Author: Victor B. Kassey, Maciej M. Kmiec, Periannan Kuppusamy, Sergey V. Petryakov, Conner Ubert 👨🔬
Affiliation: Dartmouth College 🌍
Purpose: Tumor hypoxia—a state of reduced oxygen supply—is well known to affect treatment response, particularly in radiotherapy and chemotherapy. Oxygen-enhanced magnetic resonance imaging (OE-MRI) uses oxygen’s paramagnetic properties to map tissue oxygenation, where increased oxygen raises the spin-lattice relaxation rate R1. Modulating inhaled oxygen levels identifies tumor regions with differing oxygenation. This study applies OE-MRI on a 9.4T MRI system to exploit high SNR and spatial resolution for oxygen mapping and to validate the R1-pO2 relationship.
Methods: In-vitro and in-vivo experiments confirmed the expected R1-pO2 linear relationship. An in-vitro study established a correlation using aerated de-ionized water solutions (0%, 10%, 30%, 100% O2) containing 10 µM trityl (Ox0-63), enabling EPR-based pO2 level confirmation without perturbing the MRI signal. Comparing R1 values with EPR pO2 data verified the expected calibration curve, confirming OE-MRI's accuracy and reproducibility.
An OE-MRI evaluation of a murine brain alternated breathing gases (21% and 100% O2) and simulated severe hypoxia with post-euthanasia imaging. R1 maps using saturation-inversion-recovery confirmed OE-MRI’s sensitivity to oxygen changes in brain tissue. A tumor study used OxyChips implanted in an SCC7 tumor on a C3H mouse. Micro-CT verified chip positions. R1 mapping and EPR oximetry measured pO2 while inhaling 21% and 100% O2 to generate a tissue-specific calibration curve for quantitative pO2 mapping.
Results: R1 values correlated with EPR pO2 measurements agreed well with previous experiments in the relaxivity range (1.42–2.08 x10-4 1/s/mmHg). The murine brain evaluation demonstrated OE-MRI’s oxygen sensitivity at high field strength. Tumor studies produced a tissue-specific calibration curve linking R1 to pO2, enabling high resolution quantified hypoxia mapping.
Conclusion: OE-MRI calibrated with EPR oximetry can generate useful hypoxia maps. These results support its potential applicability in adaptive radiation therapy and precision oncology. Future work includes refining calibration, reducing OxyChip size, and exploring these techniques using low-field MR-LINAC systems.