Co-registered Multimodal Endoscope for Early Ovarian Cancer

Abstract

Ovarian cancer (OC) has the highest mortality rate of all gynecological cancers, affecting 22,000patients and causing 14,000 deaths a year in the United States alone. The lack of non-invasive technology to detect OC and lack of specific OC symptoms results in late diagnosis and motivates the development of new methods to detect OC at early stages. A successful early detection technique can improve the survival rate from 17% to 90% if OC is detected at stage 1. High-grade serous carcinomas are considered to originate in the distal fallopian tube and then migrate to the ovary. Therefore, successful early detection of OC must incorporate the ability to detect the distal serous tubal intraepithelial carcinoma (STIC) at the fallopian tubes as well as to detect early stage OC at the ovaries. This work demonstrates the feasibility of a triple multimodality imaging endoscope (salpingoscope) that is minimally invasive and could be used as a screening method for various cancers in the future, especially OC. The endoscope incorporates optical imaging, irrigation, and biopsy accessory channels. The optical modalities are narrowband reflectance, optical coherence microscopy (OCM), and multiphoton microscopy (MPM). Narrowband reflectance enables the identification of regions with increased vascularity. OCM provides depth-resolved, micron-scale resolution images of tissue microstructure, and MPM provides high-resolution non-linear imaging of fluorescent molecules such as lipopigments and porphyrins that are known to be altered in cancerous tissue. The work is presented in three sections. The first validates a novel dual-path optical system through modeling and testing of the optical assembly. The system’s dual-path allows co-registration of the images from the different imaging technologies. Patterned dichroic surfaces 9 embedded within the optical system provide reflective optical power and enable the wavelength-dependent two optical paths. The different optical paths are used to accommodate multiple imaging technologies by selecting the proper illumination wavelength. The second section describes a combined proximal system, whose components can be used for reflectance, OCM, and MPM imaging, including light sources, fibers, detectors, data acquisition, software, and actuator control for either a scanning endoscope (such as the salpingoscope) or a tabletop scanning microscope. The light sources and photonic components are selected to be compatible with the dual-path co-registered optical system described in section 1. Feasibility images are included of ex-vivo ovine ovarian tissue taken with a tabletop microscope. The third section presents the design and feasibility testing of a co-registered endoscope using the optical assembly from section 1, the proximal system from section 2, a quartered-piezo scanning assembly with a cantilevered fiber, and optomechanical components of an approximately 3.5 mm diameter endoscope. The common component of all the systems is a dual-clad fiber that provides illumination and collection mechanisms for the optical imaging modalities.