High speed spectral domain optical coherence tomography for retinal imaging at 500,000 A‑lines per second

Lin An, Peng Li, Tueng T Shen, Ruikang Wang, Lin An, Peng Li, Tueng T Shen, Ruikang Wang

Abstract

We present a new development of ultrahigh speed spectral domain optical coherence tomography (SDOCT) for human retinal imaging at 850 nm central wavelength by employing two high-speed line scan CMOS cameras, each running at 250 kHz. Through precisely controlling the recording and reading time periods of the two cameras, the SDOCT system realizes an imaging speed at 500,000 A-lines per second, while maintaining both high axial resolution (~8 μm) and acceptable depth ranging (~2.5 mm). With this system, we propose two scanning protocols for human retinal imaging. The first is aimed to achieve isotropic dense sampling and fast scanning speed, enabling a 3D imaging within 0.72 sec for a region covering 4x4 mm(2). In this case, the B-frame rate is 700 Hz and the isotropic dense sampling is 500 A-lines along both the fast and slow axes. This scanning protocol minimizes the motion artifacts, thus making it possible to perform two directional averaging so that the signal to noise ratio of the system is enhanced while the degradation of its resolution is minimized. The second protocol is designed to scan the retina in a large field of view, in which 1200 A-lines are captured along both the fast and slow axes, covering 10 mm(2), to provide overall information about the retinal status. Because of relatively long imaging time (4 seconds for a 3D scan), the motion artifact is inevitable, making it difficult to interpret the 3D data set, particularly in a way of depth-resolved en-face fundus images. To mitigate this difficulty, we propose to use the relatively high reflecting retinal pigmented epithelium layer as the reference to flatten the original 3D data set along both the fast and slow axes. We show that the proposed system delivers superb performance for human retina imaging.

Keywords: (170.3880) medical and biological imaging; (170.4460) Ophthalmic optics and devices; (170.4500) Optical coherence tomography.

Figures

Fig. 1
Fig. 1
(a) Schematic of the ultrahigh speed SDOCT system; and (b) the trigger signal sequences for dual-camera system. SLD: superluminescent diode; PC: polarization controller; OC: optical circulator.
Fig. 2
Fig. 2
System performance of the ultrahigh speed SDOCT. (a), light source spectrums captured by the two spectrometers of the system; (b) the PSF of the two spectrometers before (red and blue) and after (yellow and green) the digital beam shaping. (c) the system sensitivity falling off curves. (d) the measured optical delay line positions. (d) the measured system axial resolution.
Fig. 3
Fig. 3
B-frame retinal images obtained from (a) the combined used of two spectrometers, and (b) the spectrometer that employed the camera 1, respectively. (Scale bar = 200 μm)
Fig. 4
Fig. 4
In vivo experimental results obtained by high speed isotropic dense sampling 3D retinal imaging. (a) Cross-sectional images along the fast scan-axis, where (i) to (v) correspond to the results after averaging adjacent one, three, six, nine and twelve fast-scan images, respectively. (b) Cross-sectional images along the slow axis, where (i) to (v) are resulted from averaging adjacent one, three, six, nine and twelve slow cross-sectional images, respectively. (c) Cross sectional images, where (i) to (iii) are resulted from averaging adjacent two, three and four frames along both the fast and slow axes. (d) OCT fundus image [also see Media 1]. (e) 3D rendering volumetric image. (Scale bar = 200 μm)
Fig. 5
Fig. 5
In vivo results of a large field of view isotropic dense sampling retina imaging. (a) OCT fundus image. (b) 3D rendering volumetric image.
Fig. 6
Fig. 6
(a) One typical fast B-scan cross sectional image. (b) Processed B-scan image after flattening according to the ISP layer. (c) One typical slow axis cross sectional image. (d) Collapse-averaged slow-axis image. (e) Finally processed slow-scan image. Scale bar = 200µm
Fig. 7
Fig. 7
After flattening the data set according to the ISP layer on both the directions, ultrahigh speed SDOCT provides ability for comprehensive assessment of the retina status over a large field view. (a) 3D rendered volumetric image. (b) to (f) are typical depth resolved fundus (en-face) images, which are corresponding to the depth positions marked by the red, yellow, green, blue and purple lines in (a). [Also see Media 2.]

References

    1. Huang D., Swanson E. A., Lin C. P., Schuman J. S., Stinson W. G., Chang W., Hee M. R., Flotte T., Gregory K., Puliafito C. A., Fujimoto J. G., “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).10.1126/science.1957169
    1. Fercher A. F., Drexler W., Hitzenberger C. K., Lasser T., “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).10.1088/0034-4885/66/2/204
    1. Tomlins P. H., Wang R. K., “Theory, developments and applications of optical coherence tomography,” J. Phys. D Appl. Phys. 38(15), 2519–2535 (2005).10.1088/0022-3727/38/15/002
    1. Fercher A. F., Hitzenberger C. K., Drexler W., Kamp G., Sattmann H., “In vivo optical coherence tomography,” Am. J. Ophthalmol. 116(1), 113–114 (1993).
    1. Hitzenberger C. K., Trost P., Lo P. W., Zhou Q. Y., “Three-dimensional imaging of the human retina by high-speed optical coherence tomography,” Opt. Express 11(21), 2753–2761 (2003).10.1364/OE.11.002753
    1. Fercher A. F., Hitzenberger C. K., Kamp G., Elzaiat S. Y., “Measurement of intraocular distances by backscattering spectral interferometry,” Opt. Commun. 117(1-2), 43–48 (1995).10.1016/0030-4018(95)00119-S
    1. Häusler G., Lindner M. W., “Coherence radar’ and ‘spectral radar’-new tools for dermatological diagnosis,” J. Biomed. Opt. 3(1), 21–31 (1998).10.1117/1.429899
    1. Chinn S. R., Swanson E. A., Fujimoto J. G., “Optical coherence tomography using a frequency-tunable optical source,” Opt. Lett. 22(5), 340–342 (1997).10.1364/OL.22.000340
    1. Haberland U., Jansen P., Blazek V., Schmitt H. J., “Optical coherence tomography of scattering media using frequency-modulated continuous-wave techniques with tunable near-infrared laser,” Proc. SPIE 2981, 20–28 (1997).10.1117/12.274318
    1. de Boer J. F., Cense B., Park B. H., Pierce M. C., Tearney G. J., Bouma B. E., “Improved signal-to-noise ratio in spectral-domain compared with time-domain optical coherence tomography,” Opt. Lett. 28(21), 2067–2069 (2003).10.1364/OL.28.002067
    1. Choma M., Sarunic M., Yang C., Izatt J., “Sensitivity advantage of swept source and Fourier domain optical coherence tomography,” Opt. Express 11(18), 2183–2189 (2003).10.1364/OE.11.002183
    1. Leitgeb R., Hitzenberger C., Fercher A., “Performance of Fourier domain vs. time domain optical coherence tomography,” Opt. Express 11(8), 889–894 (2003).10.1364/OE.11.000889
    1. Wojtkowski M., Leitgeb R., Kowalczyk A., Bajraszewski T., Fercher A. F., “In vivo human retinal imaging by Fourier domain optical coherence tomography,” J. Biomed. Opt. 7(3), 457–463 (2002).10.1117/1.1482379
    1. Cense B., Nassif N., Chen T., Pierce M., Yun S.-H., Park B., Bouma B., Tearney G., de Boer J., “Ultrahigh-resolution high-speed retinal imaging using spectral-domain optical coherence tomography,” Opt. Express 12(11), 2435–2447 (2004).10.1364/OPEX.12.002435
    1. de Bruin D. M., Burnes D. L., Loewenstein J., Chen Y., Chang S., Chen T. C., Esmaili D. D., de Boer J. F., “In vivo three-dimensional imaging of neovascular age-related macular degeneration using optical frequency domain imaging at 1050 nm,” Invest. Ophthalmol. Vis. Sci. 49(10), 4545–4552 (2008).10.1167/iovs.07-1553
    1. Lee E. C., de Boer J. F., Mujat M., Lim H., Yun S. H., “In vivo optical frequency domain imaging of human retina and choroid,” Opt. Express 14(10), 4403–4411 (2006).10.1364/OE.14.004403
    1. Lim H., Mujat M., Kerbage C., Lee E. C., Chen Y., Chen T. C., de Boer J. F., “High-speed imaging of human retina in vivo with swept-source optical coherence tomography,” Opt. Express 14(26), 12902–12908 (2006).10.1364/OE.14.012902
    1. Wojtkowski M., Srinivasan V., Ko T., Fujimoto J., Kowalczyk A., Duker J., “Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation,” Opt. Express 12(11), 2404–2422 (2004).10.1364/OPEX.12.002404
    1. Leitgeb R., Drexler W., Unterhuber A., Hermann B., Bajraszewski T., Le T., Stingl A., Fercher A., “Ultrahigh resolution Fourier domain optical coherence tomography,” Opt. Express 12(10), 2156–2165 (2004).10.1364/OPEX.12.002156
    1. Srinivasan V. J., Huber R., Gorczynska I., Fujimoto J. G., Jiang J. Y., Reisen P., Cable A. E., “High-speed, high-resolution optical coherence tomography retinal imaging with a frequency-swept laser at 850 nm,” Opt. Lett. 32(4), 361–363 (2007).10.1364/OL.32.000361
    1. Bachmann A. H., Villiger M. L., Blatter C., Lasser T., Leitgeb R. A., “Resonant Doppler flow imaging and optical vivisection of retinal blood vessels,” Opt. Express 15(2), 408–422 (2007).10.1364/OE.15.000408
    1. An L., Wang R. K., “In vivo volumetric imaging of vascular perfusion within human retina and choroids with optical micro-angiography,” Opt. Express 16(15), 11438–11452 (2008).10.1364/OE.16.011438
    1. Vakoc B. J., Lanning R. M., Tyrrell J. A., Padera T. P., Bartlett L. A., Stylianopoulos T., Munn L. L., Tearney G. J., Fukumura D., Jain R. K., Bouma B. E., “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med. 15(10), 1219–1223 (2009).10.1038/nm.1971
    1. White B. R., Pierce M. C., Nassif N., Cense B., Park B. H., Tearney G. J., Bouma B. E., Chen T. C., de Boer J., “In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography,” Opt. Express 11(25), 3490–3497 (2003).10.1364/OE.11.003490
    1. Fingler J., Zawadzki R. J., Werner J. S., Schwartz D., Fraser S. E., “Volumetric microvascular imaging of human retina using optical coherence tomography with a novel motion contrast technique,” Opt. Express 17(24), 22190–22200 (2009).10.1364/OE.17.022190
    1. An L., Subhush H. M., Wilson D. J., Wang R. K., “High-resolution wide-field imaging of retinal and choroidal blood perfusion with optical microangiography,” J. Biomed. Opt. 15(2), 026011 (2010).10.1117/1.3369811
    1. Yu L., Chen Z., “Doppler variance imaging for three-dimensional retina and choroid angiography,” J. Biomed. Opt. 15(1), 016029 (2010).10.1117/1.3302806
    1. Szkulmowski M., Szkulmowska A., Bajraszewski T., Kowalczyk A., Wojtkowski M., “Flow velocity estimation using joint spectral and time domain optical coherence tomography,” Opt. Express 16(9), 6008–6025 (2008).10.1364/OE.16.006008
    1. Wang R. K., An L., Saunders S., Wilson D. J., “Optical microangiography provides depth-resolved images of directional ocular blood perfusion in posterior eye segment,” J. Biomed. Opt. 15(2), 020502 (2010).10.1117/1.3353958
    1. Makita S., Jaillon F., Yamanari M., Miura M., Yasuno Y., “Comprehensive in vivo micro-vascular imaging of the human eye by dual-beam-scan Doppler optical coherence angiography,” Opt. Express 19(2), 1271–1283 (2011).10.1364/OE.19.001271
    1. Makita S., Hong Y., Yamanari M., Yatagai T., Yasuno Y., “Optical coherence angiography,” Opt. Express 14(17), 7821–7840 (2006).10.1364/OE.14.007821
    1. Zotter S., Pircher M., Torzicky T., Bonesi M., Götzinger E., Leitgeb R. A., Hitzenberger C. K., “Visualization of microvasculature by dual-beam phase-resolved Doppler optical coherence tomography,” Opt. Express 19(2), 1217–1227 (2011).10.1364/OE.19.001217
    1. Tao Y. K., Kennedy K. M., Izatt J. A., “Velocity-resolved 3D retinal microvessel imaging using single-pass flow imaging spectral domain optical coherence tomography,” Opt. Express 17(5), 4177–4188 (2009).10.1364/OE.17.004177
    1. Potsaid B., Baumann B., Huang D., Barry S., Cable A. E., Schuman J. S., Duker J. S., Fujimoto J. G., “Ultrahigh speed 1050nm swept source/Fourier domain OCT retinal and anterior segment imaging at 100,000 to 400,000 axial scans per second,” Opt. Express 18(19), 20029–20048 (2010).10.1364/OE.18.020029
    1. Eigenwillig C. M., Klein T., Wieser W., Biedermann B. R., Huber R., “Wavelength swept amplified spontaneous emission source for high speed retinal optical coherence tomography at 1060 nm,” J. Biophotonics 4(7–8), 522–528 (2011).
    1. Gora M., Karnowski K., Szkulmowski M., Kaluzny B. J., Huber R., Kowalczyk A., Wojtkowski M., “Ultra high-speed swept source OCT imaging of the anterior segment of human eye at 200 kHz with adjustable imaging range,” Opt. Express 17(17), 14880–14894 (2009).10.1364/OE.17.014880
    1. Srinivasan V. J., Adler D. C., Chen Y., Gorczynska I., Huber R., Duker J. S., Schuman J. S., Fujimoto J. G., “Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head,” Invest. Ophthalmol. Vis. Sci. 49(11), 5103–5110 (2008).10.1167/iovs.08-2127
    1. Potsaid B., Gorczynska I., Srinivasan V. J., Chen Y. L., Jiang J., Cable A., Fujimoto J. G., “Ultrahigh speed spectral / Fourier domain OCT ophthalmic imaging at 70,000 to 312,500 axial scans per second,” Opt. Express 16(19), 15149–15169 (2008).10.1364/OE.16.015149
    1. Kim D. Y., Fingler J., Werner J. S., Schwartz D. M., Fraser S. E., Zawadzki R. J., “In vivo volumetric imaging of human retinal circulation with phase-variance optical coherence tomography,” Biomed. Opt. Express 2(6), 1504–1513 (2011).10.1364/BOE.2.001504
    1. Wang R. K., An L., Francis P., Wilson D. J., “Depth-resolved imaging of capillary networks in retina and choroid using ultrahigh sensitive optical microangiography,” Opt. Lett. 35(9), 1467–1469 (2010).10.1364/OL.35.001467
    1. Wieser W., Biedermann B. R., Klein T., Eigenwillig C. M., Huber R., “Multi-megahertz OCT: High quality 3D imaging at 20 million A-scans and 4.5 GVoxels per second,” Opt. Express 18(14), 14685–14704 (2010).10.1364/OE.18.014685
    1. Klein T., Wieser W., Eigenwillig C. M., Biedermann B. R., Huber R., “Megahertz OCT for ultrawide-field retinal imaging with a 1050 nm Fourier domain mode-locked laser,” Opt. Express 19(4), 3044–3062 (2011).10.1364/OE.19.003044
    1. An L., Guan G., Wang R. K., “High-speed 1310 nm-band spectral domain optical coherence tomography at 184,000 lines per second,” J. Biomed. Opt. 16(6), 060506 (2011).10.1117/1.3592492
    1. Hendargo H. C., Zhao M., Shepherd N., Izatt J. A., “Synthetic wavelength based phase unwrapping in spectral domain optical coherence tomography,” Opt. Express 17(7), 5039–5051 (2009).10.1364/OE.17.005039
    1. Jiao S. L., Knighton R., Huang X. R., Gregori G., Puliafito C. A., “Simultaneous acquisition of sectional and fundus ophthalmic images with spectral-domain optical coherence tomography,” Opt. Express 13(2), 444–452 (2005).10.1364/OPEX.13.000444

Source: PubMed

3
订阅