To improve early detection of ovarian cancer, we have designed and built a microendoscope that combines optical coherence tomography (OCT) and multispectral fluorescence imaging (MFI) into a 0.7 mm diameter package. An endoscope of this size allows access to the ovaries through the fallopian tubes creating a minimally invasive procedure. We characterize the falloposcope’s imaging behavior and show that this system provides contrast on ex vivo surgical samples of ovary and fallopian tube. In addition, we show the mechanical performance of the endoscope in an anatomically correct model of the female reproductive treatment.

Early detection of ovarian cancer is only achieved in around 20% of women due to lack of effective screening. We propose a method for surveillance of high risk women based on a microendoscope introduced transvaginally to image the fallopian tubes and ovaries. This requires extreme miniaturization of the optics and catheter sheath. We describe the design of a falloposcope that combines optical coherence tomography (OCT) and wide field imaging into a sub-1 mm diameter package. We characterize the systems and show that they provide contrast on ex-vivo samples of ovary and fallopian tube. In addition, we show the mechanical performance of the endoscope in an anatomically correct model of the female reproductive tract.

A miniature wide-field multispectral endoscopic imaging system was developed enabling reflectance and fluorescence imaging over a broad wavelength range. At 0.8-mm diameter, the endoscope can be utilized for natural orifice imaging in small lumens such as the fallopian tubes. Five lasers from 250 to 642 nm are coupled into a 125 - ? m diameter multimode fiber and transmitted to the endoscope distal tip for illumination. Ultraviolet and blue wavelengths excite endogenous fluorophores, which can provide differential fluorescence emission images for health and disease. Visible wavelengths provide reflectance images that can be combined for pseudo-white-light imaging and navigation. Imaging is performed by a 300 - ? m diameter three-element lens system connected to a 3000-element fiber. The lens system was designed for a 70-deg full field of view, working distance from 3 mm to infinity, and 40% contrast at the Nyquist cutoff of the fiber bundle. Measured performance characteristics are near design goals. The endoscope was utilized to obtain example monochromatic, pseudo-white-light, and composite fluorescence images of phantoms and porcine reproductive tract. This work shows the feasibility of packaging a highly capable multispectral fluorescence imaging system into a miniature endoscopic system that may have applications in early detection of cancer.

The optical design for a dual modality endoscope based on piezo scanning fiber technology is presented including a novel technique to combine forward-viewing navigation and side viewing OCT. Potential applications include navigating body lumens such as the fallopian tube, biliary ducts and cardiovascular system. A custom cover plate provides a rotationally symmetric double reflection of the OCT beam to deviate and focus the OCT beam out the side of the endoscope for cross-sectional imaging of the tubal lumen. Considerations in the choice of the scanning fiber are explored and a new technique to increase the divergence angle of the scanning fiber to improve system performance is presented. Resolution and the necessary scanning density requirements to achieve Nyquist sampling of the full image are considered. The novel optical design lays the groundwork for a new approach integrating side-viewing OCT into multimodality endoscopes for small lumen imaging. KEYWORDS:

With early detection, five year survival rates for ovarian cancer are over 90%, yet no effective early screening method exists. Emerging consensus suggests that perhaps over 50% of the most lethal form of the disease, high grade serous ovarian cancer, originates in the Fallopian tube. Cancer changes molecular concentrations of various endogenous fluorophores. Using specific excitation wavelengths and emissions bands on a Multispectral Fluorescence Imaging (MFI) system, spatial and spectral data over a wide field of view can be collected from endogenous fluorophores. Wavelength specific reflectance images provide additional information to normalize for tissue geometry and blood absorption. Ratiometric combination of the images may create high contrast between neighboring normal and abnormal tissue. Twenty-six women undergoing oophorectomy or debulking surgery consented the use of surgical discard tissue samples for MFI imaging. Forty-nine pieces of ovarian tissue and thirty-two pieces of Fallopian tube tissue were collected and imaged with excitation wavelengths between 280 nm and 550 nm. After imaging, each tissue sample was fixed, sectioned and HE stained for pathological evaluation. Comparison of mean intensity values between normal, benign, and cancerous tissue demonstrate a general trend of increased fluorescence of benign tissue and decreased fluorescence of cancerous tissue when compared to normal tissue. The predictive capabilities of the mean intensity measurements are tested using multinomial logistic regression and quadratic discriminant analysis. Adaption of the system for in vivo Fallopian tube and ovary endoscopic imaging is possible and is briefly described.

The 5-year survival rate for ovarian cancer is only 45% largely due to lack of effective screening methods. Current methods include palpation, transvaginal ultrasound, and the CA-125 blood test. Finding disease reliably and at an early stage increase survival to 92%. We have designed and built a 0.7 mm endoscope for the early detection of ovarian cancer. Inserted transvaginally through the working channel of a hysteroscope, the falloposcope creates a minimally invasive procedure for the screening of high risk women. To improve the ease-of-use and safety of falloposcope deployment, we are working to create an everting balloon. Currently, the falloposcope would require a skilled user to operate due to the challenging anatomy of the fallopian tubes - a small opening from the uterus (< 1 mm), tortuous path, and delicate lumenal features. A balloon delivery system would gently open the fallopian tube and guide the falloposcope down the center of lumen. We show balloon design and discuss integration with the falloposcope prototype. We test possible mechanical damage to the tissue due to scraping, puncture, or overstretching. Successful introduction of the everting balloon to simplify falloposcope delivery could expand screening beyond specialized centers to smaller clinical locations.

Stray light in an endoscope largely contributes to whether a signal can be detected or not. This FRED analysis used a novel endoscope designed for the fallopian tubes to show how common endoscope elements cause stray light contamination, and to offer suggestions on how to mitigate it. Standard and advanced optical raytracing was performed. Raytrace reports determined which ray paths caused the highest power and irradiance distributions after reflecting one or more times from an element in the system. The analysis revealed that the cover plate introduced significantly more stray light into the system than other endoscope components. The imaging lenses and variable stop reflectivity had a negligible impact on the signal. To obtain acceptable signal-to- noise ratio, the source numerical aperture (NA) was lowered to 0.35 and 0.25 to keep the stray light within the same order of magnitude and an order of magnitude lower, respectively than the desired signal. There was a single specular reflection off of the cover plate distal surface. This illumination reflected back into the imaging fiber without first scattering off the tissue, which resulted in high stray power at the back of the imaging lenses. The specular light appeared brighter at higher source NAs and saturated the desired signal at the edge of the imaging fiber. An NA between 0.25 and 0.35 provides maximum illumination to image the tissue, with minimal stray light degrading the desired signal.

A Q-switched alexandrite laser is frequency doubled and tripled to the ultraviolet, combined with 3 visible wavelengths, and fiber coupled to form the illumination source for a micro-endoscope designed for minimally invasive ovarian cancer screening.

We are combining multispectral fluorescence imaging (MFI) and optical coherence tomography (OCT) into a 0.6mm diameter endoscope. This size allows access to the fallopian tubes transvaginally, creating a minimally-invasive screening method for high risk women.

The five year survival rate for ovarian cancer is over 90% if early detection occurs, yet no effective early screening method exists. We have designed and are constructing a dual modality Optical Coherence Tomography (OCT) and Multispectral Fluorescence Imaging (MFI) endoscope to optically screen the Fallopian tube and ovary for early stage cancer. The endoscope reaches the ovary via the natural pathway of the vagina, cervix, uterus and Fallopian tube. In order to navigate the Fallopian tube the endoscope must have an outer diameter of 600 lam, be highly flexible, steerable, tracking and non-perforating. The imaging systems consists of six optical subsystems, two from OCT and four from MFI. The optical subsystems have independent and interrelated design criteria. The endoscope will be tested on realistic tissue models and ex vivo tissue to prove feasibility of future human trials. Ultimately the project aims to provide women the first effective ovarian cancer screening technique.

To develop a multi-modal endoscope to screen the human Fallopian tubes and ovaries for ovarian cancer.