Retrieving time-dependent Green's functions in optics with low-coherence interferometry.

We report on the passive measurement of time-dependent Green's functions in the optical frequency domain with low-coherence interferometry. Inspired by previous studies in acoustics and seismology, we show how the correlations of a broadband and incoherent wave field can directly yield the Green's functions between scatterers of a complex medium. Both the ballistic and multiple scattering components of the Green's function are retrieved. This approach opens important perspectives for optical imaging and characterization in complex scattering media.

Cellular structural and functional imaging of donor and pathological corneas with label-free dual-mode full-field optical coherence tomography.

In this study, a dual-mode full-field optical coherence tomography (FFOCT) was customized for label-free static and dynamic imaging of corneal tissues, including donor grafts and pathological specimens. Static images effectively depict relatively stable structures such as stroma, scar, and nerve fibers, while dynamic images highlight cells with active intracellular metabolism, specifically for corneal epithelial cells. The dual-mode images complementarily demonstrate the 3D microstructural features of the cornea and limbus. Dual-modal imaging reveals morphological and functional changes in corneal epithelial cells without labeling, indicating cellular apoptosis, swelling, deformation, dynamic signal alterations, and distinctive features of inflammatory cells in keratoconus and corneal leukoplakia. These findings propose dual-mode FFOCT as a promising technique for cellular-level cornea and limbus imaging.

Carbon monoxide and prognosis in smokers hospitalised with acute cardiac events: a multicentre, prospective cohort study.

Background: Smoking cigarettes produces carbon monoxide (CO), which can reduce the oxygen-carrying capacity of the blood. We aimed to determine whether elevated expiratory CO levels would be associated with a worse prognosis in smokers presenting with acute cardiac events. Methods: From 7 to 22 April 2021, expiratory CO levels were measured in a prospective registry including all consecutive patients admitted for acute cardiac event in 39 centres throughout France. The primary outcome was 1-year all-cause death. Initial in-hospital major adverse cardiac events (MAE; death, resuscitated cardiac arrest and cardiogenic shock) were also analysed. The study was registered at ClinicalTrials.gov (NCT05063097). Findings: Among 1379 patients (63 ± 15 years, 70% men), 368 (27%) were active smokers. Expiratory CO levels were significantly raised in active smokers compared to non-smokers. A CO level >11 parts per million (ppm) found in 94 (25.5%) smokers was associated with a significant increase in death (14.9% for CO > 11 ppm vs. 2.9% for CO ≤ 11 ppm; p < 0.001). Similar results were found after adjustment for comorbidities (hazard ratio [HR] [95% confidence interval (CI)]): 5.92 [2.43-14.38]) or parameters of in-hospital severity (HR 6.09, 95% CI [2.51-14.80]) and propensity score matching (HR 7.46, 95% CI [1.70-32.8]). CO > 11 ppm was associated with a significant increase in MAE in smokers during initial hospitalisation after adjustment for comorbidities (odds ratio [OR] 15.75, 95% CI [5.56-44.60]) or parameters of in-hospital severity (OR 10.67, 95% CI [4.06-28.04]). In the overall population, CO > 11 ppm but not smoking was associated with an increased rate of all-cause death (HR 4.03, 95% CI [2.33-6.98] and 1.66 [0.96-2.85] respectively). Interpretation: Elevated CO level is independently associated with a 6-fold increase in 1-year death and 10-fold in-hospital MAE in smokers hospitalized for acute cardiac events. Funding: Grant from Fondation Coeur & Recherche.

TAPSE/sPAP prognostic value for In-Hospital Adverse Events in Patients Hospitalized for Acute Coronary Syndrome.

AIMS: Although several studies have shown that the right ventricular to pulmonary artery (RV-PA) coupling, assessed by the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure (TAPSE/sPAP) using echocardiography, is strongly associated with cardiovascular events, its prognostic value is not established in acute coronary syndrome (ACS). We aimed to assess the in-hospital prognostic value of TAPSE/sPAP among patients hospitalized for ACS in a retrospective analysis from the prospective ADDICT-ICCU study. METHODS AND RESULTS: 481 consecutive patients hospitalized in intensive cardiac care unit (mean age 65±13 years, 73% of male, 46% STEMI) for ACS (either ST-elevation [STEMI] or non-ST-elevation [NSTEMI] myocardial infarction) with TAPSE/sPAP available were included in this prospective French multicentric study (39 centers). The primary outcome was in-hospital major adverse cardiovascular events (MACEs) defined as all-cause death, resuscitated cardiac arrest or cardiogenic shock and occurred in 33 (7%) patients. ROC-curve analysis identified 0.55 mm/mmHg as the best TAPSE/sPAP cut-off to predict in-hospital MACEs. TAPSE/sPAP <0.55 was associated with in-hospital MACEs, even after adjustment with comorbidities (OR:19.1, 95%CI[7.78-54.8]), clinical severity including left ventricular ejection fraction (OR:14.4, 95%CI[5.70-41.7]) and propensity-matched population analysis (OR:22.8, 95%CI[7.83-97.2], all p<0.001). After adjustment, TAPSE/sPAP <0.55 showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.16; global chi-square improvement: 52.8; LR-test p<0.001) with similar results for both STEMI and NSTEMI subgroups. CONCLUSION: A low RV-PA coupling defined as TAPSE/sPAP ratio <0.55 was independently associated with in-hospital MACEs and provided incremental prognostic value over traditional prognosticators in patients hospitalized for ACS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05063097.

Time-domain full-field optical coherence tomography (TD-FF-OCT) in ophthalmic imaging.

Ocular imaging plays an irreplaceable role in the evaluation of eye diseases. Developing cellular-resolution ophthalmic imaging technique for more accurate and effective diagnosis and pathogenesis analysis of ocular diseases is a hot topic in the cross-cutting areas of ophthalmology and imaging. Currently, ocular imaging with traditional optical coherence tomography (OCT) is limited in lateral resolution and thus can hardly resolve cellular structures. Conventional OCT technology obtains ultra-high resolution at the expense of a certain imaging range and cannot achieve full field of view imaging. In the early years, Time-domain full-field OCT (TD-FF-OCT) has been mainly used for ex vivo ophthalmic tissue studies, limited by the low speed and low full-well capacity of existing two-dimensional (2D) cameras. The recent improvements in system design opened new imaging possibilities for in vivo applications thanks to its distinctive optical properties of TD-FF-OCT such as a spatial resolution almost insensitive to aberrations, and the possibility to control the curvature of the optical slice. This review also attempts to look at the future directions of TD-FF-OCT evolution, for example, the potential transfer of the functional-imaging dynamic TD-FF-OCT from the ex vivo into in vivo use and its expected benefit in basic and clinical ophthalmic research. Through non-invasive, wide-field, and cellular-resolution imaging, TD-FF-OCT has great potential to be the next-generation imaging modality to improve our understanding of human eye physiology and pathology.

Prevalence of psychoactive drug use in patients hospitalized for acute cardiac events: Rationale and design of the ADDICT-ICCU trial, from the Emergency and Acute Cardiovascular Care Working Group and the National College of Cardiologists in Training of the French Society of Cardiology.

BACKGROUND: Psychoactive drugs, including illicit drugs, are associated with an increased rate of cardiovascular events. The prevalence and outcome of patients using these drugs at the time of admission to an intensive cardiac care unit is unknown. AIM: To assess the prevalence of psychoactive drugs detected in consecutive patients hospitalized in an intensive cardiac care unit for an acute cardiovascular event. METHODS: This is a nationwide prospective multicentre study, involving 39 centres throughout France, including all consecutive patients hospitalized in an intensive cardiac care unit within 2weeks. Psychoactive drug use will be assessed systematically by urine drug assay within 2hours of intensive cardiac care unit admission, to detect illicit (cannabinoids, cocaine, amphetamines, ecstasy, heroin and other opioids) and non-illicit (barbiturates, benzodiazepines, tricyclic antidepressants, methadone and buprenorphine) psychoactive drugs. Smoking will be investigated systematically by exhaled carbon monoxide measurement, and alcohol consumption using a standardized questionnaire. In-hospital major adverse events, including death, resuscitated cardiac arrest and cardiogenic shock, will be recorded. After discharge, all-cause death and major adverse cardiovascular events will be recorded systematically and adjudicated at 12months of follow-up. RESULTS: The primary outcome will be the prevalence of psychoactive drugs detected by systematic screening among all patients hospitalized in an intensive cardiac care unit. The in-hospital major adverse events will be analysed according to the presence or absence of detected psychoactive drugs. Subgroup analysis stratified by initial clinical presentation and type of psychoactive drug will be performed. CONCLUSIONS: This is the first prospective multicentre study to assess the prevalence of psychoactive drugs detected by systematic screening in consecutive patients hospitalized for acute cardiovascular events.

In-vacuum optical isolation changes by heating in a Faraday isolator.

We describe a model evaluating changes in the optical isolation of a Faraday isolator when passing from air to vacuum in terms of different thermal effects in the crystal. The changes are particularly significant in the crystal thermal lensing (refraction index and thermal expansion) and in its Verdet constant and can be ascribed to the less efficient convection cooling of the magneto-optic crystal of the Faraday isolator. An isolation decrease by a factor of 10 is experimentally observed in a Faraday isolator that is used in a gravitational wave experiment (Virgo) with a 10 W input laser when going from air to vacuum. A finite element model simulation reproduces with a great accuracy the experimental data measured on Virgo and on a test bench. A first set of measurements of the thermal lensing has been used to characterize the losses of the crystal, which depend on the sample. The isolation factor measured on Virgo confirms the simulation model and the absorption losses of 0.0016 +/- 0.0002/cm for the TGG magneto-optic crystal used in the Faraday isolator.

The role of prefrontal cortex in a moral judgment task using functional near-infrared spectroscopy.

BACKGROUND: Understanding the neural basis of moral judgment (MJ) and human decision-making has been the subject of numerous studies because of their impact on daily life activities and social norms. Here, we aimed to investigate the neural process of MJ using functional near-infrared spectroscopy (fNIRS), a noninvasive, portable, and affordable neuroimaging modality. METHODS: We examined prefrontal cortex (PFC) activation in 33 healthy participants engaging in MJ exercises. We hypothesized that participants presented with personal (emotionally salient) and impersonal (less emotional) dilemmas would exhibit different brain activation observable through fNIRS. We also investigated the effects of utilitarian and nonutilitarian responses to MJ scenarios on PFC activation. Utilitarian responses are those that favor the greatest good while nonutilitarian responses favor moral actions. Mixed effect models were applied to model the cerebral hemodynamic changes that occurred during MJ dilemmas. RESULTS AND CONCLUSIONS: Our analysis found significant differences in PFC activation during personal versus impersonal dilemmas. Specifically, the left dorsolateral PFC was highly activated during impersonal MJ when a nonutilitarian decision was made. This is consistent with the majority of relevant fMRI studies, and demonstrates the feasibility of using fNIRS, with its portable and motion tolerant capacities, to investigate the neural basis of MJ dilemmas.

Cortical blood flow assessment with frequency-domain laser Doppler microscopy.

We report the assessment of cerebral blood flow (CBF) changes with a wide-field laser Doppler imager based on a CCD camera detection scheme, in vivo, in mice. The setup enables the acquisition of data in minimally invasive conditions. In contrast with conventional laser Doppler velocimeters and imagers, the Doppler signature of moving scatterers is measured in the frequency domain, by detuning a heterodyne optical detection. The quadratic mean of the measured frequency shift is used as an indicator of CBF. We observe a significant variability of this indicator in an experiment designed to induce blood flow changes.

Utilization of interferometric light microscopy for the rapid analysis of virus abundance in a river.

There is a constant need for direct counting of biotic nanoparticles such as viruses to unravel river functioning. We used, for the first time in freshwater, a new method based on interferometry differentiating viruses from other particles such as membrane vesicles. In the French Marne River, viruses represented between 42 and 72% of the particles. A spring monitoring in 2014 revealed their increase (2.1 × 107 to 2.1 × 108 mL-1) linked to an increase in algal biomass and diversity of bacterial plankton. Predicted virus size distributions were in agreement with transmission electron microscopy analysis suggesting a dominance of large viruses (≥60 nm).

Adaptive optics full-field optical coherence tomography.

We describe a simple and compact full-field optical coherence tomography (FFOCT) setup coupled to a transmissive liquid crystal spatial light modulator (LCSLM) to induce or correct aberrations. To reduce the system complexity, strict pupil conjugation was abandoned because low-order aberrations are often dominant. We experimentally confirmed a recent theoretical and experimental demonstration that the image resolution was almost insensitive to aberrations that mostly induce a reduction of the signal level. As a consequence, an image-based algorithm was applied for the optimization process by using the FFOCT image intensity as the metric. Aberration corrections were demonstrated with both an USAF resolution target and biological samples for LCSLM-induced and sample-induced wavefront distortions.

Intracellular dynamics measurements with full field optical coherence tomography suggest hindering effect of actomyosin contractility on organelle transport.

Intracellular motion can be quantitatively monitored in tissues using coherence-gated microscopic techniques. With full-field optical coherence tomography (FFOCT), the use of high numerical aperture microscope objectives provides a high resolution mapping of intracellular dynamics that are probed with subwavelength sensitivity. In the upper temporal bandwidth that we have used (1-6 Hz) the main contribution to the dynamic signal arises from the overall dynamical, optically heterogeneous cytoplasm. We propose a method to specifically study the impact of actomyosin contractility on the intracellular dynamic signal by performing high throughput, comparative measurements of multicellular aggregates with and without blebbistatin action, a selective inhibitor of class-II myosins that disrupts actomyosin contractile activity. Our results indicate a significant increase in the fraction of the signal that decorrelates within 1 second after inhibition of contractility. This observation mitigates the anticipated importance of actomyosin contractile forces to directly move organelles, but highlights their role in hindering organelle transport via their stiffening effect of the viscoelastic cytoplasm.

Full-field interferometry for counting and differentiating aquatic biotic nanoparticles: from laboratory to Tara Oceans.

There is a huge abundance of viruses and membrane vesicles in seawater. We describe a new full-field, incoherently illuminated, shot-noise limited, common-path interferometric detection method that we couple with the analysis of Brownian motion to detect, quantify, and differentiate biotic nanoparticles. We validated the method with calibrated nanoparticles and homogeneous DNA or RNA viruses. The smallest virus size that we characterized with a suitable signal-to-noise ratio was around 30 nm in diameter. Analysis of Brownian motions revealed anisotropic trajectories for myoviruses.We further applied the method for vesicles detection and for analysis of coastal and oligotrophic samples from Tara Oceans circumnavigation.

Enhancement of hidden structures of early skin fibrosis using polarization degree patterns and Pearson correlation analysis.

The skin of athymic nude mice is irradiated with a single dose of x-ray irradiation that initiated fibrosis. Digital photographs of the irradiated mice are taken by illuminating the mouse skin with linearly polarized probe light of 650 nm. The specific pattern of the surface distribution of the degree of polarization enables the detection of initial skin fibrosis structures that were not visually apparent. Data processing of the raw spatial distributions of the degree of polarization based on Fourier filtering of the high-frequency noise improves subjective perception of the revealed structure in the images. In addition, Pearson correlation analysis provides information about skin structural size and directionality.

Early invasive strategy in high-risk acute coronary syndrome without ST-segment elevation. The Sisca randomized trial.

BACKGROUND: The optimal therapeutic strategy for patients with high-risk acute coronary syndrome without ST-segment elevation (NSTE-ACS) remains unclear. OBJECTIVE: Our aim was to compare the effectiveness of an early invasive strategy and a delayed invasive strategy in the management of high-risk NSTE-ACS patients. METHODS: This randomized clinical trial in a primarily pre-hospital setting enrolled patients with chest pain, electrocardiographic criteria for an NSTE-ACS, and at least one criterion of severity (ESC criterion or TIMI score >5). Patients were randomized to either an early invasive strategy (tirofiban infusion and coronary angiography within 6h) or delayed invasive strategy (as per guidelines and physician discretion; coronary angiography within 6h was not advised). The primary endpoint was the cumulative incidence of deaths, myocardial infarctions, or urgent revascularizations at 30days of follow-up. Secondary endpoints were failure of delayed management, length of hospital stay and long-term mortality. RESULTS: Between January 2007 and February 2010, 170 patients were enrolled. The cumulative incidence of adverse outcomes was significantly lower for early invasive than delayed management (2% [95% CI 0-9] vs. 24% [95% CI 16-35], p<10(-4)). Delayed management failed in 24% of cases. The length of hospital stay was significantly shorter in patients undergoing angioplasty or treated with tirofiban within 6h (p=0.0003). Long-term mortality was 16% in both arms after a median follow-up of 4.1years. CONCLUSION: An early invasive strategy reduced major adverse cardiac events in patients with high-risk NSTE-ACS. Early angiography or tirofiban (GP IIb/IIIa inhibitor) infusion proved necessary in a quarter of patients assigned to delayed management.

State-of-the art of acousto-optic sensing and imaging of turbid media.

Acousto-optic (AO) is an emerging hybrid technique for measuring optical contrast in turbid media using coherent light and ultrasound (US). A turbid object is illuminated with a coherent light source leading to speckle formation in the remitted light. With the use of US, a small volume is selected,which is commonly referred to as the "tagging" volume. This volume acts as a source of modulated light, where modulation might involve phase and intensity change. The tagging volume is created by focusing ultrasound for good lateral resolution; the axial resolution is accomplished by making either the US frequency, amplitude, or phase time-dependent. Typical resolutions are in the order of 1 mm. We will concentrate on the progress in the field since 2003. Different schemes will be discussed to detect the modulated photons based on speckle detection, heterodyne detection, photorefractive crystal (PRC) assisted detection, and spectral hole burning (SHB) as well as Fabry-Perot interferometers. The SHB and Fabry-Perot interferometer techniques are insensitive to speckle decorrelation and therefore suitable for in vivo imaging. However, heterodyne and PRC methods also have potential for in vivo measurements. Besides measuring optical properties such as scattering and absorption, AO can be applied in fluorescence and elastography applications.

Image transmission through an opaque material.

Optical imaging relies on the ability to illuminate an object, collect and analyse the light it scatters or transmits. Propagation through complex media such as biological tissues was so far believed to degrade the attainable depth, as well as the resolution for imaging, because of multiple scattering. This is why such media are usually considered opaque. Recently, we demonstrated that it is possible to measure the complex mesoscopic optical transmission channels that allow light to traverse through such an opaque medium. Here, we show that we can optimally exploit those channels to coherently transmit and recover an arbitrary image with a high fidelity, independently of the complexity of the propagation.

Polarization-sensitive full-field optical coherence tomography.

We present a polarization-sensitive full-field optical coherence tomography system that can produce high-resolution images of the linear retardance and reflectivity properties of biological media. En face images can be delivered at a frame rate of 3.5 Hz by combination of interferometric images acquired by two CCD cameras in an interference microscope illuminated with a tungsten halogen lamp. Isotropic spatial resolution of approximately 1.0 microm is achieved. The technique is demonstrated on ex vivo muscle tissues.

Early chloroplastic alterations analysed by optical coherence tomography during a harpin-induced hypersensitive response.

The hypersensitive response has been mostly studied by molecular and biochemical methods after sample destruction. The development of imaging techniques allows the monitoring of physiological changes before any signs of cell death. Here, we follow the early steps of a hypersensitive-like response induced by the bacterial elicitor harpin in Nicotiana sp. We describe cytological modifications after inoculation of the harpin protein, using confocal fluorescence microscopy (CFM) and optical coherence tomography (OCT), an interferometric-based microscopy. The changes detected by CFM occurred 5 h after harpin infiltration and corresponded to a redistribution of the chloroplasts from the upper to the inner regions of the palisade mesophyll cells which could be related to a perturbation in the microtubule network. Using OCT, we were able to detect a decrease in chloroplast backscattered signal as early as 30 min after harpin infiltration. A simple physical model, which accounted for the structure and distribution of thylakoid membranes, suggested that this loss of scattering could be associated with a modification in the refractive index of the thylakoid membranes. Our OCT observations were correlated with a decrease in photosynthesis, emphasizing changes in chloroplast structure as one of the earliest hallmarks of plant hypersensitive cell death.

Measurement of the optical parameters of the Virgo interferometer.

The Virgo interferometer, aimed at detecting gravitational waves, is now in a commissioning phase. Measurements of its optical properties are needed for the understanding of the instrument. We present the techniques developed for the measurement of the optical parameters of Virgo. These parameters are compared with the Virgo specifications.