Furthering Optical Techniques for Micro-Endoscope Development: The Cell-Acquiring Fallopian Endoscope for Early Detection of Ovarian Cancer

Abstract

This dissertation discusses the efforts made to advance the field of submillimeter microendoscopy, with emphasis on detection of early signs of ovarian cancer in the fallopian tubes. The dissertation begins with the medical and technical background knowledge necessary to understand the motivation for building submillimeter diameter endoscopes and introduces the Cell-Acquiring Fallopian Endoscope (CAFE) as a potential screening method for early ovarian cancer. The CAFE is a coherent fiber bundle-based submillimeter endoscope capable of reflectance and fluorescence imaging, as well as cell collection. The reasoning behind many of the optical and mechanical design decisions made is provided.The dissertation contains details on three projects, with details in appendices, undertaken to support a microendoscope approach to early ovarian cancer detection. The first project is the overall design of the CAFE. A manuscript ready for submission describes its working principles and as-built performance, including initial human test data. The endoscope has proven capable of imaging at the desired resolution, illuminating and collecting reflectance and fluorescence images, and collecting an adequate number of cells for analysis. Detailed standard operating procedures for building, testing and operating the CAFE are included. The second project explores the optical limitations imposed on submillimeter endoscopes for small lumens, and a 3D-printed approach to distal objective microlenses. We characterize and compare the performance of a custom gradient refractive index (GRIN) rod lens, a 3D-printed monolithic doublet, and a 3D-printed monolithic triplet. The 3D-printed doublet’s performance had the largest margin of success, but due to low manufacturing yield, the GRIN lens was deemed best to address the needs of a submillimeter endoscope. A manuscript published in the Journal of Optical Microsystems is provided, along with supplementary material. The third project description describes the theoretical modulation transfer function of a coherent fiber bundle-based endoscope, including the effects of a distal lens, fiber bundle, relay lens group, and camera sensor. Experimental results from four configurations are compared to theory, showing that the simulated model is accurate in describing the trend of the modulation transfer equation of a fiber bundle-based endoscope. A software package that takes user input and implements the theoretical equation is also described and shared. A manuscript prepared for publication is included in this dissertation. The dissertation ends with a discussion of planned and potential future work. First, this section summarizes the CAFE’s in vivo study procedure for 10 patients. Then, this section reviews the assembly challenges of the CAFE, the attempts to address those challenges, and the final design for in vivo use. Lastly, it discusses the opportunities for design improvements in the distal lens and ferrule.