The cervix is a collagen-rich connective tissue that must remain closed during pregnancy while undergoing progressive remodeling in preparation for delivery, which begins before the onset of the preterm labor process. Therefore, it is important to resolve the changes of collagen fibers during cervical remodeling for the prevention of preterm labor. Herein, we assessed the spatial organization of collagen fibers in a three-dimensional (3D) context within cervical tissues of mice on day 3, 9, 12, 15 and 18 of gestation. We found that the 3D directional variance, a novel metric of alignment, was higher on day 9 than that on day 3 and then gradually decreased from day 9 to day 18. Compared with two-dimensional (2D) approach, a higher sensitivity was achieved from 3D analysis, highlighting the importance of truly 3D quantification. Moreover, the depth-dependent variation of 3D directional variance was investigated. By combining multiple 3D directional variance-derived metrics, a high level of classification accuracy was acquired in distinguishing different periods of pregnancy. These results demonstrate that 3D directional variance is sensitive to remodeling of collagen fibers within cervical tissues, shedding new light on highly-sensitive, early detection of preterm birth (PTB).

Among all the structural formations, fiber-like structure is one of the most common modalities in organisms that undertake essential functions. Alterations in spatial organization of fibrous structures can reflect information of physiological and pathological activities, which is of significance in both researches and clinical applications. Hence, the quantification of subtle changes in fiber-like structures is potentially meaningful in studying structure-function relationships, disease progression, carcinoma staging and engineered tissue remodeling. In this study, we examined a wide range of methodologies that quantify organizational and morphological features of fibrous structures, including orientation, alignment, waviness and thickness. Each method was demonstrated with specific applications. Finally, perspectives of future quantification analysis techniques were explored.

提出了一种基于光学相干层析成像（OCT）技术实现人工心脏生物瓣膜三维缺陷检测的方法，发展了一种生物瓣膜表面边界拟合算法。根据拟合结果进行坐标变换，使瓣膜表面边界趋于水平但保留表面纤维束高度和异常起伏的高频变化。利用所提方法对人工心脏生物瓣膜三尖瓣支架和其中的瓣膜小叶进行成像实验，实现了高分辨率、大视场、实时三维结构成像，成像结果可以显示生物瓣膜纤维层、光滑层、层间缺陷以及切割缺陷。该技术有望被广泛应用于人工心脏生物瓣膜制造检测领域。

近年来，面向生物组织大深度光学成像的方法不断发展，其中包括光学相干层析、多光子成像和自适应光学等。介绍了浙江大学光电科学与工程学院近年来在生物组织大深度定量光学成像方面的一系列重要进展，包括光学相干层析结构与功能成像、基于三光子荧光显微的大深度脑血管成像和新型的畸变误差波前校正方法等，并进一步概述了如何对上述方法获取的光学图像实施定量表征以获取生物组织的生理与病理信息。

光学相干层析成像(OCT)能通过微型光纤探头实现人体内部组织和器官的三维结构或功能成像，在生物医学成像领域具有重要应用。本课题组提出并改进了基于大纤芯光纤的微型探头，同时通过调制大纤芯光纤的模式能量分布、模式相位差、模式干涉场的放大方式以及模式数量实现了出射光束的调控和成像性能的优化，以期同时获得较高的横向分辨率、较长的焦深和工作距以及较好的轴向光强均匀性。本文提出了相应的快速仿真方法，解决了模式数量多、模式干涉场复杂情况下探头参数的优化问题。仿真和实验显示，基于大纤芯光纤的探头能实现2～3.8倍的焦深拓展和2.1倍的工作距拓展，且在成像效果上相对于传统光纤探头有显著提升。由于具有尺寸小、成像质量好、结构牢固的优点，基于大纤芯光纤的探头在OCT内窥成像尤其是窄小空间内的高分辨率成像方面具有巨大的应用潜力。

We propose a k-domain spline interpolation method with constrained polynomial fit based on spectral phase in swept-source optical coherence tomography (SS-OCT). A Mach–Zehnder interferometer (MZI) unit is connected to the swept-source of the SS-OCT system to generate calibration signal in sync with the fetching of interference spectra. The spectral phase of the calibration signal is extracted by Hilbert transformation. The fitted phase–time relationship is obtained by polynomial fitting with the constraint of passing through the central spectral phase. The fitting curve is then adopted for k-domain uniform interpolation based on evenly spaced phase. In comparison with conventional k-domain spline interpolation, the proposed method leads to improved axial resolution and peak response of the axial point spread function (PSF) of the SS-OCT system. Enhanced performance resulting from the proposed method is further verified by OCT imaging of a home-constructed microspheres-agar sample and a fresh lemon. Besides SS-OCT, the proposed method is believed to be applicable to spectral domain OCT as well.

小型化探头是内窥光学相干层析成像(Optical coherence tomography, OCT)中的普遍需求。介绍了包括基于球透镜、光纤透镜、自聚焦光纤、自由曲面透镜、无透镜的OCT技术的发展历程,总结和比较了各种技术的优劣,为探头的小型化设计提出了建议。研究探头的焦深拓展技术对分辨人体内细胞的在体成像的发展具有重要意义。介绍了几种重要的适用于小型化探头的焦深拓展技术,其中基于模式干涉的探头由于易于制作、结构紧凑、传输效率高,同时具有可以优化工作距离、焦深和轴向光强均匀性的优点,在拓展小型化探头的焦深方面具有一定的发展潜力。

光学相干层析显微成像(OCM)技术是一种使用相干探测的光学显微成像技术。OCM不仅具有光学相干层析成像技术(OCT)高轴向分辨、高信噪比、无需标记的优势,而且能通过高倍物镜获得高横向分辨能力,能实现微米量级的空间分辨率。首先介绍OCM技术的基本原理和实现方案,然后详细阐述OCM技术的原理以及在国际上的研究进展。针对OCM技术中如何实现超高分辨成像、焦深限制成像深度等问题,对目前该研究领域一些先进的OCM技术进行总结。OCM技术在生物医学、材料检测等领域具有广泛的应用前景。