An efficient noninvasive method for in vivo imaging of
tumor oxygenation by using a low-field magnetic resonance scanner and a paramagnetic
contrast agent is described. The methodology is based on Overhauser enhanced magnetic resonance imaging (OMRI), a functional imaging technique. OMRI experiments were performed on
tumor-bearing mice (
squamous cell carcinoma) by i.v. administration of the
contrast agent Oxo63 (a highly derivatized triarylmethyl radical) at nontoxic doses in the range of 2-7 mmol/kg either as a bolus or as a continuous infusion. Spatially resolved pO(2) (
oxygen concentration) images from OMRI experiments of
tumor-bearing mice exhibited heterogeneous oxygenation profiles and revealed regions of
hypoxia in
tumors (<10 mmHg; 1 mmHg = 133 Pa). Oxygenation of
tumors was enhanced on
carbogen (95% O(2)/5% CO(2)) inhalation. The pO(2) measurements from OMRI were found to be in agreement with those obtained by independent polarographic measurements using a pO(2) Eppendorf
electrode. This work illustrates that anatomically coregistered pO(2) maps of
tumors can be readily obtained by combining the good anatomical resolution of water
proton-based MRI, and the superior pO(2) sensitivity of EPR. OMRI affords the opportunity to perform noninvasive and repeated pO(2) measurements of the same animal with useful spatial (approximately 1 mm) and temporal (2 min) resolution, making this method a powerful imaging modality for small animal research to understand
tumor physiology and potentially for human applications.