Abstract

Ultrahigh-resolution optical coherence tomography uses broadband light sources to achieve axial image resolutions on the few micron scale. Fourier domain detection methods enable more than an order of magnitude increase in imaging speed and sensitivity, thus overcoming the sensitivity limitations inherent in ultrahigh-resolution OCT using standard time domain detection. Fourier domain methods also provide direct access to the spectrum of the optical signal. This enables automatic numerical dispersion compensation, a key factor in achieving ultrahigh image resolutions. We present ultrahigh-resolution, high-speed Fourier domain OCT imaging with an axial resolution of 2.1 µm in tissue and 16,000 axial scans per second at 1024 pixels per axial scan. Ultrahigh-resolution spectral domain OCT is shown to provide a ~100x increase in imaging speed when compared to ultrahigh-resolution time domain OCT. In vivo imaging of the human retina is demonstrated. We also present a general technique for automatic numerical dispersion compensation, which is applicable to spectral domain as well as swept source embodiments of Fourier domain OCT.

© 2004 Optical Society of America

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Am. J. Ophthalmol.

M. Wojtkowski, T. Bajraszewski, I. Gorczynska, P. Targowski, A. Kowalczyk, W. Wasilewski, and C. Radzewicz, "Opthalmic Imaging by Spectral Optical Coherence Tomography," Am. J. Ophthalmol. (accepted).

Appl. Opt.

Archiv. Ophthalmol.

M. R. Hee, J. A. Izatt, E. A. Swanson, D. Huang, J. S. Schuman, C. P. Lin, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography of the human retina," Archiv. Ophthalmol. 113, 325-332 (1995).
[CrossRef]

W. Drexler, H. Sattmann, B. Hermann, T. H. Ko, M. Stur, A. Unterhuber, C. Scholda, O. Findl, M. Wirtitsch, J. G. Fujimoto, and A. F. Fercher, "Enhanced visualization of macular pathology with the use of ultrahigh-resolution optical coherence tomography," Archiv. Ophthalmol. 121, 695-706 (2003).
[CrossRef]

J. Biomed Opt.

C. K. Hitzenberger, A. Baumgartner, W. Drexler, and A. F. Fercher, "Dispersion effects in partial coherence interferometry: implications for intraocular ranging," J. Biomed. Opt. 4, 144-151 (1999).
[CrossRef] [PubMed]

J. Biomed. Opt.

G. Hausler and M. W. Linduer, "Coherence radar and spectral radar-new tools for dermatological diagnosis," J. Biomed. Opt. 3, 21-31 (1998).
[CrossRef]

M. Wojtkowski, R. Leitgeb, A. Kowalczyk, T. Bajraszewski, and A. F. Fercher, "In vivo human retinal imaging by Fourier domain optical coherence tomography," J. Biomed. Opt. 7, 457-463 (2002).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A. Opt. Image Sci. Vis.

D. X. Hammer, A. J. Welch, G. D. Noojin, R. J. Thomas, D. J. Stolarski, and B. A. Rockwell, "Spectrally resolved white-light interferometry for measurement of ocular dispersion," J. Opt. Soc. Am. A. Opt. Image Sci. Vis. 16, 2092-2102 (1999).
[CrossRef] [PubMed]

Nat. Biotechnol.

J. G. Fujimoto, "Optical coherence tomography for ultrahigh resolution in vivo imaging," Nat. Biotechnol. 21, 1361-1367 (2003).
[CrossRef] [PubMed]

Nature medicine

W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kärtner, J. S. Schuman, and J. G. Fujimoto, "Ultrahigh-resolution ophthalmic optical coherence tomography," Nature medicine 7, 502-507 (2001).
[CrossRef] [PubMed]

Ophthalmol.

C. A. Puliafito, M. R. Hee, C. P. Lin, E. Reichel, J. S. Schuman, J. S. Duker, J. A. Izatt, E. A. Swanson, and J. G. Fujimoto, "Imaging of macular diseases with optical coherence tomography," Ophthalmol. 102, 217-229 (1995).

Opt. Commun.

A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, "Measurement of Intraocular Distances by Backscattering Spectral Interferometry," Opt. Commun. 117, 43-48 (1995).
[CrossRef]

P. Targowski, M. Wojtkowski, A. Kowalczyk, T. Bajraszewski, M. Szkulmowski, and W. Gorczynska, "Complex spectral OCT in human eye imaging in vivo," Opt. Commun. 229, 79-84 (2004).
[CrossRef]

Opt. Express

N. Nassif, B. Cense, B. H. Park, S. H. Yun, T. C. Chen, B. E. Bouma, G. J. Tearney, and J. F. de Boer, "In vivo human retinal imaging by ultrahigh-speed spectral domain optical coherence tomography," Opt. Express 29, 480-482 (2004), <a href="http://www.opticsexpress.org/abstract.cfm?URI=OPEX-12-3-367">http://www.opticsexpress.org/abstract.cfm?URI=OPEX-12-3-367</a>

S. H. Yun, G. J. Tearney, J. F. de Boer, N. Iftimia, and B. E. Bouma, "High-speed optical frequency-domain imaging," Opt. Express 11, 2953-2963 (2003).
[CrossRef] [PubMed]

R. A. Leitgeb, L. Schmetterer, W. Drexler, A. F. Fercher, R. J. Zawadzki, and T. Bajraszewski, "Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography," Opt. Express 11, 3116-3121 (2003), <a href="http://www.opticsexpress.org/abstract.cfm?URI=OPEX-11-23-3116">http://www.opticsexpress.org/abstract.cfm?URI=OPEX-11-23-3116</a>
[CrossRef] [PubMed]

S. Bourquin, A. D. Aguirre, I. Hartl, P. Hsiung, T. H. Ko, J. G. Fujimoto, T. A. Birks, W. J. Wadsworth, U. Bunting, and D. Kopf, "Ultrahigh resolution real time OCT imaging using a compact femtosecond Nd : Glass laser and nonlinear fiber," Opt. Express 11, 3290-3297 (2003),<a href=" http://www.opticsexpress.org/abstract.cfm?URI=OPEX-11-24-3290"> http://www.opticsexpress.org/abstract.cfm?URI=OPEX-11-24-3290</a>
[CrossRef] [PubMed]

A. F. Fercher, C. K. Hitzenberger, M. Sticker, R. Zawadzki, B. Karamata, and T. Lasser, "Numerical dispersion compensation for partial coherence interferometry and optical coherence tomography," Opt. Express 9, (2001), <a href= "http://www.opticsexpress.org/abstract.cfm?URI=OPEX-9-12-610">http://www.opticsexpress.org/abstract.cfm?URI=OPEX-9-12-610</a>
[CrossRef] [PubMed]

R. Leitgeb, C. K. Hitzenberger, and A. F. Fercher, "Performance of fourier domain vs. time domain optical coherence tomography," Opt. Express 11, 889-894 (2003), <a href="http://www.opticsexpress.org/abstract.cfm?URI=OPEX-11-8-889">http://www.opticsexpress.org/abstract.cfm?URI=OPEX-11-8-889</a>
[CrossRef] [PubMed]

M. A. Choma, M. V. Sarunic, C. H. Yang, and J. A. Izatt, "Sensitivity advantage of swept source and Fourier domain optical coherence tomography," Opt. Express 11, 2183-2189 (2003), <a href=" http://www.opticsexpress.org/abstract.cfm?URI=OPEX-11-18-2183">http://www.opticsexpress.org/abstract.cfm?URI=OPEX-11-18-2183</a>
[CrossRef] [PubMed]

Opt. Lett

M. Wojtkowski, T. Bajraszewski, P. Targowski, and A. Kowalczyk, "Real-time in vivo imaging by high-speed spectral optical coherence tomography," Opt. Lett. 28, 1745-1747 (2003).
[CrossRef] [PubMed]

Opt. Lett.

R. Leitgeb, M. Wojtkowski, A. Kowalczyk, C. K. Hitzenberger, M. Sticker, and A. F. Fercher, "Spectral measurement of absorption by spectroscopic frequency-domain optical coherence tomography," Opt. Lett. 25, 820-822 (2000).
[CrossRef]

R. L. Fork, C. H. B. Cruz, P. C. Becker, and C. V. Shank, "Compression of Optical Pulses to 6 Femtoseconds by Using Cubic Phase Compensation," Opt. Lett. 12, 483-485 (1987).
[CrossRef] [PubMed]

K. Naganuma, K. Mogi, and H. Yamada, "Group-Delay Measurement Using the Fourier-Transform of an Interferometric Cross-Correlation Generated by White-Light," Opt. Lett. 15, 393-395 (1990).
[CrossRef] [PubMed]

E. A. Swanson, D. Huang, M. R. Hee, J. G. Fujimoto, C. P. Lin, and C. A. Puliafito, "High-speed optical coherence domain reflectometry," Opt. Lett. 17, 151-153 (1992).
[CrossRef] [PubMed]

B. E. Lemoff and C. P. J. Barty, "Cubic-Phase-Free Dispersion Compensation in Solid-State Ultrashort-Pulse Lasers," Opt. Lett. 18, 57-59 (1993).
[CrossRef] [PubMed]

M. Wojtkowski, A. Kowalczyk, R. Leitgeb, and A. F. Fercher, "Full range complex spectral optical coherence tomography technique in eye imaging," Opt. Lett. 27, 1415-1417 (2002).
[CrossRef]

B. Povazay, K. Bizheva, A. Unterhuber, B. Hermann, H. Sattmann, A. F. Fercher, W. Drexler, A. Apolonski, W. J. Wadsworth, J. C. Knight, P. S. J. Russell, M. Vetterlein, and E. Scherzer, "Submicrometer axial resolution optical coherence tomography," Opt. Lett. 27, 1800-1802 (2002).
[CrossRef]

Y. Wang, Y. Zhao, J. S. Nelson, Z. Chen, and R. S. Windeler, "Ultrahigh-resolution optical coherence tomography by broadband continuum generation from a photonic crystal fiber," Opt. Lett. 28, 182-184 (2003).
[CrossRef] [PubMed]

K. Bizheva, B. Povazay, B. Hermann, H. Sattmann, W. Drexler, M. Mei, R. Holzwarth, T. Hoelzenbein, V. Wacheck, and H. Pehamherger, "Compact, broad-bandwidth fiber laser for sub-2- mu m axial resolution optical coherence tomography in. The 1300-nm wavelength region," Opt. Lett. 28, 707-709 (2003).
[CrossRef] [PubMed]

B. Bouma, G. J. Tearney, S. A. Boppart, M. R. Hee, M. E. Brezinski, and J. G. Fujimoto, "High-resolution optical coherence tomographic imaging using a mode-locked Ti-Al2O3 laser source," Opt. Lett. 20, 1486-1488 (1995).
[CrossRef] [PubMed]

S. R. Chinn, E. A. Swanson, and J. G. Fujimoto, "Optical coherence tomography using a frequency-tunable optical source," Opt. Lett. 22, 340-342 (1997)
[CrossRef] [PubMed]

B. Golubovic, B. E. Bouma, G. J. Tearney, and J. G. Fujimoto, "Optical frequency-domain reflectometry using rapid wavelength tuning of a Cr/sup 4+/:forsterite laser," Opt. Lett. 22, 1704-1706 (1997).
[CrossRef]

U. Morgner, F. X. Kartner, S. H. Cho, Y. Chen, H. A. Haus, J. G. Fujimoto, E. P. Ippen, V. Scheuer, G. Angelow, and T. Tschudi, "Sub-two-cycle pulses from a Kerr-lens mode-locked Ti:sapphire laser," Opt. Lett. 24, 411-413 (1999).
[CrossRef]

W. Drexler, U. Morgner, F. X. Kartner, C. Pitris, S. A. Boppart, X. D. Li, E. P. Ippen, and J. G. Fujimoto, "In vivo ultrahigh-resolution optical coherence tomography," Opt. Lett. 24, 1221-1223 (1999).
[CrossRef]

I. Hartl, X. D. Li, C. Chudoba, R. K. Hganta, T. H. Ko, J. G. Fujimoto, J. K. Ranka, and R. S. Windeler, "Ultrahigh-resolution optical coherence tomography using continuum generation in an air-silica microstructure optical fiber," Opt. Lett. 26, 608-610 (2001).
[CrossRef]

R. A. Leitgeb, L. Schmetterer, C. K. Hitzenberger, A. F. Fercher, F. Berisha, M. Wojtkowski, and T. Bajraszewski, "Real-time measurement of in vitro flow by Fourier-domain color Doppler optical coherence tomography," Opt. Lett. 29, 171-173 (2004).
[CrossRef] [PubMed]

S. H. Yun, C. Boudoux, G. J. Tearney, and B. E. Bouma, "High-speed wavelength-swept semiconductor laser with a polygon-scanner-based wavelength filter," Opt. Lett. 28, 1981-1983 (2003).
[CrossRef] [PubMed]

J. F. de Boer, B. Cense, B. H. Park, M. C. Pierce, G. J. Tearney, and B. E. Bouma, "Improved signal-to-noise ratio in spectral-domain compared with time-domain optical coherence tomography," Opt. Lett. 28, 2067-2069 (2003).
[CrossRef] [PubMed]

R. A. Leitgeb, C. K. Hitzenberger, A. F. Fercher, and T. Bajraszewski, "Phase-shifting algorithm to achieve high-speed long-depth-range probing by frequency-domain optical coherence tomography," Opt. Lett. 28, 2201-2203 (2003).
[CrossRef] [PubMed]

Science

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Other

J. W. Goodman, Statistical Optics (Wiley, New York, 2000), p. 550.

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Fig. 1.
Fig. 1.

Flow chart of spectral OCT dispersion compensation procedure. The interference spectrum is first rescaled to convert from wavelength to frequency and then resampled. In standard spectral OCT, this spectrum is Fourier transformed to calculate the axial scan, which gives backreflection/backscattering versus distance (solid path). For dispersion compensation (dashed path), the Hilbert transform is used to calculate the complex representation of the input signal. The phase of this signal is modified by using adjustable second- and third-order terms. The modified spectrum is Fourier transformed to calculate the axial scan. In order to perform automatic dispersion compensation, the sharpness of the axial scan or image is measured. The second- and third-order phase correction is iteratively adjusted to achieve optimum sharpness, as shown in the dotted path. This procedure may be generalized to correct higher orders of dispersion.

Fig. 2.
Fig. 2.

Schematic diagram of the ultrahigh-resolution spectral domain OCT system. Retinal imaging is performed by using a modified slitlamp biomicroscope. Optical materials are used in the reference arm to compensate for dispersion mismatch between the reference and sample arm optical components. The spectrometer consists of a collimating lens, a transmission grating, and a lens that images the spectrum onto a 2048-element CCD linescan camera.

Fig. 3.
Fig. 3.

Spectrum from the Ti:Sapphire laser source registered by the OCT spectrometer, as shown in Fig. 2. The bandwidth is 144 nm FWHM.

Fig. 4.
Fig. 4.

Characterization of point spread function with matched (no water cell in reference arm) and unmatched (2 cm water cell in reference arm) dispersion. a, b) Comparison of theoretically calculated and experimentally measured point spread functions (PSF) with dispersion matched between the reference and sample arms. c, d) Comparison of the theoretical PSF, measured PSF with unmatched dispersion, and measured PSF with unmatched dispersion and numerical compensation. e) Phase comparison of the measured PSF with matched dispersion, the measured PSF with unmatched dispersion, and the measured PSF with unmatched dispersion and numerical dispersion correction. f) Comparison of the phase derivative (proportional to inverse of group velocity) for the same three cases. In all cases, dispersion is compensated by iteratively adjusting second- and third-order terms to maximize the sharpness metric M.

Fig. 5.
Fig. 5.

a) Plot of axial resolution (FWHM of the measured point spread function) with matched dispersion and unmatched dispersion with numerical compensation. Dispersion is induced with a 2 cm water cell in the reference arm. The FWHM increases with optical path difference due to the loss of fringe visibility away from the center wavelength of the spectrometer λ0. The loss in fringe visibility is more severe for larger optical path differences. This effect is shown in b), where the interferometric fringes after the scale transformation are shown for sample reflections from 0.05 mm (top) and 1.2 mm (bottom). c) The maximum sensitivity is achieved for zero optical path difference and it decreases by 18 dB over the 1.4 mm scan range.

Fig. 6.
Fig. 6.

a) Ultrahigh-resolution spectral OCT image of human macula with dispersion matched by a water cell in the reference arm. b) Image with unmatched dispersion. c) Same image with dispersion numerically corrected to second and third orders. The image with numerically compensated dispersion has a resolution comparable to or better than the image with physically matched dispersion. These spectral OCT images consist of 3000 axial scans acquired in 150 ms. d) Ultrahigh-resolution OCT image obtained by using time domain detection. The image consists of 300 axial scans acquired in 2 seconds.

Fig. 7.
Fig. 7.

Spectral OCT images of the human retina in vivo. Scans was taken along the papillomacular axis with 3000 axial scans acquired in 150 ms. a) The high transverse pixel density and high sensitivity allow a better discrimination of thin retinal layers, including the external limiting membrane (ELM), the photoreceptor inner and outer segment junction (IS/OS), and the retinal pigment epithelium (RPE). b) The inner limiting membrane (ILM) can also be discriminated from the nerve fiber layer (NFL) in the 4x image. Note that the image quality is maintained in the zoomed images due to the high transverse pixel density.

Fig. 8.
Fig. 8.

(2.8 MB) High-speed spectral OCT movie of the optic disk using numerical dispersion compensation. This movie was acquired using images with 512 axial scans of 1024 pixels at a rate of 31 frames per second.

Fig. 9.
Fig. 9.

The sharpness metric M defined in the theory section is shown for both second- and third-order dispersion correction, as applied to 300 A-scans in Fig. 6(b). The metric was first optimized with respect to a2 and then with respect to a3. Each curve has a well-defined maximum, which corresponds visually to the sharpest image. The dispersion-corrected image is shown in Fig. 6(c).

Fig. 10.
Fig. 10.

a) (1.6 MB) High-speed spectral OCT movie of the optic disc with second- and third-order dispersion compensation using the automatic iterative method. b) (1.6 MB) High-speed spectral OCT movie of the optic disk with approximate dispersion compensation achieved by varying the scale or bandwidth parameter in the scale transformation. The movie in a) is sharp for all depths, while the movie in b) is dispersion compensated at only one depth. This is seen in the sharpening of the retinal pigment epithelium (RPE) on the left side of the image. These movies were acquired by using frames with 512 axial scans of 1024 pixels at a rate of 31 frames per second.

Equations (7)

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S out ( ω ) = E R ( ω ) 2 + 2 Re { E R ( ω ) * E S ( ω ) } + E S ( ω ) 2
S int ( ω ) = 2 Re { E R ( ω ) * E S ( ω ) } = 2 Re { n I n ( ω ) I r ( ω ) exp [ i ( ω τ n + Φ ( ω , τ n ) ) ] } .
Δ z = 2 ln 2 π λ 0 2 Δ λ ,
Δ Λ = 1 2 λ 0 2 ( Δ z 2 ) = π 2 ln 2 Δ λ .
Δ L z = Δ z 2 N 2 = ln 2 2 π λ 0 2 Δ λ N
β ( ω ) = β ( ω 0 ) + d β d ω ω 0 ( ω ω 0 ) + 1 2 d 2 β d ω 2 ω 0 ( ω ω 0 ) 2 + 1 6 d 3 β d ω 3 ω 0 ( ω ω 0 ) 3 +
Φ ¯ ( ω ) = a 2 ( ω ω 0 ) 2 a 3 ( ω ω 0 ) 3

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