Broadband superluminescent diode-based ultrahigh resolution optical coherence tomography for ophthalmic imaging

Spectral domain optical coherence tomography (SD-OCT) with ultrahigh resolution can be used to measure precise structures in the context of ophthalmic imaging. We designed an ultrahigh resolution SD-OCT system based on broadband superluminescent diode (SLD) as the light source. An axial resolution of 2.2 μm in tissue, a scan depth of 1.48 mm, and a high sensitivity of 93 dB were achieved by the spectrometer designed. The ultrahigh-resolution SD-OCT system was employed to image the human cornea and retina with a cross-section image of 2048 × 2048 pixels. Our research demonstrated that ultrahigh -resolution SD-OCT can be achieved using broadband SLD in a simple way.     

In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an achromatized endoscope

Endoscopic ultrahigh-resolution optical coherence tomography (OCT) enables collection of minimally invasive cross-sectional images in vivo, which may be used to facilitate rapid development of reliable mouse models of colon disease as well as assess chemopreventive and therapeutic agents. The small physical scale of mouse colon makes light penetration less problematic than in other tissues and high resolution acutely necessary. In our 2-mm diameter endoscopic time domain OCT system, isotropic ultrahigh-resolution is supported by a center wavelength of 800 nm and full-width-at-half-maximum bandwidth of 150 nm (mode-locked titanium:sapphire laser) combined with 1:1 conjugate imaging of a small core fiber. A pair of KZFSN5/SFPL53 doublets provides excellent color correction to support wide bandwidth throughout the imaging depth. A slight deviation from normal beam exit angle suppresses collection of the strong back reflection at the exit window surface. Our system achieves axial resolution of 3.2 microm in air and 4.4-microm lateral spot diameter with 101-dB sensitivity. Microscopic features too small to see in mouse tissue with conventional resolution systems, including colonic crypts, are clearly resolved. Resolution near the cellular level is potentially capable of identifying abnormal crypt formation and dysplastic cellular organization.     

Ultrahigh-resolution optical coherence tomography

In the past two decades, optical coherence tomography (OCT) has been established as an adjunct diagnostic technique for noninvasive, high-resolution, cross-sectional imaging in a variety of medical fields. The rapid development of ultrabroad bandwidth light sources has recently enabled a significant improvement in OCT imaging resolution, demonstrating the potential of OCT to accomplish its original goal of performing noninvasive optical biopsies, i.e., the in vivo visualization of microstructural morphology in situ, which had previously only been possible with histopathology. In addition, these novel light sources might also enable the use of spectroscopic OCT, an extension of ultrahigh-resolution OCT, for enhancing image contrast as well as detecting spatially resolved functional, biochemical tissue information. State-of-the-art-light sources that now permit ultrahigh-resolution OCT covering the whole wavelength region from 500 to 1600 nm are reviewed and fundamental limitations of OCT image resolution are discussed. Ex vivo ultrahigh-resolution OCT tomograms are compared with histological results; first clinical in vivo ultrahigh-resolution OCT and preliminary spectroscopic OCT results are presented and their impact for future clinical and research applications is discussed.     

Quantitative analysis on tongue inspection in traditional Chinese medicine using optical coherence tomography

Tongue inspection (TI) is an important and unique diagnostic method in traditional Chinese medicine (TCM), because significant connections between various viscerae diseases and abnormalities in the tongue have been verified. In TCM, TI is simple and non invasive, but in clinical applications, TI is subjectively based on the experience and technique of physicians. To avoid this problem, optical coherence tomography (OCT) imaging is introduced here for TI. We study OCT imaging in rats in vivo from chronic gastritis group (model) and normal group (control) and quantitatively analyze the relative parameters, such as the thickness and the moisture degree of TI. Our results show that OCT images properly demonstrate the thickness of the tongue coating and the moisture degree of the tongue in both groups, and the thickness is increased in the model group from that in the normal group, while the moisture degree decreases. As a result, OCT technology has the potential to provide physicians with an objective diagnostic standard for visual TI in TCM clinical practice and research.     

Feasibility study on bonding quality inspection of microfluidic devices by optical coherence tomography

This paper reports the feasibility of optical coherence tomography (OCT) technology for inspection of bonding quality of microfluidic devices in manufacturing environments. A compact optical-fiber-based OCT is developed and its measurement performance is characterized. A series of microfluidic devices respectively bonded by adhesive tape, thermal method, and oxygen plasma, are inspected. The defects of geometry deformation and sealing completeness are emphasized during measurements. Based on the inspection results, some discoveries related to the production of microfluidic devices are discussed.     

基于卷积神经网络的眼科光学相干断层成像图像的自动分类

目的 提出一种基于卷积神经网络(convolutional neural network,CNN)的眼科光学相干断层成像(optical coherence tomography,OCT)图像自动分类方法,实现对视网膜OCT图像的自动分类,缓解人工诊断依赖医生的临床经验、费时费力等问题.方法 基于公开的数据集2014_BOE_Srinivasan构建了2个样本数据集.其中样本数据集一为仅对数据集中的图像进行预处理后裁剪,样本数据集二为对取出测试集后剩余图像的裁剪过程中引入随机平移和水平翻转技术对图像进行扩充,并划分为训练集和验证集.搭建基于CNN的视网膜OCT图像分类网络,并分别使用两个数据集训练网络得到分类模型.最后使用独立的测试集对模型进行测试,并通过输出混淆矩阵查看模型对3种类别图像的分类情况.结果 通过混淆矩阵计算得出,使用扩充后的图像训练的分类模型的准确度为93.43％,灵敏度为91.38％,特异度为95.88％.结论 提出的基于CNN的视网膜OCT图像自动分类方法可以对老年性黄斑变性、糖尿病性黄斑水肿和正常3种类别的视网膜OCT图像进行分类.同时,数据扩充有助于提高分类算法的性能.     

In situ imaging of lung alveoli with an optical coherence tomography needle probe

In situ imaging of alveoli and the smaller airways with optical coherence tomography (OCT) has significant potential in the assessment of lung disease. We present a minimally invasive imaging technique utilizing an OCT needle probe. The side-facing needle probe comprises miniaturized focusing optics consisting of no-core and GRIN fiber encased within a 23-gauge needle. 3D-OCT volumetric data sets were acquired by rotating and retracting the probe during imaging. The probe was used to image an intact, fresh (not fixed) sheep lung filled with normal saline, and the results validated against a histological gold standard. We present the first published images of alveoli acquired with an OCT needle probe and demonstrate the potential of this technique to visualize other anatomical features such as bifurcations of the bronchioles.     

Design of a handheld optical coherence microscopy endoscope

Optical coherence microscopy (OCM) combines coherence gating, high numerical aperture optics, and a fiber-core pinhole to provide high axial and lateral resolution with relatively large depth of imaging. We present a handheld rigid OCM endoscope designed for small animal surgical imaging, with a 6-mm diam tip, 1-mm scan width, and 1-mm imaging depth. X-Y scanning is performed distally with mirrors mounted to micro galvonometer scanners incorporated into the endoscope handle. The endoscope optical design consists of scanning doublets, an afocal Hopkins relay lens system, a 0.4 numerical aperture water immersion objective, and a cover glass. This endoscope can resolve laterally a 1.4-μm line pair feature and has an axial resolution (full width half maximum) of 5.4 μm. Images taken with this endoscope of fresh ex-vivo mouse ovaries show structural features, such as corpus luteum, primary follicles, growing follicles, and fallopian tubes. This rigid handheld OCM endoscope can be useful for a variety of minimally invasive and surgical imaging applications.     

Enhancing the signal-to-noise ratio in ophthalmic optical coherence tomography by image registration--method and clinical examples

Optical coherence tomography (OCT) has already proven an important clinical tool for imaging and diagnosing retinal diseases. Concerning the standard commercial ophthalmic OCT systems, speckle noise is a limiting factor with respect to resolving relevant retinal features. We demonstrate successful suppression of speckle noise from mutually aligning a series of in vivo OCT recordings obtained from the same retinal target using the Stratus system from Humphrey-Zeiss. Our registration technique is able to account for the axial movements experienced during recording as well as small transverse movements of the scan line from one scan to the next. The algorithm is based on a regularized shortest path formulation for a directed graph on a map formed by interimage (B-scan) correlations. The resulting image enhancement typically increases the contrast-to-noise ratio (CNR) with a factor of three or more and facilitates segmentation and quantitative characterization of pathologies. The method is currently successfully being applied by medical doctors in a number of specific retinal case studies.     

光相干层析成像中的散斑

由于光相干层析成像中测量的干涉信号空间频带有限 ,因此会产生散斑。在高散射的生物组织图像中 ,散斑具有双重身份 ,即作为噪声源和作为组织微结构的信号载体。本文的前半部分对于光相干层析成像中散斑的产生原因、统计特性以及分类作了综述。通过采样束的相位和振幅扰动可以定义信号载体散斑和信号降低散斑。本文的后半部分讨论了减少散斑的 4种方法 :偏振合成法、空间合成法、频率合成法和数字信号处理方法 ,并且通过举例对每一种方法的有效性作了简单的分析。最后 ,文章提出了需进一步研究的问题     

Dynamic focus in optical coherence tomography for retinal imaging

Imaging the human retina still represents the main field of application of optical coherence tomography (OCT). A major advantage of OCT is the decoupling of depth resolution (given by the coherence length of the light source) and transverse resolution (given by the focal spot size). This enables images of the retina with high depth resolution. On the other hand, in most OCT systems, a limited transverse resolution has been accepted to provide a sufficiently large (approximately 1 mm) depth of focus. However, to obtain images with high transverse resolution throughout the whole depth of the retina (especially in the nerve head region) a tracking of coherence gate and focus position (dynamic focus) is essential. This study realizes a dynamic focus in a time domain transversal (en face) scanning system for retinal imaging. We show that maintenance of a transverse resolution of approximately 4.4 microm can be achieved over an optical depth of 1 mm in a model eye and apply our method to imaging the human retina in vivo.     

Active retinal tracker for clinical optical coherence tomography systems

An active, hardware-based retinal tracker is integrated with a clinical optical coherence tomography (OCT) system to investigate the effects of stabilization on acquisition of high-resolution retinal sections. The prototype retinal tracker locks onto common fundus features, detects transverse eye motion via changes in feature reflectance, and positions the OCT diagnostic beam to fixed coordinates on the retina with mirrors driven by a feedback control loop. The system is tested in a full clinical protocol on subjects with normal and glaucomatous eyes. Experimental analysis software is developed to coalign and coadd multiple fundus and OCT images and to extract quantitative information on the location of structures in the images. Tracking is highly accurate and reproducible on all but one subject, resulting in the ability to scan the same retinal location continually over long periods of time. The results show qualitative improvement in 97% of coadded OCT scans and a reduction in the variance of the position of the optic disc cup edge to less than 1 pixel (< 60 microm). The tracking system can be easily configured for use in research on ultra-high-resolution OCT systems for advanced image modalities. For example, tracking will enable very high density 3-D scans of the retina, which are susceptible to eye motion artifacts even for new high-speed systems.     

Megahertz streak-mode Fourier domain optical coherence tomography

Here we present an ultrahigh-speed Fourier-domain optical coherence tomography (OCT) that records the OCT spectrum in streak mode with a high-speed area scan camera, which allows higher OCT imaging speed than can be achieved with a line-scan camera. Unlike parallel OCT techniques that also use area scan cameras, the conventional single-mode fiber-based point-scanning mechanism is retained to provide a confocal gate that rejects multiply scattered photons from the sample. When using a 1000 Hz resonant scanner as the streak scanner, 1,016,000 A-scans have been obtained in 1 s. This method's effectiveness has been demonstrated by recording in vivo OCT-image sequences of embryonic chick hearts at 1000 frames/s. In addition, 2-megahertz OCT data have been obtained with another high speed camera.     

Advanced modelling of optical coherence tomography systems

Analytical and numerical models for describing and understanding the light propagation in samples imaged by optical coherence tomography (OCT) systems are presented. An analytical model for calculating the OCT signal based on the extended Huygens-Fresnel principle valid both for the single and multiple scattering regimes is reviewed. An advanced Monte Carlo model for calculating the OCT signal is also reviewed, and the validity of this model is shown through a mathematical proof based on the extended Huygens-Fresnel principle. Moreover, for the first time the model is verified experimentally. From the analytical model, an algorithm for enhancing OCT images is developed: the so-called true-reflection algorithm in which the OCT signal may be corrected for the attenuation caused by scattering. For the first time, the algorithm is demonstrated by using the Monte Carlo model as a numerical tissue phantom. Such algorithm holds promise for improving OCT imagery and to extend the possibility for functional imaging.     

定量血管内光学相干层析成像的研究进展

血管内光学相干层析成像(IVOCT)是目前分辨率最高的血管内成像技术,可对冠状动脉血管腔及管壁内膜下病变进行快速、清晰的成像。仅根据组织结构的层析图像无法精确识别粥样硬化斑块成分(如钙化、纤维化、脂质和混合斑块),需要形态结构之外的生理信息的对比机制,获得具有临床诊断价值的组织参数,即定量IVOCT(qIVOCT)。本文针对根据IVOCT原始背向散射信号和灰阶图像定量测量血管壁组织的光学特性参数、弹性参数和血流动力学参数的研究现状进行归纳和总结,分析目前存在的问题,展望可能的发展方向。     

Frequency domain multiplexing for speckle reduction in optical coherence tomography

Quantitative analysis of optical coherence tomography data can be strongly hampered by speckle. Here, we introduce a new method to reduce speckle, which leverages from Fourier-domain configurations and operates on individual axial scans. By subdividing the digitized spectrum into a number of distinct narrower windows, each with a different center frequency, several independent speckle patterns result. These can be averaged to yield a lower-resolution image with strongly reduced speckle. The full resolution image remains available for human interpretation; the low resolution version can be used for parametric imaging or quantitative analysis. We demonstrate this technique using intravascular optical frequency domain imaging data acquired in vivo.     

Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography

Raman spectroscopy (RS) and optical coherence tomography (OCT) are powerful tools for optical analysis of tissues with mutually complementary strengths and limitations. OCT excels at visualizing tissue microstructure but lacks molecular specificity, while RS can relay tissue biochemical composition but typically cannot relate microstructure. Previous implementations of combined RS-OCT have utilized a common sample arm while maintaining independent RS and OCT detection arms. We present the design and application of an integrated RS-OCT instrument with a common detection arm for both RS and OCT. The detector is a spectrograph capable of sequential detection of the 855-nm OCT signal and the Raman scatter generated by a 785-nm source. The capabilities of the instrument are demonstrated ex vivo in the calvaria and retina of rodents, as well as in vivo in human skin.     

In vivo video-rate cellular-level full-field optical coherence tomography

Full-field optical coherence tomography (FF-OCT) capable of in vivo cellular-level imaging is demonstrated for nonscanning horizontal cross-sectional imaging. The system is based on a white light interference microscope illuminated by a thermal light source. A dual-channel two-dimensional (2-D) detection technique incorporated with a pair of CCD cameras has been developed, where a pair of interferometric images with phase difference of pi/2 are simultaneously captured using an achromatic phase shifter. By acquiring an additional pair of images with a conventional phase shift method, a horizontal cross section is derived from every two consecutive CCD frames, enabling OCT imaging at the video rate. Using an ultrabroad bandwidth illumination incorporated with relatively high NA (0.8 NA) water immersion objectives, an axial resolution of 0.8 microm and a transverse resolution of 0.7 microm are experimentally confirmed. A field of view of 215 microm x 215 microm is covered by the 500 x 500 pixel CCD cameras. We demonstrate, for what is believed to be the first time, in vivo cellular-level blood flow imaging of a Xenopus laevis tadpole by FF-OCT.