Abstract
The cervix softens and shortens as its collagen microstructure rearranges in preparation for birth, but premature change may lead to premature birth. The global preterm birth rate has not decreased despite decades of research, likely because cervical microstructure is poorly understood. Our group has developed a multilevel approach to evaluating the human cervix. We are developing quantitative ultrasound (QUS) techniques for noninvasive interrogation of cervical microstructure and corroborating those results with high-resolution images of microstructure from second harmonic generation imaging (SHG) microscopy. We obtain ultrasound measurements from hysterectomy specimens, prepare the tissue for SHG, and stitch together several hundred images to create a comprehensive view of large areas of cervix. The images are analyzed for collagen orientation and alignment with curvelet transform, and registered with QUS data, facilitating multiscale analysis in which the micron-scale SHG images and millimeter-scale ultrasound data interpretation inform each other. This novel combination of modalities allows comprehensive characterization of cervical microstructure in high resolution. Through a detailed comparative study, we demonstrate that SHG imaging both corroborates the quantitative ultrasound measurements and provides further insight. Ultimately, a comprehensive understanding of specific microstructural cervical change in pregnancy should lead to novel approaches to the prevention of preterm birth.
Highlights
Spontaneous preterm birth, the leading global cause of neonatal death, affects more than 13 million babies every year.[1]
Interest in the cervix has recently exploded as its critical role in preterm birth has been elucidated; the complex and overlapping pathways to Spontaneous preterm birth (sPTB) dovetail into the singular process of remodeling of cervical microstructure, and it is hypothesized that a comprehensive understanding of that microstructure would allow targeted study of upstream molecular mechanisms.[5,7,8]
To acquire the data for composite second harmonic generation imaging (SHG) images, we developed software for WiscScan to automatically control the xystage on the microscope and acquire individual images at each location in a rasterized grid configuration
Summary
Spontaneous preterm birth (sPTB), the leading global cause of neonatal death, affects more than 13 million babies every year.[1] Premature babies that survive are at lifetime risk for cerebral palsy, respiratory morbidity, mental retardation, blindness, deafness, cardiovascular disease, and cancer.[2] The financial and emotional ramifications of preterm birth are staggering; one of every eight births in the U.S is preterm, costing in excess of $26 billion annually.[3,4] Decades of concerted research effort has not reduced the incidence of sPTB; we do not understand the problem.[5,6]. This is not surprising given its complexity. sPTB is multifactorial, the final common denominator of the interaction of a multitude of factors including social stress, infection/inflammation, poor nutrition, genetics, and others.[5,6,7,8,9] Interest in the cervix has recently exploded as its critical role in preterm birth has been elucidated; the complex and overlapping pathways to sPTB dovetail into the singular process of remodeling of cervical microstructure, and it is hypothesized that a comprehensive understanding of that microstructure would allow targeted study of upstream molecular mechanisms.[5,7,8]
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