A randomized, blinded study of photobiomodulation in a mouse model of Alzheimer's disease showed no preventive effect.

Photobiomodulation (PBM), the process of exposing tissue to red or near-infrared light, has become a topic of great interest as a therapy for diverse pathologies, including neurodegenerative disorders. Here, we aimed to evaluate the potential beneficial effect of PBM on Alzheimer's disease (AD) using behavioral and histological readouts from a well-established transgenic murine AD model (5xFAD mice) in a randomized and fully blinded long-term in-vivo study following GLP (Good Laboratory Practices) guidelines. The heads of the mice were illuminated with no (sham), low or high power 810 nm light, three times a week for 5 months from the first to the sixth month of life corresponding to the prodromal phase of the pathology. The results showed that there were no significant differences between the groups in behavioral tests, including the Morris water maze, novel object recognition, and Y-maze. Similarly, histological analyses showed no differences in amyloid load, neuronal loss or microglial response. In conclusion, under the conditions of our experiment, we were unable to demonstrate any therapeutic effect of PBM for AD. This study calls for further evidence and caution when considering PBM as an effective treatment for AD.

Automatic diagnosis and classification of breast surgical samples with dynamic full-field OCT and machine learning.

Purpose: The adoption of emerging imaging technologies in the medical community is often hampered when they provide a new unfamiliar contrast that requires experience to be interpreted. Dynamic full-field optical coherence tomography (D-FF-OCT) microscopy is such an emerging technique. It provides fast, high-resolution images of excised tissues with a contrast comparable to H&E histology but without any tissue preparation and alteration. Approach: We designed and compared two machine learning approaches to support interpretation of D-FF-OCT images of breast surgical specimens and thus provide tools to facilitate medical adoption. We conducted a pilot study on 51 breast lumpectomy and mastectomy surgical specimens and more than 1000 individual 1.3×1.3 mm2 images and compared with standard H&E histology diagnosis. Results: Using our automatic diagnosis algorithms, we obtained an accuracy above 88% at the image level (1.3×1.3 mm2) and above 96% at the specimen level (above cm2). Conclusions: Altogether, these results demonstrate the high potential of D-FF-OCT coupled to machine learning to provide a rapid, automatic, and accurate histopathology diagnosis with minimal sample alteration.

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.

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.

Adaptive-glasses time-domain FFOCT for wide-field high-resolution retinal imaging with increased SNR.

The highest three-dimensional (3D) resolution possible in in vivo retinal imaging is achieved by combining optical coherence tomography (OCT) and adaptive optics. However, this combination brings important limitations, such as small field-of-view and complex, cumbersome systems, preventing so far the translation of this technology from the research lab to clinics. In this Letter, we mitigate these limitations by combining our compact time-domain full-field OCT (FFOCT) with a multi-actuator adaptive lens positioned just in front of the eye, in a technique we call the adaptive-glasses wavefront sensorless approach. Through this approach, we demonstrate that ocular aberrations can be corrected, increasing the FFOCT signal-to-noise ratio (SNR) and enabling imaging of different retinal layers with a 3D cellular resolution over a 5∘×5∘ field-of-view, without apparent anisoplanatism.

Coherence gate shaping for wide field high-resolution in vivo retinal imaging with full-field OCT.

Allying high-resolution with a large field-of-view (FOV) is of great importance in the fields of biology and medicine, but it is particularly challenging when imaging non-flat living samples such as the human retina. Indeed, high-resolution is normally achieved with adaptive optics (AO) and scanning methods, which considerably reduce the useful FOV and increase the system complexity. An alternative technique is time-domain full-field optical coherence tomography (FF-OCT), which has already shown its potential for in-vivo high-resolution retinal imaging. Here, we introduce coherence gate shaping for FF-OCT, to optically shape the coherence gate geometry to match the sample curvature, thus achieving a larger FOV than previously possible. Using this instrument, we obtained high-resolution images of living human photoreceptors close to the foveal center without AO and with a 1 mm × 1 mm FOV in a single shot. This novel advance enables the extraction of photoreceptor-based biomarkers with ease and spatiotemporal monitoring of individual photoreceptors. We compare our findings with AO-assisted ophthalmoscopes, highlighting the potential of FF-OCT, as a compact system, to become a routine clinical imaging technique.

Dynamic full-field optical coherence tomography: 3D live-imaging of retinal organoids.

Optical coherence tomography offers astounding opportunities to image the complex structure of living tissue but lacks functional information. We present dynamic full-field optical coherence tomography as a technique to noninvasively image living human induced pluripotent stem cell-derived retinal organoids. Coloured images with an endogenous contrast linked to organelle motility are generated, with submicrometre spatial resolution and millisecond temporal resolution, creating a way to identify specific cell types in living tissue via their function.

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.

High-resolution in-vivo human retinal imaging using full-field OCT with optical stabilization of axial motion.

Time-domain full-field OCT (FF-OCT) represents an imaging modality capable of recording high-speed en-face sections of a sample at a given depth. One of the biggest challenges to transfer this technique to image in-vivo human retina is the presence of continuous involuntary head and eye axial motion during image acquisition. In this paper, we demonstrate a solution to this problem by implementing an optical stabilization in an FF-OCT system. This was made possible by combining an FF-OCT system, an SD-OCT system, and a high-speed voice-coil translation stage. B-scans generated by the SD-OCT were used to measure the retina axial position and to drive the position of the high-speed voice coil translation stage, where the FF-OCT reference arm is mounted. Closed-loop optical stabilization reduced the RMS error by a factor of 7, significantly increasing the FF-OCT image acquisition efficiency. By these means, we demonstrate the capacity of the FF-OCT to resolve cone mosaic as close as 1.5 o from the fovea center with high consistency and without using adaptive optics.

Motion artifact removal and signal enhancement to achieve in vivo dynamic full field OCT.

We present a filtering procedure based on singular value decomposition to remove artifacts arising from sample motion during dynamic full field OCT acquisitions. The presented method succeeded in removing artifacts created by environmental noise from data acquired in a clinical setting, including in vivo data. Moreover, we report on a new method based on using the cumulative sum to compute dynamic images from raw signals, leading to a higher signal to noise ratio, and thus enabling dynamic imaging deeper in tissues.

Probing dynamic processes in the eye at multiple spatial and temporal scales with multimodal full field OCT.

We describe recent technological progress in multimodal en face full-field optical coherence tomography that has allowed detection of slow and fast dynamic processes in the eye. We show that by combining static, dynamic and fluorescence contrasts we can achieve label-free high-resolution imaging of the retina and anterior eye with temporal resolution from milliseconds to several hours, allowing us to probe biological activity at subcellular scales inside 3D bulk tissue. Our setups combine high lateral resolution over a large field of view with acquisition at several hundreds of frames per second which make it a promising tool for clinical applications and biomedical studies. Its contactless and non-destructive nature is shown to be effective for both following in vitro sample evolution over long periods of time and for imaging of the human eye in vivo.