Electron Paramagnetic Resonance (EPR) Oxygen Images (EPROI) provide quantitative localized pO2 distributions in animal tumors of syngeneic mice, rats, and rabbits. The oxygen broadening of narrow EPR spectral lines reports the pO2 with 1-3 torr resolution in each 1mm3 image voxel. This work has successfully shown 1) the first co-localized correlation between an oxygen image and a point oxygen measurement technique (Oxylite);2) independent, statistically significant sharpening of the 50% tumor control dose with the addition of the information provided by the fraction of EPROI voxels with pO2 less than 10 torr (HF10);3) significant spatial correlation of VEGF and EPROI based HF10;4) when treated to the dose necessary to control 50% (TCD50) of all FSa fibrosarcomas, control is only 28% in tumors with HF10>8% while it increases to 92% for those with HF10<8%. In the next funding cycle we propose to explore EPROI as the basis for IMRT dose painting in 2cm rat 13762 carcinomas, chosen for ease of IMRT via increased size. We propose the following specific aims for the next funding cycle: exploring the effectiveness of 1) Adding a fixed dose to the TCD50 targeting an IMRT boost to an EPROI based hypoxic region, compared with adding the same boost dose to a well oxygenated tumor region of equal volume 2) Adding dose to the hypoxic region and reduced dose to a well oxygenated region. This would be compared with delivery of uniform TCD50. 3) Adding a graded dose to regions of the tumor proportional to the HF10. This work will test the efficacy of the use of oxygen imaging in dose painting in small mammals. It will provide a path to enhancement of radiation therapy efficacy and reduction of its side effects.

Public Health Relevance

This work continues the investigation of a new technique to predict cure likelihood using radiation therapy for cancers and to improve the cure of cancers with radiation. The technique involves a non-invasive electron magnetic resonance image of a non-toxic compound, injected in an animal, which reports the amount of oxygen in each of the 1 mm3 volumes of the animal tumor. This eventually will guide the placement of extra radiation dose to enhance human tumor treatment with radiation.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Radiation Therapeutics and Biology Study Section (RTB)
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Bernhard, Eric J
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University of Chicago
Schools of Medicine
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Christodoulou, Anthony G; Redler, Gage; Clifford, Bryan et al. (2016) Fast dynamic electron paramagnetic resonance (EPR) oxygen imaging using low-rank tensors. J Magn Reson 270:176-82
Epel, Boris; Redler, Gage; Pelizzari, Charles et al. (2016) Approaching Oxygen-Guided Intensity-Modulated Radiation Therapy. Adv Exp Med Biol 876:185-93
Epel, Boris; Redler, Gage; Tormyshev, Victor et al. (2016) Towards Human Oxygen Images with Electron Paramagnetic Resonance Imaging. Adv Exp Med Biol 876:363-9
Tseytlin, Mark; Epel, Boris; Sundramoorthy, Subramanian et al. (2016) Decoupling of excitation and receive coils in pulsed magnetic resonance using sinusoidal magnetic field modulation. J Magn Reson 272:91-99
Redler, Gage; Epel, Boris; Halpern, Howard J (2015) Maximally spaced projection sequencing in electron paramagnetic resonance imaging. Concepts Magn Reson Part B Magn Reson Eng 45:33-45
Qiao, Zhiwei; Redler, Gage; Epel, Boris et al. (2015) Implementation of GPU-accelerated back projection for EPR imaging. J Xray Sci Technol 23:423-33
Redler, Gage; Qiao, Zhiwei; Epel, Boris et al. (2015) Real-Time Image Reconstruction for Pulse EPR Oxygen Imaging Using a GPU and Lookup Table Parameter Fitting. Concepts Magn Reson Part B Magn Reson Eng 45:46-57
Qiao, Zhiwei; Redler, Gage; Epel, Boris et al. (2015) 3D pulse EPR imaging from sparse-view projections via constrained, total variation minimization. J Magn Reson 258:49-57
Epel, Boris; Halpern, Howard J (2015) Comparison of pulse sequences for R1-based electron paramagnetic resonance oxygen imaging. J Magn Reson 254:56-61
Epel, Boris; Halpern, Howard J (2015) In Vivo pO2 Imaging of Tumors: Oxymetry with Very Low-Frequency Electron Paramagnetic Resonance. Methods Enzymol 564:501-27

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