Absolute oxygen R_1eimaging in vivo with pulse electron paramagnetic resonance

<jats:sec><jats:title>Purpose</jats:title><jats:p>Tissue oxygen (O<jats:sub>2</jats:sub>) levels are among the most important and most quantifiable stimuli to which cells and tissues respond through inducible signaling pathways. Tumor O<jats:sub>2</jats:sub>levels are major determinants of the response to cancer therapy. Developing more accurate measurements and images of tissue O<jats:sub>2</jats:sub>partial pressure (pO<jats:sub>2</jats:sub>), assumes enormous practical, biological, and medical importance.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We present a fundamentally new technique to image pO<jats:sub>2</jats:sub>in tumors and tissues with pulse electron paramagnetic resonance (EPR) imaging enabled by an injected, nontoxic, triaryl methyl (trityl) spin probe whose unpaired electron's slow relaxation rates report the tissue pO<jats:sub>2</jats:sub>. Heretofore, virtually all in vivo EPR O<jats:sub>2</jats:sub>imaging measures pO<jats:sub>2</jats:sub>with the transverse electron spin relaxation rate, R<jats:sub>2e</jats:sub>, which is susceptible to the self‐relaxation confounding O<jats:sub>2</jats:sub>sensitivity.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We found that the trityl electron longitudinal relaxation rate, R<jats:sub>1e</jats:sub>, is an order of magnitude less sensitive to confounding self‐relaxation. R<jats:sub>1e</jats:sub>imaging has greater accuracy and brings EPR O<jats:sub>2</jats:sub>images to an absolute pO<jats:sub>2</jats:sub>image, within uncertainties.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>R<jats:sub>1e</jats:sub>imaging more accurately determines oxygenation of cancer and normal tissue in animal models than has been available. It will enable enhanced, rapid, noninvasive O<jats:sub>2</jats:sub>images for understanding oxygen biology and the relationship of oxygenation patterns to therapy outcome in living animal systems. Magn Reson Med 72:362–368, 2014. © 2013 Wiley Periodicals, Inc.</jats:p></jats:sec>