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Compressive hyperspectral time-resolved wide-field fluorescence lifetime imaging

Nature Photonics volume 11, pages 411–414 (2017)Cite this article

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Abstract

Spectrally resolved fluorescence lifetime imaging1,2,3 and spatial multiplexing1,4,5 have offered information content and collection-efficiency boosts in microscopy, but efficient implementations for macroscopic applications are still lacking. An imaging platform based on time-resolved structured light and hyperspectral single-pixel detection has been developed to perform quantitative macroscopic fluorescence lifetime imaging (MFLI) over a large field of view (FOV) and multiple spectral bands simultaneously. The system makes use of three digital micromirror device (DMD)-based spatial light modulators (SLMs) to generate spatial optical bases and reconstruct N by N images over 16 spectral channels with a time-resolved capability (∼40 ps temporal resolution) using fewer than N2 optical measurements. We demonstrate the potential of this new imaging platform by quantitatively imaging near-infrared (NIR) Förster resonance energy transfer (FRET) both in vitro and in vivo. The technique is well suited for quantitative hyperspectral lifetime imaging with a high sensitivity and paves the way for many important biomedical applications.

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Figure 1: System diagram and typical hyperspectral TPSF example.
Figure 2: Results of in vitro study.
Figure 3: Results of the in vivo study.

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References

  1. Hanley, Q. S., Arndt-Jovin, D. J. & Jovin, T. M. Spectrally resolved fluorescence lifetime imaging microscopy. Appl. Spectrosc. 56, 155–166 (2002).

    Article  ADS  Google Scholar 

  2. Bird, D. K., Eliceiri, K. W., Fan, C.-H. & White, J. G. Simultaneous two-photon spectral and lifetime fluorescence microscopy. Appl. Opt. 43, 5173–5182 (2004).

    Article  ADS  Google Scholar 

  3. Zhao, M., Li, Y. & Peng, L. Parallel excitation-emission multiplexed fluorescence lifetime confocal microscopy for live cell imaging. Opt. Express 22, 10221–10232 (2014).

    Article  ADS  Google Scholar 

  4. Studer, V. et al. Compressive fluorescence microscopy for biological and hyperspectral imaging. Proc. Natl Acad. Sci. USA 109, E1679–E1687 (2012).

    Article  Google Scholar 

  5. Mizuno, T. & Iwata, T. Hadamard-transform fluorescence-lifetime imaging. Opt. Express 24, 8202–8213 (2016).

    Article  ADS  Google Scholar 

  6. Roblyer, D. et al. Multispectral optical imaging device for in vivo detection of oral neoplasia. J. Biomed. Opt. 13, 024019 (2008).

    Article  ADS  Google Scholar 

  7. Lu, G. & Fei, B. Medical hyperspectral imaging: a review. J. Biomed. Opt. 19, 010901 (2014).

    Article  ADS  Google Scholar 

  8. Panasyuk, S. V. et al. Medical hyperspectral imaging to facilitate residual tumor identification during surgery. Cancer Biol. Ther. 6, 439–446 (2007).

    Article  Google Scholar 

  9. Akbari, H., Kosugi, Y., Kojima, K. & Tanaka, N. Detection and analysis of the intestinal ischemia using visible and invisible hyperspectral imaging. IEEE Trans. Biomed. Eng. 57, 2011–2017 (2010).

    Article  Google Scholar 

  10. Marcu, L. Fluorescence lifetime techniques in medical applications. Ann. Biomed. Eng. 40, 304–331 (2012).

    Article  Google Scholar 

  11. Suhling, K. et al. Fluorescence lifetime imaging (FLIM): basic concepts and some recent developments. Med. Photon. 27, 3–40 (2015).

    Article  Google Scholar 

  12. Sun, B. et al. 3D computational imaging with single-pixel detectors. Science 340, 844–847 (2013).

    Article  ADS  Google Scholar 

  13. Pham, Q. D. & Hayasaki, Y. Optical frequency comb profilometry using a single-pixel camera composed of digital micromirror devices. Appl. Opt. 54, A39–A44 (2015).

    Article  ADS  Google Scholar 

  14. Yu, W.-K., Yao, X.-R., Liu, X.-F., Li, L.-Z. & Zhai, G.-J. Three-dimensional single-pixel compressive reflectivity imaging based on complementary modulation. Appl. Opt. 54, 363–367 (2015).

    Article  ADS  Google Scholar 

  15. Chan, W. L. et al. A single-pixel terahertz imaging system based on compressed sensing. Appl. Phys. Lett. 93, 121105 (2008).

    Article  ADS  Google Scholar 

  16. Withayachumnankul, W. & Abbott, D. Terahertz imaging: compressing onto a single pixel. Nat. Photon. 8, 593–594 (2014).

    Article  ADS  Google Scholar 

  17. Ma, J. Single-pixel remote sensing. IEEE Geosci. Remote Sens. Lett. 6, 199–203 (2009).

    Article  ADS  Google Scholar 

  18. Donoho, D. L. Compressed sensing. IEEE Trans. Inf. Theory 52, 1289–1306 (2006).

    Article  MathSciNet  Google Scholar 

  19. Duarte, M. F. et al. Single-pixel imaging via compressive sampling. IEEE Signal Process. Mag. 25, 83–91 (2008).

    Article  ADS  Google Scholar 

  20. Welsh, S. S. et al. Fast full-color computational imaging with single-pixel detectors. Opt. Express 21, 23068–23074 (2013).

    Article  ADS  Google Scholar 

  21. Greenberg, J., Krishnamurthy, K. & Brady, D. Compressive single-pixel snapshot X-ray diffraction imaging. Opt. Lett. 39, 111–114 (2014).

    Article  ADS  Google Scholar 

  22. Ma, G., Gallant, P. & McIntosh, L. Sensitivity characterization of a time-domain fluorescence imager: eXplore Optix. Appl. Opt. 46, 1650–1657 (2007).

    Article  ADS  Google Scholar 

  23. Zhao, L. et al. Spatial light modulator based active wide-field illumination for ex vivo and in vivo quantitative NIR FRET imaging. Biomed. Opt. Express 5, 944–960 (2014).

    Article  Google Scholar 

  24. Streeter, L., Burling-Claridge, G. R., Cree, M. J. & Künnemeyer, R. Optical full Hadamard matrix multiplexing and noise effects. Appl. Opt. 48, 2078–2085 (2009).

    Article  ADS  Google Scholar 

  25. Mäkitalo, M. & Foi, A. Optimal inversion of the Anscombe transformation in low-count Poisson image denoising. IEEE Trans. Image Process. 20, 99–109 (2011).

    Article  ADS  MathSciNet  Google Scholar 

  26. Abe, K., Zhao, L., Periasamy, A., Intes, X . & Barroso, M. Non-invasive in vivo imaging of near infrared-labeled transferrin in breast cancer cells and tumors using fluorescence lifetime FRET. PLoS ONE 8, e80269 (2013).

    Google Scholar 

  27. Qian, Z. M., Li, H., Sun, H. & Ho, K. Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacol. Rev. 54, 561–587 (2002).

    Article  Google Scholar 

  28. Pian, Q., Yao, R., Zhao, L. & Intes, X. Hyperspectral time-resolved wide-field fluorescence molecular tomography based on structured light and single-pixel detection. Opt. Lett. 40, 431–434 (2015).

    Article  ADS  Google Scholar 

  29. Wessels, J. T. et al. In vivo imaging in experimental preclinical tumor research—a review. Cytom. A 71A, 542–549 (2007).

    Google Scholar 

  30. Christian, N. A. et al. In vivo dendritic cell tracking using fluorescence lifetime imaging and near-infrared-emissive polymersomes. Mol. Imaging Biol. 11, 167–177 (2009).

    Google Scholar 

  31. Hall, D. J. et al. Dynamic optical imaging of metabolic and NADPH oxidase-derived superoxide in live mouse brain using fluorescence lifetime unmixing. J. Cereb. Blood Flow Metab. 32, 23–32 (2012).

    Article  Google Scholar 

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Acknowledgements

This work is supported by the National Science Foundation through Career Award CBET 1149407, and National Institute of Health Grants R01 EB19443 and R01 CA207725. The authors acknowledge the support from M. Barroso and A. Rudkouskaya for the sample preparation in animal studies, and the insightful discussions with W. Cong and G. Wang.

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Authors and Affiliations

  1. Biomedical Engineering Department, Rensselaer Polytechnic Institute, 110 8th Street, Troy, 12180, New York, USA

    Qi Pian, Ruoyang Yao, Nattawut Sinsuebphon & Xavier Intes

Authors
  1. Qi Pian
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  2. Ruoyang Yao
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  3. Nattawut Sinsuebphon
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  4. Xavier Intes
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Contributions

X.I. conceived the original idea. Q.P. contributed to the platform instrumentation, control software design and experimental validation. R.Y. contributed to the pattern implementation, initial simulations and image reconstruction. N.S. contributed to the animal study protocol and experiments. All the authors contributed to the analysis of the experimental results and to writing the manuscript.

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Correspondence to Xavier Intes.

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The authors declare no competing financial interests.

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Pian, Q., Yao, R., Sinsuebphon, N. et al. Compressive hyperspectral time-resolved wide-field fluorescence lifetime imaging. Nature Photon 11, 411–414 (2017). https://doi.org/10.1038/nphoton.2017.82

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