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Abstract
An optical coherence tomography system is proposed for synchronized zoom imaging of the cornea, retina, and the whole eye. The system was combined with an electrically tunable lens provided with 15 ms zoom response time and a customized optical delay line. A full-range technique was used to extend the depth of the B-scan cross sectional image. The anterior and posterior segments of the human eye were scanned by a coaxial rotating double galvanometer system. The transverse scanning ranges can reach up to 8 mm in whole eye scanning and 14 mm in fast single-frame scanning. The speed of image acquisition is over 4 Hz, and five B-scans were stitched to obtain a whole eye image. The system with electrically tunable lens and optical delay line achieved whole eye depth imaging in vivo.
© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
1. Introduction
Common ophthalmic diseases of the whole eye, such as glaucoma, diabetic retinopathy, and refractive errors often occur on multiple parts of the eye simultaneously or successively [1–4]. Therefore, a comprehensive and high-resolution imaging system, capable of rapidly and accurately localizing diseased lesions in the whole eye, would be highly beneficial for early clinical diagnosis and treatment. It can also assist in clarifying the pathogenic mechanism of ocular diseases. Optical coherence tomography (OCT) is currently one of the most advanced ophthalmic imaging technologies. OCT is capable of detecting the internal structure and physiological function of the eye non-invasively and in vivo. Currently, commercial OCT systems are applied to imaging either the anterior segment (AS) or the posterior segment (PS) of the eye [5–7]. OCT modalities primarily include time domain OCT (TD-OCT) and Fourier domain OCT (FD-OCT), The FD-OCT was realized as spectral-domain OCT (SD-OCT) or swept-source OCT (SS-OCT) [8–10]. TD-OCT system was developed with an optical delay line (ODL) structure used to adjust the optical length. However, due to hardware limitations, the imaging depth has been restricted to 3 mm [11,12]. FD-OCT has obvious advantages over TD-OCT in terms of sensitivity and imaging speed [13]. However, the imaging depth of SD-OCT is typically limited to 5 mm by the spectral resolution [14,15], while the imaging depth for SS-OCT is about 8 mm [16,17]. Imaging modalities with functions of full-depth imaging range, high resolution at full depth, and a wide transverse scanning distance, are required for assisting clinical diagnosis.
In recent years, advanced whole eye imaging modalities are developing [18–21], incorporating the development of OCT modalities with application in ophthalmic diagnosis. The single light source SS-OCT system is developed with the light split into two orthogonal polarization components for imaging the anterior segment and retina, respectively. The whole-eye images are reconstructed based on simultaneously acquired images [18]. With the technical development, a SS-OCT prototype was proposed with functions of imaging both the whole anterior segment and the retina alternately utilizing a single source and detection channel [19]. Researchers also proposed techniques by using an optical delay line structure to change the optical length in the OCT system, thereby increasing the imaging interval to a certain extent [22,23]. These systems have not yet applied ODL to the extension of the optical path depth for whole eye imaging. The range of coherent imaging can be expanded by adjusting the optical length and then splicing images formed at different positions [24,25]. Another strategy is reported based on the inherent imaging depth of FD-OCT system, doubling the imaging depth by using a full-range technique, to achieve anterior segment and fundus imaging. However, it is difficult to achieve flexible switching of multiple optical path positions [26–28]. The whole-eye integrated optical path design is combined with ODL multi-segment flexible zoom, which is used for true whole eye depth multi-segment imaging. However, whole eye imaging modalities are required to dynamically adjust the beam focus within the eye, in order to facilitate axial high-resolution imaging and overcome the single point focusing problem caused by the refractive properties of the lens [28,29]. The electrically tunable lens (ETL) was used for dynamic focusing of the whole eye beam. ETLs have been shown to provide focusing and zooming capabilities for OCT imaging [30,31]. Compared with multi-segment single-point focus, scrolling focus under electronic control caused a certain degree of image blurring. Since the pupil diameter is limited and lateral scanning of the anterior and posterior segments are mutually restricted, the horizontal imaging range of the fundus is also limited [25,28,32]. The lateral imaging range of the system has been improved in the anterior segment and in the fundus, through an integrated optical optimization of the system sample arm [21,26,29].
At present, the commercial cost of SS-OCT is much higher than that of SD-OCT. Therefore, the usage of SD-OCT technique for whole-eye imaging system could greatly reduce the system cost. In our study, multiple techniques are used to facilitate a field-of-view (FOV) of 8 mm fast imaging through a whole eye depth. First, the SD-OCT imaging depth is doubled by full-range technique. Second, an ODL with centripetal crank slider mechanism is introduced, the maximum optical length is increased to 44 mm. In addition, an ETL is used for segmented zoom imaging by dynamically adjusting the beam focus. Third, the approach is combined with a signal synchronization algorithm to achieve segmented control of the focal length and optical length at whole eye depth. The lateral resolution of the whole eye imaging process was the same as that of previous whole-eye imaging studies, ensuring high signal-to-noise in each imaging area. In order to extend the FOV, double galvanometric scanners are used with a coaxial rotation for imaging the AS and PS of the human eye. The proposed SD-OCT system is used to acquire 5 B-scan images at different depths, which are further spliced to obtain whole eye images.
2. Methods and materials
2.1 System setup
A schematic diagram of the proposed whole eye imaging SD-OCT system is shown in Fig. 1(a). A super-luminescent diode (EXALOS) with a central wavelength of 840 nm, a bandwidth of 50 nm, and an optical power of 7 mW, was used to produce an axial resolution of 8 µm. The light source was split into a sample arm and a reference arm by using a 2×2 fiber coupler (Thorlabs, TW850R5F1) with a ratio of 50:50. With the light split, the power to the eye is about 2mw, and the radiation illuminance is calculated to meet the safety range of human eyes. A collimator (C1) (Thorlabs, CFC-11X-B, NA = 0.3) was then used to form an incident beam with a diameter of ∼3 mm. Two double cemented lenses, L1 and L2 (AC254-060-B, f1 = 60 mm, AC254-050-B, f2 = 50 mm, 1-inch diameter), were used to form a confocal lens group. The optical aperture of the ETL (Optotune AG, Switzerland, EL-10-30-C) was 10 mm and the anti-reflective coating offered 88% bidirectional transmittance near 840 nm. The ETL zoom allowed light to focus on different depths within the eye. The whole eye depth was divided into 5 segments for focus imaging, based on the total optical path length in the axial direction of the eye. The collimated beam in the reference arm was horizontally incident on a cube-corner retroreflector (CR) and emitted parallel to the plane mirror through total reflection, as shown in the reference arm section of Fig. 1. The CR was fixed in the ODL and used to adjust the optical length. A dispersion compensation unit (DC) was added to the reference arm. It effectively compensated for dispersion introduced in the two arms (lenses, CR, ETL, L1, L2, etc.) [33,34].
Fig. 1. (a)The proposed 840 nm SD-OCT system designed to acquire whole eye images in vivo. The labels are defined as follows. SLD: super-luminescent diode; ETL: electrically tunable lens; OL: offset lens; L1, L2, L3: doublet lenses; C1, C2: collimators; CR: cube-corner retroreflector; GS1, GS2: galvanometric scanners; FC: optical fiber coupler; DG: diffraction grating; LSC: linear-scan camera; ODL: optical delay line; DC: dispersion compensation unit; PC: polarization control; M: mirror. The red line in the figure represents the beam propagation path. The blue dashed frame represents the movement process for the ODL. (b) The sensitivity roll-off and the lateral resolution distributions in different optical planes. (c) Spot diagrams for on-axis and off-axis in the posterior segment (PS) and anterior segment (AS).
The interfering signals from the two arms were measured by a spectrometer to achieve photoelectric conversion. The spectrometer was primarily composed of a collimator (C2, f = 70 mm), a customized achromatic lens (L3, AC254-100-B, f3 = 100 mm), a diffraction grating (DG, 1800 lines/mm), and a line scanning camera (LSC, e2v, 2048 pixels, 130 kHz). The spectrometer offered excellent signal attenuation performance and high camera sensitivity, with a full-scale imaging depth (in air) of 4.5 mm. Full-range technology was employed here as a complex conjugate imaging technology. An adjustment phase is introduced from mechanical parts (galvanometers) to eliminate the image symmetry caused by the conjugate property of Fourier transform, so that it doubly extends the imaging range [26,27,28]. The sensitivity roll-off within the depth length is shown in Fig. 1(b). The sensitivity dropped 9 dB ${\pm} $4.0 mm from zero position. During image processing, the data sets were collected along the eye axis direction as reference, and the system was calibrated by using a dispersion compensation algorithm. High-resolution images of the whole eye were achieved by using different dispersion compensation factors at different depth ranges from the cornea to the retina [35,36]. The lateral resolutions of scanning are shown in Fig. 1(b). The spot diagrams for on-axis and off-axis in the posterior segment (PS) and anterior segment (AS) are demonstrated in Fig. 1(c).
2.2 Optical delay line
The crank slider mechanism uses motor rotation to drive a crank and connecting rod around an axis. Then, the connecting rod drives the slider linearly in a direction perpendicular to the axis [37], this is a technique primarily used in high-speed industrial production [38]. In the study, a centric slider-crank mechanism was independently designed as an ODL. The maximum optical path change of the reference arm is 44 mm. When a CR was combined, the optical path adjustment speed was twice of that in a traditional ODL. A 3D simulation diagram of the ODL is shown in Fig. 2(a). The primary components include a stepping motor, crank, connecting rod, slider, guide rail, and other connectors. First, the stepping motor is triggered by a pulse signal, then rotates on its axis and drives the crank to make circular motion, the connecting rod was pushed to drive the CR fixed on the slider to make a reciprocating motion. In a single motor rotation (360°), the ODL moves from the minimum to the maximum and then from the maximum to the minimum positions. The relationship between the slider stroke (S1), ODL stroke (S2), and motor rotation angle (θ) in the crank slider mechanism is shown in Fig. 2(b). Among these, a fourth-order relationship between S1 and θ was fitted as follows: S1(θ) = 3.8 × 10−8 × θ4 − 2.7 × 10−5 × θ3 + 0.005 × θ2 + 0.07 × θ − 1. In addition, a cube-corner retroreflector was used to replace the traditional flat mirror to form a reentrant optical path in the reference arm, which doubled ODL change speed. Therefore, the length of the crank was designed to be 1/4 of the optical length of human eye under ideal conditions. Anatomical measurements suggest the diameter of a normal human eye to be ∼24 mm, with an average refractive index of 1.33. The optical path length in the axial direction of the eye has been determined to be ∼32 mm. The maximum of the entire ODL stroke S2 was thus designed to be 44 mm. The design not only improved the scope of system applications, it also allowed for whole eye imaging of subjects with varying axial lengths.
Fig. 2. (a) A 3D ODL simulation diagram. (b) The relationship between the stroke (S1) of the slider, the stroke (S2) of the ODL, and the rotation angle (θ) of the motor.
2.3 Synchronous zoom
The zoom of the chosen ETL is controlled by current in the range of [5,10] dpt. The refractive difference between the AS and the PS was solved by adding an offset lens (OL) with a focal length of 150 mm after the ETL, which adjusted the zoom range of the combined lenses to [−1.5, 3.5] dpt. The system also has two types of beam patterns: focusing and parallel. The corresponding relationship between the resulting diopter and the drive current is shown in Fig. 3(a). The ETL offers optical focusing with a minimum response time of 15 ms. The current can be adjusted multiple times during a single motor rotation circle (360°), to achieve multi-segment zoom and focusing at whole eye depth. The relationship between the ETL zoom current and the motor angle θ is shown in Fig. 3(b). Optical length adjustments of the reference arm were synchronized with focus adjustments of the sample arm in real time by a signal synchronization control algorithm written in NI-LABVIEW. The system could achieve expected imaging results in each section of the sample.
Fig. 3. (a) The relationship between the ETL diopter, the combined lens diopter (ETL + OL), and the drive current. (b) The relationship between the electric tunable lens drive current value and the motor rotation angle θ, as the motor rotates through a single circle (360°).
2.4 Galvanometer scanning mode and protocol
A single galvanometer was usually used to scan the entire eye in early trials. The distance between the image plane and the object plane of the optical system was strictly maintained to develop a 4-F system and achieve the highest imaging quality. Here, we found the integrated optical length restricted the lateral scanning range for the AS and PS of the eye. As such, a coaxial rotating double galvanometer (GS1, GS2) system was introduced to scan and image the AS and the PS separately. The pupil of GS1 was used to scan and image the AS, with GS2 held at rest. GS2 was used to scan and image the PS, with GS1 held at rest. Deviations from the optical principal plane during scanning are shown in Fig. 4(a). A ZEMAX simulation design ensured the distance (l) between GS1 and GS2 was less than 35 mm, to achieve the maximum scanning width for AS. The coaxial rotating double galvanometer system increased the scanning width for the cornea from 2 mm to 8 mm. Similarly, the scanning width of the fundus was increased from 6 mm to 8 mm. The actual scanning range in the human eye model is shown in Fig. 4(b). The lateral resolution of the system in the AS and PS of the eye was 48 µm and 18 µm, respectively.
Fig. 4. The rotating axes of galvanometer GS1 and GS2 are parallel. (a) Deviation of the optical plane as the galvanometers (GS1 and GS2) scanning the AS and PS of the eye. (b) A schematic diagram of the scanning range as the galvanometers (GS1 and GS2) scanning the AS and PS of the eye.
The increased focal depth offered by the system allows total eye images to be formed by stitching 5 B-scans. The first two B-scans are stitched together to form the AS image and the last three B-scans form the PS. The dual galvanometers, GS1 and GS2, were performed according to the scanning protocol as shown in Fig. 5(a). The two scanners (GS1 and GS2) did not scan simultaneously. When the AS is scanned, the scanner GS1 works, and the scanner GS2 is held at rest; when the PS is scanned, GS2 works, and the GS1 is held at rest. As to the scanning protocol (20 Hz) for whole eye imaging, GS1 scans continuously for 2 frames at different depths in the AS, and GS2 scans continuously for 3 frames at different depths in the PS. During one rotation of the stepping motor, 10 B-scans could be acquired, which represents that images of two eyes could be completed. The slider was moved to a specific stroke during the rising edge of the stepper motor pulse control signal, to adjust the optical length position in the system. The ETL was simultaneously adjusted to the zero optical length point for imaging. The rising edge time should be greater than 15 ms to ensure zoom stability of the ETL. The camera was operated by the control signal, while the stepping motor and ETL had a rest. Synchronous control of the stepping motor and ETL were used to adjust the speed of the camera and control the duty cycles for GS1 and GS2. A wide range of segmented scan was provided for the AS and PS of the eye and multiple B-scans of imaging of the whole eye structure were facilitated. A constant optical length and fixed positions were required for the stepping motor and ETL. The acquisition speed 200 Hz, initially set evenly for whole eye segmented imaging, was used for single-frame high-speed imaging of local eye structure. The high-speed local scanning protocol is demonstrated in Fig. 5(b) and 5(c). As to the scanning protocol (200 Hz) for the AS, the GS1 scanner scans continuously, while GS2 is held rest. As to the scanning protocol (200 Hz) for the PS, GS1 is held rest while GS2 scans continuously.
Fig. 5. The signal synchronization scanning protocol. GS1 and GS2 represent driving signals applied to the double galvanometer scanners and B-scan denotes the driving signal for a single image frame. (a) The scanning protocol (20 Hz) for whole eye imaging. GS1 scans continuously for 2 frames at different depths in the AS. GS2 scans continuously for 3 frames at different depths in the PS. (b) The high-speed scanning protocol (200 Hz) for the AS. GS1 scans continuously, while GS2 is held rest. (c) The high-speed scanning protocol (200 Hz) for the PS, in which GS1 is held rest while GS2 scans continuously.
3. Results
3.1 Whole eye imaging
As discussed previously, the optical path length of the eye axis is ∼32 mm and the imaging depth of a single-frame is 9 mm. Under the three conditions of single-frame imaging depth, whole eye range high-sensitivity imaging, and ODL range changes, the entire eye depth can be divided into 5 imaging areas and sequentially stitched together. The optical length and focal length were adjusted to perform B-scan imaging in each area. The signal scanning protocol for fast imaging of the whole eye is shown in Fig. 5(a). The entire cross-sectional image along the eye axis was collected with 5 segments by 20 B-scan frames at 20 Hz. Herein, every 5 B-scan frames form a whole eye image at 250 ms. Each B-scan frame was composed of 1000 A-lines. The relationship between rotation angle and ODL stroke, which is shown in Fig. 2, was used to analyze the optical length difference between two adjacent B-scans, to ensure accurate splicing of segmented B-scan images. Mosaic results for multiple images are shown in Fig. 6. Due to the imaging speed, the system could achieve 20 Hz frame rate for whole eye imaging, which could reduce the effect caused by the eye movements. Therefore, the correction of lateral scan was not applied here. According to the imaging depth of each B-scan and the reference arm stroke change relationship between adjacent B-scans, Fig. 6 is obtained by superposing and splicing the B-scan images with different segments.
Fig. 6. A whole eye OCT image of a 25-year-old subject, formed by stitching 5 B-scan images segments along the axis oculi (cornea to retina).
3.2 Anterior segment imaging
The signal control protocol for high-speed scanning of the AS of the eye is shown in Fig. 5(b). Optical path and focal length parameters for the AS of the eye were used for whole-eye imaging. ODL was included to quickly adjust the optical length of the reference arm and a flexible zoom ETL was used to position the focus on the area of interest for imaging, providing high sensitivity. The imaging depth for a single OCT frame reached up to 9 mm using full-range technique. The anterior chamber was imaged, including the front half of the lens. In addition, the full-range technology can effectively eliminate mirror images of the cornea and iris. Figure 5(b) shows the scanning protocol used to collect 5 frames in 25 ms. A total of 200 cross-sectional images of the AS were continuously acquired at a frame rate of 200 Hz. Each OCT frame was composed of 1000 A-lines, with a duration of 1 s. Five sample images of the anterior chamber are shown with full-range technique in Fig. 7(a). In contrast, Fig. 7(b) and 7(c) show images of the cornea and iris without full-range technique. The corneal stromal layer and other structures at unilateral angles can be clearly distinguished in Fig. 7(b). In Fig. 7(c), the focal position was adjusted to the iris for a clearer image. The front half of the lens structure can also be observed.
Fig. 7. SD-OCT imaging of the AS at a specific optical length and focal length. (a) Five typical images of the AS with full-range technique. (b) A single frame image of the anterior chamber without full-range technique. Here, the stromal layer and other structures can be clearly distinguished and the unilateral angle can be observed. (c) A single frame image of the iris without full-range technique. The high visibility iris structure and the front surface of the lens are demonstrated.
3.3 Retinal imaging
The retina and choroid regions were captured by imaging the posterior segment of a healthy human eye. The signal scanning protocol was modified to achieve high-speed imaging of the retina, as shown in Fig. 5(c). An ETL was used to fine-tune the focal length and achieve rearward shifting of the focal plane, offering clear retina and even choroidal imaging and providing additional fundus structure information. Figure 8(a) shows an image of the fovea and optic nerve head with 14 mm FOV. The multi-layer structure of the retina and the deeper choroid layers could be distinguished. The same imaging effect for the optic nerve area and the fovea region of the retina are shown in Fig. 8(b) and 8(c).
Fig. 8. Fundus imaging using the SD-OCT whole eye system for a specific optical length and focal length. (a) The focal retinal fovea and the optic nerve head are presented simultaneously in a wide field of view 14 mm and the multilayer structure can be distinguished. (b) Imaging of the fovea of the retina. (c) Varying angle imaging of the optic nerve.
4. Discussion and summary
Expanding the longitudinal imaging range of conventional SD-OCT systems and compensating for refractive effects in different areas of the eye are two major technological breakthroughs achieved in recent studies on whole eye imaging. The imaging depth of a B-scan was doubled by full-range technique, B-scan at different depths could be acquired by the ODL movement. Five B-scans could be stitched by optical length calculations to obtain a whole eye image, so that the longitudinal imaging range were extended to the whole eye range.
The refractive characteristics of the eye make it difficult to simultaneously image the AS and PS regions. In the study, a coaxial rotating double galvanometer scanning system was used to overcome the issue and maximize the imaging range. The AS imaging was achieved by using a principal plane offset combined with a flexible ETL and GS1. Scans of the PS were performed by using a 4-F system constructed to ensure retinal imaging with a high SNR. The GS2 mirror size determined the lateral AS imaging range. In future study, both the linearity and stability of the galvanometers should be considered using larger lenses with full-range technique, since additional vibrations could affect the spot distance from the center of the galvanometer and cause image artifacts. The temperature rise will cause the liquid droplets in ETL to be expanded by heat, thus affecting the diopter of ETL. In order to solve the stability problem of ETL, we consider two aspects. 1. The absolute reappearance of ETL can reach 0.1 diopter, ensuring the stability of ETL performance; 2. In order to further reduce the deviation of the system focal length caused by temperature drift, the data sets were collected at the same normal room temperature, and the experimental data sets were selected 10 minutes after startup.
In addition, the transverse scanning range of the sample is determined by the scanning deflection angle of the galvanometer and the focal length of the focusing lens. When the focal length is fixed, the calibration of the transverse scanning range of each B-scan segment depends on the scanning angle of the galvanometer, which is determined by its voltage value. Therefore, the scanning protocol that determines each B-scan segment can calibrate the transverse scanning range of each B-scan segment. The imaging of healthy human eyes was performed with relatively transparent and weakly reflected vitreous bodies. Vitreous area is an important part of the human eye; it also plays a supporting role to protect the eye. In the ophthalmic diagnosis of OCT, since the vitreous body is full of transparent liquid, it is not easy to image. However, once the vitreous area is turbid, the OCT imaging effect is affected. In our study, all the subjects are with normal eyes, with clear lesions-free vitreous, no obvious structural features were found during imaging. In the future, we will perform clinical experiments on vitreous patients and test the imaging effect of the system in the vitreous area.
In future study, cameras with higher line speeds and imaging depths could be used to achieve higher SNR. It will increase the depth of single-frame imaging and reduce the number of segments required for whole eye imaging, increasing the scanning speed. According to test results from the supplier report, a filter circuit can shorten the ETL response time to ∼7 ms, potentially doubling the imaging rate. The rapid whole eye imaging could facilitate accurate measurement of axial direction parameters; it also can reduce the patients’ discomfort during diagnosis. Here, a coaxial rotating double galvanometer system was chosen to replace the traditional 2D galvanometer system for optical path optimization. In the future, another scanner can be employed for acquiring the volumetric images. Besides, during lateral scanning and focus tuning, the field curvature could change. We are still working on this issue to achieve high imaging performance.
In summary, we have developed an SD-OCT system to achieve whole eye depth imaging. In addition to offering fast whole eye stitch imaging, the system can scan the cornea, chamber angle, iris, lens, retina, and part of the choroid. The proposed OCT system also achieved large-scale integrated imaging of the eyeball. An optimized optical design makes the system more compact, which may expand potential commercial applications. However, the integrated system resulted in a lateral AS and PS resolution of 48 µm and 18 µm, respectively, which is non-uniform. Besides, multi-segmental switching modes along the whole eye depth reduced imaging speeds. Therefore, in Fig. 5, we provide 3 targeted scanning protocols for rapid imaging of the whole eye, high-speed imaging of the AS structure, and high-speed imaging of the PS structure.
Funding
Guangdong Provincial Pearl River Talents Program (2019ZT08Y105); National Natural Science Foundation of China (81771883, 81801746, 62005045); National Natural Science Foundation of China (61425006, 61871130, 61905040, 61975030); Thousand Young Talents Program of China.
Acknowledgments
The authors would like to acknowledge Ke He, Shenghao Lin. We thank LetPub (www.letpub.com) for its linguistic assistance and scientific consultation during the preparation of the manuscript.
Disclosures
The authors declare no conflicts of interest.
Data availability
Data underlying the results presented in this paper are not publicly available at this time but may be obtained from the authors upon reasonable request.
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