A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy
- aDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205;
- bDepartment of Obstetrics and Gynecology,
- cGreen Center for Reproductive Biology Sciences, and
- eDepartment of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390; and
- dScience and Technology Division, Corning Incorporated, Corning, NY 14831
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Edited by* David W. Russell, University of Texas Southwestern Medical Center, Dallas, TX, and approved July 2, 2012 (received for review December 28, 2011)

Abstract
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.
Footnotes
↵1Y.Z. and M.L.A. contributed equally to this work.
- ↵2To whom correspondence may be addressed. E-mail: xingde{at}jhu.edu or mala.mahendroo{at}utsouthwestern.edu.
Author contributions: Y.Z., M.L.A., M.J.L., K.L.P., M.M., and X.L. designed research; Y.Z. and M.L.A. performed research; Y.Z., M.L.A., K.M, J.X., K.L.P, M.M., and X.L. analyzed data; and Y.Z., M.L.A., K.L.P., M.M., and X.L. wrote the paper.
The authors declare no conflict of interest.
*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1121495109/-/DCSupplemental.