Numerical feasibility analysis of an epidermal glucose sensor based on time-resolved fluorescence (original) (raw)
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This paper presents numerical simulations predicting the time-resolved reflectance and autofluorescence of human skin exposed to a pulse of collimated light at 337 nm and pulse width of 1 ns. Moreover, the feasibility of using an embedded time-resolved fluorescence sensor for monitoring glucose concentration is also studied. Skin is modeled as a multilayer medium with each layer having its own optical properties and fluorophore absorption coefficients, lifetimes and quantum yields. The intensity distributions of excitation and fluorescent light in skin are then determined by solving the transient radiative transfer equation using the modified method of characteristics. In both cases, the fluorophore lifetimes are recovered from the simulated fluorescence decays and compared with the actual lifetimes used in the simulations. It was found that the fluorescence lifetime of the fluorophore contributing the least to the fluorescence signal could not be recovered while the other lifetimes could be recovered within 2.5% of input values. Such simulations could be valuable in interpreting data from time-resolved fluorescence experiments on healthy and diseased tissue as well as in designing and testing the feasibility of various optical sensors for biomedical diagnostics.
Analytical models for time resolved fluorescence spectroscopy in tissues
Physics in Medicine and Biology, 2001
Laser induced fluorescence is a rapidly growing technique for diagnostics and imaging in scattering material, most notably in in vivo biomedical testing. Most previous applications have relied on the measurements of the steadystate emission spectrum, with subsequent analysis of the spectrum for relative concentrations of potential fluorophores. Only recently a few investigators have explored the use of the fluorescence lifetimes as a diagnostic tool by taking advantage of the perturbation of the lifetime by multiple scattering of the excitation and emission light in the tissue. We have developed a model to study the fluorescence signal generated by fluorophores distributed in a scattering medium. This model is based on two coupled time-dependent photon migration phenomena: the transport of the pulsed source laser light and the transport of the induced fluorescent light excited by the source. The coupling of these two is through the source for the induced fluorescence where the strength of the local fluorescence emission depends on the absorption of the laser intensity at that location. Whereas previous research focused mainly on the fluorescence properties of various dyes, compounds and materials, transport phenomena have only recently been addressed by researchers. We have presented general analytical and numerical solutions for finite, infinite, cylindrical and spherical geometries.
Applied Optics, 1997
Fluorescence spectroscopy provides potential contrast enhancement for near-infrared tissue imaging and physiologically correlated spectroscopy. We present a fluorescence photon migration model and test its quantitative predictive capabilities with a frequency-domain measurement that involves a homogeneous multiple-scattering tissue phantom ͑with optical properties similar to those of tissue in the near infrared͒ that contains a fluorophore ͑rhodamine B͒. After demonstrating the validity of the model, we explore its ability to recover the fluorophore's spectral properties from within the multiple-scattering medium. The absolute quantum yield and the lifetime of the fluorophore are measured to within a few percent of the values measured independently in the absence of scattering. Both measurements are accomplished without the use of reference fluorophores. In addition, the model accurately predicts the fluorescence emission spectrum in the scattering medium. Implications of these absolute measurements of lifetime, quantum yield, concentration, and emission spectrum from within multiple-scattering media are discussed.
Journal of the Optical Society of America A, 2001
An analytical solution is developed to quantify a site-specific fluorophore lifetime perturbation that occurs, for example, when the local metabolic status is different from that of surrounding tissue. This solution may be used when fluorophores are distributed throughout a highly turbid media and the site of interest is embedded many mean scattering distances from the source and the detector. The perturbation in lifetime is differentiated from photon transit delays by random walk theory. This analytical solution requires a priori knowledge of the tissue-scattering and absorption properties at the excitation and emission wavelengths that may be obtained from concurrent time-resolved reflection measurements. Additionally, the solution has been compared with the exact, numerically solved solution. Thus the presented solution forms the basis for practical lifetime imaging in turbid media such as tissue.
Fluorescence lifetime-based sensing in tissues: a computational study
Biophysical Journal, 1995
We have numerically solved the photon diffusion equation to predict the distribution of light in a tissue model system with a uniform concentration of fluorophore. Our results show that time-dependent measurements of light propagation can be used to monitor the ...
Feasibility analysis of an epidermal glucose sensor based on time-resolved fluorescence
Applied Optics, 2007
The goal of this study is to test the feasibility of using an embedded time-resolved fluorescence sensor for monitoring glucose concentration. Skin is modeled as a multilayer medium with each layer having its own optical properties and fluorophore absorption coefficients, lifetimes, and quantum yields obtained from the literature. It is assumed that the two main fluorophores contributing to the fluorescence at these excitation and emission wavelengths are nicotinamide adenine dinucleotide (NAD)H and collagen. The intensity distributions of excitation and fluorescent light in skin are determined by solving the transient radiative transfer equation by using the modified method of characteristics. The fluorophore lifetimes are then recovered from the simulated fluorescence decays and compared with the actual lifetimes used in the simulations. Furthermore, the effect of adding Poissonian noise to the simulated decays on recovering the lifetimes was studied. For all cases, it was found that the fluorescence lifetime of NADH could not be recovered because of its negligible contribution to the overall fluorescence signal. The other lifetimes could be recovered to within 1.3% of input values. Finally, the glucose concentrations within the skin were recovered to within 13.5% of their actual values, indicating a possibility of measuring glucose concentrations by using a time-resolved fluorescence sensor.
Applied Spectroscopy, 1999
We describe a system capable of measuring spatially resolved reflectance spectra from 380 to 950 nm and fluorescence excitation emission matrices from 330 to 500 nm excitation and 380 to 700 nm emission in vivo. System performance was compared to that of a standard scanning spectrofluorimeter. This “FastEEM” system was used to interrogate human normal and neoplastic oral cavity mucosa in vivo. Measurements were made through a fiber-optic probe and require 4 min total measurement time. We present a method based on autocorrelation vectors to identify excitation and emission wavelengths where the spectra of normal and pathologic tissues differ most. The FastEEM system provides a tool with which to study the relative diagnostic ability of changes in absorption, scattering, and fluorescence properties of tissue.
2006
Extraction of quantitative biochemical information from measured fluorescence spectra is hindered by the presence of potentially significant distortions introduced by tissue scattering and absorption. Such distortions can be removed by extracting the intrinsic fluorescence spectra from the measured fluorescence spectra. This paper explores the potential applicability of spatially resolved fluorescence technique for simultaneous extraction of intrinsic fluorescence and evaluation of optical transport parameters, namely, reduced scattering coefficient (µ s | ), absorption coefficient (µ a ) from tissue mimicking model systems and human breast tissues. A hybrid diffusion theory-Monte Carlo simulation based theoretical model was used to estimate the values for µ s | and µ a and to recover intrinsic fluorescence from the measured spatially resolved fluorescence from the samples. The agreement between the values for µ s ' and µ a estimated for tissue mimicking phantoms using the spatially resolved fluorescence measurement technique and the corresponding calculated values are seen to be satisfactory with a maximum percentage error of ≤ 10 % and also line shape and intensity of intrinsic fluorescence recovered using this approach was observed to be free from the disentangling effects of absorption and scattering properties of the medium. Intrinsic fluorescence spectra of breast tissues show a distinct difference between malignant and its normal counterpart. A narrowing of the line shape is also observed as compared to the bulk fluorescence spectrum.
A Monte Carlo study of fluorescence generation probability in a two-layered tissue model
Physics in Medicine and Biology, 2014
It was recently reported that the time-resolved measurement of diffuse reflectance and/or fluorescence during injection of an optical contrast agent may constitute a basis for a technique to assess cerebral perfusion. In this paper, we present results of Monte Carlo simulations of the propagation of excitation photons and tracking of fluorescence photons in a two-layered tissue model mimicking intra-and extracerebral tissue compartments. Spatial 3D distributions of the probability that the photons were converted from excitation to emission wavelength in a defined voxel of the medium (generation probability) during their travel between source and detector were obtained for different optical properties in intra-and extracerebral tissue compartments. It was noted that the spatial distribution of the generation probability depends on the distribution of the fluorophore in the medium and is influenced by the absorption of the medium and of the fluorophore at excitation and emission wavelengths. Simulations were also carried out for realistic time courses of the dye concentration in both layers. The results of the study show that the knowledge of the absorption properties of the medium at excitation and emission wavelengths is essential for the interpretation of the time-resolved fluorescence signals measured on the surface of the head.
Physical modeling of tissue fluorescence: phantom development
Optical Biopsies and Microscopic Techniques III, 1999
When spectrofluorimetry is applied to the problem of diagnosis, correlation techniques relating spectral features to biotissue status should be used. But the coefficients of correlation equation should account for the relationship of spectral parameters with biochemical and morphological changes associated with the pathology. As a search for these dependencies in actual biotissue is difficult, we offer to employ tissue phantoms -the physical models mimicking , under conditions of measurement, optical characteristics of the natural object. To model human cervix tissue, we used a threelayer planar structure, with upper 0.3 -1.0 mm layer simulating epithelium, middle 0.03 -0.1 mm layer representing basal membrane, and > 1 .0 mm lower layer modeling subepithelial tissue. As a mechanical base of the structure we used 10% (per weight) gelatin gel. To simulate light scattering by biotissue, the nonabsorbing and nonluminiscent scatters were added to the upper and lower layers. NADH, FAD, and Protoporphyrin IX were added to upper layer. Collagen, as dried thin gelatin film, modeled basal membrane. To reproduse modulation of autofluorescence spectrum by reabsorption within the tissue, we added solution of human hemoglobin to the lower layer. Spectrofluorimetric measurement was performed using various excitation wavelengths (337 nm, 365 20 nm, and 405 20 nm).