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In Vivo CW-EPR Spectrometer Systems for Dosimetry and Oximetry in Preclinical and Clinical Applications

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Abstract

EPR spectrometers (and various sub-systems) have been designed and constructed to facilitate in vivo measurements with human subjects for dosimetry and oximetry. Most applications are primarily focused on surface tissue measurements; however, oximetric measurements utilizing implantable devices are also discussed. Given various specifications and considerations across these two primary applications, several embodiments and configurations of the associated sub-systems to the spectrometer have been realized and implemented. These embodiments and configurations have been developed and tested with a focus on the end-use and the end-users. This includes acknowledgement of the challenges and needs for making measurements in unanesthetized human patients, the nature of the data that are most likely to be useful for clinical decision-making, and the person who will be making the actual measurements. Significant developments in spectrometer automation and features to ensure the quality of recorded data are featured.

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Acknowledgements

Piotr Leśniewski (deceased) and Tadeuz Walczak (deceased) were instrumental (literally and figuratively) in the concept, design, development, understanding, and overall success of the in vivo EPR developments described herein. For other contributors to this work, particularly the members of the EPR Center for the Study of Viable Systems at Dartmouth, see the Editorial in this issue.

Funding

United States Dept. of Defense: HR0011-08-C-0022 & -0023 (Defense Advanced Research Projects Agency- DARPA) United States Health and Human Services Biomedical Advanced Research and Development Authority (BARDA) HHSO100201100024C (BARDA). National Institutes of Health: U19 AI091173 (Dartmouth Physically Based Biodosimetry Center for Medical Countermeasures against Radiation (Dart-Dose CMCR) and Project at prior U19 CMCR at Rochester University) P01 CA190193, R21 CA121593, R21 DK072112, R21 CA118069, R01 CA120919, P41 EB002032 (Facilities of The EPR Center). Dartmouth College and Dartmouth-Hitchcock Medical Center, Hanover & Lebanon, NH Norris Cotton Cancer Center: ACS Institutional Research Grants and Prouty grants Dartmouth Center for Clinical and Translational Science (DCCTS) Dept. of Radiology; Dept. of Medicine: Section of Radiation Oncology Other: Clin-EPR, LLC, Lyme NH.

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Authors and Affiliations

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

    Wilson Schreiber, Sergey V. Petryakov, Maciej M. Kmiec, Ann Barry Flood, Harold M. Swartz & Benjamin B. Williams

  2. Department of Medicine, Section of Radiation Oncology, Dartmouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH, 03756, USA

    Harold M. Swartz, Philip E. Schaner & Benjamin B. Williams

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  1. Wilson Schreiber
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  2. Sergey V. Petryakov
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  3. Maciej M. Kmiec
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  4. Ann Barry Flood
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  5. Harold M. Swartz
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  6. Philip E. Schaner
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  7. Benjamin B. Williams
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Correspondence to Benjamin B. Williams.

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Conflict of Interests

Harold Swartz and Ann Flood are co-owners of Clin-EPR, LLC which manufactures clinical and preclinical EPR spectrometers for investigational use only. No other authors declare a conflict of interest.

Ethics Approval/Consent to Participate

Although no preclinical or clinical studies using this equipment are reported here, all studies using animals or human subjects had been approved by the appropriate Institutional Research Boards (IRB) or Institutional Animal Care and Use Committees (IACUC) where the studies were conducted. All human subjects gave written informed consent to participate. All IRBs where the EPR spectroscopy devices were used in studies determined that they were non-significant risk devices and therefore do not require an Institutional Device Exemption (IDE) from the Food and Drug Administration. Some implanted oxygen sensors were required to have an IDE prior to first use in humans.

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Schreiber, W., Petryakov, S.V., Kmiec, M.M. et al. In Vivo CW-EPR Spectrometer Systems for Dosimetry and Oximetry in Preclinical and Clinical Applications. Appl Magn Reson 53, 123–143 (2022). https://doi.org/10.1007/s00723-021-01382-7

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