Electron paramagnetic resonance imaging of tumor hypoxia:: Enhanced spatial and temporal resolution for in vivo pO2 determination

The time-domain (TD) mode of electron paramagnetic resonance (EPR) data collection offers a means of estimating the concentration of a paramagnetic probe and the oxygen-dependent linewidth (LW) to generate pO(2) maps with minimal errors. A methodology for noninvasive pO(2) imaging based on the application of TD-EPR using oxygen-induced LW broadening of a triarylmethyl (TAM)-based radical is presented. The decay of pixel intensities in an image is used to estimate T-2(*), which is inversely proportional to pO(2). Factors affecting T-2(*) in each pixel are critically analyzed to extract the contribution of dissolved oxygen to EPR line-broadening. Suitable experimental and image-processing parameters were obtained to produce pO(2) maps with minimal artifacts. Image artifacts were also minimized with the use of a novel data collection strategy using multiple gradients. Results from a phantom and in vivo imaging of tumor-bearing mice validated this novel method of noninvasive oximetry. The current imaging protocols achieve a spatial resolution of similar to 1.0 mm and a temporal resolution of similar to 9 s for 2D pO(2) mapping, with a reliable oxygen resolution of similar to 1 mmHg (0.12% oxygen in gas phase). This work demonstrates that in vivo oximetry can be performed with good sensitivity, accuracy, and high spatial and temporal resolution.