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The Development of Time-Domain In Vivo EPR Imaging at NCI

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Abstract

Electron Paramagnetic Resonance (NMR) and Nuclear Magnetic Resonance (NMR) discovered around the middle of the twentieth century became two of the fastest evolving spectroscopic techniques with applications starting in physics and slowly developing into playing important roles in structural organic chemistry, biology, solid state, medicine, and almost any field. NMR has been developing relatively faster than EPR due to reasons of large differences in their dynamics that will be detailed below. With the development of FT-NMR and diagnostic imaging with MRI, NMR kindled the efforts in the development of FT-EPR imaging attempts. With relentless efforts supported by the developments in electronics, fast switches, and narrow-line free electron spin probes, we are now in a position to routinely generate fast in vivo EPR images of small animals using time-domain EPR. EPR imaging holds a unique promise of quantitatively mapping the in vivo tissue oxygen distribution non-invasively. However, unlike MRI, EPRI requires the use of non-toxic bio-compatible paramagnetic spin probes. Many tumors are characterized by a hypoxic core that is highly resistant to radiation and chemotherapeutic treatment. EPRI enables fast quantitative non-invasive assessment and monitoring of tumor hypoxia. The present article is confined to the development of radiofrequency Time-domain EPR imaging developed at NCI, NIH, DHHS, USA, and some representative examples.

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References

  1. P.C. Lauterbur, Image formation by induced local interactions: examples employing nuclear magnetic resonance. Nature 242, 190–191 (1973)

    Article  ADS  Google Scholar 

  2. P. Mansfield, Multi-planar image formation using NMR spin echoes. J. Phys. C: Solid State Phys. C10, L55–L58 (1977)

    Article  ADS  Google Scholar 

  3. J. Radon, P.C. Parks, On the determination of functions from their integral values along certain manifolds. IEEE Trans. Med. Imaging 5, 170–176 (1986)

    Article  Google Scholar 

  4. D. Kumar, R.R. Welti, Ernst NMR fourier zeugmatography. J. Magn. Reson. 213, 495–509 (2011)

    Article  ADS  Google Scholar 

  5. K.J. Liu, P. Gast, M. Moussavi, S.W. Norby, N. Vahidi, T. Walzak, M. Wu, H.M. Swartz, Lithium phthalocyanine: a probe for electron paramagnetic resonance oximetry in viable biologic systems. Proc. Nat. Acad. Sci. USA 90, 5438–5442 (1993)

    Article  ADS  Google Scholar 

  6. A. Manivannan, H. Yanagi, G. Ilangovan, P. Kuppusamy, Lithium naphthalocyanine as a new molecular radical probe for electron paramagnetic resonance oximetry. J. Magn. Magn. Mater. 233(3), L131–L135 (2001)

    Article  ADS  Google Scholar 

  7. S. Pfenninger, W. Froncisz, J. Forrer, J. Luglio, J.S. Hyde, General-method for adjusting the quality factor of EPR resonators. Rev. Sci. Instrum. 66(10), 4857–4865 (1995)

    Article  ADS  Google Scholar 

  8. G.A. Rinard, R.W. Quine, S.S. Eaton, G.R. Eaton, Frequency dependence of EPR sensitivity, in EPR: instrumental methods: biological magnetic resonance, vol. 21, ed. by L.J. Berliner, C.J. Bender (Springer, Boston, MA, 2004)

    Google Scholar 

  9. J.H. Ardenkjaer-Larsen, I. Laursen, I. Leunbach, G.J. Ehnholm, L.G. Wistrand, J.S. Petersson, K. Golman, EPR and dnp properties of certain novel single electroncontrast agents intended for oximetric imaging. J. Magn. Reson. 133, 1–12 (1998)

    Article  ADS  Google Scholar 

  10. K. Golman, I. Leunbach, J.H. Ardenkjaer-Larsen, G.J. Ehnholm, L.G. Wistrand, J.S. Petersson, A. Jarvi, S. Vahasalo, Overhauser-enhanced MR imaging (OMRI). Acta Radiol. 39(1), 10–17 (1998)

    Article  Google Scholar 

  11. K.I. Matsumoto, S. Subramanian, R. Murugesan, J.B. Mitchell, M.C. Krishna, Spatially resolved biologic information from in vivo EPRI, OMRI, and MRI. Antioxid. Redox Signal. 9(8), 1125–1141 (2007)

    Article  Google Scholar 

  12. N. Devasahayam, S. Subramanian, R. Murugesan, J.A. Cook, M. Afeworki, R.G. Tschudin, J.B. Mitchell, M.C. Krishna, Parallel coil resonators for time-domain radiofrequency electron paramagnetic resonance imaging of biological objects. J. Magn. Reson. 142(1), 168–176 (2000)

    Article  ADS  Google Scholar 

  13. S. Subramanian, J.W. Koscielniak, N. Devasahayam, R.H. Pursley, T.J. Pohida, M.C. Krishna, A new strategy for fast radiofrequency CW EPR imaging: direct detection with rapid scan and rotating gradients. J. Magn. Reson. 186(2), 212–219 (2007)

    Article  ADS  Google Scholar 

  14. R. Czoch, A. Francik, J. Indyka, J. Koscielniak, EPR spectrometer with rapid scan. Meas. Automatic Contr. 29, 41–43 (1983)

    Google Scholar 

  15. Hornak, J.P. The Basics of MRI; J.P. Hornak, 1996–2011; http://www.cis.rit.edu/htbooks/mri/. Accessed 5 Jan 2021

  16. V.S. Subramanian, E. Boris, H.J. Halpern, Orthogonal resonators for pulse in vivo electron paramagnetic imaging at 250 MHz. J. Magn. Reson. 240, 45–51 (2014)

    Article  ADS  Google Scholar 

  17. G.A. Rinard, R.W. Quine, L.A. Buchanan et al., Resonators for in vivo imaging: practical experience. Appl. Magn. Reson. 48, 1227–1247 (2017)

    Article  Google Scholar 

  18. S. Emid, J.H.N. Creyghton, High-resolution NMR imaging in solids. Physica 128B, 81–83 (1985)

    Google Scholar 

  19. G.G. Maresch, M. Mehring, S. Emid, High resolution ESR imaging. Physica 138B, 261–263 (1986)

    Google Scholar 

  20. M. Lustig, D. Donoho, J.M. Pauly, Sparse MRI: the application of compressed sensing for rapid MR imaging. Magn. Reson. Med. 58, 1182–1195 (2007)

    Article  Google Scholar 

  21. B. Epel, M.K. Bowman, C. Mailer, H.J. Halpern, Absolute oxygen R1e imaging in vivo with pulse electron paramagnetic resonance. Magn. Reson. Med. 72, 362–368 (2014)

    Article  Google Scholar 

  22. P.L. Pedersen, Warburg, me and hexokinase 2: multiple discoveries of key molecular events underlying one of cancers’ most common phenotypes, the “warburg effect", i.e., elevated glycolysis in the presence of oxygen. J. Bioenerg. Biomembr. 39(3), 211–222 (2007)

    Article  Google Scholar 

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Acknowledgements

This research was supported by the Intramural Research Program of the National Institute of Health at the Center for Cancer Research, where the work described herein was carried out over a period of 15 years. Several visiting Fellows and post-doctoral fellows were involved too numerous to thank individually and we thank all of them. The instrumentation help throughout the course of development from Mr. Nallathambi Devasahayam is gratefully acknowledged.

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Correspondence to Sankaran Subramanian.

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Krishna, M.C., Subramanian, S. The Development of Time-Domain In Vivo EPR Imaging at NCI. Appl Magn Reson 52, 1291–1309 (2021). https://doi.org/10.1007/s00723-021-01369-4

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