妊娠期子宫颈组织细胞和细胞外基质的内窥成像与定量表征研究

Appropriate remodeling of the cervix during gestation is an essential component of the birth process. Abnormal or inappropriately timed cervical remodeling can lead to preterm birth. Currently there are limited numbers of diagnosis techniques which can accurately predict preterm birth. During the process of cervical remodeling, both cellular metabolism and spatial organization of extracellular matrix (mainly collagen fibers) are undergoing dynamic changes, which can potentially serve as biomarkers for preterm birth prediction. In this project, we have developed a three-dimensional (3D) endomicroscopic system capable of acquiring both two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) images simultaneously, so as to provide label-free, highly-sensitive and non-invasive detection of cervical tissues. We have characterized the cellular metabolism based on the TPEF image, and 3D alignment of collagen fibers based on the SHG image. For the first time, we have assessed the tissue remodeling level and predicted the possibility of preterm birth based on both cellular functions and collagen organization. We have designed and developed this 3D endomicroscopic imaging system based on the theoretical analysis, tested its imaging performance, and applied it to mice model. Overall, this project will improve the in vivo study of cervical tissues, and offer a novel concept regarding the prediction of diseases during pregnancy.

子宫颈组织在妊娠期的正常重塑是实现生育的基本要素。不正常或时序紊乱的组织重塑将导致早产。目前，能够准确评估早产风险的诊疗手段非常有限。在组织重塑的过程中，伴随着细胞新陈代谢和细胞外基质（主要是胶原纤维）空间结构的动态变化，有望成为评估早产的特征指标。本项目发展了一种三维内窥显微成像系统，同时获取细胞的双光子荧光与胶原纤维的二次谐波图像, 对妊娠期子宫颈组织展开无标记、高灵敏、非侵入式检测。基于双光子荧光图像，表征细胞的代谢水平；基于二次谐波图像，表征胶原纤维三维空间有序度。首次同时基于细胞功能和细胞外基质结构特征，实现对妊娠期子宫颈组织重塑水平的评价和早产风险的评估。本项目在理论分析的基础上，设计并搭建内窥显微成像系统，测试成像效果，并在小鼠模型中展开应用研究。本项目的实施，将促进子宫颈组织在体成像应用研究的发展，并为妊娠期疾病的早筛提供一种全新的思路。

子宫颈组织在妊娠期的正常重塑是实现生育的基本要素。不正常或时序紊乱的组织重塑将导致早产。目前，能够准确评估早产风险的诊疗手段非常有限。在组织重塑的过程中，伴随着细胞新陈代谢和细胞外基质（主要是胶原纤维）空间结构的动态变化，有望成为评估早产的特征指标。本项目发展了一种三维多光子显微成像方法，并构建了相应的光学系统，同时获取细胞的双光子荧光与胶原纤维的二次谐波图像, 对妊娠期子宫颈组织展开无标记、高灵敏、非侵入式检测。设计了大焦深、长工作距的内窥探头，适用于子宫颈组织在体成像。基于双光子荧光图像，表征细胞的代谢水平；基于二次谐波图像，表征胶原纤维三维空间结构与形态。首次同时基于细胞功能和细胞外基质结构特征，实现对小鼠妊娠期子宫颈组织重塑水平的评价和早产风险的评估。本项目的实施，促进了子宫颈组织在体成像应用研究的发展，并为妊娠期疾病的早筛提供了一种全新的思路。在项目执行期内，授权/申请了10项发明专利；发表了标注论文19篇，包括了Laser & Photonics Reviews, Optics Letters等权威期刊论文。其中，1篇论文获得高光论文奖，4篇论文被选为封面/封底。

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