Modeling diffuse reflectance from homogeneous semi-infinite turbid media for biological tissue applications: a Monte Carlo study

Diffuse reflectance spectroscopy is one of the simplest and widely used techniques for the non-invasive study of biological tissues but no exact analytical solution exists for the problem of diffuse reflectance from turbid media such as biological tissues. In this work, a general treatment of the problem of diffuse reflectance from a homogeneous semi-infinite turbid medium is presented using Monte Carlo simulations. Based on the results of the Monte Carlo method, simple semi-empirical analytical solutions are developed valid for a wide range of collection geometries corresponding to various optical detector diameters. This approach may be useful for the quick and accurate modeling of diffuse reflectance from tissues

Critical comparison of diffuse reflectance spectroscopy and colorimetry as dermatological diagnostic tools for acanthosis nigricans: a chemometric approach

Quantification of skin changes due to acanthosis nigricans (AN), a disorder common among insulin-resistant diabetic and obese individuals, was investigated using two optical techniques: diffuse reflectance spectroscopy (DRS) and colorimetry. Measurements were obtained from AN lesions on the neck and two control sites of eight AN patients. A principal component/discriminant function analysis successfully differentiated between AN lesion and normal skin with 87.7% sensitivity and 94.8% specificity in DRS measurements and 97.2% sensitivity and 96.4% specificity in colorimetry measurements

Effect of bile absorption coefficients on the estimation of liver tissue optical properties and related implications in discriminating healthy and tumorous samples

We investigated differences between healthy tissue and metastatic tumor from ex vivo human partial liver resections using diffuse optical spectroscopy with a fiber optic probe. We extracted various physiological and morphological parameters from the spectra. During evaluation of the residual between the measurements and a fit model based on diffusion theory, we found that bile is an additional chromophore absorbing in the visible wavelength range that was missing in our model. Consistency of the residual with the absorption spectrum of bile was noticed. An accurate measurement of the absorption coefficient of bile from various human bile samples was performed and implemented into the fit model. Having the absorption coefficient of bile as a priori knowledge in the model showed a clear improvement in terms of reducing the fitting discrepancies. The addition of this chromophore yields significantly different estimates of the amount of blood. Furthermore, the estimated bile volume fraction and reduced scattering amplitude turned out to be two main relevant discriminators between normal and metastatic liver tissues

Endogenous Skin Fluorescence is a Good Marker for Objective Evaluation of Comedolysis

Objective evaluation of comedone lesions, especially in vivo, remains a challenge. We have used the rhino mouse model in combination with topical application of all-trans retinoic acid as a comedolytic agent, to investigate the potential of fluorescence spectroscopy as a noninvasive technique in the assessment of noninflammatory acne. The results indicate that there is a strong correlation between the fluorescence excitation spectral features assessed in vivo, and the histologic changes identified, particularly the size of the utriculi as well as the dermal and epidermal thickness. We conclude that fluorescence excitation spectroscopy represents a promising novel and useful tool in the quantitative evaluation of the pseudocomedones and could also be used for the rapid and noninvasive assessment of comedolysis induced by the application of pharmacologic agents such as retinoids

Design and fabrication of SiO2/TiO2 and MgO/TiO2 based high selective optical filters for diffuse reflectance and fluorescence signals extraction

This paper presents the design, optimization and fabrication of 16 MgO/TiO2 and SiO2/TiO2 based high selective narrow bandpass optical filters. Their performance to extract diffuse reflectance and fluorescence signals from gastrointestinal tissue phantoms was successfully evaluated. The obtained results prove their feasibility to correctly extract those spectroscopic signals, through a Spearman’s rank correlation test (Spearman’s correlation coefficient higher than 0.981) performed between the original spectra and the ones obtained using those 16 fabricated optical filters. These results are an important step for the implementation of a miniaturized, low-cost and minimal invasive microsystem that could help in the detection of gastrointestinal dysplasia.This work is funded by FEDER funds through the “Eixo I do Programa Operacional Fatores de Competitividade” (POFC) QREN, project reference COMPETE: FCOMP-01-0124- FEDER-020241 and by FCT—Fundação para a Ciência e a Tecnologia, project reference PTDC/EBB-EBI/120334/2010. The authors thank to the PEst-C/FIS/UI0607/2013 for the use of spectroscopic equipment. The authors also thank to V. Pinto from CMEMS-UMinho for the support during the profilometry measurements. S.P. thanks the FCT for the SFRH/BD/87605/2012 PhD grant

Direct identification of breast cancer pathologies using blind separation of label-free localized reflectance measurements

Breast tumors are blindly identified using Principal (PCA) and Independent Component Analysis (ICA) of localized reflectance measurements. No assumption of a particular theoretical model for the reflectance needs to be made, while the resulting features are proven to have discriminative power of breast pathologies. Normal, benign and malignant breast tissue types in lumpectomy specimens were imaged ex vivo and a surgeon-guided calibration of the system is proposed to overcome the limitations of the blind analysis. A simple, fast and linear classifier has been proposed where no training information is required for the diagnosis. A set of 29 breast tissue specimens have been diagnosed with a sensitivity of 96% and specificity of 95% when discriminating benign from malignant pathologies. The proposed hybrid combination PCA-ICA enhanced diagnostic discrimination, providing tumor probability maps, and intermediate PCA parameters reflected tissue optical properties.This work has been supported by the Spanish Government through CYCIT projects DA2TOI (FIS2010-19860), TFS (TEC2010-20224-C02-02) and Alma’s Eguizabal PhD Grant (FPU12/04130) and by Dartmouth College

Impact of model parameters on Monte Carlo simulations of backscattering Mueller matrix images of colon tissue

Polarimetric imaging is emerging as a viable technique for tumor detection and staging. As a preliminary step towards a thorough understanding of the observed contrasts, we present a set of numerical Monte Carlo simulations of the polarimetric response of multilayer structures representing colon samples in the backscattering geometry. In a first instance, a typical colon sample was modeled as one or two scattering “slabs” with monodisperse non absorbing scatterers representing the most superficial tissue layers (the mucosa and submucosa), above a totally depolarizing Lambertian lumping the contributions of the deeper layers (muscularis and pericolic tissue). The model parameters were the number of layers, their thicknesses and morphology, the sizes and concentrations of the scatterers, the optical index contrast between the scatterers and the surrounding medium, and the Lambertian albedo. With quite similar results for single and double layer structures, this model does not reproduce the experimentally observed stability of the relative magnitudes of the depolarizing powers for incident linear and circular polarizations. This issue was solved by considering bimodal populations including large and small scatterers in a single layer above the Lambertian, a result which shows the importance of taking into account the various types of scatterers (nuclei, collagen fibers and organelles) in the same model

Tyrosinase as a dual reporter gene for both photoacoustic and magnetic resonance imaging

Reporter genes are useful scientific tools for analyzing promoter activity, transfection efficiency, and cell migration. The current study has validated the use of tyrosinase (involved in melanin production) as a dual reporter gene for magnetic resonance and photoacoustic imaging. MCF-7 cells expressing tyrosinase appear brown due to melanin. Magnetic resonance imaging of tyrosinase-expressing MCF-7 cells in 300 μL plastic tubes displayed a 34 to 40% reduction in T1 compared to normal MCF-7 cells when cells were incubated with 250 μM ferric citrate. Photoacoustic imaging of tyrosinase-expressing MCF-7 cells in 700 μm plastic tubes displayed a 20 to 57-fold increase in photoacoustic signal compared to normal MCF-7 cells. The photoacoustic signal from tyrosinase-expressing MCF-7 cells was significantly greater than blood at 650 nm, suggesting that tyrosinase-expressing cells can be differentiated from the vasculature with in vivo photoacoustic imaging. The imaging results suggest that tyrosinase is a useful reporter gene for both magnetic resonance and photoacoustic imaging

Influence of blood pulsation on diagnostic volume in pulse oximetry and photoplethysmography measurements

Recent advances in the development of ultra-compact semiconductor lasers and technology of printed flexible hybrid electronics have opened broad perspectives for the design of new pulse oximetry and photoplethysmography devices. Conceptual design of optical diagnostic devices requires careful selection of various technical parameters, including spectral range; polarization and intensity of incident light; actual size, geometry, and sensitivity of the detector; and mutual position of the source and detector on the surface of skin. In the current study utilizing a unified Monte Carlo computational tool, we explore the variations in diagnostic volume due to arterial blood pulsation for typical transmitted and back-scattered probing configurations in a human finger. The results of computational studies show that the variations in diagnostic volumes due to arterial pulse wave are notably (up to 45%) different in visible and near-infrared spectral ranges in both transmitted and back-scattered probing geometries. While these variations are acceptable for relative measurements in pulse oximetry and/or photoplethysmography, for absolute measurements, an alignment normalization of diagnostic volume is required and can be done by a computational approach utilized in the framework of the current study

Temporal Variations of Skin Pigmentation in C57Bl/6 Mice Affect Optical Bioluminescence Quantitation

ABSTRACT PURPOSE: Depilation-induced skin pigmentation in C57Bl/6 mice is a known occurrence, and presents a unique problem for quantitative optical imaging of small animals, especially for bioluminescence. The work reported here quantitatively investigated the optical attenuation of bioluminescent light due to melanin pigmentation in the skin of transgenic C57B1/6 mice, modified such that luciferase expression is under the transcription control of a physiologically and pharmacologically inducible gene. PROCEDURE: Both in vivo and ex vivo experiments were performed to track bioluminescence signal attenuation through different stages of the mouse hair growth cycle. Simultaneous reflectance measurements were collected in vivo to estimate melanin levels. RESULTS: Biological variability of skin pigmentation was found to dramatically affect collected bioluminescent signal emerging through the skin of the mice. When compared to signal through skin with no pigmentation, the signal through highly-pigmented skin was attenuated an average of 90%. Correlation of reflectance signals to bioluminescence signal loss forms the basis of the proposed correction method. We observed, however, that variability in tissue composition, which results in inconsistent reflectance spectra, limits the accuracy of the correction method but can be improved by incorporating more complex analysis. CONCLUSION: Skin pigmentation is a significant variable in bioluminescent imaging, and should be considered in experimental design and implementation for longitudinal studies, and especially when sensitivity to small signal changes, or differences among animals, is required