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Significance: Hyperspectral cameras capture spectral information at each pixel in an image. Acquired spectra can be analyzed to estimate quantities of absorbing and scattering components, but the use of traditional fitting algorithms over megapixel images can be computationally intensive. Deep learning algorithms can be trained to rapidly analyze spectral data and can potentially process hyperspectral camera data in real time. Aim: A hyperspectral camera was used to capture 1216 × 1936 pixel wide-field reflectance images of in vivo human tissue at 205 wavelength bands from 420 to 830 nm. Approach: The optical properties of oxyhemoglobin, deoxyhemoglobin, melanin, and scattering were used with multi-layer Monte Carlo models to generate simulated diffuse reflectance spectra for 24,000 random combinations of physiologically relevant tissue components. These spectra were then used to train an artificial neural network (ANN) to predict tissue component concentrations from an input reflectance spectrum. Results: The ANN achieved low root mean square errors in a test set of 6000 independent simulated diffuse reflectance spectra while calculating concentration values more than 4000× faster than a conventional iterative least squares approach. Conclusions: In vivo finger occlusion and gingival abrasion studies demonstrate the ability of this approach to rapidly generate high-resolution images of tissue component concentrations from a hyperspectral dataset acquired from human subjects. [ABSTRACT FROM AUTHOR]

Many Alzheimer's disease (AD) patients suffer from altered cerebral blood flow and damaged cerebral vasculature. Cerebrovascular dysfunction could play an important role in this disease. However, the mechanism underlying a vascular contribution in AD is still unclear. Cerebrovascular reactivity (CVR) is a critical mechanism that maintains cerebral blood flow and brain homeostasis. Most current methods to analyze CVR require anesthesia which is known to hamper the investigation of molecular mechanisms underlying CVR. We therefore combined spectroscopy, spectral analysis software, and an implantable device to measure cerebral blood volume fraction (CBVF) and oxygen saturation (SO2) in unanesthetized, freely-moving mice. Then, we analyzed basal CBVF and SO2, and CVR of 5-month-old C57BL/6 mice during hypercapnia as well as during basic behavior such as grooming, walking and running. Moreover, we analyzed the CVR of freely-moving AD mice and their wildtype (WT) littermates during hypercapnia and could find impaired CVR in AD mice compared to WT littermates. Our results suggest that this optomechanical approach to reproducibly getting light into the brain enabled us to successfully measure CVR in unanesthetized freely-moving mice and to find impaired CVR in a mouse model of AD. [ABSTRACT FROM AUTHOR]

If a single optical fiber is used for both delivery and collection of light, two major factors affect the measurement of collected light: (1) the light transport in the medium that describes the amount of light that returns to the fiber and (2) the light coupling to the optical fiber that depends on the angular distribution of photons entering the fiber. We focus on the importance of the latter factor and describe how the efficiency of the coupling depends on the optical properties of the medium. For highly scattering tissues, the efficiency is well predicted by the numerical aperture (NA) of the fiber. For lower scattering, such as in soft tissues, photons arrive at the fiber from deeper depths, and the coupling efficiency could increase twofold to threefold above that predicted by the NA. OCIS codes: 170.3660, 170.3890.

Sustained light‐dependent coral reef communities can be found at a wide range of light environments, extending from the sea level to as deep as 150 m (i.e. esophotic). How mesophotic corals thrive despite extremely limited light conditions still requires further investigation.Here, we undertook a comprehensive ecophysiological and bio‐optical study on four depth‐generalist coral species aiming to delineate the functional role that optical trait properties have in light‐harvesting, at contrasting light regimes.We show that the optical traits of coral skeletons are adjusted to their ambient light conditions and complement the microalgal demands for sufficient light, thus exhibiting a spatially efficient photosymbiotic system.In contrast to shallow corals, mesophotic corals absorbed up to three fold more light, resulting in excellent photosynthetic response under light conditions of only ~3% of the incident surface irradiance. The enhanced light‐harvesting capacity of mesophotic corals was achieved by redistributing light in the coral skeleton through optical scattering, thereby facilitating light transport and absorption by densely pigmented host tissue.Our findings provide fundamental insight into the light‐harvesting mechanisms underlying the productivity of mesophotic coral reef ecosystems, yet also raise concerns regarding their ability to withstand prolonged environmental disturbances. A free Plain Language Summary can be found within the Supporting Information of this article. [ABSTRACT FROM AUTHOR]

While in most cases, jaundice can be effectively treated using phototherapy, severe cases require exchange transfusion, a relatively risky procedure in which the neonate's bilirubin-rich blood is replaced with donor blood. Here, we examine extracorporeal blood treatment in a microfluidic photoreactor as an alternative to exchange transfusion. This new treatment approach relies on the same principle as phototherapy but leverages microfluidics to speed up bilirubin removal. Our results demonstrate that high-intensity light at 470 nm can be used to rapidly reduce bilirubin levels without causing appreciable damage to DNA in blood cells. Light at 470 nm was more effective than light at 505 nm. Studies in Gunn rats show that photoreactor treatment for 4 h significantly reduces bilirubin levels, similar to the bilirubin reduction observed for exchange transfusion and on a similar time scale. Predictions for human neonates demonstrate that this new treatment approach is expected to exceed the performance of exchange transfusion using a low blood flow rate and priming volume, which will facilitate vascular access and improve safety. [ABSTRACT FROM AUTHOR]

We report on a technique utilizing time-resolved detection of laser-induced stress transients for the measurement of optical properties in turbid media specifically suitable for biological tissues. The method was tested initially in nonscattering absorbing media so that it could be compared with spectrophotometry. The basis of this method is provided by the conditions of temporal stress confinement in the irradiated volume where the pressure generated in tissues heated instantly by laser pulses is proportional to the absorbed laser energy density, and the exponential profile of the initial stress distribution in the irradiated volume corresponds to the z-axial distribution of the absorbed laser fluence. Planar thermoelastic waves can propagate in water-containing media with minimal distortion, and their axial profiles can be detected by an acoustic transducer with sufficient temporal resolution. The acoustic waves induced by 14-ns laser pulses in nonscattering media, turbid gels, and tissues were measured by a piezoelectric transducer with a 3-ns response time. Temporal profiles of stress transients yielded z-axial distributions of the absorbed laser energy in turbid and opaque media, provided that the speed of sound in these media was known. The absorption and effective scattering coefficients of beef liver, dog prostate, and human aortic atheroma at three wavelengths, 1064 nm (in near infrared), 532 nm (visible), and 355 nm (near UV), were deduced from laser-induced stress profiles with additional measurements of total diffuse reflectance. Key words: Acoustic transducer, stress transients, optoacoustic imaging, tissue optics, light distribution.

Fiber-optic-based oblique-incidence reflectometry is a simple and accurate method for measuring the absorption and reduced scattering coefficients [[Mu].sub.a] and [[Mu][prime].sub.s] of semi-infinite turbid media. Obliquely incident light produces a spatial distribution of diffuse reflectance that is not centered about the point of light entry. The amount of shift in the center of diffuse reflectance is directly related to the medium's diffusion length D. We developed a fiber-optic probe to deliver light obliquely and sample the relative profile of diffuse reflectance. Measurement in absolute units is not necessary. From the profile, it was possible to measure D, perform a curve fit for the effective attenuation coefficient [[Mu].sub.eff], and then calculate [[Mu].sub.a] and [[Mu][prime].sub.s]. This method was verified with Monte Carlo simulations and tested on tissue phantoms. Our measurements of D and [[Mu].sub.eff] had an accuracy of approximately 5%, thus giving us 10% and 5% accuracy for [[Mu].sub.a] and [[Mu][prime].sub.s], respectively. Key words: Tissue optics, fiber optics, biomedical optics, turbid media, scattering media, optical properties, reflectometry, oblique incidence.

The narrowing of the spectral linewidth and the increasing of the peak intensity characteristic of laser action were observed in emission spectra of dye-infused biological tissues. The tissue was infused with a solution of Rhodamine 640 perchlorate in ethanol and then excited with frequency-doubled Q-switched Nd:YAG laser pulses. The dependence of emission linewidth on the excitation radiant exposure and dye concentration was investigated. Laser action was also observed in biologically compatible fluorescein sodium dye dissolved in phosphate-buffered saline mixed with scattering polystyrene spheres. The sharp spectral peaks of laser action in tissues may find applications in the detection of superficial disease. Key words: Tissue optics, laser action, fluorescence, amplification of spontaneous emission, turbid media.

We present a method for recovering the intrinsic fluorescence coefficient, defined as the product of the fluorophore absorption coefficient and the fluorescence energy yield, of an optically thick, homogeneous, turbid medium from a surface measurement of fluorescence and from knowledge of medium optical properties. The measured fluorescence signal is related to the intrinsic fluorescence coefficient by an optical property dependent path-length factor. A simple expression was developed for the path-length factor, which characterizes the penetration of excitation light and the escape of fluorescence from the medium. Experiments with fluorescent tissue phantoms demonstrated that intrinsic fluorescence line shape could be recovered and that fluorophore concentration could be estimated within [+ or -]15%, over a wide range of optical properties. Key words: Fluorescence, diagnostics, light transport, photodynamic therapy, photosensitizer.

The Theoretical study of thermal damage processes in laser irradiated tissue provides further insight into the design of optimal coagulation procedures. Controlled laser coagulation of tissue was studied theoretically using a finite element method with a modulating laser heat source to simulate feedback controlled laser delivery with a constant surface temperature. The effects of uncertainty in scattering and absorption properties of the tissue, thermal denaturation induced changes in optical properties, and surface convection were analyzed. Compared to a single pulse CW irradiation in which a doctor would presumably stop CW laser delivery after noticing some effect such as vaporization or carbonization, the constant surface temperature scenario provided a better overall control over the coagulation process. In particular, prediction of coagulative damage in a constant temperature scenario was less sensitive to uncertainties in optical properties and their dynamic changes during the course of coagulation. Also, subsurface overheating under surface convective conditions could be compensated for under constant temperature irradiation by lowering the surface temperature.

A simple and quick approach is used to measure the reduced scattering coefficient ([[micro]seconds][prime]) of a semi-infinite turbid medium having a much smaller absorption coefficient than [[micro]seconds][prime]. A laser beam with an oblique angle of incidence to the medium causes the center of the diffuse reflectance that is several transport mean-free paths away from the incident point to shift away from the point of incidence by an amount [increment of]x. This mount is used to compute [[micro]seconds][prime] by [[micro]seconds][prime] = sin([[Alpha].sub.i])/(n[increment of]x), where n is the refractive index of the turbid medium divided by that of the incident medium and [[Alpha].sub.i] is the angle of incidence measured from the surface normal. For a turbid medium having an absorption coefficient comparable with [[micro]seconds][prime], a revision to the above formula is made. This method is tested theoretically by Monte Carlo simulations and experimentally by a video reflectometer. Key words: Tissue optics, turbid media, scattering media, scattering coefficient, optical properties.

The primary zone of deposition of optical energy is called here the optical zone. The tissue absorption, tissue scattering, laser-beam diameter, or size of pigmented structures can specify the size of the optical zone. The initial optical zone may be altered by the formation of char during high-irradiance laser exposure, and a spectrum of char absorbance is presented. The relationship between the optical zone and the pulse duration specifies the type of laser-tissue interaction that may occur. Short laser pulses can confine thermal energy and/or stress energy within the optical zone, which maximizes photothermal and photomechanical mechanisms of interaction.

Pulsed photothermal radiometry is used to map the heat deposition in human skin after a short laser pulse. It uses an IR (HgCdTe) detector for a rapid noncontact measurement of the skin surface temperature based on the blackbody emission in the 8-12-micrometer spectrum. The heat deposited by the laser pulse in the superficial epidermis causes an immediate temperature jump, and the heat deposited in basal epidermal melanin and deep port wine stains diffuses to the surface before detection. The time course of the surface temperature T(z = 0, t), indicates the initial spatial distribution of heat, T(z, t = 0), deposited by the laser.

When a picosecond light pulse is incident upon a turbid medium such as tissue, the temporal distribution of diffusely reflected and transmitted photons depends on the optical absorption and scattering properties of the medium. From diffusion theory it is possible to derive analytic expressions for the pulse shape in terms of the optical interaction coefficients of a homogeneous semi-infinite medium. Experimental tests of this simple model in tissue-simulating liquid phantoms of different geometries are presented here. The results of these tests show that, in a semi-infinite phantom, the application of the diffusion model provides estimates of the absorption and transport-scattering coefficients that are accurate to better than 10%. Comparable accuracy was also obtained with this simple model for finite slab, cylindrical, and spherical volumes as long as the objects were of sufficient size. For smaller volumes the absorption coefficient was overestimated because of the significant loss of photons at the boundaries of the object.

An algorithm that selects optimal wavelengths for spectral fitting of diffuse light reflectance spectra using a nonnegative least squares method is presented. Oxyhemoglobin, deoxyhemoglobin, and water are considered representative absorbers, but the approach is not constrained or limited by absorber selection provided native basis spectra are available. The method removes wavelengths iteratively from a scattering-modulated absorption matrix by maximizing the product of its singular values and offers considerable improvements over previously published wavelength selection schemes. Resulting wavelength selections are valid for a broad range of optical properties and yield lower RMS errors than other wavelength combinations. The method is easily modified and broadly applicable to tissue optical spectroscopy. Adaptation of the algorithm to select optimal light-emitting diodes for fitting blood is described. [ABSTRACT FROM AUTHOR]

Assessing the metabolic activity of a tissue, whether normal, damaged, aged, or pathologic, is useful for diagnosis and evaluating the effects of drugs. This report describes a handheld optical fiber probe that contacts the skin, applies pressure to blanch the superficial vascular plexus of the skin, then releases the pressure to allow refill of the plexus. The optical probe uses white light spectroscopy to record the time dynamics of blanching and refilling. The magnitude and dynamics of changes in blood content and hemoglobin oxygen saturation yield an estimate of the oxygen consumption rate (OCR) in units of attomoles per cell per second. The average value of OCR on nine forearm sites on five subjects was 10±5 (amol/cell/s). This low-cost, portable, rapid, noninvasive optical probe can characterize the OCR of a skin site to assess the metabolic activity of the epidermis or a superficial lesion. [ABSTRACT FROM AUTHOR]

To detect small-scale changes in tissue with optical techniques, small sampling volumes and, therefore, short source--detector separations are required. In this case, reflectance measurements are not adequately described by the diffusion approximation. Previous studies related subdiffusive reflectance to γ or σ, which parameterize the phase function. Recently, it was demonstrated that σ predicts subdiffusive reflectance better than γ, and that σ becomes less predictive for lower numerical apertures (NAs). We derive and evaluate the parameter RpNA, which incorporates the NA of the detector and the integral of the phase function over the NA in the backward and forward directions. Monte Carlo simulations are performed for overlapping source/detector geometries for a range of phase functions, reduced scattering coefficients, NAs, and source/detector diameters. RpNA improves prediction of the measured reflectance compared to γ and σ. It is, therefore, expected that RpNA will improve derivation of optical properties from subdiffusive measurements. [ABSTRACT FROM AUTHOR]

Corals are very efficient at using solar radiation, with photosynthetic quantum efficiencies approaching theoretical limits. Here, we investigated potential mechanisms underlying such outstanding photosynthetic performance through extracting inherent optical properties of the living coral tissue and skeleton in a massive faviid coral. Using Monte Carlo simulations developed for medical tissue optics it is shown that for the investigated faviid coral, the coral tissue was a strongly light scattering matrix with a reduced scattering coefficient of μs' = 10 cm-1 (at 636 nm). In contrast, the scattering coefficient of the coral skeleton was μs' = 3.4 cm-1, which facilitated the efficient propagation of light to otherwise shaded coral tissue layers, thus supporting photosynthesis in lower tissues. Our study provides a quantification of coral tissue optical properties in a massive faviid coral and suggests a novel light harvesting strategy, where tissue and skeletal optics act in concert to optimize the illumination of the photosynthesizing algal symbionts embedded within the living coral tissue. [ABSTRACT FROM AUTHOR]

This report describes how optical images acquired using linearly polarized light can specify the anisotropy of scattering (g) and the ratio of reduced scattering [μs′=μs(1−g)] to absorption (μa), i.e., N′=μs′/μa. A camera acquired copolarized (HH) and crosspolarized (HV) reflectance images of a tissue (skin), which yielded images based on the intensity (I=HH+HV) and difference (Q=HH−HV) of reflectance images. Monte Carlo simulations generated an analysis grid (or lookup table), which mapped Q and I into a grid of g versus N′, i.e., g(Q,I) and N′(Q,I). The anisotropy g is interesting because it is sensitive to the submicrometer structure of biological tissues. Hence, polarized light imaging can monitor shifts in the submicrometer (50 to 1000 nm) structure of tissues. The Q values for forearm skin on two subjects (one Caucasian, one pigmented) were in the range of 0.046±0.007 (24), which is the mean±SD for 24 measurements on 8 skin sites×3 visible wavelengths, 470, 524, and 625 nm, which indicated g values of 0.67±0.07 (24). [ABSTRACT FROM AUTHOR]

Sound processing in the inner ear involves separation of the constituent frequencies along the length of the cochlea. Frequencies relevant to human speech (100 to 500 Hz) are processed in the apex region. Among mammals, the guinea pig cochlear apex processes similar frequencies and is thus relevant for the study of speech processing in the cochlea. However, the requirement for extensive surgery has challenged the optical accessibility of this area to investigate cochlear processing of signals without significant intrusion. A simple method is developed to provide optical access to the guinea pig cochlear apex in two directions with minimal surgery. Furthermore, all prior vibration measurements in the guinea pig apex involved opening an observation hole in the otic capsule, which has been questioned on the basis of the resulting changes to cochlear hydrodynamics. Here, this limitation is overcome by measuring the vibrations through the unopened otic capsule using phase-sensitive Fourier domain optical coherence tomography. The optically and surgically advanced method described here lays the foundation to perform minimally invasive investigation of speech-related signal processing in the cochlea. [ABSTRACT FROM AUTHOR]

Spectroscopic and structural imaging of tissue layers is important for investigating tissue health. However, investigating superficial tissue is difficult using optical imaging, due to the convolved absorption and backscatter of light from deeper layers. This report investigates the effects of hydration and desiccation of ex vivo porcine skin on the reflectance of polarized light at different wavelengths (light-emitting diodes). We developed a spectroscopic polarized imaging system to investigate submicron changes in tissue structures. By separating polarized from depolarized backscattered light, submicron structural changes in subsurface and deeper tissue layers can be separated and monitored. The results demonstrate that (1) polarized light reflectance is about 2%, consistent with ∼6 scattering events, on average; (2) there was little wavelength dependence to the reflectance of polarized light; (3) increased hydration leads to a modest increase in total reflectance (from 0.8 to 0.9), whereas desiccation had little effect; however, hydration did not affect polarized reflectance, but desiccation slightly lowered polarized reflectance. Higher scattering from the reticular dermis was likely due to swelling of collagen fiber bundles in the dermal layers, which increased fibril spacing. The epidermal skin surface showed little change due to the stratum corneum resisting desiccation and maintaining hydration. [ABSTRACT FROM AUTHOR]

Significance: Monte Carlo (MC) methods have been applied for studying interactions between polarized light and biological tissues, but most existing MC codes supporting polarization modeling can only simulate homogeneous or multi-layered domains, resulting in approximations when handling realistic tissue structures. Aim: Over the past decade, the speed of MC simulations has seen dramatic improvement with massively parallel computing techniques. Developing hardware-accelerated MC simulation algorithms that can accurately model polarized light inside three-dimensional (3D) heterogeneous tissues can greatly expand the utility of polarization in biophotonics applications. Approach: Here, we report a highly efficient polarized MC algorithm capable of modeling arbitrarily complex media defined over a voxelated domain. Each voxel of the domain can be associated with spherical scatters of various radii and densities. The Stokes vector of each simulated photon packet is updated through photon propagation, creating spatially resolved polarization measurements over the detectors or domain surface. Results: We have implemented this algorithm in our widely disseminated MC simulator, Monte Carlo eXtreme (MCX). It is validated by comparing with a reference central-processing-unit-based simulator in both homogeneous and layered domains, showing excellent agreement and a 931-fold speedup. Conclusion: The polarization-enabled MCX offers biophotonics community an efficient tool to explore polarized light in bio-tissues, and is freely available at http://mcx.space/. [ABSTRACT FROM AUTHOR]

The Monte Carlo simulation called mcml.c was written and shared on-line since 1992. This perspective summarizes the contributions by the people involved in the development of mcml.c, and work by others extending the code. [ABSTRACT FROM AUTHOR]

The molar entropy (ΔS) and molar enthalpy (ΔH) for the denaturation event that triggers cutaneous erythema was determined to be ΔS = 190 J/(mole K) and ΔH = 146.9 × 103 J/mole. The experiment involved placing heated water against the skin of the forearm, for a range of temperatures and exposure times. Exposing the skin to 45°C for 22 s was at the threshold for producing erythema, which was similar to the threshold for a slight degree of pain. [ABSTRACT FROM AUTHOR]

This paper presents a practical approach for assessing the melanin and blood content of the skin from total diffuse reflectance spectra, R(λ), where λ is wavelength. A quick spectral analysis using just three wavelengths (585 nm, 700 nm and 800 nm) is presented, based on the 1985 work of Kollias and Baquer who documented epidermal melanin of skin using the slope of optical density (OD) between 620 nm and 720 nm. The paper describes the non-rectilinear character of such a quick analysis, and shows that almost any choice of two wavelengths in the 600-900 range can achieve the characterization of melanin. The extrapolation of the melanin slope to 585 nm serves as a baseline for subtraction from the OD (585 nm) to yield a blood perfusion score. Monte Carlo simulations created spectral data for a skin model with epidermis, papillary dermis and reticular dermis to illustrate the analysis. [ABSTRACT FROM AUTHOR]

Polarization-based optical techniques have become increasingly popular in the field of biomedical diagnosis. In the current report we exploit the directional awareness of circularly and/or elliptically polarized light backscattered from turbid tissue-like scattering media. We apply circularly and elliptically polarized laser light which illuminates the samples of interest, and a standard optical polarimeter is used to observe the polarization state of light backscattered a few millimeters away from the point of incidence. We demonstrate that the Stokes vector of backscattered light depicted on a Poincaré sphere can be used to assess a turbid tissue-like scattering medium. By tracking the Stokes vector of the detected light on the Poincaré sphere, we investigate the utility of this approach for characterization of cancerous and non-cancerous tissue samples in vitro. The obtained results are discussed in the framework of a phenomenological model and the results of a polarization tracking Monte Carlo model, developed in house. [ABSTRACT FROM AUTHOR]