We present a laparoscope for fluorescence confocal microendoscopy specifically designed for microscopic imaging during diagnostic laparoscopic surgery. The catheter consists of a disposable rigid distal tip which houses a flexible microendoscope and dye channel. The laparoscopic tip is a small disposable polycarbonate sheath containing two inner lumens with a glass window on the distal end. The sheath outer diameter suitable for use in a 5mm trocar. The smaller inner lumen provides a channel for delivering fluorescent contrast agents to the tissue through a 200um hole in the glass window. On the proximal end, the smaller lumen is coupled to a computer controlled fluid delivery system that controls the amount of contrast agent dispensed onto the tissue down to a fraction of a micro liter. The main lumen houses the microendoscope. The microendoscope incorporates a computer-controlled focus mechanism that can quickly and accurately focus while correcting for hysteresis. This fluorescence confocal micro-laparoscope will be tested in a small-scale clinical trial on women undergoing oophorectomy in the near future.

Confocal imaging in an endoscopic format is currently under-utilized as a clinical investigative tool. This is due mainly to the complex, sensitive and costly scanning systems required to produce images. We hypothesize that design potential exists for an endoscope without any type of scanning system and that consequently can simultaneously acquire an entire confocal image frame. Our design exploits the parallel structure of fiber-optic image guides to eliminate all scanning hardware. The design is based upon developing a novel method to form a miniscule aperture on the end of each fiber in an image bundle. This process creates out-of-focus light rejection space between each fiber without changing the fiber spacing or the original outer diameter of the image guide. Our modified image guide can then be incorporated into an essentially typical endoscopic system. Using parallel apertures, a confocal endoscope or "conscope" can acquire images at a rate limited only by light intensity and the acquisition rate of a camera. The research presented in this paper shows the effects of adjusting pinhole diameter on confocal performance. The marriage of endoscopes, confocal imaging, parallel optical fibers, and the conscope design offers life science an ability to quickly observe deep, in-vivo cellular structures in their natural state. Although originally intended for endoscope applications, our design may benefit other forms of microscopy as well.

We previously reported on the development and testing of a multi-spectral confocal microendoscope. Here we present a new system that will be used during an early stage clinical trial. The new microendoscope is significantly smaller, uses fewer optical elements, and is structurally more robust. The slit-scanning confocal system employs two synchronized single-axes scan mirrors and an externally coupled imaging catheter with automated focus control and dye delivery systems. In grayscale collection mode the confocal microendoscope operates at 30 frames-per-second with 3μm lateral resolution and 25μm axial resolution. The multi-spectral collection mode operates at 0.5 frames-per-second when acquiring 32 spectral channels with an average minimum resolvable wavelength difference of 12nm. The system will be used, in grayscale mode, to image ovaries during a small scale clinical trial on women undergoing oophorectomy. Recent grayscale and multi-spectral imaging results from ex-vivo human tissues are presented.

Collagenous colitis is a kind of microscopic colitis. It is characterized by chronic watery diarrhea and abdominal pain. The etiology is still unknown. So far, for the diagnose a histological evaluation was necessary with the presence of thickened subepithelial collagneous bands in the lamina propria. A new developed endoscope with a confocal laser allows analysing cellular and subcellular details of the mucosal layer at high resolution in vivo. In this case report we describe for the first time to diagnose collagenous colitis during ongoing colonoscopy by using this confocal endomicroscopy. In a 67 year old female patient with typical symptoms the characteristic histological changes could be identified in the endomicroscopic view. Biopsies could be targeted to affected areas and endomicroscopic prediction of the presence of collagenous bands could be confirmed in all targeted biopsies. First endomicroscopic experience in microscopic colitis could be confirmed in four additional patients. Future prospective studies are warranted to further evaluate these initial findings. However, collagenous colitis is frequently missed and endomicroscopy seems to be the ideal tool for accurate diagnosing collagenous colitis during ongoing endoscopy.

This paper presents a novel fibered confocal reflectance microscopy system (FCRM) specifically designed for the medical observation of biological tissues in vivo and in situ, in real time, at the cellular level: the R-600. Reflectance imaging is based on the refraction index difference between biological components while confocal imaging allow to perform the optical sectioning slice in-depth inside the tissues. The R-600 is based on a proximal scanning system, coupled with a 7 mm diameter probe made of tens of thousands of flexible optical fibers allowing in situ imaging, associated with a dedicated software performing real-time control and image processing. The R-600 provides 12 frames per second at an optical imaging depth of 30 microns, with a high lateral resolution, 1 micron, an axial resolution of 2 microns in a field of view 160 microns in diameter. Thanks to the miniaturization of the optical probe, unprecedented accessibility is made possible in organs such as the cervix or the otolaryngological sphere, in a completely non-invasive fashion. The aim of FCRM is to perform optical biopsy. As a first step towards this goal, we present here results obtained in vivo and in real-time on a human mouth , assessing the ability of the R-600 to perform rapid morphologic examination. Subcellular structures such as nuclei and membranes can be clearly distinguished on the images. Further miniaturization opens perspectives for an integrated endoscope-compatible system with broad medical applications.

The purpose of this paper is to demonstrate potential for high resolution fluorescence imaging during standard endoscopic procedures using a catheter-based confocal endoscope, compatible with standard video-endoscopes. The instrument, an F400 prototype from Mauna Kea Technologies (Paris, France), may function in various imaging modalities: auto-fluorescence or exogenous fluorescence using topical applications of fluorophores. The system is composed of a Laser Scanning Unit, a range of fibered objectives and a dedicated software, which makes it possible to obtain images at a rate of 12 frames per second. These images have a lateral resolution of 2.5 microns, an axial resolution of 15 microns, a field of view up to 600 microns x 500 microns and can be obtained at depths up to 100 microns. The miniaturized fibered probes offer unique access capabilities, specifically through the operating channel of an endoscope. So far, these studies have demonstrated the safety and efficacy of the F400 in allowing confocal laser imaging of the internal microstructure of tissues in the anatomical tract accessed by the endoscope, thanks to the miniaturization of the system. The device can be considered as a new tool towards "optical biopsies" and in vivo histology, leading to more physiologically relevant data and cost effective medicine.

A 7-mm OD, NA = 1 water immersion injection-molded plastic endoscope objective has been fabricated for a laser scanning fiber confocal reflectance microscope (FCRM) system specifically designed for in vivo detection of cervical and oral pre-cancers. Injection-molded optics was selected for the ability to incorporate aspheric surfaces into the optical design and its high volume capabilities. Our goal is high performance disposable endoscope probes. This objective has been built and tested as a stand-alone optical system, a Strehl ratio greater than 0.6 has been obtained. One of the limiting factors of optical performance is believed to be flow-induced birefringence. We have investigated different configurations for birefringence visualization and believe the circular polariscope is most useful for inspection of injection-molded plastic optics. In an effort to decrease birefringence effects, two experiments were conducted. They included: (1) annealing of the optics after fabrication and (2) modifying the injection molding prameters (packing pressures, injection rates, and hold time). While the second technique showed improvement, the annealing process could not improve quality without physically warping the lenses. Therefore, to effectively reduce flow-induced birefringence, molding conditions have to be carefully selected. These parameters are strongly connected to the physical part geometry. Both optical design and fabrication technology have to be considered together to deliver low birefringence while maintaining the required manufacturing tolerances. In this paper we present some of our current results that illustrate how flow-induced birefringence can degrade high performance injection-molded plastic optical systems.

This research shows a 1mW Low Power and real-time imaging Tx/Rx communication system via RF-delay smart Antenna using up to 10GHz UWB(Ultra WideBand) as a concept of Wireless Medical Telemetry Service (WMTS). This UTCOMS (COMmunication System for Nano-scale USLI designed Endoscope using UWB technology) results in less body loss(about 6~13dB) at high frequency, disposable and ingestible compact size of 5×10 mm² and multifunction, bidirectional communications, independent subsystem control multichannel, and high sensitivity smart receiving antenna of three-dimensional image captured still and moving images.

We evaluated a newly developed miniaturized confocal laser microscopy probe for real-time in vivo molecular and morphological imaging of normal, inflammatory, and malignant tissue in rodents. In the rigid mini-microscopy probe (diameter 7 mm), a single line laser delivers an excitation wavelength of 488 nm. Optical slice thickness is 7 μm, lateral resolution 0.7 μm. The range of the z-axis is 0 - 250 μm below the tissue surface. Organ systems were examined in vivo in rodent models of human diseases. FITC-labeled Lycopersion esculentum lectin was injected or selected cell populations stained for molecular targeting. Morphological imaging was performed using fluorescein sodium, FITC-labeled dextran, and/or acriflavine hydrochloride. Cellular and subcellular details could be readily visualised in vivo at high resolution. Tissue characteristics of different organs were rendered at real time. Selective blood cell staining allowed observation of blood flow and cell migration. Inflammatory diseases such as hepatitis were diagnosed, and tumors were characterized under microscopic control in vivo. Confocal mini-microscopy allows real time in vivo molecular and morphological histologic imaging at high resolution of normal and diseased tissue. Since confocal microscopy is applicable to humans, this technology will have a high impact on different faculties in medicine.

An endoscope test bench is presented to test the optical quality of endoscopes on a regular basis to assure optimal image quality during surgery. A power LED and a photo diode are used to measure the transmission of the illumination fibers. Captures of target images displayed on a LCD screen as seen through the endoscope with a high resolution camera are analyzed to determine the contrast for different spatial line pairs. Transmission and contrast plots are compared to reference data to determine whether an endoscope is still acceptable for clinical application. Results show that endoscopes degrade gradually but steadily over time. In time a large database of various types of endoscope will be built to fine-tune the criteria for approval or rejection of the endoscopes.