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Virtual Journal for Biomedical Optics

Virtual Journal for Biomedical Optics

| EXPLORING THE INTERFACE OF LIGHT AND BIOMEDICINE

  • Editor: Gregory W. Faris
  • Vol. 4, Iss. 12 — Nov. 10, 2009

Adaptive optics optical coherence tomography at 120,000 depth scans/s for non-invasive cellular phenotyping of the living human retina

Cristiano Torti, Boris Považay, Bernd Hofer, Angelika Unterhuber, Joseph Carroll, Peter Kurt Ahnelt, and Wolfgang Drexler  »View Author Affiliations


Optics Express, Vol. 17, Issue 22, pp. 19382-19400 (2009)
http://dx.doi.org/10.1364/OE.17.019382


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Abstract

This paper presents a successful combination of ultra-high speed (120,000 depth scans/s), ultra-high resolution optical coherence tomography with adaptive optics and an achromatizing lens for compensation of monochromatic and longitudinal chromatic ocular aberrations, respectively, allowing for non-invasive volumetric imaging in normal and pathologic human retinas at cellular resolution. The capability of this imaging system is demonstrated here through preliminary studies by probing cellular intraretinal structures that have not been accessible so far with in vivo, non-invasive, label-free imaging techniques, including pigment epithelial cells, micro-vasculature of the choriocapillaris, single nerve fibre bundles and collagenous plates of the lamina cribrosa in the optic nerve head. In addition, the volumetric extent of cone loss in two colour-blinds could be quantified for the first time. This novel technique provides opportunities to enhance the understanding of retinal pathogenesis and early diagnosis of retinal diseases.

© 2009 OSA

OCIS Codes
(120.3890) Instrumentation, measurement, and metrology : Medical optics instrumentation
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(170.4470) Medical optics and biotechnology : Ophthalmology
(170.4500) Medical optics and biotechnology : Optical coherence tomography
(220.1000) Optical design and fabrication : Aberration compensation
(110.1080) Imaging systems : Active or adaptive optics

ToC Category:
Medical Optics and Biotechnology

History
Original Manuscript: August 24, 2009
Revised Manuscript: September 26, 2009
Manuscript Accepted: September 28, 2009
Published: October 12, 2009

Virtual Issues
Vol. 4, Iss. 12 Virtual Journal for Biomedical Optics

Citation
Cristiano Torti, Boris Považay, Bernd Hofer, Angelika Unterhuber, Joseph Carroll, Peter Kurt Ahnelt, and Wolfgang Drexler, "Adaptive optics optical coherence tomography at 120,000 depth scans/s for non-invasive cellular phenotyping of the living human retina," Opt. Express 17, 19382-19400 (2009)
http://www.opticsinfobase.org/vjbo/abstract.cfm?URI=oe-17-22-19382


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References

  1. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, and C. A. Puliafito, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991). [CrossRef] [PubMed]
  2. E. A. Swanson, J. A. Izatt, M. R. Hee, D. Huang, C. P. Lin, J. S. Schuman, C. A. Puliafito, and J. G. Fujimoto, “In vivo retinal imaging by optical coherence tomography,” Opt. Lett. 18(21), 1864–1866 (1993). [CrossRef] [PubMed]
  3. A. F. Fercher, C. K. Hitzenberger, W. Drexler, G. Kamp, and H. Sattmann, “In vivo optical coherence tomography,” Am. J. Ophthalmol. 116(1), 113–114 (1993). [PubMed]
  4. W. Drexler, U. Morgner, R. K. Ghanta, F. X. Kärtner, J. S. Schuman, and J. G. Fujimoto, “Ultrahigh resolution ophthalmic optical coherence tomography,” Nat. Med. 24(7), 502–507 (2001). [CrossRef]
  5. 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(3), 457–463 (2002). [CrossRef] [PubMed]
  6. B. Cense, N. A. Nassif, T. C. Chen, M. C. Pierce, S. H. Yun, B. H. Park, B. E. Bouma, G. J. Tearney, and J. F. de Boer, “Ultrahigh-resolution high-speed retinal imaging using spectral-domain optical coherence tomography,” Opt. Express 12(11), 2435–2447 (2004). [CrossRef] [PubMed]
  7. M. Wojtkowski, V. J. Srinivasan, T. H. Ko, J. G. Fujimoto, A. Kowalczyk, and J. S. Duker, “Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation,” Opt. Express 12(11), 2404–2422 (2004). [CrossRef] [PubMed]
  8. M. Wojtkowski, V. Srinivasan, J. G. Fujimoto, T. Ko, J. S. Schuman, A. Kowalczyk, and J. S. Duker, “Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography,” Ophthalmology 112(10), 1734–1746 (2005). [CrossRef] [PubMed]
  9. W. Drexler and J. G. Fujimoto, “State-of-the-art retinal optical coherence tomography,” Prog. Retin. Eye Res. 27(1), 45–88 (2008). [CrossRef]
  10. J. Porter, A. Guirao, I. G. Cox, and D. R. Williams, “Monochromatic aberrations of the human eye in a large population,” J. Opt. Soc. Am. A 18(8), 1793–1803 (2001). [CrossRef]
  11. J. F. Castejón-Mochón, N. López-Gil, A. Benito, and P. Artal, “Ocular wave-front aberration statistics in a normal young population,” Vision Res. 42(13), 1611–1617 (2002). [CrossRef] [PubMed]
  12. L. N. Thibos, X. Hong, A. Bradley, and X. Cheng, “Statistical variation of aberration structure and image quality in a normal population of healthy eyes,” J. Opt. Soc. Am. A 19(12), 2329–2348 (2002). [CrossRef]
  13. J. Liang, D. R. Williams, and D. T. Miller, “Supernormal vision and high-resolution retinal imaging through adaptive optics,” J. Opt. Soc. Am. A 14(11), 2884–2892 (1997). [CrossRef]
  14. H. Hofer, L. Chen, G. Y. Yoon, B. Singer, Y. Yamauchi, and D. R. Williams, “Improvement in retinal image quality with dynamic correction of the eye’s aberrations,” Opt. Express 8(11), 631–643 (2001). [CrossRef] [PubMed]
  15. A. Roorda, F. Romero-Borja, W. Donnelly III, H. Queener, T. J. Hebert, and M. Campbell, “Adaptive optics scanning laser ophthalmoscopy,” Opt. Express 10(9), 405–412 (2002). [PubMed]
  16. W. Drexler, “Ultrahigh-resolution optical coherence tomography,” J. Biomed. Opt. 9(1), 47–74 (2004). [CrossRef] [PubMed]
  17. B. Hermann, E. J. Fernández, A. Unterhuber, H. Sattmann, A. F. Fercher, W. Drexler, P. M. Prieto, and P. Artal, “Adaptive-optics ultrahigh-resolution optical coherence tomography,” Opt. Lett. 29(18), 2142–2144 (2004). [CrossRef] [PubMed]
  18. E. J. Fernández, B. Považay, B. Hermann, A. Unterhuber, H. Sattmann, P. M. Prieto, R. Leitgeb, P. Ahnelt, P. Artal, and W. Drexler, “Three-dimensional adaptive optics ultrahigh-resolution optical coherence tomography using a liquid crystal spatial light modulator,” Vision Res. 45(28), 3432–3444 (2005). [CrossRef] [PubMed]
  19. Y. Zhang, J. Rha, R. S. Jonnal, and D. T. Miller, “Adaptive optics parallel spectral domain optical coherence tomography for imaging the living retina,” Opt. Express 13(12), 4792–4811 (2005). [CrossRef] [PubMed]
  20. R. J. Zawadzki, S. M. Jones, S. S. Olivier, M. Zhao, B. A. Bower, J. A. Izatt, S. Choi, S. Laut, and J. S. Werner, “Adaptive-optics optical coherence tomography for high-resolution and high-speed 3D retinal in vivo imaging,” Opt. Express 13(21), 8532–8546 (2005). [CrossRef] [PubMed]
  21. D. Merino, C. Dainty, A. Bradu, and A. G. Podoleanu, “Adaptive optics enhanced simultaneous en-face optical coherence tomography and scanning laser ophthalmoscopy,” Opt. Express 14(8), 3345–3353 (2006). [CrossRef] [PubMed]
  22. Y. Zhang, B. Cense, J. Rha, R. S. Jonnal, W. Gao, R. J. Zawadzki, J. S. Werner, S. Jones, S. Olivier, and D. T. Miller, “High-speed volumetric imaging of cone photoreceptors with adaptive optics spectral-domain optical coherence tomography,” Opt. Express 14(10), 4380–4394 (2006). [CrossRef] [PubMed]
  23. D. C. Chen, S. M. Jones, D. A. Silva, and S. S. Olivier, “High-resolution adaptive optics scanning laser ophthalmoscope with dual deformable mirrors,” J. Opt. Soc. Am. A 24(5), 1305–1312 (2007). [CrossRef]
  24. C. E. Bigelow, N. V. Iftimia, R. D. Ferguson, T. E. Ustun, B. Bloom, and D. X. Hammer, “Compact multimodal adaptive-optics spectral-domain optical coherence tomography instrument for retinal imaging,” J. Opt. Soc. Am. A 24(5), 1327–1336 (2007). [CrossRef]
  25. R. J. Zawadzki, S. S. Choi, S. M. Jones, S. S. Oliver, and J. S. Werner, “Adaptive optics-optical coherence tomography: optimizing visualization of microscopic retinal structures in three dimensions,” J. Opt. Soc. Am. A 24(5), 1373–1383 (2007). [CrossRef]
  26. R. J. Zawadzki, B. Cense, Y. Zhang, S. S. Choi, D. T. Miller, and J. S. Werner, “Ultrahigh-resolution optical coherence tomography with monochromatic and chromatic aberration correction,” Opt. Express 16(11), 8126–8143 (2008). [CrossRef] [PubMed]
  27. E. J. Fernández, B. Hermann, B. Považay, A. Unterhuber, H. Sattmann, B. Hofer, P. K. Anelt, and W. Drexler, “Ultrahigh resolution optical coherence tomography and pancorrection for cellular imaging of the living human retina,” Opt. Express 16, 11,083–11,094 (2008). [CrossRef]
  28. M. Pircher, R. J. Zawadzki, J. W. Evans, J. S. Werner, and C. K. Hitzenberger, “Simultaneous imaging of human cone mosaic with adaptive optics enhanced scanning laser ophthalmoscopy and high-speed transversal scanning optical coherence tomography,” Opt. Lett. 33(1), 22–24 (2008). [CrossRef]
  29. R. J. Zawadzki, S. S. Choi, A. R. Fuller, J. W. Evans, B. Hamann, and J. S. Werner, “Cellular resolution volumetric in vivo retinal imaging with adaptive optics-optical coherence tomography,” Opt. Express 17(5), 4084–4094 (2009). [CrossRef] [PubMed]
  30. B. Cense, E. Koperda, J. M. Brown, O. P. Kocaoglu, W. Gao, R. S. Jonnal, and D. T. Miller, “Volumetric retinal imaging with ultrahigh-resolution spectral-domain optical coherence tomography and adaptive optics using two broadband light sources,” Opt. Express 17(5), 4095–4111 (2009). [CrossRef] [PubMed]
  31. B. Považay, B. Hofer, C. Torti, B. Hermann, A. R. Tumlinson, M. Esmaeelpour, C. A. Egan, A. C. Bird, and W. Drexler, “Impact of enhanced resolution, speed and penetration on three-dimensional retinal optical coherence tomography,” Opt. Express 17(5), 4134–4150 (2009). [CrossRef] [PubMed]
  32. E. J. Fernández and W. Drexler, “Influence of ocular chromatic aberration and pupil size on transverse resolution in ophthalmic adaptive optics optical coherence tomography,” Opt. Express 13(20), 8184–8197 (2005). [CrossRef] [PubMed]
  33. E. J. Fernández, A. Unterhuber, P. M. Prieto, B. Hermann, W. Drexler, and P. Artal, “Ocular aberrations as a function of wavelength in the near infrared measured with a femtosecond laser,” Opt. Express 13(2), 400–409 (2005). [CrossRef] [PubMed]
  34. A. C. van Heel, “Correcting the spherical and chromatic aberrations of the eye,” J. Opt. Soc. Am. 36, 237–239 (1947).
  35. E. J. Fernández, A. Unterhuber, B. Považay, B. Hermann, P. Artal, and W. Drexler, “Chromatic aberration correction of the human eye for retinal imaging in the near infrared,” Opt. Express 14(13), 6213–6225 (2006). [CrossRef] [PubMed]
  36. E. J. Fernández, L. Vabre, B. Hermann, A. Unterhuber, B. Považay, and W. Drexler, “Adaptive optics with a magnetic deformable mirror: applications in the human eye,” Opt. Express 14(20), 8900–8917 (2006). [CrossRef] [PubMed]
  37. B. Potsaid, I. Gorczynska, V. J. Srinivasan, Y. Chen, J. Jiang, A. Cable, and J. G. Fujimoto, “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). [CrossRef] [PubMed]
  38. S. J. Fricker, “Dynamic measurements of horizontal eye motion. I. Acceleration and velocity matrices,” Invest. Ophthalmol. 10(9), 724–732 (1971). [PubMed]
  39. A. Unterhuber, B. Považay, B. Hermann, H. Sattmann, W. Drexler, V. Yakovlev, G. Tempea, C. Schubert, E. M. Anger, P. K. Ahnelt, M. Stur, J. E. Morgan, A. Cowey, G. Jung, T. Le, and A. Stingl, “Compact, low-cost Ti:Al2O3 laser for in vivo ultrahigh-resolution optical coherence tomography,” Opt. Lett. 28(11), 905–907 (2003). [CrossRef] [PubMed]
  40. B. Hofer, B. Považay, B. Hermann, A. Unterhuber, G. Matz, and W. Drexler, “Dispersion encoded full range frequency domain optical coherence tomography,” Opt. Express 17(1), 7–24 (2009). [CrossRef] [PubMed]
  41. “Safe Use of Lasers” by American National Standard Institute (New York, 2000).
  42. M. Shensa, “The discrete wavelet transform: wedding the a trous and Mallat algorithms,” IEEE Trans. Signal Process. 40(10), 2464–2482 (1992). [CrossRef]
  43. O. Marchal, and J. Mutterer, A trous filter plug-in for ImageJ, IBMP-CNRS Strasbourg France, http://rsbweb.nih.gov/ij/plugins/download/A_trous_filter.java , 2005.
  44. P. Thevenaz, U. E. Ruttimann, and M. Unser, “A pyramid approach to subpixel registration based on intensity,” IEEE Trans. Image Process. 7(1), 27–41 (1998). [CrossRef]
  45. P. Thevenaz, StackReg plug-in for ImageJ, EPFL/STI/IOA/LIB, Bldg. BM-Ecublens 4.137, Station 17, CH-1015 Lausanne VD, Switzerland, http://bigwww.epfl.ch/thevenaz/stackreg , 2005.
  46. The Find maxima feature is a built-in tool of ImageJ and can be found in the Binary category of options in the Process tab.
  47. J. I. Yellott., “Spectral analysis of spatial sampling by photoreceptors: topological disorder prevents aliasing,” Vision Res. 22(9), 1205–1210 (1982). [CrossRef] [PubMed]
  48. N. J. Coletta and D. R. Williams, “Psychophysical estimate of extrafoveal cone spacing,” J. Opt. Soc. Am. A 4(8), 1503–1513 (1987). [CrossRef] [PubMed]
  49. R. C. Baraas, J. Carroll, K. L. Gunther, M. Chung, D. R. Williams, D. H. Foster, and M. Neitz, “Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision deficiency,” J. Opt. Soc. Am. A 24(5), 1438–1447 (2007). [CrossRef]
  50. J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In vivo autofluorescence imaging of the human and macaque retinal pigment epithelial cell mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2008). [CrossRef] [PubMed]
  51. J. Carroll, M. Neitz, H. Hofer, J. Neitz, and D. R. Williams, “Functional photoreceptor loss revealed with adaptive optics: an alternate cause of color blindness,” Proc. Natl. Acad. Sci. U.S.A. 101(22), 8461–8466 (2004). [CrossRef] [PubMed]
  52. C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human photoreceptor topography,” J. Comp. Neurol. 292(4), 497–523 (1990). [CrossRef] [PubMed]
  53. J. Carroll, R. C. Baraas, J. I. W. Morgan, D. R. Williams, D. H. Foster, and M. Neitz, “Expression of C203R mutant cone pigment results in cone degeneration,” Invest. Ophthalmol. Vis. Sci. 48(Suppl.), 3814 (2007).
  54. G. S. Hagerman, and L. V. Johnson, “The photoreceptor-retinal pigmented epithelium interface,” in Principles and Practice of Clinical Electrophysiology of Vision, J.R. Heckenlively and G.B. Arden eds. (Mosby Year Book, St. Louis, 1991).
  55. A. M. Harman, P. A. Fleming, R. V. Hoskins, and S. R. Moore, “Development and aging of cell topography in the human retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci. 38(10), 2016–2026 (1997). [PubMed]
  56. H. Gao and J. G. Hollyfield, “Aging of the human retina. Differential loss of neurons and retinal pigment epithelial cells,” Invest. Ophthalmol. Vis. Sci. 33(1), 1–17 (1992). [PubMed]
  57. D. S. McLeod and G. A. Lutty, “High-resolution histologic analysis of the human choroidal vasculature,” Invest. Ophthalmol. Vis. Sci. 35(11), 3799–3811 (1994). [PubMed]
  58. A. Kotecha, S. Izadi, and G. Jeffery, “Age-related changes in the thickness of the human lamina cribrosa,” Br. J. Ophthalmol. 90(12), 1531–1534 (2006). [CrossRef] [PubMed]
  59. P. K. Ahnelt, “The photoreceptor mosaic,” Eye 12(Pt 3b), 531–540 (1998). [CrossRef] [PubMed]
  60. Q. V. Hoang, R. A. Linsenmeier, C. K. Chung, and C. A. Curcio, “Photoreceptor inner segments in monkey and human retina: mitochondrial density, optics, and regional variation,” Vis. Neurosci. 19(4), 395–407 (2002). [CrossRef]
  61. M. F. Cordeiro, L. Guo, V. Luong, G. Harding, W. Wang, H. E. Jones, S. E. Moss, A. M. Sillito, and F. W. Fitzke, “Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration,” Proc. Natl. Acad. Sci. U.S.A. 101(36), 13352–13356 (2004). [CrossRef] [PubMed]
  62. D. C. Gray, W. Merigan, J. I. Wolfing, B. P. Gee, J. Porter, A. Dubra, T. H. Twietmeyer, K. Ahamd, R. Tumbar, F. Reinholz, and D. R. Williams, “In vivo fluorescence imaging of primate retinal ganglion cells and retinal pigment epithelial cells,” Opt. Express 14(16), 7144–7158 (2006). [CrossRef] [PubMed]
  63. A. Roorda, Y. Zhang, and J. L. Duncan, “High-resolution in vivo imaging of the RPE mosaic in eyes with retinal disease,” Invest. Ophthalmol. Vis. Sci. 48(5), 2297–2303 (2007). [CrossRef] [PubMed]
  64. H. A. Quigley, R. W. Flower, E. M. Addicks, and D. S. McLeod, “The mechanism of optic nerve damage in experimental acute intraocular pressure elevation,” Invest. Ophthalmol. Vis. Sci. 19(5), 505–517 (1980). [PubMed]
  65. A. S. Vilupuru, N. V. Rangaswamy, L. J. Frishman, E. L. Smith, R. S. Harwerth, and A. Roorda, “Adaptive optics scanning laser ophthalmoscopy for in vivo imaging of lamina cribrosa,” J. Opt. Soc. Am. A 24(5), 1417–1425 (2007). [CrossRef]
  66. V. J. Srinivasan, D. C. Adler, Y. Chen, I. Gorczynska, R. Huber, J. S. Duker, J. S. Schuman, and J. G. Fujimoto, “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). [CrossRef] [PubMed]
  67. F. C. Delori, R. H. Webb, and D. H. Sliney, “Maximum permissible exposures for ocular safety (ANSI 2000), with emphasis on ophthalmic devices,” J. Opt. Soc. Am. A 24(5), 1250–1265 (2007). [CrossRef]
  68. L. Diaz-Santana, C. Torti, I. Munro, P. Gasson, and C. Dainty, “Benefit of higher closed-loop bandwidths in ocular adaptive optics,” Opt. Express 11(20), 2597–2605 (2003). [CrossRef] [PubMed]

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