Electron Paramagnetic Resonance Oxygen Images Correlate Spatially and Quantitatively with Oxylite Oxygen Measurements

Tumor oxygenation predicts cancer therapy response and malignant phenotype. This has spawned a number of oxymetries. Comparison of different oxymetries is crucial for the validation and understanding of these techniques. Electron paramagnetic resonance (EPR) imaging is a novel technique for providing quantitative high-resolution images of tumor and tissue oxygenation. This work compares sequences of tumor pO2 values from EPR oxygen images with sequences of oxygen measurements made along a track with an Oxylite oxygen probe. Four-dimensional (three spatial and one spectral) EPR oxygen images used spectroscopic imaging techniques to measure the width of a spectral line in each image voxel from a trityl spin probe (OX063, Amersham Health R&D) in the tissues and tumor of mice after spin probe injection. A simple calibration allows direct, quantitative translation of each line width to an oxygen concentration. These four-dimensional EPR images, obtained in 45 minutes from FSa fibrosarcomas grown in the legs of C3H mice, have a spatial resolution of ∼1 mm and oxygen resolution of ∼3 Torr. The position of the Oxylite track was measured within a 2-mm accuracy using a custom stereotactic positioning device. A total of nine images that involve 17 tracks were obtained. Of these, most showed good correlation between the Oxylite measured pO2 and a track located in the tumor within the uncertainties of the Oxylite localizability. The correlation was good both in terms of spatial distribution pattern and pO2 magnitude. The strong correlation of the two modalities corroborates EPR imaging as a useful tool for the study of tumor oxygenation.

[1]  Colin Mailer,et al.  Spin echo spectroscopic electron paramagnetic resonance imaging , 2006, Magnetic resonance in medicine.

[2]  T W Griffin,et al.  Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. , 1992, International journal of radiation oncology, biology, physics.

[3]  Colin Mailer,et al.  Spectral fitting: The extraction of crucial information from a spectrum and a spectral image , 2003, Magnetic resonance in medicine.

[4]  J R Griffiths,et al.  The OxyLite: a fibre-optic oxygen sensor. , 1999, The British journal of radiology.

[5]  Kecheng Liu,et al.  Dynamic in vivo oxymetry using overhauser enhanced MR imaging , 2000, Journal of magnetic resonance imaging : JMRI.

[6]  S Mutic,et al.  A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy. , 2001, International journal of radiation oncology, biology, physics.

[7]  P Vaupel,et al.  Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. , 1996, Cancer research.

[8]  J. Hendry,et al.  Radiobiology for the Radiologist , 1979, British Journal of Cancer.

[9]  R. Hill,et al.  Comparing techniques of measuring tumor hypoxia in different murine tumors: Eppendorf pO2 Histograph, [3H]misonidazole binding and paired survival assay. , 1996, Radiation research.

[10]  Steve Webb,et al.  Intensity-Modulated Radiation Therapy , 1996, International journal of radiation oncology, biology, physics.

[11]  B. Vojnovic,et al.  Measurement of tumor oxygenation: a comparison between polarographic needle electrodes and a time-resolved luminescence-based optical sensor. , 1997, Radiation research.

[12]  Xiaochuan Pan,et al.  EPR imaging: the relationship between CW spectra acquired from an extended sample subjected to fixed stepped gradients and the Radon transform of the resonance density. , 2005, Journal of magnetic resonance.

[13]  W. Risau,et al.  Mechanisms of angiogenesis , 1997, Nature.

[14]  D. Altman,et al.  STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT , 1986, The Lancet.

[15]  P Vaupel,et al.  Blood flow, oxygen consumption, and tissue oxygenation of human breast cancer xenografts in nude rats. , 1987, Cancer research.

[16]  J. Vanderkooi,et al.  An optical method for measurement of dioxygen concentration based upon quenching of phosphorescence. , 1987, The Journal of biological chemistry.

[17]  B Vojnovic,et al.  Measurement of Tumor Oxygenation: In Vivo Comparison of a Luminescence Fiber-optic Sensor and a Polarographic Electrode in the P22 Tumor , 2001, Radiation research.

[18]  Jinjie Jiang,et al.  In vivo Oximetry Using EPR and India Ink , 1995, Magnetic resonance in medicine.

[19]  G. Arteel,et al.  Comparisons among pimonidazole binding, oxygen electrode measurements, and radiation response in C3H mouse tumors. , 1999, Radiation research.

[20]  C. Grau,et al.  Measurement of pO2 in a murine tumour and its correlation with hypoxic fraction. , 1994, Advances in experimental medicine and biology.

[21]  P HOWARD-FLANDERS,et al.  Physical and chemical mechanisms in the injury of cells of ionizing radiations. , 1958, Advances in biological and medical physics.

[22]  J. Zweier,et al.  In vivo measurement of arterial and venous oxygenation in the rat using 3D spectral-spatial electron paramagnetic resonance imaging. , 1998, Physics in medicine and biology.

[23]  James B. Mitchell,et al.  Overhauser enhanced magnetic resonance imaging for tumor oximetry: Coregistration of tumor anatomy and tissue oxygen concentration , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[24]  M. Dewhirst,et al.  Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. , 1996, Cancer research.

[25]  David E. Housman,et al.  Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours , 1996, Nature.

[26]  L. Skarsgard,et al.  The cytotoxicity of melphalan and its relationship to pH, hypoxia and drug uptake. , 1995, Anticancer research.

[27]  Mark A Mintun,et al.  Assessing tumor hypoxia in cervical cancer by positron emission tomography with 60Cu-ATSM: relationship to therapeutic response-a preliminary report. , 2003, International journal of radiation oncology, biology, physics.

[28]  Howard J. Halpern,et al.  Imaging radio frequency electron‐spin‐resonance spectrometer with high resolution and sensitivity for in vivo measurements , 1989 .

[29]  M. Dewhirst,et al.  Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. , 1999, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[30]  Martyna Elas,et al.  Quantitative tumor oxymetric images from 4D electron paramagnetic resonance imaging (EPRI): Methodology and comparison with blood oxygen level‐dependent (BOLD) MRI , 2003, Magnetic resonance in medicine.

[31]  P. Antich,et al.  In vivo oxygen tension and temperature: Simultaneous determination using 19F NMR spectroscopy of perfluorocarbon , 1993, Magnetic resonance in medicine.

[32]  Weston A. Anderson,et al.  Electrical Current Shims for Correcting Magnetic Fields , 1961 .

[33]  B H Robinson,et al.  Linewidth analysis of spin labels in liquids. I. Theory and data analysis. , 1999, Journal of magnetic resonance.

[34]  P. Maddock Intensity modulated radiation therapy. , 2006, Medicine and health, Rhode Island.

[35]  C. Koch,et al.  Metabolism induced binding of 14C-misonidazole to hypoxic cells: kinetic dependence on oxygen concentration and misonidazole concentration. , 1984, International journal of radiation oncology, biology, physics.

[36]  L. H. Gray,et al.  The Histological Structure of Some Human Lung Cancers and the Possible Implications for Radiotherapy , 1955, British Journal of Cancer.

[37]  H. Holthusen Beiträge zur Biologie der Strahlenwirkung , 1921, Pflüger's Archiv für die gesamte Physiologie des Menschen und der Tiere.