This PDF file contains the Front Matter associated with SPIE Proceedings Volume 7893, including the Title page, Copyright information, Table of Contents, Conference Committee listing, and introduction.

Current endoscopic screening does not detect all pre-malignant (dysplastic) colorectal mucosa, thus requiring the development of more sensitive, targeted techniques to improve detection. The presented work utilizes phage display to identify a novel peptide binder to colorectal dysplasia in a CPC;Apc mouse model. A wide-field, small animal endoscope capable of fluorescence excitation (450-475 nm) identified polyps via white light and also collected fluorescence images (510 nm barrier filter) of peptide binding. The peptide bound ~2-fold greater to the colonic adenomas when compared to the control peptide. We have imaged fluorescence-labeled peptide binding in vivo that is specific towards distal colonic adenomas.

We present two FLIM endoscopes for clinical imaging and in vivo cell biology. For subcellular confocal imaging we demonstrated the first confocal FLIM endomicroscope, implementing TCSPC with a Cellvizio®GI, which we have now developed as a self-contained wheeled instrument (1.0 × 0.7 m) incorporating a tunable excitation laser and acquiring images in < 10 s. This has been applied to image FRET in live cells and to image tissue autofluorescence, for which we are implementing "FIFO" for image montaging. For diagnostic screening/guided biopsy, we have developed a complementary wide-field FLIM endoscope employing time-gated detection with violet and UV excitation for imaging over mm-cm fields of view.

We are developing a non-linear fibered endomicroscope for imaging the extracellular matrix collagen and elastin fibrillar networks during bronchoscopy. As a proof of concept, laser pulses at the output of a standard 2 meter long single-mode fibre have been obtained with pulse duration of about 50 fs and pulse energy up to 50 uJ, using a specially designed grism line for the dispersion compensation. With these pulses, we performed a spectroscopic characterization of the non-linear endogenous signal, consisting of two-photon fluorescence and second harmonic generation, and originated from human pulmonary tissue of various thickness, both in forward and backward geometry of signal collection, with excitation at 830 nm.

Multiphoton microscopic endoscopy (MPM-E) is a promising medical in vivo diagnostic imaging technique because it captures intrinsic fluorescence and second harmonic generation signals to reveal anatomical and histological information about disease states in tissue. However, maximizing light collection from multiphoton endoscopes remains a challenge: weak nonlinear emissions from endogenous structures, miniature optics, large imaging depths, and light scattering in tissue all hamper light collection. The quantity of light that may be collected using a dual-clad fiber system from scattering phantoms that mimic the properties of the in vivo environment is measured. In this experiment, 800nm excitation light from a Ti:Sapphire laser is dispersion compensated and focused through a SM800 optical fiber and lens system into the tissue phantom. Emission light from the phantom passes through the lens system, reflects off the dichroic and is then collected by a second optical fiber actuated by a micromanipulator. The lateral position of the collection fiber varies, measuring the distribution of emitted light 2000μm on either side of the focal point reimaged to the object plane. This spatial collection measurement is performed at depths up to 200μm from the phantom surface. The tissue phantoms are composed of a 15.8 μM fluorescein solution mixed with microspheres, approximating the scattering properties of human bladder and dermis tissue. Results show that commercially available dual-clad optical fibers collect more than 47% of the total emission returning to the object plane from both phantoms. Based on these results, initial MPM-E devices will image the surface of epithelial tissues.

Miniaturized video endoscopes with an imager located at the distal end and a simplified opto-mechanical layout are presented. They are based on a CMOS imager with 650 x 650 pixels of 2.8 μm pitch and provide straight view with 75° and 110° field of view at f/4.3. They have an outer diameter of 3 mm including the shell and a length of approx. 8 mm. The optics consist of polymer lenses in combination with a GRIN and a dispensed lens. Using a simple flip chip assembly, optical axis alignment better than 10 μm and a contrast of 30 % at 90 LP/mm was achieved. The 75° FOV system was sealed at the front window using a solderjetting technology, providing 10^-9 mbar*l/s leakage rates even after several autoclave cycles.

This paper is researching about the illumination system in ring field capsule endoscope. It is difficult to obtain the uniform illumination on the observed object because the light intensity of LED will be changed along its angular displacement and same as luminous intensity distribution curve. So we use the optical design software which is Advanced Systems Analysis Program (ASAP) to build a photometric model for the optimal design of LED illumination system in ring field capsule endoscope. In this paper, the optimal design of illumination uniformity in the ring field capsule endoscope is from origin 0.128 up to optimum 0.603 and it would advance the image quality of ring field capsule endoscope greatly.

Confocal microendoscopy provides real-time high resolution cellular level images via a minimally invasive procedure, but relies on exogenous fluorophores, has a relatively limited penetration depth (100 μm) and field of view (700 μm), and produces a high rate of detailed information to the user. A new catheter based multi-modal system has been designed that combines confocal imaging and oblique incidence reflectometry (OIR), which is a non-invasive method capable of rapidly extracting tissue absorption, μa, and reduced scattering, μ's, spectra from tissue. The system builds on previous developments of a custom slit-scan multi-spectral confocal microendoscope and is designed to rapidly switch between diffuse spectroscopy and confocal fluorescence imaging modes of operation. An experimental proof-of-principle catheter has been developed that consists of a fiber bundle for traditional confocal fluorescence imaging and a single OIR source fiber which is manually redirected at +/- 26 degrees. Diffusely scattered light from each orientation of the source fiber is collected via the fiber bundle, with a frame of data representing spectra collected at a range of distances from the OIR source point. Initial results with intralipid phantoms show good agreement to published data over the 550-650 nm spectral range. We successfully imaged and measured the optical properties of rodent cardiac muscle.

Optical coherence tomography (OCT) is an emerging technology for non-invasive cross-sectional imaging of biological tissue and material with um resolution. Recently, non-invasive high resolution cross-sectional imaging is desired for investigation of diseases in lung in the field of pulmonary medicine. So far, a few works have been reported about OCT imaging of lung. Since the lung consists of alveoli separated by thin wall, ultrahigh resolution (UHR) OCT is supposed to be effective for the imaging of fine structure in lung tissue. In this work, ex vivo cross-sectional imaging of isolated rat lungs was demonstrated using UHR-OCT. A 120 nm-wide, high-power, Gaussian-like supercontinuum (SC) was generated at wavelength of 0.8 um region and it was used as the light source in time domain UHR-OCT. An ultrahigh resolution of 2.1 um in tissue was obtained and the achieved sensitivity was 105 dB. For the UHR-OCT imaging of trachea, the detailed structures of the tracheal cartilage and tracheal mucosa overlying the cartilage were observed clearly. The epithelium and lamina propria were also distinguishable. For the imaging of visceral pleura and alveoli, when saline was instilled into the lung, the penetration depth was improved, and clear images of the fine structure of the lung, including alveoli, were observed owing to the index matching effect. The clear images of up to about 4 alveoli were observed below the visceral pleura. The shape of the alveolar septum was clearly observed, and the alveolar sac was clearly visible.

A rotational microelectromechanical(MEMS) motor based common-path Fourier-domain OCT for endoscopic imaging, which uses the interface between the index-match oil and distal-end surface of the fiber as a self-aligned reference mirror, is reported. The reference intensity is easy to be tuned by altering the index of the match oil to optimize the signal to noise ratio of the system. An external Michelson interferometer is used to compensate for the optical path difference and dispersion mismatch to the index-match oil and the GRIN lens. Due to this common-path design, the OCT signal is immune to bending or stretching of the endoscopic catheter. The outer diameter of the probe is 3 mm, and 22 circumferential-scans and 50,000 lines A-scans are obtained in one second.

Acute lung injury (ALI) is a severe pulmonary disease leading to hypoxemia accompanied by a reduced compliance and partial edema of the lung. Most of the patients have to be ventilated to compensate for the lack of oxygen. The treatment is strongly connected with ventilator induced lung injury (VILI), which is believed to introduce further stress to the lung and changes in its elastic performance. A thorough understanding of the organs micro-structure is crucial to gain more insight into the course of the disease. Due to backscattering of near-infrared light, detailed description of lung morphology can be obtained using optical coherence tomography (OCT), a non-invasive, non-contact, high resolution and fast three-dimensional imaging technique. One of its drawbacks lies in the non-specificity of light distribution in relation to defined substances, like elastic biomolecules. Using fluorescence detection, these chemical components can be visualized by introducing specifically binding fluorophores. This study presents a combined setup for studying alveolar compliance depending on volume changes and elastic fiber distributions. Simultaneously acquired OCT and confocal fluorescence images allow an entire view into morphological rearrangements during ventilation for an ex vivo mouse model using continuous pulmonary airway pressure at different values.

Fibered confocal fluorescence microscopy (FCFM) with spectroscopic analysis capability was used during bronchoscopy, at 488nm excitation, to record autofluorescence images and associated emission spectra of the alveoli of 5 healthy smoking volunteers and 7 non-smoking amiodarone-induced pneumonitis (AIP) patients. Alveolar fluorescent cellular infiltration was observed in both groups. Our objective was to assess the potential of spectroscopy in differentiating these two groups. Methods: We previously demonstrated that in healthy smokers alveolar elastin backbone and tobacco tar contained in macrophages contribute to the observed signal. Each normalized spectrum was modeled as a linear combination of 3 components: S_exp(λ) = C_e.S_e(λ)+C_t.S_t(λ)+C_G.S_G(λ), C_e, C_t and C_G are amplitude coefficients. S_e(λ) and S_t(λ) are respectively the normalized elastin and tobacco tar emission spectra measured experimentally and S_G(λ) a gaussian spectrum with tunable width and central wavelength. Levenbergt-Marquardt algorithm determined the optimal set of coefficients. Results: AIP patient autofluorescence spectra can be uniquely modelized by the linear combination of the elastin spectrum (C_e = 0.61) and of a gaussian spectrum (center wavelength 550nm, width 40nm); the tobacco tar spectrum coefficient C_t is found to be zero. For healthy smoking volunteers, only two spectral components were considered: the tobacco tar component (C_t = 1,03) and the elastin component (C_e = 0). Conclusion: Spectral analysis is able to distinguish cellular infiltrated images from AIP patients and healthy smoking volunteers. It appears as a powerful complementary tool for FCFM.

Optical biopsies are aimed at providing fast and thorough screening of biological tissues in vivo. Disease diagnosis is based on the morphological structures and biochemical features of tissues that can be sampled in situ with high resolution. Some optical screening techniques, such as fluorescence confocal microendoscopy, provide a limited imaging depth due to the shallow penetration of visible light. Despite confocal microendoscopy's high resolution and image quality, morphological changes that occur deeper in the tissue cannot be detected. Other imaging techniques, such as optical coherence tomography (OCT), are able to obtain information at greater depth into tissue. A combination of fluorescence confocal and OCT into a single instrument capable of rapidly switching between these modalities, has the potential of providing complementary en face confocal images showing the morphologic features of cells within a surface layer, and cross-sectional OCT images showing tissue microarchitecture below the surface. The concept for this dual system is to utilize the optical train of an existing multi-spectral confocal microendoscope as a spectral-domain OCT system. Progress made on the implementation of this combined dual integrated imaging system is presented. A performance analysis, discussion of the limitations inherent to the use of an imaging fiber bundle, and recent imaging results are presented.

For in vivo medical applications, endoscopy shows great potential for its minimally invasive manner, flexibility and close-up imaging characteristic. A miniaturized imaging probe combining ultrasound and photoacoustic endoscopy has been developed. The output of a 532-nm pulse laser was coupled into and delivered to the probe by a 200-micron-core multimode fiber. A 40 MHz ring shape ultrasound transducer was fabricated to receive pulse echo ultrasound and photoacoustic signals as well. The light-guiding optical fiber, the ring ultrasound transducer, and a mirror-based reflective material for the coaxial laser beam and ultrasound signal were integrated into the probe with a final packaged diameter of 2.5 mm. The performance of the probe was tested by imaging a graphite rod. The imaging ability of this dual-modality system was demonstrated by imaging the cross section of a rabbit aorta.