title: Low-field magnetic resonance imaging to visualize chronic and cycling hypoxia in tumor-bearing mice.
abstract: Tumors exhibit fluctuations in blood flow that influence oxygen concentrations and therapeutic resistance. To assist therapeutic planning and improve prognosis, noninvasive dynamic imaging of spatial and temporal variations in oxygen partial pressure (pO(2)) would be useful. Here, we illustrate the use of pulsed electron paramagnetic resonance imaging (EPRI) as a novel imaging method to directly monitor fluctuations in oxygen concentrations in mouse models. A common resonator platform for both EPRI and magnetic resonance imaging (MRI) provided pO(2) maps with anatomic guidance and microvessel density. Oxygen images acquired every 3 minutes for a total of 30 minutes in two different tumor types revealed that fluctuation patterns in pO(2) are dependent on tumor size and tumor type. The magnitude of fluctuations in pO(2) in SCCVII tumors ranged between 2- to 18-fold, whereas the fluctuations in HT29 xenografts were of lower magnitude. Alternating breathing cycles with air or carbogen (95% O(2) plus 5% CO(2)) distinguished higher and lower sensitivity regions, which responded to carbogen, corresponding to cycling hypoxia and chronic hypoxia, respectively. Immunohistochemical analysis suggests that the fluctuation in pO(2) correlated with pericyte density rather than vascular density in the tumor. This EPRI technique, combined with MRI, may offer a powerful clinical tool to noninvasively detect variable oxygenation in tumors.
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1002, USA.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yasui
authors.forename: Shingo
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Nallathamby
authors.initials: N
authors.lastname: Devasahayam
authors.forename: Jeeva P
authors.initials: JP
authors.lastname: Munasinghe
authors.forename: Rajani
authors.initials: R
authors.lastname: Choudhuri
authors.forename: Keita
authors.initials: K
authors.lastname: Saito
authors.forename: Sankaran
authors.initials: S
authors.lastname: Subramanian
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: Murali C
authors.initials: MC
authors.lastname: Krishna
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia / Q000502:physiology; D003110:Colonic Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000032:analysis / Q000378:metabolism*; D010313:Partial Pressure; D014183:Transplantation, Heterologous
chemical_list: D010100:Oxygen