Cervical collagen network porosity assessed by SHG endomicroscopy distinguishes preterm and normal pregnancy – a pilot study

Abstract

Structured AbstractBackgroundPreterm birth (PTB) is a global public health issue affecting millions of newborns every year. Orchestrated remodeling of the cervix is essential for normal pregnancy and birth, while PTB is closely related with premature cervical ripening and loss of cervical mechanical strength. The structure and organization of fibrillar collagen in the extracellular matrix are of vital importance to the biomechanical properties of the cervix. Second harmonic generation (SHG) microscopy has proved capable of revealing the progressive changes in cervical collagen morphology over the course of pregnancy. To translate this promising imaging technology to clinical practice, a flexible SHG endomicroscope has long been envisaged for label-free, non-invasive visualization of cervical collagen architecture and for assessment of PTB risk.ObjectiveTo evaluate the potential of our newly-developed SHG endomicroscope for imaging-based differentiation of cervical collagen architecture between normal pregnant mice and RU486/mifepristone-induced PTB mouse models.Study DesignWe undertook endomicroscopy SHG imaging of cervical collagen on two types ofex vivosamples: 1) frozen cervical tissue sections (∼50 µm thick) and 2) resected intact cervices, and performed SHG-image-based quantitative collagen morphology analysis to distinguish RU486 mouse models from normal pregnant mice.ResultsEndomicroscopic SHG images of cervical tissue sections from mifepristone-treated mouse models exhibit statistically larger collagen fiber diameter, increased pore size, and reduced pore numbers than those of normal pregnant mice. Similar changes are also observed on SHG images of subepithelial collagen fibers acquired from intact cervices by the endomicroscope.ConclusionThe experiment results demonstrated that SHG endomicroscopy along with quantitative image analysis holds promising potential for clinical assessment of cervical collagen remodeling and preterm birth risk.