Skip to main content
SpringerLink
Log in

Expanding EPR Oximetry into Transfusion Medicine

  • Review
  • Published:
Applied Magnetic Resonance Aims and scope Submit manuscript

Abstract

Factors that impact the need for and the effectiveness of blood transfusions depend on the recipient’s physiologic tolerance to acute anemia and the quality of the donor units that they receive. To date, indirect methods are used to determine the needs for blood transfusions and their efficacy in both clinical research and patient care settings. Methods that provide clear information on oxygen levels in tissues would fill both critical gaps in the global understanding of blood transfusion. However, only a limited number of techniques are truly useful to achieve the goals of assessing the direct measurement of tissue oxygen partial pressures (pO2). This is because most methods do not directly measure tissue oxygen but instead are based on surrogates presumed to adequately define oxygenation of critical organs. This does not mean that indirect substitutes for tissue pO2 have been valueless. Nonetheless, direct measurements are needed to understand oxygenation at the tissue level. This synopsis describes the potential role of electron paramagnetic resonance (EPR) oximetry to provide guidance in transfusion medicine, pointing out the current benefits and limitations of using this technique. Further, we suggest approaches toward evolving this technique to optimize measurements of oxygenation in proof-of-concept and clinical transfusion assessment settings.

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

Similar content being viewed by others

Notes

  1. A predicate product is a medical product that may be legally marketed in the U.S. and used as a point of comparison for new medical products seeking FDA approval.

References

  1. R. Sender, S. Fuchs, R. Milo, Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 14(8), e1002533 (2016)

    Article  Google Scholar 

  2. J.G. Vostal, P.W. Buehler, M.P. Gelderman et al., Proceedings of the food and drug administration’s public workshop on new red blood cell product regulatory science 2016. Transfusion 58(1), 255–266 (2018)

    Article  Google Scholar 

  3. M.I. Ochocinskaa, S.L. Spitalnik, A. Abuhamad et al., NIH Workshop 2018: towards minimally invasive or noninvasive approaches to assess tissue oxygenation pre- and post-transfusion. Transfus. Med. Rev. 20(6), S0887-7963 (2020)

    Google Scholar 

  4. L.J. Dumont, J.P. AuBuchon, Evaluation of proposed FDA criteria for the evaluation of radiolabeled red cell recovery trials. Transfusion 48(6), 1053–1060 (2008)

    Article  Google Scholar 

  5. R.O. Francis, S. Mahajan, F. Rapido et al., Re-examination of chromium-51 labeled posttransfusion red blood cell recovery method. Transfusion 59(7), 2264–2275 (2019)

    Article  Google Scholar 

  6. C. Roussel, P.A. Buffet, P. Amireault, Measuring post-transfusion recovery and survival of red blood cells: strengths and weaknesses of chromium-51 labeling and alternative methods. Front. Med. 15(5), 1–8 (2018)

    Google Scholar 

  7. J.L. Carson, S.J. Stanworth, N. Roubinian et al., Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database Syst. Rev. 16(10), 1–115 (2016)

    Google Scholar 

  8. J.L. Carson, S.J. Stanworth, J.H. Alexander et al., Clinical trials evaluating red blood cell transfusion thresholds: an updated systematic review and with additional focus on patients with cardiovascular disease. Am. Heart J. 200, 96–101 (2018)

    Article  Google Scholar 

  9. K.M. Trentino, S.L. Farmer, M.F. Leahy et al., Systematic reviews and meta-analyses comparing mortality in restrictive and liberal haemoglobin thresholds for red cell transfusion: an overview of systematic reviews. BMC Med. 18(1), 154 (2020)

    Article  Google Scholar 

  10. J.D. Roback, Perspectives on the impact of storage duration on blood quality and transfusion outcomes. Vox Sang. 111(4), 357–364 (2016)

    Article  Google Scholar 

  11. T. Yoshida, M. Prudent, A. D’Alessandro, Red blood cell storage lesion: causes and potential consequences. Blood Transfus. 17(1), 27–52 (2019)

    Google Scholar 

  12. H. Hou, J.H. Baek, H. Zhang et al., Electron paramagnetic resonance oximetry as a novel approach to measure the effectiveness and quality of red blood cell transfusions. Blood Transfus. 17(4), 296–306 (2019)

    Google Scholar 

  13. G.H.W. Lim, M. Wortis, R. Mukhopadhyay, Stomatocyte-discocyte-echinocyte sequence of the human red blood cell: evidence for the bilayer- couple hypothesis from membrane mechanics. Proc. Natl. Acad. Sci. 99(26), 16766–16769 (2002)

    Article  ADS  Google Scholar 

  14. R.M. Caston, W. Schreiber, H. Hou et al., Development of the implantable resonator system for clinical EPR oximetry. Cell Biochem. Biophys. 75(3–4), 275–283 (2017)

    Article  Google Scholar 

  15. N. Khan, H. Hou, H.M. Swartz et al., Direct and repeated measurement of heart and brain oxygenation using in vivo EPR oximetry. Methods Enzymol. 564, 529–552 (2015)

    Article  Google Scholar 

  16. J. Jiang, T. Nakashima, K.J. Liu et al., Measurement of PO2 in liver using EPR oximetry. J. Appl. Physiol. 80(2), 552–558 (1985)

    Article  Google Scholar 

  17. H. Hou, N. Khan, S. Gohain et al., Pre-clinical evaluation of OxyChip for long-term EPR oximetry. Biomed. Microdevices 20(2), 1–10 (2018)

    Article  Google Scholar 

  18. D. Tse, P. Kuppusamy, Biocompatibility of oxygen-sensing paramagnetic implants. Cell Biochem. Biophys. 77(3), 197–202 (2019)

    Article  Google Scholar 

  19. G. Meenakshisundaram, E. Eteshola, R.P. Pandian et al., Oxygen sensitivity and biocompatibility of an implantable paramagnetic probe for repeated measurements of tissue oxygenation. Biomed. Microdevices 11(4), 817–826 (2009)

    Article  Google Scholar 

  20. A.B. Flood, V.A. Wood, W. Schreiber, Guidance to transfer “bench-ready” medical technology into usual clinical practice: case study—sensors and spectrometer used in EPR oximetry. Adv. Exp. Med. Biol. 1072, 233–239 (2018)

    Article  Google Scholar 

  21. P.E. Schaner, J.R. Pettus, A.B. Flood et al., OxyChip implantation and subsequent electron paramagnetic resonance oximetry in human tumors is safe and feasible: first experience in 24 patients. Front. Oncol. 27(10), 572060 (2020)

    Article  Google Scholar 

  22. A.B. Flood, V.A. Wood, H.M. Swartz, Using India ink as a sensor for oximetry: evidence of its safety as a medical device. Adv. Exp. Med. Biol. 977, 297–312 (2017)

    Article  Google Scholar 

  23. N. Charlier, N. Beghein, B. Gallez, Development and evaluation of biocompatible inks for the local measurement of oxygen using in vivo EPR. NMR Biomed. 17(5), 303–310 (2004)

    Article  Google Scholar 

  24. H. Hou, R. Dong, H. Li et al., Dynamic changes in oxygenation of intracranial tumor and contralateral brain during tumor growth and carbogen breathing: a multisite EPR oximetry with implantable resonators. J. Magn. Reson. 214(1), 22–28 (2012)

    Article  ADS  Google Scholar 

  25. H. Hou, H. Li, R. Dong, S. Mupparaju et al., Cerebral oxygenation of the cortex and striatum following normobaric hyperoxia and mild hypoxia in rats by EPR oximetry using multi-probe implantable resonators. Adv. Exp. Med. Biol. 701, 61–67 (2011)

    Article  Google Scholar 

  26. H. Hou, N. Khan, J. Lariviere, Skeletal muscle and glioma oxygenation by carbogen inhalation in rats: a longitudinal study by EPR oximetry using single-probe implantable oxygen sensors. Adv. Exp. Med. Biol.. 812, 97–103 (2014)

    Article  Google Scholar 

  27. H. Li, H. Hou, A. Sucheta et al., Implantable resonators–a technique for repeated measurement of oxygen at multiple deep sites with in vivo EPR. Adv. Exp. Med. Biol. 662, 265–272 (2010)

    Article  Google Scholar 

Download references

Acknowledgements

The concepts presented herein are the result of extensive discussion, scientific knowledge exchange, and friendship between Drs. Harold M Swartz, Ann Barry Flood and Paul W Buehler. Dr. Buehler expresses his gratitude for the opportunity to have developed a greater understanding of EPR oximetry and its applications because of this scientific friendship and wishes Dr. Swartz many more years of scientific pursuit, success, and happiness!

Author information

Authors and Affiliations

  1. Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA

    Paul W. Buehler

  2. Center for Blood Oxygen Transport and Hemostasis, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA

    Paul W. Buehler

  3. Department of Radiology, Geisel School of Medicine at Dartmouth College, Hanover, NH, USA

    Ann Barry Flood & Harold M. Swartz

  4. Department of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

    Harold M. Swartz

Authors
  1. Paul W. Buehler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ann Barry Flood
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Harold M. Swartz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul W. Buehler.

Ethics declarations

Conflict of Interest

ABF and HMS are co-owners of Clin-EPR, LLC which manufactures EPR instruments for investigational use. PWB has no disclosures or conflicts of interest to disclose.

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

Buehler, P.W., Flood, A.B. & Swartz, H.M. Expanding EPR Oximetry into Transfusion Medicine. Appl Magn Reson 52, 1509–1519 (2021). https://doi.org/10.1007/s00723-021-01394-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00723-021-01394-3

Search

Navigation