PROJECT SUMMARY There is an unmet clinical need for accurate, minimally invasive strategies to diagnose endometriosis, a debilitating disease which affects 10% of reproductive-aged women and frequently results in chronic pain, infertility, or even cancer. Diagnosis is often delayed due to seemingly invisible and vague symptoms and the lack of definitive diagnostic methods except invasive surgery. This project aims to study the uterotubal junction (UTJ), the proximal, contractile segment of the fallopian tubes. Despite the protective role of the UTJ in retrograde menstruation, and the fact that it is structurally altered in women with endometriosis, this region is understudied. I hypothesize that there are structural and functional differences in the UTJs of women with and without endometriosis, which can be visualized with three dimensional minimally invasive imaging. My goal is to evaluate and compare these differences using optical coherence tomography (OCT), and to develop a miniature endoscope to access the UTJ through the uterus. OCT is a novel, non-destructive imaging technique capable of providing depth-based microstructural information at micron-scale resolution. Previous work has indicated the ability of OCT to define the organization of smooth muscle and collagen in tissue, differentiate endometriosis from normal tissue, and inform the functional status of tubal cilia in live mouse studies. I propose the first comparative study of the structure and function of the UTJ in the setting of endometriosis using high-resolution, volumetric imaging. Through Specific Aim 1, I will compare functional and morphological measures of explanted UTJs from women with and without endometriosis on volumetric OCT images. I will develop novel algorithms to extract quantitative measures, including texture features, the quantity and orientation of collagen (structure), and ciliary beat frequency (function). In the short term, I aim to provide effective and accurate diagnostic information which can differentiate individuals with endometriosis from controls, as well as advance our current understanding of the understudied UTJ. Through Specific Aim 2, I will design, build, and test a minimally invasive, miniature endoscope capable of providing depth-resolved structural-functional information to demonstrate that OCT can be made suitable for imaging the UTJ. In the long term, I hope to prove that a simple, low-cost office-based imaging procedure, using an OCT endoscope, can provide accurate diagnostic information to identify endometriosis at an early stage. This device could overcome limitations in current diagnostic methods by providing a means for repetitive surveillance, informing prognostic markers of endometriosis susceptibility, and improving detection times and accuracy. The proposed research will generate the preliminary data needed to design a larger in vivo study to prove the diagnostic capability of our endoscope.

PROJECT NARRATIVE This proposal aims to compare structural and functional features of the uterotubal junction in women with and without endometriosis, and to develop a miniature minimally invasive endoscope for endometriosis diagnosis. This work could profoundly advance our current understanding of an important yet critically understudied segment of female anatomy and identify microstructural features that can be used towards endometriosis diagnosis. The endoscope has potential to reduce the burden of undiagnosed endometriosis, enabling early and accurate diagnosis of endometriosis, timely treatment, and improved health outcomes.