Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):12878-83. doi: 10.1073/pnas.1121495109. Epub 2012 Jul 23.
We report the development of an all-fiber-optic scanning endomicroscope capable of high-resolution second harmonic generation (SHG) imaging of biological tissues and demonstrate its utility for monitoring the remodeling of cervical collagen during gestation in mice. The endomicroscope has an overall 2.0 mm diameter and consists of a single customized double-clad fiber, a compact rapid two-dimensional beam scanner, and a miniature compound objective lens for excitation beam delivery, scanning, focusing, and efficient SHG signal collection. Endomicroscopic SHG images of murine cervical tissue sections at different stages of normal pregnancy reveal progressive, quantifiable changes in cervical collagen morphology with resolution similar to that of bench-top SHG microscopy. SHG endomicroscopic imaging of ex vivo murine and human cervical tissues through intact epithelium has also been performed. Our findings demonstrate the feasibility of SHG endomicroscopy technology for staging normal pregnancy, and suggest its potential application as a minimally invasive tool for clinical assessment of abnormal cervical remodeling associated with preterm birth.
我们报告了一种全光纤扫描内窥显微镜的开发，该显微镜能够对生物组织进行高分辨率二次谐波产生（SHG）成像，并展示了其在监测小鼠妊娠期间宫颈胶原重塑中的效用。该内窥显微镜的整体直径为 2.0 毫米，由单个定制的双包层光纤、紧凑的快速二维光束扫描仪和微型复合物镜组成，用于激发光束传输、扫描、聚焦和高效的 SHG 信号收集。在正常妊娠的不同阶段，对小鼠宫颈组织切片进行内窥显微镜 SHG 成像，揭示了宫颈胶原形态的渐进、可量化变化，其分辨率与台式 SHG 显微镜相当。还通过完整的上皮对离体的小鼠和人宫颈组织进行了 SHG 内窥显微镜成像。我们的研究结果表明，SHG 内窥显微镜技术在正常妊娠分期方面具有可行性，并表明其可能作为一种微创工具，用于评估与早产相关的异常宫颈重塑的临床评估。
