΔR1 in oxygen‐enhanced MRI experiments.

Oxygen-enhanced MRI assessment of tumour hypoxia in head and neck cancer is feasible and well tolerated in the clinical setting

“…The dichotomisation of a voxel’s hypoxic status based on the lack of statistically significant T1 shortening is clearly an oversimplification of the underlying continuously varying oxygen tension present in tumours. The relationship between T1 times and tumour pO 2 is dependent on a number of physical and physiological variables meaning it is not possible to readily ascribe pO 2 values to imaged voxels [ 28 ]. Consequently, it is not possible to state the effective pO 2 threshold for the estimates of hypoxic fractions presented in this study.…”

“…BOLD refers to the reduction in R 2 * rate with the reduction in deoxyhaemoglobin to oxyhaemoglobin ratio as occurs in perfused hypoxic regions following an oxygen challenge. As R 1 relaxation rates are also proportional to deoxyhaemoglobin concentrations [ 28 ], the addition of BOLD measurements to T1-based OE-MRI may refine the characterisation of the oxygenation status of tumours [ 24 , 27 ].…”