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Interferometric synthetic aperture microscopy

Abstract

State-of-the-art methods in high-resolution three-dimensional optical microscopy require that the focus be scanned through the entire region of interest. However, an analysis of the physics of the light–sample interaction reveals that the Fourier-space coverage is independent of depth. Here we show that, by solving the inverse scattering problem for interference microscopy, computed reconstruction yields volumes with a resolution in all planes that is equivalent to the resolution achieved only at the focal plane for conventional high-resolution microscopy. In short, the entire illuminated volume has spatially invariant resolution, thus eliminating the compromise between resolution and depth of field. We describe and demonstrate a novel computational image-formation technique called interferometric synthetic aperture microscopy (ISAM). ISAM has the potential to broadly impact real-time three-dimensional microscopy and analysis in the fields of cell and tumour biology, as well as in clinical diagnosis where in vivo imaging is preferable to biopsy.

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Figure 1: Interferometric synthetic aperture microscopy (ISAM) system using spectral detection.
Figure 2: Interferometric data from a tissue phantom consisting of titanium dioxide scatterers suspended in silicone.
Figure 3: Volume-rendered interferometric data.
Figure 4: Cross-sectional scan of the tissue phantom.
Figure 5: En face images from human breast tissue.

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References

  1. Roentgen, W. C. On a new kind of rays. Nature 53, 274–276 (1896).

    Google Scholar 

  2. Cormack, A. Representation of a function by its line integrals, with some radiological applications. J. Appl. Phys. 34, 2722–2727 (1963).

    Article  ADS  Google Scholar 

  3. Bloch, F., Hansen, W. & Packard, M. The nuclear induction experiment. Phys. Rev. 70, 474–485 (1946).

    Article  ADS  Google Scholar 

  4. Carr, H. Y. & Purcell, E. M. Effects of diffusion on free precession in nuclear magnetic resonance experiments. Phys. Rev. 94, 630–638 (1954).

    Article  ADS  Google Scholar 

  5. Lauterbur, P. C. Image formation by induced local interactions: examples employing nuclear magnetic resonance. Nature 242, 190–191 (1973).

    Article  ADS  Google Scholar 

  6. Jakowatz, C. V. Jr Spotlight-mode Synthetic Aperture Radar: A Signal Processing Approach (Kluwer Academic, Boston, 1996).

    Book  Google Scholar 

  7. Munson, D. C. Jr., O’Brien, J. D. & Jenkins, W. K. Tomographic formulation of spotlight-mode synthetic aperture radar. Proc. IEEE 71, 917–925 (1983).

    Article  Google Scholar 

  8. Kino, G. S. & Corle, T. R. Confocal scanning optical microscopy. Phys. Today 42, 55–62 (1989).

    Article  Google Scholar 

  9. Denk, W., Strickler, J. H. & Webb, W. W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990).

    Article  ADS  Google Scholar 

  10. Izatt, J. A., Hee, M. R., Owen, G. M., Swanson, E. A. & Fujimoto, J. G. Optical coherence microscopy in scattering media. Opt. Lett. 19, 590 (1994).

    Article  ADS  Google Scholar 

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

    Article  ADS  Google Scholar 

  12. Lee, B. S. & Strand, T. C. Profilometry with a coherence scanning microscope. Appl. Opt. 29, 3784–3788 (1990).

    Article  ADS  Google Scholar 

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

    Article  ADS  Google Scholar 

  14. Deck, L. & de Groot, P. High-speed noncontact profiler based on scanning white-light interferometry. Appl. Opt. 33, 7334–7338 (1994).

    Article  ADS  Google Scholar 

  15. Beaurepaire, E., Boccara, A. C., Lebec, M., Blanchot, L. & Saint-Jalmes, H. Full-field optical coherence microscopy. Opt. Lett. 23, 244–246 (1998).

    Article  ADS  Google Scholar 

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

    Article  ADS  Google Scholar 

  17. Choma, M. A., Ellerbee, A. K., Yang, C., Creazzo, T. L. & Izatt, J. A. Spectral-domain phase microscopy. Opt. Lett. 30, 1162–1164 (2005).

    Article  ADS  Google Scholar 

  18. Barer, R. Applications of interference microscopy. Nature 4773, 315–316 (1961).

    Article  ADS  Google Scholar 

  19. Bouma, B. E. & Tearney, G. J. The Handbook of Optical Cohernce Tomography (Marcel Dekker, New York, 2002).

    Google Scholar 

  20. Schotland, J. C. Continuous-wave diffusion imaging. J. Opt. Soc. Am. A 14, 275–279 (1997).

    Article  ADS  Google Scholar 

  21. 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).

    Article  ADS  Google Scholar 

  22. Sharpe, J. et al. Optical projection tomography as a tool for 3D microscopy and gene expression studies. Science 296, 541–545 (2002).

    Article  ADS  Google Scholar 

  23. Wolf, E. Three-dimensional structure determination of semi-transparent objects from holographic data. Opt. Commun. 1, 153–156 (1969).

    Article  ADS  Google Scholar 

  24. Porter, R. P. & Devaney, A. J. Holography and the inverse source problem. J. Opt. Soc. Am. 72, 327–330 (1982).

    Article  ADS  MathSciNet  Google Scholar 

  25. Lauer, V. New approach to optical diffraction tomography yielding a vector equation of diffraction tomography and a novel tomographic microscope. J. Microsc. 205, 165–176 (2002).

    Article  MathSciNet  Google Scholar 

  26. Sheppard, C. J. R., Roy, M. & Sharma, M. D. Image formation in low-coherence and confocal interference microscopes. Appl. Opt. 43, 1493–1502 (2004).

    Article  ADS  Google Scholar 

  27. Lepetit, L., Chériaux, G. & Joffre, M. Linear techniques of phase measurement by femtosecond spectral interferometry for applications in spectroscopy. J. Opt. Soc. Am. B 12, 2467–2474 (1995).

    Article  ADS  Google Scholar 

  28. Marks, D. L., Ralston, T. S., Carney, P. S. & Boppart, S. A. Inverse scattering for rotationally scanned optical coherence tomography. J. Opt. Soc. Am. A 23, 2433–2439 (2006).

    Article  ADS  Google Scholar 

  29. Marks, D. L., Ralston, T. S., Carney, P. S. & Boppart, S. A. Inverse scattering for frequency-scanned full-field optical coherence tomography. J. Opt. Soc. Am. A (2007) (in the press).

  30. Ralston, T. S., Marks, D. L., Carney, P. S. & Boppart, S. A. Inverse scattering for optical coherence tomography. J. Opt. Soc. Am. A 23, 1027–1037 (2006).

    Article  ADS  Google Scholar 

  31. Morse, P. M. & Feschbach, H. H. Methods of Theoretical Physics (McGraw Hill, New York, 1953).

    Google Scholar 

  32. Natterer, F. The Radon Transform (Wiley, New York, 1986).

    MATH  Google Scholar 

  33. Tikhonov, A. N. On the stability of inverse problems. Dokl. Akad. Nauk SSSR 39, 195–198 (1943).

    MathSciNet  Google Scholar 

  34. Cense, B. et al. Ultrahigh-resolution high-speed retinal imaging using spectral-domain optical coherence tomography. Opt. Express 12, 2435–2447 (2004).

    Article  ADS  Google Scholar 

  35. Marks, D. L., Oldenburg, A. L., Reynolds, J. J. & Boppart, S. A. Digital algorithm for dispersion correction in optical coherence tomography for homogeneous and stratified media. Appl. Opt. 42, 204–217 (2003).

    Article  ADS  Google Scholar 

  36. Pozrikidis, C. Numerical Computation in Science and Engineering (Oxford Univ. Press, Oxford, 1998).

    MATH  Google Scholar 

  37. Oldenburg, A. L., Toublan, F. J., Suslick, K. S., Wei, A. & Boppart, S. A. Magnetomotive contrast for in vivo optical coherence tomography. Opt. Express 13, 6597–6614 (2005).

    Article  ADS  Google Scholar 

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Acknowledgements

We thank K. Rowland, P. Johnson, J. Kotynek and F. Bellafiore from Carle Foundation Hospital and Clinic Association, and F. Nguyen and E. Chaney from the Beckman Institute, for their assistance in obtaining and sectioning human tissue specimens. We thank A. Oldenburg for helping to design and fabricate tissue phantoms and the Beckman Institute Visualization Laboratory for assistance in figure design. This work was supported in part by the National Institutes of Health (NIBIB, 1 R01 EB005221 and 1 R21 EB005321, to S.A.B.), the National Science Foundation (CAREER Award, 0239265, to P.S.C.) and the Beckman Institute Graduate Fellowship Program (to T.S.R.).

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Correspondence to Stephen A. Boppart.

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Ralston, T., Marks, D., Scott Carney, P. et al. Interferometric synthetic aperture microscopy. Nature Phys 3, 129–134 (2007). https://doi.org/10.1038/nphys514

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