Injury, illness, and emotion: A review of the motivational continuum from trauma through recovery from an ecological perspective.

Image 1.

Changes in Oxygenation Levels During Moderate Altitude Simulation (Hypoxia-Induced): A Pilot Study Investigating the Impact of Skin Pigmentation in Pulse Oximetry.

The current COVID-19 pandemic has shown us that the pulse oximeter is a key medical device for monitoring blood-oxygen levels non-invasively in patients with chronic or acute illness. It has also emphasised limitations in accuracy for individuals with darker skin pigmentation, calling for new methods to provide better measurements. The aim of our study is to identify the impact of skin pigmentation on pulse oximeter measurements. We also explored the benefits of a multi-wavelength approach with an induced change of arterial oxygen saturation. A total of 20 healthy volunteers were recruited. We used time domain diffuse reflectance spectroscopy (TDDRS) from a broad band light source, collecting spectra from the index finger along with three different pulse oximeters used simultaneously for monitoring purposes. Five acute hypoxic events were induced by administering 11% FiO2, produced by a Hypoxico altitude training system, for 120 sec through a face mask with a one-way valve. Our multi-wavelength approach revealed a correlation between the signature of skin pigmentation and the dynamic range of oxygen saturation measurements. Principal component analysis (PCA) showed separation between a range of different pigmented volunteers (PC1 = 56.00%) and oxygen saturation (PC2 = 22.99%). This emphasises the need to take into account skin pigmentation in oximeter measurements. This preliminary study serves to validate the need to better understand the impact of skin pigmentation absorption on optical readings in pulse oximeters. Multi-wavelength approaches have the potential to enable robust and accurate measurements across diverse populations.

Addressing phase-curvature in Fourier ptychography.

In Fourier ptychography, multiple low resolution images are captured and subsequently combined computationally into a high-resolution, large-field of view micrograph. A theoretical image-formation model based on the assumption of plane-wave illumination from various directions is commonly used, to stitch together the captured information into a high synthetic aperture. The underlying far-field (Fraunhofer) diffraction assumption connects the source, sample, and pupil planes by Fourier transforms. While computationally simple, this assumption neglects phase-curvature due to non-planar illumination from point sources as well as phase-curvature from finite-conjugate microscopes (e.g., using a single-lens for image-formation). We describe a simple, efficient, and accurate extension of Fourier ptychography by embedding the effect of phase-curvature into the underlying forward model. With the improved forward model proposed here, quantitative phase reconstruction is possible even for wide fields-of-views and without the need of image segmentation. Lastly, the proposed method is computationally efficient, requiring only two multiplications: prior and following the reconstruction.

Snapshot volumetric imaging with engineered point-spread functions.

The biological world involves intracellular and intercellular interactions that occur at high speed, at multiple scales and in three dimensions. Acquiring 3D images, however, typically requires a compromise in either spatial or temporal resolution compared to 2D imaging. Conventional 2D fluorescence imaging provides high spatial resolution but requires plane-by-plane imaging of volumes. Conversely, snapshot methods such as light-field microscopy allow video-rate imaging, but at the cost of spatial resolution. Here we introduce 3D engineered point-spread function microscopy (3D-EPM), enabling snapshot imaging of real-world 3D extended biological structures while retaining the native resolution of the microscope in space and time. Our new computational recovery strategy is the key to volumetrically reconstructing arbitrary 3D structures from the information encapsulated in 2D raw EPM images. We validate our technique on both point-like and extended samples, and demonstrate its power by imaging the intracellular motion of chloroplasts undergoing cyclosis in a sample of Egeria densa. Our technique represents a generalised computational methodology for 3D image recovery which is readily adapted to a diverse range of existing microscopy platforms and engineered point-spread functions. We therefore expect it to find broad applicability in the study of rapid biological dynamics in 3D.

High-speed multi-objective Fourier ptychographic microscopy.

The ability of a microscope to rapidly acquire wide-field, high-resolution images is limited by both the optical performance of the microscope objective and the bandwidth of the detector. The use of multiple detectors can increase electronic-acquisition bandwidth, but the use of multiple parallel objectives is problematic since phase coherence is required across the multiple apertures. We report a new synthetic-aperture microscopy technique based on Fourier ptychography, where both the illumination and image-space numerical apertures are synthesized, using a spherical array of low-power microscope objectives that focus images onto mutually incoherent detectors. Phase coherence across apertures is achieved by capturing diffracted fields during angular illumination and using ptychographic reconstruction to synthesize wide-field, high-resolution, amplitude and phase images. Compared to conventional Fourier ptychography, the use of multiple objectives reduces image acquisition times by increasing the area for sampling the diffracted field. We demonstrate the proposed scaleable architecture with a nine-objective microscope that generates an 89-megapixel, 1.1 µm resolution image nine-times faster than can be achieved with a single-objective Fourier-ptychographic microscope. New calibration procedures and reconstruction algorithms enable the use of low-cost 3D-printed components for longitudinal biological sample imaging. Our technique offers a route to high-speed, gigapixel microscopy, for example, imaging the dynamics of large numbers of cells at scales ranging from sub-micron to centimetre, with an enhanced possibility to capture rare phenomena.

Pixel super-resolution with spatially entangled photons.

Pixelation occurs in many imaging systems and limits the spatial resolution of the acquired images. This effect is notably present in quantum imaging experiments with correlated photons in which the number of pixels used to detect coincidences is often limited by the sensor technology or the acquisition speed. Here, we introduce a pixel super-resolution technique based on measuring the full spatially-resolved joint probability distribution (JPD) of spatially-entangled photons. Without shifting optical elements or using prior information, our technique increases the pixel resolution of the imaging system by a factor two and enables retrieval of spatial information lost due to undersampling. We demonstrate its use in various quantum imaging protocols using photon pairs, including quantum illumination, entanglement-enabled quantum holography, and in a full-field version of N00N-state quantum holography. The JPD pixel super-resolution technique can benefit any full-field imaging system limited by the sensor spatial resolution, including all already established and future photon-correlation-based quantum imaging schemes, bringing these techniques closer to real-world applications.

Integrated neuroimmune processing of threat, injury, and illness: An ecological framework mapping social alienation onto lifetime health vulnerability.

Social alienation is a pre-eminent ecological threat for humans. In clinical and social care settings its impact is acknowledged in conditions as diverse as severe mood disturbance, chronic pain, and metabolic non-communicable diseases. An integrated psychoneuroimmune perspective shows how threat, injury, healing, and recovery follow through as a continuous process, but accepted cultural and clinical paradigms separating mental from physical illness provide little common ground on which to analyse and apply this continuum in practice. By reviewing the ecological relationships between emotional threat, tissue dyshomeostasis and injury, infection, pain, and mood this article explores not only how primeval somatic responses underpin the evolutionary foundations of depression and somatisation, but also links them to escalating physical non-communicable disease through archived socioeconomic adversity (allostatic load). Social alienation (in the absence of trauma) may prime and activate this ancient repertoire in which sensitised responses lay the foundation for persistent maladaptive states of aversive sensory misinterpretation, behavioural avoidance, anhedonia, and neuroinflammation presenting as widespread non-nociceptive pain, non-pain somatisation, and severe depression. The ecological perspective illuminates perverse clinical presentations, shows how some approaches to care may facilitate self-reinforcement in maladaptive syndromes, and offers pointers for inclusive rehabilitative clinical and social care.

Multi-aperture imaging for flat cameras.

Imaging with high angular resolution requires large apertures and long focal lengths. This has prevented the integration of telephoto lenses into thin devices such as modern mobile phones. We report a camera module employing multiple rotated rectangular apertures and folding of the optical system into the plane of the camera, enabling an order-of-magnitude reduction in depth compared to traditional telephoto lenses. Multiple images are fused in the frequency domain to yield a single high-resolution image equivalent to that yielded by a single circular aperture. The diameter of this equivalent aperture may be several times wider than the depth of the camera module. We propose two architectures and present illustrative optical designs to demonstrate the concept. Simulations of raytraced image acquisition and computational image reconstruction demonstrate the potential for high-quality, high-resolution imaging from thin, flat lens modules.

Computational Optical Sensing and Imaging: feature issue introduction.

This Feature Issue includes 19 articles that highlight advances in the field of Computational Optical Sensing and Imaging. Many of the articles were presented at the 2019 OSA Topical Meeting on Computational Optical Sensing and Imaging held in Munich, Germany, on June 24-27. Articles featured in the issue cover a broad array of topics ranging from imaging through scattering media, imaging round corners and compressive imaging to machine learning for recovery of images.

Publisher Correction: Holistic Monte-Carlo optical modelling of biological imaging.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Twin-Airy Point-Spread Function for Extended-Volume Particle Localization.

The localization of point sources in optical microscopy enables nm-precision imaging of single-molecules and biological dynamics. We report a new method of localization microscopy using twin Airy beams that yields precise 3D localization with the key advantages of extended depth range, higher optical throughput, and potential for imaging higher emitter densities than are possible using other techniques. A precision of better than 30 nm was achieved over a depth range in excess of 7 µm using a 60×, 1.4 NA objective. An illustrative application to extended-depth-range blood-flow imaging in a live zebrafish is also demonstrated.

Nimodipine Reduces Dysfunction and Demyelination in Models of Multiple Sclerosis.

OBJECTIVE: Treatment of relapses in multiple sclerosis (MS) has not advanced beyond steroid use, which reduces acute loss of function, but has little effect on residual disability. Acute loss of function in an MS model (experimental autoimmune encephalomyelitis [EAE]) is partly due to central nervous system (CNS) hypoxia, and function can promptly improve upon breathing oxygen. Here, we investigate the cause of the hypoxia and whether it is due to a deficit in oxygen supply arising from impaired vascular perfusion. We also explore whether the CNS-selective vasodilating agent, nimodipine, may provide a therapy to restore function, and protect from demyelination in 2 MS models. METHODS: A variety of methods have been used to measure basic cardiovascular physiology, spinal oxygenation, mitochondrial function, and tissue perfusion in EAE. RESULTS: We report that the tissue hypoxia in EAE is associated with a profound hypoperfusion of the inflamed spinal cord. Treatment with nimodipine restores spinal oxygenation and can rapidly improve function. Nimodipine therapy also reduces demyelination in both EAE and a model of the early MS lesion. INTERPRETATION: Loss of function in EAE, and demyelination in EAE, and the model of the early MS lesion, seem to be due, at least in part, to tissue hypoxia due to local spinal hypoperfusion. Therapy to improve blood flow not only protects neurological function but also reduces demyelination. We conclude that nimodipine could be repurposed to offer substantial clinical benefit in MS. ANN NEUROL 2020 ANN NEUROL 2020;88:123-136.

Fourier ptychography: current applications and future promises.

Traditional imaging systems exhibit a well-known trade-off between the resolution and the field of view of their captured images. Typical cameras and microscopes can either "zoom in" and image at high-resolution, or they can "zoom out" to see a larger area at lower resolution, but can rarely achieve both effects simultaneously. In this review, we present details about a relatively new procedure termed Fourier ptychography (FP), which addresses the above trade-off to produce gigapixel-scale images without requiring any moving parts. To accomplish this, FP captures multiple low-resolution, large field-of-view images and computationally combines them in the Fourier domain into a high-resolution, large field-of-view result. Here, we present details about the various implementations of FP and highlight its demonstrated advantages to date, such as aberration recovery, phase imaging, and 3D tomographic reconstruction, to name a few. After providing some basics about FP, we list important details for successful experimental implementation, discuss its relationship with other computational imaging techniques, and point to the latest advances in the field while highlighting persisting challenges.

Remote sensing of blood oxygenation using red-eye pupil reflection.

OBJECTIVE: To develop a technique for remote sensing of systemic blood oxygenation using red-eye pupil reflection. APPROACH: The ratio of the intensities of light from the bright pupil reflections at oxygen sensitive and isosbestic wavelengths is shown to be sensitive to the oxygenation of blood in the eye. A conventional retinal camera, fitted with an image-replicating imaging spectrometer, was used at standoff range to record snapshot spectral images of the face and eyes at eight different wavelengths. In our pilot study we measured optical-density ratios (ODRs) of pupil reflections at wavelengths of 780 nm and 800 nm, simultaneous with pulse oximetry, for ten healthy human subjects under conditions of normoxia and mild hypoxia (15% oxygen). The low absorption at these infrared wavelengths localises the sensing to the choroid. We propose that this can be used for as a proxy for systemic oximetry. MAIN RESULTS: A significant reduction (P < 0.001) in ODR of the pupil images was observed during hypoxia and returned to baseline on resumption of normoxia. We demonstrate that measurement of the choroidal ODR can be used to detect changes in blood oxygenation that correlate positively with pulse oximetry and with a noise-equivalent oximetry precision of 0.5%. SIGNIFICANCE: We describe a new method to remotely and non-invasively sense the oxygen saturation of choroidal blood. The methodology provides a proxy for remote sensing of cerebral and systemic blood oxygenation. We demonstrate the technique at short range but it has potential for systemic oximetry at large standoff ranges.

Holistic Monte-Carlo optical modelling of biological imaging.

The invention and advancement of biological microscopy depends critically on an ability to accurately simulate imaging of complex biological structures embedded within complex scattering media. Unfortunately no technique exists for rigorous simulation of the complete imaging process, including the source, instrument, sample and detector. Monte-Carlo modelling is the gold standard for the modelling of light propagation in tissue, but is somewhat laborious to implement and does not incorporate the rejection of scattered light by the microscope. On the other hand microscopes may be rigorously and rapidly modelled using commercial ray-tracing software, but excluding the interaction with the biological sample. We report a hybrid Monte-Carlo optical ray-tracing technique for modelling of complete imaging systems of arbitrary complexity. We make the software available to enable user-friendly and rigorous virtual prototyping of biological microscopy of arbitrary complexity involving light scattering, fluorescence, polarised light propagation, diffraction and coherence. Examples are presented for the modelling and optimisation of representative imaging of neural cells using light-sheet and micro-endoscopic fluorescence microscopy and imaging of retinal vasculature using confocal and non-confocal scanning-laser ophthalmoscopes.

Phase and amplitude imaging with quantum correlations through Fourier Ptychography.

Extracting as much information as possible about an object when probing with a limited number of photons is an important goal with applications from biology and security to metrology. Imaging with a few photons is a challenging task as the detector noise and stray light are then predominant, which precludes the use of conventional imaging methods. Quantum correlations between photon pairs has been exploited in a so called 'heralded imaging scheme' to eliminate this problem. However these implementations have so-far been limited to intensity imaging and the crucial phase information is lost in these methods. In this work, we propose a novel quantum-correlation enabled Fourier Ptychography technique, to capture high-resolution amplitude and phase images with a few photons. This is enabled by the heralding of single photons combined with Fourier ptychographic reconstruction. We provide experimental validation and discuss the advantages of our technique that include the possibility of reaching a higher signal to noise ratio and non-scanning Fourier Ptychographic acquisition.

Low-cost, sub-micron resolution, wide-field computational microscopy using opensource hardware.

The revolution in low-cost consumer photography and computation provides fertile opportunity for a disruptive reduction in the cost of biomedical imaging. Conventional approaches to low-cost microscopy are fundamentally restricted, however, to modest field of view (FOV) and/or resolution. We report a low-cost microscopy technique, implemented with a Raspberry Pi single-board computer and color camera combined with Fourier ptychography (FP), to computationally construct 25-megapixel images with sub-micron resolution. New image-construction techniques were developed to enable the use of the low-cost Bayer color sensor, to compensate for the highly aberrated re-used camera lens and to compensate for misalignments associated with the 3D-printed microscope structure. This high ratio of performance to cost is of particular interest to high-throughput microscopy applications, ranging from drug discovery and digital pathology to health screening in low-income countries. 3D models and assembly instructions of our microscope are made available for open source use.

Computational optical sensing and imaging: introduction.

The OSA Topical Meeting on Computational Optical Sensing and Imaging (COSI) was held June 25-June 28, 2018 in Orlando, Florida, USA, as part of the Imaging and Applied Optics Congress. In this feature issue, we present several papers that cover the techniques, topics, and advancements in the field presented at the COSI meeting highlighting the integration of opto-electric measurement and computational processing.

Computational localization microscopy with extended axial range.

A new single-aperture 3D particle-localization and tracking technique is presented that demonstrates an increase in depth range by more than an order of magnitude without compromising optical resolution and throughput. We exploit the extended depth range and depth-dependent translation of an Airy-beam PSF for 3D localization over an extended volume in a single snapshot. The technique is applicable to all bright-field and fluorescence modalities for particle localization and tracking, ranging from super-resolution microscopy through to the tracking of fluorescent beads and endogenous particles within cells. We demonstrate and validate its application to real-time 3D velocity imaging of fluid flow in capillaries using fluorescent tracer beads. An axial localization precision of 50 nm was obtained over a depth range of 120µm using a 0.4NA, 20× microscope objective. We believe this to be the highest ratio of axial range-to-precision reported to date.

High-speed extended-volume blood flow measurement using engineered point-spread function.

Experimental characterization of blood flow in living organisms is crucial for understanding the development and function of cardiovascular systems, but there has been no technique reported for snapshot imaging of thick samples in large volumes with high precision. We have combined computational microscopy and the diffraction-free, self-bending property of Airy-beams to track fluorescent beads with sub-micron precision through an extended axial range (up to 600 µm) within the flowing blood of 3 days post-fertilization (dpf) zebrafish embryos. The spatial trajectories of the tracer beads within flowing blood were recorded during transit through both cardinal and intersegmental vessels, and the trajectories were found to be consistent with the segmentation of the vasculature recorded using selective-plane illumination microscopy (SPIM). This method provides sufficiently precise spatial and temporal measurement of 3D blood flow that has the potential for directly probing key biomechanical quantities such as wall shear stress, as well as exploring the fluidic repercussions of cardiovascular diseases. Although we demonstrate the technique for blood flow, the ten-fold better enhancement in the depth range offers improvements in a wide range of applications of high-speed precision measurement of fluid flow, from microfluidics through measurement of cell dynamics to macroscopic aerosol characterizations.