Abstract

Direct Raman imaging techniques are demonstrated to study the drug distribution in living cells. The advantage of Raman imaging is that no external markers are required, which simplifies the sample preparation and minimally disturbs the drug mechanism during imaging. The major challenge in Raman imaging is the weak Raman signal. In this study, we present a Raman image model to describe the degradation of Raman signals by imaging processes. Using this model, we demonstrate special-purpose image-processing algorithms to restore the Raman images. The processing techniques are then applied to visualize the anticancer agent paclitaxel in living MDA-435 breast cancer cells. Raman images were obtained from a cancer cell before, during, and after drug treatment. The paclitaxel distribution illustrated in these images is explained by means of the binding characteristics of the paclitaxel and its molecular target—the microtubules. This result demonstrates that direct Raman imaging is a promising tool to study the distribution of a drug in living cells.

© 2002 Optical Society of America

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. E. H. Kerns, S. E. Hill, D. J. Detlefsen, K. J. Volk, B. H. Long, J. Carboni, M. S. Lee, “Cellular uptake profile of paclitaxel using liquid chromatography tandem mass spectrometry,” Rapid Commun. Mass Spectrom. 12, 620–624 (1998).
    [CrossRef] [PubMed]
  2. M. Dellinger, M. Geze, R. Santus, E. Kohen, C. Kohen, J. G. Hirschberg, M. Monti, “Imaging of cells by autofluorescence: a new tool in the probing of biopharmaceutical effects at the intracellular level,” Biotechnol. Appl. Biochem. 28, 25–32 (1998).
    [PubMed]
  3. S. D. Baker, R. M. Wadkins, C. F. Stewart, W. T. Beck, M. K. Danks, “Cell cycle analysis of amount and distribution of nuclear DNA topoisomerase I as determined by fluorescence digital imaging microscopy,” Cytometry 19, 134–145 (1995).
    [CrossRef] [PubMed]
  4. C. S. Rao, J. J. Chu, R. S. Liu, Y. K. Lai, “Synthesis and evaluation of [14C]-labelled and fluorescent-tagged paclitaxel derivatives as new biological probes,” Bioorg. Medic. Chem. 6, 2193–2204 (1998).
    [CrossRef]
  5. H. Oyama, M. Nagane, S. Shibui, K. Nomura, K. Mukai, “Intracellular distribution of CPT-11 in CPT-11-resistant cells with confocal laser scanning microscopy,” Jpn. J. Clin. Oncol. 22, 331–334 (1992).
    [PubMed]
  6. J. H. de Lange, N. W. Schipper, G. J. Schuurhuis, T. K. ten Kate, T. H. van Heijningen, H. M. Pinedo, J. Lankelma, J. P. Baak, “Quantification by laser scan microscopy of intracellular doxorubicin distribution,” Cytometry 13, 571–576 (1992).
    [CrossRef] [PubMed]
  7. J. E. Gervasoni, S. Z. Fields, S. Krishna, M. A. Baker, M. Rosado, K. Thuraisamy, A. A. Hindenburg, R. N. Taub, “Subcellular distribution of daunorubicin in P-glycoprotein-positive and -negative drug-resistant cell lines using laser-assisted confocal microscopy,” Cancer Res. 51, 4955–4963 (1991).
    [PubMed]
  8. H. M. Coley, W. B. Amos, P. R. Twentyman, P. Workman, “Examination by laser scanning confocal fluorescence imaging microscopy of the subcellular localisation of anthracyclines in parent and multidrug resistant cell lines,” Br. J. Cancer 67, 1316–1323 (1993).
    [CrossRef] [PubMed]
  9. J. Itoh, R. Y. Osamura, K. Watanabe, “Subcellular visualization of light microscopic specimens by laser scanning microscopy and computer analysis: a new application of image analysis,” J. Histochem. Cytochem. 40, 955–967 (1992).
    [CrossRef] [PubMed]
  10. K. W. Woodburn, N. J. Vardaxis, J. S. Hill, A. H. Kaye, D. R. Phillips, “Subcellular localization of porphyrins using confocal laser scanning microscopy,” Photochem. Photobiol. 54, 725–732 (1991).
    [CrossRef] [PubMed]
  11. J. J. Andrew, T. M. Hancewicz, “Rapid analysis of Raman image data using two-way multivariate curve resolution,” Appl. Spectrosc. 52, 797–807 (1998).
    [CrossRef]
  12. N. J. C. Bauer, M. Motamedi, J. P. Wicksted, W. F. March, C. A. B. Webers, F. Hendrikse, “Non-invasive assessment of ocular pharmacokinetics using confocal Raman spectroscopy,” J. Ocular Pharmacol. Therapeutics 15, 123–134 (1999).
    [CrossRef]
  13. R. Manoharan, W. Yang, M. S. Feld, “Histochemical analysis of biological tissues using Raman spectroscopy,” Spectrochim. Acta Part A 52, 215–249 (1996).
    [CrossRef]
  14. K. Chinked, “Optical diagnostics image tissues and tumors,” Laser Focus World (February1996), 71–81.
  15. S. R. Goldstein, L. H. Kidder, T. M. Herne, I. W. Levin, E. N. Lewis, “The design and implementation of a high-fidelity Raman imaging microscope,” J. Microsc. (Oxford) 184, 35–45 (1996).
    [CrossRef]
  16. A. Feofanov, S. Sharonov, P. Valisa, E. Da Silva, I. Nabiev, M. Manfait, “A new confocal stigmatic spectrometer for micro-Raman and microfluorescence spectral imaging analysis: design and applications,” Rev. Sci. Instrum. 66, 3146–3158 (1995).
    [CrossRef]
  17. C. J. H. Brenan, I. W. Hunter, M. J. Korenberg, “Volumetric Raman spectral imaging with a confocal Raman microscope: image modalities and applications,” in Three-Dimensional Microscopy: Image Acquisition and Processing III, C. J. Cogswell, G. S. Kino, T. Wilson, eds., Proc. SPIE2655, 130–139 (1996).
    [CrossRef]
  18. M. D. Schaeberle, H. R. Morris, J. F. Turner, P. J. Treado, “Raman chemical imaging spectroscopy,” Anal. Chem. News Features, 175A–181A (1March1999).
  19. T. L. Freeman, S. E. Cope, M. R. Stringer, J. E. Cruse-Sawyer, S. B. Brown, D. N. Batchelder, K. Birbeck, “Investigation of the subcellular localization of zinc phthalocyanines by Raman mapping,” Appl. Spectrosc. 52, 1257–1263 (1998).
    [CrossRef]
  20. C. A. Drumm, M. D. Morris, “Microscopic Raman line-imaging with principal component analysis,” Appl. Spectrosc. 49, 1331–1337 (1995).
    [CrossRef]
  21. S. L. Zhang, J. A. Pezzuti, M. D. Morris, A. Appadwedula, C. M. Hsiung, M. A. Leugers, D. Bank, “Hyperspectral Raman line imaging of syndiotactic polystyrene crystallinity,” Appl. Spectrosc. 52, 1264–1268 (1998).
    [CrossRef]
  22. K. A. Christensen, M. D. Morris, “Hyperspectral Raman microscopic imaging using Powell lens line illumination,” Appl. Spectrosc. 52, 1145–1147 (1998).
    [CrossRef]
  23. G. J. Puppels, J. Greve, “Whole cell studies and tissue characterization by Raman spectroscopy,” in Biomedical Applications of Spectroscopy, C. Hester, ed. (Wiley, Chichester, England, 1996), pp. 1–47.
  24. M. D. Schaeberle, V. F. Kalasinsky, J. L. Luke, E. N. Lewis, I. W. Levin, P. J. Treado, “Raman chemical imaging: histopathology of inclusions in human breast tissue,” Anal. Chem. 68, 1829–1833 (1996).
    [CrossRef] [PubMed]
  25. H. R. Morris, C. C. Hoyt, P. Miller, P. J. Treado, “Liquid crystal tunable filter Raman chemical imaging,” Appl. Spectrosc. 50, 805–811 (1996).
    [CrossRef]
  26. H. R. Morris, C. C. Hoyt, P. J. Treado, “Imaging spectrometers for fluorescence and Raman microscopy: acousto-optic and liquid crystal tunable filters,” Appl. Spectrosc. 48, 857–866 (1994).
    [CrossRef]
  27. N. J. Kline, P. J. Treado, “Raman chemical imaging of breast tissue,” J. Raman Spectrosc. 28, 119–124 (1997).
    [CrossRef]
  28. C. Otto, C. J. de Grauw, J. J. Duindam, N. M. Sijtsema, J. Greve, “Applications of micro-Raman imaging in biomedical research,” J. Raman Spectrosc. 28, 143–150 (1997).
    [CrossRef]
  29. N. M. Sijtsema, S. D. Wouters, C. J. De Grauw, C. Otto, J. Greve, “Confocal direct imaging Raman microscope: design and applications in biology,” Appl. Spectrosc. 52, 348–355 (1998).
    [CrossRef]
  30. S. Y. Arzhantsev, A. Y. Chikishev, N. I. Koroteev, J. Greve, C. Otto, N. M. Sijtsema, “Localization study of Co-phthalocyanines in cells by Raman micro(spectro)scopy,” J. Raman Spectrosc. 30, 205–208 (1999).
    [CrossRef]
  31. H. Parekh, H. Simpkins, “The transport and binding of taxol,” General Pharm. 29, 167–172 (1997).
    [CrossRef]
  32. B. Z. Leal, M. L. Meltz, N. Mohan, J. Kuhn, T. J. Prihoda, T. S. Herman, “Interaction of hyperthermia with Taxol in human MCF-7 breast adenocarcinoma cells,” Int. J. Hyperthermia 15, 225–236 (1999).
    [CrossRef] [PubMed]
  33. A. M. Yvon, P. Wadsworth, M. A. Jordan, “Taxol suppresses dynamics of individual microtubules in living human tumor cells,” Mol. Biol. Cell 10, 947–959 (1999).
    [CrossRef] [PubMed]
  34. K. Torres, S. B. Horwitz, “Mechanisms of Taxol-induced cell death are concentration dependent,” Cancer Res. 58, 3620–3626 (1998).
    [PubMed]
  35. D. A. Agard, “Optical sectioning microscopy: cellular architecture in three dimensions,” Annu. Rev. Biophys. Bioeng. 13, 191–219 (1984).
    [CrossRef] [PubMed]
  36. K. R. Castleman, Digital Image Processing (Prentice-Hall, Englewood Cliffs, N.J., 1995).
  37. J. Ling, A. C. Bovik, “Smoothing low-SNR molecular images via anisotropic median-diffusion,” IEEE Trans. Med. Imaging 21, 377–384 (2002).
    [CrossRef] [PubMed]
  38. M. J. Black, G. Sapiro, D. H. Marimont, D. Heeger, “Robust anisotropic diffusion,” IEEE Trans. Image Process. 7, 421–432 (1998).
    [CrossRef]
  39. J. Ling, “Development of Raman imaging microscopy to visualize drug actions in living cells,” Ph.D. dissertation (The University of Texas at Austin, Austin, Tex., 2001), p. 150.
  40. W. H. Richardson, “Bayesian-based iterative method of image restoration,” J. Opt. Soc. Am. 62, 55–59 (1972).
    [CrossRef]
  41. Y. H. Lucy, “An iterative technique for the rectification of observed distributions,” Astron. J. 79, 745–765 (1974).
    [CrossRef]
  42. T. J. Holmes, Y. H. Liu, “Richardson-Lucy/maximum likelihood image restoration algorithm for fluorescence microscopy: further testing,” Appl. Opt. 28, 4930–4938 (1989).
    [CrossRef] [PubMed]
  43. G. M. P. van Kempen, L. J. van Vliet, “Background estimation in nonlinear image restoration,” J. Opt. Soc. Am. A 17, 425–433 (2000).
    [CrossRef]
  44. B. Alberts, D. Bray, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, “Microtubules,” in Essential Cell Biology: an Introduction to the Molecular Biology of the Cell (Garland, New York, 1998), pp. 518–529.
  45. E. E. Morrison, J. M. Askham, P. Clissold, A. F. Markham, D. M. Meredith, “The cellular distribution of the adenomatous polyposis coli tumour suppressor protein in neuroblastoma cells is regulated by microtubule dynamics,” Neuroscience (N.Y.) 81, 553–563 (1997).
    [CrossRef]
  46. J. J. Lemasters, G. J. Gores, A. L. Nieminen, T. L. Dawson, B. E. Wray, B. Herman, “Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells,” Environ. Health Perspect. 84, 83–94 (1990).
    [PubMed]
  47. W. Malorni, C. Fiorentini, S. Paradisi, M. Giuliano, P. Mastrantonio, G. Donelli, “Surface blebbing and cytoskeletal changes induced in vitro by toxin B from Clostridium difficile: an immunochemical and ultrastructural study,” Exp. Molecular Pathology 52, 340–356 (1990).
    [CrossRef]
  48. W. Malorni, F. Iosi, F. Mirabelli, G. Bellomo, “Cytoskeleton as a target in menadione-induced oxidative stress in cultured mammalian cells: alterations underlying surface bleb formation,” Chem. Biol. Interact. 80, 217–236 (1991).
    [CrossRef] [PubMed]
  49. M. S. Jurkowitz-Alexander, R. A. Altschuld, C. M. Hohl, J. D. Johnson, J. S. McDonald, T. D. Simmons, L. A. Horrocks, “Cell swelling, blebbing, and death are dependent on ATP depletion and independent of calcium during chemical hypoxia in a glial cell line (ROC-1),” J. Neurochem. 59, 344–352 (1992).
    [CrossRef] [PubMed]
  50. G. Zahrebelski, A. L. Nieminen, K. al-Ghoul, T. Qian, B. Herman, J. J. Lemasters, “Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: a laser scanning confocal microscopic study,” Hepatology 21, 1361–1372 (1995).
    [PubMed]
  51. S. M. Laster, J. M. Mackenzie, “Bleb formation and F-actin distribution during mitosis and tumor necrosis factor-induced apoptosis,” Microsc. Res. Tech. 34, 272–280 (1996).
    [CrossRef] [PubMed]
  52. P. T. Jain, B. F. Trump, “Human breast cancer cell growth inhibition and deregulation of [Ca2+]i by estradiol,” Anti-Cancer Drugs 8, 283–287 (1997).
    [CrossRef] [PubMed]
  53. T. Jones, “Present and future capabilities of molecular imaging techniques to understand brain function,” J. Psychopharmacol. 13, 324–329 (1999).
    [CrossRef]
  54. G. D. Sockalingum, A. Beljebbar, H. Morjani, J. F. Angiboust, M. Manfait, “Characterization of island films as surface-enhanced Raman spectroscopy substrates for detecting low antitumor drug concentrations at single cell level,” Biospectrosc. 4, S71–S78 (1998).
    [CrossRef]
  55. I. R. Nabiev, V. A. Savchenko, E. S. Efremov, “Surface-enhanced Raman spectra of aromatic amino acids and proteins adsorbed by silver hydrosols,” J. Raman Spectrosc. 14, 375–379 (1983).
    [CrossRef]
  56. I. R. Nabiev, K. V. Sokolov, O. N. Voloshin, “Surface-enhanced Raman spectroscopy of biomolecules III: Determination of the local destabilization regions in the double helix,” J. Raman Spectrosc. 21, 333–336 (1990).
    [CrossRef]

2002

J. Ling, A. C. Bovik, “Smoothing low-SNR molecular images via anisotropic median-diffusion,” IEEE Trans. Med. Imaging 21, 377–384 (2002).
[CrossRef] [PubMed]

2000

1999

M. D. Schaeberle, H. R. Morris, J. F. Turner, P. J. Treado, “Raman chemical imaging spectroscopy,” Anal. Chem. News Features, 175A–181A (1March1999).

S. Y. Arzhantsev, A. Y. Chikishev, N. I. Koroteev, J. Greve, C. Otto, N. M. Sijtsema, “Localization study of Co-phthalocyanines in cells by Raman micro(spectro)scopy,” J. Raman Spectrosc. 30, 205–208 (1999).
[CrossRef]

T. Jones, “Present and future capabilities of molecular imaging techniques to understand brain function,” J. Psychopharmacol. 13, 324–329 (1999).
[CrossRef]

N. J. C. Bauer, M. Motamedi, J. P. Wicksted, W. F. March, C. A. B. Webers, F. Hendrikse, “Non-invasive assessment of ocular pharmacokinetics using confocal Raman spectroscopy,” J. Ocular Pharmacol. Therapeutics 15, 123–134 (1999).
[CrossRef]

B. Z. Leal, M. L. Meltz, N. Mohan, J. Kuhn, T. J. Prihoda, T. S. Herman, “Interaction of hyperthermia with Taxol in human MCF-7 breast adenocarcinoma cells,” Int. J. Hyperthermia 15, 225–236 (1999).
[CrossRef] [PubMed]

A. M. Yvon, P. Wadsworth, M. A. Jordan, “Taxol suppresses dynamics of individual microtubules in living human tumor cells,” Mol. Biol. Cell 10, 947–959 (1999).
[CrossRef] [PubMed]

1998

K. Torres, S. B. Horwitz, “Mechanisms of Taxol-induced cell death are concentration dependent,” Cancer Res. 58, 3620–3626 (1998).
[PubMed]

C. S. Rao, J. J. Chu, R. S. Liu, Y. K. Lai, “Synthesis and evaluation of [14C]-labelled and fluorescent-tagged paclitaxel derivatives as new biological probes,” Bioorg. Medic. Chem. 6, 2193–2204 (1998).
[CrossRef]

E. H. Kerns, S. E. Hill, D. J. Detlefsen, K. J. Volk, B. H. Long, J. Carboni, M. S. Lee, “Cellular uptake profile of paclitaxel using liquid chromatography tandem mass spectrometry,” Rapid Commun. Mass Spectrom. 12, 620–624 (1998).
[CrossRef] [PubMed]

M. Dellinger, M. Geze, R. Santus, E. Kohen, C. Kohen, J. G. Hirschberg, M. Monti, “Imaging of cells by autofluorescence: a new tool in the probing of biopharmaceutical effects at the intracellular level,” Biotechnol. Appl. Biochem. 28, 25–32 (1998).
[PubMed]

G. D. Sockalingum, A. Beljebbar, H. Morjani, J. F. Angiboust, M. Manfait, “Characterization of island films as surface-enhanced Raman spectroscopy substrates for detecting low antitumor drug concentrations at single cell level,” Biospectrosc. 4, S71–S78 (1998).
[CrossRef]

M. J. Black, G. Sapiro, D. H. Marimont, D. Heeger, “Robust anisotropic diffusion,” IEEE Trans. Image Process. 7, 421–432 (1998).
[CrossRef]

T. L. Freeman, S. E. Cope, M. R. Stringer, J. E. Cruse-Sawyer, S. B. Brown, D. N. Batchelder, K. Birbeck, “Investigation of the subcellular localization of zinc phthalocyanines by Raman mapping,” Appl. Spectrosc. 52, 1257–1263 (1998).
[CrossRef]

S. L. Zhang, J. A. Pezzuti, M. D. Morris, A. Appadwedula, C. M. Hsiung, M. A. Leugers, D. Bank, “Hyperspectral Raman line imaging of syndiotactic polystyrene crystallinity,” Appl. Spectrosc. 52, 1264–1268 (1998).
[CrossRef]

K. A. Christensen, M. D. Morris, “Hyperspectral Raman microscopic imaging using Powell lens line illumination,” Appl. Spectrosc. 52, 1145–1147 (1998).
[CrossRef]

J. J. Andrew, T. M. Hancewicz, “Rapid analysis of Raman image data using two-way multivariate curve resolution,” Appl. Spectrosc. 52, 797–807 (1998).
[CrossRef]

N. M. Sijtsema, S. D. Wouters, C. J. De Grauw, C. Otto, J. Greve, “Confocal direct imaging Raman microscope: design and applications in biology,” Appl. Spectrosc. 52, 348–355 (1998).
[CrossRef]

1997

P. T. Jain, B. F. Trump, “Human breast cancer cell growth inhibition and deregulation of [Ca2+]i by estradiol,” Anti-Cancer Drugs 8, 283–287 (1997).
[CrossRef] [PubMed]

H. Parekh, H. Simpkins, “The transport and binding of taxol,” General Pharm. 29, 167–172 (1997).
[CrossRef]

N. J. Kline, P. J. Treado, “Raman chemical imaging of breast tissue,” J. Raman Spectrosc. 28, 119–124 (1997).
[CrossRef]

C. Otto, C. J. de Grauw, J. J. Duindam, N. M. Sijtsema, J. Greve, “Applications of micro-Raman imaging in biomedical research,” J. Raman Spectrosc. 28, 143–150 (1997).
[CrossRef]

E. E. Morrison, J. M. Askham, P. Clissold, A. F. Markham, D. M. Meredith, “The cellular distribution of the adenomatous polyposis coli tumour suppressor protein in neuroblastoma cells is regulated by microtubule dynamics,” Neuroscience (N.Y.) 81, 553–563 (1997).
[CrossRef]

1996

M. D. Schaeberle, V. F. Kalasinsky, J. L. Luke, E. N. Lewis, I. W. Levin, P. J. Treado, “Raman chemical imaging: histopathology of inclusions in human breast tissue,” Anal. Chem. 68, 1829–1833 (1996).
[CrossRef] [PubMed]

S. M. Laster, J. M. Mackenzie, “Bleb formation and F-actin distribution during mitosis and tumor necrosis factor-induced apoptosis,” Microsc. Res. Tech. 34, 272–280 (1996).
[CrossRef] [PubMed]

R. Manoharan, W. Yang, M. S. Feld, “Histochemical analysis of biological tissues using Raman spectroscopy,” Spectrochim. Acta Part A 52, 215–249 (1996).
[CrossRef]

K. Chinked, “Optical diagnostics image tissues and tumors,” Laser Focus World (February1996), 71–81.

S. R. Goldstein, L. H. Kidder, T. M. Herne, I. W. Levin, E. N. Lewis, “The design and implementation of a high-fidelity Raman imaging microscope,” J. Microsc. (Oxford) 184, 35–45 (1996).
[CrossRef]

H. R. Morris, C. C. Hoyt, P. Miller, P. J. Treado, “Liquid crystal tunable filter Raman chemical imaging,” Appl. Spectrosc. 50, 805–811 (1996).
[CrossRef]

1995

C. A. Drumm, M. D. Morris, “Microscopic Raman line-imaging with principal component analysis,” Appl. Spectrosc. 49, 1331–1337 (1995).
[CrossRef]

A. Feofanov, S. Sharonov, P. Valisa, E. Da Silva, I. Nabiev, M. Manfait, “A new confocal stigmatic spectrometer for micro-Raman and microfluorescence spectral imaging analysis: design and applications,” Rev. Sci. Instrum. 66, 3146–3158 (1995).
[CrossRef]

S. D. Baker, R. M. Wadkins, C. F. Stewart, W. T. Beck, M. K. Danks, “Cell cycle analysis of amount and distribution of nuclear DNA topoisomerase I as determined by fluorescence digital imaging microscopy,” Cytometry 19, 134–145 (1995).
[CrossRef] [PubMed]

G. Zahrebelski, A. L. Nieminen, K. al-Ghoul, T. Qian, B. Herman, J. J. Lemasters, “Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: a laser scanning confocal microscopic study,” Hepatology 21, 1361–1372 (1995).
[PubMed]

1994

1993

H. M. Coley, W. B. Amos, P. R. Twentyman, P. Workman, “Examination by laser scanning confocal fluorescence imaging microscopy of the subcellular localisation of anthracyclines in parent and multidrug resistant cell lines,” Br. J. Cancer 67, 1316–1323 (1993).
[CrossRef] [PubMed]

1992

J. Itoh, R. Y. Osamura, K. Watanabe, “Subcellular visualization of light microscopic specimens by laser scanning microscopy and computer analysis: a new application of image analysis,” J. Histochem. Cytochem. 40, 955–967 (1992).
[CrossRef] [PubMed]

H. Oyama, M. Nagane, S. Shibui, K. Nomura, K. Mukai, “Intracellular distribution of CPT-11 in CPT-11-resistant cells with confocal laser scanning microscopy,” Jpn. J. Clin. Oncol. 22, 331–334 (1992).
[PubMed]

J. H. de Lange, N. W. Schipper, G. J. Schuurhuis, T. K. ten Kate, T. H. van Heijningen, H. M. Pinedo, J. Lankelma, J. P. Baak, “Quantification by laser scan microscopy of intracellular doxorubicin distribution,” Cytometry 13, 571–576 (1992).
[CrossRef] [PubMed]

M. S. Jurkowitz-Alexander, R. A. Altschuld, C. M. Hohl, J. D. Johnson, J. S. McDonald, T. D. Simmons, L. A. Horrocks, “Cell swelling, blebbing, and death are dependent on ATP depletion and independent of calcium during chemical hypoxia in a glial cell line (ROC-1),” J. Neurochem. 59, 344–352 (1992).
[CrossRef] [PubMed]

1991

W. Malorni, F. Iosi, F. Mirabelli, G. Bellomo, “Cytoskeleton as a target in menadione-induced oxidative stress in cultured mammalian cells: alterations underlying surface bleb formation,” Chem. Biol. Interact. 80, 217–236 (1991).
[CrossRef] [PubMed]

J. E. Gervasoni, S. Z. Fields, S. Krishna, M. A. Baker, M. Rosado, K. Thuraisamy, A. A. Hindenburg, R. N. Taub, “Subcellular distribution of daunorubicin in P-glycoprotein-positive and -negative drug-resistant cell lines using laser-assisted confocal microscopy,” Cancer Res. 51, 4955–4963 (1991).
[PubMed]

K. W. Woodburn, N. J. Vardaxis, J. S. Hill, A. H. Kaye, D. R. Phillips, “Subcellular localization of porphyrins using confocal laser scanning microscopy,” Photochem. Photobiol. 54, 725–732 (1991).
[CrossRef] [PubMed]

1990

I. R. Nabiev, K. V. Sokolov, O. N. Voloshin, “Surface-enhanced Raman spectroscopy of biomolecules III: Determination of the local destabilization regions in the double helix,” J. Raman Spectrosc. 21, 333–336 (1990).
[CrossRef]

J. J. Lemasters, G. J. Gores, A. L. Nieminen, T. L. Dawson, B. E. Wray, B. Herman, “Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells,” Environ. Health Perspect. 84, 83–94 (1990).
[PubMed]

W. Malorni, C. Fiorentini, S. Paradisi, M. Giuliano, P. Mastrantonio, G. Donelli, “Surface blebbing and cytoskeletal changes induced in vitro by toxin B from Clostridium difficile: an immunochemical and ultrastructural study,” Exp. Molecular Pathology 52, 340–356 (1990).
[CrossRef]

1989

1984

D. A. Agard, “Optical sectioning microscopy: cellular architecture in three dimensions,” Annu. Rev. Biophys. Bioeng. 13, 191–219 (1984).
[CrossRef] [PubMed]

1983

I. R. Nabiev, V. A. Savchenko, E. S. Efremov, “Surface-enhanced Raman spectra of aromatic amino acids and proteins adsorbed by silver hydrosols,” J. Raman Spectrosc. 14, 375–379 (1983).
[CrossRef]

1974

Y. H. Lucy, “An iterative technique for the rectification of observed distributions,” Astron. J. 79, 745–765 (1974).
[CrossRef]

1972

Agard, D. A.

D. A. Agard, “Optical sectioning microscopy: cellular architecture in three dimensions,” Annu. Rev. Biophys. Bioeng. 13, 191–219 (1984).
[CrossRef] [PubMed]

Alberts, B.

B. Alberts, D. Bray, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, “Microtubules,” in Essential Cell Biology: an Introduction to the Molecular Biology of the Cell (Garland, New York, 1998), pp. 518–529.

al-Ghoul, K.

G. Zahrebelski, A. L. Nieminen, K. al-Ghoul, T. Qian, B. Herman, J. J. Lemasters, “Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: a laser scanning confocal microscopic study,” Hepatology 21, 1361–1372 (1995).
[PubMed]

Altschuld, R. A.

M. S. Jurkowitz-Alexander, R. A. Altschuld, C. M. Hohl, J. D. Johnson, J. S. McDonald, T. D. Simmons, L. A. Horrocks, “Cell swelling, blebbing, and death are dependent on ATP depletion and independent of calcium during chemical hypoxia in a glial cell line (ROC-1),” J. Neurochem. 59, 344–352 (1992).
[CrossRef] [PubMed]

Amos, W. B.

H. M. Coley, W. B. Amos, P. R. Twentyman, P. Workman, “Examination by laser scanning confocal fluorescence imaging microscopy of the subcellular localisation of anthracyclines in parent and multidrug resistant cell lines,” Br. J. Cancer 67, 1316–1323 (1993).
[CrossRef] [PubMed]

Andrew, J. J.

Angiboust, J. F.

G. D. Sockalingum, A. Beljebbar, H. Morjani, J. F. Angiboust, M. Manfait, “Characterization of island films as surface-enhanced Raman spectroscopy substrates for detecting low antitumor drug concentrations at single cell level,” Biospectrosc. 4, S71–S78 (1998).
[CrossRef]

Appadwedula, A.

Arzhantsev, S. Y.

S. Y. Arzhantsev, A. Y. Chikishev, N. I. Koroteev, J. Greve, C. Otto, N. M. Sijtsema, “Localization study of Co-phthalocyanines in cells by Raman micro(spectro)scopy,” J. Raman Spectrosc. 30, 205–208 (1999).
[CrossRef]

Askham, J. M.

E. E. Morrison, J. M. Askham, P. Clissold, A. F. Markham, D. M. Meredith, “The cellular distribution of the adenomatous polyposis coli tumour suppressor protein in neuroblastoma cells is regulated by microtubule dynamics,” Neuroscience (N.Y.) 81, 553–563 (1997).
[CrossRef]

Baak, J. P.

J. H. de Lange, N. W. Schipper, G. J. Schuurhuis, T. K. ten Kate, T. H. van Heijningen, H. M. Pinedo, J. Lankelma, J. P. Baak, “Quantification by laser scan microscopy of intracellular doxorubicin distribution,” Cytometry 13, 571–576 (1992).
[CrossRef] [PubMed]

Baker, M. A.

J. E. Gervasoni, S. Z. Fields, S. Krishna, M. A. Baker, M. Rosado, K. Thuraisamy, A. A. Hindenburg, R. N. Taub, “Subcellular distribution of daunorubicin in P-glycoprotein-positive and -negative drug-resistant cell lines using laser-assisted confocal microscopy,” Cancer Res. 51, 4955–4963 (1991).
[PubMed]

Baker, S. D.

S. D. Baker, R. M. Wadkins, C. F. Stewart, W. T. Beck, M. K. Danks, “Cell cycle analysis of amount and distribution of nuclear DNA topoisomerase I as determined by fluorescence digital imaging microscopy,” Cytometry 19, 134–145 (1995).
[CrossRef] [PubMed]

Bank, D.

Batchelder, D. N.

Bauer, N. J. C.

N. J. C. Bauer, M. Motamedi, J. P. Wicksted, W. F. March, C. A. B. Webers, F. Hendrikse, “Non-invasive assessment of ocular pharmacokinetics using confocal Raman spectroscopy,” J. Ocular Pharmacol. Therapeutics 15, 123–134 (1999).
[CrossRef]

Beck, W. T.

S. D. Baker, R. M. Wadkins, C. F. Stewart, W. T. Beck, M. K. Danks, “Cell cycle analysis of amount and distribution of nuclear DNA topoisomerase I as determined by fluorescence digital imaging microscopy,” Cytometry 19, 134–145 (1995).
[CrossRef] [PubMed]

Beljebbar, A.

G. D. Sockalingum, A. Beljebbar, H. Morjani, J. F. Angiboust, M. Manfait, “Characterization of island films as surface-enhanced Raman spectroscopy substrates for detecting low antitumor drug concentrations at single cell level,” Biospectrosc. 4, S71–S78 (1998).
[CrossRef]

Bellomo, G.

W. Malorni, F. Iosi, F. Mirabelli, G. Bellomo, “Cytoskeleton as a target in menadione-induced oxidative stress in cultured mammalian cells: alterations underlying surface bleb formation,” Chem. Biol. Interact. 80, 217–236 (1991).
[CrossRef] [PubMed]

Birbeck, K.

Black, M. J.

M. J. Black, G. Sapiro, D. H. Marimont, D. Heeger, “Robust anisotropic diffusion,” IEEE Trans. Image Process. 7, 421–432 (1998).
[CrossRef]

Bovik, A. C.

J. Ling, A. C. Bovik, “Smoothing low-SNR molecular images via anisotropic median-diffusion,” IEEE Trans. Med. Imaging 21, 377–384 (2002).
[CrossRef] [PubMed]

Bray, D.

B. Alberts, D. Bray, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, “Microtubules,” in Essential Cell Biology: an Introduction to the Molecular Biology of the Cell (Garland, New York, 1998), pp. 518–529.

Brenan, C. J. H.

C. J. H. Brenan, I. W. Hunter, M. J. Korenberg, “Volumetric Raman spectral imaging with a confocal Raman microscope: image modalities and applications,” in Three-Dimensional Microscopy: Image Acquisition and Processing III, C. J. Cogswell, G. S. Kino, T. Wilson, eds., Proc. SPIE2655, 130–139 (1996).
[CrossRef]

Brown, S. B.

Carboni, J.

E. H. Kerns, S. E. Hill, D. J. Detlefsen, K. J. Volk, B. H. Long, J. Carboni, M. S. Lee, “Cellular uptake profile of paclitaxel using liquid chromatography tandem mass spectrometry,” Rapid Commun. Mass Spectrom. 12, 620–624 (1998).
[CrossRef] [PubMed]

Castleman, K. R.

K. R. Castleman, Digital Image Processing (Prentice-Hall, Englewood Cliffs, N.J., 1995).

Chikishev, A. Y.

S. Y. Arzhantsev, A. Y. Chikishev, N. I. Koroteev, J. Greve, C. Otto, N. M. Sijtsema, “Localization study of Co-phthalocyanines in cells by Raman micro(spectro)scopy,” J. Raman Spectrosc. 30, 205–208 (1999).
[CrossRef]

Chinked, K.

K. Chinked, “Optical diagnostics image tissues and tumors,” Laser Focus World (February1996), 71–81.

Christensen, K. A.

Chu, J. J.

C. S. Rao, J. J. Chu, R. S. Liu, Y. K. Lai, “Synthesis and evaluation of [14C]-labelled and fluorescent-tagged paclitaxel derivatives as new biological probes,” Bioorg. Medic. Chem. 6, 2193–2204 (1998).
[CrossRef]

Clissold, P.

E. E. Morrison, J. M. Askham, P. Clissold, A. F. Markham, D. M. Meredith, “The cellular distribution of the adenomatous polyposis coli tumour suppressor protein in neuroblastoma cells is regulated by microtubule dynamics,” Neuroscience (N.Y.) 81, 553–563 (1997).
[CrossRef]

Coley, H. M.

H. M. Coley, W. B. Amos, P. R. Twentyman, P. Workman, “Examination by laser scanning confocal fluorescence imaging microscopy of the subcellular localisation of anthracyclines in parent and multidrug resistant cell lines,” Br. J. Cancer 67, 1316–1323 (1993).
[CrossRef] [PubMed]

Cope, S. E.

Cruse-Sawyer, J. E.

Da Silva, E.

A. Feofanov, S. Sharonov, P. Valisa, E. Da Silva, I. Nabiev, M. Manfait, “A new confocal stigmatic spectrometer for micro-Raman and microfluorescence spectral imaging analysis: design and applications,” Rev. Sci. Instrum. 66, 3146–3158 (1995).
[CrossRef]

Danks, M. K.

S. D. Baker, R. M. Wadkins, C. F. Stewart, W. T. Beck, M. K. Danks, “Cell cycle analysis of amount and distribution of nuclear DNA topoisomerase I as determined by fluorescence digital imaging microscopy,” Cytometry 19, 134–145 (1995).
[CrossRef] [PubMed]

Dawson, T. L.

J. J. Lemasters, G. J. Gores, A. L. Nieminen, T. L. Dawson, B. E. Wray, B. Herman, “Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells,” Environ. Health Perspect. 84, 83–94 (1990).
[PubMed]

De Grauw, C. J.

N. M. Sijtsema, S. D. Wouters, C. J. De Grauw, C. Otto, J. Greve, “Confocal direct imaging Raman microscope: design and applications in biology,” Appl. Spectrosc. 52, 348–355 (1998).
[CrossRef]

C. Otto, C. J. de Grauw, J. J. Duindam, N. M. Sijtsema, J. Greve, “Applications of micro-Raman imaging in biomedical research,” J. Raman Spectrosc. 28, 143–150 (1997).
[CrossRef]

de Lange, J. H.

J. H. de Lange, N. W. Schipper, G. J. Schuurhuis, T. K. ten Kate, T. H. van Heijningen, H. M. Pinedo, J. Lankelma, J. P. Baak, “Quantification by laser scan microscopy of intracellular doxorubicin distribution,” Cytometry 13, 571–576 (1992).
[CrossRef] [PubMed]

Dellinger, M.

M. Dellinger, M. Geze, R. Santus, E. Kohen, C. Kohen, J. G. Hirschberg, M. Monti, “Imaging of cells by autofluorescence: a new tool in the probing of biopharmaceutical effects at the intracellular level,” Biotechnol. Appl. Biochem. 28, 25–32 (1998).
[PubMed]

Detlefsen, D. J.

E. H. Kerns, S. E. Hill, D. J. Detlefsen, K. J. Volk, B. H. Long, J. Carboni, M. S. Lee, “Cellular uptake profile of paclitaxel using liquid chromatography tandem mass spectrometry,” Rapid Commun. Mass Spectrom. 12, 620–624 (1998).
[CrossRef] [PubMed]

Donelli, G.

W. Malorni, C. Fiorentini, S. Paradisi, M. Giuliano, P. Mastrantonio, G. Donelli, “Surface blebbing and cytoskeletal changes induced in vitro by toxin B from Clostridium difficile: an immunochemical and ultrastructural study,” Exp. Molecular Pathology 52, 340–356 (1990).
[CrossRef]

Drumm, C. A.

Duindam, J. J.

C. Otto, C. J. de Grauw, J. J. Duindam, N. M. Sijtsema, J. Greve, “Applications of micro-Raman imaging in biomedical research,” J. Raman Spectrosc. 28, 143–150 (1997).
[CrossRef]

Efremov, E. S.

I. R. Nabiev, V. A. Savchenko, E. S. Efremov, “Surface-enhanced Raman spectra of aromatic amino acids and proteins adsorbed by silver hydrosols,” J. Raman Spectrosc. 14, 375–379 (1983).
[CrossRef]

Feld, M. S.

R. Manoharan, W. Yang, M. S. Feld, “Histochemical analysis of biological tissues using Raman spectroscopy,” Spectrochim. Acta Part A 52, 215–249 (1996).
[CrossRef]

Feofanov, A.

A. Feofanov, S. Sharonov, P. Valisa, E. Da Silva, I. Nabiev, M. Manfait, “A new confocal stigmatic spectrometer for micro-Raman and microfluorescence spectral imaging analysis: design and applications,” Rev. Sci. Instrum. 66, 3146–3158 (1995).
[CrossRef]

Fields, S. Z.

J. E. Gervasoni, S. Z. Fields, S. Krishna, M. A. Baker, M. Rosado, K. Thuraisamy, A. A. Hindenburg, R. N. Taub, “Subcellular distribution of daunorubicin in P-glycoprotein-positive and -negative drug-resistant cell lines using laser-assisted confocal microscopy,” Cancer Res. 51, 4955–4963 (1991).
[PubMed]

Fiorentini, C.

W. Malorni, C. Fiorentini, S. Paradisi, M. Giuliano, P. Mastrantonio, G. Donelli, “Surface blebbing and cytoskeletal changes induced in vitro by toxin B from Clostridium difficile: an immunochemical and ultrastructural study,” Exp. Molecular Pathology 52, 340–356 (1990).
[CrossRef]

Freeman, T. L.

Gervasoni, J. E.

J. E. Gervasoni, S. Z. Fields, S. Krishna, M. A. Baker, M. Rosado, K. Thuraisamy, A. A. Hindenburg, R. N. Taub, “Subcellular distribution of daunorubicin in P-glycoprotein-positive and -negative drug-resistant cell lines using laser-assisted confocal microscopy,” Cancer Res. 51, 4955–4963 (1991).
[PubMed]

Geze, M.

M. Dellinger, M. Geze, R. Santus, E. Kohen, C. Kohen, J. G. Hirschberg, M. Monti, “Imaging of cells by autofluorescence: a new tool in the probing of biopharmaceutical effects at the intracellular level,” Biotechnol. Appl. Biochem. 28, 25–32 (1998).
[PubMed]

Giuliano, M.

W. Malorni, C. Fiorentini, S. Paradisi, M. Giuliano, P. Mastrantonio, G. Donelli, “Surface blebbing and cytoskeletal changes induced in vitro by toxin B from Clostridium difficile: an immunochemical and ultrastructural study,” Exp. Molecular Pathology 52, 340–356 (1990).
[CrossRef]

Goldstein, S. R.

S. R. Goldstein, L. H. Kidder, T. M. Herne, I. W. Levin, E. N. Lewis, “The design and implementation of a high-fidelity Raman imaging microscope,” J. Microsc. (Oxford) 184, 35–45 (1996).
[CrossRef]

Gores, G. J.

J. J. Lemasters, G. J. Gores, A. L. Nieminen, T. L. Dawson, B. E. Wray, B. Herman, “Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells,” Environ. Health Perspect. 84, 83–94 (1990).
[PubMed]

Greve, J.

S. Y. Arzhantsev, A. Y. Chikishev, N. I. Koroteev, J. Greve, C. Otto, N. M. Sijtsema, “Localization study of Co-phthalocyanines in cells by Raman micro(spectro)scopy,” J. Raman Spectrosc. 30, 205–208 (1999).
[CrossRef]

N. M. Sijtsema, S. D. Wouters, C. J. De Grauw, C. Otto, J. Greve, “Confocal direct imaging Raman microscope: design and applications in biology,” Appl. Spectrosc. 52, 348–355 (1998).
[CrossRef]

C. Otto, C. J. de Grauw, J. J. Duindam, N. M. Sijtsema, J. Greve, “Applications of micro-Raman imaging in biomedical research,” J. Raman Spectrosc. 28, 143–150 (1997).
[CrossRef]

G. J. Puppels, J. Greve, “Whole cell studies and tissue characterization by Raman spectroscopy,” in Biomedical Applications of Spectroscopy, C. Hester, ed. (Wiley, Chichester, England, 1996), pp. 1–47.

Hancewicz, T. M.

Heeger, D.

M. J. Black, G. Sapiro, D. H. Marimont, D. Heeger, “Robust anisotropic diffusion,” IEEE Trans. Image Process. 7, 421–432 (1998).
[CrossRef]

Hendrikse, F.

N. J. C. Bauer, M. Motamedi, J. P. Wicksted, W. F. March, C. A. B. Webers, F. Hendrikse, “Non-invasive assessment of ocular pharmacokinetics using confocal Raman spectroscopy,” J. Ocular Pharmacol. Therapeutics 15, 123–134 (1999).
[CrossRef]

Herman, B.

G. Zahrebelski, A. L. Nieminen, K. al-Ghoul, T. Qian, B. Herman, J. J. Lemasters, “Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: a laser scanning confocal microscopic study,” Hepatology 21, 1361–1372 (1995).
[PubMed]

J. J. Lemasters, G. J. Gores, A. L. Nieminen, T. L. Dawson, B. E. Wray, B. Herman, “Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells,” Environ. Health Perspect. 84, 83–94 (1990).
[PubMed]

Herman, T. S.

B. Z. Leal, M. L. Meltz, N. Mohan, J. Kuhn, T. J. Prihoda, T. S. Herman, “Interaction of hyperthermia with Taxol in human MCF-7 breast adenocarcinoma cells,” Int. J. Hyperthermia 15, 225–236 (1999).
[CrossRef] [PubMed]

Herne, T. M.

S. R. Goldstein, L. H. Kidder, T. M. Herne, I. W. Levin, E. N. Lewis, “The design and implementation of a high-fidelity Raman imaging microscope,” J. Microsc. (Oxford) 184, 35–45 (1996).
[CrossRef]

Hill, J. S.

K. W. Woodburn, N. J. Vardaxis, J. S. Hill, A. H. Kaye, D. R. Phillips, “Subcellular localization of porphyrins using confocal laser scanning microscopy,” Photochem. Photobiol. 54, 725–732 (1991).
[CrossRef] [PubMed]

Hill, S. E.

E. H. Kerns, S. E. Hill, D. J. Detlefsen, K. J. Volk, B. H. Long, J. Carboni, M. S. Lee, “Cellular uptake profile of paclitaxel using liquid chromatography tandem mass spectrometry,” Rapid Commun. Mass Spectrom. 12, 620–624 (1998).
[CrossRef] [PubMed]

Hindenburg, A. A.

J. E. Gervasoni, S. Z. Fields, S. Krishna, M. A. Baker, M. Rosado, K. Thuraisamy, A. A. Hindenburg, R. N. Taub, “Subcellular distribution of daunorubicin in P-glycoprotein-positive and -negative drug-resistant cell lines using laser-assisted confocal microscopy,” Cancer Res. 51, 4955–4963 (1991).
[PubMed]

Hirschberg, J. G.

M. Dellinger, M. Geze, R. Santus, E. Kohen, C. Kohen, J. G. Hirschberg, M. Monti, “Imaging of cells by autofluorescence: a new tool in the probing of biopharmaceutical effects at the intracellular level,” Biotechnol. Appl. Biochem. 28, 25–32 (1998).
[PubMed]

Hohl, C. M.

M. S. Jurkowitz-Alexander, R. A. Altschuld, C. M. Hohl, J. D. Johnson, J. S. McDonald, T. D. Simmons, L. A. Horrocks, “Cell swelling, blebbing, and death are dependent on ATP depletion and independent of calcium during chemical hypoxia in a glial cell line (ROC-1),” J. Neurochem. 59, 344–352 (1992).
[CrossRef] [PubMed]

Holmes, T. J.

Horrocks, L. A.

M. S. Jurkowitz-Alexander, R. A. Altschuld, C. M. Hohl, J. D. Johnson, J. S. McDonald, T. D. Simmons, L. A. Horrocks, “Cell swelling, blebbing, and death are dependent on ATP depletion and independent of calcium during chemical hypoxia in a glial cell line (ROC-1),” J. Neurochem. 59, 344–352 (1992).
[CrossRef] [PubMed]

Horwitz, S. B.

K. Torres, S. B. Horwitz, “Mechanisms of Taxol-induced cell death are concentration dependent,” Cancer Res. 58, 3620–3626 (1998).
[PubMed]

Hoyt, C. C.

Hsiung, C. M.

Hunter, I. W.

C. J. H. Brenan, I. W. Hunter, M. J. Korenberg, “Volumetric Raman spectral imaging with a confocal Raman microscope: image modalities and applications,” in Three-Dimensional Microscopy: Image Acquisition and Processing III, C. J. Cogswell, G. S. Kino, T. Wilson, eds., Proc. SPIE2655, 130–139 (1996).
[CrossRef]

Iosi, F.

W. Malorni, F. Iosi, F. Mirabelli, G. Bellomo, “Cytoskeleton as a target in menadione-induced oxidative stress in cultured mammalian cells: alterations underlying surface bleb formation,” Chem. Biol. Interact. 80, 217–236 (1991).
[CrossRef] [PubMed]

Itoh, J.

J. Itoh, R. Y. Osamura, K. Watanabe, “Subcellular visualization of light microscopic specimens by laser scanning microscopy and computer analysis: a new application of image analysis,” J. Histochem. Cytochem. 40, 955–967 (1992).
[CrossRef] [PubMed]

Jain, P. T.

P. T. Jain, B. F. Trump, “Human breast cancer cell growth inhibition and deregulation of [Ca2+]i by estradiol,” Anti-Cancer Drugs 8, 283–287 (1997).
[CrossRef] [PubMed]

Johnson, A.

B. Alberts, D. Bray, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, “Microtubules,” in Essential Cell Biology: an Introduction to the Molecular Biology of the Cell (Garland, New York, 1998), pp. 518–529.

Johnson, J. D.

M. S. Jurkowitz-Alexander, R. A. Altschuld, C. M. Hohl, J. D. Johnson, J. S. McDonald, T. D. Simmons, L. A. Horrocks, “Cell swelling, blebbing, and death are dependent on ATP depletion and independent of calcium during chemical hypoxia in a glial cell line (ROC-1),” J. Neurochem. 59, 344–352 (1992).
[CrossRef] [PubMed]

Jones, T.

T. Jones, “Present and future capabilities of molecular imaging techniques to understand brain function,” J. Psychopharmacol. 13, 324–329 (1999).
[CrossRef]

Jordan, M. A.

A. M. Yvon, P. Wadsworth, M. A. Jordan, “Taxol suppresses dynamics of individual microtubules in living human tumor cells,” Mol. Biol. Cell 10, 947–959 (1999).
[CrossRef] [PubMed]

Jurkowitz-Alexander, M. S.

M. S. Jurkowitz-Alexander, R. A. Altschuld, C. M. Hohl, J. D. Johnson, J. S. McDonald, T. D. Simmons, L. A. Horrocks, “Cell swelling, blebbing, and death are dependent on ATP depletion and independent of calcium during chemical hypoxia in a glial cell line (ROC-1),” J. Neurochem. 59, 344–352 (1992).
[CrossRef] [PubMed]

Kalasinsky, V. F.

M. D. Schaeberle, V. F. Kalasinsky, J. L. Luke, E. N. Lewis, I. W. Levin, P. J. Treado, “Raman chemical imaging: histopathology of inclusions in human breast tissue,” Anal. Chem. 68, 1829–1833 (1996).
[CrossRef] [PubMed]

Kaye, A. H.

K. W. Woodburn, N. J. Vardaxis, J. S. Hill, A. H. Kaye, D. R. Phillips, “Subcellular localization of porphyrins using confocal laser scanning microscopy,” Photochem. Photobiol. 54, 725–732 (1991).
[CrossRef] [PubMed]

Kerns, E. H.

E. H. Kerns, S. E. Hill, D. J. Detlefsen, K. J. Volk, B. H. Long, J. Carboni, M. S. Lee, “Cellular uptake profile of paclitaxel using liquid chromatography tandem mass spectrometry,” Rapid Commun. Mass Spectrom. 12, 620–624 (1998).
[CrossRef] [PubMed]

Kidder, L. H.

S. R. Goldstein, L. H. Kidder, T. M. Herne, I. W. Levin, E. N. Lewis, “The design and implementation of a high-fidelity Raman imaging microscope,” J. Microsc. (Oxford) 184, 35–45 (1996).
[CrossRef]

Kline, N. J.

N. J. Kline, P. J. Treado, “Raman chemical imaging of breast tissue,” J. Raman Spectrosc. 28, 119–124 (1997).
[CrossRef]

Kohen, C.

M. Dellinger, M. Geze, R. Santus, E. Kohen, C. Kohen, J. G. Hirschberg, M. Monti, “Imaging of cells by autofluorescence: a new tool in the probing of biopharmaceutical effects at the intracellular level,” Biotechnol. Appl. Biochem. 28, 25–32 (1998).
[PubMed]

Kohen, E.

M. Dellinger, M. Geze, R. Santus, E. Kohen, C. Kohen, J. G. Hirschberg, M. Monti, “Imaging of cells by autofluorescence: a new tool in the probing of biopharmaceutical effects at the intracellular level,” Biotechnol. Appl. Biochem. 28, 25–32 (1998).
[PubMed]

Korenberg, M. J.

C. J. H. Brenan, I. W. Hunter, M. J. Korenberg, “Volumetric Raman spectral imaging with a confocal Raman microscope: image modalities and applications,” in Three-Dimensional Microscopy: Image Acquisition and Processing III, C. J. Cogswell, G. S. Kino, T. Wilson, eds., Proc. SPIE2655, 130–139 (1996).
[CrossRef]

Koroteev, N. I.

S. Y. Arzhantsev, A. Y. Chikishev, N. I. Koroteev, J. Greve, C. Otto, N. M. Sijtsema, “Localization study of Co-phthalocyanines in cells by Raman micro(spectro)scopy,” J. Raman Spectrosc. 30, 205–208 (1999).
[CrossRef]

Krishna, S.

J. E. Gervasoni, S. Z. Fields, S. Krishna, M. A. Baker, M. Rosado, K. Thuraisamy, A. A. Hindenburg, R. N. Taub, “Subcellular distribution of daunorubicin in P-glycoprotein-positive and -negative drug-resistant cell lines using laser-assisted confocal microscopy,” Cancer Res. 51, 4955–4963 (1991).
[PubMed]

Kuhn, J.

B. Z. Leal, M. L. Meltz, N. Mohan, J. Kuhn, T. J. Prihoda, T. S. Herman, “Interaction of hyperthermia with Taxol in human MCF-7 breast adenocarcinoma cells,” Int. J. Hyperthermia 15, 225–236 (1999).
[CrossRef] [PubMed]

Lai, Y. K.

C. S. Rao, J. J. Chu, R. S. Liu, Y. K. Lai, “Synthesis and evaluation of [14C]-labelled and fluorescent-tagged paclitaxel derivatives as new biological probes,” Bioorg. Medic. Chem. 6, 2193–2204 (1998).
[CrossRef]

Lankelma, J.

J. H. de Lange, N. W. Schipper, G. J. Schuurhuis, T. K. ten Kate, T. H. van Heijningen, H. M. Pinedo, J. Lankelma, J. P. Baak, “Quantification by laser scan microscopy of intracellular doxorubicin distribution,” Cytometry 13, 571–576 (1992).
[CrossRef] [PubMed]

Laster, S. M.

S. M. Laster, J. M. Mackenzie, “Bleb formation and F-actin distribution during mitosis and tumor necrosis factor-induced apoptosis,” Microsc. Res. Tech. 34, 272–280 (1996).
[CrossRef] [PubMed]

Leal, B. Z.

B. Z. Leal, M. L. Meltz, N. Mohan, J. Kuhn, T. J. Prihoda, T. S. Herman, “Interaction of hyperthermia with Taxol in human MCF-7 breast adenocarcinoma cells,” Int. J. Hyperthermia 15, 225–236 (1999).
[CrossRef] [PubMed]

Lee, M. S.

E. H. Kerns, S. E. Hill, D. J. Detlefsen, K. J. Volk, B. H. Long, J. Carboni, M. S. Lee, “Cellular uptake profile of paclitaxel using liquid chromatography tandem mass spectrometry,” Rapid Commun. Mass Spectrom. 12, 620–624 (1998).
[CrossRef] [PubMed]

Lemasters, J. J.

G. Zahrebelski, A. L. Nieminen, K. al-Ghoul, T. Qian, B. Herman, J. J. Lemasters, “Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: a laser scanning confocal microscopic study,” Hepatology 21, 1361–1372 (1995).
[PubMed]

J. J. Lemasters, G. J. Gores, A. L. Nieminen, T. L. Dawson, B. E. Wray, B. Herman, “Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells,” Environ. Health Perspect. 84, 83–94 (1990).
[PubMed]

Leugers, M. A.

Levin, I. W.

M. D. Schaeberle, V. F. Kalasinsky, J. L. Luke, E. N. Lewis, I. W. Levin, P. J. Treado, “Raman chemical imaging: histopathology of inclusions in human breast tissue,” Anal. Chem. 68, 1829–1833 (1996).
[CrossRef] [PubMed]

S. R. Goldstein, L. H. Kidder, T. M. Herne, I. W. Levin, E. N. Lewis, “The design and implementation of a high-fidelity Raman imaging microscope,” J. Microsc. (Oxford) 184, 35–45 (1996).
[CrossRef]

Lewis, E. N.

S. R. Goldstein, L. H. Kidder, T. M. Herne, I. W. Levin, E. N. Lewis, “The design and implementation of a high-fidelity Raman imaging microscope,” J. Microsc. (Oxford) 184, 35–45 (1996).
[CrossRef]

M. D. Schaeberle, V. F. Kalasinsky, J. L. Luke, E. N. Lewis, I. W. Levin, P. J. Treado, “Raman chemical imaging: histopathology of inclusions in human breast tissue,” Anal. Chem. 68, 1829–1833 (1996).
[CrossRef] [PubMed]

Lewis, J.

B. Alberts, D. Bray, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, “Microtubules,” in Essential Cell Biology: an Introduction to the Molecular Biology of the Cell (Garland, New York, 1998), pp. 518–529.

Ling, J.

J. Ling, A. C. Bovik, “Smoothing low-SNR molecular images via anisotropic median-diffusion,” IEEE Trans. Med. Imaging 21, 377–384 (2002).
[CrossRef] [PubMed]

J. Ling, “Development of Raman imaging microscopy to visualize drug actions in living cells,” Ph.D. dissertation (The University of Texas at Austin, Austin, Tex., 2001), p. 150.

Liu, R. S.

C. S. Rao, J. J. Chu, R. S. Liu, Y. K. Lai, “Synthesis and evaluation of [14C]-labelled and fluorescent-tagged paclitaxel derivatives as new biological probes,” Bioorg. Medic. Chem. 6, 2193–2204 (1998).
[CrossRef]

Liu, Y. H.

Long, B. H.

E. H. Kerns, S. E. Hill, D. J. Detlefsen, K. J. Volk, B. H. Long, J. Carboni, M. S. Lee, “Cellular uptake profile of paclitaxel using liquid chromatography tandem mass spectrometry,” Rapid Commun. Mass Spectrom. 12, 620–624 (1998).
[CrossRef] [PubMed]

Lucy, Y. H.

Y. H. Lucy, “An iterative technique for the rectification of observed distributions,” Astron. J. 79, 745–765 (1974).
[CrossRef]

Luke, J. L.

M. D. Schaeberle, V. F. Kalasinsky, J. L. Luke, E. N. Lewis, I. W. Levin, P. J. Treado, “Raman chemical imaging: histopathology of inclusions in human breast tissue,” Anal. Chem. 68, 1829–1833 (1996).
[CrossRef] [PubMed]

Mackenzie, J. M.

S. M. Laster, J. M. Mackenzie, “Bleb formation and F-actin distribution during mitosis and tumor necrosis factor-induced apoptosis,” Microsc. Res. Tech. 34, 272–280 (1996).
[CrossRef] [PubMed]

Malorni, W.

W. Malorni, F. Iosi, F. Mirabelli, G. Bellomo, “Cytoskeleton as a target in menadione-induced oxidative stress in cultured mammalian cells: alterations underlying surface bleb formation,” Chem. Biol. Interact. 80, 217–236 (1991).
[CrossRef] [PubMed]

W. Malorni, C. Fiorentini, S. Paradisi, M. Giuliano, P. Mastrantonio, G. Donelli, “Surface blebbing and cytoskeletal changes induced in vitro by toxin B from Clostridium difficile: an immunochemical and ultrastructural study,” Exp. Molecular Pathology 52, 340–356 (1990).
[CrossRef]

Manfait, M.

G. D. Sockalingum, A. Beljebbar, H. Morjani, J. F. Angiboust, M. Manfait, “Characterization of island films as surface-enhanced Raman spectroscopy substrates for detecting low antitumor drug concentrations at single cell level,” Biospectrosc. 4, S71–S78 (1998).
[CrossRef]

A. Feofanov, S. Sharonov, P. Valisa, E. Da Silva, I. Nabiev, M. Manfait, “A new confocal stigmatic spectrometer for micro-Raman and microfluorescence spectral imaging analysis: design and applications,” Rev. Sci. Instrum. 66, 3146–3158 (1995).
[CrossRef]

Manoharan, R.

R. Manoharan, W. Yang, M. S. Feld, “Histochemical analysis of biological tissues using Raman spectroscopy,” Spectrochim. Acta Part A 52, 215–249 (1996).
[CrossRef]

March, W. F.

N. J. C. Bauer, M. Motamedi, J. P. Wicksted, W. F. March, C. A. B. Webers, F. Hendrikse, “Non-invasive assessment of ocular pharmacokinetics using confocal Raman spectroscopy,” J. Ocular Pharmacol. Therapeutics 15, 123–134 (1999).
[CrossRef]

Marimont, D. H.

M. J. Black, G. Sapiro, D. H. Marimont, D. Heeger, “Robust anisotropic diffusion,” IEEE Trans. Image Process. 7, 421–432 (1998).
[CrossRef]

Markham, A. F.

E. E. Morrison, J. M. Askham, P. Clissold, A. F. Markham, D. M. Meredith, “The cellular distribution of the adenomatous polyposis coli tumour suppressor protein in neuroblastoma cells is regulated by microtubule dynamics,” Neuroscience (N.Y.) 81, 553–563 (1997).
[CrossRef]

Mastrantonio, P.

W. Malorni, C. Fiorentini, S. Paradisi, M. Giuliano, P. Mastrantonio, G. Donelli, “Surface blebbing and cytoskeletal changes induced in vitro by toxin B from Clostridium difficile: an immunochemical and ultrastructural study,” Exp. Molecular Pathology 52, 340–356 (1990).
[CrossRef]

McDonald, J. S.

M. S. Jurkowitz-Alexander, R. A. Altschuld, C. M. Hohl, J. D. Johnson, J. S. McDonald, T. D. Simmons, L. A. Horrocks, “Cell swelling, blebbing, and death are dependent on ATP depletion and independent of calcium during chemical hypoxia in a glial cell line (ROC-1),” J. Neurochem. 59, 344–352 (1992).
[CrossRef] [PubMed]

Meltz, M. L.

B. Z. Leal, M. L. Meltz, N. Mohan, J. Kuhn, T. J. Prihoda, T. S. Herman, “Interaction of hyperthermia with Taxol in human MCF-7 breast adenocarcinoma cells,” Int. J. Hyperthermia 15, 225–236 (1999).
[CrossRef] [PubMed]

Meredith, D. M.

E. E. Morrison, J. M. Askham, P. Clissold, A. F. Markham, D. M. Meredith, “The cellular distribution of the adenomatous polyposis coli tumour suppressor protein in neuroblastoma cells is regulated by microtubule dynamics,” Neuroscience (N.Y.) 81, 553–563 (1997).
[CrossRef]

Miller, P.

Mirabelli, F.

W. Malorni, F. Iosi, F. Mirabelli, G. Bellomo, “Cytoskeleton as a target in menadione-induced oxidative stress in cultured mammalian cells: alterations underlying surface bleb formation,” Chem. Biol. Interact. 80, 217–236 (1991).
[CrossRef] [PubMed]

Mohan, N.

B. Z. Leal, M. L. Meltz, N. Mohan, J. Kuhn, T. J. Prihoda, T. S. Herman, “Interaction of hyperthermia with Taxol in human MCF-7 breast adenocarcinoma cells,” Int. J. Hyperthermia 15, 225–236 (1999).
[CrossRef] [PubMed]

Monti, M.

M. Dellinger, M. Geze, R. Santus, E. Kohen, C. Kohen, J. G. Hirschberg, M. Monti, “Imaging of cells by autofluorescence: a new tool in the probing of biopharmaceutical effects at the intracellular level,” Biotechnol. Appl. Biochem. 28, 25–32 (1998).
[PubMed]

Morjani, H.

G. D. Sockalingum, A. Beljebbar, H. Morjani, J. F. Angiboust, M. Manfait, “Characterization of island films as surface-enhanced Raman spectroscopy substrates for detecting low antitumor drug concentrations at single cell level,” Biospectrosc. 4, S71–S78 (1998).
[CrossRef]

Morris, H. R.

Morris, M. D.

Morrison, E. E.

E. E. Morrison, J. M. Askham, P. Clissold, A. F. Markham, D. M. Meredith, “The cellular distribution of the adenomatous polyposis coli tumour suppressor protein in neuroblastoma cells is regulated by microtubule dynamics,” Neuroscience (N.Y.) 81, 553–563 (1997).
[CrossRef]

Motamedi, M.

N. J. C. Bauer, M. Motamedi, J. P. Wicksted, W. F. March, C. A. B. Webers, F. Hendrikse, “Non-invasive assessment of ocular pharmacokinetics using confocal Raman spectroscopy,” J. Ocular Pharmacol. Therapeutics 15, 123–134 (1999).
[CrossRef]

Mukai, K.

H. Oyama, M. Nagane, S. Shibui, K. Nomura, K. Mukai, “Intracellular distribution of CPT-11 in CPT-11-resistant cells with confocal laser scanning microscopy,” Jpn. J. Clin. Oncol. 22, 331–334 (1992).
[PubMed]

Nabiev, I.

A. Feofanov, S. Sharonov, P. Valisa, E. Da Silva, I. Nabiev, M. Manfait, “A new confocal stigmatic spectrometer for micro-Raman and microfluorescence spectral imaging analysis: design and applications,” Rev. Sci. Instrum. 66, 3146–3158 (1995).
[CrossRef]

Nabiev, I. R.

I. R. Nabiev, K. V. Sokolov, O. N. Voloshin, “Surface-enhanced Raman spectroscopy of biomolecules III: Determination of the local destabilization regions in the double helix,” J. Raman Spectrosc. 21, 333–336 (1990).
[CrossRef]

I. R. Nabiev, V. A. Savchenko, E. S. Efremov, “Surface-enhanced Raman spectra of aromatic amino acids and proteins adsorbed by silver hydrosols,” J. Raman Spectrosc. 14, 375–379 (1983).
[CrossRef]

Nagane, M.

H. Oyama, M. Nagane, S. Shibui, K. Nomura, K. Mukai, “Intracellular distribution of CPT-11 in CPT-11-resistant cells with confocal laser scanning microscopy,” Jpn. J. Clin. Oncol. 22, 331–334 (1992).
[PubMed]

Nieminen, A. L.

G. Zahrebelski, A. L. Nieminen, K. al-Ghoul, T. Qian, B. Herman, J. J. Lemasters, “Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: a laser scanning confocal microscopic study,” Hepatology 21, 1361–1372 (1995).
[PubMed]

J. J. Lemasters, G. J. Gores, A. L. Nieminen, T. L. Dawson, B. E. Wray, B. Herman, “Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells,” Environ. Health Perspect. 84, 83–94 (1990).
[PubMed]

Nomura, K.

H. Oyama, M. Nagane, S. Shibui, K. Nomura, K. Mukai, “Intracellular distribution of CPT-11 in CPT-11-resistant cells with confocal laser scanning microscopy,” Jpn. J. Clin. Oncol. 22, 331–334 (1992).
[PubMed]

Osamura, R. Y.

J. Itoh, R. Y. Osamura, K. Watanabe, “Subcellular visualization of light microscopic specimens by laser scanning microscopy and computer analysis: a new application of image analysis,” J. Histochem. Cytochem. 40, 955–967 (1992).
[CrossRef] [PubMed]

Otto, C.

S. Y. Arzhantsev, A. Y. Chikishev, N. I. Koroteev, J. Greve, C. Otto, N. M. Sijtsema, “Localization study of Co-phthalocyanines in cells by Raman micro(spectro)scopy,” J. Raman Spectrosc. 30, 205–208 (1999).
[CrossRef]

N. M. Sijtsema, S. D. Wouters, C. J. De Grauw, C. Otto, J. Greve, “Confocal direct imaging Raman microscope: design and applications in biology,” Appl. Spectrosc. 52, 348–355 (1998).
[CrossRef]

C. Otto, C. J. de Grauw, J. J. Duindam, N. M. Sijtsema, J. Greve, “Applications of micro-Raman imaging in biomedical research,” J. Raman Spectrosc. 28, 143–150 (1997).
[CrossRef]

Oyama, H.

H. Oyama, M. Nagane, S. Shibui, K. Nomura, K. Mukai, “Intracellular distribution of CPT-11 in CPT-11-resistant cells with confocal laser scanning microscopy,” Jpn. J. Clin. Oncol. 22, 331–334 (1992).
[PubMed]

Paradisi, S.

W. Malorni, C. Fiorentini, S. Paradisi, M. Giuliano, P. Mastrantonio, G. Donelli, “Surface blebbing and cytoskeletal changes induced in vitro by toxin B from Clostridium difficile: an immunochemical and ultrastructural study,” Exp. Molecular Pathology 52, 340–356 (1990).
[CrossRef]

Parekh, H.

H. Parekh, H. Simpkins, “The transport and binding of taxol,” General Pharm. 29, 167–172 (1997).
[CrossRef]

Pezzuti, J. A.

Phillips, D. R.

K. W. Woodburn, N. J. Vardaxis, J. S. Hill, A. H. Kaye, D. R. Phillips, “Subcellular localization of porphyrins using confocal laser scanning microscopy,” Photochem. Photobiol. 54, 725–732 (1991).
[CrossRef] [PubMed]

Pinedo, H. M.

J. H. de Lange, N. W. Schipper, G. J. Schuurhuis, T. K. ten Kate, T. H. van Heijningen, H. M. Pinedo, J. Lankelma, J. P. Baak, “Quantification by laser scan microscopy of intracellular doxorubicin distribution,” Cytometry 13, 571–576 (1992).
[CrossRef] [PubMed]

Prihoda, T. J.

B. Z. Leal, M. L. Meltz, N. Mohan, J. Kuhn, T. J. Prihoda, T. S. Herman, “Interaction of hyperthermia with Taxol in human MCF-7 breast adenocarcinoma cells,” Int. J. Hyperthermia 15, 225–236 (1999).
[CrossRef] [PubMed]

Puppels, G. J.

G. J. Puppels, J. Greve, “Whole cell studies and tissue characterization by Raman spectroscopy,” in Biomedical Applications of Spectroscopy, C. Hester, ed. (Wiley, Chichester, England, 1996), pp. 1–47.

Qian, T.

G. Zahrebelski, A. L. Nieminen, K. al-Ghoul, T. Qian, B. Herman, J. J. Lemasters, “Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: a laser scanning confocal microscopic study,” Hepatology 21, 1361–1372 (1995).
[PubMed]

Raff, M.

B. Alberts, D. Bray, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, “Microtubules,” in Essential Cell Biology: an Introduction to the Molecular Biology of the Cell (Garland, New York, 1998), pp. 518–529.

Rao, C. S.

C. S. Rao, J. J. Chu, R. S. Liu, Y. K. Lai, “Synthesis and evaluation of [14C]-labelled and fluorescent-tagged paclitaxel derivatives as new biological probes,” Bioorg. Medic. Chem. 6, 2193–2204 (1998).
[CrossRef]

Richardson, W. H.

Roberts, K.

B. Alberts, D. Bray, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, “Microtubules,” in Essential Cell Biology: an Introduction to the Molecular Biology of the Cell (Garland, New York, 1998), pp. 518–529.

Rosado, M.

J. E. Gervasoni, S. Z. Fields, S. Krishna, M. A. Baker, M. Rosado, K. Thuraisamy, A. A. Hindenburg, R. N. Taub, “Subcellular distribution of daunorubicin in P-glycoprotein-positive and -negative drug-resistant cell lines using laser-assisted confocal microscopy,” Cancer Res. 51, 4955–4963 (1991).
[PubMed]

Santus, R.

M. Dellinger, M. Geze, R. Santus, E. Kohen, C. Kohen, J. G. Hirschberg, M. Monti, “Imaging of cells by autofluorescence: a new tool in the probing of biopharmaceutical effects at the intracellular level,” Biotechnol. Appl. Biochem. 28, 25–32 (1998).
[PubMed]

Sapiro, G.

M. J. Black, G. Sapiro, D. H. Marimont, D. Heeger, “Robust anisotropic diffusion,” IEEE Trans. Image Process. 7, 421–432 (1998).
[CrossRef]

Savchenko, V. A.

I. R. Nabiev, V. A. Savchenko, E. S. Efremov, “Surface-enhanced Raman spectra of aromatic amino acids and proteins adsorbed by silver hydrosols,” J. Raman Spectrosc. 14, 375–379 (1983).
[CrossRef]

Schaeberle, M. D.

M. D. Schaeberle, H. R. Morris, J. F. Turner, P. J. Treado, “Raman chemical imaging spectroscopy,” Anal. Chem. News Features, 175A–181A (1March1999).

M. D. Schaeberle, V. F. Kalasinsky, J. L. Luke, E. N. Lewis, I. W. Levin, P. J. Treado, “Raman chemical imaging: histopathology of inclusions in human breast tissue,” Anal. Chem. 68, 1829–1833 (1996).
[CrossRef] [PubMed]

Schipper, N. W.

J. H. de Lange, N. W. Schipper, G. J. Schuurhuis, T. K. ten Kate, T. H. van Heijningen, H. M. Pinedo, J. Lankelma, J. P. Baak, “Quantification by laser scan microscopy of intracellular doxorubicin distribution,” Cytometry 13, 571–576 (1992).
[CrossRef] [PubMed]

Schuurhuis, G. J.

J. H. de Lange, N. W. Schipper, G. J. Schuurhuis, T. K. ten Kate, T. H. van Heijningen, H. M. Pinedo, J. Lankelma, J. P. Baak, “Quantification by laser scan microscopy of intracellular doxorubicin distribution,” Cytometry 13, 571–576 (1992).
[CrossRef] [PubMed]

Sharonov, S.

A. Feofanov, S. Sharonov, P. Valisa, E. Da Silva, I. Nabiev, M. Manfait, “A new confocal stigmatic spectrometer for micro-Raman and microfluorescence spectral imaging analysis: design and applications,” Rev. Sci. Instrum. 66, 3146–3158 (1995).
[CrossRef]

Shibui, S.

H. Oyama, M. Nagane, S. Shibui, K. Nomura, K. Mukai, “Intracellular distribution of CPT-11 in CPT-11-resistant cells with confocal laser scanning microscopy,” Jpn. J. Clin. Oncol. 22, 331–334 (1992).
[PubMed]

Sijtsema, N. M.

S. Y. Arzhantsev, A. Y. Chikishev, N. I. Koroteev, J. Greve, C. Otto, N. M. Sijtsema, “Localization study of Co-phthalocyanines in cells by Raman micro(spectro)scopy,” J. Raman Spectrosc. 30, 205–208 (1999).
[CrossRef]

N. M. Sijtsema, S. D. Wouters, C. J. De Grauw, C. Otto, J. Greve, “Confocal direct imaging Raman microscope: design and applications in biology,” Appl. Spectrosc. 52, 348–355 (1998).
[CrossRef]

C. Otto, C. J. de Grauw, J. J. Duindam, N. M. Sijtsema, J. Greve, “Applications of micro-Raman imaging in biomedical research,” J. Raman Spectrosc. 28, 143–150 (1997).
[CrossRef]

Simmons, T. D.

M. S. Jurkowitz-Alexander, R. A. Altschuld, C. M. Hohl, J. D. Johnson, J. S. McDonald, T. D. Simmons, L. A. Horrocks, “Cell swelling, blebbing, and death are dependent on ATP depletion and independent of calcium during chemical hypoxia in a glial cell line (ROC-1),” J. Neurochem. 59, 344–352 (1992).
[CrossRef] [PubMed]

Simpkins, H.

H. Parekh, H. Simpkins, “The transport and binding of taxol,” General Pharm. 29, 167–172 (1997).
[CrossRef]

Sockalingum, G. D.

G. D. Sockalingum, A. Beljebbar, H. Morjani, J. F. Angiboust, M. Manfait, “Characterization of island films as surface-enhanced Raman spectroscopy substrates for detecting low antitumor drug concentrations at single cell level,” Biospectrosc. 4, S71–S78 (1998).
[CrossRef]

Sokolov, K. V.

I. R. Nabiev, K. V. Sokolov, O. N. Voloshin, “Surface-enhanced Raman spectroscopy of biomolecules III: Determination of the local destabilization regions in the double helix,” J. Raman Spectrosc. 21, 333–336 (1990).
[CrossRef]

Stewart, C. F.

S. D. Baker, R. M. Wadkins, C. F. Stewart, W. T. Beck, M. K. Danks, “Cell cycle analysis of amount and distribution of nuclear DNA topoisomerase I as determined by fluorescence digital imaging microscopy,” Cytometry 19, 134–145 (1995).
[CrossRef] [PubMed]

Stringer, M. R.

Taub, R. N.

J. E. Gervasoni, S. Z. Fields, S. Krishna, M. A. Baker, M. Rosado, K. Thuraisamy, A. A. Hindenburg, R. N. Taub, “Subcellular distribution of daunorubicin in P-glycoprotein-positive and -negative drug-resistant cell lines using laser-assisted confocal microscopy,” Cancer Res. 51, 4955–4963 (1991).
[PubMed]

ten Kate, T. K.

J. H. de Lange, N. W. Schipper, G. J. Schuurhuis, T. K. ten Kate, T. H. van Heijningen, H. M. Pinedo, J. Lankelma, J. P. Baak, “Quantification by laser scan microscopy of intracellular doxorubicin distribution,” Cytometry 13, 571–576 (1992).
[CrossRef] [PubMed]

Thuraisamy, K.

J. E. Gervasoni, S. Z. Fields, S. Krishna, M. A. Baker, M. Rosado, K. Thuraisamy, A. A. Hindenburg, R. N. Taub, “Subcellular distribution of daunorubicin in P-glycoprotein-positive and -negative drug-resistant cell lines using laser-assisted confocal microscopy,” Cancer Res. 51, 4955–4963 (1991).
[PubMed]

Torres, K.

K. Torres, S. B. Horwitz, “Mechanisms of Taxol-induced cell death are concentration dependent,” Cancer Res. 58, 3620–3626 (1998).
[PubMed]

Treado, P. J.

M. D. Schaeberle, H. R. Morris, J. F. Turner, P. J. Treado, “Raman chemical imaging spectroscopy,” Anal. Chem. News Features, 175A–181A (1March1999).

N. J. Kline, P. J. Treado, “Raman chemical imaging of breast tissue,” J. Raman Spectrosc. 28, 119–124 (1997).
[CrossRef]

H. R. Morris, C. C. Hoyt, P. Miller, P. J. Treado, “Liquid crystal tunable filter Raman chemical imaging,” Appl. Spectrosc. 50, 805–811 (1996).
[CrossRef]

M. D. Schaeberle, V. F. Kalasinsky, J. L. Luke, E. N. Lewis, I. W. Levin, P. J. Treado, “Raman chemical imaging: histopathology of inclusions in human breast tissue,” Anal. Chem. 68, 1829–1833 (1996).
[CrossRef] [PubMed]

H. R. Morris, C. C. Hoyt, P. J. Treado, “Imaging spectrometers for fluorescence and Raman microscopy: acousto-optic and liquid crystal tunable filters,” Appl. Spectrosc. 48, 857–866 (1994).
[CrossRef]

Trump, B. F.

P. T. Jain, B. F. Trump, “Human breast cancer cell growth inhibition and deregulation of [Ca2+]i by estradiol,” Anti-Cancer Drugs 8, 283–287 (1997).
[CrossRef] [PubMed]

Turner, J. F.

M. D. Schaeberle, H. R. Morris, J. F. Turner, P. J. Treado, “Raman chemical imaging spectroscopy,” Anal. Chem. News Features, 175A–181A (1March1999).

Twentyman, P. R.

H. M. Coley, W. B. Amos, P. R. Twentyman, P. Workman, “Examination by laser scanning confocal fluorescence imaging microscopy of the subcellular localisation of anthracyclines in parent and multidrug resistant cell lines,” Br. J. Cancer 67, 1316–1323 (1993).
[CrossRef] [PubMed]

Valisa, P.

A. Feofanov, S. Sharonov, P. Valisa, E. Da Silva, I. Nabiev, M. Manfait, “A new confocal stigmatic spectrometer for micro-Raman and microfluorescence spectral imaging analysis: design and applications,” Rev. Sci. Instrum. 66, 3146–3158 (1995).
[CrossRef]

van Heijningen, T. H.

J. H. de Lange, N. W. Schipper, G. J. Schuurhuis, T. K. ten Kate, T. H. van Heijningen, H. M. Pinedo, J. Lankelma, J. P. Baak, “Quantification by laser scan microscopy of intracellular doxorubicin distribution,” Cytometry 13, 571–576 (1992).
[CrossRef] [PubMed]

van Kempen, G. M. P.

van Vliet, L. J.

Vardaxis, N. J.

K. W. Woodburn, N. J. Vardaxis, J. S. Hill, A. H. Kaye, D. R. Phillips, “Subcellular localization of porphyrins using confocal laser scanning microscopy,” Photochem. Photobiol. 54, 725–732 (1991).
[CrossRef] [PubMed]

Volk, K. J.

E. H. Kerns, S. E. Hill, D. J. Detlefsen, K. J. Volk, B. H. Long, J. Carboni, M. S. Lee, “Cellular uptake profile of paclitaxel using liquid chromatography tandem mass spectrometry,” Rapid Commun. Mass Spectrom. 12, 620–624 (1998).
[CrossRef] [PubMed]

Voloshin, O. N.

I. R. Nabiev, K. V. Sokolov, O. N. Voloshin, “Surface-enhanced Raman spectroscopy of biomolecules III: Determination of the local destabilization regions in the double helix,” J. Raman Spectrosc. 21, 333–336 (1990).
[CrossRef]

Wadkins, R. M.

S. D. Baker, R. M. Wadkins, C. F. Stewart, W. T. Beck, M. K. Danks, “Cell cycle analysis of amount and distribution of nuclear DNA topoisomerase I as determined by fluorescence digital imaging microscopy,” Cytometry 19, 134–145 (1995).
[CrossRef] [PubMed]

Wadsworth, P.

A. M. Yvon, P. Wadsworth, M. A. Jordan, “Taxol suppresses dynamics of individual microtubules in living human tumor cells,” Mol. Biol. Cell 10, 947–959 (1999).
[CrossRef] [PubMed]

Walter, P.

B. Alberts, D. Bray, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, “Microtubules,” in Essential Cell Biology: an Introduction to the Molecular Biology of the Cell (Garland, New York, 1998), pp. 518–529.

Watanabe, K.

J. Itoh, R. Y. Osamura, K. Watanabe, “Subcellular visualization of light microscopic specimens by laser scanning microscopy and computer analysis: a new application of image analysis,” J. Histochem. Cytochem. 40, 955–967 (1992).
[CrossRef] [PubMed]

Webers, C. A. B.

N. J. C. Bauer, M. Motamedi, J. P. Wicksted, W. F. March, C. A. B. Webers, F. Hendrikse, “Non-invasive assessment of ocular pharmacokinetics using confocal Raman spectroscopy,” J. Ocular Pharmacol. Therapeutics 15, 123–134 (1999).
[CrossRef]

Wicksted, J. P.

N. J. C. Bauer, M. Motamedi, J. P. Wicksted, W. F. March, C. A. B. Webers, F. Hendrikse, “Non-invasive assessment of ocular pharmacokinetics using confocal Raman spectroscopy,” J. Ocular Pharmacol. Therapeutics 15, 123–134 (1999).
[CrossRef]

Woodburn, K. W.

K. W. Woodburn, N. J. Vardaxis, J. S. Hill, A. H. Kaye, D. R. Phillips, “Subcellular localization of porphyrins using confocal laser scanning microscopy,” Photochem. Photobiol. 54, 725–732 (1991).
[CrossRef] [PubMed]

Workman, P.

H. M. Coley, W. B. Amos, P. R. Twentyman, P. Workman, “Examination by laser scanning confocal fluorescence imaging microscopy of the subcellular localisation of anthracyclines in parent and multidrug resistant cell lines,” Br. J. Cancer 67, 1316–1323 (1993).
[CrossRef] [PubMed]

Wouters, S. D.

Wray, B. E.

J. J. Lemasters, G. J. Gores, A. L. Nieminen, T. L. Dawson, B. E. Wray, B. Herman, “Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells,” Environ. Health Perspect. 84, 83–94 (1990).
[PubMed]

Yang, W.

R. Manoharan, W. Yang, M. S. Feld, “Histochemical analysis of biological tissues using Raman spectroscopy,” Spectrochim. Acta Part A 52, 215–249 (1996).
[CrossRef]

Yvon, A. M.

A. M. Yvon, P. Wadsworth, M. A. Jordan, “Taxol suppresses dynamics of individual microtubules in living human tumor cells,” Mol. Biol. Cell 10, 947–959 (1999).
[CrossRef] [PubMed]

Zahrebelski, G.

G. Zahrebelski, A. L. Nieminen, K. al-Ghoul, T. Qian, B. Herman, J. J. Lemasters, “Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: a laser scanning confocal microscopic study,” Hepatology 21, 1361–1372 (1995).
[PubMed]

Zhang, S. L.

Anal. Chem.

M. D. Schaeberle, V. F. Kalasinsky, J. L. Luke, E. N. Lewis, I. W. Levin, P. J. Treado, “Raman chemical imaging: histopathology of inclusions in human breast tissue,” Anal. Chem. 68, 1829–1833 (1996).
[CrossRef] [PubMed]

Anal. Chem. News Features

M. D. Schaeberle, H. R. Morris, J. F. Turner, P. J. Treado, “Raman chemical imaging spectroscopy,” Anal. Chem. News Features, 175A–181A (1March1999).

Annu. Rev. Biophys. Bioeng.

D. A. Agard, “Optical sectioning microscopy: cellular architecture in three dimensions,” Annu. Rev. Biophys. Bioeng. 13, 191–219 (1984).
[CrossRef] [PubMed]

Anti-Cancer Drugs

P. T. Jain, B. F. Trump, “Human breast cancer cell growth inhibition and deregulation of [Ca2+]i by estradiol,” Anti-Cancer Drugs 8, 283–287 (1997).
[CrossRef] [PubMed]

Appl. Opt.

Appl. Spectrosc.

T. L. Freeman, S. E. Cope, M. R. Stringer, J. E. Cruse-Sawyer, S. B. Brown, D. N. Batchelder, K. Birbeck, “Investigation of the subcellular localization of zinc phthalocyanines by Raman mapping,” Appl. Spectrosc. 52, 1257–1263 (1998).
[CrossRef]

S. L. Zhang, J. A. Pezzuti, M. D. Morris, A. Appadwedula, C. M. Hsiung, M. A. Leugers, D. Bank, “Hyperspectral Raman line imaging of syndiotactic polystyrene crystallinity,” Appl. Spectrosc. 52, 1264–1268 (1998).
[CrossRef]

K. A. Christensen, M. D. Morris, “Hyperspectral Raman microscopic imaging using Powell lens line illumination,” Appl. Spectrosc. 52, 1145–1147 (1998).
[CrossRef]

J. J. Andrew, T. M. Hancewicz, “Rapid analysis of Raman image data using two-way multivariate curve resolution,” Appl. Spectrosc. 52, 797–807 (1998).
[CrossRef]

N. M. Sijtsema, S. D. Wouters, C. J. De Grauw, C. Otto, J. Greve, “Confocal direct imaging Raman microscope: design and applications in biology,” Appl. Spectrosc. 52, 348–355 (1998).
[CrossRef]

H. R. Morris, C. C. Hoyt, P. Miller, P. J. Treado, “Liquid crystal tunable filter Raman chemical imaging,” Appl. Spectrosc. 50, 805–811 (1996).
[CrossRef]

C. A. Drumm, M. D. Morris, “Microscopic Raman line-imaging with principal component analysis,” Appl. Spectrosc. 49, 1331–1337 (1995).
[CrossRef]

H. R. Morris, C. C. Hoyt, P. J. Treado, “Imaging spectrometers for fluorescence and Raman microscopy: acousto-optic and liquid crystal tunable filters,” Appl. Spectrosc. 48, 857–866 (1994).
[CrossRef]

Astron. J.

Y. H. Lucy, “An iterative technique for the rectification of observed distributions,” Astron. J. 79, 745–765 (1974).
[CrossRef]

Bioorg. Medic. Chem.

C. S. Rao, J. J. Chu, R. S. Liu, Y. K. Lai, “Synthesis and evaluation of [14C]-labelled and fluorescent-tagged paclitaxel derivatives as new biological probes,” Bioorg. Medic. Chem. 6, 2193–2204 (1998).
[CrossRef]

Biospectrosc.

G. D. Sockalingum, A. Beljebbar, H. Morjani, J. F. Angiboust, M. Manfait, “Characterization of island films as surface-enhanced Raman spectroscopy substrates for detecting low antitumor drug concentrations at single cell level,” Biospectrosc. 4, S71–S78 (1998).
[CrossRef]

Biotechnol. Appl. Biochem.

M. Dellinger, M. Geze, R. Santus, E. Kohen, C. Kohen, J. G. Hirschberg, M. Monti, “Imaging of cells by autofluorescence: a new tool in the probing of biopharmaceutical effects at the intracellular level,” Biotechnol. Appl. Biochem. 28, 25–32 (1998).
[PubMed]

Br. J. Cancer

H. M. Coley, W. B. Amos, P. R. Twentyman, P. Workman, “Examination by laser scanning confocal fluorescence imaging microscopy of the subcellular localisation of anthracyclines in parent and multidrug resistant cell lines,” Br. J. Cancer 67, 1316–1323 (1993).
[CrossRef] [PubMed]

Cancer Res.

J. E. Gervasoni, S. Z. Fields, S. Krishna, M. A. Baker, M. Rosado, K. Thuraisamy, A. A. Hindenburg, R. N. Taub, “Subcellular distribution of daunorubicin in P-glycoprotein-positive and -negative drug-resistant cell lines using laser-assisted confocal microscopy,” Cancer Res. 51, 4955–4963 (1991).
[PubMed]

K. Torres, S. B. Horwitz, “Mechanisms of Taxol-induced cell death are concentration dependent,” Cancer Res. 58, 3620–3626 (1998).
[PubMed]

Chem. Biol. Interact.

W. Malorni, F. Iosi, F. Mirabelli, G. Bellomo, “Cytoskeleton as a target in menadione-induced oxidative stress in cultured mammalian cells: alterations underlying surface bleb formation,” Chem. Biol. Interact. 80, 217–236 (1991).
[CrossRef] [PubMed]

Cytometry

J. H. de Lange, N. W. Schipper, G. J. Schuurhuis, T. K. ten Kate, T. H. van Heijningen, H. M. Pinedo, J. Lankelma, J. P. Baak, “Quantification by laser scan microscopy of intracellular doxorubicin distribution,” Cytometry 13, 571–576 (1992).
[CrossRef] [PubMed]

S. D. Baker, R. M. Wadkins, C. F. Stewart, W. T. Beck, M. K. Danks, “Cell cycle analysis of amount and distribution of nuclear DNA topoisomerase I as determined by fluorescence digital imaging microscopy,” Cytometry 19, 134–145 (1995).
[CrossRef] [PubMed]

Environ. Health Perspect.

J. J. Lemasters, G. J. Gores, A. L. Nieminen, T. L. Dawson, B. E. Wray, B. Herman, “Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells,” Environ. Health Perspect. 84, 83–94 (1990).
[PubMed]

Exp. Molecular Pathology

W. Malorni, C. Fiorentini, S. Paradisi, M. Giuliano, P. Mastrantonio, G. Donelli, “Surface blebbing and cytoskeletal changes induced in vitro by toxin B from Clostridium difficile: an immunochemical and ultrastructural study,” Exp. Molecular Pathology 52, 340–356 (1990).
[CrossRef]

General Pharm.

H. Parekh, H. Simpkins, “The transport and binding of taxol,” General Pharm. 29, 167–172 (1997).
[CrossRef]

Hepatology

G. Zahrebelski, A. L. Nieminen, K. al-Ghoul, T. Qian, B. Herman, J. J. Lemasters, “Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: a laser scanning confocal microscopic study,” Hepatology 21, 1361–1372 (1995).
[PubMed]

IEEE Trans. Image Process.

M. J. Black, G. Sapiro, D. H. Marimont, D. Heeger, “Robust anisotropic diffusion,” IEEE Trans. Image Process. 7, 421–432 (1998).
[CrossRef]

IEEE Trans. Med. Imaging

J. Ling, A. C. Bovik, “Smoothing low-SNR molecular images via anisotropic median-diffusion,” IEEE Trans. Med. Imaging 21, 377–384 (2002).
[CrossRef] [PubMed]

Int. J. Hyperthermia

B. Z. Leal, M. L. Meltz, N. Mohan, J. Kuhn, T. J. Prihoda, T. S. Herman, “Interaction of hyperthermia with Taxol in human MCF-7 breast adenocarcinoma cells,” Int. J. Hyperthermia 15, 225–236 (1999).
[CrossRef] [PubMed]

J. Histochem. Cytochem.

J. Itoh, R. Y. Osamura, K. Watanabe, “Subcellular visualization of light microscopic specimens by laser scanning microscopy and computer analysis: a new application of image analysis,” J. Histochem. Cytochem. 40, 955–967 (1992).
[CrossRef] [PubMed]

J. Microsc. (Oxford)

S. R. Goldstein, L. H. Kidder, T. M. Herne, I. W. Levin, E. N. Lewis, “The design and implementation of a high-fidelity Raman imaging microscope,” J. Microsc. (Oxford) 184, 35–45 (1996).
[CrossRef]

J. Neurochem.

M. S. Jurkowitz-Alexander, R. A. Altschuld, C. M. Hohl, J. D. Johnson, J. S. McDonald, T. D. Simmons, L. A. Horrocks, “Cell swelling, blebbing, and death are dependent on ATP depletion and independent of calcium during chemical hypoxia in a glial cell line (ROC-1),” J. Neurochem. 59, 344–352 (1992).
[CrossRef] [PubMed]

J. Ocular Pharmacol. Therapeutics

N. J. C. Bauer, M. Motamedi, J. P. Wicksted, W. F. March, C. A. B. Webers, F. Hendrikse, “Non-invasive assessment of ocular pharmacokinetics using confocal Raman spectroscopy,” J. Ocular Pharmacol. Therapeutics 15, 123–134 (1999).
[CrossRef]

J. Opt. Soc. Am.

J. Opt. Soc. Am. A

J. Psychopharmacol.

T. Jones, “Present and future capabilities of molecular imaging techniques to understand brain function,” J. Psychopharmacol. 13, 324–329 (1999).
[CrossRef]

J. Raman Spectrosc.

I. R. Nabiev, V. A. Savchenko, E. S. Efremov, “Surface-enhanced Raman spectra of aromatic amino acids and proteins adsorbed by silver hydrosols,” J. Raman Spectrosc. 14, 375–379 (1983).
[CrossRef]

I. R. Nabiev, K. V. Sokolov, O. N. Voloshin, “Surface-enhanced Raman spectroscopy of biomolecules III: Determination of the local destabilization regions in the double helix,” J. Raman Spectrosc. 21, 333–336 (1990).
[CrossRef]

N. J. Kline, P. J. Treado, “Raman chemical imaging of breast tissue,” J. Raman Spectrosc. 28, 119–124 (1997).
[CrossRef]

C. Otto, C. J. de Grauw, J. J. Duindam, N. M. Sijtsema, J. Greve, “Applications of micro-Raman imaging in biomedical research,” J. Raman Spectrosc. 28, 143–150 (1997).
[CrossRef]

S. Y. Arzhantsev, A. Y. Chikishev, N. I. Koroteev, J. Greve, C. Otto, N. M. Sijtsema, “Localization study of Co-phthalocyanines in cells by Raman micro(spectro)scopy,” J. Raman Spectrosc. 30, 205–208 (1999).
[CrossRef]

Jpn. J. Clin. Oncol.

H. Oyama, M. Nagane, S. Shibui, K. Nomura, K. Mukai, “Intracellular distribution of CPT-11 in CPT-11-resistant cells with confocal laser scanning microscopy,” Jpn. J. Clin. Oncol. 22, 331–334 (1992).
[PubMed]

Laser Focus World

K. Chinked, “Optical diagnostics image tissues and tumors,” Laser Focus World (February1996), 71–81.

Microsc. Res. Tech.

S. M. Laster, J. M. Mackenzie, “Bleb formation and F-actin distribution during mitosis and tumor necrosis factor-induced apoptosis,” Microsc. Res. Tech. 34, 272–280 (1996).
[CrossRef] [PubMed]

Mol. Biol. Cell

A. M. Yvon, P. Wadsworth, M. A. Jordan, “Taxol suppresses dynamics of individual microtubules in living human tumor cells,” Mol. Biol. Cell 10, 947–959 (1999).
[CrossRef] [PubMed]

Neuroscience (N.Y.)

E. E. Morrison, J. M. Askham, P. Clissold, A. F. Markham, D. M. Meredith, “The cellular distribution of the adenomatous polyposis coli tumour suppressor protein in neuroblastoma cells is regulated by microtubule dynamics,” Neuroscience (N.Y.) 81, 553–563 (1997).
[CrossRef]

Photochem. Photobiol.

K. W. Woodburn, N. J. Vardaxis, J. S. Hill, A. H. Kaye, D. R. Phillips, “Subcellular localization of porphyrins using confocal laser scanning microscopy,” Photochem. Photobiol. 54, 725–732 (1991).
[CrossRef] [PubMed]

Rapid Commun. Mass Spectrom.

E. H. Kerns, S. E. Hill, D. J. Detlefsen, K. J. Volk, B. H. Long, J. Carboni, M. S. Lee, “Cellular uptake profile of paclitaxel using liquid chromatography tandem mass spectrometry,” Rapid Commun. Mass Spectrom. 12, 620–624 (1998).
[CrossRef] [PubMed]

Rev. Sci. Instrum.

A. Feofanov, S. Sharonov, P. Valisa, E. Da Silva, I. Nabiev, M. Manfait, “A new confocal stigmatic spectrometer for micro-Raman and microfluorescence spectral imaging analysis: design and applications,” Rev. Sci. Instrum. 66, 3146–3158 (1995).
[CrossRef]

Spectrochim. Acta Part A

R. Manoharan, W. Yang, M. S. Feld, “Histochemical analysis of biological tissues using Raman spectroscopy,” Spectrochim. Acta Part A 52, 215–249 (1996).
[CrossRef]

Other

C. J. H. Brenan, I. W. Hunter, M. J. Korenberg, “Volumetric Raman spectral imaging with a confocal Raman microscope: image modalities and applications,” in Three-Dimensional Microscopy: Image Acquisition and Processing III, C. J. Cogswell, G. S. Kino, T. Wilson, eds., Proc. SPIE2655, 130–139 (1996).
[CrossRef]

G. J. Puppels, J. Greve, “Whole cell studies and tissue characterization by Raman spectroscopy,” in Biomedical Applications of Spectroscopy, C. Hester, ed. (Wiley, Chichester, England, 1996), pp. 1–47.

K. R. Castleman, Digital Image Processing (Prentice-Hall, Englewood Cliffs, N.J., 1995).

J. Ling, “Development of Raman imaging microscopy to visualize drug actions in living cells,” Ph.D. dissertation (The University of Texas at Austin, Austin, Tex., 2001), p. 150.

B. Alberts, D. Bray, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, “Microtubules,” in Essential Cell Biology: an Introduction to the Molecular Biology of the Cell (Garland, New York, 1998), pp. 518–529.

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 (9)

Fig. 1
Fig. 1

Schematic diagram of a CCD-based direct Raman imaging system. This system is able to record the two-dimensional distribution of a specific type of molecule in a sample. The pseudocolor is used in the figure to indicate signal intensity. The red area has higher intensity, indicating the molecule has higher concentration there. The dark blue area has low intensity, indicating there is less such molecule located there.

Fig. 2
Fig. 2

Raman signals ride on a broadband fluorescence baseline for a Raman spectrum.

Fig. 3
Fig. 3

Raman spectrum of paclitaxel (neat powder). The spectrum was taken with a 20× lens for an exposure time of 30 s. The insert shows the chemical structure of paclitaxel.

Fig. 4
Fig. 4

Raman spectrum (between 750 and 1250 cm-1) of 0.3-mg/ml (or 350-µM) paclitaxel solution, taken with the 60× W/IR lens and an exposure time of 300 s.

Fig. 5
Fig. 5

Raman spectrum (750–1250 cm-1) of cytoplasm from an MDA-435 tumor cell, taken with the 60× W/IR lens and an exposure time of 300 s. A Raman spectrum of the cell nucleus shows a similar pattern.

Fig. 6
Fig. 6

Example of the image record. (a) The white-light image of an MDA-435 breast cancer cell. (b) The Raman image of the cell taken at the 1000-cm-1 Raman band with a 60× W/IR lens with an exposure time of 300 s. (c) The Raman image of the cell taken at the 1080-cm-1 Raman band with a 60× W/IR lens with an exposure time of 300 s. (d) The difference between (b) and (c) before processing. The color bar indicates the relative Raman signal intensity that increases from bottom to top.

Fig. 7
Fig. 7

Postprocessing of the Raman images in Figs. 6(b) and 6(c) are illustrated in the left and right columns, respectively: (a) and (b) smoothed images, (c) and (d) nonuniform illumination corrected images, (e) and (f) background subtracted images, (g) and (h) three-dimensional blur restored images, (i) fluorescent signal eliminated image, (j) overlay of the image of (i) on the image in Fig. 6(a). The color bars indicate the relative Raman signal intensity that increases from bottom to top.

Fig. 8
Fig. 8

Images before, during, and after an MDA-435 breast cancer cell was exposed to the paclitaxel agent. The first row illustrates the images before drug treatment. The second and third rows illustrate the images 10 and 45 min during drug treatment. The fourth to seventh rows illustrate the images 10 min, 1.75, 4, and 4.5 h after drug treatment. The left column has the white-light images of the cell that show the cell structure. The center column has the Raman images of the cell that show the intensity distribution in the 1000-cm-1 Raman band. The right column has the overlay of images in the left and center columns. The red arrows point to the cell nucleus region. The blue arrows point to the cell blebbing region. The color bar indicates the relative Raman signal intensity that increases from bottom to top.

Fig. 9
Fig. 9

Distribution and functions of the cell microtubules: (a) microtubules grow out from the centrosome and extend to the cell membrane; (b) in the dividing cell, microtubules form a mitotic spindle to help nucleus splitting; (c) paclitaxel binds to the growth end of the microtubules.

Equations (12)

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

sx, y, z=Kx, y, z+K0x, y, zix, yt,
gx, y, z=hx, y, z*Kx, y, z+K0x, y, zix, yt+nx, y, z,
gn+1=gn+λ/4cN Ng+cS Sg+cE Eg+cW Wgn, gn+1=median filtergn+1, window,
Ngi,j=gi-1,j-gi,j, Sgi,j=gi+1,j-gi,j, Egi,j=gi,j+1-gi,j,Wgi,j=gi,j-1-gi,j.
cg, K=2516K1-g/5K22|g|5 K0otherwise,
rx, y=hx, y*Kflatix, yt,
rx, y=Kflatix, yt,
cx, y=rx, ymedianrx, y=ix, ymedianix, y.
gcx, y, z=gsx, y, zcx, y =hx, y, z*Kx, y, z+K0x, y, z×medianix, yt.
fn+1x, y, z=gcx, y, zhx, y, z * fnx, y, z * hx, y, z×fnx, y, z, fn+1x, y, z0,
fx, y, z=Kx, y, z+K0x, y, z.
s=0.61λ/NA.

Metrics