全光学光声/OCT双模态成像系统及其应用

本文提出了一种新型的全光学光声/OCT双模态成像系统。该系统利用同一个低相干迈克尔逊干涉仪即可实现非接触式光声成像和OCT于一体,系统装置结构简单,可同时获取生物组织的吸收与散射结构信息。通过模拟实验证明了该双模态成像系统的可行性及成像能力,并对活体小鼠耳朵同时进行光声/OCT成像测试,实验结果表明非接触式光声/OCT双模态成像系统可以实现生物组织内的微血管及散射结构的高分辨率成像。进一步地,我们将光声/OCT双模态成像系统应用于基底细胞癌的检测中,获得了初步的研究结果,表明了该系统在皮肤肿瘤诊断中的具有潜在的应用价值。     

一体化的光声-荧光显微镜用于活体肿瘤成像

报道了一种利用单一波长激发的同时产生光声和荧光信号的显微成像系统,本成像系统具有超高的成像分辨率(<6μm)。借助外源的造影剂在近红外的吸收特性,利用光声-荧光显微成像系统对活体肿瘤进行光声/荧光成像。实验结果表明,光声-荧光显微镜在早期肿瘤的成像和检测等方面具有潜在的应用价值。因此,通过研究和选择适当的双模态造影剂,该系统在不同病理模型中可以提供更准确的组织信息及生理参数。     

基于直线电机连续-步进运动的快速光声显微成像系统

报道了一种利用直线电机连续-步进的扫描方式进行光声显微成像的系统,该系统在运动时走弓字型路线,其中直线电机在X轴方向上连续运动,在Y轴方向上以步进的方式运动,采集卡只在X轴电机运动的过程中连续采集。该成像系统较之前振镜扫描的方式扫描的范围更大,可达到厘米尺度范围内的生物组织光声成像;较之前的步进电机逐点扫描的方式扫描速度明显提高。同时本文采用电机带动光和超声换能器一同扫描的方式,较光和超声换能器不动电机带动样品扫描的方式更灵活。另外利用包埋碳丝的模拟样品和在体小鼠耳朵血管来验证系统的成像能力。实验结果表明,这种快速光声显微成像方法及其系统可以实现在体组织的高分辨率成像,有望成为一种无创、实时的光声显微镜应用于生物医学当中。     

光声成像在光动力疗法研究中的应用

组织氧合作用和光敏剂应用在疾病诊治中都有着重要的作用,因此其实时在体无损检测很有意义。光动力疗法涉及光敏剂、光和氧分子三大要素,其疗效受组织氧合作用影响。本文对光声成像(PAI)、光声寿命成像(PALI)和多光谱光声层析成像(MSOT)等光声成像技术在光动力疗法的研究和应用中的使用现状进行了综述。对相关设备系统在检测光敏剂、组织氧分压和微血管损伤等方面的应用原理和技术分别进行了介绍,并总结了这些技术的应用前景。     

用于皮肤色素病变检测的线性共焦光声显微镜

医学成像在皮肤病学的病理生理相关性的临床诊断和评估中起着不可或缺的作用。然而,现有的成像技术很难获得色素性皮肤病的黑色素空间分布和色素浓度。本文中我们提出了一种线性共焦扫描光声显微镜,用于快速无损地获取色素性皮肤病的病理结构变化和色素异常部位的黑色素分布情况。通过样品试验和动物试验证明了该显微成像系统的可行性及成像能力,并进一步对咖啡斑患者的正常表皮和病变表皮进行高分辨成像,图像结果表明,正常皮肤和咖啡斑皮肤之间黑色素分布及浓度存在着明显的差异。通过使用快速线性共焦扫描模式,可以在1 s内快速获得检测部位的光声断层图像。线性共焦扫描光声显微镜也可以扩展到诊断其他皮肤性疾病,是一种具有前景的皮肤病学成像技术。     

一体化光声乳腺成像系统

本文报道了一种一体化光声乳腺成像系统,利用光纤束与柔性探测器相匹配形成一体化光声激发-耦合-探测,因此与传统的光声成像系统相比,该系统具有形态适应性的优势,并可以实现大视场的光声成像。本文通过样品实验和离体乳腺肿瘤成像实验,探究该系统的成像能力,证明该系统具有大规模临床乳腺肿瘤筛查的潜力。     

基于环形阵列探测器的快速光声成像

构建一套基于环形阵探测器的快速光声成像系统用于生物组织的结构成像。该系统以环形阵探测器探测光声信号,采用八通道的采集系统采集光声信号,再利用有限场滤波反投影算法重建光声图像。利用埋有铅笔芯的琼脂样品来测试该系统的分辨率,利用离体猪眼和在体老鼠头部血管成像来验证系统的成像能力。实验结果表明,该系统能方便快速地实现生物组织的结构成像,有望实现早期乳腺癌的临床检测应用。     

基于光学相干检测的非接触式光声多普勒流速仪

在临床应用中,许多患处血液流速的测量都需要在无菌操作下进行。而传统的基于超声换能器实现的光声流速测量方式都需要在检测区域与探头之间填充超声耦合介质,从而无法实现无菌操作,限制了这种检测方式在临床上的应用。本文报道了一种非接触式光声多普勒流速仪,利用低相干的麦克尔逊干涉仪探测光声信号实现了流速测量。与超声探头为探测装置的光声多普勒血流仪相比,该方法可以实现非接触式的光声流速测量。在模拟血液样品实验中,定量的测量了横向流速,其速度范围在0. 2-3 mm/s,同时获得了截面流速图像。另外,活体小鼠耳部流速图像证明了该方法可以非接触、定量的测量血流信息。     

基于直线电机的大视场快速光声显微成像系统

光声成像技术是近年来发展的一种新型的无损医学成像技术,它是以脉冲激光作为激发源,以检测的声信号为信息载体,通过相应的图像重建算法重建组织内部结构和功能信息的成像方法。该方法结合了光学成像和声学成像的特点,可提供深层组织高分辨率和高对比度的组织层析图像,在生物医学临床诊断以及在体成像领域具有广泛的应用前景。目前光声成像的扫描方式主要有基于步进电机扫描方式和基于振镜的扫描方式,本文针对目前步进电机扫描速度慢(10 mm×10 mm;0.001帧/s),振镜扫描范围小(1 mm2)的不足,发展了基于直线电机扫描的大视场快速光声显微成像系统。同一条扫描线过程中直线电机速度最高可达200 mm/s。该技术采用逐线采集光声信号的方式,比逐点采集光声信号的步进电机快800倍。该系统对10 mm×10 mm全场扫描的扫描速度为0.8帧/s。最大可扫描视场范围可以达到50 mm×50 mm。大视场快速光声显微成像系统的发展将为生物医学提供新的成像工具。     

光学相干层析成像技术对关节软骨组织解剖分层表现对照研究

光学相干层析成像技术是一种高分辨率、非创伤性成像技术,它能够利用近红外光产生软骨组织的解析图像.实验的研究目的是验证光学相干层析成像技术对软骨组织解剖分层结构的成像能力.以猪膝关节软骨为样本,选择OCT检测的软骨区域运用解剖学方法获得组织切片,显微镜下观察.调查软骨OCT成像与组织学成像的相关性.结果显示OCT所测得的所有软骨的厚度值与切片显微镜结果一致,差异无显著意义 （P〉0.05）.光学相干层析成像系统能够呈现软骨组织解剖分层,该技术在软骨检测和临床关节病变诊断方面具有应用前景.     

Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography

Progress in understanding, diagnosis, and treatment of coronary artery disease (CAD) has been hindered by our inability to observe cells and extracellular components associated with human coronary atherosclerosis in situ. The current standards for microstructural investigation, histology and electron microscopy are destructive and prone to artifacts. The highest-resolution intracoronary imaging modality, optical coherence tomography (OCT), has a resolution of ~10 μm, which is too coarse for visualizing most cells. Here we report a new form of OCT, termed micro-optical coherence tomography (μOCT), whose resolution is improved by an order of magnitude. We show that μOCT images of cadaver coronary arteries provide clear pictures of cellular and subcellular features associated with atherogenesis, thrombosis and responses to interventional therapy. These results suggest that μOCT can complement existing diagnostic techniques for investigating atherosclerotic specimens, and that μOCT may eventually become a useful tool for cellular and subcellular characterization of the human coronary wall in vivo.     

Comparison of high frequency ultrasound and optical coherence tomography as modalities for high resolution and non invasive skin imaging.

High frequency ultrasound (HFUS) and optical coherence tomography (OCT) are techniques for high resolution imaging of tissues. The penetration depth of these modalities is limited, but it is sufficiently large enough for non invasive skin imaging. HFUS and OCT are based on the same concept. Waves (ultrasonic waves, respectively light waves) propagate along a narrow beam, are backscattered at tissue inhomogeneities and analyzed over time of flight to obtain spatially resolved morphological information. The objective of this paper is to compare HFUS and OCT in terms of resolution, dynamic range and contrast and to assess their value as tools for high resolution skin imaging. Measurements on phantoms and in vivo have been performed with a 100 MHz ultrasound system and an OCT-scanner working in the near infrared spectrum at 1300 nm wave-length. From the measurements, it can be concluded that OCT delivers an almost isotropic resolution (axial resolution about 5.8 microns, lateral resolution about 4.1 microns), whereas the resolution of the investigated HFUS system is more anisotropic (axial resolution about 9.3 microns, lateral resolution about 60 microns). HFUS and OCT show different penetration depths and a different contrast. Both techniques can, therefore, be combined advantageously in a multimodality approach to account for their individual characteristics.     

In vivo non-contact measurement of human iris elasticity by optical coherence elastography

Quantifying the mechanical properties of the iris can offer valuable insights into the pathophysiology of primary angle closure glaucoma. However, current techniques for iris elastography remain ex vivo with limited clinical applications. This article describes a proposition for a non-contact and non-invasive air-puff optical coherence elastography (OCE) system that can evaluate iris elasticity in vivo. Ten eyes recruited from seven subjects underwent OCE imaging acquisition under three different illumination conditions. The Young's modulus of each eye was detected and shown to be inversely proportional to the iris length, indicating a relationship between mechanical properties and morphology of the iris. With its noninvasive and high-resolution features, this air-puff system shows great potential for applications in clinical ophthalmology.     

Full‐field swept‐source optical coherence tomography and neural tissue classification for deep brain imaging

Optical coherence tomography can differentiate brain regions with intrinsic contrast and at a micron scale resolution. Such a device can be particularly useful as a real‐time neurosurgical guidance tool. We present, to our knowledge, the first full‐field swept‐source optical coherence tomography system operating near a wavelength of 1310 nm. The proof‐of‐concept system was integrated with an endoscopic probe tip, which is compatible with deep brain stimulation keyhole neurosurgery. Neuroimaging experiments were performed on ex vivo brain tissues and in vivo in rat brains. Using classification algorithms involving texture features and optical attenuation, images were successfully classified into three brain tissue types.     

传统光学相干断层成像:软骨双折射特性的研究

传统光学相干断层成像可实现无损伤在体检测,具有较高的分辨率和灵敏度。获取生物组织的双折射信息可望是其应用之一。本文用传统光学相干断层成像系统以动物模型对关节软骨进行了研究,对软骨组织的传统光学相干断层图像的层结构随脱水和机械作用的变化进行了分析。结果表明,传统光学相干断层成像系统在一定程度上可用于监测由其胶原质纤维排列决定的软骨组织的双折射和密度。     

Full-field OCT

Optical coherence tomography (OCT) is an emerging technique for imaging of biological media with micrometer-scale resolution, whose most significant impact concerns ophthalmology. Since its introduction in the early 1990's, OCT has known a lot of improvements and sophistications. Full-field OCT is our original approach of OCT, based on white-light interference microscopy. Tomographic images are obtained by combination of interferometric images recorded in parallel by a detector array such as a CCD camera. Whereas conventional OCT produces B-mode (axially-oriented) images like ultrasound imaging, full-field OCT acquires tomographic images in the en face (transverse) orientation. Full-field OCT is an alternative method to conventional OCT to provide ultrahigh resolution images (approximately 1 microm), using a simple halogen lamp instead of a complex laser-based source. Various studies have been carried, demonstrating the performances of this technology for three-dimensional imaging of ex vivo specimens. Full-field OCT can be used for non-invasive histological studies without sample preparation. In vivo imaging is still difficult because of the object motions. A lot of efforts are currently devoted to overcome this limitation. Ultra-fast full-field OCT was recently demonstrated with unprecedented image acquisition speed, but the detection sensitivity has still to be improved. Other research directions include the increase of the imaging penetration depth in highly scattering biological tissues such as skin, and the exploitation of new contrasts such as optical birefringence to provide additional information on the tissue morphology and composition.     

Super‐achromatic optical coherence tomography capsule for ultrahigh‐resolution imaging of esophagus

Endoscopic optical coherence tomography (OCT) is a noninvasive technology allowing for imaging of tissue microanatomies of luminal organs in real time. Conventional endoscopic OCT operates at 1300 nm wavelength region with a suboptimal axial resolution limited to 8‐20 μm. In this paper, we present the first ultrahigh‐resolution tethered OCT capsule operating at 800 nm and offering about 3‐ to 4‐fold improvement of axial resolution (plus enhanced imaging contrast). The capsule uses diffractive optics to manage chromatic aberration over a full ~200 nm spectral bandwidth centering around 830 nm, enabling to achieve super‐achromaticity and an axial resolution of ~2.6 μm in air. The performance of the OCT capsule is demonstrated by volumetric imaging of swine esophagus ex vivo and sheep esophagus in vivo, where fine anatomic structures including the sub‐epithelial layers are clearly identified. The ultrahigh resolution and excellent imaging contrast at 800 nm of the tethered capsule suggest the potential of the technology as an enabling tool for surveillance of early esophageal diseases on awake patients without the need for sedation.      

Staging mouse preimplantation development in vivo using optical coherence microscopy

In mammals, preimplantation development primarily occurs in the oviduct (or fallopian tube) where fertilized oocytes migrate through, develop and divide as they prepare for implantation in the uterus. Studies of preimplantation development currently rely on ex vivo experiments with the embryos cultured outside of the oviduct, neglecting the native environment for embryonic growth. This prevents the understanding of the natural process of preimplantation development and the roles of the oviduct in early embryonic health. Here, we report an in vivo optical imaging approach enabling high‐resolution visualizations of developing embryos in the mouse oviduct. By combining optical coherence microscopy (OCM) and a dorsal imaging window, the subcellular structures and morphologies of unfertilized oocytes, zygotes and preimplantation embryos can be well resolved in vivo, allowing for the staging of development. We present the results together with bright‐field microscopy images to show the comparable imaging quality. As the mouse is a well‐established model with a variety of genetic engineering strategies available, the in vivo imaging approach opens great opportunities to investigate how the oviduct and early embryos interact to prepare for successful implantation. This knowledge could have beneficial impact on understanding infertility and improving in vitro fertilization. OCM through a dorsal imaging window enables high‐resolution imaging and staging of mouse preimplantation embryos in vivo in the oviduct.      

A compact high‐speed full‐field optical coherence microscope for high‐resolution in vivo skin imaging

A compact high‐speed full‐field optical coherence microscope has been developed for high‐resolution in vivo imaging of biological tissues. The interferometer, in the Linnik configuration, has a size of 11 × 11 × 5 cm³ and a weight of 210 g. Full‐field illumination with low‐coherence light is achieved with a high‐brightness broadband light‐emitting diode. High‐speed full‐field detection is achieved by using part of the image sensor of a high‐dynamic range CMOS camera. En face tomographic images are acquired at a rate of 50 Hz, with an integration time of 0.9 ms. The image spatial resolution is 0.9 μm × 1.2 μm (axial × transverse), over a field of view of 245 × 245 μm². Images of human skin, revealing in‐depth cellular‐level structures, were obtained in vivo and in real‐time without the need for stabilization of the subject. The system can image larger fields, up to 1 × 1 mm², but at a reduced depth.      

Spectrally encoded coherence tomography and reflectometry: Simultaneous en face and cross‐sectional imaging at 2 gigapixels per second

Non‐invasive biological imaging is crucial for understanding in vivo structure and function. Optical coherence tomography (OCT) and reflectance confocal microscopy are two of the most widely used optical modalities for exogenous contrast‐free, high‐resolution, three‐dimensional imaging in non‐fluorescent scattering tissues. However, sample motion remains a critical barrier to raster‐scanned acquisition and reconstruction of wide‐field anatomically accurate volumetric datasets. We introduce spectrally encoded coherence tomography and reflectometry (SECTR), a high‐speed, multimodality system for simultaneous OCT and spectrally encoded reflectance (SER) imaging. SECTR utilizes a robust system design consisting of shared optical relays, scanning mirrors, swept laser and digitizer to achieve the fastest reported in vivo multimodal imaging rate of 2 gigapixels per second. Our optical design and acquisition scheme enable spatiotemporally co‐registered acquisition of OCT cross‐sections simultaneously with en face SER images for multivolumetric mosaicking. Complementary axial and lateral translation and rotation are extracted from OCT and SER data, respectively, for full volumetric estimation of sample motion with micron spatial and millisecond temporal resolution.