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Low-field paramagnetic resonance imaging of tumor oxygenation and glycolytic activity in mice
Shingo Matsumoto, … , James B. Mitchell, Murali C. Krishna
Shingo Matsumoto, … , James B. Mitchell, Murali C. Krishna
Published April 22, 2008
Citation Information: J Clin Invest. 2008;118(5):1965-1973. https://doi.org/10.1172/JCI34928.
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Technical Advance

Low-field paramagnetic resonance imaging of tumor oxygenation and glycolytic activity in mice

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Abstract

A priori knowledge of spatial and temporal changes in partial pressure of oxygen (oxygenation; pO2) 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 pO2 in living objects. In this study, we implemented an EPRI set-up that could acquire pO2 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 pO2 maps with anatomic guidance. Using EPRI and an air/carbogen (95% O2 plus 5% CO2) breathing cycle, we visualized perfusion-limited hypoxia in murine tumors. The relationship between tumor blood perfusion and pO2 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 pO2 in tumors, reported with anatomy, with precision. In addition, this method may also be useful for studying the relationship between pO2 status and tumor-specific phenotypes such as aerobic glycolysis.

Authors

Shingo Matsumoto, Fuminori Hyodo, Sankaran Subramanian, Nallathamby Devasahayam, Jeeva Munasinghe, Emi Hyodo, Chandramouli Gadisetti, John A. Cook, James B. Mitchell, Murali C. Krishna

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Figure 1

The pulsed EPR system.

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The pulsed EPR system.
(A) EPRI spectrometer used for pO2 imaging. Oxyge...
(A) EPRI spectrometer used for pO2 imaging. Oxygen imaging is carried out using the 300 MHz pulsed EPR scanner operating at 10 mT, having 5 ns time resolution for signal detection. (B) A 4D (3D spatial and 1D spectral) EPR image was obtained after infusion of the oxygen sensitive probe TAM equilibrated at different levels of oxygen as indicated in the figure. Spatially resolved EPR line width of TAM can be extracted from the EPR signal intensity image, which has linear relationship with partial pressure of oxygen (C), and consequently, an absolute pO2 map (D) can be obtained with anatomical overlay by sequential MRI scan of the same object.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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