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Abstract:
This dissertation presents three bodies of work related to early detection of cancer with advanced optical imaging endoscopes. The first two bodies cover the development of a fallopian tube endoscope and its first-in-human application. The third body provides a guide for the optical design of scanning-fiber forward-looking endoscopes.
Ovarian cancer is the deadliest gynecological malignancy and early detection could double the 5-year survival rate compared to late-stage diagnosis. Evidence suggests that the molecular pathogenesis of high-grade serous ovarian cancer (HGSOC) begins in the fallopian tubes (FT) prior to the onset of symptoms. Traditional optical methods have a limited depth of imaging, and obtaining access to the FTs in a minimally invasive manner is a significant challenge. Previous work in the Barton lab led from a tabletop prototype sub-millimeter microendoscopy system, the falloposcope, to a clinically-useful version that could eventually be implemented as an outpatient, minimally invasive early detection method, via visualizing putative precursors like serous tubal intraepithelial carcinoma (STIC). The falloposcope incorporates Multispectral Fluorescence Imaging (MFI) and Optical Coherence Tomography (OCT) for evaluation of the FTs. This previous work focused on the building and testing of the clinical version of the falloposcope and the conduction of a first-in-human safety and feasibility pilot study.
The first body of work describes the lessons learned while using the falloposcope in a clinical setting and the iterative modifications that were made to enhance the robustness, usability, and image quality of the endoscope. In the clinical setting, the falloposcope was used to obtain navigational video, MFI, and OCT images of human FTs. Stakeholder feedback concerning the image quality and procedural difficulty was collected and used to motivate the iterative improvements described in this body of work. While the preliminary clinical prototype of the falloposcope was able to successfully image the fallopian tubes, the iterative prototyping process was able to increase the robustness, functionality, and ease of use for the subsequent falloposcope pilot study procedures.
The second body of work discusses the results of the novel falloposcope pilot study. The pilot study procedure was conducted with 19 patients during a 15-minute pause in standard-of-care procedure. Successful insertion and FT cannulation was achieved in 12 patients, where in-vivo OCT and/or MFI images were obtained in all but one cannulated FT. After the procedure, surgical discard samples of the FTs were collected, per pathology discretion, from the proximal, medial, and distal segments of both FTs. Ninety-two specimens from 17 patients were collected, all but one patient’s specimens were imaged ex-vivo, and all were processed for histology. After histological observation, insignificant epithelial cell denudation was found in three patients, with no stromal damage discovered. Although this was a small pilot study, the qualitative and quantitative outcomes in regard to procedural success illustrate that the endoscope is viable, falloposcopy feasible, and the device is safe, warranting further investigative studies to determine diagnostic potential.
Lastly, to address the future need for forward-looking, high resolution endoscopic imaging systems, the third body of work outlines the design process for piezoelectric tube-based cantilevered scanning fiber endoscopes (SFEs). This guide provides strategies for: SFE optical design selection, how to determine the feasibility of an illumination source based on given constraints, how to discern if a catalog off-the-shelf (COTS) solution may save money and time, and how to determine if increased optical complexity is warranted. This guide is meant to help guide a designer, who may have limited optical design experience, by addressing each phase of the SFE design process, from fiber oscillation modeling to COTS element selection. The scanning fiber behavior is modeled in an accurate, yet succinct, method. Next, a confocal system geometry is defined to help illustrate the design strategies necessary to optimize the image of the source point on the tissue sample. Exemplary optical designs are then modeled in Ansys Zemax OpticStudio, 1) with paraxial elements, 2) with COTS elements, 3) with hybrid COTS and custom elements. This guide provides the design steps and details necessary to create an intuitive and well-performing SFE design, regardless of designer’s experience.