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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 5, Iss. 8 — Aug. 1, 2014
  • pp: 2726–2735
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Measurements of extrinsic fluorescence in Intralipid and polystyrene microspheres

Vinh Nguyen Du Le, Zhaojun Nie, Joseph E. Hayward, Thomas J. Farrell, and Qiyin Fang  »View Author Affiliations


Biomedical Optics Express, Vol. 5, Issue 8, pp. 2726-2735 (2014)
http://dx.doi.org/10.1364/BOE.5.002726


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Abstract

The fluorescence of Intralipid and polystyrene microspheres with sphere diameter of 1 µm at a representative lipid and microsphere concentration for simulation of mucosal tissue scattering has not been a subject of extensive experimental study. In order to elucidate the quantitative relationship between lipid and microsphere concentration and the respective fluorescent intensity, the extrinsic fluorescence spectra between 360 nm and 650 nm (step size of 5 nm) were measured at different lipid concentrations (from 0.25% to 5%) and different microsphere concentrations (0.00364, 0.0073, 0.0131 spheres per cubic micrometer) using laser excitation at 355 nm with pulse energy of 2.8 µJ. Current findings indicated that Intralipid has a broadband emission between 360 and 650 nm with a primary peak at 500 nm and a secondary peak at 450 nm while polystyrene microspheres have a single peak at 500 nm. In addition, for similar scattering properties the fluorescence of Intralipid solutions is approximately three-fold stronger than that of the microsphere solutions. Furthermore, Intralipid phantoms with lipid concentrations ~2% (simulating the bottom layer of mucosa) produce up to seven times stronger fluorescent emission than phantoms with lipid concentration ~0.25% (simulating the top layer of mucosa). The fluoresence decays of Intralipid and microsphere solutions were also recorded for estimation of fluorescence lifetime.

© 2014 Optical Society of America

1. Introduction

Mucosal tissues in the oral cavity, pharynx, esophagus, and digestive system are targets of mucosal cancer, which is responsible for approximately 200,000 deaths annually in the United States [1

1. R. Siegel, E. Ward, O. Brawley, and A. Jemal, “Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths,” CA Cancer J. Clin. 61(4), 212–236 (2011). [CrossRef] [PubMed]

]. Various optical biopsy methods have been investigated as potential minimally-invasive techniques for early diagnosis and treatment [2

2. M. Müller and B. H. Hendriks, “Recovering intrinsic fluorescence by Monte Carlo modeling,” J. Biomed. Opt. 18(2), 027009 (2013). [CrossRef] [PubMed]

4

4. Q. Wang, K. Shastri, and T. J. Pfefer, “Experimental and theoretical evaluation of a fiber-optic approach for optical property measurement in layered epithelial tissue,” Appl. Opt. 49(28), 5309–5320 (2010). [CrossRef] [PubMed]

]. In these studies, phantoms simulating key tissue optical properties (e.g. absorption and scattering coefficients) are extensively used in developing theoretical models [2

2. M. Müller and B. H. Hendriks, “Recovering intrinsic fluorescence by Monte Carlo modeling,” J. Biomed. Opt. 18(2), 027009 (2013). [CrossRef] [PubMed]

4

4. Q. Wang, K. Shastri, and T. J. Pfefer, “Experimental and theoretical evaluation of a fiber-optic approach for optical property measurement in layered epithelial tissue,” Appl. Opt. 49(28), 5309–5320 (2010). [CrossRef] [PubMed]

]. Mucosal tissues have two distinguished layers – the epithelium on top of the stromal layer [5

5. R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications,” J. Biomed. Opt. 6(4), 385–396 (2001). [CrossRef] [PubMed]

,6

6. S. K. Chang, D. Arifler, R. Drezek, M. Follen, and R. Richards-Kortum, “Analytical model to describe fluorescence spectra of normal and preneoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9(3), 511–522 (2004). [CrossRef] [PubMed]

]. The reduced-scattering coefficients (µs′) of the stromal layer is about 6-fold higher than that of the epithelium [5

5. R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications,” J. Biomed. Opt. 6(4), 385–396 (2001). [CrossRef] [PubMed]

,6

6. S. K. Chang, D. Arifler, R. Drezek, M. Follen, and R. Richards-Kortum, “Analytical model to describe fluorescence spectra of normal and preneoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9(3), 511–522 (2004). [CrossRef] [PubMed]

]. The epithelial layer thickness is approximately 300 µm [7

7. Y. Chen, A. D. Aguirre, P.-L. Hsiung, S. Desai, P. R. Herz, M. Pedrosa, Q. Huang, M. Figueiredo, S. W. Huang, A. Koski, J. M. Schmitt, J. G. Fujimoto, and H. Mashimo, “Ultrahigh resolution optical coherence tomography of Barrett’s esophagus: preliminary descriptive clinical study correlating images with histology,” Endoscopy 39(7), 599–605 (2007). [CrossRef] [PubMed]

], which is only a small fraction of the bottom layer thickness [7

7. Y. Chen, A. D. Aguirre, P.-L. Hsiung, S. Desai, P. R. Herz, M. Pedrosa, Q. Huang, M. Figueiredo, S. W. Huang, A. Koski, J. M. Schmitt, J. G. Fujimoto, and H. Mashimo, “Ultrahigh resolution optical coherence tomography of Barrett’s esophagus: preliminary descriptive clinical study correlating images with histology,” Endoscopy 39(7), 599–605 (2007). [CrossRef] [PubMed]

,8

8. V. N. Le, Q. Wang, J. C. Ramella-Roman, and T. J. Pfefer, “Monte Carlo modeling of light-tissue interactions in narrow band imaging,” J. Biomed. Opt. 18(1), 010504 (2013). [CrossRef] [PubMed]

]. Therefore, simulating scattering of the stromal layer of the mucosa is important in optical phantoms which attempt to mimic mucosal tissues.

While matching Intralipid and polystyrene microspheres scattering to tissue scattering is certainly a key requirement in the fabrication of optical phantoms for fluorescence and diffuse reflection studies, the assumption that their fluorescence is small and can be neglected has not been rigorously validated. The purpose of this study is to establish the fluorescence profile of both Intralipid and polystyrene microspheres in optical phantom studies for the broadband spectral region 360-650 nm by separately evaluating the fluorescent intensity of the Intralipid and microsphere phantoms at concentrations that mimic tissue scattering. This was achieved by performing fluorescence spectroscopy of the phantoms using an optical fiber coupled with a spectrometer. In addition, the fluorescence decays of these phantoms were measured with a time-resolved fluorescence spectroscopy system and the average fluorescence lifetime was retrieved for comparison with that of other fluorescent dyes of biological importance.

2. Methods

2.1 Intralipid phantoms

Three sets of seven Intralipid phantoms (total of 21 phantoms) with concentrations of 0.25%, 0.5%, 1%, 1.5%, 2%, 3% and 5% were created for fluorescence measurements. These phantoms were prepared by diluting the concentrated Intralipid® 20% solution (manufactured by Fresenius Kabi, Uppsala, Sweden and distributed by Baxter Healthcare Corp., Deerfield, IL) in de-ionized water. The volume of each phantom was 10 ml which was contained within 12 ml test tubes. A separate set of phantoms with much lower lipid concentration 0.05% - 0.25% was also prepared for transmission measurements using a collimated xenon lamp light source from a spectrometer (Ultraspec 3000, Pharmacia Biotech Inc., NJ). The transmission data (T) were used to calculate scattering coefficients (µs) by applying the relationshipμS=ln(T)/L, where L = 1 mm is the path length of the quartz cuvette used [20

20. S. L. Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58(11), R37–R61 (2013). [CrossRef] [PubMed]

]. The measurements allowed extrapolation of µs for phantoms with higher lipid concentration

2.2 Microsphere phantoms and Mie theory

Three microsphere phantoms with concentrations of 0.72%, 0.4%, 0.2% solids w/v aqueous suspension were prepared by diluting the 2.5% (the notation of w/v is omitted in further discussion of microspheres) stock solution of 1 μm diameter polystyrene microspheres (Polysciences Inc., Warrington, PA). The corresponding number of spheres per cubic micrometer in these phantoms is 0.0131, 0.0073, 0.00364 which were found by applying the relationship in Eq. (1). In this equation, N is number of spheres per cubic micrometer, x is particle concentration in gram per milliliter (x = 0.0072, 0.004, 0.002 g/ml, respectively), y = 1.05 g/ml is the density of polystyrene [21

21. M. Godin, A. K. Bryan, T. P. Burg, K. Babcock, and S. R. Manalis, “Measuring the mass, density, and size of particles and cells using a suspended microchannel resonator,” Appl. Phys. Lett. 91(12), 123121 (2007). [CrossRef]

,22

22. S. Stankovich, D. A. Dikin, G. H. Dommett, K. M. Kohlhaas, E. J. Zimney, E. A. Stach, R. D. Piner, S. T. Nguyen, and R. S. Ruoff, “Graphene-based composite materials,” Nature 442(7100), 282–286 (2006). [CrossRef] [PubMed]

], and d = 1 μm diameter of sphere in micrometers.

N=6xyπd3
(1)

nsphere(λ)=1.5725+0.0031080λ20.00034779λ4
(3)

As a verification of the program, the reduced scattering coefficients for microsphere phantom 0.72% were also calculated with Prof. Prahl’s Mie calculator [27

27. S. A. Prahl, “Mie Scattering Calculator”. http://omlc.ogi.edu/calc/mie_calc.html

]. Since Prof. Prahl’s calculator can only perform single wavelength calculations, the comparison with current program was performed at wavelengths with step of 25 nm.

2.3 Instruments

Fluorescence measurements of the Intralipid phantoms were performed using an excitation pulsed laser at 355 nm (PNV-001525-140, Teem Photonics, Meylan, France), a single optical fiber with core diameter of 600 µm and numerical aperture of 0.12 for illumination and detection, a calibrated spectrometer (UV-NIR-200, StellarNet Incorporation, Tampa, FL) to record fluorescence at a broadband wavelength range 350-650 nm, and a calibrated acousto-optic-tunable-filter (AOTF) -based time-resolved spectrometer for estimation of lifetime and verification of fluorescence signals. Details of the time-resolved system can be found elsewhere [28

28. Z. Nie, R. An, J. E. Hayward, T. J. Farrell, and Q. Fang, “Hyperspectral fluorescence lifetime imaging for optical biopsy,” J. Biomed. Opt. 18(9), 096001 (2013). [CrossRef] [PubMed]

,29

29. Y. Yuan, J.-Y. Hwang, M. Krishnamoorthy, J. Ning, Y. Zhang, K. Ye, R. C. Wang, M. J. Deen, and Q. Fang, “High throughput AOTF-based time-resolved fluorescence spectrometer for optical biopsy,” Opt. Lett. 34(7), 1132–1134 (2009). [CrossRef] [PubMed]

]. The advantage of using excitation wavelength at 355 nm in tissue is that most of biological fluorophores such as NADH, collagen, and elastin, etc. can be excited at this wavelength to emit light in visible region.

In all phantom measurements, the fiber tip was held perpendicular to the phantom surface and was immersed within the phantoms at a depth of approximately 2 mm from the surface. The laser power was set at approximately 2.8 µJ and the integrating time of the spectrometer was set at 0.75 second. These values were chosen to maintain good signal for observation while avoiding spectrometer saturation. Background fluorescence was also taken into account by subtracting fluorescence of the phantoms from that of test tube filled with only de-ionized water.

3. Results

3.1 Scattering of phantoms compared to mucosal tissues

Comparing with previously reported µs values of mucosal tissue [5

5. R. Drezek, K. Sokolov, U. Utzinger, I. Boiko, A. Malpica, M. Follen, and R. Richards-Kortum, “Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications,” J. Biomed. Opt. 6(4), 385–396 (2001). [CrossRef] [PubMed]

,6

6. S. K. Chang, D. Arifler, R. Drezek, M. Follen, and R. Richards-Kortum, “Analytical model to describe fluorescence spectra of normal and preneoplastic epithelial tissue: comparison with Monte Carlo simulations and clinical measurements,” J. Biomed. Opt. 9(3), 511–522 (2004). [CrossRef] [PubMed]

], it was shown that Intralipid phantoms with lipid concentrations between 0.25% and 0.5% are best for simulation of epithelial scattering while those with lipid concentration between 1.5% and 2% are best for simulation of stromal scattering (Fig. 2). Phantoms with lipid concentration 3% and 5% were also produced to further observe the fluorescence trend at high µs values.

Figure 3
Fig. 3 Numerical calculation of Mie theory using current program compared to Prahl’s calculator [27]: (a) scattering coefficients of 0.72% microsphere phantom, (b) anisotropy
compares the current numerical calculation to Prof. Prahl’ calculator for scattering coefficients µs of microsphere phantom 0.72% (Fig. 3(a)) and the sphere’s anisotropy values g (Fig. 3(b)). An excellent agreement between the two programs with average percentage error less than 0.1% was obtained. As shown in Fig. 3(b), the anisotropy of 1 µm microsphere is within range of 0.88-0.93 with the peak at around 475 nm.

3.2 Fluoresence of Intralipid and of microsphere phantoms

The fluorescent intensity spectrum of Intralipid phantoms collected with the spectrometer between 360 and 650 nm is shown in Fig. 5
Fig. 5 Fluorescent intensity of Intralipid phantoms with different lipid concentrations: 2%, 3%, 5% (a), 0.25%, 0.5%, 1%, and 1.5% (b). The inset in (b) shows auto-scales of the same curves.
. Background fluorescence was taken into account by subtracting fluorescence of the phantoms to that of test tube filled with only de-ionized water. All error bars shown in these graphs were obtained from standard deviation calculation of measurements of different phantoms with respect to a specific lipid concentration. As shown in Fig. 5, the fluorescence generally increases gradually from 360 nm to 450 nm with a peak at around 450 nm, and increases more rapidly from 477 nm to 500 nm with a peak at 500 nm. Fluorescence decreases quickly from 525 nm to 650 nm (Fig. 5). In these results, the excitation wavelength is not seen because dichroic mirror and filter were used to block back scattered excitation light [28

28. Z. Nie, R. An, J. E. Hayward, T. J. Farrell, and Q. Fang, “Hyperspectral fluorescence lifetime imaging for optical biopsy,” J. Biomed. Opt. 18(9), 096001 (2013). [CrossRef] [PubMed]

,29

29. Y. Yuan, J.-Y. Hwang, M. Krishnamoorthy, J. Ning, Y. Zhang, K. Ye, R. C. Wang, M. J. Deen, and Q. Fang, “High throughput AOTF-based time-resolved fluorescence spectrometer for optical biopsy,” Opt. Lett. 34(7), 1132–1134 (2009). [CrossRef] [PubMed]

].

Fluorescent intensity at 450 nm as function of lipid concentration (or reduced scattering coefficients) collected with both systems is plotted on the same graph in Fig. 7
Fig. 7 Fluorescent intensity collected with a time-resolved fluorometer (TRF) and spectrometer (SPEC) at 450 nm as a function of lipid concentration or µs values at 450 nm. Intensity of phantoms in each case was normalized to that of phantom with lipid concentration 5%.
for demonstration. In Fig. 7, the fluorescent intensity at 450 nm of the Intralipid phantoms was normalized to that of the Intralipid 5% phantom when using the spectrometer and the AOTF time-resolved fluorometer, respectively.

Figure 8
Fig. 8 Fluoresence of microsphere phantoms using a spectrometer (a), and a time-resolved fluorometer (b).
shows the fluorescent intensity of the microsphere phantoms measured with the spectrometer (Fig. 8(a)) and with the time-resolved fluorometer (Fig. 8(b)). Again, a trend agreement was obtained with both methods so that maximum fluorescent intensity was obtained with microsphere concentration of 0.72% (0.0131 sphere per cubic micron) followed by microsphere concentration of 0.4% (0.0073 sphere per cubic micron). The main peak in microsphere fluorescence was seen at 500 nm and is more pronounced at the highest sphere concentration at 0.72% (Fig. 8(a)).

However, the fluorescent intensity of the 0.72% microsphere phantom is much smaller than that of the 2% Intralipid phantom (Fig. 9
Fig. 9 Fluoresence of Intralipid compared to microspheres: The measurements were performed with a spectrometer.
) while both have similar scattering to that of the stromal layer (Fig. 2 and Fig. 4). On average, fluorescence of the 2% Intralipid phantom was approximately 3 times stronger than that of the 0.72% microsphere phantom (Fig. 9). As shown in Fig. 9, even the 1.5% Intralipid phantom which has lower scattering than the 0.72% microsphere, 1.5% Intralipid phantom produces fluorescence signals with intensity approximately twice as strong as the 0.72% microsphere phantom (Fig. 9).

3.3 Fluoresence decays of Intralipid and of polystyrene microsphere

Fluorescence decays of Intralipid and microsphere phantoms were also recorded with the digitizer for estimation of lifetime. Figure 10
Fig. 10 Normalized fluorescence decays of Intralipid phantoms with lipid concentration of 2% and microsphere phantom with sphere concentration of 0.72%.
shows examples of the normalized fluorescence decays for phantoms with lipid concentration 2% and microsphere 0.72% at emission peak 455 nm. A bi-exponential deconvolution method was used to retrieve the intrinsic response function from measured fluorescence signals [33

33. J. R. Lakowicz, Principles of Fluorescence Spectroscopy (Springer, 2006), Chap. 4.

]. Based on the fractional contribution of each component [33

33. J. R. Lakowicz, Principles of Fluorescence Spectroscopy (Springer, 2006), Chap. 4.

], an average lifetime of 4.53 ± 0.21 ns and 1.81 ± 0.1 ns was obtained for Intralipid and microspheres, respectively. Similar decays were obtained for phantoms with other lipid and microsphere concentrations. The calculated lifetime (τ) of Intralipid is in the similar range of the lifetime of other visible-emission-dyes used in various fluorescent studies such as Fluorescein (τ = 4 ns), Pyrene (τ = 2.97 ns), 4',6-Diamidino-2-phenylindole or DAPI (τ = 2.78 ns), Rhodamine 123 (τ = 3.97 ns), Alexa 532 (τ = 2.53 ns), and FAD (τ = 2.91 ns) [34

34. M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev. 110(5), 2641–2684 (2010). [CrossRef] [PubMed]

]. Therefore, the possibility for Intralipid to interfere with fluorescence measurements of these dyes is high if used together in a tissue phantom.

4. Conclusions

These measurements have provided a quantitative measurement of fluorescence of Intralipid and polystyrene microspheres (diameter of 1 µm) in the wavelength range 360-650 nm with consideration of microsphere and lipid concentrations that match the reduced-scattering coefficients of human mucosal tissue. It has been shown that Intralipid phantoms have a primary emission peak at 500 nm and a secondary emission peak at 450 nm while microspheres appear to have a single peak around 500 nm. The fluorescence intensity of Intralipid is significantly stronger (average approximately 3-fold) than that of microspheres considering lipid and microsphere concentration at levels which simulate tissue scattering. In addition, the calculated fluorescence lifetime of Intralipid is approximately 2.5 times longer than that of microspheres (4.53 ns vs. 1.81 ns). Most fluorescence dyes used in research strongly fluoresce in region 450-600 nm and have the average life time as close as that of Intralipid. For example, Fluorescein and Rhodamine 123 has strong emission at around 450-500 nm and 520-600 nm, respectively and average life-time of 4 ns and 3.97 ns, respectively [34

34. M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev. 110(5), 2641–2684 (2010). [CrossRef] [PubMed]

]. Consequently, the probability for fluorescence of Intralipid to interfere with fluorescence of the studied fluorophore is much higher than that of microspheres. Therefore, the fluorescence of microsphere phantoms might be neglected in optical phantom studies. However, the same assumption may not be accurate in the case of Intralipid phantoms.

In fluorescence studies, background medium consists of pure absorber and pure scatterer which do not fluoresce so that the fluorescence of fluorophore can be studied independently [11

11. J. Swartling, J. Svensson, D. Bengtsson, K. Terike, and S. Andersson-Engels, “Fluorescence spectra provide information on the depth of fluorescent lesions in tissue,” Appl. Opt. 44(10), 1934–1941 (2005). [CrossRef] [PubMed]

13

13. G. Wagnières, S. Cheng, M. Zellweger, N. Utke, D. Braichotte, J. P. Ballini, and H. van den Bergh, “An optical phantom with tissue-like properties in the visible for use in PDT and fluorescence spectroscopy,” Phys. Med. Biol. 42(7), 1415–1426 (1997). [CrossRef] [PubMed]

, 35

35. A. Kienle, L. Lilge, M. S. Patterson, R. Hibst, R. Steiner, and B. C. Wilson, “Spatially resolved absolute diffuse reflectance measurements for noninvasive determination of the optical scattering and absorption coefficients of biological tissue,” Appl. Opt. 35(13), 2304–2314 (1996). [CrossRef] [PubMed]

]. Furthermore, in diffuse reflection studies the reflected light from the phantoms is usually subtracted to background signal collected from DI water or instrument’s noise [8

8. V. N. Le, Q. Wang, J. C. Ramella-Roman, and T. J. Pfefer, “Monte Carlo modeling of light-tissue interactions in narrow band imaging,” J. Biomed. Opt. 18(1), 010504 (2013). [CrossRef] [PubMed]

,19

19. Q. Wang, D. Le, J. Ramella-Roman, and J. Pfefer, “Broadband ultraviolet-visible optical property measurement in layered turbid media,” Biomed. Opt. Express 3(6), 1226–1240 (2012). [CrossRef] [PubMed]

]. However, this method might introduce error if Intralipid is used as scatterer because it fluoresces strongly, and its fluorescence intensity might not be negligible as previously claimed [31

31. S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12(5), 510–519 (1992). [CrossRef] [PubMed]

]. Therefore, a careful data processing method such as subtraction of average fluorescence response to raw signal [36

36. M. Gao, G. Lewis, G. M. Turner, A. Soubret, and V. Ntziachristos, “Effects of background fluorescence in fluorescence molecular tomography,” Appl. Opt. 44(26), 5468–5474 (2005). [CrossRef] [PubMed]

] is necessary to correctly analyze optical properties and intrinsic fluorescence of the target fluorophore. Although mimicking tissue scattering with low-cost materials is a key factor in the use of Intralipid phantoms, our measurements indicate that fluorescence of Intralipid with lipid concentrations to mimic stromal scattering (1.5% and 2%) is significant and should not be ignored.

Acknowledgments

The authors would like to thank Prof. Leyla Soleymani of the Department of Engineering Physics at McMaster University for access to her laboratory during phantom fabrication. This project is supported in part by the Natural Sciences and Engineering Research Council (NSERC) of Canada, Canada Foundation for Innovation (CFI), Ontario Ministry of Research and Innovation (MRI), and Canada Canadian Cancer Society Research Institute (CCSRI). QF holds the Canada Research Chair in Biophotonics.

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S. L. Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58(11), R37–R61 (2013). [CrossRef] [PubMed]

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X. Quan and E. S. Fry, “Empirical equation for the index of refraction of seawater,” Appl. Opt. 34(18), 3477–3480 (1995). [CrossRef] [PubMed]

26.

X. Ma, J. Q. Lu, R. S. Brock, K. M. Jacobs, P. Yang, and X. H. Hu, “Determination of complex refractive index of polystyrene microspheres from 370 to 1610 nm,” Phys. Med. Biol. 48(24), 4165–4172 (2003). [CrossRef] [PubMed]

27.

S. A. Prahl, “Mie Scattering Calculator”. http://omlc.ogi.edu/calc/mie_calc.html

28.

Z. Nie, R. An, J. E. Hayward, T. J. Farrell, and Q. Fang, “Hyperspectral fluorescence lifetime imaging for optical biopsy,” J. Biomed. Opt. 18(9), 096001 (2013). [CrossRef] [PubMed]

29.

Y. Yuan, J.-Y. Hwang, M. Krishnamoorthy, J. Ning, Y. Zhang, K. Ye, R. C. Wang, M. J. Deen, and Q. Fang, “High throughput AOTF-based time-resolved fluorescence spectrometer for optical biopsy,” Opt. Lett. 34(7), 1132–1134 (2009). [CrossRef] [PubMed]

30.

H. J. van Staveren, C. J. Moes, J. van Marie, S. A. Prahl, and M. J. van Gemert, “Light scattering in Intralipid-10% in the wavelength range of 400-1100 nm,” Appl. Opt. 30(31), 4507–4514 (1991). [CrossRef] [PubMed]

31.

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12(5), 510–519 (1992). [CrossRef] [PubMed]

32.

B. Aernouts, E. Zamora-Rojas, R. Van Beers, R. Watté, L. Wang, M. Tsuta, J. Lammertyn, and W. Saeys, “Supercontinuum laser based optical characterization of Intralipid® phantoms in the 500-2250 nm range,” Opt. Express 21(26), 32450–32467 (2013). [CrossRef] [PubMed]

33.

J. R. Lakowicz, Principles of Fluorescence Spectroscopy (Springer, 2006), Chap. 4.

34.

M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev. 110(5), 2641–2684 (2010). [CrossRef] [PubMed]

35.

A. Kienle, L. Lilge, M. S. Patterson, R. Hibst, R. Steiner, and B. C. Wilson, “Spatially resolved absolute diffuse reflectance measurements for noninvasive determination of the optical scattering and absorption coefficients of biological tissue,” Appl. Opt. 35(13), 2304–2314 (1996). [CrossRef] [PubMed]

36.

M. Gao, G. Lewis, G. M. Turner, A. Soubret, and V. Ntziachristos, “Effects of background fluorescence in fluorescence molecular tomography,” Appl. Opt. 44(26), 5468–5474 (2005). [CrossRef] [PubMed]

OCIS Codes
(170.3650) Medical optics and biotechnology : Lifetime-based sensing
(170.6280) Medical optics and biotechnology : Spectroscopy, fluorescence and luminescence

ToC Category:
Calibration, Validation and Phantom Studies

History
Original Manuscript: March 5, 2014
Revised Manuscript: May 27, 2014
Manuscript Accepted: July 16, 2014
Published: July 22, 2014

Citation
Vinh Nguyen Du Le, Zhaojun Nie, Joseph E. Hayward, Thomas J. Farrell, and Qiyin Fang, "Measurements of extrinsic fluorescence in Intralipid and polystyrene microspheres," Biomed. Opt. Express 5, 2726-2735 (2014)
http://www.opticsinfobase.org/boe/abstract.cfm?URI=boe-5-8-2726


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  29. Y. Yuan, J.-Y. Hwang, M. Krishnamoorthy, J. Ning, Y. Zhang, K. Ye, R. C. Wang, M. J. Deen, and Q. Fang, “High throughput AOTF-based time-resolved fluorescence spectrometer for optical biopsy,” Opt. Lett.34(7), 1132–1134 (2009). [CrossRef] [PubMed]
  30. H. J. van Staveren, C. J. Moes, J. van Marie, S. A. Prahl, and M. J. van Gemert, “Light scattering in Intralipid-10% in the wavelength range of 400-1100 nm,” Appl. Opt.30(31), 4507–4514 (1991). [CrossRef] [PubMed]
  31. S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med.12(5), 510–519 (1992). [CrossRef] [PubMed]
  32. B. Aernouts, E. Zamora-Rojas, R. Van Beers, R. Watté, L. Wang, M. Tsuta, J. Lammertyn, and W. Saeys, “Supercontinuum laser based optical characterization of Intralipid® phantoms in the 500-2250 nm range,” Opt. Express21(26), 32450–32467 (2013). [CrossRef] [PubMed]
  33. J. R. Lakowicz, Principles of Fluorescence Spectroscopy (Springer, 2006), Chap. 4.
  34. M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev.110(5), 2641–2684 (2010). [CrossRef] [PubMed]
  35. A. Kienle, L. Lilge, M. S. Patterson, R. Hibst, R. Steiner, and B. C. Wilson, “Spatially resolved absolute diffuse reflectance measurements for noninvasive determination of the optical scattering and absorption coefficients of biological tissue,” Appl. Opt.35(13), 2304–2314 (1996). [CrossRef] [PubMed]
  36. M. Gao, G. Lewis, G. M. Turner, A. Soubret, and V. Ntziachristos, “Effects of background fluorescence in fluorescence molecular tomography,” Appl. Opt.44(26), 5468–5474 (2005). [CrossRef] [PubMed]

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