Characterizing close-focus lenses for microendoscopy.

Microendoscopes are commonly used in small lumens in the body, for which a focus near to the distal tip and ability to operate in an aqueous environment are paramount for navigation and disease detection. Commercially available distal optic systems below 1mm in diameter are severely limited, and custom micro lenses are generally very expensive. Gradient index of refraction (GRIN) singlets are available in small diameters but have limited optical performance adjustability. Three-dimensional (3D) printed monolithic optical systems are an emerging option that may be suitable for enabling high performance, close-focus imaging. In this manuscript, we compared the optical performance of three custom distal optic systems; a custom-pitch GRIN singlet, 3D-printed monolithic doublet, and 3D-printed monolithic triplet, with a nominal working distance (WD) of 1.5mm, 0.5mm and 0.4mm in 0.9% saline. These short WDs are ideal for microendoscopy in collapsed or flushed lumens such as pancreatic duct or fallopian tube. The GRIN singlet had performance limited only by the fiber bundle relay over 0.9mm to 1.6 mm depth of field (DOF). The 3D printed doublet was able to achieve a comparable DOF of 0.71mm, while the 3D printed triplet suffered the most limited DOF of 0.55mm. 3D printing enables flexible design of monolithic multi-element systems with aspheric surfaces of very short WDs and relative ease of integration.

Iterative prototyping based on lessons learned from the falloposcope in vivo pilot study experience.

Significance: High grade serous ovarian cancer is the most deadly gynecological cancer, and it is now believed that most cases originate in the fallopian tubes (FTs). Early detection of ovarian cancer could double the 5-year survival rate compared with late-stage diagnosis. Autofluorescence imaging can detect serous-origin precancerous and cancerous lesions in ex vivo FT and ovaries with good sensitivity and specificity. Multispectral fluorescence imaging (MFI) can differentiate healthy, benign, and malignant ovarian and FT tissues. Optical coherence tomography (OCT) reveals subsurface microstructural information and can distinguish normal and cancerous structure in ovaries and FTs. Aim: We developed an FT endoscope, the falloposcope, as a method for detecting ovarian cancer with MFI and OCT. The falloposcope clinical prototype was tested in a pilot study with 12 volunteers to date to evaluate the safety and feasibility of FT imaging prior to standard of care salpingectomy in normal-risk volunteers. In this manuscript, we describe the multiple modifications made to the falloposcope to enhance robustness, usability, and image quality based on lessons learned in the clinical setting. Approach: The ∼0.8 mm diameter falloposcope was introduced via a minimally invasive approach through a commercially available hysteroscope and introducing a catheter. A navigation video, MFI, and OCT of human FTs were obtained. Feedback from stakeholders on image quality and procedural difficulty was obtained. Results: The falloposcope successfully obtained images in vivo. Considerable feedback was obtained, motivating iterative improvements, including accommodating the operating room environment, modifying the hysteroscope accessories, decreasing endoscope fragility and fiber breaks, optimizing software, improving fiber bundle images, decreasing gradient-index lens stray light, optimizing the proximal imaging system, and improving the illumination. Conclusions: The initial clinical prototype falloposcope was able to image the FTs, and iterative prototyping has increased its robustness, functionality, and ease of use for future trials.

Sub-millimeter endoscope demonstrates feasibility of in vivo reflectance imaging, fluorescence imaging, and cell collection in the fallopian tubes.

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.