Parallel en-face optical coherence microscopy with adaptive focus

描述（由申请人提供）：自适应聚焦平行面光学相干显微镜。我们提出了一种新的平行非分层光学相干显微镜（OCM），具有自适应聚焦，用于一般高速高分辨率的生物医学成像。光学相干层析成像（OCT）已成为一种新兴的高深度分辨率成像方式。OCM是一种利用物臂共焦结构，具有较好横向和深度分辨率的OCT成像技术。典型的OCT系统生成B扫描的横截面图像。在临床上，用户更熟悉的是C-scan （en face）图像。平行OCT成像已经被研究过，但不是在OCM架构中。此外，在传统的OCT/OCM成像中，只有在靠近焦平面的区域才能保持良好的横向分辨率。动态聚焦只能通过机械运动来实现。为了克服这些问题，我们首次提出了一种具有自适应聚焦的非平移平行面OCM成像仪器。采用可编程数字微镜装置进行平行共焦采样，采用电光变焦透镜进行快速深度扫描，采用速率超过1000帧/秒的快速CMOS相机进行数据采集。通过自适应聚焦，横向分辨率在成像深度上是恒定的。三维空间分辨率可达2 <m W 2 <m W 4.5 <m左右。成像深度高于单独的共聚焦或全视野OCT成像。随着数字微镜器件（微秒）、变焦镜头和CMOS相机的快速速度，数据采集速度非常高（体积/秒）。像素停留时间增加。它允许较低的激发激光功率和较高的灵敏度。信噪比高于其他无共焦结构的全视野OCT成像。由于在目标臂中，纵向和横向扫描都是电光学的，没有平移元件，因此可以避免传统成像系统由于机械振动而引起的样品移动效应。该仪器提供了一种实时评估组织和细胞功能和形态的新工具。在这项技术驱动项目的拟议探索阶段，我们将对一般生物相关样品进行实验，以证明该系统的功能。这些样品包括基于明胶嵌入微球的组织幻影，覆盖了美国空军1951年的目标，洋葱皮和蝌蚪。来自生物样品的图像将与发表的OCT图像和我们相应薄切片样品的显微镜图像进行比较。本文还将对该成像系统在角膜疾病诊断中的应用进行初步研究。

DESCRIPTION (provided by applicant): Parallel en-face optical coherence microscopy with adaptive focus Abstract. We propose a novel parallel nonstralational optical coherence microscopy (OCM) with adaptive focus for general high-speed high-resolution en-face biomedical imaging. Optical coherence tomography (OCT) has become an emerging imaging modality with high depth resolution. OCM is one kind of OCT imaging technique with better transverse and depth resolution by using confocal architecture in the object arm. Typical OCT systems generate B- scan cross section images. In clinic, the users are more familiar with C-scan (en face) images. Parallel OCT imaging has been studied, but not in the OCM architecture. Furthermore, in the conventional OCT/OCM imaging, good transverse resolution can be maintained only in the region close to the focal plane. Dynamic focusing can only be done by mechanic movement. To overcome these problems, here we propose to demonstrate, for the first time, a nontranslational parallel en-face OCM imaging instrument with adaptive focus. A programmable digital micromirror device is used for parallel confocal sampling, an electro-optic varifocal lens for fast depth scanning, and a rapid CMOS camera with more than 1000 frames/s rate for data collection. With adaptive focusing, the transverse resolution is constant across the depth of imaging. The spatial resolution can be around 2 <m W 2 <m W 4.5 <m in three dimensions. The imaging depth is higher than that of the confocal or full-field OCT imaging alone. With the rapid speed of the digital micromirror device (microsecond), the vafifocal lens, and the CMOS camera, the data acquisition speed is very high (volume/s). The pixel dwell time is increased. It allows lower excitation laser power and higher sensitivity. The signal-to-noise ratio would be higher than other full-field OCT imaging without confocal architecture. Since in the object arm, both longitudinal and transverse scanning are performed electro- optically without translational components, the moving effect of the sample due to mechanic vibration of the conventional imaging system can be avoided. The instrument provides a new tool to assess tissue and cell function and morphology in real time. In the proposed exploratory phase of this technology-driven project, we will perform experiments on general biologic relevant samples to demonstrate the functionality of the system. These samples include tissue phantoms based on gelatin embedded micro spheres covering a USAF 1951 target, onion skin, and tadpole. Images from biological samples will be compared to published OCT images and microscopy images of our corresponding thin sectioned samples. Pilot study of application of this imaging system for diagnosis of cornea disease will be performed too. PUBLIC HEALTH RELEVANCE (provided by the applicant): We have proposed a novel parallel nonstralational optical coherence microscopy (OCM) with adaptive focus for general high-speed high-resolution en-face biomedical imaging. Our research proposal currently focuses on demonstration the feasibility of this new technique. With adaptive focusing, the transverse resolution is constant across the depth of imaging. [The spatial resolution can be around 2<m 4 2<m 4 4.5<m in three dimensions. The imaging depth is higher than that of the confocal or full-field OCT imaging alone. With the rapid speed of the digital micromirror device (microsecond), the varifocal lens, and the CMOS camera, the data acquisition speed is very high (~1190 frames/s or higher).It allows higher sensitivity. The signal-to-noise ratio would be higher than other full-field OCT imaging without confocal architecture. Since in the object arm, both longitudinal and transverse scannings are performed electro-optically without translational components, the moving effect of the sample due to mechanic vibration of the conventional imaging system can be avoided. The instrument provides a new tool to assess tissue and cell function and morphology in real time. The potential applications include general cell imaging, visualizing epithelial tissue layers or structures of the eye (cornea). Miniaturization and portability of the system will be considered in the future. Model system for epithelial tissue would be fresh samples of colon and cheek with the goal to image individual cells in epithelial tissues down to the basement membrane. This would demonstrate potential application in colon cancer screening and oral cancer screening. For eye imaging, such a system can be used for diagnosis of the ocular surface diseases.