Claude Boccara

Ultrahigh-resolution full-field optical coherence tomography.

We have developed a white-light interference microscope for ultrahigh-resolution full-field optical coherence tomography of biological media. The experimental setup is based on a Linnik-type interferometer illuminated by a tungsten halogen lamp. En face tomographic images are calculated by a combination of interferometric images recorded by a high-speed CCD camera. Spatial resolution of 1.8 microm x 0.9 microm (transverse x axial) is achieved owing to the extremely short coherence length of the source, the compensation of dispersion mismatch in the interferometer arms, and the use of relatively high-numerical-aperture microscope objectives. A shot-noise-limited detection sensitivity of 90 dB is obtained in an acquisition time per image of 4 s. Subcellular-level images of plant, animal, and human tissues are presented.

In vivo anterior segment imaging in the rat eye with high speed white light full-field optical coherence tomography

We present a new high speed full-field optical coherence tomography (OCT) instrument, the first full-field OCT system that is capable of in vivo ocular imaging. An isotropic resolution of ~ 1 mum is achieved thanks to the use of a xenon arc lamp source and relatively high numerical aperture microscope objectives in a Linnik-type interferometer. Full-field illumination allows the capture of two-dimensional en face images in parallel, using a fast CMOS camera as detector array. Each en face image is acquired in a 4 ms period, at a maximum repetition rate of 250 Hz. Detection sensitivity per en face image is 71 dB. Higher sensitivity can be achieved by image correlation and averaging, although frame rate is reduced. We present the first preliminary results of in vivo imaging in the anterior segment of the rat eye, which reveal some cellular features in the corneal layers.

Imaging of non-tumorous and tumorous human brain tissues with full-field optical coherence tomography☆

A prospective study was performed on neurosurgical samples from 18 patients to evaluate the use of full-field optical coherence tomography (FF-OCT) in brain tumor diagnosis. FF-OCT captures en face slices of tissue samples at 1 μm resolution in 3D to a penetration depth of around 200 μm. A 1 cm2 specimen is scanned at a single depth and processed in about 5 min. This rapid imaging process is non-invasive and requires neither contrast agent injection nor tissue preparation, which makes it particularly well suited to medical imaging applications. Temporal chronic epileptic parenchyma and brain tumors such as meningiomas, low-grade and high-grade gliomas, and choroid plexus papilloma were imaged. A subpopulation of neurons, myelin fibers and CNS vasculature were clearly identified. Cortex could be discriminated from white matter, but individual glial cells such as astrocytes (normal or reactive) or oligodendrocytes were not observable. This study reports for the first time on the feasibility of using FF-OCT in a real-time manner as a label-free non-invasive imaging technique in an intraoperative neurosurgical clinical setting to assess tumorous glial and epileptic margins.

Large Field, High Resolution Full-Field Optical Coherence Tomography: A Pre-Clinical Study of Human Breast Tissue and Cancer Assessment

We present a benchmark pilot study in which high-resolution Full-Field Optical Coherence Tomography (FF-OCT) was used to image human breast tissue and is evaluated to assess its ability to aid the pathologists management of intra-operative diagnoses. FF-OCT imaging safety was investigated and agreement between FF-OCT and routinely prepared histopathological images was evaluated. The compact setup used for this study provides 1μm3 resolution and 200μm imaging depth, and a 2.25 cm2 specimen is scanned in about 7 minutes. 75 breast specimens were imaged from 22 patients (21 women, 1 man) with a mean age of 58 (range: 25–83). Pathologists blind diagnosed normal/benign or malignant tissue based on FF-OCT images alone, diagnosis from histopathology followed for comparison. The contrast in the FF-OCT images is generated by intrinsic tissue scattering properties, meaning that no tissue staining or preparation is required. Major architectural features and tissue structures of benign breast tissue, including adipocytes, fibrous stroma, lobules and ducts were characterized. Subsequently, features resulting from pathological modification were characterized and a diagnosis decision tree was developed. Using FF-OCT images, two breast pathologists were able to distinguish normal/benign tissue from lesional with a sensitivity of 94% and 90%, and specificity of 75% and 79% respectively.

Spectroscopic ultrahigh-resolution full-field optical coherence microscopy

We have developed a full-field optical coherence microscopy system providing intensity-based tomographic images and spectroscopic information with ultrahigh spatial resolution. Local measurements of the backscattered light spectrum center of mass are achieved through short-time Fourier analysis of a stack of en face interferometric images acquired with a Linnik-type microscope. Using a halogen lamp as an illumination source enables us to achieve spectroscopic imaging over a wavelength range from 600 to 900 nm with a spatial resolution of approximately 1 microm. Absorption measurements of a colored gel are reported as a validation of the technique. Enhancement of tissue imaging contrast is demonstrated by imaging a Xenopus Laevis (African frog) tadpole ex vivo.

Search for gravitational-wave bursts associated with gamma-ray bursts using data from LIGO science run 5 and VIRGO science run 1.

We present the results of a search for gravitational-wave bursts associated with 137 gamma-ray bursts (GRBs) that were detected by satellite-based gamma-ray experiments during the fifth LIGO science run and first Virgo science run. The data used in this analysis were collected from 2005 November 4 to 2007 October 1, and most of the GRB triggers were from the Swift satellite. The search uses a coherent network analysis method that takes into account the different locations and orientations of the interferometers at the three LIGO-Virgo sites. We find no evidence for gravitational-wave burst signals associated with this sample of GRBs. Using simulated short-duration (<1 s) waveforms, we set upper limits on the amplitude of gravitational waves associated with each GRB. We also place lower bounds on the distance to each GRB under the assumption of a fixed energy emission in gravitational waves, with typical limits of D ~ 15 Mpc (E_GW^iso / 0.01 M_o c^2)^1/2 for emission at frequencies around 150 Hz, where the LIGO-Virgo detector network has best sensitivity. We present astrophysical interpretations and implications of these results, and prospects for corresponding searches during future LIGO-Virgo runs.

Full-field optical coherence tomography for the analysis of fresh unstained human lobectomy specimens

Background: Full-field optical coherence tomography (FFOCT) is a real-time imaging technique that generates high-resolution three-dimensional tomographic images from unprocessed and unstained tissues. Lack of tissue processing and associated artifacts, along with the ability to generate large-field images quickly, warrants its exploration as an alternative diagnostic tool. Materials and Methods: One section each from the tumor and from adjacent non-neoplastic tissue was collected from 13 human lobectomy specimens. They were imaged fresh with FFOCT and then submitted for routine histopathology. Two blinded pathologists independently rendered diagnoses based on FFOCT images. Results: Normal lung architecture (alveoli, bronchi, pleura and blood vessels) was readily identified with FFOCT. Using FFOCT images alone, the study pathologists were able to correctly identify all tumor specimens and in many cases, the histological subtype of tumor (e.g., adenocarcinomas with various patterns). However, benign diagnosis was provided with high confidence in roughly half the tumor-free specimens (others were diagnosed as equivocal or false positive). Further analysis of these images revealed two major confounding features: (a) Extensive lung collapse and (b) presence of smoker′s macrophages. On a closer inspection, however, the smoker′s macrophages could often be identified as distinct from tumor cells based on their relative location in the alveoli, size and presence of anthracosis. We posit that greater pathologist experience, complemented with morphometric analysis and color-coding of image components, may help minimize the contribution of these confounders in the future. Conclusion: Our study provides evidence for the potential utility of FFOCT in identifying and differentiating lung tumors from non-neoplastic lung tissue. We foresee its potential as an adjunct to intra-surgical frozen section analysis for margin assessment, especially in limited lung resections.

Anisotropic polyvinyl alcohol hydrogel phantom for shear wave elastography in fibrous biological soft tissue: a multimodality characterization.

Shear wave elastography can provide quantitative evaluation of soft tissues viscoelastic properties based on the measurement of shear wave speed in the medium. Muscular and cerebral tissues are composed of fibers which induce a strong anisotropic effect on the mechanical behavior. Currently, these tissues cannot be accurately represented by existing elastography phantoms and there is an urgent need of developing new anisotropic tissue mimicking phantoms. In the present study we propose an original multimodality imaging characterization of a transverse isotropic (TI) polyvinyl alcohol (PVA) cryogel. The mechanical anisotropy is induced in the PVA hydrogel by stretching the physical crosslinks of the polymeric chains while undergoing freezing cycling [1]. Multiple properties of these phantoms were investigated using a variety of techniques at different scale. The mechanical (dynamic and static) properties were studied using Supersonic Shear wave Imaging (SSI) technique [2] and Full-Field Optical Coherence Tomography (FF-OCT) strain imaging. The optical and ultrasonic spatial coherence properties were measure by FF-OCT volumetric imaging [3] and Backscatter Tensor Imaging (BTI) [4], respectively. The results suggest that this type of phantom (TI) could be used in the development of techniques and equipment to study anisotropy, such as the design of new ultrasound probes for cardiac and musculoskeletal application.

Acousto-optical coherence tomography using random phase jumps on ultrasound and light

Imaging objects embedded within highly scattering media by coupling light and ultrasounds (US) is a challenging approach. In deed, US enable direct access to the spatial localization, though resolution can be poor along their axis (cm). Up to now, several configurations have been studied, giving a millimetric axial resolution by applying to the US a microsecond pulse regime, as is the case with conventional echography. We introduce a new approach called Acousto-Optical Coherence Tomography (AOCT), enabling us to get a millimetric resolution with continuous US and light beams by applying random phase jumps on US and light. An experimental demonstration is performed with a self-adaptive holographic setup containing a photorefractive GaAs bulk crystal and a single large area photodetector.

Absorption of low-loss optical materials measured at 1064 nm by a position-modulated collinear photothermal detection technique

A collinear photothermal detection bench is described that makes use of a position-modulated heating source instead of the classic power-modulated source. This new modulation scheme increases by almost a factor 2 the sensitivity of a standard mirage bench. This bench is then used to measure the absorption coefficient of OH-free synthetic fused silica at 1064 nm in the parts per 10(6) range, which, combined with spectrophotometric measurements, confirms that the dominant absorption source is the OH content.