Ultrahigh speed volumetric ophthalmic OCT imaging at 850nm and 1050nm

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Ultrahigh speed volumetric ophthalmic OCT imaging at 850nm and 1050nm The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation As Published Publisher Benjamin Potsaid ; Jonathan Liu ; Varsha Manjunath ; Iwona Gorczynska ; Vivek J. Srinivasan ; James Jiang ; Scott Barry ; Alex Cable ; Jay S. Duker ; James G. Fujimoto; Ultrahigh-speed volumetric ophthalmic OCT imaging at 850nm and 1050nm. Proc. SPIE 7550, Ophthalmic Technologies XX, 75501K (March 02, 2010). SPIE 2010 http://dx.doi.org/10.1117/12.842846 SPIE Version Final published version Accessed Wed Dec 20 08:00:56 EST 2017 Citable Link Terms of Use Detailed Terms http://hdl.handle.net/1721.1/73961 Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.

Ultrahigh speed volumetric ophthalmic OCT imaging at 850nm and 1050nm Benjamin Potsaid 1,3, Jonathan Liu 1, Varsha Manjunath 2, Iwona Gorczynska 1,2, Vivek J. Srinivasan 1, James Jiang 3, Scott Barry 3, Alex Cable 3, Jay S. Duker 2, and James G. Fujimoto 1,2 1 Department of Electrical Engineering and Computer Science, and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139 2 New England Eye Center and Tufts Medical Center, Tufts University, Boston, MA 3 Advanced Imaging Group Thorlabs, Inc., Newton, NJ 07860 ABSTRACT The performance and imaging characteristics of ultrahigh speed ophthalmic optical coherence tomography (OCT) are investigated. In vivo imaging results are obtained at 850nm and 1050nm using different configurations of spectral and swept source / Fourier domain OCT. A spectral / Fourier domain instrument using a high speed CMOS linescan camera with SLD light source centered at 850nm achieves speeds of 91,000 axial scans per second with 3um axial resolution in tissue. A spectral / Fourier domain instrument using an InGaAs linescan camera with SLD light source centered at 1050nm achieves 47,000 axial scans per second with 7um resolution in tissue. A swept source instrument using a novel wavelength swept laser light source centered at 1050nm achieves 100,000 axial scans per second. Retinal diseases seen in the clinical setting are imaged using the 91kHz 850nm CMOS camera and 47kHz 1050nm InGaAs camera based instruments to investigate the combined effects of varying speed, axial resolution, center wavelength, and instrument sensitivity on image quality. The novel 1050nm swept source / Fourier domain instrument using a recently developed commercially available short cavity laser source images at 100,000 axial scans per second and is demonstrated in the normal retina. The dense 3D volumetric data sets obtained with ultrahigh speed OCT promise to improve reproducibility of quantitative measurements, enabling early diagnosis as well as more sensitive assessment of disease progression and response to therapy. Keywords: Ultrahigh Speed Optical Coherence Tomography; Spectral and Swept Source / Fourier Domain OCT; Ophthalmology; Retina, Fovea and Optic Nerve Head; Medical and biological imaging. 1. INTRODUCTION Optical Coherence Tomography (OCT) 1 is an imaging technology that allows for non-invasive and in vivo imaging of the human retina. Interferometric detection of backscattered light from the sample achieves micron level resolution imaging with high sensitivity and large dynamic range. Imaging with OCT enables 2D and 3D visualization of the retina, which facilitates the detection and monitoring of retinal pathologies, as well as monitoring of response to therapy. 2 The first implementations of OCT operated with time domain detection, 3 5 however more recent Fourier domain detection techniques offer a significant speed and sensitivity advantage. Fourier domain OCT imaging can be performed with a spectrometer based 6, 7 or swept laser source based 8, 9 OCT imaging system. Most demonstrations 10 13 of spectral / Fourier domain OCT imaging in the human eye have imaged at approximately 25,000-29,000 axial scans per second. Swept source ophthalmic imaging has been demonstrated in research systems with axial scan rates in the 10kHz - 40kHz range. Examples of such Send correspondence to J.G.F. at jgfuji@mit.edu I.G. now at Institute of Physics, Nicolaus Copernicus University, ul. Grudziadzka 5/7, 87-100 Torun, Poland V.J.S. now at Photon Migration Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, Massachusetts 02129 Ophthalmic Technologies XX, edited by Fabrice Manns, Per G. Söderberg, Arthur Ho, Proc. of SPIE Vol. 7550, 75501K 2010 SPIE CCC code: 1605-7422/10/$18 doi: 10.1117/12.842846 Proc. of SPIE Vol. 7550 75501K-1

demonstrations include systems with an axial scan rate of 18.8kHz centered at 1050nm, 14 43.2kHz at 855nm, 15 43kHz at 840nm, 16 16kHz at 850nm, 17 and 30kHz at 1050nm. 18 Current commercially available ophthalmic OCT imaging systems operate using spectral / Fourier domain detection and image at comparable speeds of 25-50kHz. These speeds are not yet fast enough to obtain dense 3D imaging of the retina due to patient eye movements and blinking, which impose an upper limit on image acquisition times. Recent advances in high speed linescan camera technology and wavelength swept laser light sources have led to the development of a new class of ultrahigh speed OCT instrumentation that can perform in vivo retinal imaging at speeds 2-10 times faster than commercially available systems. Ultrahigh speed spectral / Fourier domain OCT retinal imaging of a normal eye has recently been demonstrated at speeds up to 312,500 axial scans per second using a high speed CMOS linescan camera 19 at 800nm wavelengths. Ultrahigh speed swept source / Fourier domain OCT retinal imaging of a normal eye was also recently performed using a Fourier domain model locked (FDML) laser operating at 1050nm with an axial scan rate of 236kHz 20 and at 1060nm with an axial scan rate of 249kHz. 21 Imaging at longer 1050nm wavelengths may offer advantages in terms of increased tissue 22, 23 penetration. However, the relatively narrow width of the water absorption window in the eye at 1050nm limits the maximum bandwidth of the light that can be used. Thus, 850nm imaging is able to achieve finer axial resolutions in tissue. This paper investigates high speed OCT imaging of the human retina in vivo. Representative pathologies are imaged using spectral / Fourier domain OCT with a CMOS linescan camera based instrument operating at 91kHz with light source centered at 850nm and with an InGaAS linescan camera based instrument operating at 47kHz with light source centered at 1050nm. The faster speed of the CMOS linescan camera based instrument enables acquisition of greater lateral sample density 3D volumes when compared to the InGaAs linescan camera based instrument. However, the InGaAs linescan camera based instrument achieves higher sensitivity and improved penetration into retinal tissue. A novel swept source / Fourier domain OCT instrument based on a newly developed commercially available frequency swept laser technology is also presented for the first time. The light source is based on a short cavity laser operating at 100kHz and centered at 1050nm. This new instrument is evaluated in a normal eye and achieves high sensitivity with long imaging range. 2. CLINICAL IMAGING WITH SPECTRAL / FOURIER DOMAIN OCT AT 850nm AND 1050nm OCT imaging was performed on selected patients in the ophthalmology clinic at the New England Eye Center, Tufts Medical Center, Boston, MA using the spectral / Fourier domain OCT imaging systems at 850nm and 1050nm. Using a multiplexed SLD light source (Exalos AG) and high speed CMOS linescan camera (Basler AG), the 850nm system operates at 91,000 axial scans per second to achieve 3um axial resolution in tissue with 92dB sensitivity. A more detailed description of a study using the Basler Sprint linescan camera for ultrahigh speed ophthalmic imaging of normal eyes can be found in a previously published paper. 19 Using a single SLD light source (Superlum) and high speed InGaAs linescan camera (Sensors Unlimited Inc, Goodrich), the 1050nm system operates at 47,000 axial scans per second to achieve 7um axial resolution in tissue with 105dB sensitivity (measured in air without equivalent water attenuation of the eye). A more detailed description of this system can be found in a previously published paper. 24 The prototype ophthalmic OCT imaging systems were used to acquire images of the macula and optic disc in the human retina. Study protocols were approved by the investigational review boards (IRB) of the Massachusetts Institute of Technology and Tufts Medical Center. Written informed consent was obtained prior to the study. Retinal imaging was performed with an incident average power of 750μW for the 850nm system and 1.8mW for the 1050nm system, consistent with safe retinal exposure as determined by the American National Standards Institute (ANSI) 25 and with exposure levels used in commercial ophthalmic OCT imaging instruments. Imaging was performed using several different scanning and acquisition protocols, as described for each data set below. Figure 1 demonstrates images obtained with the 850nm spectral / Fourier domain OCT imaging system using the high speed CMOS linescan camera. Images from patient A (Right eye of a 67 year old subject diagnosed with multifocal choroiditis) are shown in Figs. 1(A1-A12) and are extracted from a 400x400 axial scan volume acquired in 2.2 seconds. Images from patient B (Left eye of a 79 year old subject with a posterior vitreous Proc. of SPIE Vol. 7550 75501K-2

6mm (400 pixels) A1 A2 6mm (500 pixels) B1 B2 6mm (400 pixels) C1 C2 6mm (400 pixels) 6mm (180 pixels) 6mm (400 pixels) A3 A4 A5 A6 A7 A8 A9 A10 A11 A12 400 x 400 axial scans acquired in 2.2 seconds B3 B4 B5 B6 B7 B8 B9 B10 B11 B12 500 x 180 axial scans acquired in 1.2 seconds C3 C4 C5 C6 C7 C8 C9 C10 C11 C12 400 x 400 axial scans acquired in 2.2 seconds Figure 1: Pathologies from patients A, B and C imaged with the 91kHz axial scan rate 850nm wavelength CMOS linescan camera based spectral / Fourier domain instrument. (A1) OCT fundus image of patient A diagnosed with multifocal choroiditis. (A2) Y-Z and (A3)-(A12) X-Z cross sectional images of patient A extracted from a 500x180 axial scan volume. (B1) OCT fundus image of patient B with a posterior vitreous detachment (PVD). (B2) Y-Z and (B3)-(B12) X-Z cross sectional images of patient B extracted from a 500x180 axial scan volume. (C1) OCT fundus image of patient C diagnosed with with drusen and an epiretinal membrane. (C2) Y-Z and (C3)-(C12) X-Z cross sectional images of patient C extracted from a 400x400 axial scan volume. Cross sectional images are shown vertically cropped to highlight the pathologies. Proc. of SPIE Vol. 7550 75501K-3

D1 D2 D3 D4 D5 D6 2050 x 21 axial scans acquired in 1.4 seconds 6mm (300 pixels) E3 E4 E5 E6 E7 E1 6mm (300 pixels) 4 E2 E8 E9 E10 E11 E12 1.6mm 300 x 300 axial scans acquired in 2.3 seconds F1 F2 F3 F4 F5 F6 2050 x 21 axial scans acquired in 1.4 seconds Figure 2: Pathologies from patients D, E and F imaged with the 47kHz axial scan rate 1050nm wavelength InGaAs linescan camera based spectral / Fourier domain instrument. (D1) Y-Z cross sectional image of patient D with normal tension glaucoma and optic disc drusen. (D2)-(D6) X-Z cross sectional images of patient D. (E1) OCT fundus image of patient E diagnosed with wet age-related macular degeneration. (E2) Y-Z and (E3)-(E12) X-Z cross sectional images of patient E. (F1) Y-Z cross sectional image of patient F diagnosed with dry agerelated macular degeneration. (F2)-(F6) Y-Z cross sectional images of patient F. All images are uncropped and show the full depth range of the instrument. Proc. of SPIE Vol. 7550 75501K-4

detachment (PVD)) are shown in Figs. 1(B1-B12) and are extracted from a 500x180 axial scan volume acquired in 1.2 seconds. Images from patient C (Right eye of an 83 year old subject with drusen and an epiretinal membrane) are shown in Figs. 1(C1-C12) and are extracted from a 400x400 axial scan volume acquired in 2.2 seconds. Compared to the standard 200x200 axial scan volume acquired by the commercially available Zeiss Cirrus (Carl Zeiss Meditec) at 27,000 axial scans per second with 5um axial resolution, the data sets acquired by the high speed prototype instrument acquire 4 the lateral scan data with 2 the axial resolution. However, sensitivities at the high speeds are lower and imaging through ocular opacities can be challenging, as can be seen by the relatively low dynamic range observed in some of the images. Figure 2 shows images obtained with the 1050nm spectral / Fourier domain OCT imaging system using the high speed InGaAs linescan camera. Images from patient D (Right eye of a 62 year old subject with normal tension glaucoma and optic disc drusen) are shown in Figs. 2(D1-D6) and are extracted from a 2050x21 axial scan volume acquired in 1.4 seconds. Images from patient E (Left eye of a 61 year old subject with wet agerelated macular degeneration) are shown in Figs. 2(E1-E12) and are extracted from a 300x300 axial scan volume acquired in 2.3 seconds. Images from patient F (Right eye of a 77 year old subject with dry age-related macular degeneration) are shown in Figs. 2(F1-F6) and are extracted from a 2050x21 axial scan volume acquired in 1.4 seconds. The higher sensitivity and reduced scattering at the longer 1050nm wavelength of the InGaAs camera based prototype instrument enables deeper penetration into the retina when compared to the 850nm prototype instrument. Imaging through ocular opacities also appears to be improved. However, the axial resolution of the prototype 1050nm instrument is 2-3 worse than the 850nm instrument, which is able to better resolve the thin fine retinal layers (Figure 1). 3. SWEPT SOURCE / FOURIER DOMAIN OCT IMAGING AT 1050nm A novel prototype ophthalmic OCT imaging instrument using a recently commercialized swept light source (Axsun Technologies,) at 1050nm was also developed. This light source consists of a MEMS filter, active element, and short cavity. The laser operates at speeds of 100kHz axial scans per second with an approximately 50% duty cycle. The swept source OCT imaging instrument achieves a sensitivity of 105dB (measured in air without equivalent water attenuation of the eye) with an incident power of 1.8mW. The prototype instrument was used to acquire in vivo images of the optic disc in the human retina. Retinal imaging was performed with an incident average power of 1.8mW at 1050nm wavelengths, consistent with safe retinal exposure as determined by the American National Standards Institute (ANSI). 25 Figure 3 shows images from a 3D volume consisting of 400x400 axial scans acquired in 1.9 seconds from a normal eye. The OCT fundus image generated from the 3D data set is shown in Fig. 3(G1) and has no noticeable motion in the transverse directions. The cross sectional images shown in Figs. 3(G2)-(G18) exhibit good penetration into the choroid and optic nerve head. However, fixed pattern noise can be observed as horizontal lines spanning the width of the images. This noise may be directly from the swept laser itself since it is observed even when an interferometer is not used. However the source of this noise requires further investigation. Figure 4 shows cross sectional images of the optic nerve head consisting of 2000 axial scans across the image. Figure 4(A) shows a single cross sectional image acquired in 20ms. Figure 4(B) shows a composite image consisting of 8 cross sectional images acquired in rapid succession from the same location on the retina that have been registered and averaged. The averaged image shows improved contrast and reduced speckle. Compared to the InGaAs linescan camera based spectral / Fourier domain OCT instrument described in Section 2, the swept source instrument achieves a longer imaging range and reduced sensitivity roll-off at deeper imaging depth. 4. CONCLUSIONS We have developed and demonstrated multiple configurations of high speed spectral and swept source / Fourier domain OCT ophthalmic imaging systems at 850nm and 1050nm. One instrument was developed using a high speed CMOS linescan camera. Ultrahigh resolution spectral / Fourier domain OCT imaging at 3um axial resolution was performed at 91kHz axial scan rates centered at 850nm wavelength. A second instrument used a high speed InGaAs linescan camera. Spectral / Fourier domain OCT imaging at 7um axial resolution was performed at 47kHz axial scan rates at 1050nm wavelength. Imaging of clinical pathologies was performed to Proc. of SPIE Vol. 7550 75501K-5

6mm (400 pixels) G1 6mm (400 pixels) G2 G3 G4 G5 G6 G7 G8 G9 G10 G11 G12 G13 G14 G15 G16 G17 G18 400 x 400 axial scans acquired in 1.9 seconds Figure 3: Images obtained from normal subject G acquired with the 100kHz axial scan rate 1050nm wavelength short cavity laser swept source OCT instrument. (G1) OCT fundus image of the optic disc generated from a 3D-OCT data set. (G2)-(G18) cross sectional images extracted from a 400 400 axial 3D volumetric data set of subject G. The cross sectional images are shown cropped. 6mm (2000 pixels) 3mm (A) Single B-scan (B) Average of 8 B-scans Figure 4: Cross sectional images obtained from normal subject G with the 100kHz 1050nm short cavity laser swept source instrument consisting of 2000 axial scans each. (A) A single 2000 axial scan image. (B) Composite image formed by registering and averaging 8 B-scans from a rapidly repeated line acquisition protocol. Proc. of SPIE Vol. 7550 75501K-6

compare the effects of varying speed, axial resolution, center wavelength, and sensitivity on a representative cross sectional set of patient data with these systems. A novel third instrument images at 100kHz using a recently developed commercially available wavelength swept light source centered at 1050nm and based on short cavity laser technology. The three high speed systems described in this paper are able to acquire dense 3D volumetric data sets with minimal motion artifacts. Dense volumetric data sets offer continuous retinal coverage which promises to aid in the detection of focal disease and improve the ability to correlate data from visit to visit. Higher instrument sensitivities and deeper imaging into the optic nerve head and choroid are observed with both the spectral and swept source 1050nm systems when compared to the 850nm system. The 1050nm systems also appear to image with higher retinal signal through ocular opacities. However, higher axial resolutions of 3um are obtained with the 850nm system when compared to the 7um resolution of the 1050nm systems. The swept source system demonstrates a longer imaging range and superior sensitivity roll-off performance when compared to the spectral systems. However, the swept source system exhibits a fixed pattern and structural noise in the image that is not present in the spectral systems. The results of this study support the conclusions of previous studies which show that 1050nm wavelengths can achieve increased penetration into the retina. In addition, the superior sensitivity roll off performance observed in swept source OCT extends the imaging range compared to standard and ultrahigh resolution spectral / Fourier domain instruments. Ultrahigh speed imaging can achieve a significant improvement in performance for ophthalmic imaging by obtaining dense 3D data sets of the retina. Imaging at 1050nm wavelengths and/or swept source OCT may lead to the development of practical ultrahigh speed imaging in the clinic where patients often have ocular opacities that reduce signal levels or significant eye motion that hinders data acquisition. ACKNOWLEDGMENTS This research is sponsored in part by the National Institutes of Health 5R01-EY011289-23, 5R01-EY013178-09, 2R01-EY013516-16, 1R01-EY019029-01, Air Force Office of Scientific Research contract FA9550-07-1-0014 and Medical Free Electron Laser Program contract FA9550-07-1-0101. The authors would like to thank Chao Zhou, Tsung-Han Tsai, and Bernhard Baumann for helpful discussions about the Swept Source OCT instrument. 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., and Fujimoto, J. G., Optical coherence tomography, Science 254(5035), 1178 1181 (1991). [2] Schuman, J. S., Puliafito, C. A., and Fujimoto, J. G., [Optical Coherence Tomography of Ocular Diseases], Slack, Inc., New Jersey, USA (2004). [3] Hitzenberger, C. K., Optical measurement of the axial eye length by laser doppler interferometry., Invest. Ophthalmol. Vis. Sci. 32, 616 624 (1991). [4] Swanson, E. A., Izatt, J. A., Hee, M. R., Huang, D., Lin, C. P., Schuman, J. S., Puliafito, C. A., and Fujimoto, J. G., In-vivo retinal imaging by optical coherence tomography, Opt. Lett. 18(21), 1864 1866 (1993). [5] Fercher, A. F., Hitzenberger, C. K., Drexler, W., Kamp, G., and Sattmann, H., In vivo optical coherence tomography, Am. J. Ophthalmol. 1(116), 113 114 (1993). [6] Fercher, A. F., Hitzenberger, C. K., Kamp, G., and El-Zaiat, S. Y., Measurement of intraocular distances by backscattering spectral interferometry, Opt. Commun. 117, 43 48 (1995). [7] Häusler, G. and Lindner, M. W., Coherence Radar and Spectral Radar New Tools for Dermatological Diagnosis, J. Biomed. Opt. 3, 21 31 (Jan. 1998). [8] Haberland, U., Jansen, P., Blazek, V., and Schmitt, H. J., Optical coherence tomography of scattering media using frequency-modulated continuous-wave techniques with tunable near-infrared laser, in Coherence Domain Optical Methods in Biomedical Science and Clinical Applications, Proc. SPIE 2981, 20 28 (1997). [9] Chinn, S. R., Swanson, E. A., and Fujimoto, J. G., Optical coherence tomography using a frequency-tunable optical source, Opt. Lett. 22(5), 340 342 (1997). Proc. of SPIE Vol. 7550 75501K-7

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