Time-Domain Radio Frequency EPR Imaging

  • Sankaran Subramanian
  • James B. Mitchell
  • Murali C. Krishna
Part of the Biological Magnetic Resonance book series (BIMR, volume 18)


The development of a radio frequency time domain EPR spectrometer/imager operating at 300 MHz for in vivo applications is described. The ways we have addressed the challenges originating from the very short relaxation times of the unpaired spin ensemble such as the design of broad band low Q resonators, the necessity of providing ultra short pulses of sub microsecond duration, reduction of the receiver recovery time (resonator dead time and preamplifier recovery time), the need to sample the time response at Gigasamples/s rates, etc., are outlined. The reduction in the sensitivity by lowering the frequency of measurement to radio frequency regime necessitates the use of fast signal averaging strategies. The spectrometer/imager can address objects up to the size of a whole mouse, and well resolved 2-D and 3-D images could be obtained using narrow line spin probes based on triarylmethyl radicals, using volume excitations in presence of static gradients and filtered back-projection techniques. The imaging modalities are outlined and representative examples from phantoms and in vivo studies are presented. The use of local relaxation time differences brought about by changes in the tissue pO2to provide contrasts in the images is also described. Time domain RF FT-EPR method may turn out to be an important imaging tool to provide valuable information on tumor hypoxia, vascular perfusion profiles and the assessment of in vivo pO2and will act as an useful adjunct to CT, BOLD-MRI and PET.


Electron Paramagnetic Resonance Spin Probe Gradient Magnitude Back Projection Quadrature Mode 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Afeworki, M., van Dam, G. M., Devasahayam, N., Murugesan, R., Cook, J., Coffin, D., Larsen, J. H. A., Mitchell, J. B., Subramanian, S., and Krishna, M. C. (2000) Three-dimensional whole body imaging of spin probes in mice by time-domain radiofrequency electron paramagnetic resonance. Magn. Reson. Med. 43, 375–382.Google Scholar
  2. Alecci, M., Brivati, J. A., Placidi, G., and Sotgiu, A. (1998a) A radiofrequency (220 MHz) Fourier transform EPR spectrometer. J. Magn. Reson. 130, 272–280.CrossRefGoogle Scholar
  3. Alecci, M., Brivati, J. A., Placidi, G., Testa, L., Lurie, D. J., and Sotgiu, A. (1998b) A submicrosecond resonator and receiver system for pulsed magnetic resonance with large samples. J. Magn. Reson. 132, 162–166.CrossRefGoogle Scholar
  4. Berliner, J. L., and Fujii, H. (1985) Magnetic resonance imaging of biological specimens by electron paramagnetic resonance of nitroxide spin labels. Science 227, 517–519.PubMedCrossRefGoogle Scholar
  5. Bracewell, R. N. (1979) Image reconstruction in radioastronomy.Google Scholar
  6. Crawford, C. R., and Kak, A. C. (1979) Aliasing artifacts in computerized tomography. Appl. Opt. 18, 3704–3709.Google Scholar
  7. Devasahayam, N., Subramanian, S., Murugesan, R., Cook, J. A., Afeworki, M., Tschudin, R. G., Mitchell, J. B., and Krishna, M. C. (1999) Parallel coil resonators for time-domain radiofrequency electron paramagnetic resonance imaging of biological objects..J. Magn. Reson 141Google Scholar
  8. Ernst, R. R., and Anderson, W. A. (1966) Application of Fourier spectroscopy to nuclear magnetic resonance. Rev. Sci. Instr. 37, 93–103.CrossRefGoogle Scholar
  9. Ewert, U., and Herriing, T. (1986) Spectrally resolved EPR tomography with stationary gradient. Chem. Phys. Lett. 129, 516–520.CrossRefGoogle Scholar
  10. Halpern, H. J., Yu, C., Peric, M., Barth, E., Grdina, D. J., and Teicher, B. A. (1994) Oximetry deep in tissues with low-frequency electron paramagnetic resonance. Proc. Natl. Acad. Sci. USA 91, 13047–13051.PubMedCentralPubMedCrossRefGoogle Scholar
  11. Herman, G. T. (1980) Image reconstruction from projections. Academic Press, New YorkGoogle Scholar
  12. Kak, A. C., and Slaney, M. (1988) Principles of computerized tomographic imaging. IEEE Press New York.Google Scholar
  13. Kuppusamy, P., Chzhan, M., Vij, K., Shteynbuk, M., Lefer, D. J., Giannella, E., and Zweier, J. L. (1994) Three-dimensional spectral-spatial EPR imaging of free radicals in the heart: a technique for imaging tissue metabolism and oxygenation. Proc. Natl. Acad. Sci. U S A 91,3388–3392.PubMedCentralPubMedCrossRefGoogle Scholar
  14. Lauterbur, P. C., Levin, D. N., and Marr, R. B. (1984) Theory and simulation of NMR spectroscopic imaging and field plotting by projection reconstruction involving an intrinsic frequency dimension. J. Magn. Reson. 1984, 536–541.Google Scholar
  15. Liu, K. J., Gast, P., Moussavi, M., Norby, S. W., Vahidi, N., Walzak, T., Wu, M., and Swartz, H. M. (1993) Lithium phthalocyanine: a probe for electron paramagnetic resonance oximetry in viable biologic systems. Proc. Natl. Acad. Sci. USA 90, 5438–5442.PubMedCentralPubMedCrossRefGoogle Scholar
  16. Maltempo, M. M. (1986) Differentiation of spectral and spatial components in EPR imaging using 2-D image reconstruction algorithms. J. Magn. Reson. 69, 156–163.Google Scholar
  17. Maltempo, M. M., Eaton, S. S., and Eaton, G. R. (1987) Spectral-spatial two dimensional EPR imaging. J. Magn. Reson. 72, 449–455.Google Scholar
  18. Marr, R. B., Chen, C. N., and Lauterbur, P. C. (1981) On two approaches to 3D reconstruction in NMR zeugmatography, in Mathematical Aspects of Computerized Tomography (Herman, G. T. and Natterer, F., eds) Springer-Verlag, Berlin.Google Scholar
  19. Murugesan, R., Cook, J. A., Devasahayam, N., Afeworki, M., Subramanian, S., Tschudin, R., Larsen, J. H. A., Mitchell, J. B., Russo, A., and Krishna, M. C. (1997) In vivo imaging of a stable paramagnetic probe by pulsed-radiofrequency electron paramagnetic resonance spectroscopy. Magn. Reson. Med. 38, 409–414.Google Scholar
  20. Murugesan, R., Afeworki, M., Cook, J. A., Devasahayam, N., Tschudin, R., Mitchell, J. B., Subramanian, S., and Krishna, M. C. (1998) A broadband pulsed radio frequency electron paramagnetic resonance spectrometer for biological applications. Rev.Sci. Instr. 69, 1869–1876.CrossRefGoogle Scholar
  21. Natterer, F. (1986) The mathematics of computerized tomography. Wiley New York.Google Scholar
  22. Orfanidis, S. J. (1996) Introduction to signal processing. Prentice Hall, Englewood Cliffs, N.JGoogle Scholar
  23. Placidi, G., Brivati, J. A., Alecci, M., Testa, L., and Sotgiu, A. (1998) Two-dimensional 220 MHz Fourier transform EPR imaging.Phys. Med. Biol. 431845–1850.PubMedCrossRefGoogle Scholar
  24. Poole, C. P. (1996) Electron spin resonance: A comprehensive treatise on experimental techniques. Dover Publications, Mineola, N.Y.Google Scholar
  25. Prisner, T. F., Rohrer, M., and Mobius, K. (1994) Pulsed 95 GHz high field EPR heterodyne spectrometer with high spectral and time resolution.Appl. Magn. Reson. 7167–183.CrossRefGoogle Scholar
  26. Ramachandran, G. N., and Lakshminarayanan, A. V. (1971) Three-dimensional reconstruction from radiographs and electron-micrographs: application of convolutions instead of Fourier transforms.Proc. Natl. Acad. Sci. (USA) 682236–2240.CrossRefGoogle Scholar
  27. Rinard, G. A., Quine, R. W., Eaton, S. S., Eaton, G. R., and Froncisz, W. (1994) Relative benefits of overcoupled resonators vs inherently low-Q resonators for pulsed magnetic resonance.J. Magn. Reson. A. 10871–81.CrossRefGoogle Scholar
  28. Roeder, S. B. W., Fukushima, E., and Gibson, A. A. V. (1984) NMR coils with segments in parallel achieve higher frequencies or larger sample volumes.J. Magn. Reson. 59307–317.Google Scholar
  29. Rollett, J. S., and Higgs, L. S. (1962) Correction of spectroscopic line profiles for instrumental broadening by a Fourier analysis method.Proc. Roy. Soc. Lond. 7987–91.CrossRefGoogle Scholar
  30. Shepp, L. A., and Logan, B. F. (1974) The Fourier reconstruction of a head section.IEEE Trans. Nucl. Sci. NS2121.CrossRefGoogle Scholar
  31. Shepp, L. A. (1980) Computerized tomography and nuclear magnetic resonance.J. Comp. Assist. Tomogr. 494–101.CrossRefGoogle Scholar
  32. Subramanian, S., Murugesan, R., Devasahayam, N., Cook, J. A., Afeworki, M., Pohida, T., Tschudin, R. G., Mitchell, J. B., and Krishna, M. C. (1999) High-speed data acquisition system and receiver configurations for time-domain radiofrequency electron paramagnetic resonance spectroscopy and imaging.J Magn. Reson. 137379–388.PubMedCrossRefGoogle Scholar
  33. Woods, R. K., Hyslop, W. B., Marr, R. B., and Lauterbur, P. C. (1991) Image reconstruction, inEPR Imaging and in vivo EPR. (G. Eaton, S. Eaton and K. Ohno, Eds.) CRC Press, Boca Raton, FL, 91–118.Google Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Sankaran Subramanian
    • 1
  • James B. Mitchell
    • 1
  • Murali C. Krishna
    • 1
  1. 1.Radiation Biology Branch, Division of Clinical SciencesNational Cancer Institute, National Institutes of HealthBethesdaUSA

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