Abstract

Annually, nearly half a million neonates in the United States and 15 million globally are born preterm, defined as prior to 37 completed weeks of gestation. These births present elevated risks of neonatal mortality and long-term neurological deficits. The predominant obstetric precursors of preterm birth (PTB) include spontaneous preterm labor (45%), medically-indicated deliveries (30%), and preterm premature rupture of membranes (PPROM, 25%). Each precursor is associated with distinct physiological or structural alterations such as uterine contractions, placental dysfunction, or cervical insufficiency. Current methodologies for monitoring uterine contractions, such as intrauterine pressure catheters and electrohysterography, possess limitations in spatial resolution, coverage, and specificity. Likewise, imaging techniques like optical-based methods and positron emission tomography have shown promise in animal studies for assessing placental immune response but are constrained by factors like invasiveness and temporal resolution, preventing their real-time, in vivo application in human subjects. Furthermore, various techniques, including cervical elastography, quantitative ultrasound, magnetic resonance elastography, optical coherence tomography, Raman spectroscopy, and second harmonic generation imaging have been employed to quantitatively evaluate cervical remodeling, primarily in ex vivo specimens. Despite these advancements, existing methodologies lack the capability to discriminate and quantitatively assess cellularity, collagen fibers, and muscle fibers within each imaging voxel. Thus, a comprehensive understanding of the in vivo microstructure of the human cervix remains elusive. This dissertation targets the multifaceted issue of PTB by focusing on three core biomarkers: uterine contractility, placental inflammatory processes, and cervical integrity. It is designed to advance imaging methodologies pertinent to each area. Aim 1 centers on the development and validation of noninvasive 3D imaging tools for analyzing uterine contractions. Aim 2 seeks to develop novel imaging modalities for evaluating inflammatory and immune responses in the placenta. Aim 3 concentrates on the development and validation of imaging methods for quantitative analysis of cervical microstructure. Through these efforts, the dissertation aspires to furnish clinicians and researchers with intuitive imaging tools for a more targeted, patient-specific understanding of the etiological factors contributing to PTB.

Committee Chair

Yong Wang

Degree

Doctor of Philosophy (PhD)

Author's Department

Biomedical Engineering

Author's School

McKelvey School of Engineering

Document Type

Dissertation

Date of Award

12-22-2023

Language

English (en)

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