Development of a hybrid EPR/NMR coimaging system

Electron paramagnetic resonance imaging (EPRI) is a powerful technique that enables spatial mapping of free radicals or other paramagnetic compounds; however, it does not in itself provide anatomic visualization of the body. Proton magnetic resonance imaging (MRI) is well suited to provide anatomical visualization. A hybrid EPR/NMR coimaging instrument was constructed that utilizes the complementary capabilities of both techniques, superimposing EPR and proton‐MR images to provide the distribution of paramagnetic species in the body. A common magnet and field gradient system is utilized along with a dual EPR and proton‐NMR resonator assembly, enabling coimaging without the need to move the sample. EPRI is performed at ∼1.2 GHz/∼40 mT and proton MRI is performed at 16.18 MHz/∼380 mT; hence the method is suitable for whole‐body coimaging of living mice. The gradient system used is calibrated and controlled in such a manner that the spatial geometry of the two acquired images is matched, enabling their superposition without additional postprocessing or marker registration. The performance of the system was tested in a series of phantoms and in vivo applications by mapping the location of a paramagnetic probe in the gastrointestinal (GI) tract of mice. This hybrid EPR/NMR coimaging instrument enables imaging of paramagnetic molecules along with their anatomic localization in the body. Magn Reson Med 58:156–166, 2007. © 2007 Wiley‐Liss, Inc.

[1]  Jimmy D Bell,et al.  1H NMR study of cerebral development in the rat , 1989, NMR in biomedicine.

[2]  D. Lurie Commentary: electron spin resonance imaging studies of biological systems. , 1996, The British journal of radiology.

[3]  J. Zweier,et al.  Cardiac applications of EPR imaging , 2004, NMR in biomedicine.

[4]  James B. Mitchell,et al.  High-Resolution Mapping of Tumor Redox Status by Magnetic Resonance Imaging Using Nitroxides as Redox-Sensitive Contrast Agents , 2006, Clinical Cancer Research.

[5]  H J Halpern,et al.  Measurement of differences in pO2 in response to perfluorocarbon/carbogen in FSa and NFSa murine fibrosarcomas with low-frequency electron paramagnetic resonance oximetry. , 1996, Radiation research.

[6]  W. Perman,et al.  Spatially resolved high resolution spectroscopy by “four-dimensional” NMR , 1983 .

[7]  Murali C Krishna,et al.  Electron paramagnetic resonance imaging of tumor hypoxia: Enhanced spatial and temporal resolution for in vivo pO2 determination , 2006, Magnetic resonance in medicine.

[8]  P. Lauterbur,et al.  Three-dimensional electron spin resonance imaging , 1989 .

[9]  Howard J Halpern,et al.  General synthesis of persistent trityl radicals for EPR imaging of biological systems. , 2002, The Journal of organic chemistry.

[10]  J. Zweier,et al.  Electron paramagnetic resonance measurements of free radicals in the intact beating heart: a technique for detection and characterization of free radicals in whole biological tissues. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. Hogg Magnetic resonance imaging. , 1994, Journal of the Royal Naval Medical Service.

[12]  N.m.r. imaging of intact biological systems. , 1980, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[13]  Gareth R Davies,et al.  Field-cycled PEDRI imaging of free radicals with detection at 450 mT. , 2005, Magnetic resonance imaging.

[14]  J. Zweier,et al.  Noninvasive measurement of anatomic structure and intraluminal oxygenation in the gastrointestinal tract of living mice with spatial and spectral EPR imaging. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Zweier,et al.  EPR spectroscopy of free radicals in the perfused heart , 1994 .

[16]  H J Halpern,et al.  In vivo spin-label murine pharmacodynamics using low-frequency electron paramagnetic resonance imaging. , 1996, Biophysical journal.

[17]  R R Edelman,et al.  Magnetic resonance imaging (1). , 1993, The New England journal of medicine.

[18]  Yuanmu Deng,et al.  In vivo proton electron double resonance imaging of the distribution and clearance of nitroxide radicals in mice , 2006, Magnetic resonance in medicine.

[19]  James S. Hyde,et al.  Theory of Saturation and Double Resonance Effects in ESR Spectra. III. rf Coherence and Line Shapes , 1967 .

[20]  J. Zweier,et al.  Development and optimization of three-dimensional spatial EPR imaging for biological organs and tissues. , 1995, Journal of magnetic resonance. Series B.

[21]  J. Berliner,et al.  Magnetic resonance imaging of biological specimens by electron paramagnetic resonance of nitroxide spin labels. , 1985, Science.

[22]  J. Hutchinson Electron spin resonance spectrometry on the whole mouse in vivo: optimum frequency considerations. , 1971 .

[23]  J. Zweier,et al.  Three‐Dimensional gated EPR imaging of the beating heart: Time‐resolved measurements of free radical distribution during the cardiac contractile cycle , 1996, Magnetic resonance in medicine.

[24]  J. Zweier,et al.  Three‐dimensional spatial EPR imaging of the rat heart , 1995, Magnetic resonance in medicine.

[25]  D. Gadian NMR and its Applications to Living Systems , 1996 .

[26]  Mitsuhiro Ono,et al.  A composite resonator assembly suitable for EPR/NMR coregistration imaging , 2005 .

[27]  Hiroshi Hirata,et al.  Mapping of the B1 field distribution of a surface coil resonator using EPR imaging , 2002, Magnetic resonance in medicine.

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

[29]  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.

[30]  J. Zweier,et al.  Mapping the spin-density and lineshape distribution of free radicals using 4D spectral-spatial EPR imaging. , 1995, Journal of magnetic resonance. Series B.

[31]  Yuanmu Deng,et al.  EPR/NMR co‐imaging for anatomic registration of free‐radical images , 2002, Magnetic resonance in medicine.

[32]  G. Rinard,et al.  Frequency Dependence of EPR Sensitivity , 2004 .

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

[34]  J. Zweier,et al.  Three-dimensional spectral-spatial EPR imaging of free radicals in the heart: a technique for imaging tissue metabolism and oxygenation. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[35]  J. Zweier,et al.  Reactivity of molecular oxygen with ethoxycarbonyl derivatives of tetrathiatriarylmethyl radicals. , 2006, The Journal of organic chemistry.

[36]  R. Edelman,et al.  Magnetic resonance imaging (2) , 1993, The New England journal of medicine.