Manifestation of aberrations in full-field optical coherence tomography.

We report on a theoretical model for image formation in full-field optical coherence tomography (FFOCT). Because the spatial incoherence of the illumination acts as a virtual confocal pinhole in FFOCT, its imaging performance is equivalent to a scanning time-gated coherent confocal microscope. In agreement with optical experiments enabling a precise control of aberrations, FFOCT is shown to have nearly twice the resolution of standard imaging at moderate aberration level. Beyond a rigorous study on the sensitivity of FFOCT with respect to aberrations, this theoretical model paves the way towards an optimized design of adaptive optics and computational tools for high-resolution and deep imaging of biological tissues.

Full-field spatially incoherent illumination interferometry: a spatial resolution almost insensitive to aberrations.

We show that with spatially incoherent illumination, the point spread function (PSF) width/spatial resolution of an imaging interferometer like that used in full-field optical coherence tomography (OCT) is almost insensitive to aberrations. In these systems, aberrations mostly induce a reduction of the signal level that leads to a loss of the signal-to-noise ratio without broadening the system PSF. This is demonstrated by comparison with traditional scanning OCT and wide-field OCT with spatially coherent illuminations. Theoretical analysis and numerical calculation as well as experimental results are provided to show this specific merit of incoherent illumination in full-field OCT. To the best of our knowledge, this is the first time that such a result has been demonstrated.

Dark-field full-field optical coherence tomography.

Full-field optical coherence tomography (FF-OCT) provides en face images from deep in the tissue with high spatial resolution. Specular reflections, however, may reduce image contrast as it can be much stronger than the backscattered signal from a specimen. To this end, we demonstrate dark-field FF-OCT (d-FF-OCT) that can block specular reflections by the help of an opaque disk in the pupil-conjugated plane. The reference mirror is replaced by a blazed grating, which eliminates a walk-off between the sample and the reference beams on a camera that otherwise limits the imaging field-of-view (FOV). We show that d-FF-OCT can suppress specular reflections efficiently from the glass-specimen interface by at least two orders of magnitude and yield higher contrast images compared to the conventional FF-OCT.

Optical phase modulation by natural eye movements: application to time-domain FF-OCT image retrieval.

Eye movements are commonly seen as an obstacle to high-resolution ophthalmic imaging. In this context we study the natural axial movements of the in vivo human eye and show that they can be used to modulate the optical phase and retrieve tomographic images via time-domain full-field optical coherence tomography (TD-FF-OCT). This approach opens a path to a simplified ophthalmic TD-FF-OCT device, operating without the usual piezo motor-camera synchronization. The device demonstrates in vivo human corneal images under the different image retrieval schemes (2-phase and 4-phase) and different exposure times (3.5 ms, 10 ms, 20 ms). Data on eye movements, acquired with a spectral-domain OCT with axial eye tracking (180 B-scans/s), are used to study the influence of ocular motion on the probability of capturing high-signal tomographic images without phase washout. The optimal combinations of camera acquisition speed and amplitude of piezo modulation are proposed and discussed.

Exploiting the time-reversal operator for adaptive optics, selective focusing, and scattering pattern analysis.

We report on the experimental measurement of the backscattering matrix of a weakly scattering medium in optics, composed of a few dispersed gold nanobeads. The decomposition of the time-reversal operator is applied to this matrix and we demonstrate selective and efficient focusing on individual scatterers, even through an aberrating layer. Moreover, we show that this approach provides the decomposition of the scattering pattern of a single nanoparticle. These results open important perspectives for optical imaging, characterization, and selective excitation of nanoparticles.

Theoretical study of acousto-optical coherence tomography using random phase jumps on ultrasound and light.

Acousto-optical coherence tomography (AOCT) is a variant of acousto-optic imaging (also called ultrasonic modulation imaging) that makes it possible to get the z resolution with acoustic and optic continuous wave beams. We describe here theoretically the AOCT effect, and we show that the acousto-optic "tagged photons" remain coherent if they are generated within a specific z region of the sample. We quantify the z selectivity for both the "tagged photon" field and for the Lesaffre et al. [Opt. Express 17, 18211 (2009)] photorefractive signal.

Measuring the transmission matrix in optics: an approach to the study and control of light propagation in disordered media.

We introduce a method to experimentally measure the monochromatic transmission matrix of a complex medium in optics. This method is based on a spatial phase modulator together with a full-field interferometric measurement on a camera. We determine the transmission matrix of a thick random scattering sample. We show that this matrix exhibits statistical properties in good agreement with random matrix theory and allows light focusing and imaging through the random medium. This method might give important insight into the mesoscopic properties of a complex medium.

Distortion matrix concept for deep optical imaging in scattering media.

In optical imaging, light propagation is affected by the inhomogeneities of the medium. Sample-induced aberrations and multiple scattering can strongly degrade the image resolution and contrast. On the basis of a dynamic correction of the incident and/or reflected wavefronts, adaptive optics has been used to compensate for those aberrations. However, it only applies to spatially invariant aberrations or to thin aberrating layers. Here, we propose a global and noninvasive approach based on the distortion matrix concept. This matrix basically connects any focusing point of the image with the distorted part of its wavefront in reflection. A singular value decomposition of the distortion matrix allows to correct for high-order aberrations and forward multiple scattering over multiple isoplanatic modes. Proof-of-concept experiments are performed through biological tissues including a turbid cornea. We demonstrate a Strehl ratio enhancement up to 2500 and recover a diffraction-limited resolution until a depth of 10 scattering mean free paths.

Real-time non-contact cellular imaging and angiography of human cornea and limbus with common-path full-field/SD OCT.

In today's clinics, a cell-resolution view of the cornea can be achieved only with a confocal microscope (IVCM) in contact with the eye. Here, we present a common-path full-field/spectral-domain OCT microscope (FF/SD OCT), which enables cell-detail imaging of the entire ocular surface in humans (central and peripheral cornea, limbus, sclera, tear film) without contact and in real-time. Real-time performance is achieved through rapid axial eye tracking and simultaneous defocusing correction. Images contain cells and nerves, which can be quantified over a millimetric field-of-view, beyond the capability of IVCM and conventional OCT. In the limbus, palisades of Vogt, vessels, and blood flow can be resolved with high contrast without contrast agent injection. The fast imaging speed of 275 frames/s (0.6 billion pixels/s) allows direct monitoring of blood flow dynamics, enabling creation of high-resolution velocity maps. Tear flow velocity and evaporation time can be measured without fluorescein administration.

Detection of the tagged or untagged photons in acousto-optic imaging of thick highly scattering media by photorefractive adaptive holography.

We propose an original adaptive wavefront holographic setup based on the photorefractive effect (PR), to make real-time measurements of acousto-optic signals in thick scattering media, with a high flux collection at high rates for breast tumor detection. We describe here our present state of the art and understanding on the problem of breast imaging with PR detection of the acousto-optic signal.

In vivo high resolution human corneal imaging using full-field optical coherence tomography.

We present the first full-field optical coherence tomography (FFOCT) device capable of in vivo imaging of the human cornea. We obtained images of the epithelial structures, Bowman's layer, sub-basal nerve plexus (SNP), anterior and posterior stromal keratocytes, stromal nerves, Descemet's membrane and endothelial cells with visible nuclei. Images were acquired with a high lateral resolution of 1.7 µm and relatively large field-of-view of 1.26 mm x 1.26 mm - a combination, which, to the best of our knowledge, has not been possible with other in vivo human eye imaging methods. The latter together with a contactless operation, make FFOCT a promising candidate for becoming a new tool in ophthalmic diagnostics.

Optimization and characterization of a structured illumination microscope.

Structured illumination microscopy provides a simple and cheap mean to obtain optical sections of a sample. It can be implemented easily on a regular fluorescent microscope and is a scanning free alternative to confocal microscopy.We have analyzed theoretically the performances of the technique in terms of sectioning strength, resolution enhancement along the optical axis, and signal to background as a function of the objective used and the grid's characteristics (pitch and contrast). We show that under optimized conditions, the axial resolution can be improved by a factor of 1.5 in comparison with an epifluorescence microscope, and that optical cuts with a thickness of less than 400nm can be obtained with a 1.4 numerical aperture objective. We modified the original grid in-step modulation pattern and used a sinusoidal modulation for the grid displacement. Optical sections are computed by combining four images acquired during one modulation period. This algorithm is very stable even for modulations at high frequencies. The speed of the acquisition is thus only limited by the performance of the detector and the signal/background ratio of the sample. Finally, we compared our technique to commercial setups: a confocal microscope, a Spinning Disk Microscope and a Zeiss Apotome.

In situ monitoring of the photorefractive response time in a self-adaptive wavefront holography setup developed for acousto-optic imaging.

The measurement of optical contrasts within thick biological tissues can be performed with the hybrid technique of acousto-optic imaging, but it has been shown that an acquisition rate in the 1-10kHz range is required for a good efficiency. This comes from the interferometric nature of the signal, blurred by speckle decorrelation in a time t(c), due to a decrease of the speckle pattern contrast at the exit of the sample. An holographic setup that associates a fast and large area single photodetector and a photorefractive crystal, can measure in real-time the acousto-optic signal: this is the so-called self-adaptive wavefront holography technique. Nevertheless, it is essential to size the photorefractive response time ( t(PR)) of the crystal with t(c) in order to optimize the signal-to-noise ratio of the measurement. This time mainly depends on the overall light intensity within the crystal. We have developed an original in situ method to determine t(PR) with the combination of acoustic pulses and a frequency de-tuning of the reference beam. We can measure precisely this time but also monitor it according to a theoretical model that we have previously described. We are able to adapt the response time of the setup to the decorrelation time of the medium under study.

Fast subsurface fingerprint imaging with full-field optical coherence tomography system equipped with a silicon camera.

Images recorded below the surface of a finger can have more details and be of higher quality than the conventional surface fingerprint images. This is particularly true when the quality of the surface fingerprints is compromised by, for example, moisture or surface damage. However, there is an unmet need for an inexpensive fingerprint sensor that is able to acquire high-quality images deep below the surface in short time. To this end, we report on a cost-effective full-field optical coherent tomography system comprised of a silicon camera and a powerful near-infrared LED light source. The system, for example, is able to record 1.7 cm×1.7 cmen face images in 0.12 s with the spatial sampling rate of 2116 dots per inch and the sensitivity of 93 dB. We show that the system can be used to image internal fingerprints and sweat ducts with good contrast. Finally, to demonstrate its biometric performance, we acquired subsurface fingerprint images from 240 individual fingers and estimated the equal-error-rate to be ∼0.8%. The developed instrument could also be used in other en face deep-tissue imaging applications because of its high sensitivity, such as in vivo skin imaging.

En face coherence microscopy [Invited].

En face coherence microscopy or flying spot or full field optical coherence tomography or microscopy (FF-OCT/FF-OCM) belongs to the OCT family because the sectioning ability is mostly linked to the source coherence length. In this article we will focus our attention on the advantages and the drawbacks of the following approaches: en face versus B scan tomography in terms of resolution, coherent versus incoherent illumination and influence of aberrations, and scanning versus full field imaging. We then show some examples to illustrate the diverse applications of en face coherent microscopy and show that endogenous or exogenous contrasts can add valuable information to the standard morphological image. To conclude we discuss a few domains that appear promising for future development of en face coherence microscopy.

Dynamic full field optical coherence tomography: subcellular metabolic contrast revealed in tissues by interferometric signals temporal analysis.

We developed a new endogenous approach to reveal subcellular metabolic contrast in fresh ex vivo tissues taking advantage of the time dependence of the full field optical coherence tomography interferometric signals. This method reveals signals linked with local activity of the endogenous scattering elements which can reveal cells where other OCT-based techniques fail or need exogenous contrast agents. We benefit from the micrometric transverse resolution of full field OCT to image intracellular features. We used this time dependence to identify different dynamics at the millisecond scale on a wide range of organs in normal or pathological conditions.

Smart optical coherence tomography for ultra-deep imaging through highly scattering media.

Multiple scattering of waves in disordered media is a nightmare whether it is for detection or imaging purposes. So far, the best approach to get rid of multiple scattering is optical coherence tomography. This basically combines confocal microscopy and coherence time gating to discriminate ballistic photons from a predominant multiple scattering background. Nevertheless, the imaging-depth range remains limited to 1 mm at best in human soft tissues because of aberrations and multiple scattering. We propose a matrix approach of optical imaging to push back this fundamental limit. By combining a matrix discrimination of ballistic waves and iterative time reversal, we show, both theoretically and experimentally, an extension of the imaging-depth limit by at least a factor of 2 compared to optical coherence tomography. In particular, the reported experiment demonstrates imaging through a strongly scattering layer from which only 1 reflected photon out of 1000 billion is ballistic. This approach opens a new route toward ultra-deep tissue imaging.

Can we provide reperfusion therapy to all unselected patients admitted with acute myocardial infarction?

OBJECTIVES: This study sought to assess the maximal rate of acute Thrombolysis in Myocardial Infarction (TIMI) grade 3 patency that can be achieved in unselected patients. BACKGROUND: Early and complete (TIMI grade 3 flow) reperfusion is an important therapeutic goal during acute myocardial infarction. However, thrombolysis, although widely used, is often contraindicated or ineffective. The selective use of primary and rescue percutaneous transluminal coronary angioplasty (PTCA) may increase the number of patients receiving reperfusion therapy. METHODS: A cohort of 500 consecutive unselected patients with acute myocardial infarction were prospectively treated using a patency-oriented scheme: Thrombolysis-eligible patients received thrombolysis (n = 257) and underwent 90-min angiography to detect persistent occlusion for treatment with rescue PTCA. Emergency PTCA (n = 193) was attempted in patients with contraindications to thrombolysis, cardiogenic shock or uncertain diagnosis and in a subset of patients admitted under "ideal conditions." A small group of patients (n = 38) underwent acute angiography without PTCA. Conventional medical therapy was used in 12 patients with contraindications to both thrombolysis and PTCA. RESULTS: Ninety-eight percent of patients received reperfusion therapy (thrombolysis, PTCA or acute angiography), and angiographically proven early TIMI grade 3 patency was achieved in 78%. Among patients with TIMI grade 3 patency, thrombolysis alone was the strategy used in 37%, emergency PTCA in 40% and rescue PTCA after failed thrombolysis in 15%; spontaneous patency occurred in 8%. CONCLUSIONS: Reperfusion therapy can be provided to nearly every patient (98%) with acute myocardial infarction. Rescue and direct PTCA provided effective early reperfusion to patients in whom thrombolysis failed or was excluded.

Theoretical description of the photorefractive detection of the ultrasound modulated photons in scattering media.

Acousto-optic imaging of thick biological tissues can be obtained in real-time with an adaptive-wavefront holographic setup, where the holographic media is a self-developping photorefractive crystal. As a consequence, the interference signal resulting from the acousto-optic effect can be easily collected with a high etendue and fast single photodetector. We present a statistical model of the field propagating through the scattering media and show why the various acoustic frequency components contained in the speckle output pattern are uncorrelated. We then give a detailed description of the signal measured through the photorefractive effect, in order to explain the quadratic pressure response observed for the two commonly used configurations setup e.g an amplitude or a phase modulation of the ultrasound.

Fingerprint imaging from the inside of a finger with full-field optical coherence tomography.

Imaging below fingertip surface might be a useful alternative to the traditional fingerprint sensing since the internal finger features are more reliable than the external ones. One of the most promising subsurface imaging technique is optical coherence tomography (OCT), which, however, has to acquire 3-D data even when a single en face image is required. This makes OCT inherently slow for en face imaging and produce unnecessary large data sets. Here we demonstrate that full-field optical coherence tomography (FF-OCT) can be used to produce en face images of sweat pores and internal fingerprints, which can be used for the identification purposes.