Abstract

We have developed a novel optical method for observing submicrometer intracellular structures in living cells, which is called confocal light absorption and scattering spectroscopic (CLASS) microscopy. It combines confocal microscopy, a well-established high-resolution microscopic technique, with light-scattering spectroscopy. CLASS microscopy requires no exogenous labels and is capable of imaging and continuously monitoring individual viable cells, enabling the observation of cell and organelle functioning at scales of the order of 100 nm.

© 2007 Optical Society of America

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. J.-A. Conchello and J. W. Lichtman, "Optical sectioning microscopy," Nat. Methods 2, 920-931 (2005).
    [CrossRef] [PubMed]
  2. J. Lippincott-Schwartz and G. H. Patterson, "Development and use of fluorescent protein markers in living cells," Science 300, 87-91 (2003).
    [CrossRef] [PubMed]
  3. J. W. Lichtman and J.-A. Conchello, "Fluorescence microscopy," Nat. Methods 2, 910-919 (2005).
    [CrossRef] [PubMed]
  4. W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nature Biotechnol. 21, 1369-1377 (2003).
    [CrossRef]
  5. N. C. Shaner, P. A. Steinbach, and R. Y. Tsien, "A guide to choosing fluorescent proteins," Nat. Methods 2, 905-909 (2005).
    [CrossRef] [PubMed]
  6. P. J. Dwyer, C. A. Dimarzio, J. M. Zavislan, W. J. Fox, and M. Rajadhyaksha, "Confocal reflectance theta line scanning microscope for imaging human skin in vivo," Opt. Lett. 31, 942-944 (2006).
    [CrossRef] [PubMed]
  7. J. G. Fujimoto, "Optical coherence tomography for ultrahigh resolution in vivo imaging," Nature Biotechnol. 21, 1361-1367 (2003).
    [CrossRef]
  8. L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
    [CrossRef]
  9. I. J. Bigio and J. R. Mourant, "Ultraviolet and visible spectroscopies for tissue diagnostics: fluorescence spectroscopy and elastic-scattering spectroscopy," Phys. Med. Biol. 42, 803-814 (1997).
    [CrossRef] [PubMed]
  10. F. Helmchen and W. Denk, "Deep tissue two-photon microscopy," Nat. Methods 2, 932-940 (2005).
    [CrossRef] [PubMed]
  11. W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
    [CrossRef] [PubMed]
  12. E. L. Evan, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. U.S.A. 102, 16807-16812 (2005).
    [CrossRef]
  13. L. H. Laiho, S. Pelet, T. M. Hancewicz, P. D. Kaplan, and P. T. C. So, "Two-photon 3D mapping of ex vivo human skin endogenous fluorescence species based on fluorescence emission spectra," J. Biomed. Opt. 10, 024016 (2005).
    [PubMed]
  14. A. Zoumi, A. Yeh, and B. J. Tromberg, "Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence," Proc. Natl. Acad. Sci. U.S.A. 99, 11014-1019 (2002).
    [CrossRef] [PubMed]
  15. J. X. Cheng, A. Volkmer, and X. S. Xie, "Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy," J. Opt. Soc. Am. B 19, 1363-1375 (2002).
    [CrossRef]
  16. C. Joo, T. Akkin, B. Cense, B. H. Park, and J. F. de Boer, "Spectral-domain optical coherence phase microscopy for quantitative phase-contrast imaging," Opt. Lett. 30, 2131-2133 (2005).
    [CrossRef] [PubMed]
  17. C. Xu, C. Vinegoni, T. S. Ralston, W. Luo, W. Tan, and S. A. Boppart, "Spectroscopic spectra-domain optical coherence microscopy," Opt. Lett. 31, 1079-1081 (2006).
    [CrossRef] [PubMed]
  18. Y. Liu, X. Li, Y. L. Kim, and V. Backman, "Elastic backscattering spectroscopic microscopy," Opt. Lett. 30, 2445-2447 (2005).
    [CrossRef] [PubMed]
  19. V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
    [CrossRef] [PubMed]
  20. V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structure in situ," IEEE J. Sel. Top. Quantum Electron. 5, 1019-1026 (1999).
    [CrossRef]
  21. M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
    [CrossRef] [PubMed]
  22. V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Geogakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, "Measuring cellular structure at submicrometer scale with light scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 7, 887-893 (2001).
    [CrossRef]
  23. R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, "Imaging human epithelial properties with polarized light-scattering spectroscopy," Nature Med. 7, 1245-1248 (2001).
    [CrossRef] [PubMed]
  24. H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, "Noninvasive sizing of subcellular organelles with light-scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 9, 267-276 (2003).
    [CrossRef]
  25. G. Schuele, E. Vitkin, P. Huie, D. Palanker, and L. T. Perelman, "Optical detection of the reaction of organelles to cellular stress," J. Biomed. Opt. 10, 051404-1-8 (2005).
    [PubMed]
  26. T. Zimmermann, J. Rietdorf, and R. Pepperkok, "Spectral imaging and its applications in live cell microscopy," FEBS Lett. 546, 87-92 (2003).
    [CrossRef] [PubMed]
  27. W. Weise, P. Zinin, T. Wilson, A. Briggs, and S. Boseck, "Imaging of spheres with the confocal scanning optical microscope," Opt. Lett. 21, 1800-1802 (1996).
    [CrossRef] [PubMed]
  28. J. F. Aguilar, M. Lera, and C. J. R. Sheppard, "Imaging of spheres and surface profiling by confocal microscopy," Appl. Opt. 39, 4621-4628 (2000).
    [CrossRef]
  29. I. J. D. Craig and J. C. Brown, Inverse Problems in Astronomy: a Guide to Inversion Strategies for Remotely Sensed Data (Hilger, 1986).
  30. R. J. Hanson, "Least squares with bounds and linear constraints," SIAM (Soc. Ind. Appl. Math.) J. Sci. Stat. Comput. 7, 826-834 (1986).
    [CrossRef]
  31. R. J. Hanson, A Cyclic Reduction Solver for the IMSL Mathematics Library Report 9002 (International Mathematical and Statistical Library, 1990).
  32. T. Wilson and A. R. Carlini, "Size of the detector in confocal imaging systems," Opt. Lett. 12, 227-229 (1987).
    [CrossRef] [PubMed]
  33. E. Marx and G. W. Mulholland, "Size and refractive index determination of single polystyrene spheres," J. Res. Natl. Bur. Stand. 88, 321-338 (1983).
  34. J. S. Bonifacino, M. Dasso, J. B. Hartford, J. Lippincott-Schwartz, and K. M. Yamada, Current Protocols in Cell Biology (Wiley, 2001).
    [CrossRef]
  35. G. Monika, G. Pal, and J. S. Adam, "Epithelia and bacterial metalloproteinases and their inhibitor in H. pylori infection of human gastric cells," Am. J. Physiol. Gastrointest. Liver Physiol. 281, 823-832 (2001).
  36. M. I. Mishchenko, J. W. Hovenier, and L. D. Travis, Light Scattering by Nonspherical Particles (Academic, 2000).

2006 (2)

2005 (8)

C. Joo, T. Akkin, B. Cense, B. H. Park, and J. F. de Boer, "Spectral-domain optical coherence phase microscopy for quantitative phase-contrast imaging," Opt. Lett. 30, 2131-2133 (2005).
[CrossRef] [PubMed]

Y. Liu, X. Li, Y. L. Kim, and V. Backman, "Elastic backscattering spectroscopic microscopy," Opt. Lett. 30, 2445-2447 (2005).
[CrossRef] [PubMed]

J. W. Lichtman and J.-A. Conchello, "Fluorescence microscopy," Nat. Methods 2, 910-919 (2005).
[CrossRef] [PubMed]

N. C. Shaner, P. A. Steinbach, and R. Y. Tsien, "A guide to choosing fluorescent proteins," Nat. Methods 2, 905-909 (2005).
[CrossRef] [PubMed]

F. Helmchen and W. Denk, "Deep tissue two-photon microscopy," Nat. Methods 2, 932-940 (2005).
[CrossRef] [PubMed]

E. L. Evan, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef]

G. Schuele, E. Vitkin, P. Huie, D. Palanker, and L. T. Perelman, "Optical detection of the reaction of organelles to cellular stress," J. Biomed. Opt. 10, 051404-1-8 (2005).
[PubMed]

J.-A. Conchello and J. W. Lichtman, "Optical sectioning microscopy," Nat. Methods 2, 920-931 (2005).
[CrossRef] [PubMed]

2003 (6)

J. Lippincott-Schwartz and G. H. Patterson, "Development and use of fluorescent protein markers in living cells," Science 300, 87-91 (2003).
[CrossRef] [PubMed]

T. Zimmermann, J. Rietdorf, and R. Pepperkok, "Spectral imaging and its applications in live cell microscopy," FEBS Lett. 546, 87-92 (2003).
[CrossRef] [PubMed]

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, "Noninvasive sizing of subcellular organelles with light-scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 9, 267-276 (2003).
[CrossRef]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

J. G. Fujimoto, "Optical coherence tomography for ultrahigh resolution in vivo imaging," Nature Biotechnol. 21, 1361-1367 (2003).
[CrossRef]

W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nature Biotechnol. 21, 1369-1377 (2003).
[CrossRef]

2002 (2)

J. X. Cheng, A. Volkmer, and X. S. Xie, "Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy," J. Opt. Soc. Am. B 19, 1363-1375 (2002).
[CrossRef]

A. Zoumi, A. Yeh, and B. J. Tromberg, "Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence," Proc. Natl. Acad. Sci. U.S.A. 99, 11014-1019 (2002).
[CrossRef] [PubMed]

2001 (3)

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Geogakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, "Measuring cellular structure at submicrometer scale with light scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 7, 887-893 (2001).
[CrossRef]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, "Imaging human epithelial properties with polarized light-scattering spectroscopy," Nature Med. 7, 1245-1248 (2001).
[CrossRef] [PubMed]

G. Monika, G. Pal, and J. S. Adam, "Epithelia and bacterial metalloproteinases and their inhibitor in H. pylori infection of human gastric cells," Am. J. Physiol. Gastrointest. Liver Physiol. 281, 823-832 (2001).

2000 (3)

J. F. Aguilar, M. Lera, and C. J. R. Sheppard, "Imaging of spheres and surface profiling by confocal microscopy," Appl. Opt. 39, 4621-4628 (2000).
[CrossRef]

M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
[CrossRef] [PubMed]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

1999 (1)

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structure in situ," IEEE J. Sel. Top. Quantum Electron. 5, 1019-1026 (1999).
[CrossRef]

1998 (1)

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

1997 (1)

I. J. Bigio and J. R. Mourant, "Ultraviolet and visible spectroscopies for tissue diagnostics: fluorescence spectroscopy and elastic-scattering spectroscopy," Phys. Med. Biol. 42, 803-814 (1997).
[CrossRef] [PubMed]

1996 (1)

1987 (1)

1986 (1)

R. J. Hanson, "Least squares with bounds and linear constraints," SIAM (Soc. Ind. Appl. Math.) J. Sci. Stat. Comput. 7, 826-834 (1986).
[CrossRef]

1983 (1)

E. Marx and G. W. Mulholland, "Size and refractive index determination of single polystyrene spheres," J. Res. Natl. Bur. Stand. 88, 321-338 (1983).

Adam, J. S.

G. Monika, G. Pal, and J. S. Adam, "Epithelia and bacterial metalloproteinases and their inhibitor in H. pylori infection of human gastric cells," Am. J. Physiol. Gastrointest. Liver Physiol. 281, 823-832 (2001).

Aguilar, J. F.

Akkin, T.

Arendt, J. T.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

Backman, V.

Y. Liu, X. Li, Y. L. Kim, and V. Backman, "Elastic backscattering spectroscopic microscopy," Opt. Lett. 30, 2445-2447 (2005).
[CrossRef] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Geogakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, "Measuring cellular structure at submicrometer scale with light scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 7, 887-893 (2001).
[CrossRef]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, "Imaging human epithelial properties with polarized light-scattering spectroscopy," Nature Med. 7, 1245-1248 (2001).
[CrossRef] [PubMed]

M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
[CrossRef] [PubMed]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structure in situ," IEEE J. Sel. Top. Quantum Electron. 5, 1019-1026 (1999).
[CrossRef]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Badizadegan, K.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, "Imaging human epithelial properties with polarized light-scattering spectroscopy," Nature Med. 7, 1245-1248 (2001).
[CrossRef] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Geogakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, "Measuring cellular structure at submicrometer scale with light scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 7, 887-893 (2001).
[CrossRef]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structure in situ," IEEE J. Sel. Top. Quantum Electron. 5, 1019-1026 (1999).
[CrossRef]

Bigio, I. J.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, "Noninvasive sizing of subcellular organelles with light-scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 9, 267-276 (2003).
[CrossRef]

I. J. Bigio and J. R. Mourant, "Ultraviolet and visible spectroscopies for tissue diagnostics: fluorescence spectroscopy and elastic-scattering spectroscopy," Phys. Med. Biol. 42, 803-814 (1997).
[CrossRef] [PubMed]

Bonifacino, J. S.

J. S. Bonifacino, M. Dasso, J. B. Hartford, J. Lippincott-Schwartz, and K. M. Yamada, Current Protocols in Cell Biology (Wiley, 2001).
[CrossRef]

Boone, C. W.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Geogakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, "Measuring cellular structure at submicrometer scale with light scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 7, 887-893 (2001).
[CrossRef]

Boppart, S. A.

Boseck, S.

Briggs, A.

Brown, J. C.

I. J. D. Craig and J. C. Brown, Inverse Problems in Astronomy: a Guide to Inversion Strategies for Remotely Sensed Data (Hilger, 1986).

Carlini, A. R.

Cense, B.

Cheng, J. X.

Christie, R.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

Cipolloni, P. B.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, "Noninvasive sizing of subcellular organelles with light-scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 9, 267-276 (2003).
[CrossRef]

Conchello, J.-A.

J. W. Lichtman and J.-A. Conchello, "Fluorescence microscopy," Nat. Methods 2, 910-919 (2005).
[CrossRef] [PubMed]

J.-A. Conchello and J. W. Lichtman, "Optical sectioning microscopy," Nat. Methods 2, 920-931 (2005).
[CrossRef] [PubMed]

Cote, D.

E. L. Evan, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef]

Craig, I. J. D.

I. J. D. Craig and J. C. Brown, Inverse Problems in Astronomy: a Guide to Inversion Strategies for Remotely Sensed Data (Hilger, 1986).

Crawford, J. M.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
[CrossRef] [PubMed]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Dam, J. V.

M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
[CrossRef] [PubMed]

Dasari, R. R.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, "Imaging human epithelial properties with polarized light-scattering spectroscopy," Nature Med. 7, 1245-1248 (2001).
[CrossRef] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Geogakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, "Measuring cellular structure at submicrometer scale with light scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 7, 887-893 (2001).
[CrossRef]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structure in situ," IEEE J. Sel. Top. Quantum Electron. 5, 1019-1026 (1999).
[CrossRef]

Dasso, M.

J. S. Bonifacino, M. Dasso, J. B. Hartford, J. Lippincott-Schwartz, and K. M. Yamada, Current Protocols in Cell Biology (Wiley, 2001).
[CrossRef]

de Boer, J. F.

Denk, W.

F. Helmchen and W. Denk, "Deep tissue two-photon microscopy," Nat. Methods 2, 932-940 (2005).
[CrossRef] [PubMed]

Dimarzio, C. A.

Dwyer, P. J.

Evan, E. L.

E. L. Evan, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef]

Fang, H.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, "Noninvasive sizing of subcellular organelles with light-scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 9, 267-276 (2003).
[CrossRef]

Feld, M. S.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, "Imaging human epithelial properties with polarized light-scattering spectroscopy," Nature Med. 7, 1245-1248 (2001).
[CrossRef] [PubMed]

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Geogakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, "Measuring cellular structure at submicrometer scale with light scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 7, 887-893 (2001).
[CrossRef]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structure in situ," IEEE J. Sel. Top. Quantum Electron. 5, 1019-1026 (1999).
[CrossRef]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Fitzmaurice, M.

M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
[CrossRef] [PubMed]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

Fox, W. J.

Freedman, S. D.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, "Noninvasive sizing of subcellular organelles with light-scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 9, 267-276 (2003).
[CrossRef]

Fujimoto, J. G.

J. G. Fujimoto, "Optical coherence tomography for ultrahigh resolution in vivo imaging," Nature Biotechnol. 21, 1361-1367 (2003).
[CrossRef]

Geogakoudi, I.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Geogakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, "Measuring cellular structure at submicrometer scale with light scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 7, 887-893 (2001).
[CrossRef]

Georgakoudi, I.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, "Imaging human epithelial properties with polarized light-scattering spectroscopy," Nature Med. 7, 1245-1248 (2001).
[CrossRef] [PubMed]

Gopal, V.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Geogakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, "Measuring cellular structure at submicrometer scale with light scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 7, 887-893 (2001).
[CrossRef]

Gurjar, R.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Geogakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, "Measuring cellular structure at submicrometer scale with light scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 7, 887-893 (2001).
[CrossRef]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structure in situ," IEEE J. Sel. Top. Quantum Electron. 5, 1019-1026 (1999).
[CrossRef]

Gurjar, R. S.

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, "Imaging human epithelial properties with polarized light-scattering spectroscopy," Nature Med. 7, 1245-1248 (2001).
[CrossRef] [PubMed]

Hamano, T.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Hancewicz, T. M.

L. H. Laiho, S. Pelet, T. M. Hancewicz, P. D. Kaplan, and P. T. C. So, "Two-photon 3D mapping of ex vivo human skin endogenous fluorescence species based on fluorescence emission spectra," J. Biomed. Opt. 10, 024016 (2005).
[PubMed]

Hanlon, E. B.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, "Noninvasive sizing of subcellular organelles with light-scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 9, 267-276 (2003).
[CrossRef]

Hanson, R. J.

R. J. Hanson, "Least squares with bounds and linear constraints," SIAM (Soc. Ind. Appl. Math.) J. Sci. Stat. Comput. 7, 826-834 (1986).
[CrossRef]

R. J. Hanson, A Cyclic Reduction Solver for the IMSL Mathematics Library Report 9002 (International Mathematical and Statistical Library, 1990).

Hartford, J. B.

J. S. Bonifacino, M. Dasso, J. B. Hartford, J. Lippincott-Schwartz, and K. M. Yamada, Current Protocols in Cell Biology (Wiley, 2001).
[CrossRef]

Helmchen, F.

F. Helmchen and W. Denk, "Deep tissue two-photon microscopy," Nat. Methods 2, 932-940 (2005).
[CrossRef] [PubMed]

Hovenier, J. W.

M. I. Mishchenko, J. W. Hovenier, and L. D. Travis, Light Scattering by Nonspherical Particles (Academic, 2000).

Huie, P.

G. Schuele, E. Vitkin, P. Huie, D. Palanker, and L. T. Perelman, "Optical detection of the reaction of organelles to cellular stress," J. Biomed. Opt. 10, 051404-1-8 (2005).
[PubMed]

Hyman, B. T.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

Itzkan, I.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, "Noninvasive sizing of subcellular organelles with light-scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 9, 267-276 (2003).
[CrossRef]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, "Imaging human epithelial properties with polarized light-scattering spectroscopy," Nature Med. 7, 1245-1248 (2001).
[CrossRef] [PubMed]

M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
[CrossRef] [PubMed]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structure in situ," IEEE J. Sel. Top. Quantum Electron. 5, 1019-1026 (1999).
[CrossRef]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Joo, C.

Kabani, S.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

Kalashnikov, M.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Geogakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, "Measuring cellular structure at submicrometer scale with light scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 7, 887-893 (2001).
[CrossRef]

Kaplan, P. D.

L. H. Laiho, S. Pelet, T. M. Hancewicz, P. D. Kaplan, and P. T. C. So, "Two-photon 3D mapping of ex vivo human skin endogenous fluorescence species based on fluorescence emission spectra," J. Biomed. Opt. 10, 024016 (2005).
[PubMed]

Kim, Y. L.

Kimerer, L. M.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, "Noninvasive sizing of subcellular organelles with light-scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 9, 267-276 (2003).
[CrossRef]

Kline, E.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

Laiho, L. H.

L. H. Laiho, S. Pelet, T. M. Hancewicz, P. D. Kaplan, and P. T. C. So, "Two-photon 3D mapping of ex vivo human skin endogenous fluorescence species based on fluorescence emission spectra," J. Biomed. Opt. 10, 024016 (2005).
[PubMed]

Lera, M.

Levin, H. S.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

Li, X.

Lichtman, J. W.

J.-A. Conchello and J. W. Lichtman, "Optical sectioning microscopy," Nat. Methods 2, 920-931 (2005).
[CrossRef] [PubMed]

J. W. Lichtman and J.-A. Conchello, "Fluorescence microscopy," Nat. Methods 2, 910-919 (2005).
[CrossRef] [PubMed]

Lima, C.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Lin, C. P.

E. L. Evan, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef]

Lippincott-Schwartz, J.

J. Lippincott-Schwartz and G. H. Patterson, "Development and use of fluorescent protein markers in living cells," Science 300, 87-91 (2003).
[CrossRef] [PubMed]

J. S. Bonifacino, M. Dasso, J. B. Hartford, J. Lippincott-Schwartz, and K. M. Yamada, Current Protocols in Cell Biology (Wiley, 2001).
[CrossRef]

Liu, Y.

Luo, W.

Manoharan, R.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Marx, E.

E. Marx and G. W. Mulholland, "Size and refractive index determination of single polystyrene spheres," J. Res. Natl. Bur. Stand. 88, 321-338 (1983).

McGillican, T.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

Mishchenko, M. I.

M. I. Mishchenko, J. W. Hovenier, and L. D. Travis, Light Scattering by Nonspherical Particles (Academic, 2000).

Monika, G.

G. Monika, G. Pal, and J. S. Adam, "Epithelia and bacterial metalloproteinases and their inhibitor in H. pylori infection of human gastric cells," Am. J. Physiol. Gastrointest. Liver Physiol. 281, 823-832 (2001).

Mourant, J. R.

I. J. Bigio and J. R. Mourant, "Ultraviolet and visible spectroscopies for tissue diagnostics: fluorescence spectroscopy and elastic-scattering spectroscopy," Phys. Med. Biol. 42, 803-814 (1997).
[CrossRef] [PubMed]

Mueller, M.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Geogakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, "Measuring cellular structure at submicrometer scale with light scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 7, 887-893 (2001).
[CrossRef]

Mulholland, G. W.

E. Marx and G. W. Mulholland, "Size and refractive index determination of single polystyrene spheres," J. Res. Natl. Bur. Stand. 88, 321-338 (1983).

Muller, M. G.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

Nikitin, A. Y.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

Nusrat, A.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Ollero, M.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, "Noninvasive sizing of subcellular organelles with light-scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 9, 267-276 (2003).
[CrossRef]

Pal, G.

G. Monika, G. Pal, and J. S. Adam, "Epithelia and bacterial metalloproteinases and their inhibitor in H. pylori infection of human gastric cells," Am. J. Physiol. Gastrointest. Liver Physiol. 281, 823-832 (2001).

Palanker, D.

G. Schuele, E. Vitkin, P. Huie, D. Palanker, and L. T. Perelman, "Optical detection of the reaction of organelles to cellular stress," J. Biomed. Opt. 10, 051404-1-8 (2005).
[PubMed]

Park, B. H.

Patterson, G. H.

J. Lippincott-Schwartz and G. H. Patterson, "Development and use of fluorescent protein markers in living cells," Science 300, 87-91 (2003).
[CrossRef] [PubMed]

Pelet, S.

L. H. Laiho, S. Pelet, T. M. Hancewicz, P. D. Kaplan, and P. T. C. So, "Two-photon 3D mapping of ex vivo human skin endogenous fluorescence species based on fluorescence emission spectra," J. Biomed. Opt. 10, 024016 (2005).
[PubMed]

Pepperkok, R.

T. Zimmermann, J. Rietdorf, and R. Pepperkok, "Spectral imaging and its applications in live cell microscopy," FEBS Lett. 546, 87-92 (2003).
[CrossRef] [PubMed]

Perelman, L. T.

G. Schuele, E. Vitkin, P. Huie, D. Palanker, and L. T. Perelman, "Optical detection of the reaction of organelles to cellular stress," J. Biomed. Opt. 10, 051404-1-8 (2005).
[PubMed]

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, "Noninvasive sizing of subcellular organelles with light-scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 9, 267-276 (2003).
[CrossRef]

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, "Imaging human epithelial properties with polarized light-scattering spectroscopy," Nature Med. 7, 1245-1248 (2001).
[CrossRef] [PubMed]

M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
[CrossRef] [PubMed]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structure in situ," IEEE J. Sel. Top. Quantum Electron. 5, 1019-1026 (1999).
[CrossRef]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Potma, E. O.

E. L. Evan, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef]

Puoris'haag, M.

E. L. Evan, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef]

Rajadhyaksha, M.

Ralston, T. S.

Rietdorf, J.

T. Zimmermann, J. Rietdorf, and R. Pepperkok, "Spectral imaging and its applications in live cell microscopy," FEBS Lett. 546, 87-92 (2003).
[CrossRef] [PubMed]

Schuele, G.

G. Schuele, E. Vitkin, P. Huie, D. Palanker, and L. T. Perelman, "Optical detection of the reaction of organelles to cellular stress," J. Biomed. Opt. 10, 051404-1-8 (2005).
[PubMed]

Seiler, M.

M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
[CrossRef] [PubMed]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Shaner, N. C.

N. C. Shaner, P. A. Steinbach, and R. Y. Tsien, "A guide to choosing fluorescent proteins," Nat. Methods 2, 905-909 (2005).
[CrossRef] [PubMed]

Shapshay, S.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

Sheppard, C. J. R.

Shields, S.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Shields, S. J.

M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
[CrossRef] [PubMed]

So, P. T. C.

L. H. Laiho, S. Pelet, T. M. Hancewicz, P. D. Kaplan, and P. T. C. So, "Two-photon 3D mapping of ex vivo human skin endogenous fluorescence species based on fluorescence emission spectra," J. Biomed. Opt. 10, 024016 (2005).
[PubMed]

Steinbach, P. A.

N. C. Shaner, P. A. Steinbach, and R. Y. Tsien, "A guide to choosing fluorescent proteins," Nat. Methods 2, 905-909 (2005).
[CrossRef] [PubMed]

Tan, W.

Travis, L. D.

M. I. Mishchenko, J. W. Hovenier, and L. D. Travis, Light Scattering by Nonspherical Particles (Academic, 2000).

Tromberg, B. J.

A. Zoumi, A. Yeh, and B. J. Tromberg, "Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence," Proc. Natl. Acad. Sci. U.S.A. 99, 11014-1019 (2002).
[CrossRef] [PubMed]

Tsien, R. Y.

N. C. Shaner, P. A. Steinbach, and R. Y. Tsien, "A guide to choosing fluorescent proteins," Nat. Methods 2, 905-909 (2005).
[CrossRef] [PubMed]

Valdez, T.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

Van Dam, J.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Vinegoni, C.

Vitkin, E.

G. Schuele, E. Vitkin, P. Huie, D. Palanker, and L. T. Perelman, "Optical detection of the reaction of organelles to cellular stress," J. Biomed. Opt. 10, 051404-1-8 (2005).
[PubMed]

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, "Noninvasive sizing of subcellular organelles with light-scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 9, 267-276 (2003).
[CrossRef]

Volkmer, A.

Wallace, M.

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Wallace, M. B.

M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
[CrossRef] [PubMed]

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

Wax, A.

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Geogakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, "Measuring cellular structure at submicrometer scale with light scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 7, 887-893 (2001).
[CrossRef]

Webb, W. W.

W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nature Biotechnol. 21, 1369-1377 (2003).
[CrossRef]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

Weise, W.

Williams, R. M.

W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nature Biotechnol. 21, 1369-1377 (2003).
[CrossRef]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

Wilson, T.

Xie, X. S.

E. L. Evan, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef]

J. X. Cheng, A. Volkmer, and X. S. Xie, "Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy," J. Opt. Soc. Am. B 19, 1363-1375 (2002).
[CrossRef]

Xu, C.

Yamada, K. M.

J. S. Bonifacino, M. Dasso, J. B. Hartford, J. Lippincott-Schwartz, and K. M. Yamada, Current Protocols in Cell Biology (Wiley, 2001).
[CrossRef]

Yeh, A.

A. Zoumi, A. Yeh, and B. J. Tromberg, "Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence," Proc. Natl. Acad. Sci. U.S.A. 99, 11014-1019 (2002).
[CrossRef] [PubMed]

Zaman, M. M.

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, "Noninvasive sizing of subcellular organelles with light-scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 9, 267-276 (2003).
[CrossRef]

Zavislan, J. M.

Zhang, Q.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

Zimmermann, T.

T. Zimmermann, J. Rietdorf, and R. Pepperkok, "Spectral imaging and its applications in live cell microscopy," FEBS Lett. 546, 87-92 (2003).
[CrossRef] [PubMed]

Zinin, P.

Zipfel, W. R.

W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nature Biotechnol. 21, 1369-1377 (2003).
[CrossRef]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

Zonios, G.

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Zoumi, A.

A. Zoumi, A. Yeh, and B. J. Tromberg, "Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence," Proc. Natl. Acad. Sci. U.S.A. 99, 11014-1019 (2002).
[CrossRef] [PubMed]

Am. J. Physiol. Gastrointest. Liver Physiol. (1)

G. Monika, G. Pal, and J. S. Adam, "Epithelia and bacterial metalloproteinases and their inhibitor in H. pylori infection of human gastric cells," Am. J. Physiol. Gastrointest. Liver Physiol. 281, 823-832 (2001).

Appl. Opt. (1)

FEBS Lett. (1)

T. Zimmermann, J. Rietdorf, and R. Pepperkok, "Spectral imaging and its applications in live cell microscopy," FEBS Lett. 546, 87-92 (2003).
[CrossRef] [PubMed]

Gastroenterology (1)

M. B. Wallace, L. T. Perelman, V. Backman, J. M. Crawford, M. Fitzmaurice, M. Seiler, K. Badizadegan, S. J. Shields, I. Itzkan, R. R. Dasari, J. V. Dam, and M. S. Feld, "Endoscopic detection of dysplasia in patients with Barrett's esophagus using light scattering spectroscopy," Gastroenterology 119, 677-682 (2000).
[CrossRef] [PubMed]

IEEE J. Sel. Top. Quantum Electron. (3)

V. Backman, V. Gopal, M. Kalashnikov, K. Badizadegan, R. Gurjar, A. Wax, I. Geogakoudi, M. Mueller, C. W. Boone, R. R. Dasari, and M. S. Feld, "Measuring cellular structure at submicrometer scale with light scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 7, 887-893 (2001).
[CrossRef]

H. Fang, M. Ollero, E. Vitkin, L. M. Kimerer, P. B. Cipolloni, M. M. Zaman, S. D. Freedman, I. J. Bigio, I. Itzkan, E. B. Hanlon, and L. T. Perelman, "Noninvasive sizing of subcellular organelles with light-scattering spectroscopy," IEEE J. Sel. Top. Quantum Electron. 9, 267-276 (2003).
[CrossRef]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, "Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structure in situ," IEEE J. Sel. Top. Quantum Electron. 5, 1019-1026 (1999).
[CrossRef]

J. Biomed. Opt. (2)

G. Schuele, E. Vitkin, P. Huie, D. Palanker, and L. T. Perelman, "Optical detection of the reaction of organelles to cellular stress," J. Biomed. Opt. 10, 051404-1-8 (2005).
[PubMed]

L. H. Laiho, S. Pelet, T. M. Hancewicz, P. D. Kaplan, and P. T. C. So, "Two-photon 3D mapping of ex vivo human skin endogenous fluorescence species based on fluorescence emission spectra," J. Biomed. Opt. 10, 024016 (2005).
[PubMed]

J. Opt. Soc. Am. B (1)

J. Res. Natl. Bur. Stand. (1)

E. Marx and G. W. Mulholland, "Size and refractive index determination of single polystyrene spheres," J. Res. Natl. Bur. Stand. 88, 321-338 (1983).

J. Sci. Stat. Comput. (1)

R. J. Hanson, "Least squares with bounds and linear constraints," SIAM (Soc. Ind. Appl. Math.) J. Sci. Stat. Comput. 7, 826-834 (1986).
[CrossRef]

Nat. Methods (4)

N. C. Shaner, P. A. Steinbach, and R. Y. Tsien, "A guide to choosing fluorescent proteins," Nat. Methods 2, 905-909 (2005).
[CrossRef] [PubMed]

F. Helmchen and W. Denk, "Deep tissue two-photon microscopy," Nat. Methods 2, 932-940 (2005).
[CrossRef] [PubMed]

J.-A. Conchello and J. W. Lichtman, "Optical sectioning microscopy," Nat. Methods 2, 920-931 (2005).
[CrossRef] [PubMed]

J. W. Lichtman and J.-A. Conchello, "Fluorescence microscopy," Nat. Methods 2, 910-919 (2005).
[CrossRef] [PubMed]

Nature (1)

V. Backman, M. B. Wallace, L. T. Perelman, J. T. Arendt, R. Gurjar, M. G. Muller, Q. Zhang, G. Zonios, E. Kline, T. McGillican, S. Shapshay, T. Valdez, K. Badizadegan, J. M. Crawford, M. Fitzmaurice, S. Kabani, H. S. Levin, M. Seiler, R. R. Dasari, I. Itzkan, J. Van Dam, and M. S. Feld, "Detection of preinvasive cancer cells," Nature 406, 35-36 (2000).
[CrossRef] [PubMed]

Nature Biotechnol. (2)

J. G. Fujimoto, "Optical coherence tomography for ultrahigh resolution in vivo imaging," Nature Biotechnol. 21, 1361-1367 (2003).
[CrossRef]

W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nature Biotechnol. 21, 1369-1377 (2003).
[CrossRef]

Nature Med. (1)

R. S. Gurjar, V. Backman, L. T. Perelman, I. Georgakoudi, K. Badizadegan, I. Itzkan, R. R. Dasari, and M. S. Feld, "Imaging human epithelial properties with polarized light-scattering spectroscopy," Nature Med. 7, 1245-1248 (2001).
[CrossRef] [PubMed]

Opt. Lett. (6)

Phys. Med. Biol. (1)

I. J. Bigio and J. R. Mourant, "Ultraviolet and visible spectroscopies for tissue diagnostics: fluorescence spectroscopy and elastic-scattering spectroscopy," Phys. Med. Biol. 42, 803-814 (1997).
[CrossRef] [PubMed]

Phys. Rev. Lett. (1)

L. T. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, "Observation of period find structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution," Phys. Rev. Lett. 80, 627-630 (1998).
[CrossRef]

Proc. Natl. Acad. Sci. U.S.A. (3)

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

E. L. Evan, E. O. Potma, M. Puoris'haag, D. Cote, C. P. Lin, and X. S. Xie, "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," Proc. Natl. Acad. Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef]

A. Zoumi, A. Yeh, and B. J. Tromberg, "Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence," Proc. Natl. Acad. Sci. U.S.A. 99, 11014-1019 (2002).
[CrossRef] [PubMed]

Science (1)

J. Lippincott-Schwartz and G. H. Patterson, "Development and use of fluorescent protein markers in living cells," Science 300, 87-91 (2003).
[CrossRef] [PubMed]

Other (4)

I. J. D. Craig and J. C. Brown, Inverse Problems in Astronomy: a Guide to Inversion Strategies for Remotely Sensed Data (Hilger, 1986).

R. J. Hanson, A Cyclic Reduction Solver for the IMSL Mathematics Library Report 9002 (International Mathematical and Statistical Library, 1990).

J. S. Bonifacino, M. Dasso, J. B. Hartford, J. Lippincott-Schwartz, and K. M. Yamada, Current Protocols in Cell Biology (Wiley, 2001).
[CrossRef]

M. I. Mishchenko, J. W. Hovenier, and L. D. Travis, Light Scattering by Nonspherical Particles (Academic, 2000).

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (7)

Fig. 1
Fig. 1

Comparison of a standard LSS spectrum with two CLASS spectra calculated using Eq. (6). The spectra are presented on a composite graph of the differential scattering coefficients for spherical particles in range of diameters from 20 to 900   nm and wavelength range from 400 to 800   nm versus inverse size parameter 1 / x = λ / ( 2 π a ) . Region 1 shows the spectra over the wavelength range from 400 to 800   nm for 900   nm particles. Regions 2 and 3 show the spectra over the same wavelength range for 300   nm particles and for 100   nm particles, respectively. All the spectra are calculated for the case of a spherical particle with a relative refractive index of n = 1.06 surrounded by the medium with a refractive index equal to 1.36. The dotted curve is a LSS spectrum with a scattering angle of 180°, the dashed curve is a CLASS spectrum with a NA of 0.5, and the solid curve is a CLASS spectrum with a NA of 0.75. On the right side of the graph all three curves converge to a 1 / λ 4 Rayleigh scattering behavior.

Fig. 2
Fig. 2

(a) Schematic of the prototype CLASS microscope, (b) cell imaging chamber, (c) depth sectioning at three wavelengths.

Fig. 3
Fig. 3

(a) CLASS spectra and (b) extracted size distributions for polystyrene beads in water and glycerol. Dots, experimental data; solid curves, spectra reconstructed from the theoretical model; points, calculated values; dotted curves, a guide for the eye.

Fig. 4
Fig. 4

(a) Image of a 771   nm diameter polystyrene bead at a wavelength of 600   nm , (b) comparison of the CLASS spectrum collected at the center of the bead (dotted curve) with calculated spectrum (solid curve), (c) reconstructed sizes of 12 individual beads. The CLASS measurements are all within 10   nm of the manufacturer's specified sizes.

Fig. 5
Fig. 5

Mixture of two types of organelle, microsomes and peroxisomes. (a) Electron micrograph of the mixture taken at 63,492 magnification and (b) comparison of the distribution reconstructed with CLASS microscopy and with EM morphometry performed on the same fraction. Both distributions clearly show two groups of organelle, microsomes and peroxisomes.

Fig. 6
Fig. 6

(a) Unprocessed cross-sectional images of two 16HBE14o-human bronchial epithelial cells collected with the CLASS microscope at 640   nm wavelength. The left cell is a normal untreated cell and the right cell was treated with DHA for 24 h and is undergoing apoptosis. (b) Images of the same cells reconstructed from the CLASS microscope spectra. The diameters of the spheres in the image represent the reconstructed sizes of the individual organelles, and the gray scale represents their refractive indices. (c) CLASS spectra taken from two different locations in a cell: dotted curves, experimental results; solid and dashed curves, theoretical fits. The spectra show oscillations with periodicity related to the size of the organelle in the confocal volume.

Fig. 7
Fig. 7

(a) Cross-sectional image of an AGS gastric epithelial cell reconstructed from the CLASS microscope spectra. Mucin granules are clearly seen. (b) Fluorescence-based image of the same type of cell from Ref. [35] with mucin granules labeled by a FITC antibody.

Tables (1)

Tables Icon

Table 1 Size Distribution Parameters for Polystyrene Beads

Equations (7)

Equations on this page are rendered with MathJax. Learn more.

S ( λ , NA ) = 0 I ( λ δ , n , NA ) N ( δ ) d δ + ε ( λ ) ,
S ^ ( λ , NA ) = C R λ 4 N R + δ R δ max I ^ ( λ δ , n , NA ) N ^ ( δ ) + E ^ ( λ ) ,
S ^ = I ^ N ^ + E ^ .
A ( R ) = Ω Ω P ( k ^ ) P ( k ^ ) exp ( i 2 π λ R ( k ^ k ^ ) ) × f ( δ λ , n , k ^ , k ^ ) d k ^ d k ^ ,
A ( 0 ) = Ω Ω P ( k ^ ) P ( k ^ ) f ( δ λ , n , k ^ , k ^ ) d k ^ d k ^ .
I ( δ λ , n , NA ) = | A ( 0 ) | 2 I 0 = | Ω Ω P ( k ^ ) P ( k ^ ) f ( δ λ , n , k ^ , k ^ ) d k ^ d k ^ | 2 | Ω Ω P ( k ^ ) P ( k ^ ) d k ^ d k ^ | 2 .
I ^ T S ^ ( C ^ + α k H ^ ) N ^ min N ^ 0 ,

Metrics