Oblique Polarized Reflectance Spectroscopy for Depth Sensitive Measurements in the Epithelial Tissue

Optical spectroscopy has shown potential as a tool for precancer detection by discriminating alterations in the optical properties within epithelial tissues. Identifying depth-dependent alterations associated with the progression of epithelial cancerous lesions can be especially challenging in the oral cavity due to the variable thickness of the epithelium and the presence of keratinization. Optical spectroscopy of epithelial tissue with improved depth resolution would greatly assist in the isolation of optical properties associated with cancer progression. Here, we report a fiber optic probe for oblique polarized reflectance spectroscopy (OPRS) that is capable of depth sensitive detection by combining the following three approaches: multiple beveled fibers, oblique collection geometry, and polarization gating. We analyze how probe design parameters are related to improvements in collection efficiency of scattered photons from superficial tissue layers and to increased depth discrimination within epithelium. We have demonstrated that obliquely-oriented collection fibers increase both depth selectivity and collection efficiency of scattering signal. Currently, we evaluate this technology in a clinical trial of patients presenting lesions suspicious for dysplasia or carcinoma in the oral cavity. We use depth sensitive spectroscopic data to develop automated algorithms for analysis of morphological and architectural changes in the context of the multilayer oral epithelial tissue. Our initial results show that OPRS has the potential to improve the detection and monitoring of epithelial precancers in the oral cavity.Biomedical Engineerin

Broadband ultraviolet-visible optical property measurement in layered turbid media

The ability to accurately measure layered biological tissue optical properties (OPs) may improve understanding of spectroscopic device performance and facilitate early cancer detection. Towards these goals, we have performed theoretical and experimental evaluations of an approach for broadband measurement of absorption and reduced scattering coefficients at ultraviolet-visible wavelengths. Our technique is based on neural network (NN) inverse models trained with diffuse reflectance data from condensed Monte Carlo simulations. Experimental measurements were performed from 350 to 600 nm with a fiber-optic-based reflectance spectroscopy system. Two-layer phantoms incorporating OPs relevant to normal and dysplastic mucosal tissue and superficial layer thicknesses of 0.22 and 0.44 mm were used to assess prediction accuracy. Results showed mean OP estimation errors of 19% from the theoretical analysis and 27% from experiments. Two-step NN modeling and nonlinear spectral fitting approaches helped improve prediction accuracy. While limitations and challenges remain, the results of this study indicate that our technique can provide moderately accurate estimates of OPs in layered turbid media

Depth-selective fiber-optic probe for characterization of superficial tissue at a constant physical depth

The in vivo assessment of superficial tissue has shown great promise in many biomedical applications. Significant efforts have been expended in designing compact fiber-optic probes with short tissue penetration depth targeting the superficial epithelium. In this paper, we present a compact and simple two-channel fiber-optic probe with superior depth selectivity for the superficial tissue. This probe employs a high-index ball-lens with an optimized illumination area and the maximal overlap between light illumination and collection spots, while maintaining sufficient light collection efficiency with minimized specular reflection. Importantly, we show that this probe allows the selection of a constant and shallow physical penetration depth, insensitive to a wide range of tissue-relevant scattering coefficients and anisotropy factors. We demonstrate the capability of this depth-selective fiber-optic probe to accurately quantify the absorber concentration in superficial tissue without the distortion of tissue scattering properties; and characterize the optical properties of superficial skin tissue

Detectability of low-oxygenated regions in human muscle tissue using near-infrared spectroscopy and phantom models

The present work aims to describe the detectability limits of hypoxic regions in human muscle under moderate thicknesses of adipose tissue to serve as a groundwork for the development of a wearable device to prevent pressure injuries. The optimal source-detector distances, detection limits, and the spatial resolution of hypoxic volumes in the human muscle are calculated using finite element method-based computer simulations conducted on 3-layer tissue models. Silicone phantoms matching the simulation geometries were manufactured, and their measurement results were compared to the simulations. The simulations showed good agreement with the performed experiments. Our results show detectability of hypoxic volumes under adipose tissue thicknesses of up to 1.5 cm. The maximum tissue depth, at which hypoxic volumes could be detected was 2.8 cm. The smallest detectable hypoxic volume in our study was 1.2 cm3. We thus show the detectability of hypoxic volumes in sizes consistent with those of early-stage pressure injury formation and, consequently, the feasibility of a device to prevent pressure injuries

Determination of tissue optical properties by steady-state spatial frequency-domain reflectometry

A new non-invasive method to measure the optical properties of biological tissue is described. This method consists of illuminating the investigated sample with light which is spatially periodically modulated in intensity. The spatial modulation of the backscattered light and the diffuse reflectivity of the sample, both detected with an imaging technique, are used to deduce the absorption and reduced scattering coefficient from a table generated by Monte Carlo simulations. This principle has three major advantages: Firstly, it permits the immediate acquisition of the average values of the optical coefficients over a relatively large area (typ. 20 mm in diameter), thus avoiding the perturbations generated by small tissue heterogeneities; It also provides good flexibility for measuring the optical coefficients at various wavelengths and it does not require the use of a detector with a large dynamic range. The method was first validated on phantoms with known optical properties. Finally, we measured the optical properties of human skin at 400 nm, 500 nm, 633 nm and 700 nm in viv

Diffuse optical spectroscopy of melanoma-simulating silicone phantoms

Currently the only method for positively identifying malignant melanoma involves invasive and often undesirable biopsy procedures. Available ex-vivo data indicates increased vascularization in the lower regions of excised melanoma, as compared to dysplastic nevi. The ability to interrogate this region of tissue in-vivo could lead to useful diagnostic information. Using a newly developed fiber based superficial probe in conjunction with a steady-state frequency-domain photon migration (SSFDPM) system, we can probe the upper 1-2 mm of tissue, extracting functional information in the near infrared (650-1000 nm) range. To test the resolution and detection range of the superficial probe in this context,deformable silicone phantoms have been fabricated that simulate normal skin with melanocytic lesions. These phantoms consist of a two-layered matrix with the optical properties of normal light skin, containing several cylindrical inclusions that simulate highly absorbing pigmented lesions such as melanoma. The e inclusions are varied in depth, diameter, and optical properties in order to fully test the probe's detection capabilities. It was found that, depending on absorption, we can typically probe to a depth of 1.0-1.5 mm in an inclusion, likely reaching the site of angiogenesis in an early-stage melanoma. Additionally, we can successfully interrogate normal tissue below lesions 1.5mm deep when absorption is about 0.4/mm or less. This data indicates that the superficial probe shows great promise for non-invasive diagnosis of pigmented lesions.© 2009 SPIE

Sub-Diffusive Scattering Parameter Maps Recovered Using Wide-Field High-Frequency Structured Light Imaging

This study investigates the hypothesis that structured light reflectance imaging with high spatial frequency patterns (fx) can be used to quantitatively map the anisotropic scattering phase function distribution (P(θs)) in turbid media. Monte Carlo simulations were used in part to establish a semi-empirical model of demodulated reflectance (Rd) in terms of dimensionless scattering (μ′sf−1x) and γ, a metric of the first two moments of the P(θs) distribution. Experiments completed in tissue-simulating phantoms showed that simultaneous analysis of Rd spectra sampled at multiple fx in the frequency range [0.05-0.5] mm−1 allowed accurate estimation of both μ′s(λ) in the relevant tissue range [0.4-1.8] mm−1, and γ(λ) in the range [1.4-1.75]. Pilot measurements of a healthy volunteer exhibited γ-based contrast between scar tissue and surrounding normal skin, which was not as apparent in wide field diffuse imaging. These results represent the first wide-field maps to quantify sub-diffuse scattering parameters, which are sensitive to sub-microscopic tissue structures and composition, and therefore, offer potential for fast diagnostic imaging of ultrastructure on a size scale that is relevant to surgical applications

頭部構造と各層内血流変化が光マッピング画像に及ぼす影響

Optical mapping has been applied to image brain activation two-dimensionally along the head surface by detecting the intensity changes of light that passes through the brain. In optical mapping for imaging brain activity, it is assumed that the head tissue is spatially homogeneous and temporally invariable except the activated region in the brain. However, in the superficial layers above the brain, the tissues are inhomogeneous and vary hemodynamically. Furthermore, light propagation and the optical pathlength inside the head are highly dependent on the anatomy and physiology in the head. In particular, the spatial variations in the thickness of skull and cerebrospinal fluid (CSF) layers, the existence of the blood vessels and the hemodynamic changes in the superficial layers such as the CSF and skin layers would have significant influences on light propagation and would result in the difference in the mapping images. However, itis difficult to know these influences by in vivo experiments. The aim of this study is to investigate these influences by numerical and experimental methods. Three-dimensional head models are used to simulate light propagation in the head by solving the photon diffusion equation using the finite element method (FEM), and the optical mapping images are constructed from the simulated measurement data. Tissue-mimicking phantoms with spatially varying thickness and changeable optical properties of head layers were also developed and multi-channel near-infrared spectroscopy (NIRS) experiments were performed on the dynamic phantoms. In the numerical simulations and phantom experiments, the changes in the optical densities (ΔOD) due to activated regions are obtained to construct the mapping images, and the light path probability distributions between one pair of source and detector are calculated to show the sensitivity of the tissue regions to the mapping images. As theresults, the influences of (1) the spatial variations of the skull and CSF layers and (2) the blood volume changes in the skin and CSF layers on the mapping images of brain activities are investigated quantitatively. The optical mapping for the single or multiple activated regions and the effects of the position of the activated regions relative to theprobe arrays on mapping images are also discussed. The quantitative results about the influences of the superficial layers in this study provide information for compensating the optical mapping images among different individuals or different head regions in an individual. In vivo experiments considering the influences of structural and hemodynamic differences in the superficial layers onoptical mapping remain as a future subject.電気通信大学201

Scattering phase Function Spectrum Makes Reflectance Spectrum Measured from Intralipid phantoms and Tissue Sensitive to the Device Detection Geometry

Reflectance spectra measured in Intralipid (IL) close to the source are sensitive to wavelength -dependent changes in reduced scattering coefficient (μs′)and scattering phase function (PF). Experiments and simulations were performed using device designs with either single or separate optical fibers for delivery and collection of light in varying concentrations of IL. Spectral reflectance is not consistentl y linear with varying IL concentration, with PF -dependent effects observed for single fiber devices with diameters smaller than ten transport lengths and for separate source- detector devices that collected light at less than half of a transport length from the source. Similar effects are thought to be seen in tissue, limiting the ability to quantitatively compare spectra from different devices without compensation