title: Absolute oxygen R1e imaging in vivo with pulse electron paramagnetic resonance.
abstract: OBJECTIVE
  Tissue oxygen (O2) levels are among the most important and most quantifiable stimuli to which cells and tissues respond through inducible signaling pathways. Tumor O2 levels are major determinants of the response to cancer therapy. Developing more accurate measurements and images of tissue O2 partial pressure (pO2), assumes enormous practical, biological, and medical importance.
  
  
  METHODS
  We present a fundamentally new technique to image pO2 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 pO2. Heretofore, virtually all in vivo EPR O2 imaging measures pO2 with the transverse electron spin relaxation rate, R2e, which is susceptible to the self-relaxation confounding O2 sensitivity.
  
  
  RESULTS
  We found that the trityl electron longitudinal relaxation rate, R1e, is an order of magnitude less sensitive to confounding self-relaxation. R1e imaging has greater accuracy and brings EPR O2 images to an absolute pO2 image, within uncertainties.
  
  
  CONCLUSIONS
  R1e imaging more accurately determines oxygenation of cancer and normal tissue in animal models than has been available. It will enable enhanced, rapid, noninvasive O2 images for understanding oxygen biology and the relationship of oxygenation patterns to therapy outcome in living animal systems.
authors.affiliation: Center for EPR Imaging In Vivo Physiology, The University of Chicago, Department of Radiation and Cellular Oncology (MC 1105), Chicago, Illinois, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Epel
authors.forename: Michael K
authors.initials: MK
authors.lastname: Bowman
authors.forename: Colin
authors.initials: C
authors.lastname: Mailer
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Halpern
mesh_terms: D000465:Algorithms; D000818:Animals; D045744:Cell Line, Tumor; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005354:Fibrosarcoma / Q000378:metabolism*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D057054:Molecular Imaging / Q000379:methods*; D010092:Oximetry / Q000379:methods*; D010100:Oxygen / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted
chemical_list: D010100:Oxygen
keywords: EPR; R1; imaging; in vivo; oxygen; pulse; spin lattice relaxation; tumor