Non-Invasive Monitoring of Tumor Hypoxia Using FD-NIRS

Numerous studies have found that hypoxia (lack of oxygen) leads to enhanced tumor metastasis and resistance to radiation and drugs. Strategies to reduce hypoxia by increasing oxygen delivery and decreasing oxygen consumption within the tumor are being explored to overcome hypoxia-induced resistance. Thus, there is a growing demand for technologies that noninvasively measure tumor hypoxia, as these technologies will enable advances in therapeutic drug development and trials.

The Biophotonics Laboratory has developed a side-firing fiber optic probe based on frequency-domain near-infrared spectroscopy (FD-NIRS) that quantifies tissue hemoglobin content (THb) and oxygenation level (SO2) noninvasively.

FD-NIRS uses RF-modulated red and near-infrared lasers as the light source and phase-sensitive detection system. It measures the amplitude attenuation and phase-shift of the diffuse reflectance signal from the tissue relative to the source. A diffusion model of light transport in tissue is used to extract the tissue absorption and scattering properties from the measured reflectance spectra. The sensor can be easily and reliably attached to a tumor surface for continuous and uninterrupted measurement and thus is an ideal tool for tumor hypoxia monitoring in vivo.


FD-NIRS instrumentation and data

Fig. 4:  FD-NIRS for tumor hypoxia monitoring with (left) instrument, (middle top) experimental setup for animal studies, (middle bottom) SO2 measured from an A549 tumor when the rat breathed forced cycling hypoxic gas (O2: 30% → 12% → 30% → 12% → 30%), and (right) normalized tissue SO2 in EO771 or A549 tumor-bearing mice (n=5) after injection of 2 mg/kg PPV or saline.


Selected Publications

Martin Benej, Xiangqian Hong, Sandip Vibhute, Sabina Scott, Jinghai Wu, Edward Graves, Quynh-Thu Le, Albert C Koong, Amato J Giaccia, Bing Yu, Shih-Ching Chen, Ioanna Papandreou, Nicholas C Denko, "Papavarine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism," Proceedings of the National Academy of Sciences (PNAS), September 10, 2018. 

Bing Yu, Amy Shah, Bingqing Wang, Narasimhan Rajaram, Quanli Wang, Nirmala Ramanujam, Gregory M. Palmer, and Mark W. Dewhirst, "Measuring Tumor Cycling Hypoxia and Angiogenesis using a Side-firing Fiber Optic Probe," Journal of Biophotonics, Volume 7, Issue 7, pages 552-564, 2014.



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