Skip to main content
SpringerLink
Log in

Evaluation of Fast Scan EPR for High-Resolution Imaging Using Nitroxide Radical Probes at 1.2 GHz

  • Original Paper
  • Published:
Applied Magnetic Resonance Aims and scope Submit manuscript

Abstract

Nitroxide probes have been commonly used for biomedical EPR imaging applications; however, image quality has been limited by the number of image projections, as well as the probe linewidth and hyperfine structure. In the current study, we evaluate the use of fast millisecond scan EPR projection acquisition along with a novel reconstruction algorithm optimized for 3D spatial EPR image reconstruction from a high number of noisy projections. This reconstruction method utilizes the raw image projection data and zero gradient spectrum to account for EPR line shape and hyperfine structure of any given paramagnetic probe without the need for deconvolution that is poorly suited for high noise data. Using fast scan EPR imaging with this reconstruction method, we image non-deuterated, deuterated and 15N substituted nitroxide probes in experimental phantoms of complex geometries. We evaluate the image resolution that can be obtained and the imaging time required. With 16,384 projections acquired over 1 min, and a field gradient of 8 G/cm, with a 2503 voxel 3D matrix, spatial resolutions of up to 100 µm are theoretically possible for a cubical volume of 25 × 25 × 25 mm3. In experiments with a variety of phantoms with mM nitroxide radical probes, resolutions of 600–250 µm were obtained with 1–10 min acquisitions, respectively. The presently obtainable signal sensitivity and noise levels of these acquisitions limited the obtainable resolution. With longer time acquisitions or further improvements in sensitivity and noise reduction, image resolutions approaching 100 µm should be possible.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Availability of Data and Materials

Imaging data are available from the corresponding author upon request.

Code Availability

The reconstruction algorithm with an example of its application is available for download at https://gitlab.com/dkomarov/art3dx/ under the terms of the General Public License.

References

  1. Z. Chen, L.A. Reyes, D.H. Johnson, M. Velayutham, C. Yang, A. Samouilov, J.L. Zweier, Fast gated EPR imaging of the beating heart: spatiotemporally resolved 3D imaging of free-radical distribution during the cardiac cycle. Magn. Reson. Med. 69, 594–601 (2013)

    Google Scholar 

  2. A. Samouilov, R. Ahmad, J. Boslett, X. Liu, S. Petryakov, J.L. Zweier, Development of a fast-scan EPR imaging system for highly accelerated free radical imaging. Magn. Reson. Med. 82, 842–853 (2019)

    Google Scholar 

  3. H. Sato-Akaba, H. Fujii, H. Hirata, Improvement of temporal resolution for three-dimensional continuous-wave electron paramagnetic resonance imaging. Rev. Sci Instrum. 79, 123701 (2008)

    ADS  Google Scholar 

  4. U. Ewert, K.-U. Thiessenhusen, Deconvolution for the stationary-gradient method, in: EPR imaging and in vivo EPR, CRC Press, 2018, pp. 119–126

  5. F. Momo, S. Colacicchi, A. Sotgiu, Limits of deconvolution in enhancing the resolution in EPR imaging experiments. Meas. Sci. Technol. 4, 60 (1993)

    ADS  Google Scholar 

  6. P. Kuppusamy, J.L. Zweier, Hyperfine artifacts in electron paramagnetic resonance imaging. Res. Chem. Intermed. 22, 593–604 (1996)

    Google Scholar 

  7. P. Kuppusamy, J.L. Zweier, A forward-subtraction procedure for removing hyperfine artifacts in electron paramagnetic resonance imaging. Magn. Reson. Med. 35, 316–322 (1996)

    Google Scholar 

  8. A. Sotgiu, D. Gazzillo, F. Momo, ESR imaging: spatial deconvolution in the presence of an asymmetric hyperfine structure. J. Phys. C: Solid State Phys. 20, 6297 (1987)

    ADS  Google Scholar 

  9. Y. Deng, G. He, P. Kuppusamy, J.L. Zweier, Deconvolution algorithm based on automatic cutoff frequency selection for EPR imaging, Magnetic Resonance in Medicine: an Official Journal of the International Society for. Magn. Reson. Med. 50, 444–448 (2003)

    Google Scholar 

  10. H. Hirata, T. Itoh, K. Hosokawa, Y. Deng, H. Susaki, Systematic approach to cutoff frequency selection in continuous-wave electron paramagnetic resonance imaging. J. Magn. Reson. 175, 177–184 (2005)

    ADS  Google Scholar 

  11. R. Ahmad, B. Clymer, D.S. Vikram, Y. Deng, H. Hirata, J.L. Zweier, P. Kuppusamy, Enhanced resolution for EPR imaging by two-step deblurring. J. Magn. Reson. 184, 246–257 (2007)

    ADS  Google Scholar 

  12. Y. Ikebata, H. Sato-Akaba, T. Aoyama, H. Fujii, K. Itoh, H. Hirata, Resolution-recovery for EPR imaging of free radical molecules in mice, Magnetic Resonance in Medicine: an Official Journal of the International Society for. Magn. Reson. Med. 62, 788–795 (2009)

    Google Scholar 

  13. T. Yokoyama, A. Taguchi, H. Kubota, N.J. Stewart, S. Matsumoto, I.A. Kirilyuk, H. Hirata, Simultaneous T2* mapping of 14N-and 15N-labeled dicarboxy-PROXYLs using CW-EPR-based single-point imaging. J. Magn. Reson. 305, 122–130 (2019)

    ADS  Google Scholar 

  14. D.A. Komarov, A. Samouilov, R. Ahmad, J.L. Zweier, Algebraic reconstruction of 3D spatial EPR images from high numbers of noisy projections: An improved image reconstruction technique for high resolution fast scan EPR imaging. J. Magn. Reson. 319, 106812 (2020)

    Google Scholar 

  15. D.A. Komarov, H. Hirata, Fast backprojection-based reconstruction of spectral-spatial EPR images from projections with the constant sweep of a magnetic field. J. Magn. Reson. 281, 44–50 (2017)

    ADS  Google Scholar 

  16. M. Frigo, S.G. Johnson, The design and implementation of FFTW3. Proc. IEEE 93, 216–231 (2005)

    Google Scholar 

  17. A. Samouilov, D. Komarov, S. Petryakov, A. Iosilevich, J.L. Zweier, Development of an L-band resonator optimized for fast scan EPR imaging of the mouse head. Magn. Reson. Med. (2021). https://doi.org/10.1002/mrm.28821

    Article  Google Scholar 

  18. D.A. Komarov, A. Samouilov, H. Hirata, J.L. Zweier, High fidelity triangular sweep of the magnetic field for millisecond scan EPR imaging. J. Magn. Reson. (2021). https://doi.org/10.1016/j.jmr.2021.107024

    Article  Google Scholar 

  19. R.W. Chan, E.A. Ramsay, C.H. Cunningham, D.B. Plewes, Temporal stability of adaptive 3D radial MRI using multidimensional golden means, Magnetic Resonance in Medicine: an Official Journal of the International Society for. Magn. Reson. Med. 61, 354–363 (2009)

    Google Scholar 

  20. K.-H. Ahn, H.J. Halpern, Spatially uniform sampling in 4-D EPR spectral-spatial imaging. J. Magn. Reson. 185, 152–158 (2007)

    ADS  Google Scholar 

  21. P. Kuppusamy, P.H. Wang, J.L. Zweier, Evaluation of nitroxides for the study of myocardial metabolism and oxygenation. Magn. Reson. Chem. 33, S123–S128 (1995)

    Google Scholar 

  22. H.M. Swartz, M. Sentjurc, P.D. Morse, Cellular-metabolism of water-soluble nitroxides—effect on rate of reduction of cell nitroxide ratio, oxygen concentrations and permeability of nitroxides. Biochim. Biophys. Acta. 888, 82–90 (1986)

    Google Scholar 

  23. M.C. Emoto, H. Sato-Akaba, H. Hirata, H.G. Fujii, Dynamic changes in the distribution and time course of blood–brain barrier-permeative nitroxides in the mouse head with EPR imaging: visualization of blood flow in a mouse model of ischemia. Free. Radical. Biol. Med. 74, 222–228 (2014)

    Google Scholar 

  24. P. Kuppusamy, M. Chzhan, K. Vij, M. Shteynbuk, D.J. Lefer, E. Giannella, J.L. Zweier, Three-dimensional spectral-spatial EPR imaging of free radicals in the heart: a technique for imaging tissue metabolism and oxygenation. Proc. Natl. Acad. Sci. 91, 3388–3392 (1994)

    ADS  Google Scholar 

  25. P. Kuppusamy, M. Chzhan, J.L. Zweier, Development and optimization of 3-dimensional spatial EPR imaging for biological organs and tissues. J. Magn. Reson. Ser. B. 106, 122–130 (1995)

    Google Scholar 

  26. P. Kuppusamy, P. Wang, J.L. Zweier, Three-dimensional spatial EPR imaging of the rat heart. Magn. Reson. Med. 34, 99–105 (1995)

    Google Scholar 

  27. P. Kuppusamy, M. Chzhan, P.H. Wang, J.L. Zweier, Three-dimensional gated EPR imaging of the beating heart: time-resolved measurements of free radical distribution during the cardiac contractile cycle. Magn. Reson. Med. 35, 323–328 (1996)

    Google Scholar 

  28. G.L. He, A. Samouilov, P. Kuppusamy, J.L. Zweier, In vivo EPR imaging of the distribution and metabolism of nitroxide radicals in human skin. J. Magn. Reson. 148, 155–164 (2001)

    ADS  Google Scholar 

  29. G.L. He, Y.M. Deng, H.H. Li, P. Kuppusamy, J.L. Zweier, EPR/NMR co-imaging for anatomic registration of free-radical images. Magn. Reson. Med. 47, 571–578 (2002)

    Google Scholar 

  30. D.A. Komarov, Y. Ichikawa, K. Yamamoto, N.J. Stewart, S. Matsumoto, H. Yasui, I.A. Kirilyuk, V.V. Khramtsov, O. Inanami, H. Hirata, In vivo extracellular pH mapping of tumors using electron paramagnetic resonance. Anal. Chem. 90, 13938–13945 (2018)

    Google Scholar 

  31. N. Kocherginsky, H.M. Swartz, Nitroxide Spin Labels. Reactions in Biology and Chemistry, in, CRC Press, Boca Raton, LA, 1995

  32. M.C. Emoto, K. Sasaki, K. Maeda, H.G. Fujii, S. Sato, Synthesis and evaluation as a blood-brain barrier-permeable probe of 7-N-(PROXYL-3-yl-methyl)theophylline. Chem. Pharm. Bull. 66, 887–891 (2018)

    Google Scholar 

  33. M.C. Emoto, M. Yamato, H. Sato-Akaba, K. Yamada, Y. Matsuoka, H.G. Fujii, Brain imaging in methamphetamine-treated mice using a nitroxide contrast agent for EPR imaging of the redox status and a gadolinium contrast agent for MRI observation of blood-brain barrier function. Free. Radic. Res. 49, 1038–1047 (2015)

    Google Scholar 

  34. H.G. Fujii, M.C. Emoto, H. Sato-Akaba, Brain redox imaging using in vivo electron paramagnetic resonance imaging and nitroxide imaging probes. Magnetochemistry 5, 11 (2019)

    Google Scholar 

  35. K.I. Matsumoto, J.B. Mitchell, M.C. Krishna, Comparative studies with EPR and MRI on the in vivo tissue redox status estimation using redox-sensitive nitroxyl probes: influence of the choice of the region of interest. Free Radic. Res. 52, 248–255 (2018)

    Google Scholar 

  36. M.J. Hoch, U. Ewert, Resolution in EPR imaging, in: EPR imaging and in vivo EPR, CRC Press, 2018, pp. 153–160

  37. R. Ahmad, A. Samouilov, J.L. Zweier, Accelerated dynamic EPR imaging using fast acquisition and compressive recovery. J. Magn. Reson. 273, 105–112 (2016)

    ADS  Google Scholar 

  38. S. Durand, Y.-M. Frapart, M. Kerebel, Electron paramagnetic resonance image reconstruction with total variation and curvelets regularization. Inverse Probl. 33, 114002 (2017)

    ADS  MathSciNet  MATH  Google Scholar 

  39. D.H. Johnson, R. Ahmad, G. He, A. Samouilov, J.L. Zweier, Compressed sensing of spatial electron paramagnetic resonance imaging. Magn. Reson. Med. 72, 893–901 (2014)

    Google Scholar 

  40. Z. Qiao, D. Liang, S. Tang, H. Halpern, Optimization-based image reconstruction from fast-scanned, noisy projections in EPR imaging. IEEE Access 7, 19590–19601 (2019)

    Google Scholar 

  41. Z. Qiao, G. Redler, B. Epel, Y. Qian, H. Halpern, 3D pulse EPR imaging from sparse-view projections via constrained, total variation minimization. J. Magn. Reson. 258, 49–57 (2015)

    ADS  Google Scholar 

  42. H. Kubota, D.A. Komarov, H. Yasui, S. Matsumoto, O. Inanami, I.A. Kirilyuk, V.V. Khramtsov, H. Hirata, Feasibility of in vivo three-dimensional T 2* mapping using dicarboxy-PROXYL and CW-EPR-based single-point imaging. Magn. Reson. Mater. Phys., Biol. Med. 30, 291–298 (2017)

    Google Scholar 

  43. O. Tseytlin, P. Guggilapu, A.A. Bobko, H. AlAhmad, X. Xu, B. Epel, R. O’Connell, E.H. Hoblitzell, T.D. Eubank, V.V. Khramtsov, Modular imaging system: Rapid scan EPR at 800 MHz. J. Magn. Reson. 305, 94–103 (2019)

    ADS  Google Scholar 

  44. H. Sato-Akaba, M.C. Emoto, H. Hirata, H.G. Fujii, Design and testing of a 750MHz CW-EPR digital console for small animal imaging. J. Magn. Reson. 284, 48–58 (2017)

    ADS  Google Scholar 

  45. M. Tseitlin, R.W. Quine, G.A. Rinard, S.S. Eaton, G.R. Eaton, Digital EPR with an arbitrary waveform generator and direct detection at the carrier frequency. J. Magn. Reson. 213, 119–125 (2011)

    ADS  Google Scholar 

  46. M. Gonet, M. Baranowski, T. Czechowski, M. Kucinska, A. Plewinski, P. Szczepanik, S. Jurga, M. Murias, Multiharmonic electron paramagnetic resonance imaging as an innovative approach for in vivo studies. Free Radic. Biol. Med. 152, 271–279 (2020)

    Google Scholar 

  47. M. Tseitlin, S.S. Eaton, G.R. Eaton, Reconstruction of the first-derivative EPR spectrum from multiple harmonics of the field-modulated continuous wave signal. J. Magn. Reson. 209, 277–281 (2011)

    ADS  Google Scholar 

  48. J.W. Stoner, D. Szymanski, S.S. Eaton, R.W. Quine, G.A. Rinard, G.R. Eaton, Direct-detected rapid-scan EPR at 250 MHz. J. Magn. Reson. 170, 127–135 (2004)

    ADS  Google Scholar 

Download references

Acknowledgements

Authors are grateful to Dr. Kirilyuk (Novosibirsk Institute of Organic Chemistry, Novosibirsk, Russia) for providing the dMCP radical.

Funding

This work was supported by NIH grants HL135648, HL131941, and EB016096.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Division of Cardiovascular Medicine, and the EPR Center, Davis Heart & Lung Research Institute, College of Medicine, The Ohio State University, 420 West 12th Ave, Columbus, OH, 43210, USA

    Jay L. Zweier, Alexandre Samouilov & Denis A. Komarov

Authors
  1. Jay L. Zweier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexandre Samouilov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Denis A. Komarov
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.S. performed experiments, analyzed data, composed and edited manuscript; D.K. performed experiments, analyzed data, composed and edited manuscript; J.L.Z. wrote manuscript and obtained funding for the work.

Corresponding author

Correspondence to Jay L. Zweier.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest/competing interests.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent of publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zweier, J.L., Samouilov, A. & Komarov, D.A. Evaluation of Fast Scan EPR for High-Resolution Imaging Using Nitroxide Radical Probes at 1.2 GHz. Appl Magn Reson 53, 233–246 (2022). https://doi.org/10.1007/s00723-021-01443-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00723-021-01443-x

Search

Navigation