Recovery of intrinsic fluorescence from single-point interstitial measurements for quantification of doxorubicin concentration.
ABSTRACT We developed a method for the recovery of intrinsic fluorescence from single-point measurements in highly scattering and absorbing samples without a priori knowledge of the sample optical properties. The goal of the study was to demonstrate accurate recovery of fluorophore concentration in samples with widely varying background optical properties, while simultaneously recovering the optical properties.
Tissue-simulating phantoms containing doxorubicin, MnTPPS, and Intralipid-20% were created, and fluorescence measurements were performed using a single isotropic probe. The resulting spectra were analyzed using a forward-adjoint fluorescence model in order to recover the fluorophore concentration and background optical properties.
We demonstrated recovery of doxorubicin concentration with a mean error of 11.8%. The concentration of the background absorber was recovered with an average error of 23.2% and the scattering spectrum was recovered with a mean error of 19.8%.
This method will allow for the determination of local concentrations of fluorescent drugs, such as doxorubicin, from minimally invasive fluorescence measurements. This is particularly interesting in the context of transarterial chemoembolization (TACE) treatment of liver cancer. Lasers Surg. Med. © 2013 Wiley Periodicals, Inc.
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ABSTRACT: Lipid and water together typically make up more than 90% of the body's adipose tissue mass. Although some reports have shown that the fraction of lipid in adipose tissue is greater in obese people than in lean ones, the quantitative relationship between adipose lipid fraction and overall adiposity of the body has never been investigated. We dissected six male unembalmed cadavers and weighed all adipose tissue (range 9.7-25.7 kg), allowing the calculation of percentage adiposity as 100 x total adipose mass/body mass (range 17.8-43.9%). Adipose tissue volume was determined by hydrostatic weighing of all portions of the dissected adipose tissue. For the six cadavers, whole body adipose tissue density ranged from 0.925-0.970 g/ml. Based on a three-component model of adipose tissue (lipid, water and dry fat-free solids), an expression for lipid fraction, F, was derived. After assuming densities for adipose lipid (0.905 g/ml), water at 36 degrees C (0.997 g/ml) and the dry fat-free component (1.38 g/ml), the equation simplified to F = 6.256/D-5.912, where D is adipose tissue density (g/ml). Lipid fraction was then calculated for each of the six cadavers: the range (0.54-0.85) was in excellent agreement with published data. There was a significant correlation (r = 0.95, P < 0.005) between calculated lipid fraction and percentage adiposity. The regression equation predicting lipid fraction from percentage adiposity was y = 0.327 + 0.0124x. We conclude that the estimated fraction of lipid in human adipose tissue shows both a wide range and a strong positive linear relationship with overall body fatness.International Journal of Obesity 02/1994; 18(2):79-83. · 5.39 Impact Factor
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ABSTRACT: Steady-state diffusion theory models of fluorescence in tissue have been investigated for recovering fluorophore concentrations and fluorescence quantum yield. Spatially resolved fluorescence, excitation and emission reflectance Carlo simulations, and measured using a multi-fibre probe on tissue-simulating phantoms containing either aluminium phthalocyanine tetrasulfonate (AlPcS4), Photofrin meso-tetra-(4-sulfonatophenyl)-porphine dihydrochloride The accuracy of the fluorophore concentration and fluorescence quantum yield recovered by three different models of spatially resolved fluorescence were compared. The models were based on: (a) weighted difference of the excitation and emission reflectance, (b) fluorescence due to a point excitation source or (c) fluorescence due to a pencil beam excitation source. When literature values for the fluorescence quantum yield were used for each of the fluorophores, the fluorophore absorption coefficient (and hence concentration) at the excitation wavelength (mu(a,x,f)) was recovered with a root-mean-square accuracy of 11.4% using the point source model of fluorescence and 8.0% using the more complicated pencil beam excitation model. The accuracy was calculated over a broad range of optical properties and fluorophore concentrations. The weighted difference of reflectance model performed poorly, with a root-mean-square error in concentration of about 50%. Monte Carlo simulations suggest that there are some situations where the weighted difference of reflectance is as accurate as the other two models, although this was not confirmed experimentally. Estimates of the fluorescence quantum yield in multiple scattering media were also made by determining mu(a,x,f) independently from the fitted absorption spectrum and applying the various diffusion theory models. The fluorescence quantum yields for AlPcS4 and TPPS4 were calculated to be 0.59 +/- 0.03 and 0.121 +/- 0.001 respectively using the point source model, and 0.63 +/- 0.03 and 0.129 +/- 0.002 using the pencil beam excitation model. These results are consistent with published values.Physics in Medicine and Biology 01/2004; 48(24):4135-49. · 2.92 Impact Factor
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ABSTRACT: The autofluorescence properties of normal human skin in the near-infrared (NIR) spectral range were studied using Monte Carlo simulation. The light-tissue interactions including scattering, absorption and anisotropy propagation of the regenerated autofluorescence photons in the skin tissue were taken into account in the theoretical modeling. Skin was represented as a turbid seven-layered medium. To facilitate the simulation, ex vivo NIR autofluorescence spectra and images from different skin layers were measured from frozen skin vertical sections to define the intrinsic fluorescence properties. Monte Carlo simulation was then used to study how the intrinsic fluorescence spectra were distorted by the tissue reabsorption and scattering during in vivo measurements. We found that the reconstructed model skin spectra were in good agreement with the measured in vivo skin spectra from the same anatomical site as the ex vivo tissue sections, demonstrating the usefulness of this modeling. We also found that difference exists over the melanin fluorescent wavelength range (880-910 nm) between the simulated spectrum and the measured in vivo skin spectrum from a different anatomical site. This difference suggests that melanin contents may affect in vivo skin autofluorescence properties, which deserves further investigation.Journal of photochemistry and photobiology. B, Biology 09/2011; 105(3):183-9. · 3.11 Impact Factor