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.
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-μm 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-μm 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 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
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 properties of multi-spectral fluorescence imaging using deep-UV-illumination have recently been explored using a fiber-coupled thermal source at 280 nm. The resulting images show a remarkable level of contrast thought to result from the signal being overwhelmingly generated in the uppermost few cell layers of tissue, making this approach valuable for the study of diseases that originate in the endothelial tissues of the body. With a view to extending the technique with new wavelengths, and improving beam quality for efficient small core fiber coupling we have developed a mobile self-contained tunable solid-state laser source of deep UV light. An alexandrite laser, lasing at around 750 nm is frequency doubled to produce 375 nm and then tripled to produce 250 nm light. An optical deck added to the system allows other laser sources to be incorporated into the UV beam-line and a lens system has been designed to couple these sources into a single delivery fiber with core diameters down to 50 microns. Our system incorporates five wavelengths [250 nm, 375 nm, 442 nm (HeCd), 543 nm (HeNe) and 638 nm (diode laser)] as the illumination source for a small diameter falloposcope designed for the study of the distal Fallopian tube origins of high grade serous ovarian cancer. The tunability of alexandrite offers the potential to generate other wavelengths in the 720–800, 360–400 and 240–265 nm ranges, plus other non-linear optical conversion techniques taking advantage of the high peak powers of the laser.
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.
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 μm, be highly flexible, steerable, tracking and nonperforating. 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.
The accepted model of colorectal cancer assumes the paradigm that aberrant crypt foci (ACF) are the earliest events in tumorigenesis and develop into adenoma, which further develop into adenocarcinoma. Under this assumption, basic research and drug studies have been performed using ACF as substitute markers for fully developed carcinoma. While studies have shown a correlation between the number of ACF present and the presence of adenoma/adenocarcinoma, a causal relationship has yet to be determined. The mouse has shown to be an excellent model for colorectal cancer; however, the outcomes of such experiments require sacrifice and histologic examination of ex vivo tissue. To better utilize the mouse model to study ACF and adenoma development, an endoscope was constructed for non-destructive in vivo surface visualization, molecular imaging and cross-sectional imaging of the colon. Our system combines surface magnifying chromoendoscopy (SMC) and optical coherence tomography (OCT) to image colon microstructure. Sixteen mice, treated with the carcinogen azoxymethane, were imaged at 2 week intervals, to visualize carcinogenesis events. With this dual-modality system we are able to visualize crypt structure alteration over time as well as adenoma development over time.