Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Real-time in vivo computed optical interferometric tomography

Abstract

High-resolution real-time tomography of scattering tissues is important for many areas of medicine and biology1,2,3,4,5,6. However, the compromise between transverse resolution and depth-of-field, in addition to low sensitivity deep in tissue, continues to impede progress towards cellular-level volumetric tomography. Computed imaging has the potential to solve these long-standing limitations. Interferometric synthetic aperture microscopy7,8,9 is a computed imaging technique enabling high-resolution volumetric tomography with spatially invariant resolution. However, its potential for clinical diagnostics remains largely untapped because full volume reconstructions required lengthy post-processing, and the phase-stability requirements have been difficult to satisfy in vivo. Here, we demonstrate how three-dimensional Fourier-domain resampling, in combination with high-speed optical coherence tomography, can achieve high-resolution in vivo tomography. Enhanced depth sensitivity was achieved over a depth of field extended in real time by more than an order of magnitude. This work lays the foundation for high-speed volumetric cellular-level tomography.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Real-time in vivo ISAM of healthy human skin from the fingerprint region of the index finger.
Figure 2: Focus placement with real-time ISAM on ex vivo mouse muscle.
Figure 3: Real-time in vivo ISAM of skin from a healthy human wrist.

Similar content being viewed by others

References

  1. Boppart, S. A. et al. In vivo cellular optical coherence tomography imaging. Nature Med. 4, 861–865 (1998).

    Article  Google Scholar 

  2. Adler, D. C. et al. Three-dimensional endomicroscopy using optical coherence tomography. Nature Photon. 1, 709–716 (2007).

    Article  ADS  Google Scholar 

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

    Article  ADS  Google Scholar 

  4. Vakoc, B. J. et al. Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging. Nature Med. 15, 1219–1223 (2009).

    Article  Google Scholar 

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

    Article  Google Scholar 

  6. Drexler, W. et al. Ultrahigh-resolution ophthalmic optical coherence tomography. Nature Med. 7, 502–507 (2001).

    Article  Google Scholar 

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

    Article  ADS  Google Scholar 

  8. Davis, B. J., Marks, D. L., Ralston, T. S., Carney, P. S. & Boppart, S. A. Interferometric synthetic aperture microscopy: computed imaging for scanned coherent microscopy. Sensors 8, 3903–3931 (2008).

    Article  Google Scholar 

  9. Davis, B. J. et al. Nonparaxial vector-field modeling of optical coherence tomography and interferometric synthetic aperture microscopy. J. Opt. Soc. Am. A 24, 2527–2542 (2007).

    Article  ADS  Google Scholar 

  10. Srinivasan, V. J., Radhakrishnan, H., Jiang, J. Y., Barry, S. & Cable, A. E. Optical coherence microscopy for deep tissue imaging of the cerebral cortex with intrinsic contrast. Opt. Express 20, 2220–2239 (2012).

    Article  ADS  Google Scholar 

  11. Rolland, J. P., Meemon, P., Murali, S., Thompson, K. P. & Lee, K-S. Gabor-based fusion technique for optical coherence microscopy. Opt. Express 18, 3632–3642 (2010).

    Article  ADS  Google Scholar 

  12. Rajadhyaksha, M., Gonzalez, S., Zavislan, J. M., Anderson, R. R. & Webb, R. H. In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology. J. Invest. Dermatol. 113, 293–303 (1999).

    Article  Google Scholar 

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

    Article  Google Scholar 

  14. 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).

    Article  ADS  Google Scholar 

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

    Article  ADS  Google Scholar 

  16. Yasuno, Y. et al. Non-iterative numerical method for laterally superresolving Fourier domain optical coherence tomography. Opt. Express 14, 1006–1020 (2006).

    Article  ADS  Google Scholar 

  17. Yu, L. et al. Improved lateral resolution in optical coherence tomography by digital focusing using two-dimensional numerical diffraction method. Opt. Express 15, 7634–7641 (2007).

    Article  ADS  Google Scholar 

  18. Colomb, T. et al. Numerical parametric lens for shifting, magnification, and complete aberration compensation in digital holographic microscopy. J. Opt. Soc. Am. A 23, 3177–3190 (2006).

    Article  ADS  Google Scholar 

  19. Adie, S. G., Graf, B. W., Ahmad, A., Carney, P. S. & Boppart, S. A. Computational adaptive optics for broadband optical interferometric tomography of biological tissue. Proc. Natl Acad. Sci. USA 109, 7175–7180 (2012).

    Article  ADS  Google Scholar 

  20. Hillmann, D., Franke, G., Lührs, C., Koch, P. & Hüttmann, G. Efficient holoscopy image reconstruction. Opt. Express 20, 21247–21263 (2012).

    Article  ADS  Google Scholar 

  21. Kim, M-K. Tomographic three-dimensional imaging of a biological specimen using wavelength-scanning digital interference holography. Opt. Express 7, 305–310 (2000).

    Article  ADS  Google Scholar 

  22. Ralston, T. S., Marks, D. L., Carney, P. S. & Boppart, S. A. Real-time interferometric synthetic aperture microscopy. Opt. Express 16, 2555–2569 (2008).

    Article  ADS  Google Scholar 

  23. Wilke, K., Martin, A., Terstegen, L. & Biel, S. S. A short history of sweat gland biology. Int. J. Cosmetic Sci. 29, 169–179 (2007).

    Article  Google Scholar 

  24. Gabarda, S. & Cristóbal, G. Blind image quality assessment through anisotropy. J. Opt. Soc. Am. A 24, B42–B51 (2007).

    Article  ADS  Google Scholar 

  25. Blatter, C. et al. In situ structural and microangiographic assessment of human skin lesions with high-speed OCT. Biomed. Opt. Express 3, 2636–2646 (2012).

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank E.J. Chaney (University of Illinois at Urbana-Champaign) for providing the tissue samples used throughout this study, D.L. Marks (formerly at University of Illinois at Urbana-Champaign) for providing the tissue phantom and D. Spillman (University of Illinois at Urbana-Champaign) for administrative and information technology support related to this research. This research was supported in part by grants from the National Institutes of Health (NIH; R01 EB012479 to S.A.B.) and an NIH Bioengineering Research Partnership (R01 EB013723 to S.A.B.). A.A. was funded in part by the NIH National Cancer Institute Alliance for Nanotechnology in Cancer (Midwest Cancer Nanotechnology Training Center; grant R25-CA154015A) and Texas Instruments.

Author information

Authors and Affiliations

Authors

Contributions

Experimental data were acquired by A.A., N.D.S. and S.G.A. Analysis and interpretation of data was carried out by A.A., N.D.S. and S.G.A. Additional processing and visualization was performed by A.A. and N.D.S. GPU code was written by A.A., N.D.S. and H.K., and reviewed by W.W.H. The manuscript was written and edited by all authors. S.A.B. and P.S.C. made seminal contributions to the core ideas carried out in this study, and obtained funding to support this research.

Corresponding author

Correspondence to Stephen A. Boppart.

Ethics declarations

Competing interests

S.A.B. and P.S.C are co-founders of Diagnostic Photonics, Inc., which is licensing intellectual property from the University of Illinois at Urbana-Champaign related to Interferometric Synthetic Aperture Microscopy. S.A.B. received patent royalties from the Massachusetts Institute of Technology for technology related to optical coherence tomography. Other authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 1180 kb)

Supplementary video

Supplementary video (MOV 9588 kb)

Supplementary video

Supplementary video (MOV 5086 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ahmad, A., Shemonski, N., Adie, S. et al. Real-time in vivo computed optical interferometric tomography. Nature Photon 7, 444–448 (2013). https://doi.org/10.1038/nphoton.2013.71

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nphoton.2013.71

This article is cited by

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