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  • Review Article
  • Published:

Near-infrared luminescence high-contrast in vivo biomedical imaging

Abstract

Luminescence imaging in biomedical research has allowed new insights into the architecture of pathological tissues, signalling networks and cell interactions, and is now turning into a powerful tool for diagnostics and image-guided surgery. Luminescence in the near-infrared (NIR) window (700–1,700 nm), in particular, exhibits less interaction of scattering and absorption photons with biological tissues than imaging in the visible range, resulting in deeper optical penetration depth and reduced autofluorescence interference, and thus enabling higher imaging contrast. Despite promising preclinical results, few NIR fluorophores have been clinically approved so far. In this Review, we discuss important engineering challenges that need to be addressed to enable successful clinical translation of NIR luminescence imaging, including enhancement of imaging contrast by optimizing fluorescent probe design, reducing tissue autofluorescence and improving local accumulation of the luminescent probes in the body.

Key points

  • Luminescence imaging has revolutionized fundamental studies in life sciences, and its clinical application has allowed new insights into diagnostics and image-guided surgery.

  • Luminescence imaging with high contrast enables faster, safer, easier, more precise and less expensive clinical testing than positron emission tomography or computed tomography.

  • Luminescence in the near-infrared window benefits from minimal photon scattering/autofluorescence in biological tissues, enabling deep optical penetration and high imaging contrast.

  • The imaging contrast can be further improved by optimizing fluorophore performance (wavelength, brightness and Stokes shift), increasing fluorophore accumulation at target sites or reducing tissue background.

  • Although luminescence imaging shows great preclinical promise, its clinical application has been limited. A multidisciplinary effort for optimizing fluorophores, instruments, imaging and manufacturing standards is needed.

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Fig. 1: Biomedical imaging techniques.
Fig. 2: Light attenuation in biological tissues.
Fig. 3: Biological barriers for fluorophore transport.
Fig. 4: Fluorescent probe performance affects imaging contrast.
Fig. 5: High-contrast biomedical imaging with low background signal.
Fig. 6: Imaging specific tissues.

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Acknowledgements

F.Z. acknowledges support from the National Natural Science Foundation of China (NSFC, grant nos 22088101, 21725502, 51961145403). F.Z. acknowledges support by the Research Program of Science and Technology Commission of Shanghai Municipality (grant no. 20JC1411700, 21142201000, 22JC1400400).

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Y.C., S.W. and F.Z. contributed to the preparation of the synopsis. Y.C. and F.Z. wrote the paper and drew the figures. S.W. and F.Z. helped in refining the content of the paper. All authors contributed to the discussion, editing and reviewing of the synopsis and manuscript.

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Chen, Y., Wang, S. & Zhang, F. Near-infrared luminescence high-contrast in vivo biomedical imaging. Nat Rev Bioeng 1, 60–78 (2023). https://doi.org/10.1038/s44222-022-00002-8

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