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Optics Express

Optics Express

  • Editor: Michael Duncan
  • Vol. 12, Iss. 17 — Aug. 23, 2004
  • pp: 4103–4112
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Time and wavelength resolved spectroscopy of turbid media using light continuum generated in a crystal fiber

Christoffer Abrahamsson, Tomas Svensson, Sune Svanberg, Stefan Andersson-Engels, Jonas Johansson, and Staffan Folestad  »View Author Affiliations


Optics Express, Vol. 12, Issue 17, pp. 4103-4112 (2004)
http://dx.doi.org/10.1364/OPEX.12.004103


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Abstract

We report a novel system for time-resolved diffuse remission spectral measurements, based on short light continuum pulses generated in an index-guided crystal fiber, and a spectrometer-equipped streak camera. The system enables spectral recordings of absorption and reduced scattering coefficients of turbid media in the wavelength range 500–1200 nm with a spectral resolution of 5 nm and a temporal resolution of 30 ps. The optical properties are calculated by fitting the solution of the diffusion equation to the time-dispersion curve at each wavelength. Example measurements are presented from an apple, a finger and a pharmaceutical tablet.

© 2004 Optical Society of America

1. Introduction

Over the last decade there has been a lot of effort to develop techniques to extract the absorption and sometimes scattering properties of turbid media. Several areas of research need a tool for such measurements - biomedical applications including tissue diagnostics and physiological measurements, the pharmaceutical industry for on-line measurements of active substance concentration in pharmaceutical preparations, and the food industry for non-destructive measurements of the quality of products. Two, generally different approaches, have been employed to do this. The first one is based on measurements from which it is possible to extract the absorption and scattering properties more or less independently. The measurements can be time-resolved, spatially-resolved or be made in the frequency domain with a modulated light source. The other approach uses spectrally-resolved measurements and utilizes multivariate analysis following training on a large set of known samples. The latter method has been developed mainly within NIR spectroscopy, where scattering has been seen as a complication, yielding uncertainties in the evaluation of the recorded data [1

1. P. Geladi, D. MacDougall, and H. Martens, “Linearization and scatter correction for near-infrared reflectance spectra of meat,” Appl. Spectrosc. 39, 491–500 (1985). [CrossRef]

,2

2. S. Wold, H. Antii, F. Lindgren, and J. Ohman“Orthogonal signal correction of near-infrared spectra,” Chemom. Intell. Lab. Syst. 44, 175–185 (1998). [CrossRef]

]. Large training sets and complex calibration models have often been necessary to span the entire region of the important parameters of the samples under investigation [3

3. V. Centner, J. Verdú-Andrés, B. Walczak, D. Jouan-Rimbaud, F. Despagne, L. Pasti, R. Poppi, D-L. Massart, and O. E. de Noord, “Comparison of multivariate calibration techniques applied to experimental NIR data sets,” Appl. Spectrosc. 54, 608–629 (2000). [CrossRef]

]. This approach has two major limitations - it needs frequent calibrations and it is not very robust.

In many respects it is more appealing to use the model-based approach to obtain the absorption and/or scattering properties [4

4. I. Georgakoudi, B. C. Jacobson, J. van Dam, V. Backman, M. B. Wallace, M. G. Muller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology. 120, 1620–1629 (2001). [CrossRef] [PubMed]

6

6. O. Berntsson, T. Burger, S. Folestad, L. G. Danielsson, J. Kuhn, and J. Fricke, “Effective sample size in diffuse reflectance near-IR spectrometry,” Anal. Chem. 71, 617–623 (1999). [CrossRef] [PubMed]

]. Frequently time-resolved techniques have been employed (see, for example [7

7. M. S. Patterson, B. Chance, and B. C. Wilson, “Time resolved reflectance and transmittance for the non-invasive measurement of optical properties,” Appl. Opt. 28, 2331–2336 (1989). [CrossRef] [PubMed]

12

12. R. Cubeddu, C. D’Andrea, A. Pifferi, P. Taroni, A. Torricelli, G. Valentini, M. Ruiz-Altisent, C. Valero, C. Ortiz, C. Dover, and D. Johnson, “Time-resolved reflectance spectroscopy applied to the nondestructive monitoring of the internal optical properties in apples,” Appl. Spectrosc. 55, 1368–1374 (2001). [CrossRef]

]), but also frequency domain [13

13. J. R. Lakowicz and K. Berndt, “Frequency-domain measurements of photon migration in tissues,” Chem. Phys. Lett. 166, 246 (1990). [CrossRef]

19

19. F. Bevilacqua, A. J. Berger, A. E. Cerussi, D. Jakubowski, and B. J. Tromberg, “Broadband absorption spectroscopy in turbid media by combined frequency-domain and steady-state methods,” Appl. Opt. 39, 6498–6507 (2000). [CrossRef]

] and spatially resolved [20

20. T. J. Farrell, B. C. Wilson, and M. S. Patterson, “The use of a neural network to determine tissue optical properties from spatially resolved diffuse reflectance measurements,” Phys. Med. Biol. 37, 2281–2286 (1992). [CrossRef] [PubMed]

22

22. R. L. P. van Veen, W. Verkruysse, and H. J. C. M. Sterenborg, “Diffuse-reflectance spectroscopy from 500 to 1060 nm by correction for inhomogeneously distributed absorbers,” Opt. Lett. 27, 246–248 (2002). [CrossRef]

] techniques have been utilized. Such measurements are most often performed at multiple wavelengths in order to enable the desired information to be obtained. This can be achieved with diode lasers at fixed wavelengths or by scanning a tunable laser over the wavelength region of interest [23

23. R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “Noninvasive absorption and scattering spectroscopy of bulk diffusive media: An application to the optical characterization of human breast,” Appl. Phys. Lett. 74, 874–876 (1999). [CrossRef]

,24

24. A. Pifferi, J. Swartling, E. Chikoidze, A. Torricelli, P. Taroni, S. Andersson-Engels, and R. Cubeddu, “Spectroscopic time-resolved diffuse reflectance and transmittance measurements of the female breast at different interfiber distances,” J. Biomedical Optics. (to be published).

]. Parallel detection of all wavelengths of interest is possible with a short-pulsed broad light source. Such a suitable source is continuum generation employing non-linear interaction in a special optical medium as a result of high peak-power illumination [25

25. R. R. Alfano and S. L. Shapiro, “Observation of self-phase modulation and small-scale filaments in crystals and glasses,” Phys. Rev. Lett. 24, 592–594 (1970). [CrossRef]

,26

26. R. L. Fork, C. V. Shank, C. Hirlimann, R. Yen, and W. J. Tomlinson, “Femotsecond white-light continuum pulses,” Opt. Lett. 8, 1–3 (1983). [CrossRef] [PubMed]

]. A system based on this technology has been developed in our laboratory. It relies on focusing a high-power laser beam in a sapphire crystal or a cuvette of water [11

11. S. Andersson-Engels, R. Berg, A. Persson, and S. Svanberg, “Multispectral tissue characterization with time-resolved detection of diffusely scattered white light,” Opt. Lett. 18, 1697–1699 (1993). [CrossRef] [PubMed]

,27

27. O. Jarlman, R. Berg, S. Andersson-Engels, S. Svanberg, and H. Pettersson, “Time-resolved white light transillumination for optical imaging,” Acta Radiol. 38, 185–189 (1997). [PubMed]

,28

28. J. Johansson, S. Folestad, M. Josefson, A. Sparen, C. Abrahamsson, S. Andersson-Engels, and S. Svanberg, “Time-resolved NIR/Vis spectroscopy for analysis of solids: Pharmaceutical tablets,” Appl. Spectrosc. 56, 725–731 (2002). [CrossRef]

]. The laser system in that work runs at 10 Hz, and some averaging is required to achieve a sufficient signal-to-noise ratio to extract the absorption properties with reasonable accuracy. This results in a substantial acquisition time and the time-jitter between the pulses also reduces the time resolution of the system.

Light continuum generation has been utilized for many spectroscopy applications. Recently, non-linear effects in microstructured fibers, designed to have a very low dispersion and thus retain a high pulse peak power throughout the full length of the fiber, have been employed for this purpose [29

29. J. K. Ranka, R. S. Windeler, and A. J. Stentz, “Visible continuum generation in air-silica microstructure optical fibers with anomalous dispersion at 800 nm,” Opt. Lett. 25, 25–27 (2000). [CrossRef]

,30

30. J. C. Knight, T. A. Birks, R. F. Cregan, P. S. J. Russell, and J. P. de Sandro, “Photonic crystals as optical fibres - physics and applications,” Optical Materials. 11, 143–151 (1999). [CrossRef]

]. Since the non-linear efficiency is very high for these fibers, it is sufficient to use it the with moderate peak powers, obtained by mode-locked lasers. Thus a relatively compact new light source is available for spectroscopy of turbid media [31

31. C. Abrahamsson, S. Andersson-Engels, S. Folestad, J. Johansson, and S. Svanberg. “New measuring technique”, Patent Application PCT WO 2002075286 (2002)

].

The objectives of this study were twofold: first to demonstrate the function of a complete time-resolved spectroscopy system based on continuum generation in an index-guiding crystal fiber in the entire wavelength range 500–1200 nm, covering most of the wavelengths of interest for the applications mentioned above. Next, we show measurements conducted on three types of samples to demonstrate the capability of the system.

2. Material and methods

2.1 System description

The arrangement of the system is depicted in Fig. 1. The Ar-ion laser pumped mode-locked Ti:Sapphire laser produced pulses shorter than 100 fs at a repetition rate of 80 MHz. The wavelength of the laser light was centered around 800 nm, and the energy of each pulse was 4 nJ. An optical isolator was used after the laser, to prevent optical reflections that provide unwanted feedback to the laser causing unstable output conditions. A prism compressor was used in the set-up to compensate for the time dispersion caused by the different optical components. The light output from the compressor was focused into a 100 cm long index-guiding crystal fiber (ICF) (Crystal Fiber A/S, Copenhagen, Denmark) using a conventional x40 microscope objective lens with a numeric aperture of 0.65. The ICF had a core diameter of 2 µm and was manufactured to have minimum dispersion at 760 nm. A light continuum was generated by employing non-linear optical effects in the fiber, mainly self-phase modulation and stimulated Raman scattering [32

32. G. Genty, M. Lehtonen, H. Ludvigsen, J. Broeng, and M. Kaivola, “Spectral broadening of femtosecond pulses into continuum radiation in microstructured fibers,” Opt. Express. 10, 1083–1098 (2002), http://www.opticsexpress.org/abstract.cfm?URI=OPEX-10-20-1083. [CrossRef] [PubMed]

]. A low dispersion of the light inside the fiber combined with small core diameter results in a high peak power of the light in the entire length of the fiber, yielding a high non-linear efficacy resulting in widely spectrally broadened light emission. As a result of this, light pulses with a spectral width spanning from 500 nm to at least 1200 nm were accessible. The light distribution was, however, not perfectly flat throughout the entire wavelength region, but relatively modulated. An advantage of this technique is that it is totally independent of such modulations as long as sufficient light intensity was obtained for all wavelengths of interest, since the optical properties are derived from the time dispersion curves in the sample.

Fig. 1. Optical arrangement of the system. Three types of sample geometry were employed, a fiber-based probe in diffuse transmission or reflection, as well as a direct transmission of a slightly focused beam from the crystal fiber.

For the sample measurements, either of three geometries was employed as indicated in Fig. 1. Most samples have been measured with a fiber-based probe. The light from the distal end of the ICF is coupled into a 600 µm diameter gradient index fiber that is held in contact with the sample to be measured. Another fiber was used to pick up the remitted light at a certain position of the sample. This was performed either in reflectance or in transmission mode. A third probe geometry, employed mainly for measurements of pharmaceutical tablets, utilized a non-contact beam arrangement. Here, light from the distal end of the ICF was slightly focused onto the tablet surface using a lens. The spot size on the tablet was approximately 2 mm. The tablet was held into place by a circular iris holder, suppressing any light scattered away outside the tablet. Another lens system was used to image the transmitted light onto the entrance slit of the detection system. The detection comprised an imaging spectrometer and a streak camera, yielding spectrally and temporally resolved data in the wavelength region from 500 to 1200 nm. A 25 cm imaging spectrometer (Chromex, Model 250 IS) was equipped with an adjustable entrance slit and three gratings with 30 to 150 grooves/mm. If the entire wavelength range was to be measured, it was necessary to take more than one recording, with different positions of the grating. The spectrally dispersed light at the output of the spectrometer was captured by the streak camera (Hamamatsu, Model C5680). The streak tube utilized an S1 photocathode in order to cover the entire wavelength range of interest. The streak camera operated in synchro-scan mode, allowing all light pulses to be collected. A small portion of the laser light was redirected by a beam splitter onto a photodiode that triggered the streak camera sweep. The system had a total temporal range of 2.1 ns with resolution of 4.5 ps. The instrumental response function was in the range of 30 ps when averaging over 50 s.

2.2 Measurement procedure

Fig. 2. Detected light intensity without any sample as a function of wavelength Three settings of the spectrometer was employed to cover the entire range. The middle region was measured using the Ti:Sapphire laser only, without any crystal fiber.

Prior to each sample measurement, an instrumental response function was recorded. This was either done by connecting two fibers to each end of a thin metal tube indented at the middle to decrease the light measured, or by inserting a pin-hole in the light path. The light intensity was further reduced by inserting absorbing glass filters. The instrumental response function was important in the subsequent analysis to determine the time of the laser pulse in the camera streak without the dispersion caused by the sample and to measure the dispersion of the measured pulse due to the system characteristics.

2.3 Sample measurements

Before the system was utilized for measurements on various samples, its potential to extract optical properties from a homogenous turbid medium was evaluated. For this check, four tissue phantoms as prepared according to Ref. [33

33. J. Swartling, J. S. Dam, and S. Andersson-Engels, “Comparison of spatially and temporally resolved diffuse-reflectance measurement systems for determination of biomedical optical properties,” Appl. Opt. 42, 4612–4620 (2003). [CrossRef] [PubMed]

] were employed. The 6.5 cm diameter and 5.5 cm thick epoxy phantoms contained TiO2 particles as scattering centers and toner powder as absorber. The phantoms were measured in a diffuse reflectance geometry using a 1.0 meter long 600 µm core diameter gradient index fiber as a source and collection fiber, respectively. The inter-fiber distance during the recordings was 8 mm. As a gold standard for the determination of expected optical properties, integrating sphere measurements of 1.00 mm thick samples, prepared simultaneously as the phantoms were used [33

33. J. Swartling, J. S. Dam, and S. Andersson-Engels, “Comparison of spatially and temporally resolved diffuse-reflectance measurement systems for determination of biomedical optical properties,” Appl. Opt. 42, 4612–4620 (2003). [CrossRef] [PubMed]

].

Following these initial measurements, a number of samples were studied, to illustrate the potential of this system in determining absorption and scattering spectra of turbid samples. Firstly, apples were analysed. A small piece of a fresh Golden Delicious apple obtained from a nearby grocery store was removed, creating a flat skinless surface with a diameter of approximately 30 mm. The apple was measured immediately after the cut with the same diffuse reflection geometry as used for the phantoms.

Next, the tip of the index finger of a volunteer was measured. The finger was measured in transillumination using the same fibers as above for light delivery and collection. The measurement was conducted through the nail. The thickness of the finger was 7 mm. The evaluation was conducted assuming transmission through a infinite slab of thickness 7 mm. Finally, a pharmaceutical tablet (typical immediate release tablet, AstraZeneca R&D Mölndal, Sweden) especially prepared for optical measurements was examined. The tablet was produced in a cylindrical shape with flat end surfaces and a diameter of 13 mm and a thickness of 2 mm. For this measurement, the light continuum from the crystal fiber was slightly focused with a microlens to form a convergent beam with a diameter of 2 mm at the surface of the tablet. The diffuse light transmitted through the tablet was collected and focused onto the entrance slit of the spectrometer using two achromatic lenses.

2.4 Evaluation of absorption and scattering spectra

The recorded data images were evaluated as indicated in Fig. 3. A recorded image contained temporally (x-axis) and spectrally (y-axis) resolved information of the remitted light, accumulated from a sample during typically one minute. The optical properties were then analyzed at each wavelength independently by fitting the experimental data to an analytical solution of the diffusion approximation of the transport equation for a homogeneous semi-infinite medium or an infinite slab [7

7. M. S. Patterson, B. Chance, and B. C. Wilson, “Time resolved reflectance and transmittance for the non-invasive measurement of optical properties,” Appl. Opt. 28, 2331–2336 (1989). [CrossRef] [PubMed]

]. In the evaluation procedure, boundaries are accounted for by employing an extrapolated boundary condition [34

34. R. C. Haskell, L. O. Svaasand, T.-T. Tsay, T.-C. Feng, M. S. McAdams, and B. J. Tromberg, “Boundary conditions for the diffusion equation in radiative transfer,” J. Opt. Soc. Am. A. 11, 2727–2741 (1994). [CrossRef]

]. The best fit was reached iteratively with a Levenberg-Marquardt algorithm, where µs’, µa and an overall amplitude factor are varied in order to minimize a χ 2 merit norm. The temporal shift between the IRF and experimental data is known and is thus not regarded as a free fit parameter. Each iteration involves a convolution between the theoretical time-dispersion curve and the IRF. The fitting range included all points with a number of counts higher than 80% of the peak value on the rising edge of the curve and 1% on the tail [35

35. R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “Experimental test of theoretical models for time-resolved reflectance,” Med. Phys. 23, 1625–1633 (1996). [CrossRef] [PubMed]

]. A typical outcome is presented in Fig. 3, and an example of the proceedings of the algorithm is given in Fig. 4.

Fig. 3. A recorded data set is shown (upper left). Remitted light intensity is presented versus time along the horizontal axis and wavelength along the vertical axis. A spectral profile of the remitted light at a time gate around 150 ps is shown in the plot to the upper right, while the temporal dispersion of the detected light at 900 nm is illustrated in the lower left graph. In the latter plot, the instrumental response function (IRF) is also indicated (in red), together with the best obtainable fit (green curve). In the lower right plot, the optical properties evaluated from this image are shown as a function of wavelength.
Fig. 4. Levenberg-Marquardt Minimization. The elliptical pattern is built up of equidistant iso-curves of the merit norm. The elliptical shape implies an apparent correlation between fitted parameter values, giving rise to certain limitations when trying to separate absorption from scattering.

3. Results and discussion

An estimation of accuracy in the evaluation of optical properties from the recordings of the system is given by correlating with those estimated for four phantoms, produced with different absorption and scattering properties. A correlation plot is presented in Fig. 5, illustrating the agreement between estimated and evaluated optical properties at 916 nm. The estimated values were obtained in agreement with integrating sphere measurements of thin slabs of the phantoms and time-resolved measurements at a specific wavelength using a time-correlated single photon counting system [33

33. J. Swartling, J. S. Dam, and S. Andersson-Engels, “Comparison of spatially and temporally resolved diffuse-reflectance measurement systems for determination of biomedical optical properties,” Appl. Opt. 42, 4612–4620 (2003). [CrossRef] [PubMed]

]. As can be seen the obtained values agree within approximately 10% with the estimated values for the absorption and within 20% for the scattering.

Spectra of optical properties from an apple fruit are illustrated in Fig. 6a. As can be seen the reduced scattering coefficient decreases almost linearly with increasing wavelength. By fitting the spectrum to the expression for reduced scattering coefficient as a function of wavelength, µs’=-b, where b=0.3, it is obvious from Mie theory that the size of the effective scattering centers in the apple are relatively large. The absorption spectrum is dominated by water absorption peaking around 975 nm.

Fig. 5. Correlation plot for measured and estimated optical properties from five epoxy phantoms containing TiO2 particles as scattering material and ink toner as absorber.
Fig. 6. Data evaluated from time-resolved diffuse (a) reflectance measurements on a green apple, and (b) transmission measurements through the tip of an index finger.

A last spectrum illustrates a typical pharmaceutical example. In Fig. 7 an evaluated absorption spectrum of a pharmaceutical tablet especially produced for these measurements in order to obtain a thin tablet and simple measurement geometry, is shown. The absorption spectrum is in good agreement with the active substance in the tablet [36

36. C. Abrahamsson, J. Johansson, A. Sparén, and F. Lindgren, “Comparison of different variable selection methods conducted on NIR transmission measurements on intact tablets,” Chemom. Intell. Lab. Syst. 69, 3–12 (2003). [CrossRef]

]. The scattering coefficient for this tablet was about 500 cm-1.

Fig. 7. Data evaluated from transmission measurements on a pharmaceutical tablet.

The source of the system developed is based on a light continuum generated in a crystal fiber. The crystal fiber technology is rapidly developing and key features of continuum generation in such fibers, such as spectral profile and bandwidth, are quickly improving. The system described in this paper is, however, relatively insensitive to the exact spectral profile of the continuum. As long as the light is sufficiently high at each wavelength of interest, the optical properties can, as seen above, be obtained from a measurement. The detection unit of the system comprises a spectrometer and a streak camera. The spectrometer allows the recording of a wide spectral range, with a relatively high resolution. This is very important for most NIR spectroscopy applications. The streak-camera, on the other hand, provides a very high temporal resolution, enabling measurements of relatively low dispersion objects. As compared to a time-correlated single photon counting system used by several other groups in time-resolved diffuse remission spectroscopy, this system provides a unique combination of relatively short acquisition time in combination with high spectral and temporal resolution.

Acknowledgments

The authors would like to thank Fabien Chauchard, Cemagref, Montpellier, France, for assistance in the measurements and discussions regarding the fruit samples. We are also grateful to Anders Persson for keeping the performance of the laser at a very high level. The work was financially supported by AstraZeneca R&D Mölndal, Sweden, the Swedish Research Foundation, and the Swedish Research Council.

References and links

1.

P. Geladi, D. MacDougall, and H. Martens, “Linearization and scatter correction for near-infrared reflectance spectra of meat,” Appl. Spectrosc. 39, 491–500 (1985). [CrossRef]

2.

S. Wold, H. Antii, F. Lindgren, and J. Ohman“Orthogonal signal correction of near-infrared spectra,” Chemom. Intell. Lab. Syst. 44, 175–185 (1998). [CrossRef]

3.

V. Centner, J. Verdú-Andrés, B. Walczak, D. Jouan-Rimbaud, F. Despagne, L. Pasti, R. Poppi, D-L. Massart, and O. E. de Noord, “Comparison of multivariate calibration techniques applied to experimental NIR data sets,” Appl. Spectrosc. 54, 608–629 (2000). [CrossRef]

4.

I. Georgakoudi, B. C. Jacobson, J. van Dam, V. Backman, M. B. Wallace, M. G. Muller, Q. Zhang, K. Badizadegan, D. Sun, G. A. Thomas, L. T. Perelman, and M. S. Feld, “Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett’s esophagus,” Gastroenterology. 120, 1620–1629 (2001). [CrossRef] [PubMed]

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6.

O. Berntsson, T. Burger, S. Folestad, L. G. Danielsson, J. Kuhn, and J. Fricke, “Effective sample size in diffuse reflectance near-IR spectrometry,” Anal. Chem. 71, 617–623 (1999). [CrossRef] [PubMed]

7.

M. S. Patterson, B. Chance, and B. C. Wilson, “Time resolved reflectance and transmittance for the non-invasive measurement of optical properties,” Appl. Opt. 28, 2331–2336 (1989). [CrossRef] [PubMed]

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11.

S. Andersson-Engels, R. Berg, A. Persson, and S. Svanberg, “Multispectral tissue characterization with time-resolved detection of diffusely scattered white light,” Opt. Lett. 18, 1697–1699 (1993). [CrossRef] [PubMed]

12.

R. Cubeddu, C. D’Andrea, A. Pifferi, P. Taroni, A. Torricelli, G. Valentini, M. Ruiz-Altisent, C. Valero, C. Ortiz, C. Dover, and D. Johnson, “Time-resolved reflectance spectroscopy applied to the nondestructive monitoring of the internal optical properties in apples,” Appl. Spectrosc. 55, 1368–1374 (2001). [CrossRef]

13.

J. R. Lakowicz and K. Berndt, “Frequency-domain measurements of photon migration in tissues,” Chem. Phys. Lett. 166, 246 (1990). [CrossRef]

14.

J. Fishkin, E. Gratton, M. J. vandeVen, and W. W. Mantulin, “Diffusion of intensity modulated near-infrared light in turbid media,” in Time-Resolved Spectroscopy and Imaging of TissueB. Chance, ed. Proc. SPIE1431, 122–135 (1991).

15.

M. Patterson, J. D. Moulton, B. C. Wilson, K. W. Berndt, and J. R. Lakowicz, “Frequency-domain reflectance for the detemination of the scanttering and absorption properties of tissue,” Appl. Opt. 30, 4474–4476 (1991). [CrossRef] [PubMed]

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S. J. Madsen, E. R. Anderson, R. C. Haskell, and B. J. Tromberg, “Portable, high-bandwidth frequency-domain photon migration instrument for tissue spectroscopy,” Opt. Lett. 19, 1934–1936 (1994). [CrossRef] [PubMed]

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E. Gratton and J. Maier, “Frequency-domain measurements of photon migration in highly scattering media,” Medical Optical Tomography.534–544 (1996).

18.

M. A. Franceschini, V. Toronov, M. E. Filiaci, E. Gratton, and S. Fantini, “On-line optical imaging of the human brain with 160-ms temporal resolution,” Opt. Express. 6, 49–57 (2000), http://www.opticsexpress.org/abstract.cfm?URI=OPEX-6-3-49. [CrossRef] [PubMed]

19.

F. Bevilacqua, A. J. Berger, A. E. Cerussi, D. Jakubowski, and B. J. Tromberg, “Broadband absorption spectroscopy in turbid media by combined frequency-domain and steady-state methods,” Appl. Opt. 39, 6498–6507 (2000). [CrossRef]

20.

T. J. Farrell, B. C. Wilson, and M. S. Patterson, “The use of a neural network to determine tissue optical properties from spatially resolved diffuse reflectance measurements,” Phys. Med. Biol. 37, 2281–2286 (1992). [CrossRef] [PubMed]

21.

J. S. Dam, C. B. Pedersen, T. Dalgaard, P. E. Fabricius, P. Aruna, and S. Andersson-Engels, “Fiber optic probe for non-invasive real-time determination of tissue optical properties at multiple wavelengths,” Appl. Opt. 40, 1155–1164 (2001). [CrossRef]

22.

R. L. P. van Veen, W. Verkruysse, and H. J. C. M. Sterenborg, “Diffuse-reflectance spectroscopy from 500 to 1060 nm by correction for inhomogeneously distributed absorbers,” Opt. Lett. 27, 246–248 (2002). [CrossRef]

23.

R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “Noninvasive absorption and scattering spectroscopy of bulk diffusive media: An application to the optical characterization of human breast,” Appl. Phys. Lett. 74, 874–876 (1999). [CrossRef]

24.

A. Pifferi, J. Swartling, E. Chikoidze, A. Torricelli, P. Taroni, S. Andersson-Engels, and R. Cubeddu, “Spectroscopic time-resolved diffuse reflectance and transmittance measurements of the female breast at different interfiber distances,” J. Biomedical Optics. (to be published).

25.

R. R. Alfano and S. L. Shapiro, “Observation of self-phase modulation and small-scale filaments in crystals and glasses,” Phys. Rev. Lett. 24, 592–594 (1970). [CrossRef]

26.

R. L. Fork, C. V. Shank, C. Hirlimann, R. Yen, and W. J. Tomlinson, “Femotsecond white-light continuum pulses,” Opt. Lett. 8, 1–3 (1983). [CrossRef] [PubMed]

27.

O. Jarlman, R. Berg, S. Andersson-Engels, S. Svanberg, and H. Pettersson, “Time-resolved white light transillumination for optical imaging,” Acta Radiol. 38, 185–189 (1997). [PubMed]

28.

J. Johansson, S. Folestad, M. Josefson, A. Sparen, C. Abrahamsson, S. Andersson-Engels, and S. Svanberg, “Time-resolved NIR/Vis spectroscopy for analysis of solids: Pharmaceutical tablets,” Appl. Spectrosc. 56, 725–731 (2002). [CrossRef]

29.

J. K. Ranka, R. S. Windeler, and A. J. Stentz, “Visible continuum generation in air-silica microstructure optical fibers with anomalous dispersion at 800 nm,” Opt. Lett. 25, 25–27 (2000). [CrossRef]

30.

J. C. Knight, T. A. Birks, R. F. Cregan, P. S. J. Russell, and J. P. de Sandro, “Photonic crystals as optical fibres - physics and applications,” Optical Materials. 11, 143–151 (1999). [CrossRef]

31.

C. Abrahamsson, S. Andersson-Engels, S. Folestad, J. Johansson, and S. Svanberg. “New measuring technique”, Patent Application PCT WO 2002075286 (2002)

32.

G. Genty, M. Lehtonen, H. Ludvigsen, J. Broeng, and M. Kaivola, “Spectral broadening of femtosecond pulses into continuum radiation in microstructured fibers,” Opt. Express. 10, 1083–1098 (2002), http://www.opticsexpress.org/abstract.cfm?URI=OPEX-10-20-1083. [CrossRef] [PubMed]

33.

J. Swartling, J. S. Dam, and S. Andersson-Engels, “Comparison of spatially and temporally resolved diffuse-reflectance measurement systems for determination of biomedical optical properties,” Appl. Opt. 42, 4612–4620 (2003). [CrossRef] [PubMed]

34.

R. C. Haskell, L. O. Svaasand, T.-T. Tsay, T.-C. Feng, M. S. McAdams, and B. J. Tromberg, “Boundary conditions for the diffusion equation in radiative transfer,” J. Opt. Soc. Am. A. 11, 2727–2741 (1994). [CrossRef]

35.

R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “Experimental test of theoretical models for time-resolved reflectance,” Med. Phys. 23, 1625–1633 (1996). [CrossRef] [PubMed]

36.

C. Abrahamsson, J. Johansson, A. Sparén, and F. Lindgren, “Comparison of different variable selection methods conducted on NIR transmission measurements on intact tablets,” Chemom. Intell. Lab. Syst. 69, 3–12 (2003). [CrossRef]

OCIS Codes
(060.5060) Fiber optics and optical communications : Phase modulation
(170.1470) Medical optics and biotechnology : Blood or tissue constituent monitoring
(170.3660) Medical optics and biotechnology : Light propagation in tissues
(290.7050) Scattering : Turbid media
(300.6500) Spectroscopy : Spectroscopy, time-resolved

ToC Category:
Research Papers

History
Original Manuscript: July 16, 2004
Revised Manuscript: August 16, 2004
Published: August 23, 2004

Citation
Christoffer Abrahamsson, Tomas Svensson, Sune Svanberg, Stefan Andersson-Engels, Jonas Johansson, and Staffan Folestad, "Time and wavelength resolved spectroscopy of turbid media using light continuum generated in a crystal fiber," Opt. Express 12, 4103-4112 (2004)
http://www.opticsinfobase.org/oe/abstract.cfm?URI=oe-12-17-4103


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