Noninvasive in vivo oximetric imaging by radiofrequency FT EPR

A novel method, called relaxo-oximetry, for rapid spatially resolved in vivo measurements of oxygen concentration using time-domain radiofrequency (RF) electron paramagnetic resonance (EPR) is described. Time-domain data from triaryl methyl (TAM)-based single-electron contrast agents were processed by systematic deletion of the initial time points to arrive at T2*-weighted discrimination of signal amplitudes. In experiments involving phantoms, the line widths [ approximately (T2*)(-1)] increased as a function of oxygen, and the slope (line width/pO(2)) was the same for both absorption- and magnitude-mode line shapes. Line widths derived from T2* weighting and the computed pO(2) values agreed favorably with the measured ones from phantoms of known oxygen tension. In vivo relaxo-oximetry was performed on C3H mice, and it was found that the liver was more hypoxic than the kidneys. For tumors, 2D oxygen maps were generated while the animal breathed room air or Carbogen(R) (95% O(2)/5% CO(2)). Carbogen(R) enhanced oxygen concentration within the tumor, and the pO(2) histograms showed considerable heterogeneity. Clark electrode oxygen measurements on organs and tumors were in good agreement with tissue oxygen measurements done by relaxo-oximetry. Thus, from a single spatial image data set, pO(2) measurements can be done noninvasively by relaxo-oximetry, and 3D imaging can be performed in less than 3 min.