Realistic three-dimensional epithelial tissue phantoms for biomedical optics

Sokolov, Konstantin; Galvan, Javier; Myakov, Alexey V.; Lacy, Alicia; Lotan, R.; Richards‐Kortum, Rebecca

doi:10.1117/1.1427052

Cited by 100 publications

(102 citation statements)

References 33 publications

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“…For this particular excitation wavelength, we expect to be able to measure fluorescence signals from the metabolite, flavo adenine dinucleotide (FAD) [27] and the intercellular matrix components, collagen [28,29] and elastin [27]. These endogenous fluorophores are considered to be potential biomarkers for disease progression [30].…”

Section: Biophotonicsmentioning

confidence: 99%

A flexible wide‐field FLIM endoscope utilising blue excitation light for label‐free contrast of tissue

Sparks

Warren

Guedes

et al. 2014

Journal of Biophotonics

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Fluorescence lifetime imaging (FLIM) has previously been shown to provide contrast between normal and diseased tissue. Here we present progress towards clinical and preclinical FLIM endoscopy of tissue autofluorescence, demonstrating a flexible wide‐field endoscope that utilised a low average power blue picosecond laser diode excitation source and was able to acquire ∼mm‐scale spatial maps of autofluorescence lifetimes from fresh ex vivo diseased human larynx biopsies in ∼8 seconds using an average excitation power of ∼0.5 mW at the specimen. To illustrate its potential for FLIM at higher acquisition rates, a higher power mode‐locked frequency doubled Ti:Sapphire laser was used to demonstrate FLIM of ex vivo mouse bowel at up to 2.5 Hz using 10 mW of average excitation power at the specimen. (© 2014 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)

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Section: Biophotonicsmentioning

confidence: 99%

A flexible wide‐field FLIM endoscope utilising blue excitation light for label‐free contrast of tissue

Sparks

Warren

Guedes

et al. 2014

Journal of Biophotonics

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“…Previous research shows that the main stromal fluorophores are collagen and elastin cross-links. 28 The thickness of each sublayer was derived from confocal fluorescence images of a representative normal tongue tissue slice that was used to determine the tissue geometry shown in Fig. 1(a).…”

Section: Tissue Geometry and Model Input Parametersmentioning

confidence: 99%

Monte Carlo model to describe depth selective fluorescence spectra of epithelial tissue: applications for diagnosis of oral precancer

et al. 2008

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We present a Monte Carlo model to predict fluorescence spectra of the oral mucosa obtained with a depth-selective fiber optic probe as a function of tissue optical properties. A model sensitivity analysis determines how variations in optical parameters associated with neoplastic development influence the intensity and shape of spectra, and elucidates the biological basis for differences in spectra from normal and premalignant oral sites. Predictions indicate that spectra of oral mucosa collected with a depth-selective probe are affected by variations in epithelial optical properties, and to a lesser extent, by changes in superficial stromal parameters, but not by changes in the optical properties of deeper stroma. The depth selective probe offers enhanced detection of epithelial fluorescence, with 90% of the detected signal originating from the epithelium and superficial stroma. Predicted depth-selective spectra are in good agreement with measured average spectra from normal and dysplastic oral sites. Changes in parameters associated with dysplastic progression lead to a decreased fluorescence intensity and a shift of the spectra to longer emission wavelengths. Decreased fluorescence is due to a drop in detected stromal photons, whereas the shift of spectral shape is attributed to an increased fraction of detected photons arising in the epithelium.

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“…The procedure used for the preparation of the collagen gels was described previously. 13 Three types of fluorescent microsphere were used, with the following excitationemission peak wavelengths, diameters, and concentrations: (a) 370-425 nm, 1.89-µm diameter, 1.2×10 9 spheres/mL; (b) 450-490 nm, 2.72-µm diameter, 5.7×10 8 spheres/mL; (c) 633-650-680 nm, 5.49-µm diameter, 5.0×10 7 spheres/mL. The scattering parameters of each tissue phantom were calculated by Mie theory at the corresponding excitation wavelength.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

mentioning

confidence: 99%

Ball lens coupled fiber-optic probe for depth-resolved spectroscopy of epithelial tissue

et al. 2005

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A ball lens coupled fiber-optic probe design is described for depth-resolved measurements of the fluorescence and reflectance properties of epithelial tissue. A reflectance target, fluorescence targets, and a two-layer tissue phantom consisting of fluorescent microspheres suspended in collagen are used to characterize the performance of the probe. Localization of the signal to within 300 µm of the probe tip is observed by use of reflectance and fluorescence targets in air. Differential enhancement of the fluorescence signal from the top layer of the two-layer tissue phantom is observed. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptOptical spectroscopy is emerging as an effective diagnostic technique for noninvasive detection of cancers and precancers that originate in the epithelial lining of organs such as the uterine cervix, the oral cavity, the urinary bladder, and the esophagus. 1 The progression of precancer in these tissues produces morphologic and biochemical changes in the epithelium and supporting stroma. These changes include alterations in epithelial cell morphology and metabolic activity, changes in stromal protein morphology and cross-linking, and increasing stromal angiogenesis. As a result, the concentration and distribution of endogenous fluorophores such as reduced nicotinamide adenine dinucleotide, flavin adenine dinucleotide, keratin, tryptophan, and collagen cross-links, and absorbers such as hemoglobin, are altered with the progression of precancer. 2 Thus knowledge of the depth-dependent distribution of chromophores may have important diagnostic significance.Endogenous chromophores can be detected noninvasively in vivo by use of fiber-optic fluorescence and reflectance spectroscopy. Many fiber-optic probe designs collect the integrated signal from both the epithelium (which is typically of the order of 300 µm thick) and the underlying stroma. In these systems, sophisticated analysis strategies are required for deconvolution of spectroscopic data to yield quantitative concentrations of chromophores, and little information about depth-related changes is obtained. Fiber probes that can localize spectroscopic information by depth to distinguish epithelial and stromal optical signatures should improve the ability of spectroscopy to evaluate noninvasively the progression of precancerous changes.A variety of probe designs for obtaining localized or depth-resolved spectroscopic data have been reported. 3,4 Single-fiber probe configurations, in which the same fiber is used for illumination and collection, are sensitive to light scattering from superficial tissue regions. 5,6 However, the use of single-fiber probes for optical measurements is limited by lower signalto-noise ratios that are due to autofluorescence generated by impurities in the fiber core and by specular reflection from fiber surfaces. With multiple-fiber probes, many configurations are possible. Straight-fiber geometries with different source-detector separations permit some depth discrimination; ...

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Realistic three-dimensional epithelial tissue phantoms for biomedical optics

Cited by 100 publications

References 33 publications

A flexible wide‐field FLIM endoscope utilising blue excitation light for label‐free contrast of tissue

A flexible wide‐field FLIM endoscope utilising blue excitation light for label‐free contrast of tissue

Monte Carlo model to describe depth selective fluorescence spectra of epithelial tissue: applications for diagnosis of oral precancer

Ball lens coupled fiber-optic probe for depth-resolved spectroscopy of epithelial tissue

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