This PDF file contains the front matter associated with SPIE Proceedings Volume 9304, including the Title Page, Copyright information, Table of Contents, Invited Panel Discussion, and Conference Committee listing.

Diagnosis of peripheral lung nodules is challenging because they are rarely visualized endobronchially. Imaging techniques such as endobronchial ultrasound (EBUS) are employed to improve tumor localization. The current EBUS probe provides limited nodule characterization and has an outer diameter of 1.4 mm that restricts access to small peripheral airways. We report a novel co-registered autofluoresence Doppler optical coherence tomography (AF/DOCT) system with a 0.9 mm diameter probe to characterize peripheral lung nodules prior to biopsy in vivo. Method: Patients referred for evaluation of peripheral lung nodules underwent bronchoscopy with examination of standard EBUS and the novel AF/DOCT system. The lesion of interest was first identified with EBUS and then imaged with the AF/DOCT system. The abnormal area was biopsied. AF/DOCT images of pathology proved lung malignancies were reviewed by a panel of a pathologist, respirologists, and AF/DOCT experts. Results: Eleven patients with biopsy proven lung cancer underwent examination with AF/DOCT. The majority of the cancers were adenocarcinoma. AF/DOCT images were obtained in all patients. There were no complications to the procedures. Lung abnormalities visualized in AF/ OCT images were observed in 11 cases. In one case large blood vessels were identified and biopsy was avoided. Conclusion: In this pilot study, AF/DOCT obtained high quality images of peripheral pulmonary nodules. The present study supports the safety and feasibility of AF/DOCT for the evaluation of lung cancer. The addition of Doppler information may improve biopsy site selection and reduce hemorrhage.

Inherited mutations in BRCA1 and BRCA2 lead to 20-50% lifetime risk of ovarian, tubal, or peritoneal carcinoma. Clinical recommendations for women with these genetic mutations include the prophylactic removal of ovaries and fallopian tubes by age 40 after child-bearing. Recent findings suggest that many presumed ovarian or peritoneal carcinomas arise in fallopian tube epithelium. Although survival rate is <90% when ovarian cancer is detected early (Stage_I), 70% of women have advanced disease (Stage_III/IV) at presentation when survival is less than 30%. Over the years, effective early detection of ovarian cancer has remained elusive, possibly because screening techniques have mistakenly focused on the ovary as origin of ovarian carcinoma. Unlike ovaries, the fallopian tubes are amenable to direct visual imaging without invasive surgery, using access through the cervix. To develop future screening protocols, we investigated using our 1.2- mm diameter, forward-viewing, scanning fiber endoscope (SFE) to image luminal surfaces of the fallopian tube before laparoscopic surgical removal. Three anesthetized human subjects participated in our protocol development which eventually led to 70-80% of the length of fallopian tubes being imaged in scanning reflectance, using red (632nm), green (532nm), and blue (442nm) laser light. A hysteroscope with saline uterine distention was used to locate the tubal ostia. To facilitate passage of the SFE through the interstitial portion of the fallopian tube, an introducer catheter was inserted 1- cm through each ostia. During insertion, saline was flushed to reduce friction and provide clearer viewing. This is likely the first high-resolution intraluminal visualization of fallopian tubes.

Peritoneal carcinomatosis is metastatic stage aggravating digestive, gynecological or bladder cancer dissemination and the preoperative evaluation of lesions remains difficult. There is therefore a need for minimal invasive innovative techniques to establish a precise preoperative assessment of cancer peritoneal cavity. Probe-based confocal laser endomicroscopy (pCLE) provides dynamic images of the microarchitecture of tissues during an endoscopy. The PERSEE project proposes new developments in robotics and pCLE for the exploration of the peritoneal cavity during laparoscopy. Two fluorescent dyes, Patent blue V and Indocyanine green have been evaluated on human ex vivo samples to improve the contrast of pCLE images. For a future implementation in clinical study, two topically staining protocols operable in vivo have been validated on 70 specimens from 25 patients with a peritoneal carcinomatosis. The specimens were then imaged by pCLE with an optical probe designed for the application. A histo-morphological correlative study was performed on 350 pCLE images and 70 standard histological preparations. All images were interpreted in a random way by two pathologists. Differential histological diagnostics such as normal peritoneum or pseudomyxoma could be recognized on fluorescence images. The statistical analysis of the correlative study is underway. These dyes already approved for human use are interesting for pCLE imaging because some micromorphological criteria look like to conventional histology and are readable by pathologist. Thus pCLE images using both dyes do not require a specific semiology unlike to what is described in the literature, for pCLE associated with fluorescein for the in vivo imaging of pancreatic cysts.

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.

This work aims to apply a fiber-optic Raman spectroscopy technique for in vivo assessment of adenomatous polyps during clinical colonoscopy. We have developed a fiber-optic Raman endoscopic technique capable of simultaneously acquiring both the fingerprint (FP) (i.e., 800–1800 cm^-1) and high-wavenumber (HW) (i.e., 2800–3600 cm^-1) Raman spectra for real-time assessment of colorectal carcinogenesis. Simultaneous FP/HW Raman endoscopy provides a diagnostic sensitivity of 90.9% and specificity of 83.3% for differentiating adenoma from hyperplastic polyps, which is superior to either the FP or HW Raman technique alone. This study shows that simultaneous FP/HW Raman spectroscopy has the potential for improving early diagnosis of adenomatous polyps in vivo during colonoscopic examination.

Optical fiber bundle based endomicroscopy is a low-cost optical biopsy technique for in vivo cellular level imaging. A limitation of such an imaging system, however, is its small field-of-view (FOV), typically less than 1 mm2. With such a small FOV it is difficult to associate individual image frames with the larger scale anatomical structure. Video-sequence mosaicking algorithms have been proposed as a solution for increasing the image FOV while maintaining cellular-level resolution by stitching together the endomicroscopy images. Although extensive research has focused on image processing and mosaicking algorithms, there has been limited work on localization of the probe to assist with building high quality mosaics over large areas of tissue. In this paper, we propose the use of electromagnetic (EM) navigation to assist with large-area mosaicking of hand-held high-resolution endomicroscopy probes. A six degree-of-freedom EM sensor is used to track in real-time the position and orientation of the tip of the imaging probe during free-hand scanning. We present a proof-of-principle system for EM-video data co-calibration and registration and then describe a two-step image registration algorithm that assists mosaic reconstruction. Preliminary experimental investigations are carried out on phantoms and ex vivo porcine tissue for free-hand scanning. The results demonstrate that the proposed methodology significantly improves the quality and accuracy of reconstructed mosaics compared to reconstructions based only on conventional pair-wise image registration. In principle, this approach can be applied to other optical biopsy techniques such as confocal endomicroscopy and endocytoscopy.

Gastrointestinal tract cancer, the most common type of cancer, has a very low survival rate, especially for pancreatic cancer (five year survival rate of 5%) and bile duct cancer (five year survival rate of 12%). Here, we propose to use an integrated OCT-US catheter for cancer detection. OCT is targeted to acquire detailed information, such as dysplasia and neoplasia, for early detection of tumors. US is used for staging cancers according to the size of the primary tumor and whether or not it has invaded lymph nodes and other parts of the body. Considering the lumen size of the GI tract, an OCT system with a long image range (>10mm) and a US imaging system with a center frequency at 40MHz (penetration depth > 5mm) were used. The OCT probe was also designed for long-range imaging. The side-view OCT and US probes were sealed inside one probe cap piece and one torque coil and became an integrated probe. This probe was then inserted into a catheter sheath which fits in the channel of a duodenoscope and is able to be navigated smoothly into the bile duct by the elevator of the duodenoscope. We have imaged 5 healthy and 2 diseased bile ducts. In the OCT images, disorganized layer structures and heterogeneous regions demonstrated the existence of tumors. Micro-calcification can be observed in the corresponding US images.

Polarization Sensitive Optical Coherence Tomography (PSOCT) is a functional extension of Optical Coherence Tomography (OCT) that is sensitive to well-structured, birefringent tissue such as scars, smooth muscle and cartilage. In this work, we present a novel completely fiber based swept source PSOCT system using a fiber-optic rotary pullback catheter. This PSOCT implementation uses only passive optical components and requires no calibration while adding minimal additional cost to a standard structural OCT imaging system. Due to its complete fiber construction, the system can be made compact and robust, while the fiber-optic catheter allows access to most endoscopic imaging sites. The 1.5mm diameter endoscopic probe can capture 100 frames per second at pullback speeds up to 15 mm/s allowing rapid traversal of large imaging fields. We validate the PSOCT system with known birefringent tissues and demonstrate in vivo PSOCT imaging of human oral scar tissue.

Endomicroscopic objectives have been used for linear confocal as well as nonlinear quasi-confocal imaging processes for many years, especially in medical and neuroscience applications. State-of-the-art devices achieve sub-cellular resolutions by combining plano-convex lenses with special high-NA silver-doped GRIN lenses and diffractive optical elements for their chromatic correction. NAs of 0.8 are achieved while keeping the outer diameter of the mounted objective as thin as 1.4 mm. Recently developed designs correct two major drawbacks of the state-of-the-art devices and are presented in comparison with their precursors. With these developments, the diffraction-limited field of view is increased by 350% in diameter for monochromatic corrected devices and even more for the polychromatic corrected ones. Besides, solutions for chromatic corrected objectives are presented which avoid diffractive optical elements and rather make use of achromatic lenses. The design concepts of those recently developed objectives are presented here and corresponding prototypes are evaluated by confocal and quasi-confocal experiments as well as by wavefront measurements.

Two-photon fluorescence (TPE) and second harmonic generation (SHG) can been used to extract biological information from tissues at the molecular level, which is blind to traditional microscopes. Through these two image contrast mechanisms, a nonlinear laser scanning endoscope (NLSE) is able to image tissue cells and the extra cellular matrix (ECM) through a special fiber and miniaturized scanner without the requirement of poisonous chemical staining. Therefore, NLSE reserves high potential for in-vivo pathological study and disease diagnosis. However, the high cost and bulky size of a NLSE system has become one of the major issues preventing this technology from practical clinical operation. In this paper, we report a fiber laser based multi-modality NLSE system with compact size and low cost, ideal for in-vivo applications in clinical environments. The demonstration of the developed NLSE nonlinear imaging capability on different bio-structures in liver, retina and skin are also presented.

Based on Awaiba’s NanEye CMOS image sensor family and a FPGA platform with USB3 interface, the aim of this paper is to demonstrate a novel technique to perfectly synchronize up to 8 individual self-timed cameras. Minimal form factor self-timed camera modules of 1 mm x 1 mm or smaller do not generally allow external synchronization. However, for stereo vision or 3D reconstruction with multiple cameras as well as for applications requiring pulsed illumination it is required to synchronize multiple cameras. In this work, the challenge to synchronize multiple self-timed cameras with only 4 wire interface has been solved by adaptively regulating the power supply for each of the cameras to synchronize their frame rate and frame phase. To that effect, a control core was created to constantly monitor the operating frequency of each camera by measuring the line period in each frame based on a well-defined sampling signal. The frequency is adjusted by varying the voltage level applied to the sensor based on the error between the measured line period and the desired line period. To ensure phase synchronization between frames of multiple cameras, a Master-Slave interface was implemented. A single camera is defined as the Master entity, with its operating frequency being controlled directly through a PC based interface. The remaining cameras are setup in Slave mode and are interfaced directly with the Master camera control module. This enables the remaining cameras to monitor its line and frame period and adjust their own to achieve phase and frequency synchronization. The result of this work will allow the realization of smaller than 3mm diameter 3D stereo vision equipment in medical endoscopic context, such as endoscopic surgical robotic or micro invasive surgery.

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.

In recent year, for the treatment of gastric cancer the laparoscopic surgery is performed, which has good benefits, such as low-burden, low-invasive and the efficacy is equivalent to the open surgery. For identify location of the tumor intraperitoneally for extirpation of the gastric cancer, several points of charcoal ink is injected around the primary tumor. However, in the time of laparoscopic operation, it is difficult to estimate specific site of primary tumor, because the injected charcoal ink diffusely spread to the area distant from the tumor in the stomach. Therefore, a broad area should be resected which results in a great stress for the patients. To overcome this problem, we focused in the near-infrared wavelength of 1000nm band which have high biological transmission. In this study, we developed a fluorescent clip which was realized with glass phosphor (Yb³⁺, Nd³⁺ doped to Bi₂O₃-B₂O₃ based glasses. λp: 976 nm, FWHM: 100 nm, size: 2x1x3 mm) and the laparoscopic fluorescent detection system for clip-derived near-infrared light. To evaluate clinical performance of a fluorescent clip and the laparoscopic fluorescent detection system, we used resected stomach (thickness: 13 mm) from the patients. Fluorescent clip was fixed on the gastric mucosa, and an excitation light (λ: 808 nm) was irradiated from outside of stomach for detection of fluorescence through stomach wall. As a result, fluorescence emission from the clip was successfully detected. Furthermore, we confirmed that detection sensitivity of the emission of fluorescence from the clip depends on the output power of the excitation light. We conformed that the fluorescent clip in combination with laparoscopic fluorescent detection system is very useful method to identify the exact location of the primary gastric cancer.