Optical coherence tomography for whole eye ... - OSA Publishing

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3Department. of Biomedical Engineering, College of Engineering, Peking ... of Ophthalmology Keck School of Medicine, University of Southern California, Los ...
Optical coherence tomography for whole eye segment imaging Cuixia Dai,1,2 Chuanqing Zhou,1,5 Shanhui Fan,1 Zhe Chen,1 Xinyu Chai,1 Qiushi Ren,3 and Shuliang Jiao4,6 1

School of Biomedical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China 2 College of Science, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai 201418, China 3 Department. of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China 4 Department of Ophthalmology Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA 5 [email protected] 6 [email protected]

Abstract: We proposed a dual focus dual channel spectral domain optical coherence tomography (SD-OCT) for simultaneous imaging of the whole eye segments from cornea to the retina. By using dual channels the system solved the problem of limited imaging depth of SD-OCT. By using dual focus the system solved the problem of simultaneous light focusing on the anterior segment of the eye and the retina. Dual focusing was achieved by adjusting the collimating lenses so the divergence of the two probing beams was tuned to make them focused at different depth in the eye. We further achieved full range complex (FRC) SD-OCT in one channel to increase the depth range for anterior segment imaging. The system was successfully tested by imaging a human eye in vivo. 2012 Optical Society of America OCIS codes: (170.4500) Optical coherence tomography; (170.4470) Ophthalmology; (170.3880) Medical and biological imaging.

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1. Introduction Millions of people are affected by eye diseases like myopia, presbyopia, cataract, and

glaucoma. These eye diseases can affect the shape and dimensions of segments of the whole eye. For examination of ocular pathological changes caused by these diseases simultaneous high resolution imaging of the whole eye segments is desired. Current technologies applied for whole eye imaging, such as ultrasound imaging and magnetic resonance imaging (MRI) have their advantages and limitations [1-4]. The advantage of ultrasound is its long imaging depth whereas it is a contact imaging technique [1, 2] and its contrast mechanism and resolution are not suitable for imaging the retina. High resolution MRI [3, 4] can be applied for whole eye imaging, but it is too costly to be used routinely while its resolution is not high enough to image the retinal layers. Optical coherence tomography (OCT) is a noninvasive imaging technology that provides high resolution cross-sectional imaging of biological tissues [5, 6]. High speed high resolution SD-OCT [7, 8] has been becoming an indispensable diagnostic tool in ophthalmology for imaging the retina and anterior segment of the eye. Due to the refractive power of the anterior segment a light beam cannot be focused on both the anterior segment and the retina simultaneously. This is one of the major reasons why the whole eye segments cannot be imaged simultaneously with SD-OCT [9]. Another major limitation of SD-OCT for whole eye segment imaging is its limited imaging depth. The depth range of a SD-OCT system is restricted by the Hermitian symmetry of Fourier transformation of the real-valued spectral interferogram and the intrinsic limitation of spectral resolution of the spectrometer [10, 11]. Efforts have been made to extend the ranging capability by improving the spectral resolution of the spectrometer in the case of SD-OCT [10], narrowing the line width of a swept-laser source in the case of swept-laser OCT [11], adding detecting depths of two OCT systems with the two channel arrangement [12], and using full range complex (FRC) technique to image in the full complex space [13-16]. Recently, an easy-to-achieve FRC method was proposed to double the depth range by scanning the probing light off the pivot of the scanner mirror [17-20]. By using this method, the whole anterior segment of eye could be imaged. However, the reported longest imaging depth of SD-OCT is ~10 mm, which is still not enough for imaging the whole eye. To solve the two major limitations for whole eye segment imaging we developed a dual channel SD-OCT system, in which the anterior segment of the eye is imaged using the off-pivot-point-illumination FRC technique in one channel [17-20], and the retina is simultaneously imaged in the other. This technique provides a potentially powerful imaging

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method for clinical whole eye segment examination and ophthalmic research. 2. Experimental performance 2.1 Experimental system A schematic of the experimental system is shown in Fig. 1. Two fiber-based SD-OCT systems were integrated, one of which was configured to image the anterior segment of the eye while the other was configured for imaging the retina. Two super-luminescent diodes (SLD, Inphenix, USA and Superlum, Russia) both with a FWHM bandwidth of 45nm and a center wavelength of 840 nm were used for the two OCT systems. In the sample arm, light beams coming out of the sample fibers were first transformed by two collimating lenses and then combined by a beam-splitter cube. The combined probing beams were delivered to the eye by the same x-y galvanometer scanner and light delivering optics which were built on a modified slit lamp. By adjusting the collimating lenses the divergence of the two probing beams was tuned to make them focused at different depth in the eye. The light beam for imaging the anterior segment of the eye (OCT-1, consisting of light source SLD 1, optics of channel 1, and spectrometer 1) was focused at the position just below the iris; The collimated light beam (OCT-2, consisting of light source SLD 2, optics of channel 2, and spectrometer 2) was focused at the retina by the refractive elements of the eye. In the detection arms the reflected beams from the sample and reference arms were collimated and detected by two spectrometers. Spectrometer 1 consists of an 1800 line/mm transmission grating, a multi-element imaging lens (f=150 mm), and a line scan CCD camera (Aviiva-SM2-CL-2010, 2048 pixels with 10 micron pixel size, e2V); Spectrometer 2 consists of an 1800 line/mm transmission grating, a multi-element imaging lens (f=100 mm), and a line scan CCD camera (Aviiva-SM2-CL-2014, 2048 pixels with 14 micron pixel size, e2V). The linear CCD cameras were synchronized and operated at a rate of 20k lines per second, and the integration time of CCD cameras was set to be 36μs. Image acquisition boards (NI IMAQ PCI 1428) acquired the images captured by the camera and transferred them to a computer for signal processing and image display. Other details can be found in our previous publication [12]. To image in full space range in OCT-1, the method of off-pivot-point-illumination FRC was used [18]. The collimating optical assembly (COA) was mounted on an x-y-z translation stage to adjust the position of the light beams on the X-scanning mirror of the scanner to achieve a constant phase shift between adjacent A scans. The reference arms of the two OCT systems were first adjusted by using a model eye as the sample. We first adjusted the reference arm of OCT-1 to place the reference plane just behind the iris so the anterior segments of eye and their overlapping mirror image can be seen. Then we adjusted the reference arm of OCT-2 to image the retina by placing the reference plane behind the retina. The distance between the two reference planes was then measured by using a mirror as the sample, which was mounted on a translation stage in the sample arm. The measured distance is 16.744 mm in air. Knowing the distance between the two reference planes a composite cross-sectional image can be constructed from the two simultaneously acquired OCT images. Thus, the whole eye segments can be imaged simultaneously. The total light power in front of the cornea was 2mW, which is safe for the eye and is below the ANSI Z136.1 limits. The beams were set at different focus: The light in OCT-1 was focused on the anterior segment with a power of 1.4mW; the light of OCT-2 was focused on the retina with a power of 0.6mW. In experiments, a fixation target was put on a wall a few meters away in front of the eye. Both the two OCT channels were controlled by a single computer and the whole segment of the eye was imaged simultaneously in real time.

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Received 10 Jan 2012; revised 20 Feb 2012; accepted 20 Feb 2012; published 29 Feb 2012 12 March 2012 / Vol. 20, No. 6 / OPTICS EXPRESS 6111

Fig. 1. Schematic of the dual focus dual channel OCT experimental system for whole-eye-segment imaging. L1-L7: Lens, M1-M2: Mirror, BS: Beam splitter, COA: Collimating optical assembly.

2.2 Signal processing Figure 2 shows a diagram illustrating the signal processing. The left column represents the process for reconstruction of the full range of OCT-1 for imaging the anterior segment of the eye. The FRC algorithm was used to remove the mirror image [17, 20]. Since the probing light beam hit the X-scanning mirror slightly off its axis, a constant phase difference (approximately π/2)between adjacent A-scans was generated. After removing the fixed pattern noise and the DC components, the measured 2D spectral data were line by line Fourier transformed (FFT) in the transversal scanning direction followed by filtering with the Heaviside step function to keep only the positive modulation frequency. Once the complex spectral data were reconstructed by an inverse Fourier transform (IFFT), they were interpolated to achieve linear sampling in the k space. A final FFT was applied to each A-line’s complex spectral interferogram to get the OCT B-scan image.

Fig. 2. Illustration of signal processing.

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After processing the measured spectra in OCT-2 by using the standard process the retinal cross sectional image can be obtained. Cross sectional image of the whole eye can be constructed by first scaling the images according to their calibrated imaging depths and then placing the images together according to the separation of the reference planes. 3. Results and discussions 3.1 Simultaneous imaging of the whole eye segments To demonstrate the capability of the OCT system we imaged the left eye of a healthy volunteer (50 years old) in vivo. No drug was used to stabilize the eyeball or for mydriasis. Figure 3 shows the acquired image of the anterior segment of the eye in OCT-1. Figure 3(a) shows the image before applying FRC to remove the complex conjugate of the OCT signal where the images with positive and negative path length differences are overlapped. Figure 3(b) shows the image after applying FRC technique to remove the complex conjugate of the OCT signal. We can see that the mirror image is suppressed sufficiently and the imaging depth range is doubled, which allows imaging the whole anterior segment of the eye from the front surface of the cornea to the posterior surface of the lens.

Fig. 3. Imaging the anterior segment of the eye with OCT-1. (a): image using standard SD-OCT signal processing; (b): full range reconstruction by FRC technique. Image size: 9.8mm (depth) × 12mm (width). Bar: 1mm.

Figure 4 shows the cross-sectional image of the retina simultaneously acquired in OCT-2. As we can see from the figure, the microstructures of the retina are clearly visualized. Although the image quality is not as good as a state-of-the-art OCT dedicated to retinal imaging, it is good enough for the proof-of-concept purpose.

Fig. 4. The simultaneously acquired retinal image in OCT-2. Image size: 2.5mm (depth) × 9.8(width) mm. Bar: 0.5mm.

3.2 Optical correction Figure 5 shows the OCT images corrected for distortions caused by the angular scanning pattern and the refraction of light on the ocular surface [21, 22]. In correction of the anterior segment image, both types of distortion were considered. For correction of the retinal OCT image, only the distortion caused by the angular scanning is considered. When correcting

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image warping caused by light refraction at the ocular surface, the corneal refractive index of 1.389 for 820nm light is used. Since the refraction distortion in the OCT images is mainly caused by the curved air-cornea interface, the distortion caused by the difference of refractive index among the aqueous humour, lens, and vitreous body is neglected in the correction.

Fig. 5. The optically corrected images. (a): the anterior segment of eye, (b): retina.

3.3 Constructed image of the whole eye segments Figure 6 shows the constructed image of the whole eye segments. The OCT images were scaled according to their corresponding imaging depth range. Since the thickness of the retina is much less than the axial length of the eye, the image of retina is compressed and details of the retina cannot be distinguished.

Fig. 6. Constructed image of the whole eye segments. Bar: 1mm.

3.4 Discussions We admit that the current result of the anterior segment imaging in OCT-1 is not satisfactory:

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the upper part of the cornea isn’t clearly visible. Several reasons may contribute to the degradation of image quality: (1) 50% attenuation to the back reflected probing light in the sample arm caused by the beam splitter cube; (2) the fan scanning pattern increased the light incident angle at the corneal surface; (3) the sensitivity fall-off along the depth due to that the reference plane was placed at the iris; (4) the position of the focal plane is not close to the corneal surface. The attenuation problem caused by the beam splitter cube can be solved by using different wavelength bands for OCT-1 and OCT-2 and replace the beam splitter with a dichroic mirror to couple the two OCT channels. For example, we can replace the light source in OCT-1 with one centered at 1310 nm, which is more suitable for imaging the anterior segment of eye. The problem of sensitivity fall-off can be alleviated by using a spectrometer with finer spectral resolution (longer imaging depth). As we can see from the image in OCT-2, only a small area of the retina is imaged. Since the two OCT systems share the same beam delivering optics we placed the scanning pivotal point in front of the cornea. With this configuration only the center portion of the scanning light can reach the retina while the other portion is blocked by the iris. In our tests the pupil of the imaging subject was not dilated, which caused the limited imaging area of the retina. In order to image a larger area in the future pupil dilation is needed. Furthermore, as shown in the constructed image of whole eye segments, part of the space of the vitreous body is blank. The problem can be also solved by using a spectrometer with finer spectral resolution for longer imaging depth in OCT-2. Then the vitreous body could be imaged, which is important in detection of vitreous opacity and other pathological changes. 4. Conclusions In conclusion, we have developed a dual channel dual focus SD-OCT system with an extended depth range for whole eye segment imaging. With this system, the anterior segment of the eye and the retina can be imaged in vivo simultaneously. Potential clinical application of our system may be in the detection of the pathological changes of the whole eye, and this SD-OCT system also provides a powerful imaging method for ophthalmic research, such as accommodation, ocular growth, and biometry of the eye. Acknowledgments The research is supported in part by the following grant: National Natural Science Foundation of China (81171377), National Basic Research Program of China (No.2011CB707504, No.2010CB933903), Science and Technology Commission of Shanghai Municipality (No.09ZR1431300), Shanghai Municipal Education Commission (No.11YZ226), and ‘111’ project from MOE China (No. B08020).

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Received 10 Jan 2012; revised 20 Feb 2012; accepted 20 Feb 2012; published 29 Feb 2012 12 March 2012 / Vol. 20, No. 6 / OPTICS EXPRESS 6115