Abstract

Ultrahigh-resolution optical coherence tomography (UR-OCT) has been used for the first time to our knowledge to study single-cell basal cell carcinoma (BCC) in vitro. This noninvasive, in situ, label-free technique with deep imaging depth enables three-dimensional analysis of scattering properties of single cells with cellular spatial resolution. From three-dimensional UR-OCT imaging, live and dead BCC cells can be easily identified based on morphological observation. We developed a novel method to automatically extract characteristic parameters of a single cell from data volume, and quantitative comparison and parametric analysis were performed. The results demonstrate the capability of UR-OCT to detect cell death at the cellular level.

© 2012 OSA

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2012

S. Earley, C. Vinegoni, J. Dunham, R. Gorbatov, P. F. Feruglio, and R. Weissleder, “In vivo imaging of drug-induced mitochondrial outer membrane permeabilization at single-cell resolution,” Cancer Res.72(12), 2949–2956 (2012).
[CrossRef] [PubMed]

Y. Reis, M. Bernardo-Faura, D. Richter, T. Wolf, B. Brors, A. Hamacher-Brady, R. Eils, and N. R. Brady, “Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis,” PLoS ONE7(1), e28694 (2012).
[CrossRef] [PubMed]

X. Zhang, M. B. Roeffaers, S. Basu, J. R. Daniele, D. Fu, C. W. Freudiger, G. R. Holtom, and X. S. Xie, “Label-free live-cell imaging of nucleic acids using stimulated Raman scattering microscopy,” ChemPhysChem13(4), 1054–1059 (2012).
[CrossRef] [PubMed]

J. P. Dunkers, Y. J. Lee, and K. Chatterjee, “Single cell viability measurements in 3D scaffolds using in situ label free imaging by optical coherence microscopy,” Biomaterials33(7), 2119–2126 (2012).
[CrossRef] [PubMed]

2011

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
[CrossRef] [PubMed]

M. Rehberg, F. Krombach, U. Pohl, and S. Dietzel, “Label-free 3D visualization of cellular and tissue structures in intact muscle with second and third harmonic generation microscopy,” PLoS ONE6(11), e28237 (2011).
[CrossRef] [PubMed]

J. D. Orth, R. H. Kohler, F. Foijer, P. K. Sorger, R. Weissleder, and T. J. Mitchison, “Analysis of mitosis and antimitotic drug responses in tumors by in vivo microscopy and single-cell pharmacodynamics,” Cancer Res.71(13), 4608–4616 (2011).
[CrossRef] [PubMed]

S. B. Nicholls, J. Chu, G. Abbruzzese, K. D. Tremblay, and J. A. Hardy, “Mechanism of a genetically encoded dark-to-bright reporter for caspase activity,” J. Biol. Chem.286(28), 24977–24986 (2011).
[CrossRef] [PubMed]

M. J. Pittet and R. Weissleder, “Intravital imaging,” Cell147(5), 983–991 (2011).
[CrossRef] [PubMed]

S. L. Spencer and P. K. Sorger, “Measuring and modeling apoptosis in single cells,” Cell144(6), 926–939 (2011).
[CrossRef] [PubMed]

P. O. Bagnaninchi, C. Holmes, N. Drummond, J. Daoud, and M. Tabrizian, “Two-dimensional and three-dimensional viability measurements of adult stem cells with optical coherence phase microscopy,” J. Biomed. Opt.16(8), 086003 (2011).
[CrossRef] [PubMed]

2010

C. C. Tsai, T. H. Chen, Y. S. Lin, Y. T. Wang, W. Chang, K. Y. Hsu, Y. H. Chang, P. K. Hsu, D. Y. Jheng, K. Y. Huang, E. Sun, and S. L. Huang, “Ce3+:YAG double-clad crystal-fiber-based optical coherence tomography on fish cornea,” Opt. Lett.35(6), 811–813 (2010).
[CrossRef] [PubMed]

H. C. Huang, T. J. Mitchison, and J. Shi, “Stochastic competition between mechanistically independent slippage and death pathways determines cell fate during mitotic arrest,” PLoS ONE5(12), e15724 (2010).
[CrossRef] [PubMed]

S. V. Sharma, D. Y. Lee, B. Li, M. P. Quinlan, F. Takahashi, S. Maheswaran, U. McDermott, N. Azizian, L. Zou, M. A. Fischbach, K. K. Wong, K. Brandstetter, B. Wittner, S. Ramaswamy, M. Classon, and J. Settleman, “A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations,” Cell141(1), 69–80 (2010).
[CrossRef] [PubMed]

2009

M. Niepel, S. L. Spencer, and P. K. Sorger, “Non-genetic cell-to-cell variability and the consequences for pharmacology,” Curr. Opin. Chem. Biol.13(5-6), 556–561 (2009).
[CrossRef] [PubMed]

S. L. Spencer, S. Gaudet, J. G. Albeck, J. M. Burke, and P. K. Sorger, “Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis,” Nature459(7245), 428–432 (2009).
[CrossRef] [PubMed]

J. W. Tjiu, J. S. Chen, C. T. Shun, S. J. Lin, Y. H. Liao, C. Y. Chu, T. F. Tsai, H. C. Chiu, Y. S. Dai, H. Inoue, P. C. Yang, M. L. Kuo, and S. H. Jee, “Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction,” J. Invest. Dermatol.129(4), 1016–1025 (2009).
[CrossRef] [PubMed]

X. Liang, B. W. Graf, and S. A. Boppart, “Imaging engineered tissues using structural and functional optical coherence tomography,” J. Biophotonics2(11), 643–655 (2009).
[CrossRef] [PubMed]

W. C. Kuo, C. H. Chan, C. H. Chou, and J. C. Cheng, “Swept source optical coherence tomography for radiation-enhanced hepatocellular carcinoma cell invasion imaging,” Phys. Med. Biol.54(13), 4289–4297 (2009).
[CrossRef] [PubMed]

S. M. Rey, B. Povazay, B. Hofer, A. Unterhuber, B. Hermann, A. Harwood, and W. Drexler, “Three- and four-dimensional visualization of cell migration using optical coherence tomography,” J. Biophotonics2(6-7), 370–379 (2009).
[CrossRef] [PubMed]

2008

J. G. Albeck, J. M. Burke, B. B. Aldridge, M. Zhang, D. A. Lauffenburger, and P. K. Sorger, “Quantitative analysis of pathways controlling extrinsic apoptosis in single cells,” Mol. Cell30(1), 11–25 (2008).
[CrossRef] [PubMed]

R. Weissleder and M. J. Pittet, “Imaging in the era of molecular oncology,” Nature452(7187), 580–589 (2008).
[CrossRef] [PubMed]

A. Raj and A. van Oudenaarden, “Nature, nurture, or chance: stochastic gene expression and its consequences,” Cell135(2), 216–226 (2008).
[CrossRef] [PubMed]

A. A. Cohen, N. Geva-Zatorsky, E. Eden, M. Frenkel-Morgenstern, I. Issaeva, A. Sigal, R. Milo, C. Cohen-Saidon, Y. Liron, Z. Kam, L. Cohen, T. Danon, N. Perzov, and U. Alon, “Dynamic proteomics of individual cancer cells in response to a drug,” Science322(5907), 1511–1516 (2008).
[CrossRef] [PubMed]

K. E. Gascoigne and S. S. Taylor, “Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs,” Cancer Cell14(2), 111–122 (2008).
[CrossRef] [PubMed]

2007

O. J. Rando and K. J. Verstrepen, “Timescales of genetic and epigenetic inheritance,” Cell128(4), 655–668 (2007).
[CrossRef] [PubMed]

2006

J. W. Tjiu, Y. H. Liao, S. J. Lin, Y. L. Huang, W. L. Tsai, C. Y. Chu, M. L. Kuo, and S. H. Jee, “Cyclooxygenase-2 overexpression in human basal cell carcinoma cell line increases antiapoptosis, angiogenesis, and tumorigenesis,” J. Invest. Dermatol.126(5), 1143–1151 (2006).
[CrossRef] [PubMed]

K. L. Reckamp, K. Krysan, J. D. Morrow, G. L. Milne, R. A. Newman, C. Tucker, R. M. Elashoff, S. M. Dubinett, and R. A. Figlin, “A phase I trial to determine the optimal biological dose of celecoxib when combined with erlotinib in advanced non-small cell lung cancer,” Clin. Cancer Res.12(11), 3381–3388 (2006).
[CrossRef] [PubMed]

W. Tan, A. L. Oldenburg, J. J. Norman, T. A. Desai, and S. A. Boppart, “Optical coherence tomography of cell dynamics in three-dimensional tissue models,” Opt. Express14(16), 7159–7171 (2006).
[CrossRef] [PubMed]

2005

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(16), 2131–2133 (2005).
[CrossRef] [PubMed]

I. Csiki, J. D. Morrow, A. Sandler, Y. Shyr, J. Oates, M. K. Williams, T. Dang, D. P. Carbone, and D. H. Johnson, “Targeting cyclooxygenase-2 in recurrent non-small cell lung cancer: a phase II trial of celecoxib and docetaxel,” Clin. Cancer Res.11(18), 6634–6640 (2005).
[CrossRef] [PubMed]

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, 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(46), 16807–16812 (2005).
[CrossRef] [PubMed]

2003

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt.8(1), 7–16 (2003).
[CrossRef] [PubMed]

A. B. Vakhtin, D. J. Kane, W. R. Wood, and K. A. Peterson, “Common-path interferometer for frequency-domain optical coherence tomography,” Appl. Opt.42(34), 6953–6958 (2003).
[CrossRef] [PubMed]

2001

Z. Darzynkiewicz, E. Bedner, and P. Smolewski, “Flow cytometry in analysis of cell cycle and apoptosis,” Semin. Hematol.38(2), 179–193 (2001).
[CrossRef] [PubMed]

T. Reya, S. J. Morrison, M. F. Clarke, and I. L. Weissman, “Stem cells, cancer, and cancer stem cells,” Nature414(6859), 105–111 (2001).
[CrossRef] [PubMed]

1999

1998

1997

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, and F. Traganos, “Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis),” Cytometry27(1), 1–20 (1997).
[CrossRef] [PubMed]

1991

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Abbruzzese, G.

S. B. Nicholls, J. Chu, G. Abbruzzese, K. D. Tremblay, and J. A. Hardy, “Mechanism of a genetically encoded dark-to-bright reporter for caspase activity,” J. Biol. Chem.286(28), 24977–24986 (2011).
[CrossRef] [PubMed]

Akkin, T.

Albeck, J. G.

S. L. Spencer, S. Gaudet, J. G. Albeck, J. M. Burke, and P. K. Sorger, “Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis,” Nature459(7245), 428–432 (2009).
[CrossRef] [PubMed]

J. G. Albeck, J. M. Burke, B. B. Aldridge, M. Zhang, D. A. Lauffenburger, and P. K. Sorger, “Quantitative analysis of pathways controlling extrinsic apoptosis in single cells,” Mol. Cell30(1), 11–25 (2008).
[CrossRef] [PubMed]

Aldridge, B. B.

J. G. Albeck, J. M. Burke, B. B. Aldridge, M. Zhang, D. A. Lauffenburger, and P. K. Sorger, “Quantitative analysis of pathways controlling extrinsic apoptosis in single cells,” Mol. Cell30(1), 11–25 (2008).
[CrossRef] [PubMed]

Alon, U.

A. A. Cohen, N. Geva-Zatorsky, E. Eden, M. Frenkel-Morgenstern, I. Issaeva, A. Sigal, R. Milo, C. Cohen-Saidon, Y. Liron, Z. Kam, L. Cohen, T. Danon, N. Perzov, and U. Alon, “Dynamic proteomics of individual cancer cells in response to a drug,” Science322(5907), 1511–1516 (2008).
[CrossRef] [PubMed]

Azizian, N.

S. V. Sharma, D. Y. Lee, B. Li, M. P. Quinlan, F. Takahashi, S. Maheswaran, U. McDermott, N. Azizian, L. Zou, M. A. Fischbach, K. K. Wong, K. Brandstetter, B. Wittner, S. Ramaswamy, M. Classon, and J. Settleman, “A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations,” Cell141(1), 69–80 (2010).
[CrossRef] [PubMed]

Bagnaninchi, P. O.

P. O. Bagnaninchi, C. Holmes, N. Drummond, J. Daoud, and M. Tabrizian, “Two-dimensional and three-dimensional viability measurements of adult stem cells with optical coherence phase microscopy,” J. Biomed. Opt.16(8), 086003 (2011).
[CrossRef] [PubMed]

Basu, S.

X. Zhang, M. B. Roeffaers, S. Basu, J. R. Daniele, D. Fu, C. W. Freudiger, G. R. Holtom, and X. S. Xie, “Label-free live-cell imaging of nucleic acids using stimulated Raman scattering microscopy,” ChemPhysChem13(4), 1054–1059 (2012).
[CrossRef] [PubMed]

Bedner, E.

Z. Darzynkiewicz, E. Bedner, and P. Smolewski, “Flow cytometry in analysis of cell cycle and apoptosis,” Semin. Hematol.38(2), 179–193 (2001).
[CrossRef] [PubMed]

Bernardo-Faura, M.

Y. Reis, M. Bernardo-Faura, D. Richter, T. Wolf, B. Brors, A. Hamacher-Brady, R. Eils, and N. R. Brady, “Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis,” PLoS ONE7(1), e28694 (2012).
[CrossRef] [PubMed]

Boiko, I.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt.8(1), 7–16 (2003).
[CrossRef] [PubMed]

Boppart, S. A.

X. Liang, B. W. Graf, and S. A. Boppart, “Imaging engineered tissues using structural and functional optical coherence tomography,” J. Biophotonics2(11), 643–655 (2009).
[CrossRef] [PubMed]

W. Tan, A. L. Oldenburg, J. J. Norman, T. A. Desai, and S. A. Boppart, “Optical coherence tomography of cell dynamics in three-dimensional tissue models,” Opt. Express14(16), 7159–7171 (2006).
[CrossRef] [PubMed]

Bouma, B. E.

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A. A. Cohen, N. Geva-Zatorsky, E. Eden, M. Frenkel-Morgenstern, I. Issaeva, A. Sigal, R. Milo, C. Cohen-Saidon, Y. Liron, Z. Kam, L. Cohen, T. Danon, N. Perzov, and U. Alon, “Dynamic proteomics of individual cancer cells in response to a drug,” Science322(5907), 1511–1516 (2008).
[CrossRef] [PubMed]

Smolewski, P.

Z. Darzynkiewicz, E. Bedner, and P. Smolewski, “Flow cytometry in analysis of cell cycle and apoptosis,” Semin. Hematol.38(2), 179–193 (2001).
[CrossRef] [PubMed]

Sorger, P. K.

S. L. Spencer and P. K. Sorger, “Measuring and modeling apoptosis in single cells,” Cell144(6), 926–939 (2011).
[CrossRef] [PubMed]

J. D. Orth, R. H. Kohler, F. Foijer, P. K. Sorger, R. Weissleder, and T. J. Mitchison, “Analysis of mitosis and antimitotic drug responses in tumors by in vivo microscopy and single-cell pharmacodynamics,” Cancer Res.71(13), 4608–4616 (2011).
[CrossRef] [PubMed]

M. Niepel, S. L. Spencer, and P. K. Sorger, “Non-genetic cell-to-cell variability and the consequences for pharmacology,” Curr. Opin. Chem. Biol.13(5-6), 556–561 (2009).
[CrossRef] [PubMed]

S. L. Spencer, S. Gaudet, J. G. Albeck, J. M. Burke, and P. K. Sorger, “Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis,” Nature459(7245), 428–432 (2009).
[CrossRef] [PubMed]

J. G. Albeck, J. M. Burke, B. B. Aldridge, M. Zhang, D. A. Lauffenburger, and P. K. Sorger, “Quantitative analysis of pathways controlling extrinsic apoptosis in single cells,” Mol. Cell30(1), 11–25 (2008).
[CrossRef] [PubMed]

Spencer, S. L.

S. L. Spencer and P. K. Sorger, “Measuring and modeling apoptosis in single cells,” Cell144(6), 926–939 (2011).
[CrossRef] [PubMed]

S. L. Spencer, S. Gaudet, J. G. Albeck, J. M. Burke, and P. K. Sorger, “Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis,” Nature459(7245), 428–432 (2009).
[CrossRef] [PubMed]

M. Niepel, S. L. Spencer, and P. K. Sorger, “Non-genetic cell-to-cell variability and the consequences for pharmacology,” Curr. Opin. Chem. Biol.13(5-6), 556–561 (2009).
[CrossRef] [PubMed]

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Sun, E.

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Tabrizian, M.

P. O. Bagnaninchi, C. Holmes, N. Drummond, J. Daoud, and M. Tabrizian, “Two-dimensional and three-dimensional viability measurements of adult stem cells with optical coherence phase microscopy,” J. Biomed. Opt.16(8), 086003 (2011).
[CrossRef] [PubMed]

Takahashi, F.

S. V. Sharma, D. Y. Lee, B. Li, M. P. Quinlan, F. Takahashi, S. Maheswaran, U. McDermott, N. Azizian, L. Zou, M. A. Fischbach, K. K. Wong, K. Brandstetter, B. Wittner, S. Ramaswamy, M. Classon, and J. Settleman, “A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations,” Cell141(1), 69–80 (2010).
[CrossRef] [PubMed]

Tan, W.

Taylor, S. S.

K. E. Gascoigne and S. S. Taylor, “Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs,” Cancer Cell14(2), 111–122 (2008).
[CrossRef] [PubMed]

Tearney, G. J.

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
[CrossRef] [PubMed]

Tjiu, J. W.

J. W. Tjiu, J. S. Chen, C. T. Shun, S. J. Lin, Y. H. Liao, C. Y. Chu, T. F. Tsai, H. C. Chiu, Y. S. Dai, H. Inoue, P. C. Yang, M. L. Kuo, and S. H. Jee, “Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction,” J. Invest. Dermatol.129(4), 1016–1025 (2009).
[CrossRef] [PubMed]

J. W. Tjiu, Y. H. Liao, S. J. Lin, Y. L. Huang, W. L. Tsai, C. Y. Chu, M. L. Kuo, and S. H. Jee, “Cyclooxygenase-2 overexpression in human basal cell carcinoma cell line increases antiapoptosis, angiogenesis, and tumorigenesis,” J. Invest. Dermatol.126(5), 1143–1151 (2006).
[CrossRef] [PubMed]

Toussaint, J. D.

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
[CrossRef] [PubMed]

Traganos, F.

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, and F. Traganos, “Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis),” Cytometry27(1), 1–20 (1997).
[CrossRef] [PubMed]

Tremblay, K. D.

S. B. Nicholls, J. Chu, G. Abbruzzese, K. D. Tremblay, and J. A. Hardy, “Mechanism of a genetically encoded dark-to-bright reporter for caspase activity,” J. Biol. Chem.286(28), 24977–24986 (2011).
[CrossRef] [PubMed]

Tsai, C. C.

Tsai, T. F.

J. W. Tjiu, J. S. Chen, C. T. Shun, S. J. Lin, Y. H. Liao, C. Y. Chu, T. F. Tsai, H. C. Chiu, Y. S. Dai, H. Inoue, P. C. Yang, M. L. Kuo, and S. H. Jee, “Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction,” J. Invest. Dermatol.129(4), 1016–1025 (2009).
[CrossRef] [PubMed]

Tsai, W. L.

J. W. Tjiu, Y. H. Liao, S. J. Lin, Y. L. Huang, W. L. Tsai, C. Y. Chu, M. L. Kuo, and S. H. Jee, “Cyclooxygenase-2 overexpression in human basal cell carcinoma cell line increases antiapoptosis, angiogenesis, and tumorigenesis,” J. Invest. Dermatol.126(5), 1143–1151 (2006).
[CrossRef] [PubMed]

Tucker, C.

K. L. Reckamp, K. Krysan, J. D. Morrow, G. L. Milne, R. A. Newman, C. Tucker, R. M. Elashoff, S. M. Dubinett, and R. A. Figlin, “A phase I trial to determine the optimal biological dose of celecoxib when combined with erlotinib in advanced non-small cell lung cancer,” Clin. Cancer Res.12(11), 3381–3388 (2006).
[CrossRef] [PubMed]

Unterhuber, A.

S. M. Rey, B. Povazay, B. Hofer, A. Unterhuber, B. Hermann, A. Harwood, and W. Drexler, “Three- and four-dimensional visualization of cell migration using optical coherence tomography,” J. Biophotonics2(6-7), 370–379 (2009).
[CrossRef] [PubMed]

Vakhtin, A. B.

van Oudenaarden, A.

A. Raj and A. van Oudenaarden, “Nature, nurture, or chance: stochastic gene expression and its consequences,” Cell135(2), 216–226 (2008).
[CrossRef] [PubMed]

Verstrepen, K. J.

O. J. Rando and K. J. Verstrepen, “Timescales of genetic and epigenetic inheritance,” Cell128(4), 655–668 (2007).
[CrossRef] [PubMed]

Vinegoni, C.

S. Earley, C. Vinegoni, J. Dunham, R. Gorbatov, P. F. Feruglio, and R. Weissleder, “In vivo imaging of drug-induced mitochondrial outer membrane permeabilization at single-cell resolution,” Cancer Res.72(12), 2949–2956 (2012).
[CrossRef] [PubMed]

Wang, Y. T.

Weissleder, R.

S. Earley, C. Vinegoni, J. Dunham, R. Gorbatov, P. F. Feruglio, and R. Weissleder, “In vivo imaging of drug-induced mitochondrial outer membrane permeabilization at single-cell resolution,” Cancer Res.72(12), 2949–2956 (2012).
[CrossRef] [PubMed]

J. D. Orth, R. H. Kohler, F. Foijer, P. K. Sorger, R. Weissleder, and T. J. Mitchison, “Analysis of mitosis and antimitotic drug responses in tumors by in vivo microscopy and single-cell pharmacodynamics,” Cancer Res.71(13), 4608–4616 (2011).
[CrossRef] [PubMed]

M. J. Pittet and R. Weissleder, “Intravital imaging,” Cell147(5), 983–991 (2011).
[CrossRef] [PubMed]

R. Weissleder and M. J. Pittet, “Imaging in the era of molecular oncology,” Nature452(7187), 580–589 (2008).
[CrossRef] [PubMed]

Weissman, I. L.

T. Reya, S. J. Morrison, M. F. Clarke, and I. L. Weissman, “Stem cells, cancer, and cancer stem cells,” Nature414(6859), 105–111 (2001).
[CrossRef] [PubMed]

Williams, M. K.

I. Csiki, J. D. Morrow, A. Sandler, Y. Shyr, J. Oates, M. K. Williams, T. Dang, D. P. Carbone, and D. H. Johnson, “Targeting cyclooxygenase-2 in recurrent non-small cell lung cancer: a phase II trial of celecoxib and docetaxel,” Clin. Cancer Res.11(18), 6634–6640 (2005).
[CrossRef] [PubMed]

Wittner, B.

S. V. Sharma, D. Y. Lee, B. Li, M. P. Quinlan, F. Takahashi, S. Maheswaran, U. McDermott, N. Azizian, L. Zou, M. A. Fischbach, K. K. Wong, K. Brandstetter, B. Wittner, S. Ramaswamy, M. Classon, and J. Settleman, “A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations,” Cell141(1), 69–80 (2010).
[CrossRef] [PubMed]

Wolf, T.

Y. Reis, M. Bernardo-Faura, D. Richter, T. Wolf, B. Brors, A. Hamacher-Brady, R. Eils, and N. R. Brady, “Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis,” PLoS ONE7(1), e28694 (2012).
[CrossRef] [PubMed]

Wong, K. K.

S. V. Sharma, D. Y. Lee, B. Li, M. P. Quinlan, F. Takahashi, S. Maheswaran, U. McDermott, N. Azizian, L. Zou, M. A. Fischbach, K. K. Wong, K. Brandstetter, B. Wittner, S. Ramaswamy, M. Classon, and J. Settleman, “A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations,” Cell141(1), 69–80 (2010).
[CrossRef] [PubMed]

Wood, W. R.

Xie, X. S.

X. Zhang, M. B. Roeffaers, S. Basu, J. R. Daniele, D. Fu, C. W. Freudiger, G. R. Holtom, and X. S. Xie, “Label-free live-cell imaging of nucleic acids using stimulated Raman scattering microscopy,” ChemPhysChem13(4), 1054–1059 (2012).
[CrossRef] [PubMed]

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, 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(46), 16807–16812 (2005).
[CrossRef] [PubMed]

Yagi, Y.

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
[CrossRef] [PubMed]

Yang, P. C.

J. W. Tjiu, J. S. Chen, C. T. Shun, S. J. Lin, Y. H. Liao, C. Y. Chu, T. F. Tsai, H. C. Chiu, Y. S. Dai, H. Inoue, P. C. Yang, M. L. Kuo, and S. H. Jee, “Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction,” J. Invest. Dermatol.129(4), 1016–1025 (2009).
[CrossRef] [PubMed]

Zhang, M.

J. G. Albeck, J. M. Burke, B. B. Aldridge, M. Zhang, D. A. Lauffenburger, and P. K. Sorger, “Quantitative analysis of pathways controlling extrinsic apoptosis in single cells,” Mol. Cell30(1), 11–25 (2008).
[CrossRef] [PubMed]

Zhang, X.

X. Zhang, M. B. Roeffaers, S. Basu, J. R. Daniele, D. Fu, C. W. Freudiger, G. R. Holtom, and X. S. Xie, “Label-free live-cell imaging of nucleic acids using stimulated Raman scattering microscopy,” ChemPhysChem13(4), 1054–1059 (2012).
[CrossRef] [PubMed]

Zou, L.

S. V. Sharma, D. Y. Lee, B. Li, M. P. Quinlan, F. Takahashi, S. Maheswaran, U. McDermott, N. Azizian, L. Zou, M. A. Fischbach, K. K. Wong, K. Brandstetter, B. Wittner, S. Ramaswamy, M. Classon, and J. Settleman, “A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations,” Cell141(1), 69–80 (2010).
[CrossRef] [PubMed]

Appl. Opt.

Biomaterials

J. P. Dunkers, Y. J. Lee, and K. Chatterjee, “Single cell viability measurements in 3D scaffolds using in situ label free imaging by optical coherence microscopy,” Biomaterials33(7), 2119–2126 (2012).
[CrossRef] [PubMed]

Cancer Cell

K. E. Gascoigne and S. S. Taylor, “Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs,” Cancer Cell14(2), 111–122 (2008).
[CrossRef] [PubMed]

Cancer Res.

S. Earley, C. Vinegoni, J. Dunham, R. Gorbatov, P. F. Feruglio, and R. Weissleder, “In vivo imaging of drug-induced mitochondrial outer membrane permeabilization at single-cell resolution,” Cancer Res.72(12), 2949–2956 (2012).
[CrossRef] [PubMed]

J. D. Orth, R. H. Kohler, F. Foijer, P. K. Sorger, R. Weissleder, and T. J. Mitchison, “Analysis of mitosis and antimitotic drug responses in tumors by in vivo microscopy and single-cell pharmacodynamics,” Cancer Res.71(13), 4608–4616 (2011).
[CrossRef] [PubMed]

Cell

S. L. Spencer and P. K. Sorger, “Measuring and modeling apoptosis in single cells,” Cell144(6), 926–939 (2011).
[CrossRef] [PubMed]

S. V. Sharma, D. Y. Lee, B. Li, M. P. Quinlan, F. Takahashi, S. Maheswaran, U. McDermott, N. Azizian, L. Zou, M. A. Fischbach, K. K. Wong, K. Brandstetter, B. Wittner, S. Ramaswamy, M. Classon, and J. Settleman, “A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations,” Cell141(1), 69–80 (2010).
[CrossRef] [PubMed]

A. Raj and A. van Oudenaarden, “Nature, nurture, or chance: stochastic gene expression and its consequences,” Cell135(2), 216–226 (2008).
[CrossRef] [PubMed]

O. J. Rando and K. J. Verstrepen, “Timescales of genetic and epigenetic inheritance,” Cell128(4), 655–668 (2007).
[CrossRef] [PubMed]

M. J. Pittet and R. Weissleder, “Intravital imaging,” Cell147(5), 983–991 (2011).
[CrossRef] [PubMed]

ChemPhysChem

X. Zhang, M. B. Roeffaers, S. Basu, J. R. Daniele, D. Fu, C. W. Freudiger, G. R. Holtom, and X. S. Xie, “Label-free live-cell imaging of nucleic acids using stimulated Raman scattering microscopy,” ChemPhysChem13(4), 1054–1059 (2012).
[CrossRef] [PubMed]

Clin. Cancer Res.

I. Csiki, J. D. Morrow, A. Sandler, Y. Shyr, J. Oates, M. K. Williams, T. Dang, D. P. Carbone, and D. H. Johnson, “Targeting cyclooxygenase-2 in recurrent non-small cell lung cancer: a phase II trial of celecoxib and docetaxel,” Clin. Cancer Res.11(18), 6634–6640 (2005).
[CrossRef] [PubMed]

K. L. Reckamp, K. Krysan, J. D. Morrow, G. L. Milne, R. A. Newman, C. Tucker, R. M. Elashoff, S. M. Dubinett, and R. A. Figlin, “A phase I trial to determine the optimal biological dose of celecoxib when combined with erlotinib in advanced non-small cell lung cancer,” Clin. Cancer Res.12(11), 3381–3388 (2006).
[CrossRef] [PubMed]

Curr. Opin. Chem. Biol.

M. Niepel, S. L. Spencer, and P. K. Sorger, “Non-genetic cell-to-cell variability and the consequences for pharmacology,” Curr. Opin. Chem. Biol.13(5-6), 556–561 (2009).
[CrossRef] [PubMed]

Cytometry

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, and F. Traganos, “Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis),” Cytometry27(1), 1–20 (1997).
[CrossRef] [PubMed]

J. Biol. Chem.

S. B. Nicholls, J. Chu, G. Abbruzzese, K. D. Tremblay, and J. A. Hardy, “Mechanism of a genetically encoded dark-to-bright reporter for caspase activity,” J. Biol. Chem.286(28), 24977–24986 (2011).
[CrossRef] [PubMed]

J. Biomed. Opt.

G. Häusler and M. W. Lindner, “Coherence radar and spectral radar—new tools for dermatological diagnosis,” J. Biomed. Opt.3(1), 21–31 (1998).
[CrossRef]

P. O. Bagnaninchi, C. Holmes, N. Drummond, J. Daoud, and M. Tabrizian, “Two-dimensional and three-dimensional viability measurements of adult stem cells with optical coherence phase microscopy,” J. Biomed. Opt.16(8), 086003 (2011).
[CrossRef] [PubMed]

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. Macaulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt.8(1), 7–16 (2003).
[CrossRef] [PubMed]

J. Biophotonics

X. Liang, B. W. Graf, and S. A. Boppart, “Imaging engineered tissues using structural and functional optical coherence tomography,” J. Biophotonics2(11), 643–655 (2009).
[CrossRef] [PubMed]

S. M. Rey, B. Povazay, B. Hofer, A. Unterhuber, B. Hermann, A. Harwood, and W. Drexler, “Three- and four-dimensional visualization of cell migration using optical coherence tomography,” J. Biophotonics2(6-7), 370–379 (2009).
[CrossRef] [PubMed]

J. Invest. Dermatol.

J. W. Tjiu, Y. H. Liao, S. J. Lin, Y. L. Huang, W. L. Tsai, C. Y. Chu, M. L. Kuo, and S. H. Jee, “Cyclooxygenase-2 overexpression in human basal cell carcinoma cell line increases antiapoptosis, angiogenesis, and tumorigenesis,” J. Invest. Dermatol.126(5), 1143–1151 (2006).
[CrossRef] [PubMed]

J. W. Tjiu, J. S. Chen, C. T. Shun, S. J. Lin, Y. H. Liao, C. Y. Chu, T. F. Tsai, H. C. Chiu, Y. S. Dai, H. Inoue, P. C. Yang, M. L. Kuo, and S. H. Jee, “Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction,” J. Invest. Dermatol.129(4), 1016–1025 (2009).
[CrossRef] [PubMed]

Mol. Cell

J. G. Albeck, J. M. Burke, B. B. Aldridge, M. Zhang, D. A. Lauffenburger, and P. K. Sorger, “Quantitative analysis of pathways controlling extrinsic apoptosis in single cells,” Mol. Cell30(1), 11–25 (2008).
[CrossRef] [PubMed]

Nat. Med.

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
[CrossRef] [PubMed]

Nature

R. Weissleder and M. J. Pittet, “Imaging in the era of molecular oncology,” Nature452(7187), 580–589 (2008).
[CrossRef] [PubMed]

T. Reya, S. J. Morrison, M. F. Clarke, and I. L. Weissman, “Stem cells, cancer, and cancer stem cells,” Nature414(6859), 105–111 (2001).
[CrossRef] [PubMed]

S. L. Spencer, S. Gaudet, J. G. Albeck, J. M. Burke, and P. K. Sorger, “Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis,” Nature459(7245), 428–432 (2009).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Phys. Med. Biol.

W. C. Kuo, C. H. Chan, C. H. Chou, and J. C. Cheng, “Swept source optical coherence tomography for radiation-enhanced hepatocellular carcinoma cell invasion imaging,” Phys. Med. Biol.54(13), 4289–4297 (2009).
[CrossRef] [PubMed]

PLoS ONE

H. C. Huang, T. J. Mitchison, and J. Shi, “Stochastic competition between mechanistically independent slippage and death pathways determines cell fate during mitotic arrest,” PLoS ONE5(12), e15724 (2010).
[CrossRef] [PubMed]

Y. Reis, M. Bernardo-Faura, D. Richter, T. Wolf, B. Brors, A. Hamacher-Brady, R. Eils, and N. R. Brady, “Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis,” PLoS ONE7(1), e28694 (2012).
[CrossRef] [PubMed]

M. Rehberg, F. Krombach, U. Pohl, and S. Dietzel, “Label-free 3D visualization of cellular and tissue structures in intact muscle with second and third harmonic generation microscopy,” PLoS ONE6(11), e28237 (2011).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A.

C. L. Evans, E. O. Potma, M. Puoris’haag, D. Côté, 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(46), 16807–16812 (2005).
[CrossRef] [PubMed]

Science

A. A. Cohen, N. Geva-Zatorsky, E. Eden, M. Frenkel-Morgenstern, I. Issaeva, A. Sigal, R. Milo, C. Cohen-Saidon, Y. Liron, Z. Kam, L. Cohen, T. Danon, N. Perzov, and U. Alon, “Dynamic proteomics of individual cancer cells in response to a drug,” Science322(5907), 1511–1516 (2008).
[CrossRef] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Semin. Hematol.

Z. Darzynkiewicz, E. Bedner, and P. Smolewski, “Flow cytometry in analysis of cell cycle and apoptosis,” Semin. Hematol.38(2), 179–193 (2001).
[CrossRef] [PubMed]

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