title: Electron paramagnetic resonance imaging of tumor hypoxia: enhanced spatial and temporal resolution for in vivo pO2 determination.
abstract: The time-domain (TD) mode of electron paramagnetic resonance (EPR) data collection offers a means of estimating the concentration of a paramagnetic probe and the oxygen-dependent linewidth (LW) to generate pO2 maps with minimal errors. A methodology for noninvasive pO2 imaging based on the application of TD-EPR using oxygen-induced LW broadening of a triarylmethyl (TAM)-based radical is presented. The decay of pixel intensities in an image is used to estimate T2*, which is inversely proportional to pO2. Factors affecting T2* in each pixel are critically analyzed to extract the contribution of dissolved oxygen to EPR line-broadening. Suitable experimental and image-processing parameters were obtained to produce pO2 maps with minimal artifacts. Image artifacts were also minimized with the use of a novel data collection strategy using multiple gradients. Results from a phantom and in vivo imaging of tumor-bearing mice validated this novel method of noninvasive oximetry. The current imaging protocols achieve a spatial resolution of approximately 1.0 mm and a temporal resolution of approximately 9 s for 2D pO2 mapping, with a reliable oxygen resolution of approximately 1 mmHg (0.12% oxygen in gas phase). This work demonstrates that in vivo oximetry can be performed with good sensitivity, accuracy, and high spatial and temporal resolution.
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892-1002, USA.
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Sankaran
authors.initials: S
authors.lastname: Subramanian
authors.forename: Nallathamby
authors.initials: N
authors.lastname: Devasahayam
authors.forename: Thirumaran
authors.initials: T
authors.lastname: Aravalluvan
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Murugesan
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: D000465:Algorithms; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism*; D015687:Cell Hypoxia; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D010092:Oximetry / Q000379:methods*; D010100:Oxygen / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D010100:Oxygen