title: Overhauser enhanced magnetic resonance imaging for tumor oximetry: coregistration of tumor anatomy and tissue oxygen concentration.
abstract: 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.
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. murali@helix.nih.gov
authors.forename: Murali C
authors.initials: MC
authors.lastname: Krishna
authors.forename: Sean
authors.initials: S
authors.lastname: English
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamada
authors.forename: John
authors.initials: J
authors.lastname: Yoo
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Murugesan
authors.forename: Nallathamby
authors.initials: N
authors.lastname: Devasahayam
authors.forename: John A
authors.initials: JA
authors.lastname: Cook
authors.forename: Klaes
authors.initials: K
authors.lastname: Golman
authors.forename: Jan Henrik
authors.initials: JH
authors.lastname: Ardenkjaer-Larsen
authors.forename: Sankaran
authors.initials: S
authors.lastname: Subramanian
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
mesh_terms: D000465:Algorithms; D000818:Animals; D003287:Contrast Media / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D000860:Hypoxia; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption
chemical_list: D003287:Contrast Media; D010100:Oxygen