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Maps of in vivo oxygen pressure with submillimetre resolution and nanomolar sensitivity enabled by Cherenkov-excited luminescence scanned imaging

Nature Biomedical Engineeringvolume 2pages254264 (2018) | Download Citation

Abstract

Low signal-to-noise ratios and limited imaging depths restrict the ability of optical-imaging modalities to detect and accurately quantify molecular emissions from tissue. Here, by using a scanning external X-ray beam from a clinical linear accelerator to induce Cherenkov excitation of luminescence in tissue, we demonstrate in vivo mapping of the oxygenation of tumours at depths of several millimetres, with submillimetre resolution and nanomolar sensitivity. This was achieved by scanning thin sheets of the X-ray beam orthogonally to the emission-detection plane, and by detecting the signal via a time-gated CCD camera synchronized to the radiation pulse. We also show with experiments using phantoms and with simulations that the performance of Cherenkov-excited luminescence scanned imaging (CELSI) is limited by beam size, scan geometry, probe concentration, radiation dose and tissue depth. CELSI might provide the highest sensitivity and resolution in the optical imaging of molecular tracers in vivo.

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Acknowledgements

This work has been funded by the Congressionally Directed Medical Research Program for Breast Cancer Research Program, US Army USAMRAA contract W81XWH-16-1-0004 and National Institutes of Health research grants R01 EB024498 and R01 EB018464.

Author information

Affiliations

  1. Thayer School of Engineering, Dartmouth College, Hanover, NH, USA

    • Brian W. Pogue
    • , Ethan P. LaRochelle
    • , Petr Bruža
    • , Rongxiao Zhang
    • , Jennifer R. Shell
    • , Scott C. Davis
    •  & David J. Gladstone
  2. Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

    • Brian W. Pogue
    • , Scott C. Davis
    • , David J. Gladstone
    •  & Lesley A. Jarvis
  3. Faculty of Information Technology, Beijing University of Technology, Beijing, China

    • Jinchao Feng
  4. Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou, China

    • Huiyun Lin
  5. School of Computer Science, University of Birmingham, Birmingham, UK

    • Hamid Dehghani
  6. Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    • Sergei A. Vinogradov
  7. Department of Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA

    • David J. Gladstone
    •  & Lesley A. Jarvis

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Contributions

B.W.P. conceived the study, supervised all aspects of the work and drafted the manuscript; J.F., H.L., P.B., E.P.L., R.Z. and J.R.S. each completed measurements and data analysis as well as designed the experiments, wrote initial parts of the manuscript, and edited the entire manuscript. H.D. and S.C.D. helped design and analyse the tomography work with J.F., and each edited the manuscript. S.A.V. provided the molecular probe, provided advice on experimental design and data analysis and edited the manuscript. D.J.G. and L.A.J. each contributed advice on radiotherapy design and data interpretation, as well as edited the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Brian W. Pogue.

Supplementary information

  1. Supplementary Information

    Supplementary discussion, methods, figures, tables and video captions.

  2. Reporting Summary

  3. Supplementary Video 1

    Three-dimensional view of a xenograft tumour imaged by CELSI.

  4. Supplementary Video 2

    Real-time scanned acquisition of CELSI data in vivo.

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DOI

https://doi.org/10.1038/s41551-018-0220-3

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