In vivo Fourier-domain full-field OCT of the human retina with 1.5 million A-lines/s

In vivo full-field (FF) optical coherence tomography (OCT) images of human retina are presented by using a rapidly tunable laser source in combination with an ultra-high-speed camera. Fourier-domain FF-OCT provided a way to increase the speed of retinal imaging by parallel acquisition of A-scans. Reduced contrast caused by cross talk was observed only below the retinal pigment epithelium. With a 100Hz sweep rate, FF-OCT was fast enough to acquire OCT images with acceptable motion artifacts. FF-OCT allows ultrafast retinal imaging, boosting image speed by a lack of moving parts and a considerably higher irradiation power.     

Retinal cone mosaic imaged with transverse scanning optical coherence tomography

We improved our recently reported retinal OCT system based on transverse priority scanning to achieve high resolution in both the transverse and the axial directions. The implementation of an additional SLO channel enables precise on-line focusing. The system enables imaging of the human retinal cone mosaic off the foveal center without adaptive optics. We demonstrate, for what is believed to be the first time, cone mosaic imaging simultaneously in the scanning laser ophthalmoscope and optical coherence tomography (OCT) channels. OCT B-scan images demonstrate that the cone mosaic is observable in two adjacent layers. Furthermore, we present what are believed to be the first C-scan OCT images of the cone mosaic and show that the major part of light backscattered from below the photoreceptor layer is not guided back toward the pupil by the photoreceptors.     

Simultaneous swept source optical coherence tomography of the anterior segment and retina using coherence revival

We report on an implementation of coherence revival-based heterodyne swept source optical coherence tomography that is capable of simultaneously imaging the anterior and posterior eye. A polarization-encoded sample arm was used to efficiently focus orthogonal polarizations on the anterior segment and retina. Depth encoding was achieved using coherence revival, which allows for multiple depths within a sample to be simultaneously imaged and frequency encoded by carefully controlling the optical pathlength of each sample path. This design is a significant step toward whole-eye optical coherence tomography (OCT), which would enable customized ray-traced modeling of patient eyes to improve refractive surgical interventions and eliminate optical artifacts in retinal OCT diagnostics. We demonstrated the feasibility of this system for in vivo imaging by simultaneously acquiring images of the anterior segments and retinas in healthy human volunteers.     

Full range complex ultrahigh sensitive optical microangiography

This Letter presents a useful method that combines the full range complex Fourier domain optical coherence tomography (OCT) with the ultrahigh sensitive optical microangiography (OMAG) to achieve full range complex imaging of blood flow within microcirculatory tissue beds in vivo. We propose to use the fast scanning axis to realize the full range complex imaging, while using the slow axis to achieve OMAG imaging of blood flow. We demonstrate the proposed method by using a high speed 1310?nm OCT/OMAG system running at 92?kHz line scan rate to image the flow phantoms in vitro, and the blood flows in tissue beds in vivo.     

In vivo human retinal imaging by ultrahigh-speed spectral domain optical coherence tomography

An ultrahigh-speed spectral domain optical coherence tomography (SD-OCT) system is presented that achieves acquisition rates of 29,300 depth profiles/s. The sensitivity of SD-OCT and time domain OCT (TD-OCT) are experimentally compared, demonstrating a 21.7-dB improvement of SD-OCT over TD-OCT. In vivo images of the human retina are presented, demonstrating the ability to acquire high-quality structural images with an axial resolution of 6 microm at ultrahigh speed and with an ocular exposure level of less than 600 microW.     

Adaptive-optics ultrahigh-resolution optical coherence tomography

Merging of ultrahigh-resolution optical coherence tomography (UHR OCT) and adaptive optics (AO), resulting in high axial (3 microm) and improved transverse resolution (5-10 microm) is demonstrated for the first time to our knowledge in in vivo retinal imaging. A compact (300 mm x 300 mm) closed-loop AO system, based on a real-time Hartmann-Shack wave-front sensor operating at 30 Hz and a 37-actuator membrane deformable mirror, is interfaced to an UHR OCT system, based on a commercial OCT instrument, employing a compact Ti:sapphire laser with 130-nm bandwidth. Closed-loop correction of both ocular and system aberrations results in a residual uncorrected wave-front rms of 0.1 microm for a 3.68-mm pupil diameter. When this level of correction is achieved, OCT images are obtained under a static mirror configuration. By use of AO, an improvement of the transverse resolution of two to three times, compared with UHR OCT systems used so far, is obtained. A significant signal-to-noise ratio improvement of up to 9 dB in corrected compared with uncorrected OCT tomograms is also achieved.     

Extraction of optical scattering parameters and attenuation compensation in optical coherence tomography images of multilayered tissue structures

A recently developed analytical optical coherence tomography (OCT) model [Thrane et al., J. Opt. Soc. Am. A 17, 484 (2000)] allows the extraction of optical scattering parameters from OCT images, thereby permitting attenuation compensation in those images. By expanding this theoretical model, we have developed a new method for extracting optical scattering parameters from multilayered tissue structures in vivo. To verify this, we used a Monte Carlo (MC) OCT model as a numerical phantom to simulate the OCT signal for heterogeneous multilayered tissue. Excellent agreement between the extracted values of the optical scattering properties of the different layers and the corresponding input reference values of the MC simulation was obtained, which demonstrates the feasibility of the method for in vivo applications. This is to our knowledge the first time such verification has been obtained, and the results hold promise for expanding the functional imaging capabilities of OCT.     

Combined Raman spectroscopy and optical coherence tomography device for tissue characterization

We report a dual-modal device capable of sequential acquisition of Raman spectroscopy (RS) and optical coherence tomography (OCT) along a common optical axis. The device enhances application of both RS and OCT by precisely guiding RS acquisition with OCT images while also compensating for the lack of molecular specificity in OCT with the biochemical specificity of RS. We characterize the system performance and demonstrate the capability to identify structurally ambiguous features within an OCT image with RS in a scattering phantom, guide acquisition of RS from a localized malignancy in ex vivo breast tissue, and perform in vivo tissue analysis of a scab.     

Dual-core ytterbium fiber amplifier for high-power 1060 nm swept source multichannel optical coherence tomography imaging

A novel (to our knowledge) dual-core ytterbium (Yb(3+)) doped fiber, as an optically pumped amplifier, boosts the output power from a 1060 nm swept source laser beyond 250 mW, while providing a wavelength tuning range of 93 nm, for optical coherence tomography (OCT) imaging. The design of the dual-core Yb-doped fiber amplifier and its multiple wavelength optical pumping scheme to optimize output bandwidth are discussed. Use of the dual-core fiber amplifier showed no appreciable degradation to the coherence length of the seed laser. The signal intensity improvement of this amplifier is demonstrated on a multichannel in vivo OCT imaging system at 1060 nm.     

Tracking optical coherence tomography

An experimental tracking optical coherence tomography (OCT) system has been clinically tested. The prototype instrument uses a secondary sensing beam and steering mirrors to compensate for eye motion with a closed-loop bandwidth of 1 kHz and tracking accuracy, to within less than the OCT beam diameter. The retinal tracker improved image registration accuracy to <1 transverse pixel (<60 microm). Composite OCT images averaged over multiple scans and visits show a sharp fine structure limited only by transverse pixel size. As the resolution of clinical OCT systems improves, the capability to reproducibly map complex structures in the living eye at high resolution will lead to improved understanding of disease processes and improved sensitivity and specificity of diagnostic procedures.     

Swept source optical coherence tomography based on non-uniform discrete fourier transform

A high-speed high-sensitivity swept source optical coherence tomography （SSOCT） system using a high speed swept laser source is developed. Non-uniform discrete fourier transform （NDFT） method is introduced in the SSOCT system for data processing. Frequency calibration method based on a Mach-Zender interferometer （MZI） and conventional data interpolation method is also adopted in the system for comparison. Optical coherence tomography （OCT） images from SSOCT based on the NDFT method, the MZI method, and the interpolation method are illustrated. The axial resolution of the SSOCT based on the NDFT method is comparable to that of the SSOCT system using MZI calibration method and conventional data interpolation method. The SSOCT system based on the NDFT method can achieve higher signal intensity than that of the system based on the MZI calibration method and conventional data interpolation method because of the better utilization of the power of source.     

OCT图像法测量折射率

基于光程匹配原理提出了一种用光学相干断层成像(OCT)系统获得的图像测量样品折射率的方法。通过分析光程匹配原理,给出用OCT图像法测量样品折射率的原理及过程。以玻璃载波片和黄瓜组织为样品进行实验。实验结果表明,用OCT图像法获得的载玻片和黄瓜组织的折射率测量值分别为1.499和1.353,与发表或已知的折射率结果相吻合,测试结果的随机误差可小于0.01。另外,使用OCT图像法通过短时间所采集的两幅图像可对横向扫描任意位置的折射率同时进行测量。该方法进一步简化了基于光程匹配原理的折射率测量法的过程,缩短了测量时间,是一种快速测量样品折射率的实用方法。     

Imaging of subcutaneous blood vessels and flow velocity profiles by optical coherence tomography

We have applied a compact low power rapid scanning Doppler Optical Coherence Tomography system to monitor multi-dimensional velocity profiles within the complex vessels and simultaneous real-time non-invasive imaging of skin tissues morphology in vivo, in the wavelength range of 1.3–1.5 nm. Optical clearing of skin tissues has been utilized to achieve depth of OCT images up to 1.7 mm. Current approach enables applying low-power (0.4–0.5 mW) and low-noise broadband near-infrared light sources and obtaining OCT images with down to 12 μm spatial resolution. Two-dimensional time-domain OCT images of complex flow velocity profiles in blood vessel phantom and in vivo subcutaneous human skin tissues are presented. The effect of optical clearing on in vivo images is demonstrated and discussed.     

Phase-resolved optical coherence tomography and optical Doppler tomography for imaging blood flow in human skin with fast scanning speed and high velocity sensitivity

We have developed a novel phase-resolved optical coherence tomography (OCT) and optical Doppler tomography (ODT) system that uses phase information derived from a Hilbert transformation to image blood flow in human skin with fast scanning speed and high velocity sensitivity. Using the phase change between sequential scans to construct flow-velocity imaging, this technique decouples spatial resolution and velocity sensitivity in flow images and increases imaging speed by more than 2 orders of magnitude without compromising spatial resolution or velocity sensitivity. The minimum flow velocity that can be detected with an axial-line scanning speed of 400 Hz and an average phase change over eight sequential scans is as low as 10 microm/s, while a spatial resolution of 10 microm is maintained. Using this technique, we present what are to our knowledge the first phase-resolved OCT/ODT images of blood flow in human skin.     

Multiple Backscattering Effects in Optical Coherence Tomography Images of Layered Turbid Media

We study the influence of multiple backscattering on optical coherence tomography (OCT) images or pulsed-sounding images of layered turbid media. A method for calculating the signal of various orders of backscattering is proposed. The retarding effects of OCT-signal dropping are analyzed. The contrast attenuation of an image of a layered medium due to multiple backscattering is examined. The blurring effect of an image of the back boundary of a scattering layer, caused by a delay of multiply scattered photons compared with single-scattered ones, is studied theoretically and experimentally using an OCT device.     

Noninvasive monitoring of glucose concentration with optical coherence tomography

We have proposed a tested in tissue phantoms and in vivo a novel sensor based on optical coherence tomography (OCT) for noninvasive and continuous monitoring of blood glucose concentration. OCT images were obtained from pig and rabbit skin before and after glucose administration. Slopes of OCT signals decreased substantially (~40% in tissues in vivo) and linearly with the increase of blood glucose concentration from 4 to 30 mM, typical for normal and diabetic subjects. Phantom studies demonstrated 1% accuracy of scattering-coefficient measurement. Our theoretical and experimental studies suggest that glucose concentration can potentially be measured noninvasively with high sensitivity and accuracy with OCT systems.     

Sequential optical coherence tomography and confocal imaging

We report a system capable of sequentially acquiring two en-face images of different depth resolutions. The two images are generated by use of different principles, optical coherence tomography (OCT) and confocal microscopy, and have depth resolutions, at present, of better than 20 microm and over 0.12 mm, respectively. The lower-depth-resolution image is ideal for target positioning before collection of stacks of en-face OCT images. Switching between the two types of image by flipping an opaque screen in the reference arm, coupled with self-adjusting gain operation of avalanche photodiodes in the receiver. We illustrate the usefulness of the system by imaging a leaf and an optic nerve in vivo.     

光学相干层析成像系统的蒙特卡罗模拟

将光学相干层析成像系统采样臂的光纤与聚焦系统和被测样品作为一个整体来模拟光学相干层析成像信号的形成机理.通过追迹采样光束中每一光子在聚焦系统和被测样品中的随机传输轨迹,来决定该光子对光学相干层析成像信号是否有贡献及贡献大小.对样品IntralipidTM的模拟结果与实验结果表明：1）高散射系数和弱前向散射是引起光学相干层析成像信号随测量深度增加迅速减弱的主要原因;2）对于确定的聚焦系统,光纤的数值孔径有一最佳取值范围.数值孔径太小,则光学相干层析成像信号很弱;数值孔径超出这一范围继续增大,光学相干层析成像信号变化很小.3）当光纤的光轴偏离聚焦系统的光轴h距离时,光学相干层析成像信号随h的增加而减弱.     

基于受激辐射信号的谱域光学相干层析分子成像方法

鉴于不同生理病理状态下组织复折射率实部的变化不大,传统光学相干层析(OCT)成像技术在分子特异性识别上存在先天不足.为此,本文提出了基于受激辐射信号的OCT成像方法,可在实现传统散射成像的同时,实现基于受激辐射信号的分子成像.在超高分辨率谱域OCT系统的基础上,通过增设光谱分光与调制抽运光支路,建立了基于单宽谱光源的抽运探测谱域OCT系统,详细推导了调制抽运下受激辐射信号的获取与成像公式.利用搭建的抽运探测谱域OCT系统,实现了瞬态受激辐射信号的相干探测.基于同时获取的受激辐射OCT信号和传统OCT信号,成功重构了氮化物粉末构建样品的基于受激辐射信号的分子对比OCT图像.     

Multilevel Deep Feature Generation Framework for Automated Detection of Retinal Abnormalities Using OCT Images

Optical coherence tomography (OCT) images coupled with many learning techniques have been developed to diagnose retinal disorders. This work aims to develop a novel framework for extracting deep features from 18 pre-trained convolutional neural networks (CNN) and to attain high performance using OCT images. In this work, we have developed a new framework for automated detection of retinal disorders using transfer learning. This model consists of three phases: deep fused and multilevel feature extraction, using 18 pre-trained networks and tent maximal pooling, feature selection with ReliefF, and classification using the optimized classifier. The novelty of this proposed framework is the feature generation using widely used CNNs and to select the most suitable features for classification. The extracted features using our proposed intelligent feature extractor are fed to iterative ReliefF (IRF) to automatically select the best feature vector. The quadratic support vector machine (QSVM) is utilized as a classifier in this work. We have developed our model using two public OCT image datasets, and they are named database 1 (DB1) and database 2 (DB2). The proposed framework can attain 97.40% and 100% classification accuracies using the two OCT datasets, DB1 and DB2, respectively. These results illustrate the success of our model.