Research Papers: Imaging

Optical imaging of tumor hypoxia dynamics

[+] Author Affiliations
Gregory M. Palmer

Duke University Medical Center, Department of Radiation Oncology, P.O. Box 3455 Durham, North Carolina 27710

Andrew N. Fontanella

Duke University, Department of Biomedical Engineering, P.O. Box 3455 Durham, North Carolina 27710

Guoqing Zhang

University of Virginia, Department of Chemistry, P.O. Box 400319 Charlottesville, Virginia 22904

Gabi Hanna

Duke University Medical Center, Department of Radiation Oncology P.O. Box 3455 Durham, North Carolina 27710

Cassandra L. Fraser

University of Virginia, Department of Chemistry, P.O. Box 400319 Charlottesville, Virginia 22904

Mark W. Dewhirst

Duke University Medical Center Department of Radiation Oncology, Duke University, Department of Biomedical Engineering, P.O. Box 3455 Durham, North Carolina 27710

J. Biomed. Opt. 15(6), 066021 (December 20, 2010). doi:10.1117/1.3523363
History: Received July 09, 2010; Revised October 06, 2010; Accepted October 07, 2010; Published December 20, 2010; Online December 20, 2010
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The influence of the tumor microenvironment and hypoxia plays a significant role in determining cancer progression, treatment response, and treatment resistance. That the tumor microenvironment is highly heterogeneous with significant intratumor and intertumor variability presents a significant challenge in developing effective cancer therapies. Critical to understanding the role of the tumor microenvironment is the ability to dynamically quantify oxygen levels in the vasculature and tissue in order to elucidate the roles of oxygen supply and consumption, spatially and temporally. To this end, we describe the use of hyperspectral imaging to characterize hemoglobin absorption to quantify hemoglobin content and oxygen saturation, as well as dual emissive fluorescent/phosphorescent boron nanoparticles, which serve as ratiometric indicators of tissue oxygen tension. Applying these techniques to a window-chamber tumor model illustrates the role of fluctuations in hemoglobin saturation in driving changes in tissue oxygenation, the two being significantly correlated (r = 0.77). Finally, a green-fluorescence-protein reporter for hypoxia inducible factor-1 (HIF-1) provides an endpoint for hypoxic stress in the tumor, which is used to demonstrate a significant association between tumor hypoxia dynamics and HIF-1 activity in an in vivo demonstration of the technique.

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© 2010 Society of Photo-Optical Instrumentation Engineers

Citation

Gregory M. Palmer ; Andrew N. Fontanella ; Guoqing Zhang ; Gabi Hanna ; Cassandra L. Fraser, et al.
"Optical imaging of tumor hypoxia dynamics", J. Biomed. Opt. 15(6), 066021 (December 20, 2010). ; http://dx.doi.org/10.1117/1.3523363


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