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

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 3

In vivo oxygen mapping of SCC tumor-bearing and normal mouse legs, and visualization of the effect of carbogen breathing on tumor pO2.

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In vivo oxygen mapping of SCC tumor-bearing and normal mouse legs, and v...
(A) Cartoon showing the positioning of the tumor-bearing and normal legs along with the fiducials in the resonator for combined EPRI and MRI. (B) T2-weighted anatomical images (axial and coronal), in which tumor region could be clearly discriminated. Bright small circles are positional markers (fiducials) for coregistration of EPRI and MRI. (C) pO2 images (axial and coronal) when breathing medical air. (D) pO2 images (axial and coronal) 30 minutes after changing to breathing carbogen. (E) Histograms of pO2 in the tumor region of the same mouse breathing medical air (blue) and carbogen (red). A net increase in the median pO2 was noted upon carbogen breathing. (F) Blood volume image of coronal slice, in which a large blood vessel running vertically can be seen in the center of the tumor. Blood volume was calculated from a difference in image intensity before and after USPIO injection, therefore image intensity from positional markers was canceled. White lines indicate ROI.