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Evaluation of a Refined Implantable Resonator for Deep-Tissue EPR Oximetry in the Clinic

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Abstract

(1) Summarize revisions made to the implantable resonator (IR) design and results of testing to characterize biocompatibility; (2) Demonstrate safety of implantation and feasibility of deep tissue oxygenation measurement using electron paramagnetic resonance (EPR) oximetry. In vitro testing of the revised IR and in vivo implantation in rabbit brain and leg tissues. Revised IRs were fabricated with 1–4 OxyChips with a thin wire encapsulated with two biocompatible coatings. Biocompatibility and chemical characterization tests were performed. Rabbits were implanted with either an IR with 2 oxygen sensors or a biocompatible-control sample in both the brain and hind leg. The rabbits were implanted with IRs using a catheter-based, minimally invasive surgical procedure. EPR oximetry was performed for rabbits with IRs. Cohorts of rabbits were euthanized and tissues were obtained at 1 week, 3 months, and 9 months after implantation and examined for tissue reaction. Biocompatibility and toxicity testing of the revised IRs demonstrated no abnormal reactions. EPR oximetry from brain and leg tissues were successfully executed. Blood work and histopathological evaluations showed no significant difference between the IR and control groups. IRs were functional for up to 9 months after implantation and provided deep tissue oxygen measurements using EPR oximetry. Tissues surrounding the IRs showed no more tissue reaction than tissues surrounding the control samples. This pre-clinical study demonstrates that the IRs can be safely implanted in brain and leg tissues and that repeated, non-invasive, deep-tissue oxygen measurements can be obtained using in vivo EPR oximetry.

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Acknowledgements

The authors would like to acknowledge Robyn Mosher for her assistance during the execution of this study, including technical and lab managerial aspects. We also acknowledge Karen Moodie and Kirk Maurer for their veterinary expertise and Sassan Hodge for his histopathological evaluations.

Funding

This study was supported by NIH grants P01 CA190193 and EB004031.

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Authors and Affiliations

  1. Section of Otolaryngology, Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

    Eunice Y. Chen

  2. Geisel School of Medicine at Dartmouth, Hanover, NH, USA

    Eunice Y. Chen, Dan Tse, Huagang Hou, Wilson A. Schreiber, Philip E. Schaner, Maciej M. Kmiec, Kendra A. Hebert, Periannan Kuppusamy, Harold M. Swartz & Benjamin B. Williams

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

    Dan Tse, Huagang Hou, Wilson A. Schreiber, Maciej M. Kmiec, Kendra A. Hebert, Periannan Kuppusamy, Harold M. Swartz & Benjamin B. Williams

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

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

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Contributions

EYC, PK, HMS, and BBW contributed to the study conception and design. Material preparation, data collection and analysis were performed by all authors. All authors read and approved the final manuscript.

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Correspondence to Benjamin B. Williams.

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Conflict of interest

Harold Swartz is a co-owner of Clin-EPR, LLC which manufactures clinical and preclinical EPR spectrometers for investigational use only. No other authors have any conflicts of interest or competing interests to disclose.

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Chen, E.Y., Tse, D., Hou, H. et al. Evaluation of a Refined Implantable Resonator for Deep-Tissue EPR Oximetry in the Clinic. Appl Magn Reson 52, 1321–1342 (2021). https://doi.org/10.1007/s00723-021-01376-5

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