Understanding the role of cervical change in preterm birth using combined fingerprint and high wavenumber Raman spectroscopy

Abstract

Preterm birth, defined as birth that occurs before 37 weeks gestation, is the leading cause of neonatal mortality in the United States. For vaginal delivery to occur, whether at term or preterm, the cervix must transform from a rigid, noncompliant structure into one that is flexible and able to dilate to allow passage of the fetus. Raman spectroscopy (RS), a feature-rich, biochemically-sensitive vibrational spectroscopy technique, can be used to evaluate changes in cervical biochemistry, thus enhancing the study of the parturition process and the prediction of preterm labor. Conventionally, clinical RS has been limited to the fingerprint spectral region (800-1800 cm-1), though critical information regarding tissue hydration is accessible only in the high wavenumber region (2800-3800 cm-1). Despite dramatic changes throughout pregnancy, tissue hydration in cervical remodeling has not been studied in vivo in humans. Integrating tissue hydration into biochemical assessment of cervical remodeling throughout pregnancy was hypothesized to improve understanding of the parturition process towards the prediction of preterm birth. To characterize the onset and progression of term labor, in vivo Raman spectra were collected from the cervices of laboring women, revealing increased collagen dispersion, increased blood flow, and increased lipid-associated signals as delivery approached. A dual-excitation wavelength RS system was then designed to enable sequential acquisition of the fingerprint and high wavenumber spectral regions for studying cervical hydration in subsequent studies. Its ability to probe tissue hydration and shifts in the hydrogen-bonding interactions of water molecules was demonstrated in a murine model of pregnancy. The pairing of this configuration with a fiber optic probe incorporating a spatial offset between the excitation source and collection enabled sensing of depth-dependent changes in water and other biochemical components. Dual-excitation fingerprint and high wavenumber Raman spectra were acquired from the cervices of women throughout their pregnancy and labor, and a shift in the hydrogen bonding states of water molecules was found to accompany collagen matrix remodeling with increasing gestational age. By identifying biochemical changes in the laboring cervix and probing shifting water-tissue interactions during pregnancy, the technology presented in this dissertation makes strides towards improved understanding and prediction of preterm labor.