Abstract

Acquisition of high-resolution images from within internal organs using endoscopic optical imaging has numerous clinical applications. However, difficulties associated with optical aberrations and the trade-off between transverse resolution and depth of focus significantly limit the scope of applications. Here, we integrate a metalens, with the ability to modify the phase of incident light at subwavelength level, into the design of an endoscopic optical coherence tomography catheter (termed nano-optic endoscope) to achieve near diffraction-limited imaging through negating non-chromatic aberrations. Remarkably, the tailored chromatic dispersion of the metalens in the context of spectral interferometry is utilized to maintain high-resolution imaging beyond the input field Rayleigh range, easing the trade-off between transverse resolution and depth of focus. We demonstrate endoscopic imaging in resected human lung specimens and in sheep airways in vivo. The combination of the superior resolution and higher imaging depth of focus of the nano-optic endoscope is likely to increase the clinical utility of endoscopic optical imaging.

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References

  1. 1.

    Tearney, G. J. et al. Scanning single-mode fiber optic catheter-endoscope for optical coherence tomography: erratum. Opt. Lett. 21, 912 (1996).

  2. 2.

    Tearney, G. J. et al. In vivo endoscopic optical biopsy with optical coherence tomography. Science 276, 2037–2039 (1997).

  3. 3.

    Fujimoto, J. G. et al. High resolution in vivo intra-arterial imaging with optical coherence tomography. Heart 82, 128–133 (1999).

  4. 4.

    Yabushita, H. et al. Characterization of human atherosclerosis by optical coherence tomography. Circulation 106, 1640–1645 (2002).

  5. 5.

    Kume, T. et al. Assessment of coronary arterial thrombus by optical coherence tomography. Am. J. Cardiol. 97, 1713–1717 (2006).

  6. 6.

    Rollins, A. M. et al. Real-time in vivo imaging of human gastrointestinal ultrastructure by use of endoscopic optical coherence tomography with a novel efficient interferometer design. Opt. Lett. 24, 1358–1360 (1999).

  7. 7.

    Li, X. D. et al. Optical coherence tomography: advanced technology for the endoscopic imaging of Barrett’s esophagus. Endoscopy 32, 921–930 (2000).

  8. 8.

    Sergeev, A. et al. In vivo endoscopic OCT imaging of precancer and cancer states of human mucosa. Opt. Express 1, 432–440 (1997).

  9. 9.

    Lam, S. et al. In vivo optical coherence tomography imaging of preinvasive bronchial lesions. Clin. Cancer Res. 14, 2006–2011 (2008).

  10. 10.

    Youngquist, R. C., Carr, S. & Davies, D. E. Optical coherence-domain reflectometry: a new optical evaluation technique. Opt. Lett. 12, 158–160 (1987).

  11. 11.

    Huang, D. et al. Optical coherence tomography. Science 254, 1178–1181 (1991).

  12. 12.

    Fujimoto, J. G. et al. Femtosecond optical ranging in biological systems. Opt. Lett. 11, 150–152 (1986).

  13. 13.

    Fercher, A. F., Mengedoht, K. & Werner, W. Eye-length measurement by interferometry with partially coherent light. Opt. Lett. 13, 186–188 (1988).

  14. 14.

    Choma, M., Sarunic, M., Yang, C. & Izatt, J. Sensitivity advantage of swept source and Fourier domain optical coherence tomography. Opt. Express 11, 2183–2189 (2003).

  15. 15.

    de Boer, J. F. et al. Improved signal-to-noise ratio in spectral-domain compared with time-domain optical coherence tomography. Opt. Lett. 28, 2067–2069 (2003).

  16. 16.

    Leitgeb, R., Hitzenberger, C. & Fercher, A. Performance of fourier domain vs. time domain optical coherence tomography. Opt. Express 11, 889–894 (2003).

  17. 17.

    Wojtkowski, M., Bajraszewski, T., Targowski, P. & Kowalczyk, A. Real-time in vivo imaging by high-speed spectral optical coherence tomography. Opt. Lett. 28, 1745–1747 (2003).

  18. 18.

    Yun, S., Tearney, G., de Boer, J., Iftimia, N. & Bouma, B. High-speed optical frequency-domain imaging. Opt. Express 11, 2953–2963 (2003).

  19. 19.

    Liu, L. et al. Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography. Nat. Med. 17, 1010–1014 (2011).

  20. 20.

    Spoler, F. et al. Simultaneous dual-band ultra-high resolution optical coherence tomography. Opt. Express 15, 10832–10841 (2007).

  21. 21.

    Cimalla, P., Walther, J., Mehner, M., Cuevas, M. & Koch, E. Simultaneous dual-band optical coherence tomography in the spectral domain for high resolution in vivo imaging. Opt. Express 17, 19486–19500 (2009).

  22. 22.

    Shu, X., Beckmann, L. & Zhang, H. Visible-light optical coherence tomography: a review. J. Biomed. Opt. 22, 121707 (2017).

  23. 23.

    Kim, J. et al. Endoscopic micro-optical coherence tomography with extended depth of focus using a binary phase spatial filter. Opt. Lett. 42, 379–382 (2017).

  24. 24.

    Xi, J. et al. Diffractive catheter for ultrahigh-resolution spectral-domain volumetric OCT imaging. Opt. Lett. 39, 2016–2019 (2014).

  25. 25.

    Cui, D. et al. Flexible, high-resolution micro-optical coherence tomography endobronchial probe toward in vivo imaging of cilia. Opt. Lett. 42, 867–870 (2017).

  26. 26.

    Drexler, W. et al. In vivo ultrahigh-resolution optical coherence tomography. Opt. Lett. 24, 1221–1223 (1999).

  27. 27.

    Standish, B. A. et al. In vivo endoscopic multi-beam optical coherence tomography. Phys. Med. Biol. 55, 615–622 (2010).

  28. 28.

    Singh, K., Yamada, D. & Tearney, G. Astigmatism corrected common path probe for optical coherence tomography. Lasers Surg. Med. 49, 312–318 (2017).

  29. 29.

    Fang, Q. et al. Ultrahigh-resolution optical coherence elastography through a micro-endoscope: towards in vivo imaging of cellular-scale mechanics. Biomed. Opt. Express 8, 5127–5138 (2017).

  30. 30.

    Shishkov, M., Bouma, B. E. & Tearney, G. J. System and method for optical coherence imaging. US patent 20060067620A1 (2006).

  31. 31.

    Ohmi, S. et al. Gradient-index rod lens made by a double ion-exchange process. Appl. Opt. 27, 496–499 (1988).

  32. 32.

    Khorasaninejad, M. & Capasso, F. Metalenses: versatile multifunctional photonic components. Science 358, eaam8100 (2017).

  33. 33.

    Yu, N. et al. Light propagation with phase discontinuities: generalized laws of reflection and refraction. Science 334, 333–337 (2011).

  34. 34.

    Khorasaninejad, M. et al. Metalenses at visible wavelengths: diffraction-limited focusing and subwavelength resolution imaging. Science 352, 1190–1194 (2016).

  35. 35.

    Huang, Y. W. et al. Aluminum plasmonic multicolor meta-hologram. Nano Lett. 15, 3122–3127 (2015).

  36. 36.

    Balthasar Mueller, J. P., Rubin, N. A., Devlin, R. C., Groever, B. & Capasso, F. Metasurface polarization optics: independent phase control of arbitrary orthogonal states of polarization. Phys. Rev. Lett. 118, 113901 (2017).

  37. 37.

    Ralston, T. S., Marks, D. L., Carney, P. S. & Boppart, S. A. Interferometric synthetic aperture microscopy. Nat. Phys. 3, 129–134 (2007).

  38. 38.

    Khorasaninejad, M. & Crozier, K. B. Silicon nanofin grating as a miniature chirality-distinguishing beam-splitter. Nat. Commun. 5, 5386 (2014).

  39. 39.

    Khorasaninejad, M. & Capasso, F. Broadband multifunctional efficient meta-gratings based on dielectric waveguide phase shifters. Nano Lett. 15, 6709–6715 (2015).

  40. 40.

    Fercher, A. F., Hitzenberger, C. K., Kamp, G. & El-Zaiat, S. Y. Measurement of intraocular distances by backscattering spectral interferometry. Opt. Commun. 117, 43–48 (1995).

  41. 41.

    Ha Usler, G. & Lindner, M. W. “Coherence radar” and “spectral radar”-new tools for dermatological diagnosis. J. Biomed. Opt. 3, 21–31 (1998).

  42. 42.

    Khorasaninejad, M., Chen, W. T., Oh, J. & Capasso, F. Super-dispersive off-axis meta-lenses for compact high resolution spectroscopy. Nano Lett. 16, 3732–3737 (2016).

  43. 43.

    Khorasaninejad, M. et al. Achromatic metasurface lens at telecommunication wavelengths. Nano Lett. 15, 5358–5362 (2015).

  44. 44.

    Khorasaninejad, M. et al. Achromatic metalens over 60 nm bandwidth in the visible and metalens with reverse chromatic dispersion. Nano Lett. 17, 1819–1824 (2017).

  45. 45.

    Yun, S. H. et al. Comprehensive volumetric optical microscopy in vivo. Nat. Med. 12, 1429–1433 (2006).

  46. 46.

    Yun, S., Tearney, G., de Boer, J. & Bouma, B. Removing the depth-degeneracy in optical frequency domain imaging with frequency shifting. Opt. Express 12, 4822–4828 (2004).

  47. 47.

    Hariri, L. P. et al. Toward the guidance of transbronchial biopsy: identifying pulmonary nodules with optical coherence tomography. Chest 144, 1261–1268 (2013).

  48. 48.

    Hariri, L. P. et al. Seeing beyond the bronchoscope to increase the diagnostic yield of bronchoscopic biopsy. Am. J. Respir. Crit. Care Med. 187, 125–129 (2013).

  49. 49.

    Adams, D. C. et al. Birefringence microscopy platform for assessing airway smooth muscle structure and function in vivo. Sci. Transl. Med. 8, 359ra131 (2016).

  50. 50.

    Hariri, L. P. et al. Endobronchial optical coherence tomography for low-risk microscopic assessment and diagnosis of idiopathic pulmonary fibrosis in vivo. Am. J. Respir. Crit. Care Med. 197, 949–952 (2018).

  51. 51.

    Nadkarni, S. K. et al. Measurement of collagen and smooth muscle cell content in atherosclerotic plaques using polarization-sensitive optical coherence tomography. J. Am. Coll. Cardiol. 49, 1474–1481 (2007).

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Acknowledgements

This project was supported by funding from the National Institutes of Health (R01CA167827, R01HL133664 awarded to M.J.S.), Air Force Office of Scientific Research (MURI: FA9550-14-1-0389, FA9550-16-1-0156 awarded to F.C.), and the LUNGevity Foundation/Upstage Lung Cancer. Y.-W.H. and C.-W.Q. are supported by the National Research Foundation, Prime Minister’s Office, Singapore under its Competitive Research Program (CRP award no. NRF-CRP15-2015-03). This work was performed in part at Harvard’s Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Coordinated Infrastructure (NNCI), supported by the National Science Foundation (NSF) under NSF award no. 1541959. Y.-W.H. thanks Y.-C. Chen for helpful comments and discussions.

Author information

Author notes

  1. These authors contributed equally to this work: Hamid Pahlevaninezhad, Mohammadreza Khorasaninejad, Yao-Wei Huang.

Affiliations

  1. Department of Medicine, Pulmonary and Critical Care Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    • Hamid Pahlevaninezhad
    • , Lida P. Hariri
    • , David C. Adams
    •  & Melissa J. Suter
  2. Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA

    • Hamid Pahlevaninezhad
    • , Mohammadreza Khorasaninejad
    • , Yao-Wei Huang
    • , Vivien Ding
    • , Alexander Zhu
    •  & Federico Capasso
  3. Department of Electrical and Computer Engineering, National University of Singapore, Singapore, Singapore

    • Yao-Wei Huang
    •  & Cheng-Wei Qiu
  4. Department of Physics, Harvard University, Cambridge, MA, USA

    • Zhujun Shi
  5. University of Waterloo, Waterloo, Ontario, Canada

    • Vivien Ding

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Contributions

H.P., M.K. and Y.-W.H. carried out analyses, fabricated endoscopes, and planned and executed the experiments. Z.S. performed computational analysis for metalens design. L.P.H., M.J.S. and H.P. performed the ex vivo and in vivo imaging. M.J.S. and D.C.A. implemented the OCT system. H.P. and D.C.A. processed imaging data. V.D. and A.Z. assisted with experiments and fabrication. H.P. prepared the original manuscript with significant contributions from M.K., Y.-W.H. and C.-W.Q. M.J.S. and F.C. supervised the project and participated in manuscript preparation.

Competing interests

H.P., M.K., Y.-W.H., Z.S., M.J.S. and F.C. are the inventors on a relevant provisional patent application (application number: 62598455) owned by Harvard University and Massachusetts General Hospital.

Corresponding authors

Correspondence to Federico Capasso or Melissa J. Suter.

Supplementary Information

  1. Supplementary Information

    Additional information on the phase profile calculation for the metalens used, computational analysis of the nanopillars, endoscope wave analysis, analytic approach to spectral interferometry with a chromatic lens, endoscope characterization and the OCT imaging system implemented in the work

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DOI

https://doi.org/10.1038/s41566-018-0224-2