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Suspicious nodules detected by radiography are often investigated by biopsy, but the diagnostic yield of biopsies of small nodules is poor. Here we report a method—NIR-nCLE—to detect cancer at the cellular level in real-time during biopsy. This technology integrates a cancer-targeted near-infrared (NIR) tracer with a needle-based confocal laser endomicroscopy (nCLE) system modified to detect NIR signal. We develop and test NIR-nCLE in preclinical models of pulmonary nodule biopsy including human specimens. We find that the technology has the resolution to identify a single cancer cell among normal fibroblast cells when co-cultured at a ratio of 1:1000, and can detect cancer cells in human tumors less than 2 cm in diameter. The NIR-nCLE technology rapidly delivers images that permit accurate discrimination between tumor and normal tissue by non-experts. This proof-of-concept study analyzes pulmonary nodules as a test case, but the results may be generalizable to other malignancies.

Environmental enteric dysfunction (EED) is a disease of the small intestine affecting children and adults in low and middle income countries. Arising as a consequence of repeated infections, gut inflammation results in impaired intestinal absorptive and barrier function, leading to poor nutrient uptake and ultimately to stunting and other developmental limitations. Progress towards new biomarkers and interventions for EED is hampered by the practical and ethical difficulties of cross-validation with the gold standard of biopsy and histology. Optical biopsy techniques - which can provide minimally invasive or noninvasive alternatives to biopsy - could offer other routes to validation and could potentially be used as point-of-care tests among the general population. This Consensus Statement identifies and reviews the most promising candidate optical biopsy technologies for applications in EED, critically assesses them against criteria identified for successful deployment in developing world settings, and proposes further lines of enquiry. Importantly, many of the techniques discussed could also be adapted to monitor the impaired intestinal barrier in other settings such as IBD, autoimmune enteropathies, coeliac disease, graft-versus-host disease, small intestinal transplantation or critical care.

A first review of the InVivo-ONL project is presented. The aim of the project is to develop a non-linear endomicroscopic system dedicated in first intention to in vivo imaging of the lung extracellular matrix.

The DIAPRECA project is aimed at exploiting conjointly or consecutively optical microscopy exploration techniques such as reflectance and Raman in a perspective of a better early and in vivo discrimination between healthy, precancerous and cancerous tissues. DIAPRECA brings together the laboratories LTSI-INSERM U 642, ProCadec-CNRS 6164, IGDR-CNRS 6061 of the university of Rennes 1, the service of gastroenterology university hospital of Brest and the company Mauna Kea Technologies. This project covered both aspects of dedicated instrument and software design and ex vivo and in vivo experiments.

We describe a fluorescence lifetime imaging endomicroscope employing a fibre bundle probe and time correlated single photon counting. Preliminary images of stained pollen grains, eGFP-labelled cells exhibiting Förster resonant energy transfer and tissue autofluorescence are presented.

International audience; Context: Since the discovery of its dusty disk in 1984, β Pictoris has become the prototype of young early-type planetary systems, and there are now various indications that a massive Jovian planet is orbiting the star at ~10 AU. However, no planets have been detected around this star so far. Aims: Our goal was to investigate the close environment of β Pic, searching for planetary companion(s). Methods: Deep adaptive-optics L'-band images of β Pic were recorded using the NaCo instrument at the Very Large Telescope. Results: A faint point-like signal is detected at a projected distance of ≃8 AU from the star, within the northeastern extension of the dust disk. Various tests were made to rule out possible instrumental or atmospheric artefacts at a good confidence level. The probability of a foreground or background contaminant is extremely low, based in addition on the analysis of previous deep HST images. Its L'=11.2 apparent magnitude would indicate a typical temperature of ~1500 K and a mass of ~8 M_Jup. If confirmed, it could explain the main morphological and dynamical peculiarities of the β Pic system. The present detection is unique among A-stars by the proximity of the resolved planet to its parent star. Its closeness and location inside the β Pic disk suggest a formation process by core accretion or disk instabilities rather than binary-like formation processes. Based on observations collected at the European Southern Observatory, Chile, ESO (runs 072.C-0624(B) and 60.A-9026(A)) and on observations made with the Space Telescope Imaging Spectrograph onboard the NASA/ESA Hubble Space Telescope.

With the increasing maturity of optical biopsy techniques, routine clinical use has become more widespread. This wider adoption of the technique demands effective tracking and retargeting of the biopsy sites, as no visible markers are left following examination. This study presents a high-speed framework for intra-procedural retargeting of probe-based optical biopsies in gastrointestinal endoscopy. A probe tip localisation method using active shape models and geometric heuristics, which eliminates the traditional dependency on shaft visibility, is proposed for automated initialisation. Partial occlusion and tissue deformation are addressed by exploiting the benefits of indirect and direct tracking through a novel combination of geometric association and online learning. Robustness to rapid endoscope motion and improvements in computational efficiency are achieved by restricting processing to the automatically detected video content area and through a feature-based rejection of non-informative frames. Performance evaluation in phantom and in-vivo environments demonstrates accurate biopsy site initialisation, robust retargeting and significant improvements over the state-of-the-art in processing time and memory usage.

International audience; Probe-based Confocal Laser Endomicroscopy (pCLE) provides physicians with real-time access to histological information during standard endoscopy procedures, through high-resolution cellular imaging of internal tissues. Earlier work on mosaicing has enhanced the potential of this imaging modality by meeting the need to get a complete representation of the imaged region. However, with approaches, the dynamic information, which may be of clinical interest, is lost. In this study, we propose a new mosaic construction algorithm for pCLE sequences based on a min-cut optimization and gradient-domain composition. Its main advantage is that the motion of some structures within the tissue such as blood cells in capillaries, is taken into account. This allows physicians to get both a sharper static representation and a dynamic representation of the imaged tissue. Results on 16 sequences acquired in vivo on six different organs demonstrate the clinical relevance of our approach.

International audience; We report VLT/NACO imaging observations of the stars GSC 08047-00232 and HIP 6856, probable members of the large Tucana-Horologium association. During our previous ADONIS/SHARPII deep imaging survey, a substellar candidate companion was discovered around each star. Based on VLT/NACO astrometric measurements, we find that GSC 08047-00232 and the faint candidate companion near to it share the same proper motion with a significance of 3.1 σ. On the contrary, the candidate companion to HIP 6856 is probably a background object with a significance of 4.3 σ. We also detect a new fainter and closer candidate companion to HIP 6856, but which is likely a background object too with a significance of 4 σ. Recent VLT/NACO spectroscopic measurements of GSC 08047-00232 finally confirm the substellar nature of this young brown dwarf with a derived spectral type M 9.5±1. GSC 08047-00232 B, with an estimated mass of 25±10 MJup and an effective temperature of 2100±200 K, is presently the third substellar companion identified among young, nearby associations. Based on observations obtained at the VLT in ESO with programs 70.C-0677 and 072.C-0644.

L' -band ($\lambda=$ 3.8 μ m) and M' -band ($\lambda=$ 4.8 μ m) observations of the Galactic Center region, performed in 2003 at VLT (ESO) with the adaptive optics imager NACO, have lead to the detection of an infrared counterpart of the radio source Sgr A* at both wavelengths. The measured fluxes confirm that the Sgr A* infrared spectrum is dominated by the synchrotron emission of nonthermal electrons. The infrared counterpart exhibits no significant short term variability but demonstrates flux variations on daily and yearly scales. The observed emission arises away from the position of the dynamical center of the S2 orbit and would then not originate from the closest regions of the black hole.

An on-line estimation of turbulence parameters (r0, L0 and wind speed) and adaptive optics (AO) performance is presented. The method is based on the reconstruction of open-loop data from deformable mirror voltages and residual wavefront sensor slopes obtained in closed loop. This dedicated tool implemented in the real time computer of the NAOS (Nasmyth adaptive optics system) system (first AO of the very large telescope) allows us without any loop opening to automatically monitor and display (every 15 s) both the atmospheric conditions and the system performance. We have validated the algorithm and tested its robustness on simulated and experimental data (both in the laboratory and on sky). Using data obtained over more than one year (from January 2002 to June 2003), a statistical study on NAOS performance and turbulence characteristics is proposed.

International audience; The advent of the NAOS/CONICA adaptive optics system at the ESO Very Large Telescope recently gave us the opportunity to map the surface of Titan and to search for atmospheric variations at high spatial resolution and contrast. We report here the first results from a series of observations of Titan performed with this instrument in a number of near-infrared narrow-band filters, covering various altitude regions and three different longitudes (out of the 16 days of Titan's orbit). We have achieved unequaled contrast on images showing complex topography on Titan's trailing hemisphere and have found robust evidence for the north-south asymmetry inversion. The presence of other interesting atmospheric features at Titan's South Pole is described.

NAOS is the first adaptive optics (AO) system of the Very Large Telescope and will provide CONICA with diffraction-limited images. CONICA is a near infrared camera that offers a variety of imaging and spectroscopic observing modes. A technique will be described to benefit of the AO system to correct not only for atmospheric turbulence but also for the internal optical aberrations of the high-resolution camera and the beam splitters of NAOS. The aberrant optical components in the light path of CONICA as well as the beam splitters are outside of the AO loop and therefore no self-acting correction is possible. Independently of the AO wavefront sensor, a separate measurement of these aberrations using a method called phase diversity allows one to predict for a certain instrument configuration the corresponding aberrations. They are quantified by sets of Zernike coefficients that are rendered to the adaptive optics. This technique turns out to be very flexible and results in a further improvement of the optical overall performance. The application of phase diversity to the instrument is investigated in a preceding paper (Blanc et al. 2003). In the present paper we present in detail the instrumental implementation of phase diversity, the obtained calibration results, and the achieved gain in optical performance.

Three‐dimensional spectroscopy has the advantage of providing (quasi‐) simultaneously both spatial and spectral information. Coupled to adaptive optics, it conjugates spectroscopic power with high angular resolution. GriF offers these capabilities in the near‐infrared. As a new observing mode of KIR, the camera behind PUEO, the Canada‐France‐Hawaii Telescope adaptive optics bonnette, it provides images at the diffraction limit of the telescope in the K band. Spectroscopy at a resolution of 2000 is provided by a Fabry‐Perot interferometer coupled with a grism, cooled to limit the background. This setup offers a large multiplex gain by observing simultaneously up to five monochromatic images. This article first describes the instrument and the calibration procedures. Next, we demonstrate GriF performances from its first observations, obtained on the Orion molecular cloud OMC‐1.

Resume DOT-IMAGER a reuni des physiciens, des chimistes et des biologistes des secteurs academique et industriel dans un programme de developpement de nouveaux traceurs multimodaux specifiques et de leurs techniques d’imagerie associees. Ont participe au projet deux laboratoires du CEA (SHFJ et SMMCB), le laboratoire de spectroscopie en lumiere polarisee de l’ESPCI, et la societe Mauna Kea Technologies (MKT), porteur du projet. Le projet a couvert a la fois les aspects synthese des traceurs (ESPCI-SMMCB), fonctionnalisation et tests sur l’animal (SHFJ), et developpement de techniques d’imagerie microscopiques in vivo (MKT) adaptees.

During diseases such as age-related macular degeneration, glaucoma, or retinal degeneration, visualizing and counting retinal cells would be of interest to diagnose early stages and to determine the short-term progression rate of these conditions. This is of major interest to optimize neuroprotective/regenerative therapies in these slowly progressive diseases. Such cellular imaging is already feasible in the eye of laboratory animals. In the near future, it is likely that visualization of individual neuronal cells in humans will become a routine clinical procedure, thanks to continuous technological improvements in optical imaging technologies. In mice, commercially available confocal scanning laser ophthalmoscope (cSLO) allows imaging of axons, capillaries, as well as dye-labelled cells (such as gfp-expressing cells). In humans, commercially available optical coherence tomography (OCT) allows routine imaging of retinal layering, but not of individual cells. Several research groups (including ours) are working in the highly competitive area of retinal cellular-imaging in humans. Different systems of adaptive optics, SLO, and OCT (in spectral domain a-mode or en face mode) and second harmonic generation imaging are under evaluation. These techniques have demonstrated cellular-level imaging capabilities of photoreceptors, of the nerve fibre layer and of capillaries. The main challenges that these systems face are biological (determination of the origin of the signal), medical (the clinical pertinence of the information) and technical (optimization of hardware, development of user interface).

A new 1-5 μm high-resolution camera dedicated to the ESO adaptive optics system ADONIS has been developed as a collaborative project of Observatoire de Paris-Meudon and Observatoire de Grenoble, under ESO contract. Since this camera has been designed to correctly sample the diffraction, two focal plate scales are available: 36 mas pixel–1 for the 1-2.5 μm range and 100 mas pixel–1 for the 3-5 μm range, yielding fields of view of and , respectively. Several broadband and narrowband filters are available as well as two circular variable filters, allowing low spectral resolution (R ~ 60-120) imagery between 1.2 and 4.8 μm. This camera is equipped with a 128 × 128 HgCdTe/CCD array detector built by the CEA-LETI-LIR (Grenoble, France). Among its main characteristics, this detector offers a remarkably high storage capacity (more than 106 electrons) with a total system readout noise of ≈1000 electrons rms, making it particularly well suited for long integration time imagery in the 3-5 μm range of the near-infrared domain. The measured dark current is 2000 electrons s–1 pixel–1 at the regular operating temperature of 77 K, allowing long exposure times at short wavelengths (λ 3 μm), the performances are background-noise limited. We have estimated the ADONIS + COMIC imaging performances using a method specially dedicated to high angular resolution cameras.

ADONIS is an adaptive optics (AO) user friendly instrument offered to the European astronomical community on the ESO 3.6-m telescope at La Silla. It is an upgraded version of COME-ON-PLUS, the VLT AO prototype, which already produced significative astrophysical results in a wide range of fields, from planetology to extragalactic astrophysics. ADONIS is now allowing the astronomer to use adaptive optics as a common user instrument thanks to the implementation of an open artificial intelligence software that handles the large number of parameters needed to optimise the AO correction. We will describe the ADONIS system, including the two dedicated infrared cameras, summarize its performances and discuss the observing procedures.

Since its inception in the field of in vivo imaging, endomicroscopy through optical fiber bundles, or probe-based Confocal Laser Endomicroscopy (pCLE), has extensively proven the benefit of in situ and real-time examination of living tissues at the microscopic scale. By continuously increasing image quality, reducing invasiveness and improving system ergonomics, Mauna Kea Technologies has turned pCLE not only into an irreplaceable research instrument for small animal imaging, but also into an accurate clinical decision making tool with applications as diverse as gastrointestinal endoscopy, pulmonology and urology. The current implementation of pCLE relies on a single fluorescence spectral band making different sources of in vivo information challenging to distinguish. Extending the pCLE approach to multi-color endomicroscopy therefore appears as a natural plan. Coupling simultaneous multi-laser excitation with minimally invasive, microscopic resolution, thin and flexible optics, allows the fusion of complementary and valuable biological information, thus paving the way to a combination of morphological and functional imaging. This paper will detail the architecture of a new system, Cellvizio Dual Band, capable of video rate in vivo and in situ multi-spectral fluorescence imaging with a microscopic resolution. In its standard configuration, the system simultaneously operates at 488 and 660 nm, where it automatically performs the necessary spectral, photometric and geometric calibrations to provide unambiguously co-registered images in real-time. The main hardware and software features, including calibration procedures and sub-micron registration algorithms, will be presented as well as a panorama of its current applications, illustrated with recent results in the field of pre-clinical imaging.

International audience; This work deals with label free multiphoton imaging of the human lung tissue extra-cellular matrix (ECM) through optical fibers. Two devices were developed, the first one using distal scanning associated to a double clad large mode area (LMA) air-silica microstructured fiber, the second one using proximal scanning of a miniature multicore image guide (30000 cores inside a 0.8 mm diameter). In both cases, the main issue has been efficient linear and nonlinear distortion pre-compensation of excitation pulses. By inserting before the delivery fiber a compact (10 cm × 10 cm footprint) grisms-based stretcher (a grating in close contact with a prism) made of readily available commercial components, we achieved as short as 35-femtosecond-duration pulses that were temporally compressed at the direct exit of a 2-meter-long fiber. Interestingly, this femtosecond pulse fiber delivery device is also wavelength tunable over more than 100 nm inside the Ti: Sapphire emission band. With the help of distal scan system, those unique features allowed us to record elastin (through two-photon fluorescence) and collagen (through second harmonic generation) fibered network images. These images were obtained ex-vivo with only 15 mW @ 80 MHz of IR radiation delivered to the alveoli or bronchus tissues. 3D imaging with 400-μm-penetration depth inside the tissue was possible working with a 2-meter-long LMA fiber. With the help of proximal scanning, the miniature image guide allowed us to perform endoscopic real time microimaging of the ECM ex vivo. © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

The DENIS project is the first attempt to carry out a complete digitized survey of the southern sky in the range 1–2.5 μm. The main objectives of the programme and the main specifications of the camera and of the data processing stream are briefly outlined

We present infrared images at 3.3 μ (line and continuum) of two edge-on galaxies: NGC891, a “quiet” spiral and M82, the prototype of starburst galaxies. The interest of those images is two-fold: (i) they prove that PAH molecules, through their characteristic emission, are ubiquitously found in the large scale diffuse interstellar medium of “quiet” spiral galaxies, a result up to now obtained only in the Milky Way; (ii) they confirm that the intensity of the 3.3μ PAH feature is a sensitive indicator of physical conditions since it depends both on the Interstellar Radiation field intensity through the heating and destruction of the molecules and on the ISM density: here, destruction of PAHs is put in evidence in the most central part of M82 where the energy density is high. All images were done using the Paris-Meudon Observatory CIRCUS IR Camera at the Canada-France-Hawaii 3m60 telescope.

Many galaxies are thought to have supermassive black holes at their centres-more than a million times the mass of the Sun. Measurements of stellar velocities and the discovery of variable X-ray emission have provided strong evidence in favour of such a black hole at the centre of the Milky Way, but have hitherto been unable to rule out conclusively the presence of alternative concentrations of mass. Here we report ten years of high-resolution astrometric imaging that allows us to trace two-thirds of the orbit of the star currently closest to the compact radio source (and massive black-hole candidate) Sagittarius A*. The observations, which include both pericentre and apocentre passages, show that the star is on a bound, highly elliptical keplerian orbit around Sgr A*, with an orbital period of 15.2 years and a pericentre distance of only 17 light hours. The orbit with the best fit to the observations requires a central point mass of (3.7 +/- 1.5) x 10(6) solar masses (M(*)). The data no longer allow for a central mass composed of a dense cluster of dark stellar objects or a ball of massive, degenerate fermions.

A fluorescence lifetime imaging (FLIM) technology platform intended to read out changes in Förster resonance energy transfer (FRET) efficiency is presented for the study of protein interactions across the drug-discovery pipeline. FLIM provides a robust, inherently ratiometric imaging modality for drug discovery that could allow the same sensor constructs to be translated from automated cell-based assays through small transparent organisms such as zebrafish to mammals. To this end, an automated FLIM multiwell-plate reader is described for high content analysis of fixed and live cells, tomographic FLIM in zebrafish and FLIM FRET of live cells via confocal endomicroscopy. For cell-based assays, an exemplar application reading out protein aggregation using FLIM FRET is presented, and the potential for multiple simultaneous FLIM (FRET) readouts in microscopy is illustrated.

International audience

International audience; Retinal pathologies, like ARMD or glaucoma, need to be early detected, requiring imaging instruments with resolution at a cellular scale. However, in vivo retinal cells studies and early diagnoses are severely limited by the lack of resolution on eye-fundus images from classical ophthalmologic instruments. We built a 2D retina imager using Adaptive Optics to improve lateral resolution. This imager is currently used in clinical environment. We are currently developing a time domain full-field optical coherence tomograph. The first step was to conceive the images reconstruction algorithms and validation was realized on non-biological samples. Ex vivo retina are currently being imaged. The final step will consist in coupling both setups to acquire high resolution retina cross-sections.

International audience; High resolution wide-field imaging of the human retina calls for a 3D deconvolution. In this communication, we report on a regularized 3D deconvolution method, developed in a Bayesian framework in view of retinal imaging, which is fully unsupervised, i.e., in which all the usual tuning parameters, a.k.a. "hyper-parameters", are estimated from the data. The hyper-parameters are the noise level and all the parameters of a suitably chosen model for the object's power spectral density (PSD). They are estimated by a maximum likelihood (ML) method prior to the deconvolution itself. This 3D deconvolution method takes into account the 3D nature of the imaging process, can take into account the non-homogeneous noise variance due to the mixture of photon and detector noises, and can enforce a positivity constraint on the recovered object. The performance of the ML hyper-parameter estimation and of the deconvolution are illustrated both on simulated 3D retinal images and on non-biological 3D experimental data.

International audience; We describe here two parts of our future 3D fundus camera coupling Adaptive Optics and full-field Optical Coherence Tomography. The first part is an Adaptive Optics flood imager installed at the Quinze-Vingts Hospital, regularly used on healthy and pathological eyes. A posteriori image reconstruction is performed, increasing the final image quality and field of view. The instrument lateral resolution is better than 2 microns. The second part is a full-field Optical Coherence Tomograph, which has demonstrated capability of performing a simple kind of "4 phases" image reconstruction of non biological samples and ex situ retinas. Final aim is to couple both parts in order to achieve 3D high resolution mapping of in vivo retinas.

Confocal endomicroscopy provides tools for in vivo imaging of human cell architecture endoscopically. These technologies are a tough challenge since multiple trade-offs have to be overcome: resolution versus field of view, dynamic versus stability, contrast versus low laser power or low contrast agent doses. Many difficult clinical applications, such as lung, bile duct, urethral imaging and NOTES applications, need to optimize miniaturization, resolution, frame rate and contrast agent dose simultaneously. We propose one solution based on real-time video image processing to efficiently address these trade-offs. Dynamic imaging provides a flow of images that we process in real time. Images are aligned using efficientalgorithms specifically adapted to confocal devices. From the displacement that we find across the images, instantaneous velocities are computed and used to compensate for motion distortions. All images are stitched together onto the same reference space and displayed in real-time to reconstruct an image of the entire surface explored during the clinical procedure. This representation brings both stability and an increased field of view. Moreover, because a given area can be imaged by several frames, the contrast can be improved using temporal adaptive averaging. Such processing enhances the visualization of the video sequence, overcoming most classical trade-offs. The stability and increased field of view help the clinician better focus his attention on his practice which improves the patient benefit. Our tools are currently evaluated in a multicenter clinical trial to assess the improvement of the clinical practice.

A flexible multicore fiber bundle is fed by temporally and spectrally shaped femtosecond pulses allowing for the pre-compensation of both chromatic dispersion and non-linear effects encountered in the bundle. We demonstrate that the pulse duration at the fiber bundle output can be significantly reduced in comparison with linear pre-compensation only. The scheme for femtosecond pulse fiber delivery is applied to the optimization of two-photon fluorescence (TPF) imaging. Experiments and calculations show a five-fold improvement of the TPF signal produced at the end of the fiber bundle in comparison with linear pre-compensation. This is applied to the recording, in real time (12 image/s), of TPF laser-scanning images of human colon cells stained with a fluorescent marker. Further optimizations are discussed.

3D deconvolution is an established technique in microscopy that may be useful for low-cost high-resolution imaging of the retina. We report on a myopic 3D deconvolution method developed in a Bayesian framework. This method uses a 3D imaging model, a noise model that accounts for both photon and detector noises, a regularization term that is appropriate for objects that are a mix of sharp edges and smooth areas, a positivity constraint, and a smart parameterization of the point-spread function (PSF) by the pupil phase. It estimates the object and the PSF jointly. The PSF parameterization through the pupil phase constrains the inversion by dramatically reducing the number of unknowns. The joint deconvolution is further constrained by an additional longitudinal support constraint derived from a 3D interpretation of the phase-diversity technique. This method is validated by simulated retinal images.

Confocal fluorescence high resolution imaging during standard endoscopic procedures has been presented as a very promising tool to enhance patient care and physician practice by providing supplementary diagnostic information in real-time. The purpose of this paper is to show not only potential, but convincing results of endoscopic microscopy using a catheter-based approach. Mauna Kea Technologies' core technology, Cellvizio, delivers dynamic imaging at 12 frames/second using confocal miniprobes inserted through the operating channel of regular endoscopes. Cellvizio is composed of 3 parts including (a) a Laser Scanning Unit, (b) Confocal Miniprobe TM with the following characteristics: 5-15 mm axial resolution, 2-5 mm lateral resolution, 15-100 mm depth of penetration, field of view of 600x500 mm and (c) a software package with onthe- fly processing capabilities. With several tens of patients examined during routine GI endoscopy procedures, the most relevant clinical parameters could be assessed in a doubled-blinded fashion between the endoscopist and a pathologist and results showing very high accuracy in the differentiation of neoplasia from normal and hyperplastic tissue were obtained. In the field of pulmonology, the micro-autofluorescence properties of tissues could be assessed and structures never before accessed in vivo were observed. Cellvizio® may be useful to study bronchial remodeling in asthma and chronic obstructive pulmonary diseases. Using appropriate topical fluorescent dye, the Confocal Miniprobes may also make it possible to perform optical biopsy of precancerous and superficial bronchial cancers. Cellvizio® is as a new tool towards "targeted biopsies", leading to earlier, more reliable and cost effective diagnostic procedures. Other applications, specifically in molecular imaging are also made possible by the miniaturization of the probe (combination with biopsy needle for solid organs use or lymph node detection) and by the compatibility of the system with other imaging modalities (auto-fluorescence and narrow-band imaging endoscopy, MRI, PET, etc).

International audience; We now know that our Galaxy harbors at its centre a supermassive 3.6×10M black hole. This result came after more than 2 decades of infrared studies of the Galactic Centre and important instrumental developments in infrared detectors and in high spatial resolution techniques. Adaptive optics, which allows diffraction-limited infrared observations and enhanced sensitivity, was actually the major breakthrough in this respect. We introduce in the first section of this article what was our knowledge of the Galactic Centre before the advent of adaptive optics. In the second section, after a reminder of the first adaptive optics observations of this region, we highlight the specificities of Galactic Centre adaptive optics observations. In the third and fourth sections, we present the major results obtained from adaptive optics observations of the Galactic Centre: the case of the supermassive black hole and the paradox of youth. In the fifth section, we introduce two main future facilities that will provide even higher spatial resolutions, Gravity---a second generation VLTI instrument---and Extremely Large Telescopes, and the improvements that we expect with these new instruments in our knowledge of the Galactic Centre region. We conclude in the last section. To cite this article: Y. Clénet et al., C. R. Physique 8 (2007).

In a retinal imaging instrument, the ocular aberrations are time-varying, leading to images degradation. Adaptive Optics improves resolution. We describe here several modifications made on our system and their impact in terms of image quality.

The high angular resolution provided by adaptive optics allows detailed study of the environment of bright objects such as stars or AGNs, provided that dazzling by the direct and scattered light from the central source does not become the main limitation. Masking the bright source with a coronagraph is the way to alleviate this problem. Rabbia and Gay (this conference) propose a possible solution. We recently described another concept of faint object coronagraph using a phase mask with 4 quadrants, which presents an excellent rejection factor, and that can be rather easily made achromatic. We propose to install such a device within the NAOS/CONICA instrument. We first examine the properties of this device in terms of rejection gain versus the different factors (residual AO phase error, central obscuration, chromatism). We estimate the performances under different conditions of adaptive optics correction with NAOS/CONICA and of phase errors due to chromatism within the K band. Results of realistic simulations at K show that a gain of 10–12 magnitude is reachable. We finally describe some technical aspects of the mask manufacturing and achromatisation using two dispersive materials, as well as the implementation of the 4QC within CONICA.

Adaptive Optics assisted eye fundus imaging now provides high resolution images of the very contents of the retinal tissue. Impressive images of the mosaic of the photoreceptors have obtained by several groups and the best reported images even show the circulatory activity in capillars. Nevertheless, the natural eye movements, such as drifts or micro-saccades, generally prevent from an accurate registration of the field of view. Moreover, images obtained through scanning techniques also suffer from field distorsion. These two effects make it difficult to unambiguously extract blood cell density and velocity information. We report how Adaptive Optics assisted flood imaging of the retina, associated with an original a posteriori image registration and data analysis now permits evaluating and mapping the flow activity in the retinal micro-vessels. Examples where capillars as thin as a few micrometers are revealed only by their circulatory activity will be given. Larger field of view along the retinal vascular network will also be produced. Thanks to this high resolution functional mapping, we'll demonstrate how blood cells direct observation can be enhanced and how quantitative parameters such as velocity or density can be derived. Velocity maps of the macular vascular network at the eye's diffraction limit will finally be produced.

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.

Since the advent of Adaptive Optics in ophthalmic instrumentation, several attempts for improving the performances of the existing observing techniques, either in imaging or tomography, have been made. For long, Adaptive Optics have proven its ability to restore high lateral resolution with the SLO or flood imaging, or more recently to enhance the interferometric contrast and hence, the sensitivity, of OCT. Nevertheless, the direct acquisition of en face tomographic images equivalent to horizontal optical sections of the retinal tissue is still the objective of intensive developments. We report here a new instrumental approach where a time domain full field OCT setup has been coupled with a double pass adaptive optics system, providing 300 x 300 x 4 μm instantaneous optical sections of biological tissues. We will describe how the interferometric contrast is derived without any modulation of the optical path, thus giving access to targets as critical, because unstable, as the retinal tissue during in vivo ophthalmic examinations. The advantages of this new design, which benefits from the implementation of very recent deformable mirrors, featuring simultaneously a higher actuators density and a much larger stroke, will be discussed, and the ability of the system to accommodate for variable pupil sizes, thanks to wavefront sensing techniques optimized for ophthalmology, are commented. The performances of the system, in terms of X,Y,Z resolution, sensitivity, registration capability and / or image stabilisation are discussed and illustrated with results obtained in the laboratory and in clinical environment.

We report on a deconvolution method developed in a Bayesian framework for adaptive-optics corrected images of the human retina. The method takes into account the three-dimensional nature of the imaging process; it incorporates a positivity constraint and a regularization metric in order to avoid uncontrolled noise amplification. This regularization metric is designed to simultaneously smooth noise out and preserve edges, while staying convex in order to keep the solution unique. We demonstrate the effectiveness of the method, and in particular of the edge-preserving regularization, on realistic simulated data.

The advancement in adaptive optics in recent years has increased the interest in the dynamic aberrations of the eye, including those introduced by the first optical surface provided by the tear film. A curvature sensing system to measure the dynamic topography of the tear film is described. This optical system was used to measure the aberrations of the tear film on 14 eyes. The evolution of this surface is monitored through videos of the tear film topography. The effect on optical quality is studied from the time-evolution of the RMS wavefront error showing non-negligible aberration variations attributed to the tear film layer; the effect of tear film break-up on the ocular optical quality is also discussed. Furthermore, the aberration maps are decomposed into their constituent Zernike components showing stronger contributions from 4th order terms, and also from those components with vertical symmetry which can be attributed to the effect of the eye lids on the tear film. Finally, the power spectra of the RMS wavefront error evolution show that the strongest contributions of the tear film aberrations are to be found at low frequencies, typically below 2Hz.

Pluto and its satellite, Charon (discovered in 1978; ref. 1), appear to form a double planet, rather than a hierarchical planet/satellite couple. Charon is about half Pluto's size and about one-eighth its mass. The precise radii of Pluto and Charon have remained uncertain, leading to large uncertainties on their densities2. Although stellar occultations by Charon are in principle a powerful way of measuring its size, they are rare, as the satellite subtends less than 0.3 microradians (0.06 arcsec) on the sky. One occultation (in 1980) yielded a lower limit of 600 km for the satellite's radius 3, which was later refined to 601.5 km (ref. 4). Here we report observations from a multi-station stellar occultation by Charon, which we use to derive a radius, RC = 603.6 ± 1.4 km (1σ), and a density of ρ = 1.71 ± 0.08 g cm-3. This occultation also provides upper limits of 110 and 15 (3σ) nanobar for an atmosphere around Charon, assuming respectively a pure nitrogen or pure methane atmosphere. © 2006 Nature Publishing Group. Fil: Sicardy, B.. Universite Pierre et Marie Curie; Francia. Gepi - Galaxies, Etoiles, Physique, Instrumentation; Fil: Bellucci, A.. Gepi - Galaxies, Etoiles, Physique, Instrumentation; Fil: Gendron, E.. Gepi - Galaxies, Etoiles, Physique, Instrumentation; Fil: Lacombe, F.. Gepi - Galaxies, Etoiles, Physique, Instrumentation; Fil: Lacour, S.. Gepi - Galaxies, Etoiles, Physique, Instrumentation; Fil: Lecacheux, J.. Gepi - Galaxies, Etoiles, Physique, Instrumentation; Fil: Lellouch, E.. Gepi - Galaxies, Etoiles, Physique, Instrumentation; Fil: Renner, S.. Gepi - Galaxies, Etoiles, Physique, Instrumentation; Fil: Pau, S.. Gepi - Galaxies, Etoiles, Physique, Instrumentation; Fil: Roques, F.. Gepi - Galaxies, Etoiles, Physique, Instrumentation; Fil: Widemann, T.. Gepi - Galaxies, Etoiles, Physique, Instrumentation; Fil: Colas, F.. Imcce - Institut de Mecanique Celeste Et de Calcul Des Ephemerides; Fil: Vachier, F.. Imcce - Institut de Mecanique Celeste Et de Calcul Des Ephemerides; Fil: Martins, R. Vieira. Imcce - Institut de Mecanique Celeste Et de Calcul Des Ephemerides; . Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil Fil: Ageorges, N.. European Southern Observatory Santiago; Chile Fil: Hainaut, O.. European Southern Observatory Santiago; Chile Fil: Marco, O.. European Southern Observatory Santiago; Chile Fil: Beisker, W.. International Occultation Timing Association; Fil: Hummel, E.. International Occultation Timing Association; Fil: Feinstein Baigorri, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Instituto de Ciencias Astronómicas, de la Tierra y del Espacio. Universidad Nacional de San Juan. Instituto de Ciencias Astronómicas, de la Tierra y del Espacio; Argentina Fil: Levato, Orlando Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Complejo Astronómico ; Argentina Fil: Maury, A.. Gene Shoemaker Observatory; Chile Fil: Frappa, E.. Planétarium de Saint-etienne; Fil: Gaillard, B.. Association Des Utilisateurs de Détecteurs Electroniques (aude); Fil: Lavayssière, M.. Association Des Utilisateurs de Détecteurs Electroniques (aude); Fil: Di Sora, M.. Campo Catino Austral Observatory; Chile Fil: Mallia, F.. Campo Catino Austral Observatory; Chile Fil: Masi, G.. Campo Catino Austral Observatory; Chile. Universita Tor Vergata; Italia Fil: Behrend, R.. Universidad de Ginebra; Suiza Fil: Carrier, F.. Universidad de Ginebra; Suiza Fil: Mousis, O.. Observatoire de Besancon; Fil: Rousselot, P.. Observatoire de Besancon; Fil: Alvarez Candal, Alvaro Augusto. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil Fil: Lazzaro, D.. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil Fil: Veiga, C.. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil Fil: Andrei, A.H.. Ministério de Ciencia, Tecnologia e Innovacao. Observatorio Nacional; Brasil. Universidade Federal do Rio de Janeiro; Brasil Fil: Assafin, M.. Universidade Federal do Rio de Janeiro; Brasil Fil: Da Silva Neto, D.N.. Universidade Federal do Rio de Janeiro; Brasil Fil: Jacques, C.. Observatório CEAMIG-REA; Brasil Fil: Pimentel, E.. Observatório CEAMIG-REA; Brasil Fil: Weaver, D.. Universidade de Fortaleza; Fil: Lecampion, J.-F.. Observatoire Aquitain Des Sciences de L'univers; Fil: Doncel, F.. Universidad Nacional de Asunción; Paraguay Fil: Momiyama, T.. Universidad Nacional de Asunción; Paraguay Fil: Tancredi, G.. Facultad de Ciencias; Uruguay

A flexible image guide is excited by femtoseconde pulses. Precompensation of dispersion and nonlinear effects encountered in the waveguide allows the recording of two photon fluorescence endoscopic images of colon cells.

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