Low-field paramagnetic resonance imaging of tumor oxygenation and glycolytic activity in mice

A priori knowledge of spatial and temporal changes in partial pressure of oxygen (oxygenation; pO₂) in solid tumors, a key prognostic factor in cancer treatment outcome, could greatly improve treatment planning in radiotherapy and chemotherapy. Pulsed electron paramagnetic resonance imaging (EPRI) provides quantitative 3D maps of tissue pO₂ in living objects. In this study, we implemented an EPRI set-up that could acquire pO₂ maps in almost real time for 2D and in minutes for 3D. We also designed a combined EPRI and MRI system that enabled generation of pO₂ maps with anatomic guidance. Using EPRI and an air/carbogen (95% O₂ plus 5% CO₂) breathing cycle, we visualized perfusion-limited hypoxia in murine tumors. The relationship between tumor blood perfusion and pO₂ status was examined, and it was found that significant hypoxia existed even in regions that exhibited blood flow. In addition, high levels of lactate were identified even in normoxic tumor regions, suggesting the predominance of aerobic glycolysis in murine tumors. This report presents a rapid, noninvasive method to obtain quantitative maps of pO₂ in tumors, reported with anatomy, with precision. In addition, this method may also be useful for studying the relationship between pO₂ status and tumor-specific phenotypes such as aerobic glycolysis.