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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. 2, Iss. 1 — Jan. 19, 2007
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Hybrid retinal imager using line-scanning laser ophthalmoscopy and spectral domain optical coherence tomography

Nicusor V. Iftimia, Daniel X. Hammer, Chad E. Bigelow, Teoman Ustun, Johannes F. de Boer, and R. Daniel Ferguson  »View Author Affiliations


Optics Express, Vol. 14, Issue 26, pp. 12909-12914 (2006)
http://dx.doi.org/10.1364/OE.14.012909


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Abstract

We demonstrate for the first time the integration of two technologies, Spectral Domain Optical Coherence Tomography (SDOCT) and Line-Scanning Laser Ophthalmoscopy (LSLO) into a single compact instrument that shares the same imaging optics and line scan camera for both OCT and LSLO imaging. Co-registered high contrast wide-field en face retinal LSLO and SDOCT images are obtained non-mydriatically with less than 600 microwatts of broadband illumination at 15 frames/sec. The LSLO/SDOCT hybrid instrument could have important applications in clinical ophthalmic diagnostics and emergency medicine.

© 2006 Optical Society of America

1. Introduction

Optical coherence tomography (OCT) is an emerging technology for micrometer-scale, cross-sectional imaging of biological tissue and materials.[1

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, 1178–1181 (1991). [CrossRef] [PubMed]

] A major application of optical coherence tomography (OCT) is ophthalmic imaging of the human retina in vivo.[2

2. N. Nassif, B. Cense, B. Park, M. Pierce, S. Yun, B. Bouma, G. Tearney, T. Chen, and J. de Boer, “In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve,” Opt. Express 12, 367–376 (2004). [CrossRef] [PubMed]

,3

3. R. Leitgeb, L. Schmetterer, W. Drexler, and A. Fercher, “Real-time assessment of retinal blood flow with ultrafast acquisition by color doppler fourier domain optical coherence tomography,” Opt. Express 11, 3116–3121 (2003). [CrossRef] [PubMed]

] The Spectral-Domain OCT (SDOCT) improvement of the traditional time domain OCT (TDOCT) technique, known also as Fourier domain OCT (FDOCT), makes this technology suitable for real-time cross-sectional retinal imaging at video rate. [4–8

4. 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, 2435–2447 (2004). [CrossRef] [PubMed]

]. At high speed, the need for vertical realignment of “A-scan” depth profiles is effectively eliminated across single B-scans, revealing a truer representation of retinal topography and the optic nerve head. Although B-scan image distortion by involuntary eye movement is reduced, transverse eye motion remains an issue for 3-D imaging and individual scan registration.[9

9. Daniel X. Hammer, R. Daniel Ferguson, Teoman E. Ustun, Chad E. Bigelow, Nicusor V. Iftimia, and Robert H. Webb, “Line-scanning laser ophthalmoscope”, J. Biomed. Opt. 11, 041126(1–10), (2006). [CrossRef] [PubMed]

,10

10. D. X. Hammer, R. D. Ferguson, J. C. Magill, M. A. White, A. E. Elsner, and R. H. Webb, “Image stabilization for scanning laser ophthalmoscopy,” Opt. Express 10, 1542–1549 (2002). [PubMed]

] On the expense of higher complexity, stabilized 3D OCT imaging [11

11. D. Hammer, R. D. Ferguson, N. Iftimia, T. Ustun, G. Wollstein, H. Ishikawa, M. Gabriele, W. Dilworth, L. Kagemann, and J. Schuman, “Advanced scanning methods with tracking optical coherence tomography,” Opt. Express 13, 7937–7947 (2005). [CrossRef] [PubMed]

,12

12. N. V. Iftimia, D. X. Hammer, C. E. Bigelow, D. I. Rosen, T. Ustun, A. A. Ferrante, D. Vu, and R. D. Ferguson, “Toward noninvasive measurement of blood hematocrit using spectral domain low coherence interferometry and retinal tracking,” Opt. Express 14, 3377–88(2006). [CrossRef] [PubMed]

] can provide an en face fundus views for locating any given B-scan relative to retinal landmarks. Alternatively, simultaneous or interleaved live fundus imaging can also provide good retinal coordinates for a given B-scan, subject to the limitations of inter-frame eye motion. Work performed by Podoleanu’s group [13

13. A.G. Podoleanu, G.M. Dobre, R.C. Cucu, R.B. Rosen, P. Garcia, J. Nieto, D. Will, R. Gentile, T. Muldoon, J. Walsh, L.A. Yannuzzi, Y. Fisher, D. Orlock, R. Weitz, J.A. Rogers, S. Dunne, and A. Boxer, “Combined multiplanar optical coherence tomography and confocal scanning ophthalmoscopy”, J Biomed Opt. 9, 86–93 (2004). [CrossRef] [PubMed]

] shows that scanning transversal SLO/OCT imaging techniques can also accomplish en face and B-scan co-registration directly, although with more complex instrumentation.

The fusion of wide-field, line scanning laser ophthalmoscope (LSLO) retinal imaging with SDOCT imaging can enhance the clinician’s ability to quickly assess pathologies in linked, complementary views with a simple, compact instrument. As will be seen, this concept evolved naturally from the like requirements of the LSLO and SDOCT imaging instruments (e.g., both require a linear array detector, both use galvanometers for transverse scanning, both operate at tens of kHz line rates, with similar optical power and bandwidth requirements, etc.). In order to make the ocular interface of future SDOCT systems more efficient, cost-effective, compact, and eventually field portable, neither complex motion stabilization systems nor optomechanical integration of secondary fundus cameras is desirable. Yet without precise knowledge of the OCT scan coordinates within the live fundus image to guide scan acquisition and interpretation, the diagnostic utility of this powerful imaging modality is limited.

In this paper we present a novel integration method for real-time LSLO-SDOCT image co-registration using a relatively simple optical scheme that shares the same imaging optics and line scan camera for both imaging modalities. OCT and LSLO interleaved images are obtained at 15 frames/second. The short time interval between LSLO and SDOCT scans minimize registration errors.

2. Methods and materials

A simplified schematic of our proposed approach is shown in Figure 1. The same scanning lenses, imaging lenses and linear array detector are used for the acquisition of both LSLO and OCT images.

The SDOCT portion of the system shares most of the LSLO parts: the SDOCT spectrometer shares the same imaging lens system and array detector with the LSLO system; and the sample arm of the SDOCT system shares the same scanning lenses. The separation of the LSLO and OCT beam input paths (via BC) is accomplished using two identical dichroic mirrors, one mounted on scanner (DGx) and one in a fixed position (D). The LSLO uses only one scanner (Gy) to generate a raster, while the SDOCT can use one or both scanners to generate arbitrarily oriented cross-sectional or raster images. During the LSLO portion of scan DGx is fixed. The SDOCT signal beam path de-scans to the SLD fiber and the LSLO signal beam de-scans to the linear array.

The instrument can run in three modes: LSLO mode only, OCT mode only, and frame-interleaved LSLO/SDOCT mode. No moving parts are required to change imaging modes: a simple software switch controls the hardware configuration for each imaging mode “on the fly”. When switched, the desired source is turned on (and the other off) and the camera gain is changed if necessary, as are the transverse scan parameters of the data acquisition card. Thus, the LSLO and SDOCT systems are integrated in a unique manner with a common detection path that conserves sub-system capabilities and minimizes size, cost, and complexity.

Fig. 1. Schematic of the hybrid LSLO/SD-OCT approach.

A schematic of the command lines, imaging raster, and timing sequence are shown in Figure 2.

Fig. 2. Hybrid timing. (a) Instrumentation, (b) Example of raster scan, and (c) frame timing diagram.

Based on the above mentioned approach we have built a preliminary benchtop version of the LSLO/SDOCT system. A picture of this system is shown in Figure 3. A broadband super-luminescent diode (SLD-37MP, Superlum-Russia) with 830 nm central wavelength and approximately 50 nm bandwidth is used as OCT light source. A 920 nm SLD (QSDM-920-2, Q-Photonics) with about 35 nm FWHM and 2 mW output power is used for LSLO imaging. Custom designed objectives that include meniscus lenses to control field flatness and chromatic aberration are used for the scan lens system, imaging lens system, and OCT collimators. Short focal length scan and ophthalmoscopic lenses are used to reduce system dimensions and susceptibility to reflections.

Fig. 3. (a). Photograph of the LSLO/SDOCT system. (b). Photograph detail showing most of the major parts of the LSLO/SDOCT system.

The graphical user interface for the system is shown in Fig. 4. The LSLO and SDOCT images are displayed separately or simultaneously (depending on the imaging mode), and the SDOCT scan can be positioned anywhere in the LSLO raster (see the yellow line). Other controls for SDOCT processing, display, and saving or streaming to disk are in a tab box at the bottom. The raw spectrum and processed profile are shown below the images and the integrated fixation target is also displayed.

3. Results and discussion

Fig. 4. Graphical user interface (GUI) of the LSLO/SDOCT system

In order to achieve the optimal resolution OCT images consistent with the light source bandwidth, it was necessary to carefully compensate the dispersion between the two arms of the interferometer. The standard technique balances the dispersion of the sample by adding a dispersive material in the reference arm. However, this correction technique might provide sub-optimal compensation of dispersion and requires adjustment from one sample to another. Our numeric dispersion algorithm enables automatic dispersion correction of depth reflectivity profiles at different positions with the eye. A detailed description of this algorithm is presented elsewhere. [12

12. N. V. Iftimia, D. X. Hammer, C. E. Bigelow, D. I. Rosen, T. Ustun, A. A. Ferrante, D. Vu, and R. D. Ferguson, “Toward noninvasive measurement of blood hematocrit using spectral domain low coherence interferometry and retinal tracking,” Opt. Express 14, 3377–88(2006). [CrossRef] [PubMed]

].

Preliminary cross-sectional retinal OCT images acquired from the hybrid system are presented in Fig. 5 The cross-sectional image was obtained over 5 mm transverse scan range and includes 1024 A-lines. Each processed A-line has 512 pixels. The dynamic range within the image was approximately 44 dB. Most of the anatomic layers can be recognized in these images. It is to be noted that the external limiting membrane (ELM) can be clearly seen over the whole width of the image. This layer is in general not visible if dispersion correction is not performed properly.

Fig. 5. Preliminary SDOCT retinal cross-sectional scans acquired from the system. (a) Single image, (b) Composite image averaged from 20 single frames. NFL: nerve fiber layers, GCL: ganglion cell layer, IPL: inner plexiform layer, INL: inner nuclear layer, OPL: outer plexiform layer, ONL: outer nuclear layer, ELM: external limiting membrane, CC: connecting cilia between photoreceptor inner and outer segments, RPE: retinal pigment epithelium, C: choriocapillaris and choroid.

We have carefully designed our OCT system to provide good sensitivity, over 95dB, which has proven capable of letting us see the most important anatomical features within the retina. Inherent losses on all optical elements, especially on the dichroic mirrors (about 10%), have some impact on the system’s sensitivity. The LSLO mode sensitivity is affected as well by the wavelength dependent losses on the dichroic mirrors. Fortunately, LSLO imaging tolerates this loss since LSLO power is well bellow the ANSI limit and therefore a slight increase in the power can compensate these losses. However, we regard the simplicity of the optical layout and its compactness as net benefits which more than compensate other limitations. Future work will also focus on minimizing losses with new sources and improved custom optical coatings.

4. Conclusions

In conclusion, we have demonstrated that real-time interleaved SDOCT imaging and wide-field LSLO fundus imaging with a compact, single sensor design is possible. Both imaging modalities are necessary to provide to the clinician the optimal diagnostic information. The more conventional en face LSLO view of the entire retina provides the bigger picture on global ocular health and orientation, while the cross-sectional OCT view provides a high resolution detail of retinal layers and cellular and sub-cellular structures in a region of interest. By overlaying fiducial lines or boxes over the live LSLO image display, the position and orientation of the SDOCT scan(s) to be captured in the subsequent frame can be precisely scaled and oriented to show retinal features at the desired location and resolution.

In future work, improved spectrometer and high throughput optical design will be used to improve the imaging resolution as well as the dynamic range and the imaging depth. Higher frame-rate and more flexible image acquisition and processing systems are currently in development. More intuitive LSLO registration and novel SDOCT imaging modalities will be integrated simply by creating new scan configurations with corresponding overlays. For example, local 3D image capture and display of very small features or lesions is possible. Small square “micro-rasters” can be captured in real time with many small amplitude scans instead of single long linear scan, and displayed together as one composite B-scan for high-resolution SDOCT representation of compact volumes. Such an approach would be ideal for elucidating columnar lesions due to laser damage or other localized pathology.

Acknowledgments

This work was supported by Air Force contract FA9550-05-C-0181 and NIH grant R44 NR009866-02.

References and links

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, 1178–1181 (1991). [CrossRef] [PubMed]

2.

N. Nassif, B. Cense, B. Park, M. Pierce, S. Yun, B. Bouma, G. Tearney, T. Chen, and J. de Boer, “In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve,” Opt. Express 12, 367–376 (2004). [CrossRef] [PubMed]

3.

R. Leitgeb, L. Schmetterer, W. Drexler, and A. Fercher, “Real-time assessment of retinal blood flow with ultrafast acquisition by color doppler fourier domain optical coherence tomography,” Opt. Express 11, 3116–3121 (2003). [CrossRef] [PubMed]

4.

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, 2435–2447 (2004). [CrossRef] [PubMed]

5.

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]

6.

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). [CrossRef] [PubMed]

7.

J.F. de Boer, B. Cense, and B.H. Park et al., “Improved signal-to-noise ratio in spectral-domain compared with timedomain optical coherence tomography,” Opt. Lett. 28, 2067–2069 (2003). [CrossRef] [PubMed]

8.

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). [CrossRef] [PubMed]

9.

Daniel X. Hammer, R. Daniel Ferguson, Teoman E. Ustun, Chad E. Bigelow, Nicusor V. Iftimia, and Robert H. Webb, “Line-scanning laser ophthalmoscope”, J. Biomed. Opt. 11, 041126(1–10), (2006). [CrossRef] [PubMed]

10.

D. X. Hammer, R. D. Ferguson, J. C. Magill, M. A. White, A. E. Elsner, and R. H. Webb, “Image stabilization for scanning laser ophthalmoscopy,” Opt. Express 10, 1542–1549 (2002). [PubMed]

11.

D. Hammer, R. D. Ferguson, N. Iftimia, T. Ustun, G. Wollstein, H. Ishikawa, M. Gabriele, W. Dilworth, L. Kagemann, and J. Schuman, “Advanced scanning methods with tracking optical coherence tomography,” Opt. Express 13, 7937–7947 (2005). [CrossRef] [PubMed]

12.

N. V. Iftimia, D. X. Hammer, C. E. Bigelow, D. I. Rosen, T. Ustun, A. A. Ferrante, D. Vu, and R. D. Ferguson, “Toward noninvasive measurement of blood hematocrit using spectral domain low coherence interferometry and retinal tracking,” Opt. Express 14, 3377–88(2006). [CrossRef] [PubMed]

13.

A.G. Podoleanu, G.M. Dobre, R.C. Cucu, R.B. Rosen, P. Garcia, J. Nieto, D. Will, R. Gentile, T. Muldoon, J. Walsh, L.A. Yannuzzi, Y. Fisher, D. Orlock, R. Weitz, J.A. Rogers, S. Dunne, and A. Boxer, “Combined multiplanar optical coherence tomography and confocal scanning ophthalmoscopy”, J Biomed Opt. 9, 86–93 (2004). [CrossRef] [PubMed]

OCIS Codes
(120.3890) Instrumentation, measurement, and metrology : Medical optics instrumentation
(170.0170) Medical optics and biotechnology : Medical optics and biotechnology

ToC Category:
Medical Optics and Biotechnology

History
Original Manuscript: October 13, 2006
Revised Manuscript: December 8, 2006
Manuscript Accepted: December 15, 2006
Published: December 22, 2006

Virtual Issues
Vol. 2, Iss. 1 Virtual Journal for Biomedical Optics

Citation
Nicusor V. Iftimia, Daniel X. Hammer, Chad E. Bigelow, Teoman Ustun, Johannes F. de Boer, and R. D. Ferguson, "Hybrid retinal imager using line-scanning laser ophthalmoscopy and spectral domain optical coherence tomography," Opt. Express 14, 12909-12914 (2006)
http://www.opticsinfobase.org/vjbo/abstract.cfm?URI=oe-14-26-12909


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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, C. A. Puliafito, "Optical coherence tomography," Science 254, 1178-1181 (1991). [CrossRef] [PubMed]
  2. N. Nassif, B. Cense, B. Park, M. Pierce, S. Yun, B. Bouma, G. Tearney, T. Chen, and J. de Boer, "In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve," Opt. Express 12, 367-376 (2004). [CrossRef] [PubMed]
  3. R. Leitgeb, L. Schmetterer, W. Drexler, A. Fercher, "Real-time assessment of retinal blood flow with ultrafast acquisition by color doppler fourier domain optical coherence tomography," Opt. Express 11, 3116-3121 (2003). [CrossRef] [PubMed]
  4. 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, 2435-2447 (2004). [CrossRef] [PubMed]
  5. M. Wojtkowski, T. Bajraszewski, P. Targowski, A. Kowalczyk, "Real-time in vivo imaging by high-speed spectral optical coherence tomography," Opt. Lett. 28, 1745-1747 (2003). [CrossRef] [PubMed]
  6. 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). [CrossRef] [PubMed]
  7. J.F. de Boer, B. Cense, B.H. Park,  et al., "Improved signal-to-noise ratio in spectral-domain compared with timedomain optical coherence tomography," Opt. Lett. 28, 2067-2069 (2003). [CrossRef] [PubMed]
  8. 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). [CrossRef] [PubMed]
  9. Daniel X. Hammer, R. Daniel Ferguson,Teoman E. Ustun, Chad E. Bigelow, Nicusor V . Iftimia, and Robert H. Webb, "Line-scanning laser ophthalmoscope", J. Biomed. Opt. 11, 041126, (2006). [CrossRef] [PubMed]
  10. D. X. Hammer, R. D. Ferguson, J. C. Magill, M. A. White, A. E. Elsner, and R. H. Webb, "Image stabilization for scanning laser ophthalmoscopy," Opt. Express 10, 1542-1549 (2002). [PubMed]
  11. D. Hammer, R. D. Ferguson, N. Iftimia, T. Ustun, G. Wollstein, H. Ishikawa, M. Gabriele, W. Dilworth, L. Kagemann, and J. Schuman, "Advanced scanning methods with tracking optical coherence tomography," Opt. Express 13, 7937-7947 (2005). [CrossRef] [PubMed]
  12. N. V. Iftimia, D. X. Hammer, C. E. Bigelow, D. I. Rosen, T. Ustun, A. A. Ferrante, D. Vu, and R. D. Ferguson, "Toward noninvasive measurement of blood hematocrit using spectral domain low coherence interferometry and retinal tracking," Opt. Express 14, 3377-88(2006). [CrossRef] [PubMed]
  13. A.G. Podoleanu, G.M. Dobre, R.C. Cucu, R.B. Rosen, P. Garcia, J. Nieto, D. Will, R. Gentile, T. Muldoon, J. Walsh, L.A. Yannuzzi, Y. Fisher, D. Orlock, R. Weitz, J.A. Rogers, S. Dunne, A. Boxer, "Combined multiplanar optical coherence tomography and confocal scanning ophthalmoscopy", J Biomed Opt. 9, 86-93 (2004). [CrossRef] [PubMed]

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