Optical coherence refraction tomography

Abstract

Optical coherence tomography (OCT) is a cross-sectional, micrometre-scale imaging modality with widespread clinical application. Typical OCT systems sacrifice lateral resolution to achieve long depths of focus for bulk tissue imaging, and therefore tend to have better axial than lateral resolution. Such anisotropic resolution can obscure fine ultrastructural features. Furthermore, conventional OCT suffers from refraction-induced image distortions. Here, we introduce optical coherence refraction tomography (OCRT), which extends the superior axial resolution to the lateral dimension, synthesizing undistorted cross-sectional image reconstructions from multiple conventional images acquired with angular diversity. In correcting refraction-induced distortions to register the OCT images, OCRT also achieves spatially resolved refractive index imaging. We demonstrate greater than threefold improvement in lateral resolution as well as speckle reduction in imaging the tissue ultrastructure, consistent with histology. With further optimization in optical designs to incorporate angular diversity into clinical instruments, OCRT could be widely applied as an enhancement over conventional OCT.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: OCRT, like CT, is a Fourier synthesis technique.
Fig. 2: Overview of the iterative OCRT reconstruction algorithm.
Fig. 3: Experimental validation of the isotropic resolution and RI estimates of OCRT.
Fig. 4: OCRT of mouse vas deferens and femoral artery.
Fig. 5: OCRT of mouse bladder and trachea.
Fig. 6: OCRT of human cornea and crane fly leg reveals additional RI information.

Data availability

The multi-angle datasets for the biological samples in Figs. 46 are available at https://doi.org/10.6084/m9.figshare.8297138.

Code availability

The Python code used for generating the OCRT results in Figs. 46 is available at https://github.com/kevinczhou/optical-coherence-refraction-tomography.

References

  1. 1.

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

    ADS  Article  Google Scholar 

  2. 2.

    Povazay, B. et al. Submicrometer axial resolution optical coherence tomography. Opt. Lett. 27, 1800–1802 (2002).

    ADS  Article  Google Scholar 

  3. 3.

    Izatt, J. A. & Choma, M. A. in Optical Coherence Tomography: Technology and Applications (eds Drexler, W. & Fujimoto, J. G.) 47–72 (Springer, 2008).

  4. 4.

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

    Article  Google Scholar 

  5. 5.

    Bo, E. et al. Depth-of-focus extension in optical coherence tomography via multiple aperture synthesis. Optica 4, 701–706 (2017).

    ADS  Article  Google Scholar 

  6. 6.

    Blatter, C. et al. Extended focus high-speed swept source OCT with self-reconstructive illumination. Opt. Express 19, 12141–12155 (2011).

    ADS  Article  Google Scholar 

  7. 7.

    Lee, K.-S. & Rolland, J. P. Bessel beam spectral-domain high-resolution optical coherence tomography with micro-optic axicon providing extended focusing range. Opt. Lett. 33, 1696–1698 (2008).

    ADS  Article  Google Scholar 

  8. 8.

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

    ADS  Article  Google Scholar 

  9. 9.

    Lorenser, D., Yang, X. & Sampson, D. D. Ultrathin fiber probes with extended depth of focus for optical coherence tomography. Opt. Lett. 37, 1616–1618 (2012).

    ADS  Article  Google Scholar 

  10. 10.

    Mo, J., de Groot, M. & de Boer, J. F. Focus-extension by depth-encoded synthetic aperture in optical coherence tomography. Opt. Express 21, 10048–10061 (2013).

    ADS  Article  Google Scholar 

  11. 11.

    Ding, Z., Ren, H., Zhao, Y., Nelson, J. S. & Chen, Z. High-resolution optical coherence tomography over a large depth range with an axicon lens. Opt. Lett. 27, 243–245 (2002).

    ADS  Article  Google Scholar 

  12. 12.

    Leitgeb, R. A., Villiger, M., Bachmann, A. H., Steinmann, L. & Lasser, T. Extended focus depth for Fourier domain optical coherence microscopy. Opt. Lett. 31, 2450–2452 (2006).

    ADS  Article  Google Scholar 

  13. 13.

    Coquoz, S., Bouwens, A., Marchand, P. J., Extermann, J. & Lasser, T. Interferometric synthetic aperture microscopy for extended focus optical coherence microscopy. Opt. Express 25, 30807–30819 (2017).

    ADS  Article  Google Scholar 

  14. 14.

    Pircher, M., Götzinger, E. & Hitzenberger, C. K. Dynamic focus in optical coherence tomography for retinal imaging. J. Biomed. Opt. 11, 054013 (2006).

    ADS  Article  Google Scholar 

  15. 15.

    Huber, R., Wojtkowski, M., Fujimoto, J. G., Jiang, J. Y. & Cable, A. E. Three-dimensional and C-mode OCT imaging with a compact, frequency swept laser source at 1,300 nm. Opt. Express 13, 10523–10538 (2005).

    ADS  Article  Google Scholar 

  16. 16.

    Qi, B. et al. Dynamic focus control in high-speed optical coherence tomography based on a microelectromechanical mirror. Opt. Commun. 232, 123–128 (2004).

    ADS  Article  Google Scholar 

  17. 17.

    Podoleanu, A., Charalambous, I., Plesea, L., Dogariu, A. & Rosen, R. Correction of distortions in optical coherence tomography imaging of the eye. Phys. Med. Biol. 49, 1277 (2004).

    Article  Google Scholar 

  18. 18.

    Ortiz, S. et al. Optical distortion correction in optical coherence tomography for quantitative ocular anterior segment by three-dimensional imaging. Opt. Express 18, 2782–2796 (2010).

    ADS  Article  Google Scholar 

  19. 19.

    Westphal, V., Rollins, A. M., Radhakrishnan, S. & Izatt, J. A. Correction of geometric and refractive image distortions in optical coherence tomography applying Fermat’s principle. Opt. Express 10, 397–404 (2002).

    ADS  Article  Google Scholar 

  20. 20.

    Willi, A. K. X-ray computed tomography. Phys. Med. Biol. 51, R29 (2006).

    Article  Google Scholar 

  21. 21.

    Takahiro, K. & Takanori, N. Refractive index tomography based on optical coherence tomography and tomographic reconstruction algorithm. Jpn J. Appl. Phys. 56, 09NB03 (2017).

    Article  Google Scholar 

  22. 22.

    Zysk, A. M., Reynolds, J. J., Marks, D. L., Carney, P. S. & Boppart, S. A. Projected index computed tomography. Opt. Lett. 28, 701–703 (2003).

    ADS  Article  Google Scholar 

  23. 23.

    Wang, Y. & Wang, R. K. High-resolution computed tomography of refractive index distribution by transillumination low-coherence interferometry. Opt. Lett. 35, 91–93 (2010).

    ADS  Article  Google Scholar 

  24. 24.

    Binding, J. et al. Brain refractive index measured in vivo with high-NA defocus-corrected full-field OCT and consequences for two-photon microscopy. Opt. Express 19, 4833–4847 (2011).

    ADS  Article  Google Scholar 

  25. 25.

    Tearney, G. J. et al. Determination of the refractive index of highly scattering human tissue by optical coherence tomography. Opt. Lett. 20, 2258–2260 (1995).

    ADS  Article  Google Scholar 

  26. 26.

    Knuttel, A. & Boehlau-Godau, M. Spatially confined and temporally resolved refractive index and scattering evaluation in human skin performed with optical coherence tomography. J. Biomed. Opt. 5, 83–92 (2000).

    ADS  Article  Google Scholar 

  27. 27.

    Zvyagin, A. V. et al. Refractive index tomography of turbid media by bifocal optical coherence refractometry. Opt. Express 11, 3503–3517 (2003).

    ADS  Article  Google Scholar 

  28. 28.

    Hsieh, J. in Computed Tomography: Principles, Design, Artifacts, and Recent Advances Ch. 3 (SPIE, 2015).

  29. 29.

    Shepp, L. A. & Logan, B. F. The Fourier reconstruction of a head section. IEEE Trans. Nucl. Sci. 21, 21–43 (1974).

    ADS  Article  Google Scholar 

  30. 30.

    Saleh, B. E. A. & Teich, M. C. in Fundamentals of Photonics Ch. 1 (Wiley-Interscience, 2007).

  31. 31.

    Nadaraya, E. On estimating regression. Theory Probab. Appl. 9, 141–142 (1964).

    MATH  Article  Google Scholar 

  32. 32.

    Dormand, J. R. & Prince, P. J. A family of embedded Runge–Kutta formulae. J. Comput. Appl. Math. 6, 19–26 (1980).

    MathSciNet  MATH  Article  Google Scholar 

  33. 33.

    Kingma, D. P. & Ba, J. Adam: a method for stochastic optimization. Preprint at https://arxiv.org/abs/1412.6980 (2014).

  34. 34.

    Abadi, M. et al. TensorFlow: large-scale machine learning on heterogeneous distributed systems. Preprint at https://arxiv.org/abs/1603.04467 (2016).

  35. 35.

    Uhlhorn, S. R., Manns, F., Tahi, H., Rol, P. O. & Parel, J.-M. A. Corneal group refractive index measurement using low-coherence interferometry. In BiOS ‘98 International Biomedical Optics Symposium Vol. 3246, 14–21 (SPIE, 1998).

  36. 36.

    Hitzenberger, C. K. Optical measurement of the axial eye length by laser doppler interferometry. Invest. Ophthalmol. Vis. Sci. 32, 616–624 (1991).

    Google Scholar 

  37. 37.

    Young, L. K., Joseph, T. W.Jr, Thomas, K. G. & Matthew, R. G. Variation of corneal refractive index with hydration. Phys. Med. Biol. 49, 859–868 (2004).

    Article  Google Scholar 

  38. 38.

    Sharpe, J. Optical projection tomography. Annu. Rev. Biomed. Eng. 6, 209–228 (2004).

    Article  Google Scholar 

  39. 39.

    Wu, C. et al. Comparison and combination of rotational imaging optical coherence tomography and selective plane illumination microscopy for embryonic study. Biomed. Opt. Express 8, 4629–4639 (2017).

    Article  Google Scholar 

  40. 40.

    Fuchs, S. et al. Optical coherence tomography with nanoscale axial resolution using a laser-driven high-harmonic source. Optica 4, 903–906 (2017).

    ADS  Article  Google Scholar 

  41. 41.

    Wang, H. & Rollins, A. M. Speckle reduction in optical coherence tomography using angular compounding by B-scan Doppler-shift encoding. J. Biomed. Opt. 14, 030512 (2009).

    ADS  Article  Google Scholar 

  42. 42.

    Desjardins, A. E., Vakoc, B. J., Tearney, G. J. & Bouma, B. E. Speckle reduction in OCT using massively-parallel detection and frequency-domain ranging. Opt. Express 14, 4736–4745 (2006).

    ADS  Article  Google Scholar 

  43. 43.

    Iftimia, N., Bouma, B. E. & Tearney, G. J. Speckle reduction in optical coherence tomography by ‘path length encoded’ angular compounding. J. Biomed. Opt. 8, 260–263 (2003).

    ADS  Article  Google Scholar 

  44. 44.

    Yao, J., Meemon, P., Ponting, M. & Rolland, J. P. Angular scan optical coherence tomography imaging and metrology of spherical gradient refractive index preforms. Opt. Express 23, 6428–6443 (2015).

    ADS  Article  Google Scholar 

  45. 45.

    Carrasco-Zevallos, O. et al. Pupil tracking optical coherence tomography for precise control of pupil entry position. Biomed. Opt. Express 6, 3405–3419 (2015).

    Article  Google Scholar 

  46. 46.

    Tam, K. C. & Perez-Mendez, V. Tomographical imaging with limited-angle input. J. Opt. Soc. Am. 71, 582–592 (1981).

    ADS  MathSciNet  Article  Google Scholar 

  47. 47.

    Klein, T. & Huber, R. High-speed OCT light sources and systems [Invited]. Biomed. Opt. Express 8, 828–859 (2017).

    Article  Google Scholar 

  48. 48.

    Fang, L., Li, S., Cunefare, D. & Farsiu, S. Segmentation based sparse reconstruction of optical coherence tomography images. IEEE Trans. Med. Imaging 36, 407–421 (2017).

    Article  Google Scholar 

  49. 49.

    Kaganovsky, Y. et al. Compressed sampling strategies for tomography. J. Opt. Soc. Am. A 31, 1369–1394 (2014).

    ADS  Article  Google Scholar 

  50. 50.

    Horstmeyer, R., Chung, J., Ou, X., Zheng, G. & Yang, C. Diffraction tomography with Fourier ptychography. Optica 3, 827–835 (2016).

    ADS  Article  Google Scholar 

  51. 51.

    Chowdhury, S., Eldridge, W. J., Wax, A. & Izatt, J. Refractive index tomography with structured illumination. Optica 4, 537–545 (2017).

    ADS  Article  Google Scholar 

  52. 52.

    Lim, J. et al. Comparative study of iterative reconstruction algorithms for missing cone problems in optical diffraction tomography. Opt. Express 23, 16933–16948 (2015).

    ADS  Article  Google Scholar 

  53. 53.

    Fiolka, R., Wicker, K., Heintzmann, R. & Stemmer, A. Simplified approach to diffraction tomography in optical microscopy. Opt. Express 17, 12407–12417 (2009).

    ADS  Article  Google Scholar 

  54. 54.

    Sung, Y. et al. Optical diffraction tomography for high resolution live cell imaging. Opt. Express 17, 266–277 (2009).

    ADS  Article  Google Scholar 

  55. 55.

    Guizar-Sicairos, M., Thurman, S. T. & Fienup, J. R. Efficient subpixel image registration algorithms. Opt. Lett. 33, 156–158 (2008).

    ADS  Article  Google Scholar 

Download references

Acknowledgements

We thank G. Waterman for designing the rotation stage, M. Stern for helpful advice regarding TensorFlow, A. Kuo for providing the human cornea samples and M. Fitzmaurice for helpful discussions regarding the biological data. K.C.Z. was supported by the National Science Foundation (DGF-1106401), J.A.I. was supported in part by the National Institutes of Health (U01EY028079) and S.F. was supported in part by the National Institutes of Health (P30EY005722) and the Google Faculty Research Award.

Author information

Affiliations

Authors

Contributions

K.C.Z. and J.A.I. conceived and developed the idea. R.Q. and S.F. helped to further develop the idea. K.C.Z. developed the algorithms, wrote the code, and collected and analysed the data. R.Q. assisted with data collection and performed the Zemax simulations. All authors contributed to data interpretation. S.D. prepared all biological samples for data collection and histology.

Corresponding author

Correspondence to Joseph A. Izatt.

Ethics declarations

Competing interests

K.C.Z., R.Q., S.F. and J.A.I. have submitted a patent application for this work, assigned to Duke University. J.A.I. is also an inventor on multiple patents, including those licensed to Leica Microsystems and Carl Zeiss Meditec.

Additional information

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

Supplementary information

Supplementary Information

This file contains more information about the work and Supplementary Figs. 1–12.

Reporting Summary

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhou, K.C., Qian, R., Degan, S. et al. Optical coherence refraction tomography. Nat. Photonics 13, 794–802 (2019). https://doi.org/10.1038/s41566-019-0508-1

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing