title: Low-field paramagnetic resonance imaging of tumor oxygenation and glycolytic activity in mice.
abstract: A priori knowledge of spatial and temporal changes in partial pressure of oxygen (oxygenation; pO(2)) in solid tumors, a key prognostic factor in cancer treatment outcome, could greatly improve treatment planning in radiotherapy and chemotherapy. Pulsed electron paramagnetic resonance imaging (EPRI) provides quantitative 3D maps of tissue pO(2) in living objects. In this study, we implemented an EPRI set-up that could acquire pO(2) maps in almost real time for 2D and in minutes for 3D. We also designed a combined EPRI and MRI system that enabled generation of pO(2) maps with anatomic guidance. Using EPRI and an air/carbogen (95% O(2) plus 5% CO(2)) breathing cycle, we visualized perfusion-limited hypoxia in murine tumors. The relationship between tumor blood perfusion and pO(2) status was examined, and it was found that significant hypoxia existed even in regions that exhibited blood flow. In addition, high levels of lactate were identified even in normoxic tumor regions, suggesting the predominance of aerobic glycolysis in murine tumors. This report presents a rapid, noninvasive method to obtain quantitative maps of pO(2) in tumors, reported with anatomy, with precision. In addition, this method may also be useful for studying the relationship between pO(2) status and tumor-specific phenotypes such as aerobic glycolysis.
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1002, USA.
authors.forename: Shingo
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Fuminori
authors.initials: F
authors.lastname: Hyodo
authors.forename: Sankaran
authors.initials: S
authors.lastname: Subramanian
authors.forename: Nallathamby
authors.initials: N
authors.lastname: Devasahayam
authors.forename: Jeeva
authors.initials: J
authors.lastname: Munasinghe
authors.forename: Emi
authors.initials: E
authors.lastname: Hyodo
authors.forename: Chandramouli
authors.initials: C
authors.lastname: Gadisetti
authors.forename: John A
authors.initials: JA
authors.lastname: Cook
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: Murali C
authors.initials: MC
authors.lastname: Krishna
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging / Q000295:instrumentation / Q000379:methods*; D004578:Electron Spin Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods; D006019:Glycolysis; D007091:Image Processing, Computer-Assisted; D051379:Mice; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic; D010101:Oxygen Consumption