Optically deviated focusing method based high-speed SD-OCT for in vivo retinal clinical applications

The aim of this study is to provide accurately focused, high-resolution in vivo human retinal depth images using an optically deviated focusing method with spectral-domain optical coherence tomography (SD-OCT) system. The proposed method was applied to increase the retinal diagnosing speed of patients with various values of retinal distances (i.e., the distance between the crystalline eye lens and the retina). The increased diagnosing speed was facilitated through an optical modification in the OCT sample arm configuration. Moreover, the optical path length matching process was compensated using the proposed optically deviated focusing method. The developed system was mounted on a bench-top cradle to overcome the motion artifacts. Further, we demonstrated the capability of the system by carrying out in vivo retinal imaging experiments. The clinical trials confirmed that the system was effective in diagnosing normal and abnormal retinal layers as several retinal abnormalities were identified using non-averaged single-shot OCT images, which demonstrate the feasibility of the method for clinical applications.     

Applying LED in full-field optical coherence tomography for gastrointestinal endoscopy

Optical coherence tomography (OCT) has become an important medical imaging technology due to its non-invasiveness and high resolution. Full-field optical coherence tomography (FF-OCT) is a scanning scheme especially suitable for en face imaging as it employs a CMOS/CCD device for parallel pixels processing. FF-OCT can also be applied to high-speed endoscopic imaging. Applying cylindrical scanning and a right-angle prism, we successfully obtained a 360° tomography of the inner wall of an intestinal cavity through an FF-OCT system with an LED source. The 10-μm scale resolution enables the early detection of gastrointestinal lesions, which can increase detection rates for esophageal, stomach, or vaginal cancer. All devices used in this system can be integrated by MOEMS technology to contribute to the studies of gastrointestinal medicine and advanced endoscopy technology.     

Multilayered scattering reference mirror for full field optical coherence tomography with application to cell profiling

A multilayered scattering structure is proposed and demonstrated as a reference mirror for use with full field optical coherence tomography (FF-OCT) to increase contrast of tissue imaging and provide compensation. Common-path FF-OCT systems were built demonstrating high resolution cell profiling. The use of this mirror with frequency domain FF-OCT allows 3D images in real time.     

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.     

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.     

Fourier domain mode locking at 1050 nm for ultra-high-speed optical coherence tomography of the human retina at 236,000 axial scans per second

A Fourier domain mode-locked (FDML) laser at 1050 nm for ultra-high-speed optical coherence tomography (OCT) imaging of the human retina is demonstrated. Achievable performance, physical limitations, design rules, and scaling principles for FDML operation and component choice in this wavelength range are discussed. The fiber-based FDML laser operates at a sweep rate of 236 kHz over a 63 nm tuning range, with 7 mW average output power. Ultra-high-speed retinal imaging is demonstrated at 236,000 axial scans per second. This represents a speed improvement of approximately10x over typical high-speed OCT systems, paving the way for densely sampled volumetric data sets and new imaging protocols.     

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.     

Tomographic imaging of a suspending single live cell using optical tweezer-combined full-field optical coherence tomography

We propose a label-free depth-resolved tomographic scheme for imaging a single live cell in fluid. This approach utilizes a modified time-domain full-field optical coherence tomography (FF-OCT) system combined with an optical tweezer technique. The optical trap for holding a moving specimen is made by tightly focusing a 1064 nm Q-switching pulsed laser beam with a 1.0 NA microscope objective in the sample arm of the FF-OCT part. By cosharing the probe for both systems, the optical actions of trapping and cellular resolution tomographic imaging could be achieved simultaneously. Feasibility of the combined system is demonstrated by imaging micron-sized polystyrene beads and a living suspension cell in medium.     

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.     

光学相干层析术用于鲜红斑痣诊断

光学相干层析术(optical coherence tomography,简称OCT)具有非侵入性,高分辨及高速成像的优点,特别适合于生物医学领域。但由于大部分生物组织具高散射系数,通常仅能对表层组织下数毫米深度内进行成像。穿透深度不足限制了OCT在皮肤科等领域应用。作为常见多发病的鲜红斑痣具有病变组织浅,血管增生明显等特点,所以OCT非常适于鲜红斑痣的检测。通过选择皮肤穿透性好的中心波长为1310nm超辐射二极管,合理优化样品臂和参考臂光强比例及偏振控制,实现了对鲜红斑痣在体成像研究,采集了清晰的OCT图像,得到其关键特征参数,如表皮层厚度,血管直径等,对鲜红斑痣的诊断及制定合理治疗方案具有重要意义。     

Optical coherence tomography

Optical Coherence Tomography (OCT) is a new technology for performing high-resolution cross sectional imaging. OCT is analogous to ultrasound imaging, except that it uses light instead of sound. OCT can provide cross sectional images of tissue structure on the micron scale in situ and in real time. OCT functions as a type of optical biopsy and is a powerful imaging technology for medical diagnostics because unlike conventional histopathology which requires removal of a tissue specimen and processing for microscopic examination, OCT can provide images of tissue in situ and in real time. OCT can be used where standard excisional biopsy is hazardous or impossible, to reduce sampling errors associated with excisional biopsy, and to guide interventional procedures.     

聚吡咯修饰的金纳米棒对肿瘤的光学相干层析成像的影响

聚吡咯(PPy)制备简单、生物相容性好,且在近红外(NIR)光谱范围内有很强的吸收,可作为一种良好的光热治疗试剂;同时,其NIR光吸收性质也可用于增强光学相干层析成像(OCT)的对比效果。因此,采用PPy对传统的OCT对比试剂——金纳米棒(GNR)进行表面修饰,有望获得对比效果更好且生物毒性较小的新型OCT对比试剂。选用吡咯为起始原料,在GNR表面进行一步简单的氧化聚合反应即可制备得到PPy修饰的金纳米棒(GNR-PPy)。利用紫外-可见吸收光谱,拉曼光谱和透射电子显微镜对制备的样品进行了分析和表征。构建小鼠荷瘤模型,以研究GNR-PPy对肿瘤OCT图像对比度的增强效果。采用中心波长为840 nm的OCT系统对注射了纳米粒子的肿瘤区域进行OCT成像。结果表明,肿瘤组织注射了GNR-PPy后,OCT信号衰减非常明显;与注射了GNR的OCT图像相比,840 nm光在GNR-PPy的OCT图像中的穿透深度明显更低。从OCT图像中抽提出一维的衰减曲线对OCT图像进行定量分析,发现注射有GNR-PPy肿瘤组织的OCT信号衰减系数明显高于注射了GNR的组织。表明,相对于GNR,GNR-PPy具有更好的OCT信号对比效果,这在增强肿瘤成像效果方面具有潜在应用价值。     

Integrated multimodal endomicroscopy platform for simultaneous en face optical coherence and two-photon fluorescence imaging

We report an all-fiber-optic scanning, multimodal endomicroscope capable of simultaneous optical coherence tomography (OCT) and two-photon fluorescence (TPF) imaging. Both imaging modalities share the same miniature fiber-optic scanning endomicroscope, which consists of a double-clad fiber with a core operating in single mode at both the OCT (1310 nm) and two-photon excitation (1550 nm) wavelengths, a piezoelectric two-dimensional fiber-optic beam scanner, and a miniature aspherical compound lens suitable for simultaneous acquisition of en face OCT and TPF images. A fiber-optic wavelength division multiplexer was employed in the integrated platform to combine the low coherence OCT light source and the femtosecond two-photon excitation laser into the same optical path. Preliminary imaging results of cell cultures and mouse tissue ex vivo demonstrate the feasibility of simultaneous real-time OCT and TPF imaging in a scanning endomicroscopy setting for the first time.     

Simultaneous optical coherence tomography--Indocyanine Green dye fluorescence imaging system for investigations of the eye's fundus

We have developed a dual-channel optical coherence tomography-Indocyanine Green dye (OCT-ICG) fluorescence system based on a previously reported ophthalmic OCT confocal imaging system. The confocal channel is tuned to the fluorescence wavelength range of the ICG, and light from the same optical source is used to generate the OCT image and to excite the ICG fluorescence. The system enables the clinician to visualize simultaneously en face OCT slices and corresponding ICG angiograms of the ocular fundus, displayed side by side. C-scan (constant depth) and B-scan (cross section) images are collected by a fast en face scan (T scan). The pixel-to-pixel correspondence between the OCT and angiography images allows the user to capture OCT B scans precisely at selected points on the ICG confocal images.     

基于平稳小波变换的时域光学相干层析系统

以平衡检测原理为基础,利用中心波长为700 nm的宽带低相干白光光源,在自由空间中搭建了分辨率为0.93 m的基于平稳小波变换（SWT）的时域光学相干层析（TDOCT）系统,并将其应用于塑料薄片与透明胶纸多层薄膜结构的无损评价。针对现有算法重构效果不够理想的问题,通过对OCT成像过程中的图像增强手段的对比,提出利用SWT分解算法处理多层薄膜结构的光学相干层析二维图像。由薄膜检测的实验结果可知,从SWT细节系数中可以提取更显著的多层薄膜界面干涉信号,从而提高多层薄膜界面的增强效果。     

Ultrahigh-resolution full-field optical coherence tomography using spatial coherence gating and quasi-monochromatic illumination

We developed an ultrahigh-resolution full-field optical coherence tomography (FF-OCT) microscope that is based on the spatial, rather than the temporal, coherence gating. The microscope is capable of observing three-dimensional microbiological structures as small as 0.4 μm × 0.4 μm × 1.0 μm (xyz) using quasi-monochromatic light and a liquid crystal retarder. Unlike traditional FF-OCT systems, this microscope can be operated in high resolution for any preferable wavelength with minimized defocusing and dispersion effects. High-resolution images of an onion cell are presented.     

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.     

Statistics and reduction of speckle in optical coherence tomography

Studies have shown that optical coherence tomography (OCT) is useful in imaging microscopic structures through highly scattering media. Because spatially coherent light is used in OCT, speckle in the reconstructed image is unavoidable, resulting in degradation of the quality of the OCT images and impaired ability to differentiate subsurface structures. Therefore speckle reduction is an important issue in OCT imaging. We develop speckle statistics that are appropriate to the OCT measurements and demonstrate a simple and practical speckle-reduction technique.     

Polarization-resolved second-harmonic-generation optical coherence tomography in collagen

We describe a novel imaging technique, second-harmonic-generation optical coherence tomography (SHOCT). This technique combines the spatial resolution and depth penetration of optical coherence tomography (OCT) with the molecular sensitivity of second-harmonic-generation spectroscopy. As a consequence of the coherent detection required for OCT, polarization-resolved images arise naturally. We demonstrate this new technique on a skin sample from the belly of Icelandic salmon, acquiring polarization-resolved SHOCT and OCT images simultaneously.     

光学相干断层扫描成像新技术OCT

光学相干层析成像技术（optical coherence tomography,简称OCT）是一种新型成像方法,在生物医学和材料等许多领域有广泛的应用。本文介绍了OCT的基本原理,并给出了用该装置对生物组织样品的成像结果。此外还用计算机图像处理的方法,使得图像分辨率得到了进一步提高。