A Photoplethysmography Melanin Evaluation System by Modified Boltzmann Transport Equation (BTE)

With the advance in cosmetic medical technology in recent years, more and more people get cosmetic medical treatments, especially skin whitening treatments. Nevertheless, people usually assess the effect of skin whitening products by vision, which is subjective and will be different from each person. To acquire the value of melanin concentration objectively, people need to go to cosmetic medical clinics. This will cause inconvenience to people. This paper develops a novel evaluation platform based on optical assessment methods, which employ different absorption and scattering properties to different wavelengths of light in human tissue to obtain melanin concentration. Moreover, this paper proposes a new method that compensates the interaction between epidermis and dermis to acquire the melanin concentration more accurately. The novel platform designed in this paper is smaller and consumes lower-power and smaller when comparing to other conventional devices in market.

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title: Precise analysis of frequency domain photon migration measurement for characterization of concentrated colloidal suspensions
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title: Frequency-Domain Techniques for Tissue Spectroscopy and Imaging
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In this chapter, we describe frequency-domain instrumentation (Section 7.2), diffusion theory (Section 7.3), and representative in vivo applications of frequency-domain spectroscopy (Section 7.4) and imaging (Section 7.5). We have aimed to make this chapter self-contained, while providing extensive references to the literature as a guide for additional reading and for in-depth coverage of topics that are merely mentioned here due to space considerations.

title: Measurements of scattering and absorption changes in muscle and brain.
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title: Quantitative determination of the absorption spectra of chromophores in strongly scattering media: a light-emitting-diode based technique.
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title: Frequency-domain method for measuring spectral properties in multiple-scattering media: methemoglobin absorption spectrum in a tissuelike phantom.
abstract: We have measured the optical absorption and scattering coefficient spectra of a multiple-scattering medium (i.e., a biological tissue-simulating phantom comprising a lipid colloid) containing methemoglobin by using frequency-domain techniques. The methemoglobin absorption spectrum determined in the multiple-scattering medium is in excellent agreement with a corrected methemoglobin absorption spectrum obtained from a steady-state spectrophotometer measurement of the optical density of a minimally scattering medium. The determination of the corrected methemoglobin absorption spectrum takes into account the scattering from impurities in the methemoglobin solution containing no lipid colloid. Frequency-domain techniques allow for the separation of the absorbing from the scattering properties of multiple-scattering media, and these techniques thus provide an absolute measurement of the optical absorption spectra of the methemoglobin/lipid colloid suspension. One accurately determines the absolute methemoglob in absorption spectrum in the frequency domain by extracting the scattering and absorption coefficients from the phase shift Φ and average light intensity DC (or Φ and the amplitude of the light-intensity oscillations AC) data with relationships provided by diffusion theory, but one determines it less accurately by using the Φ and modulation M (M ≡ AC/DC) data and the diffusion theory relationships. In addition to the greater uncertainty in the absorption and scattering coefficients extracted from the Φ and M data, the optical parameters extracted from the Φ and M data exhibit systematically inaccurate behavior that cannot be explained by random noise in the system. Possible reasons for the systematically lower accuracy of the methemoglobin absorption spectrum obtained from Φ and M data are discussed.

title: Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy.
abstract: Frequency-domain photon migration (FDPM) is a non-invasive optical technique that utilizes intensity-modulated, near-infrared (NIR) light to quantitatively measure optical properties in thick tissues. Optical properties (absorption, mu(a), and scattering, mu(s)', parameters) derived from FDPM measurements can be used to construct low-resolution (0.5 to 1 cm) functional images of tissue hemoglobin (total, oxy-, and deoxy-forms), oxygen saturation, blood volume fraction, water content, fat content and cellular structure. Unlike conventional NIR transillumination, FDPM enables quantitative analysis of tissue absorption and scattering parameters in a single non-invasive measurement. The unique functional information provided by FDPM makes it well-suited to characterizing tumors in thick tissues. In order to test the sensitivity of FDPM for cancer diagnosis, we have initiated clinical studies to quantitatively determine normal and malignant breast tissue optical and physiological properties in human subjects. Measurements are performed using a non-invasive, multi-wavelength, diode-laser FDPM device optimized for clinical studies. Results show that ductal carcinomas (invasive and in situ) and benign fibroadenomas exhibit 1.25 to 3-fold higher absorption than normal breast tissue. Within this group, absorption is greatest for measurements obtained from sites of invasive cancer. Optical scattering is approximately 20% greater in pre-menopausal versus post-menopausal subjects due to differences in gland/cell proliferation and collagen/fat content. Spatial variations in tissue scattering reveal the loss of differentiation associated with breast disease progression. Overall, the metabolic demands of hormonal stimulation and tumor growth are detectable using photon migration techniques. Measurements provide quantitative optical property values that reflect changes in tissue perfusion, oxygen consumption, and cell/matrix development.

title: Multiparameter Respiratory Rate Estimation From the Photoplethysmogram
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title: Modeling diffuse reflectance from semi-infinite turbid media: application to the study of skin optical properties.
abstract: Diffuse reflectance spectroscopy in the visible and NIR spectral ranges is an effective and extensively used technique for the non-invasive study and characterization of various biological tissues. In this article, a short review of currently available modeling techniques for diffuse reflectance from semi-infinite turbid media is presented. Starting from the basic physical picture of the diffuse reflectance problem, a simple and practical model is then proposed for use with fiber optic probes. The validity of the model is tested on tissue phantoms and it is then applied to the analysis of diffuse reflectance spectra collected from human skin in vivo.

title: Melanin absorption spectroscopy: new method for noninvasive skin investigation and melanoma detection.
abstract: We present a new method for studying melanin in vivo based on diffuse reflectance spectroscopy of human skin. We find that the optical absorption spectrum of in vivo melanin exhibits an exponential dependence on wavelength, consistent with, but with a higher decay slope than, in vitro results. We offer theoretical justification for this exponential dependence on the basis of a recently proposed model for the structure of eumelanin protomolecules. Moreover, we report on a new method for analysis of diffuse reflectance spectra, which identifies intrinsic differences in absorption spectra between malignant melanoma and dysplastic nevi in vivo. These preliminary results are confirmed both by analysis of our own clinical data as well as by analysis of data from three independent, previously published studies. In particular, we find evidence that the histologic transition from dysplastic nevi to melanoma in situ and then to malignant melanoma is reflected in the melanin absorption spectra. Our results are very promising for the development of techniques for the noninvasive detection of melanoma and, more generally, for the study and characterization of pigmented skin lesions. It is also a promising approach for a better understanding of the biological role, structure, and function of melanin.

title: In vivo characterization of melanin in melanocytic lesions: spectroscopic study on 1671 pigmented skin lesions.
abstract: The purpose of this study is to determine the role of melanin in the various steps of progression of melanocytic neoplasia. To this aim, we perform a retrospective analysis on 1671 multispectral images of in vivo pigmented skin lesions previously recruited in the framework of a study focused on the computer-assisted diagnosis of melanoma. The series included 288 melanomas in different phases of progression, i.e., in situ, horizontal and vertical growth phase invasive melanomas, 424 dysplastic nevi, and other 957 melanocytic lesions. Analysis of the absorbance spectra in the different groups shows that the levels of eumelanin and pheomelanin increase and decrease, respectively, from dysplastic nevi to invasive melanomas. In both cases, the trend of melanin levels is associated to the progression from dysplastic nevi to vertical growth phase melanomas, reflecting a possible hierarchy in the natural history of the early phases of the disease. Our results suggest that diffuse reflectance spectroscopy used to differentiate eumelanin and pheomelanin in in vivo lesions is a promising technique useful to develop better strategies for the characterization of various melanocytic lesions, for instance, by monitoring melanin in a time-lapse study of a lesion that was supposed to be benign.

title: Dermatology: An Illustrated Colour Text
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title: The skin barrier as an innate immune element
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title: The skin: an indispensable barrier
abstract: The skin forms an effective barrier between the organism and the environment preventing invasion of pathogens and fending off chemical and physical assaults, as well as the unregulated loss of water and solutes. In this review we provide an overview of several components of the physical barrier, explaining how barrier function is regulated and altered in dermatoses. The physical barrier is mainly localized in the stratum corneum (SC) and consists of protein‐enriched cells (corneocytes with cornified envelope and cytoskeletal elements, as well as corneodesmosomes) and lipid‐enriched intercellular domains. The nucleated epidermis also contributes to the barrier through tight, gap and adherens junctions, as well as through desmosomes and cytoskeletal elements. During epidermal differentiation lipids are synthesized in the keratinocytes and extruded into the extracellular domains, where they form extracellular lipid‐enriched layers. The cornified cell envelope, a tough protein/lipid polymer structure, resides below the cytoplasmic membrane on the exterior of the corneocytes. Ceramides A and B are covalently bound to cornified envelope proteins and form the backbone for the subsequent addition of free ceramides, free fatty acids and cholesterol in the SC. Filaggrin is cross‐linked to the cornified envelope and aggregates keratin filaments into macrofibrils. Formation and maintenance of barrier function is influenced by cytokines, 3′,5′‐cyclic adenosine monophosphate and calcium. Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier, which allows the entry of environmental allergens, immunological reaction and inflammation in atopic dermatitis. A disturbed skin barrier is important for the pathogenesis of contact dermatitis, ichthyosis, psoriasis and atopic dermatitis.

title: The Protective Role of Melanin Against UV Damage in Human Skin †
abstract: Human skin is repeatedly exposed to UVR that influences the function and survival of many cell types and is regarded as the main causative factor in the induction of skin cancer. It has been traditionally believed that skin pigmentation is the most important photoprotective factor, as melanin, besides functioning as a broadband UV absorbent, has antioxidant and radical scavenging properties. Besides, many epidemiological studies have shown a lower incidence for skin cancer in individuals with darker skin compared to those with fair skin. Skin pigmentation is of great cultural and cosmetic importance, yet the role of melanin in photoprotection is still controversial. This article outlines the major acute and chronic effects of UVR on human skin, the properties of melanin, the regulation of pigmentation and its effect on skin cancer prevention.

title: Radiative Relaxation Quantum Yields for Synthetic Eumelanin¶
abstract: We report absolute values for the radiative relaxation quantum yield of synthetic eumelanin as a function of excitation energy. These values were determined by correcting for pump beam attenuation and emission reabsorption in both eumelanin samples and fluorescein standards over a large range of concentrations. Our results confirm that eumelanins are capable of dissipating >99.9% of absorbed UV and visible radiation through nonradiative means. Furthermore, we have found that the radiative quantum yield of synthetic eumelanin is excitation energy dependent. This observation is supported by corrected emission spectra, which also show a clear dependence of both peak position and peak width on excitation energy. Our findings indicate that photoluminescence emission in eumelanins is derived from ensembles of small chemically distinct oligomeric units that can be selectively pumped. This hypothesis lends support to the theory that the basic structural unit of eumelanin is oligomeric rather than heteropolymeric.

title: The optics of human skin.
abstract: An integrated review of the transfer of optical radiation into human skin is presented, aimed at developing useful models for photomedicine. The component chromophores of epidermis and stratum corneum in general determine the attenuation of radiation in these layers, moreso than does optical scattering. Epidermal thickness and melanization are important factors for UV wavelengths less than 300 nm, whereas the attenuation of UVA (320-400 nm) and visible radiation is primarily via melanin. The selective penetration of all optical wavelengths into psoriatic skin can be maximized by application of clear lipophilic liquids, which decrease regular reflectance by a refractive-index matching mechanism. Sensitivity to wavelengths less than 320 nm can be enhanced by prolonged aqueous bathing, which extracts urocanic acid and other diffusible epidermal chromophores. Optical properties of the dermis are modelled using the Kubelka-Munk approach, and calculations of scattering and absorption coefficients are presented. This simple approach allows estimates of the penetration of radiation in vivo using noninvasive measurements of cutaneous spectral remittance (diffuse reflectance). Although the blood chromophores Hb, HbO2, and bilirubin determine dermal absorption of wavelengths longer than 320 nm, scattering by collagen fibers largely determines the depths to which these wavelengths penetrate the dermis, and profoundly modifies skin colors. An optical "window" exists between 600 and 1300 nm, which offers the possibility of treating large tissue volumes with certain long-wavelength photosensitizers. Moreover, whenever photosensitized action spectra extend across the near UV and/or visible spectrum, judicious choice of wavelengths allows some selection of the tissue layers directly affected.

title: Chromophores in human skin.
abstract: Human skin, especially the epidermis, contains several major solar ultraviolet-radiation- (UVR-) absorbing endogenous chromophores including DNA, urocanic acid, amino acids, melanins and their precursors and metabolites. The lack of solubility of melanins prevents their absorption spectra being defined by routine techniques. Indirect spectroscopic methods show that their spectral properties depend on the stimulus for melanogenesis. The photochemical consequences of UVR absorption by some epidermal chromophores are relatively well understood whereas we lack a detailed understanding of the consequent photobiological and clinical responses. Skin action spectroscopy is not a reliable way of relating a photobiological outcome to a specific chromophore but is important for UVR hazard assessment. Exogenous chromophores may be administered to the skin in combination with UVR exposure for therapeutic benefit, or as sunscreens for the prevention of sunburn and possibly skin cancer.

title: Melanin type and concentration determination using inverse model
abstract: Abnormality of melanin production causes skin pigmentation disorders. Currently, assessment of treatment efficacy (under Physician's Global Assessment framework) only refers to visual conditions of skin surface and not the condition of the underlying skin layers and pigments. Albeit researches on models and simulations of light interaction with human skin have been reported, none has been specifically developed for pigmentation analysis of melanin types - eumelanin and pheomelanin. Therefore, our research objectives are to develop image analysis of skin pigmentation for classification and quantification of eumelanin and pheomelanin pigment types in human skin. In this research, the model is developed using data collected from clinical study. It is hypothesised that the multispectral approach will provide an accurate characterisation of skin layers to determine melanin types namely eumelanin and pheomelanin. Monte Carlo method is then used to determine skin model parameters such as concentration of eumelanin and pheomelanin.

title: Anisotropy of light propagation in human skin.
abstract: Using spatially resolved, steady state diffuse reflectometry, a directional dependence was found in the propagation of visible and near infrared light through human skin in vivo. The skin's reduced scattering coefficient mu(s)' varies by up to a factor of two between different directions of propagation at the same position. This anisotropy is believed to be caused by the preferential orientation of collagen fibres in the dermis, as described by Langer's skin tension lines. Monte Carlo simulations that examine the effect of partial collagen fibre orientation support this hypothesis. The observation has consequences for non-invasive diagnostic methods relying on skin optical properties, and it could be used non-invasively to determine the direction of lines of cleavage in order to minimize scars due to surgical incisions.

title: Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy.
abstract: Frequency-domain photon migration (FDPM) is a non-invasive optical technique that utilizes intensity-modulated, near-infrared (NIR) light to quantitatively measure optical properties in thick tissues. Optical properties (absorption, mu(a), and scattering, mu(s)', parameters) derived from FDPM measurements can be used to construct low-resolution (0.5 to 1 cm) functional images of tissue hemoglobin (total, oxy-, and deoxy-forms), oxygen saturation, blood volume fraction, water content, fat content and cellular structure. Unlike conventional NIR transillumination, FDPM enables quantitative analysis of tissue absorption and scattering parameters in a single non-invasive measurement. The unique functional information provided by FDPM makes it well-suited to characterizing tumors in thick tissues. In order to test the sensitivity of FDPM for cancer diagnosis, we have initiated clinical studies to quantitatively determine normal and malignant breast tissue optical and physiological properties in human subjects. Measurements are performed using a non-invasive, multi-wavelength, diode-laser FDPM device optimized for clinical studies. Results show that ductal carcinomas (invasive and in situ) and benign fibroadenomas exhibit 1.25 to 3-fold higher absorption than normal breast tissue. Within this group, absorption is greatest for measurements obtained from sites of invasive cancer. Optical scattering is approximately 20% greater in pre-menopausal versus post-menopausal subjects due to differences in gland/cell proliferation and collagen/fat content. Spatial variations in tissue scattering reveal the loss of differentiation associated with breast disease progression. Overall, the metabolic demands of hormonal stimulation and tumor growth are detectable using photon migration techniques. Measurements provide quantitative optical property values that reflect changes in tissue perfusion, oxygen consumption, and cell/matrix development.

title: Wearable Forehead Pulse Oximetry: Minimization of Motion and Pressure Artifacts
abstract: i ACKNOWLEDGEMENTS I wish to extend my deepest gratitude to the following: Professor Mendelson for his guidance, support, and patience. My fiancée Nicole and the rest of my family and friends for their support and patience throughout the past two years.  Although steady progress has been made towards the development of a wearable pulse oximeter to aid in remote physiological status monitoring (RPSM) and triage operations, the ability to extract accurate physiological data from a forehead pulse oximeter during extended periods of activity and in the presence of pressure disturbances acting on the sensor remains a significant challenge. This research was undertaken to assess whether the attachment method used to secure a pulse oximeter sensor affects arterial oxygen saturation (SpO 2) and heart rate (HR) accuracy during motion. Additionally, two sensor housings were prototyped to assess whether isolating the sensor from external pressure disturbances could improve SpO 2 and HR accuracy. The research revealed that measurement accuracy during walking is significantly affected by the choice of an attachment method. Specifically, the research indicated that an elastic band providing a contact pressure of 60 mmHg can result in decreased measurement error and improved reliability. Furthermore, the research validated that the two isolating housings we have investigated improve SpO 2 and HR errors significantly at pressures as high as 1200 mmHg (160 kPa) compared to current commercial housings. This information may be helpful in the design of a more robust pulse oximeter sensor for use in RPSM.

title: Optical non-invasive methods for characterization of the human health status
abstract: The absorption of whole blood in the visible and near infrared range is dominated by the different haemoglobin derivates and the blood plasma. It is well known that pulsatile changes of blood volume in tissue can be observed by measuring the transmission or the reflection of light. This diagnostic method is called photo-plethysmography PPG. The pulsatile change of blood volume is caused by the heart-circulation system. The measured PPG time signals and the ratio between the peak to peak pulse amplitudes at different wavelengths and its dependence on the optical absorbability characteristics of human blood yields information on the human health status. A photometric device PMD will be described which is based on the realisation of a photoplethysmography measurement device developed for the German Space Agency DLR. The non-invasive in vivo multi-spectral method described here is based on the radiation of monochromatic light, emitted by laser diodes, through an area of skin on the finger. Deferrals between the proportions of haemoglobin and water in the intravasal volume should be detected photo-electrically by signal-analytic evaluation of the signals. The computed coefficients are used for the measurement and calculation of the relative haemoglobin and haematocrit concentration change. First results with this photometric method to measure changes in the haemoglobin concentration will be shown during measurements with healthy subjects. Additionally the Wigner-Wille distribution will be used for the analysis of PPG time series. This is a specific, sensitive method for the identification of heart-circulation and microcirculation patterns.

title: Optical image reconstruction using frequency-domain simulations: Optimization of detector positions
abstract: Diffusion optical tomography in a heterogeneous turbid medium with the use of frequency-domain is in research, as it can provide the great significance optical parameters used to reconstruct and then we can obtain the new physiological information about biological tissue function and pathological transformation. In this paper, we introduce a simulation for the system of near-infrared diffusion optical tomography, and in the system we can simulate the propagation characteristics of light in tissue. In the traditional tissue boundaries scheme, the detectors are equal distribution, but some of detectors are small role in tissue reconstruction, so in this paper, we discuss the optimization problem of the number and placement for detectors, which has been confirmed and verified in simulation. The simulation results indicate that about eight detectors and the opposite position of source can provide a more accurate reconstruction of tissue optical parameters with high spatial resolution and less time.

title: Frequency-domain diffuse optical tomography with single source-detector pair for breast cancer detection
abstract: An experimental setup for multicolor frequency-domain diffuse optical tomography (FD DOT) was created to visualize neoplasia of breast tissue and to estimate its size. The breast is gently pressed between two glass plates and scanned in the transilluminative configuration by a single source and detector pair. Illumination at three wavelengths (684 nm, 794 nm, and 850 nm) which correspond to different parts of the absorption spectrum in a therapeutic transparency window provides information about concentration of the main absorbers (oxygenated hemoglobin, deoxygenated hemoglobin, and fat/water). Source amplitude modulation at 140 MHz increases spatial resolution and provides separate reconstruction of scattering and absorption coefficients. Moreover, it gives information about breast thickness, which is important for reconstruction. The sensitivity of the system enables one to detect the light propagated through tissue having thickness up to 8 cm. Studies on model media and preliminary in vivo experiments with normal breast and breast carcinoma were performed. An increase of scattering coefficient and total hemoglobin concentration is observed in the tumor area. This corroborates validity of the FD DOT method for breast cancer diagnosis.

title: Non-invasive and quantitative near-infrared haemoglobin spectrometry in the piglet brain during hypoxic stress, using a frequency-domain multidistance instrument.
abstract: The frequency-domain multiple-distance (FDMD) method is capable of measuring the absolute absorption and reduced scattering coefficients of optically turbid media. Absolute measurement of absorption at two near-infrared (NIR) wavelengths makes possible the quantitation of tissue haemoglobin concentration and tissue haemoglobin oxygen-saturation (StO2). However, errors are introduced by the uncertainties of background absorption and the dissimilarities between real tissues and the simplified mathematical model on which these measurements are based. An FDMD-based tissue instrument has been used for the monitoring of tissue haemoglobin concentration and oxygenation in the brain of newborn piglets during periods of hypoxia and hyperoxia. These tissue haemoglobin saturation values were compared with arterial saturation (SaO2) and venous saturation (SvO2) measured by blood gas analyses. A linear correlation was observed between StO2 and the average of SaO2 and SvO2. However, StO2 is not equal to any fixed weighted average of SaO2 and SvO2 unless we introduce an effective background tissue absorption. The magnitude of the background absorption was about 0.08 cm(-1) at 758 nm and 0.06 cm(-1) at 830 nm, and it was nearly consistent between piglets. The origin of this 'effective' background absorption may be real, an artefact caused by the application of a simplified model to a complex sample, or a combination of factors.

title: Mini-FDPM and heterodyne mini-FDPM: handheld non-invasive breast cancer detectors based on frequency-domain photon migration
abstract: This paper describes a handheld instrument for noninvasive detection of breast cancer based on a broad-band optical spectroscopy technique called frequency-domain photon migration (FDPM). It performs broad-band modulation on the intensity of near-infrared laser diodes and derives the scattering and absorption coefficients of the bulk tissue from phase and amplitude data measurements. Two different schematics of mini-FDPM were designed and fabricated. One is a homodyne structure that performs direct comparison of modulated and demodulated frequencies, and the other is a heterodyne structure that compares downconverted demodulated frequencies. The former has a simple structure but lower accuracy due to noise. The latter is more complex but more accurate due to the filtering of noise. The miniature size makes it possible to eliminate fiberoptic cables and enables direct contact between the laser diode and the tissue, making the instrument more power efficient while enhancing detection capabilities. Measurement results show that these miniature systems match or outperform the current prototype while costing two orders of magnitude less.

title: New Window on Optical Brain Imaging; Medical Development, Simulations and Applications
abstract: Chemseddine Mansouri1 and Nasser H. Kashou2,3,4 1CRAN UMR 7039 CNRS-UHP-INPL, Nancy University Vandoeuvre-les-Nancy, 2Department of Radiology, Children’s Radiological Institute, Nationwide Children’s Hospital 3Department of Radiology, Department of Ophthalmology, The Ohio State University Medical Center 4Department of Biomedical, Industrial and Human Factors Engineering, Wright State University, 1France 2,3,4USA

title: Propagation of photon-density waves in strongly scattering media containing an absorbing semi-infinite plane bounded by a straight edge.
abstract: Light propagation in strongly scattering media can be described by the diffusion approximation to the Boltzmann transport equation. We have derived analytical expressions based on the diffusion approximation that describe the photon density in a uniform, infinite, strongly scattering medium that contains a sinusoidally intensity-modulated point source of light. These expressions predict that the photon density will propagate outward from the light source as a spherical wave of constant phase velocity with an amplitude that attenuates with distance r from the source as exp(-alpha r)/r. The properties of the photon-density wave are given in terms of the spectral properties of the scattering medium. We have used the Green's function obtained from the diffusion approximation to the Boltzmann transport equation with a sinusoidally modulated point source to derive analytic expressions describing the diffraction and the reflection of photon-density waves from an absorbing and/or reflecting semi-infinite plane bounded by a straight edge immersed in a strongly scattering medium. The analytic expressions given are in agreement with the results of frequency-domain experiments performed in skim-milk media and with Monte Carlo simulations. These studies provide a basis for the understanding of photon diffusion in strongly scattering media in the presence of absorbing and reflecting objects and allow for a determination of the conditions for obtaining maximum resolution and penetration for applications to optical tomography.

title: Semi-infinite-geometry boundary problem for light migration in highly scattering media: a frequency-domain study in the diffusion approximation
abstract: We have studied light migration in highly scattering media theoretically and experimentally, using the We approximation in a semi-infinite-geometry boundary condition. Both the light source and the diffusion detector were located on the surface of a semi-infinite medium. Working with frequency-domain spectroscopy, we approached the problem in three areas: (1) we derived theoretical expressions for the measured quantities spectroscopy by applying appropriate boundary conditions to the diffusion equation; (2) in frequency-domain we experimentally verified the theoretical expressions by performing measurements on a macroscopically medium in quasi-semi-infinite-geometry conditions; (3) we applied Monte Carlo methods to homogeneous the semi-infinite-geometry boundary problem. The experimental results and the confirming Monte simulate Carlo simulation show that the diffusion approximation, under the appropriate boundary conditions, accurately estimates the optical parameters of the medium.

title: Boundary conditions for the diffusion equation in radiative transfer.
abstract: Using the method of images, we examine the three boundary conditions commonly applied to the surface of a semi-infinite turbid medium. We find that the image-charge configurations of the partial-current and extrapolated-boundary conditions have the same dipole and quadrupole moments and that the two corresponding solutions to the diffusion equation are approximately equal. In the application of diffusion theory to frequency-domain photon-migration (FDPM) data, these two approaches yield values for the scattering and absorption coefficients that are equal to within 3%. Moreover, the two boundary conditions can be combined to yield a remarkably simple, accurate, and computationally fast method for extracting values for optical parameters from FDPM data. FDPM data were taken both at the surface and deep inside tissue phantoms, and the difference in data between the two geometries is striking. If one analyzes the surface data without accounting for the boundary, values deduced for the optical coefficients are in error by 50% or more. As expected, when aluminum foil was placed on the surface of a tissue phantom, phase and modulation data were closer to the results for an infinite-medium geometry. Raising the reflectivity of a tissue surface can, in principle, eliminate the effect of the boundary. However, we find that phase and modulation data are highly sensitive to the reflectivity in the range of 80-100%, and a minimum value of 98% is needed to mimic an infinite-medium geometry reliably. We conclude that noninvasive measurements of optically thick tissue require a rigorous treatment of the tissue boundary, and we suggest a unified partial-current--extrapolated boundary approach.

title: The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy.
abstract: A method is described for measuring optical properties and deriving chromophore concentrations from diffuse reflection measurements at the surface of a turbid medium. The method uses a diffusion approximation model for the diffuse reflectance, in combination with models for the absorption and scattering coefficients. An optical fibre-based set-up, capable of measuring nine spectra from 400 to 1050 nm simultaneously, is used to test the method experimentally. Results of the analyses of phantom and in vivo measurements are presented. These demonstrate that in the wavelength range from 600 to 900 nm, tissue scattering can be described as a simple power dependence of the wavelength and that the tissue absorption can be accurately described by the addition of water, oxy- and deoxyhaemoglobin absorption.

title: Low-cost frequency-domain photon migration instrument for tissue spectroscopy, oximetry, and imaging
abstract: We described a low-cost, frequency-domain photon migration spectroscopy instrument by using in-phase and quadrature demodula- tion technique in a 140-MHz homodyne system. A time constant of 1 ms was obtained. A frequency-division multiplexing technique was used for multiposition or multiwavelength applications, such as for tissue oxim- etry. By conducting several experiments on tissue/blood models, we show that the optical properties of tissue can be determined with this system by either using multiple source-detector separations at accuracy better than 8% or using single source-detector separation. The accuracy with the latter method can be improved to be 10% or better by choosing a proper calibration sample. A frequency-sweep system (30 to 700 MHz) was also implemented; the phase and amplitude measured on a tissue- like solution at 780 nm agreed to their theoretical values within 5% and 10% accuracy, respectively.

title: Frequency-domain multichannel optical detector for noninvasive tissue spectroscopy and oximetry
abstract: We have designed a multisource frequency-domain spectrometer for the optical study of biological tissues. Eight multiplexed, intensity-modulated LEDs are employed as the light sources. Four of them emit light at a peak wavelength of 715 nm (λ1); the other four, 850 nm (λ2). The frequency of intensity modulation is 120 MHz. This instrument measures the frequency-domain parameters phase, dc intensity, and ac amplitude at the two wavelengths λ1 and λ2 and for different distances between light source and detector. From these frequency-domain raw data, the absolute values of the absorption and reduced scattering coefficients of tissue at λ1 and λ2 are obtained. The oxy- and deoxyhemoglobin concentrations, and hence the hemoglobin saturation, are then analytically derived from the molar extinction coefficients. Acquisition times as short as hundreds of milliseconds provide real-time monitoring of the measured parameters. We performed a systematic test in vitro to quantify the precision and accuracy of the instrument reading. We also report in vivo measurements. This spectrometer can be packaged as a compact portable unit.

title: Non-invasive measurements of breast tissue optical properties using frequency-domain photon migration.
abstract: A multiwavelength, high bandwidth (1 GHz) frequency-domain photon migration (FDPM) instrument has been developed for quantitative, non-invasive measurements of tissue optical and physiological properties. The instrument produces 300 kHz to 1 GHz photon density waves (PDWs) in optically turbid media using a network analyser, an avalanche photodiode detector and four amplitude-modulated diode lasers (674 nm, 811 nm, 849 nm, and 956 nm). The frequency of PDW phase and amplitude is measured and compared to analytically derived model functions in order to calculate absorption, mu a, and reduced scattering, mu s, parameters. The wavelength-dependence of absorption is used to determine tissue haemoglobin concentration (total, oxy- and deoxy- forms), oxygen saturation and water concentration. We present preliminary results of non-invasive FDPM measurements obtained from normal and tumour-containing human breast tissue. Our data clearly demonstrate that physiological changes caused by the presence of small (about 1 cm diameter) palpable lesions can be detected using a handheld FDPM probe.

title: Noninvasive monitoring of hemodynamic stress using quantitative near-infrared frequency-domain photon migration spectroscopy.
abstract: Hemorrhagic hypovolemia and inotropic agent administration were used to manipulate cardiac output (CO) and oxygen delivery in rabbits to investigate the correlation between noninvasive frequency domain photon migration (FDPM) spectroscopy and invasive hemodynamic monitoring parameters. Frequency-domain photon migration provides quantitative measurements of light absorption and reduced scattering (mu(a) and mu(s)(prime prime or minute), respectively) in tissue. Wavelength dependent mu(a) values were used to calculate in vivo tissue concentration of deoxyhemoglobin [Hb], oxyhemoglobin [HbO(2)], total hemoglobin [TotHb], and water [H(2)O] as well as mixed arterial-venous oxygen saturation (S(t)O(2)) in tissue. FDPM-derived physiologic properties were correlated with invasive measurements of CO and mean pulmonary artery pressure (mPAP), FDPM-derived [TotHb] and S(t) O(2) correlated significantly with hemorrhaged volume (HV), mPAP, and CO. Correlation coefficients for [TotHb] vs HV, mPAP, and CO were -0.77, 0.86, and 0.70, respectively. Correlation coefficients of S(t)O( 2) vs HV, mPAP, and CO were -0.71, 0.55, and 0.61, respectively. Dobutamine induced changes resulted in correlation coefficients between FDPM-derived and invasively measured physiologic parameters that are comparable to those induced by hypovolemia. FDPM spectroscopy is sensitive to changes in mPAP and CO of as little as 15%. These results suggest that FDPM spectroscopy may be used in clinical settings to noninvasively monitor central hemodynamic parameters and to directly assess oxygenation of tissues.

title: Estimation of melanin and hemoglobin in skin tissue using multiple regression analysis aided by Monte Carlo simulation.
abstract: To estimate the concentrations of melanin and blood and the oxygen saturation in human skin tissue, we propose a method using a multiple regression analysis aided by a Monte Carlo simulation for diffuse reflectance spectra from the skin tissue. By using the absorbance spectrum as a response variable and the extinction coefficients of melanin, oxygenated hemoglobin, and deoxygenated hemoglobin as predictor variables, the multiple regression analysis gives regression coefficients. The concentrations of melanin and blood are determined from the regression coefficients using conversion vectors that are estimated numerically in advance, while the oxygen saturation is obtained directly from the regression coefficients. Numerical and experimental investigations were performed for layered skin tissue models and phantoms. Measurements of human skin were also carried out to monitor variations in the melanin and blood contents and oxygenation during cuff occlusion. The results confirmed the usefulness of the proposed method.

title: Spectroscopic assessment of cutaneous hemodynamics in the presence of high epidermal melanin concentration.
abstract: For individuals with lightly pigmented skin, early stage pressure ulcers appear as areas of redness, which have compromised microcirculation and do not blanch in response to pressure. The lack of a visible blanch (hemodynamic response) to pressure is a convenient diagnostic test for stage I sores. However, the blanch response is not visually apparent in people with highly pigmented skin color due to the overwhelming contribution of melanin to the reflectance of skin.



A simple least squares projection operator method is described, which can separate the reflectance contributions from melanin and hemoglobin. The methodology was tested in a study population of 20 subjects with healthy skin. The study population was evenly divided into a lightly pigmented skin group (visible blanch response) and a highly pigmented skin group (no visible blanch response).



The hemodynamic response to pressure being applied to the skin could clearly be distinguished spectroscopically in both groups at a high level of statistical significance.



The specific aim of this work was directed towards developing a spectroscopic basis for distinguishing the healthy blanch response in a manner that was independent of skin pigmentation. However, the technique has a general application when optical hemodynamic measurements are being made over a diverse patient population or under conditions of varying pigmentation such as the seasonal changes in skin color.

title: New closed-form approximation for skin chromophore mapping.
abstract: The concentrations of blood and melanin in skin can be estimated based on the reflectance of light. Many models for this estimation have been built, such as Monte Carlo simulation, diffusion models, and the differential modified Beer-Lambert law. The optimization-based methods are too slow for chromophore mapping of high-resolution spectral images, and the differential modified Beer-Lambert is not often accurate enough. Optimal coefficients for the differential Beer-Lambert model are calculated by differentiating the diffusion model, optimized to the normal skin spectrum. The derivatives are then used in predicting the difference in chromophore concentrations from the difference in absorption spectra. The accuracy of the method is tested both computationally and experimentally using a Monte Carlo multilayer simulation model, and the data are measured from the palm of a hand during an Allen's test, which modulates the blood content of skin. The correlations of the given and predicted blood, melanin, and oxygen saturation levels are correspondingly r = 0.94, r = 0.99, and r = 0.73. The prediction of the concentrations for all pixels in a 1-megapixel image would take ∼ 20 min, which is orders of magnitude faster than the methods based on optimization during the prediction.

title: Skin melanin, hemoglobin, and light scattering properties can be quantitatively assessed in vivo using diffuse reflectance spectroscopy.
abstract: Noninvasive and real-time analysis of skin properties is useful in a wide variety of applications. In particular, the quantitative assessment of skin in terms of hemoglobin and melanin content, as well as in terms of its light scattering properties, is a challenging problem in dermatology. We present here a technique for examining human skin, based on the in vivo measurement of diffuse reflectance spectra in the visible and near-infrared ranges of the electromagnetic spectrum. Spectra were measured by means of a fiber optic probe, and they were analyzed using an analytical model of light diffusion in the skin. The results of the analysis indicate that it is possible to obtain quantitative information about hemoglobin and melanin content, as well as basic information regarding the scattering properties of the skin.

title: Analysis on performance and optimization of frequency-domain near-infrared instruments.
abstract: Frequency-domain near-infrared techniques have been widely used to detect the optical properties of biological tissues noninvasively. In this paper we propose an analytical model to evaluate the performance of frequency-domain instruments. Based on the diffusion equation and the transfer properties of optoelectronic components, we treat all parts, including the medium, as two-port networks and apply systematic methods to answer questions concerning frequency-domain instruments. Experiments show that this method can reasonably reflect the properties of the instrument within an accuracy of 7%. This kind of method can be used to design suitable instruments for various applications. We also analyze the selection of the instrument parameters to achieve optimal performance at an efficient cost using this analytical model.