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Ultrafast timing enables reconstruction-free positron emission imaging

Abstract

X-ray and gamma-ray photons are widely used for imaging but require a mathematical reconstruction step, known as tomography, to produce cross-sectional images from the measured data. Theoretically, the back-to-back annihilation photons produced by positron–electron annihilation can be directly localized in three-dimensional space using time-of-flight information without tomographic reconstruction; however, this has not yet been demonstrated due to the insufficient timing performance of available radiation detectors. Here we develop techniques based on detecting prompt Cherenkov photons, which, when combined with a convolutional neural network for timing estimation, resulted in an average timing precision of 32 ps, corresponding to a spatial precision of 4.8 mm. We show this is sufficient to produce cross-sectional images of a positron-emitting radionuclide directly from the detected coincident annihilation photons, without using any tomographic reconstruction algorithm. The reconstruction-free imaging demonstrated here directly localizes positron emission and frees the design of an imaging system from the geometric and sampling constraints that are normally present for tomographic reconstruction.

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Fig. 1: Basis for direct imaging of positron-emitting radiotracers using ultrafast timing.
Fig. 2: Timing resolution of 32 ps measured with MCP-PMT radiation detectors.
Fig. 3: Acquiring a cross-sectional image using a pair of CRI-MCP-PMT detectors.
Fig. 4: Cross-sectional images for different scale objects directly measured from a single angular view and without image reconstruction.

Data and code availability

The data and code used to produce the results presented in this study are available online at ref. 28.

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Acknowledgements

We thank H. Ohba, S. Nishiyama and M. Kanazawa at Hamamatsu Photonics for their technical support, and G. Burkett and S. Lucero at the University of California Davis for fabricating the spatial resolution phantom and three-dimensionally printed holders used in this study. This study was supported by National Institutes of Health grants R35 CA197608 and R03 EB027268.

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Contributions

This study was conceived of by S.R.C, R.O., S.I.K., E.B., F.H., T.O. and T.H. The methodology was designed by all authors. R.O. and T.O. provided specific resources. Experiments were conducted by S.I.K., R.O., E.B. and F.H. Data analysis was conducted by S.I.K., R.O. and E.B., with supervision by S.R.C., T.O. and T.H. The original draft of the manuscript was written by S.R.C., S.I.K., R.O. and E.B., and reviewed and edited by all authors.

Corresponding author

Correspondence to Simon R. Cherry.

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The authors declare no competing interests.

Additional information

Peer review information Nature Photonics thanks Paul Lecoq, Stefaan Vandenberghe and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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

Extended data

Extended Data Fig. 1 Accuracy of source localization based on measured timing difference.

Location of a radioactive point source as determined by the timing difference tAtB (equation 1) versus the known location of the source, across a distance of 10 cm, using the data in Fig. 2c. Error bar represents ± (FWHM of the distribution at each location ÷ 2). The source location is accurately determined over the entire range.

Extended Data Fig. 2 Effect of number of detected events on dPEI images.

dPEI images of the 2-D Hoffman brain phantom generated using a different number of events: a, ~10,000 events, b, ~20,000 events, c, ~30,000 events, and d, ~40,000 events. Each acquisition was performed over 44 different x-positions (4-mm intervals) and each scan took a total of 6 hours and used ~850 MBq (~23 mCi) of 18F-FDG activity. All images were post-processed (analytical attenuation correction, Gaussian smoothing (𝜎=0.8), and 4-fold up-sampling) as shown in Extended Data Fig. 6. This image demonstrates the relatively modest number of detected events needed to form an image of a slice representing the human brain, with little improvement above 20,000 events.

Supplementary information

Supplementary Information

Supplementary Figs. 1–4, and Tables 1 and 2.

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Kwon, S.I., Ota, R., Berg, E. et al. Ultrafast timing enables reconstruction-free positron emission imaging. Nat. Photon. 15, 914–918 (2021). https://doi.org/10.1038/s41566-021-00871-2

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