Ovarian cancer is the deadliest gynecological cancer, with most cases of high-grade serous ovarian carcinoma originating as serous tubal intraepithelial carcinoma (STIC) lesions in the fallopian tube epithelium. The Cell-Acquiring Fallopian Endoscope (CAFE) was designed to optically detect these STIC lesions and collect cells from the suspicious site for further analysis. While approximately 0.93 mm in diameter, the CAFE is able to perform multispectral fluorescence imaging (MFI), white light imaging for navigation, and cell collection. Each of these modalities is useful to locating potentially pathological areas. To find these regions, the CAFE looks for alterations of the autofluorescence of the tissue. Upon identification of a potential STIC lesion, a scrape biopsy collects cells from the region of interest. The prototype CAFE achieved an imaging resolution of 88 μm at a 5 mm distance, and 45° full field of view in air. When tested on ex vivo porcine tissue, hemocytometry counts determined that on the order of 105 cells per scrape biopsy could be collected. Current progress on the CAFE includes cell collection testing on ex vivo porcine and human tissue, and improvements in the imaging resolution.
We present the design and feasibility testing of a multimodal co-registered endoscope based on a dual-path optical system integrated with a scanning piezo. This endoscope incorporates three different imaging modalities. A large field-of-view (FOV) reflectance imaging system enables visualization of objects several millimeters in front of the endoscope, while optical coherence microscopy (OCM) and multiphoton microscopy (MPM) are employed in contact with tissue to further analyze suspicious areas. The optical system allows multiple different imaging modalities by employing a dual optical path. One path features a low numerical aperture (NA) and wide FOV to allow reflectance imaging of distant objects. The other path features a high NA and short working distance to allow microscopy techniques such as OCM and MPM. Images of test targets were obtained with each imaging modality to verify and characterize the imaging capabilities of the endoscope. The reflectance modality was demonstrated with a 561 nm laser to allow high contrast with blood vessels. It achieved a lateral resolution of 24.8 μm at 5 mm and a working distance from 5 to 30 mm. OCM was performed with a 1300 nm super-luminescent diode since this wavelength experiences low relative scattering to allow for deeper tissue imaging. Measured OCM lateral and axial resolution was 4.0 and 14.2 μm, respectively. MPM was performed with a custom 1400 nm femtosecond fiber laser, a wavelength suitable for exciting multiple exogenous, and some endogenous fluorophores, as well as providing information on tissue composition through harmonic generation processes. A 4.0 μm MPM lateral resolution was measured.
Significance: Most cases of high-grade serous ovarian carcinoma originate as serous tubal intraepithelial carcinoma (STIC) lesions in the fallopian tube epithelium (FTE), enabling early endoscopic detection.
Aim: The cell-acquiring fallopian endoscope (CAFE) was built to meet requirements for locating potentially pathological tissue indicated by an alteration in autofluorescence or presence of a targeted fluorophore. A channel was included for directed scrape biopsy of cells from regions of interest.
Approach: Imaging resolution and fluorescence sensitivity were measured using a standard resolution target and fluorescence standards, respectively. A prototype was tested in ex vivo tissue, and collected cells were counted and processed.
Results: Measured imaging resolution was 88 μm at a 5-mm distance, and full field of view was ∼45 deg in air. Reflectance and fluorescence images in ex vivo porcine reproductive tracts were captured, and fit through human tracts was verified. Hemocytometry counts showed that on the order of 105 cells per scrape biopsy could be collected from ex vivo porcine tissue.
Conclusions: All requirements for viewing STIC in the FTE were met, and collected cell counts exceeded input requirements for relevant analyses. Our benchtop findings suggest the potential utility of the CAFE device for in vivo imaging and cell collection in future clinical trials.
Multimodal imaging is an advantageous method to increase the accuracy of disease classification. As an example, we and others have shown that optical coherence tomography images and fluorescence spectroscopy contain complementary information that can increase the sensitivity and specificity for cancer detection. A common challenge in multimodal imaging is image co-registration. The different images are often taken with separate imaging setups, making it challenging to precisely image the same tissue area or co-register the images computationally. To solve this problem, we have developed a co-registered multimodal imaging system that images the same tissue location with reflectance, multi-photon, and optical coherence microscopy. The co-registration mechanism is a dual-clad fiber that integrates with a scanning microscope or scanning endoscope, collecting all three signals using the same optical path. In the current implementation, optical coherence tomography utilizes a 1300 nm super luminescent diode, multi-photon signals are excited by a custom femtosecond 1400 nm fiber laser producing two- and three-photon signals in the 460-900 nm band, and reflectance imaging operates at 561 nm. The system separates the different signals using fiber wavelength division multiplexers, a dual-clad fiber coupler, and dichroic mirrors to deliver the different signals to the corresponding detector. This wavelength selection enables the system to work passively, meaning that there is no need for devices such as filter wheels. Using the scanning microscope configuration, we have obtained multimodal images of ex-vivo ovine ovary tissue.
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