Measurement of the optical properties of a two-layer model of the human head using broadband near-infrared spectroscopy

We present the development of a continuous-wave method of quantifying the optical properties of a two-layered model of the human head using a broadband spectral approach. Absolute absorption and scattering properties of the upper and lower layers of phantoms with known optical properties were reconstructed from steady-state multi-distance measurements by performing differential fit analysis of the near-infrared reflectance spectrum between 700 and 1000 nm. From spectra acquired at 10, 20, and 30 mm, the concentration of a chromophore in the bottom layer was determined within an error of 10% in the presence of a 15 mm thick top layer. These results demonstrate that our method was able to determine the optical properties of the lower layer, which represents brain, with acceptable error at specific source-detector distances.     

Near-infrared light propagation in an adult head model. I. Modeling of low-level scattering in the cerebrospinal fluid layer

Adequate modeling of light propagation in a human head is important for quantitative near-infrared spectroscopy and optical imaging. The presence of a nonscattering cerebrospinal fluid (CSF) that surrounds the brain has been previously shown to have a strong effect on light propagation in the head. However, in reality, a small amount of scattering is caused by the arachnoid trabeculae in the CSF layer. In this study, light propagation in an adult head model with discrete scatterers distributed within the CSF layer has been predicted by Monte Carlo simulation to investigate the effect of the small amount of scattering caused by the arachnoid trabeculae in the CSF layer. This low scattering in the CSF layer is found to have little effect on the mean optical path length, a parameter that can be directly measured by a time-resolved experiment. However, the partial optical path length in brain tissue that relates the sensitivity of the detected signal to absorption changes in the brain is strongly affected by the presence of scattering within the CSF layer. The sensitivity of the near-infrared signal to hemoglobin changes induced by brain activation is improved by the effect of a low-scattering CSF layer.     

Experimental test of a perturbation model for time-resolved imaging in diffusive media

We report what to our knowledge is a novel perturbation approach for time-resolved transmittance imaging in diffusive media, based on the diffusion approximation with extrapolated boundary conditions. The model relies on the method of Padé approximants and consists of a nonlinear approximation of time-resolved transmittance curves in the presence of an inclusion. The proposed model is intended to extend the range of applicability of perturbation models when applied to inclusions that are non-point-like. We test the model on different tissue phantoms with scattering only, absorbing only, and both scattering and absorbing inclusions. Maps of the optical properties are displayed, and the results are compared with those obtained by means of the usual linear approximation of time-resolved transmittance curves. We found that the nonlinear approach gives a better prediction for absolute values of the scattering and absorption coefficients of inclusions, when the inclusion optical properties are higher than the surrounding background. Furthermore, better-resolved spots and a reduced cross talk between the two parameters are found in the reconstructed maps. Because the range of the optical properties spanned by the considered phantoms covers the values expected for optical mammography, the application of the reported reconstruction method to in vivo images of a breast appears promising from a diagnostic viewpoint.     

Three-dimensional time-resolved optical tomography of a conical breast phantom

A 32-channel time-resolved imaging device for medical optical tomography has been employed to evaluate a scheme for imaging the human female breast. The fully automated instrument and the reconstruction procedure have been tested on a conical phantom with tissue-equivalent optical properties. The imaging protocol has been designed to obviate compression of the breast and the need for coupling fluids. Images are generated from experimental data with an iterative reconstruction algorithm that employs a three-dimensional (3D) finite-element diffusion-based forward model. Embedded regions with twice the background optical properties are revealed in separate 3D absorption and scattering images of the phantom. The implications for 3D time-resolved optical tomography of the breast are discussed.     

Portable, Fiber-Based, Diffuse Reflection Spectroscopy (DRS) Systems for Estimating Tissue Optical Properties

Steady-state diffuse reflection spectroscopy is a well-studied optical technique that can provide a noninvasive and quantitative method for characterizing the absorption and scattering properties of biological tissues. Here, we compare three fiber-based diffuse reflection spectroscopy systems that were assembled to create a light-weight, portable, and robust optical spectrometer that could be easily translated for repeated and reliable use in mobile settings. The three systems were built using a broadband light source and a compact, commercially available spectrograph. We tested two different light sources and two spectrographs (manufactured by two different vendors). The assembled systems were characterized by their signal-to-noise ratios, the source-intensity drifts, and detector linearity. We quantified the performance of these instruments in extracting optical properties from diffuse reflectance spectra in tissue-mimicking liquid phantoms with well-controlled optical absorption and scattering coefficients. We show that all assembled systems were able to extract the optical absorption and scattering properties with errors less than 10%, while providing greater than ten-fold decrease in footprint and cost (relative to a previously well-characterized and widely used commercial system). Finally, we demonstrate the use of these small systems to measure optical biomarkers in vivo in a small-animal model cancer therapy study. We show that optical measurements from the simple portable system provide estimates of tumor oxygen saturation similar to those detected using the commercial system in murine tumor models of head and neck cancer.     

Investigation of two-layered turbid media with time-resolved reflectance

Light propagation in two-layered turbid media that have an infinitely thick second layer is investigated with time-resolved reflectance. We used a solution of the diffusion equation for this geometry to show that it is possible to derive the absorption and the reduced scattering coefficients of both layers if the relative reflectance is measured in the time domain at two distances and if the thickness of the first layer is known. Solutions of the diffusion equation for semi-infinite and homogeneous turbid media are also applied to fit the reflectance from the two-layered turbid media in the time and the frequency domains. It is found that the absorption coefficient of the second layer can be more precisely derived for matched than for mismatched boundary conditions. In the frequency domain, its determination is further improved if phase and modulation data are used instead of phase and steady-state reflectance data. Measurements of the time-resolved reflectance were performed on solid two-layered tissue phantoms that confirmed the theoretical results.     

Spatially resolved absolute diffuse reflectance measurements for noninvasive determination of the optical scattering and absorption coefficients of biological tissue

The absorption and transport scattering coefficients of biological tissues determine the radial dependence of the diffuse reflectance that is due to a point source. A system is described for making remote measurements of spatially resolved absolute diffuse reflectance and hence noninvasive, noncontact estimates of the tissue optical properties. The system incorporated a laser source and a CCD camera. Deflection of the incident beam into the camera allowed characterization of the source for absolute reflectance measurements. It is shown that an often used solution of the diffusion equation cannot be applied for these measurements. Instead, a neural network, trained on the results of Monte Carlo simulations, was used to estimate the absorption and scattering coefficients from the reflectance data. Tests on tissue-simulating phantoms with transport scattering coefficients between 0.5 and 2.0 mm(-1) and absorption coefficients between 0.002 and 0.1 mm(-1) showed the rms errors of this technique to be 2.6% for the transport scattering coefficient and 14% for the absorption coefficients. The optical properties of bovine muscle, adipose, and liver tissue, as well as chicken muscle (breast), were also measured ex vivo at 633 and 751 nm. For muscle tissue it was found that the Monte Carlo simulation did not agree with experimental measurements of reflectance at distances less than 2 mm from the incident beam.     

Influence of a superficial layer in the quantitative spectroscopic study of strongly scattering media

We have experimentally investigated the meaning of the effective optical absorption [mu(a)((eff))] and the reduced scattering [mu(s)?((eff))] coefficients measured on the surfaces of two-layered turbid media, using the diffusion equation for homogeneous, semi-infinite media. We performed frequency-domain spectroscopy in a reflectance geometry, using source-detector distances in the range 1.5-4.5 cm. We measured 100 samples, each made of one layer (thickness in the range 0.08-1.6 cm) on top of one semi-infinite block. The optical properties of the samples were similar to those of soft tissues in the near infrared. We found that the measured effective optical coefficients are representative of the underlying block if the superficial layer is less than ~0.4 cm thick, whereas they are representative of the superficial layer if it is more than ~1.3 cm thick.     

Comparison of spatially and temporally resolved diffuse-reflectance measurement systems for determination of biomedical optical properties

Time-resolved and spatially resolved measurements of the diffuse reflectance from biological tissue are two well-established techniques for extracting the reduced scattering and absorption coefficients. We have performed a comparison study of the performance of a spatially resolved and a time-resolved instrument at wavelengths 660 and 786 nm and also of an integrating-sphere setup at 550-800 nm. The first system records the diffuse reflectance from a diode laser by means of a fiber bundle probe in contact with the sample. The time-resolved system utilizes picosecond laser pulses and a single-photon-counting detection scheme. We extracted the optical properties by calibration using known standards for the spatially resolved system, by fitting to the diffusion equation for the time-resolved system, and by using an inverse Monte Carlo model for the integrating sphere. The measurements were performed on a set of solid epoxy tissue phantoms. The results showed less than 10% difference in the evaluation of the reduced scattering coefficient among the systems for the phantoms in the range 9-20 cm(-1), and absolute differences of less than 0.05 cm(-1) for the absorption coefficient in the interval 0.05-0.30 cm(-1).     

Empirical model functions to calculate hematocrit-dependent optical properties of human blood

The absorption coefficient, scattering coefficient, and effective scattering phase function of human red blood cells (RBCs) in saline solution were determined for eight different hematocrits (Hcts) between 0.84% and 42.1% in the wavelength range of 250-1100 nm using integrating sphere measurements and inverse Monte Carlo simulation. To allow for biological variability, averaged optical parameters were determined under flow conditions for ten different human blood samples. Based on this standard blood, empirical model functions are presented for the calculation of Hct-dependent optical properties for the RBCs. Changes in the optical properties when saline solution is replaced by blood plasma as the suspension medium were also investigated.     

Multichannel time-resolved tissue oximeter for functional imaging of the brain

This paper reports the development and characterization of a novel multichannel time-resolved (TR) instrument for functional brain imaging studies. The instrument is based on picosecond diode lasers, fiber optics for light injection and delivery, a compact multianode photomultiplier, and a personal computer (PC) board for time-correlated single photon counting (TCSPC). The instrument has been characterized in terms of reproducibility among the nine sources and the 12 collection channels, linearity in the determination of optical properties (absorption and reduced scattering), and stability. Preliminary in vivo measurements were performed on volunteers to monitor the optical response to stimuli following a motor task (finger opposition, 5 Hz).     

Ocean optics estimation for absorption,backscattering, and phase function parameters

We propose and test an inverse ocean optics procedure with numerically simulated data for the determination of inherent optical properties using in-water radiance measurements. If data are available at only one depth within a deep homogeneous water layer, then the single-scattering albedo and the single parameter that characterizes the Henyey-Greenstein phase function can be estimated. If data are available at two depths, then these two parameters can be determined along with the optical thickness so that the absorption and scattering coefficients, and also the backscattering coefficient, can be estimated. With a knowledge of these parameters, the albedo and Lambertian fraction of reflected radiance of the bottom can be determined if measurements are made close to the bottom. A simplified method for determining the optical properties of the water also is developed for only three irradiance-type measurements if the radiance is approximately in the asymptotic regime.     

Sensitivity studies for imaging a spherical object embedded in a spherically symmetric, two-layer turbid medium with photon-density waves

We present analytic expressions for the amplitude and phase of photon-density waves in strongly scattering, spherically symmetric, two-layer media containing a spherical object. This layered structure is a crude model of multilayered tissues whose absorption and scattering coefficients lie within a range reported in the literature for most tissue types. The embedded object simulates a pathology, such as a tumor. The normal-mode-series method is employed to solve the inhomogeneous Helmholtz equation in spherical coordinates, with suitable boundary conditions. By comparing the total field at points in the outer layer at a fixed distance from the origin when the object is present and when it is absent, we evaluate the potential sensitivity of an optical imaging system to inhomogeneities in absorption and scattering. For four types of background media with different absorption and scattering properties, we determine the modulation frequency that achieves an optimal compromise between signal-detection reliability and sensitivity to the presence of an object, the minimum detectable object radius, and the smallest detectable change in the absorption and scattering coefficients for a fixed object size. Our results indicate that (l) enhanced sensitivity to the object is achieved when the outer layer is more absorbing or scattering than the inner layer; (2) sensitivity to the object increases with the modulation frequency, except when the outer layer is the more absorbing; (3) amplitude measurements are proportionally more sensitive to a change in absorption, phase measurements are proportionally more sensitive to a change in scattering, and phase measurements exhibit a much greater capacity for distinguishing an absorption perturbation from a scattering perturbation.     

Fabrication and characterization of a solid polyurethane phantom for optical imaging through scattering media

A phantom based on a polyurethane system that replicates the optical properties of tissue for use in near-infrared imaging is described. The absorption properties of tissue are simulated by a dye that absorbs in the near infrared, and the scattering properties are simulated by TiO2 particles. The scattering and absorption coefficients of the plastic were measured with a new technique based on time-resolved transmission through two slabs of materials that have different thicknesses. An image of a representative phantom was obtained from time-gated transmission.     

Optical properties of apple skin and flesh in the wavelength range from 350 to 2200 nm

Optical measurement of fruit quality is challenging due to the presence of a skin around the fruit flesh and the multiple scattering by the structured tissues. To gain insight in the light-tissue interaction, the optical properties of apple skin and flesh tissue are estimated in the 350-2200 nm range for three cultivars. For this purpose, single integrating sphere measurements are combined with inverse adding-doubling. The observed absorption coefficient spectra are dominated by water in the near infrared and by pigments and chlorophyll in the visible region, whose concentrations are much higher in skin tissue. The scattering coefficient spectra show the monotonic decrease with increasing wavelength typical for biological tissues with skin tissue being approximately three times more scattering than flesh tissue. Comparison to the values from time-resolved spectroscopy reported in literature showed comparable profiles for the optical properties, but overestimation of the absorption coefficient values, due to light losses.     

Performance of fitting procedures in curved geometry for retrieval of the optical properties of tissue from time-resolved measurements

By use of the solution of the diffusion equation for cylindrical and spherical geometry, two fitting procedures for retrieval of the optical properties from time-resolved measurements have been implemented. The fitting procedures are based on the Levenberg-Marquardt algorithm, in which the fitting parameters are the absorption coefficient, the reduced scattering coefficient, and an amplitude factor. Monte Carlo data generated for cylindrical and spherical geometry were fitted by these fitting procedures, and the retrieved optical properties were compared with those obtained from the inversion procedure with a mismatched geometry of a semi-infinite medium. The effects of refractive-index mismatch and of different boundary conditions of the diffusion equation were also studied, together with the effects of several sources of error that are typically found in time-resolved measurements. The advantages and drawbacks of these fitting procedures, including many details in several situations of interest in the field of tissue optics, are discussed. The results also offer a guideline to understanding the effects of mismatching in curved geometry as functions of source-detector distance and radii of cylinders or spheres.     

Efficient vector radiative transfer calculations in vertically inhomogeneous cloudy atmospheres

Accurate radiative transfer calculations in cloudy atmospheres are generally time consuming, limiting their practical use in satellite remote sensing applications. We present a model to efficiently calculate the radiative transfer of polarized light in atmospheres that contain homogeneous cloud layers. This model combines the Gauss-Seidel method, which is efficient for inhomogeneous cloudless atmospheres, with the doubling method, which is efficient for homogeneous cloud layers. Additionally to reduce the computational effort for radiative transfer calculations in absorption bands, the cloud reflection and transmission matrices are interpolated over the absorption and scattering optical thicknesses within the cloud layer. We demonstrate that the proposed radiative transfer model in combination with this interpolation technique is efficient for the simulation of satellite measurements for inhomogeneous atmospheres containing one homogeneous cloud layer. For example, the Scanning Imaging Absorption Spectrometer for Atmospheric Cartography (SCIAMACHY) measurements in the oxygen A band (758-773 nm) and the Hartley-Huggins ozone band (295-335 nm) with a spectral resolution of 0.4 nm can be simulated for these atmospheres within 1 min on a 2.8 GHz PC with an accuracy better than 0.1%.     

Influence of layered tissue architecture on estimates of tissue optical properties obtained from spatially resolved diffuse reflectometry

Most instruments used to measure tissue optical properties noninvasively employ data-analysis algorithms that rely on the simplifying assumption that the tissue is semi-infinite and homogeneous. The influence of a layered tissue architecture on the determination of the scattering and absorption coefficients has been investigated in this study. Reflectance as a function of distance from a point source for a two-layered tissue architecture that simulates skin overlying fat was calculated by using a Monte Carlocode. These data were analyzed by using a diffusion theory modelfor a homogeneous semi-infinite medium to calculate the scatter and absorption coefficients. Depending on the algorithm and the radial distance, the estimated tissue optical properties were different from those of either layer, and under some circumstances, physically impossible. In addition, the sensitivity and cross talk of the estimated optical properties to changes in input optical properties were calculated for different layered geometries. For typical optical properties of skin, the sensitivity to changes in optical properties is highly dependent on the layered architecture, the measurement distance, and the fitting algorithm. Furthermore, a change in the input absorption coefficient may result in an apparent change in the measured scatter coefficient, and a change in the in put scatter coefficient may result in an apparent change in the measured absorption coefficient.     

Imaging with diffusing light: an experimental study of the effect of background optical properties

The overall image quality and diagnostic potential of time-resolved transmittance imaging depend on sensitivity to optical contrast, capacity to discriminate scattering from absorption contributions, and spatial resolution. We have investigated experimentally the effects of the optical properties of the background medium on the overall image quality of optical imaging based on fitting the experimental data to the solution of the diffusion equation and on time gating. Images were acquired from phantoms with different background optical properties, while the optical contrast between inhomogeneities and background is kept constant. Data were collected every 0.2 cm over a 6 cm x 6 cm area from realistic tissue phantoms containing cylindrical inhomogeneities (1 cm high and 1 cm in diameter) embedded in a 5-cm-thick turbid slab. The optical coefficients of the background were varied in the ranges of 5-15 cm(-1) for transport scattering and 0.02-0.08 cm(-1) for absorption. The optical contrast for the inclusions was kept at values of -50% and +50% for the scattering and -75% and +300% for the absorption. The results show that both high scattering and high absorption are beneficial.     

Fiber-optic probe for noninvasive real-time determination of tissue optical properties at multiple wavelengths

We present a compact, fast, and versatile fiber-optic probe system for real-time determination of tissue optical properties from spatially resolved continuous-wave diffuse reflectance measurements. The system collects one set of reflectance data from six source-detector distances at four arbitrary wavelengths with a maximum overall sampling rate of 100 Hz. Multivariate calibration techniques based on two-dimensional polynomial fitting are employed to extract and display the absorption and reduced scattering coefficients in real-time mode. The four wavelengths of the current configuration are 660, 785, 805, and 974 nm, respectively. Cross-validation tests on a 6 x 7 calibration matrix of Intralipid-dye phantoms showed that the mean prediction error at, e.g., 785 nm was 2.8% for the absorption coefficient and 1.3% for the reduced scattering coefficient. The errors are relative to the range of the optical properties of the phantoms at 785 nm, which were 0-0.3/cm for the absorption coefficient and 6-16/cm for the reduced scattering coefficient. Finally, we also present and discuss results from preliminary skin tissue measurements.