Abstract

In vitro three-dimensional models for metastatic ovarian cancer have been useful for recapitulating the human disease. These spheroidal tumor cultures, however, can grow in excess of 1 mm in diameter, which are difficult to visualize without suitable imaging technology. Optical coherence tomography (OCT) is an ideal live imaging method for non-perturbatively visualizing these complex systems. OCT enabled detailed observations of the model at both nodular and cellular levels, revealing growth dynamics not previously observed. The development of a time-lapse OCT system, capable of automated, multidimensional acquisition, further provided insights into the growth and chemotherapeutic response of ovarian cancer.

© 2009 Optical Society of America

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G. Y. Lee, P. A. Kenny, E. H. Lee, and M. J. Bissell, "Three-dimensional culture models of normal and malignant breast epithelial cells," Nature Methods 4, 359-365 (2007).
[CrossRef] [PubMed]

M. Mujat, B. Park, B. Cense, T. Chen, and J. F. de Boer, "Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination," J. Biomed. Opt. 12, 041205 (2007).
[CrossRef] [PubMed]

2006

C. M. Nelson and M. J. Bissell, "Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer," Annu. Rev. Cell Dev. Biol. 22, 287-309 (2006).
[CrossRef] [PubMed]

K. S. M. Smalley, M. Lioni, and M. Herlyn, "Life isn’t flat: Taking cancer biology to the next dimension," In vitro cell. dev. biol. - Animal 42, 242-247 (2006).
[CrossRef]

C. Xu, C. Vinegoni, T. S. Ralston, W. Luo, W. Tan, and S. A. Boppart, "Spectroscopic spectral-domain optical coherence microscopy." Opt. Lett. 31, 1079-1081 (2006).
[CrossRef] [PubMed]

2005

A. L. Oldenburg, J. R. Gunther, and S. A. Boppart, "Imaging magnetically labeled cells with magnetomotive optical coherence tomography." Opt. Lett. 30, 747-749 (2005).
[CrossRef] [PubMed]

H. Naora and D. Montell, "Ovarian cancer metastasis: integrating insights from disparate model organisms." Nat. Rev. Cancer 5, 355-366 (2005).
[CrossRef] [PubMed]

J. Debnath and J. S. Brugge, "Modeling glandular epithelial cancers in three-dimensional cultures," Nat. Rev. Cancer 5, 675-88 (2005).
[CrossRef] [PubMed]

M. G. del Carmen, I. Rizvi, Y. Chang, A. C. E. Moor, E. Oliva, M. Sherwood, B. Pogue, and T. Hasan, "Synergism of Epidermal Growth Factor Receptor-Targeted Immunotherapy With Photodynamic Treatment of Ovarian Cancer In Vivo," JNCI 97, 1516-1524 (2005).
[PubMed]

T. Chen, B. Cense, M. Pierce, N. Nassif, B. Park, S. Yun, B. White, B. Bouma, G. Tearney, and J. F. de Boer, "Spectral Domain Optical Coherence Tomography Ultra-high Speed, Ultra-high Resolution Ophthalmic Imaging," Arch. Ophthalmol. 123, 1715-1720 (2005).
[CrossRef] [PubMed]

2004

2003

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

2002

R. Jain, L. Munn, and D. Fukumura, "Dissecting tumour pathophysiology using intravital microscopy." Nat. Rev. Cancer 2, 266-76 (2002).
[CrossRef] [PubMed]

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, and E. Pomerantsev, "Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound," J. Am. Coll. Cardio. 39, 604-609 (2002).
[CrossRef]

J. Debnath, K. Mills, N. Collins, M. Reginato, S. Muthuswamy, and J. Brugge, "The Role of Apoptosis in Creating and Maintaining Luminal Space within Normal and Oncogene-Expressing Mammary Acini," Cell 111, 29-40 (2002).
[CrossRef] [PubMed]

2001

J. M. Poneros, S. Brand, B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, "Diagnosis of Specialized Intestinal Metaplasia by Optical Coherence Tomography," Gastroenterology 120, 7-12 (2001).
[CrossRef] [PubMed]

1999

B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, "High-resolution imaging of the human esophagus and stomach in vivo using optical coherence tomography," Gastrointest. Endosc. 51, 467-474 (1999).
[CrossRef]

1998

1997

W. Mueller-Klieser, "Three-dimensional cell cultures: from molecular mechanisms to clinical applications," Am. Physiological Soc. 273, 1109-1123 (1997).

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos,  et al., "Cytometry in cell necrobiology: Analysis of apoptosis and accidental cell death(necrosis)," Cytometry 27, 1-20 (1997).
[CrossRef] [PubMed]

1996

K. L. Molpus, D. Koelliker, L. Atkins, D. T. Kato, J. Buczek-Thomas, A. F. Fuller Jr, and T. Hasan, "Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice," Int. J. Cancer 68, 588-95 (1996).
[CrossRef] [PubMed]

1995

A. Fercher, C. Hitzenberger, G. Kamp, and S. El-Zaiat, "Measurement of intraocular distances by backscattering spectral interferometry," Opt. Commun. 117, 43-48 (1995).
[CrossRef]

1994

S. Frisch and H. Francis, "Disruption of epithelial cell-matrix interactions induces apoptosis." J. Cell. Biol. 124, 619-626 (1994).
[CrossRef] [PubMed]

1990

W. Denk, J. Strickler, and W. Webb, "Two-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990).
[CrossRef] [PubMed]

1986

R. Knox, F. Friedlos, D. Lydall, and J. Roberts, "Mechanism of Cytotoxicity of Anticancer Platinum Drugs: Evidence That cis-Diamminedichloroplatinum (II) and cis-Diammine-(1, 1-cyclobutanedicarboxylato) platinum (II) Differ Only in the Kinetics of Their Interaction with DNA," Cancer Research 46, 1972-1979 (1986).
[PubMed]

Atkins, L.

K. L. Molpus, D. Koelliker, L. Atkins, D. T. Kato, J. Buczek-Thomas, A. F. Fuller Jr, and T. Hasan, "Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice," Int. J. Cancer 68, 588-95 (1996).
[CrossRef] [PubMed]

Bissell, M. J.

G. Y. Lee, P. A. Kenny, E. H. Lee, and M. J. Bissell, "Three-dimensional culture models of normal and malignant breast epithelial cells," Nature Methods 4, 359-365 (2007).
[CrossRef] [PubMed]

C. M. Nelson and M. J. Bissell, "Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer," Annu. Rev. Cell Dev. Biol. 22, 287-309 (2006).
[CrossRef] [PubMed]

Boppart, S. A.

Bouma, B.

T. Chen, B. Cense, M. Pierce, N. Nassif, B. Park, S. Yun, B. White, B. Bouma, G. Tearney, and J. F. de Boer, "Spectral Domain Optical Coherence Tomography Ultra-high Speed, Ultra-high Resolution Ophthalmic Imaging," Arch. Ophthalmol. 123, 1715-1720 (2005).
[CrossRef] [PubMed]

N. Nassif, B. Cense, B. Park, M. Pierce, S. Yun, B. Bouma, G. Tearney, T. Chen, and J. F. de Boer, "In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve," Opt. Express 12, 367-376 (2004).
[CrossRef] [PubMed]

Bouma, B. E.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, and E. Pomerantsev, "Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound," J. Am. Coll. Cardio. 39, 604-609 (2002).
[CrossRef]

J. M. Poneros, S. Brand, B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, "Diagnosis of Specialized Intestinal Metaplasia by Optical Coherence Tomography," Gastroenterology 120, 7-12 (2001).
[CrossRef] [PubMed]

B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, "High-resolution imaging of the human esophagus and stomach in vivo using optical coherence tomography," Gastrointest. Endosc. 51, 467-474 (1999).
[CrossRef]

Brand, S.

J. M. Poneros, S. Brand, B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, "Diagnosis of Specialized Intestinal Metaplasia by Optical Coherence Tomography," Gastroenterology 120, 7-12 (2001).
[CrossRef] [PubMed]

Brugge, J.

J. Debnath, K. Mills, N. Collins, M. Reginato, S. Muthuswamy, and J. Brugge, "The Role of Apoptosis in Creating and Maintaining Luminal Space within Normal and Oncogene-Expressing Mammary Acini," Cell 111, 29-40 (2002).
[CrossRef] [PubMed]

Brugge, J. S.

J. Debnath and J. S. Brugge, "Modeling glandular epithelial cancers in three-dimensional cultures," Nat. Rev. Cancer 5, 675-88 (2005).
[CrossRef] [PubMed]

Buczek-Thomas, J.

K. L. Molpus, D. Koelliker, L. Atkins, D. T. Kato, J. Buczek-Thomas, A. F. Fuller Jr, and T. Hasan, "Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice," Int. J. Cancer 68, 588-95 (1996).
[CrossRef] [PubMed]

Cense, B.

M. Mujat, B. Park, B. Cense, T. Chen, and J. F. de Boer, "Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination," J. Biomed. Opt. 12, 041205 (2007).
[CrossRef] [PubMed]

T. Chen, B. Cense, M. Pierce, N. Nassif, B. Park, S. Yun, B. White, B. Bouma, G. Tearney, and J. F. de Boer, "Spectral Domain Optical Coherence Tomography Ultra-high Speed, Ultra-high Resolution Ophthalmic Imaging," Arch. Ophthalmol. 123, 1715-1720 (2005).
[CrossRef] [PubMed]

N. Nassif, B. Cense, B. Park, M. Pierce, S. Yun, B. Bouma, G. Tearney, T. Chen, and J. F. de Boer, "In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve," Opt. Express 12, 367-376 (2004).
[CrossRef] [PubMed]

Chang, Y.

M. G. del Carmen, I. Rizvi, Y. Chang, A. C. E. Moor, E. Oliva, M. Sherwood, B. Pogue, and T. Hasan, "Synergism of Epidermal Growth Factor Receptor-Targeted Immunotherapy With Photodynamic Treatment of Ovarian Cancer In Vivo," JNCI 97, 1516-1524 (2005).
[PubMed]

Chen, T.

M. Mujat, B. Park, B. Cense, T. Chen, and J. F. de Boer, "Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination," J. Biomed. Opt. 12, 041205 (2007).
[CrossRef] [PubMed]

T. Chen, B. Cense, M. Pierce, N. Nassif, B. Park, S. Yun, B. White, B. Bouma, G. Tearney, and J. F. de Boer, "Spectral Domain Optical Coherence Tomography Ultra-high Speed, Ultra-high Resolution Ophthalmic Imaging," Arch. Ophthalmol. 123, 1715-1720 (2005).
[CrossRef] [PubMed]

N. Nassif, B. Cense, B. Park, M. Pierce, S. Yun, B. Bouma, G. Tearney, T. Chen, and J. F. de Boer, "In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve," Opt. Express 12, 367-376 (2004).
[CrossRef] [PubMed]

Chen, Z. P.

Choi, K. B.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, and E. Pomerantsev, "Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound," J. Am. Coll. Cardio. 39, 604-609 (2002).
[CrossRef]

Collins, N.

J. Debnath, K. Mills, N. Collins, M. Reginato, S. Muthuswamy, and J. Brugge, "The Role of Apoptosis in Creating and Maintaining Luminal Space within Normal and Oncogene-Expressing Mammary Acini," Cell 111, 29-40 (2002).
[CrossRef] [PubMed]

Compton, C. C.

J. M. Poneros, S. Brand, B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, "Diagnosis of Specialized Intestinal Metaplasia by Optical Coherence Tomography," Gastroenterology 120, 7-12 (2001).
[CrossRef] [PubMed]

B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, "High-resolution imaging of the human esophagus and stomach in vivo using optical coherence tomography," Gastrointest. Endosc. 51, 467-474 (1999).
[CrossRef]

Darzynkiewicz, Z.

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos,  et al., "Cytometry in cell necrobiology: Analysis of apoptosis and accidental cell death(necrosis)," Cytometry 27, 1-20 (1997).
[CrossRef] [PubMed]

de Boer, J. F.

M. Mujat, B. Park, B. Cense, T. Chen, and J. F. de Boer, "Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination," J. Biomed. Opt. 12, 041205 (2007).
[CrossRef] [PubMed]

T. Chen, B. Cense, M. Pierce, N. Nassif, B. Park, S. Yun, B. White, B. Bouma, G. Tearney, and J. F. de Boer, "Spectral Domain Optical Coherence Tomography Ultra-high Speed, Ultra-high Resolution Ophthalmic Imaging," Arch. Ophthalmol. 123, 1715-1720 (2005).
[CrossRef] [PubMed]

N. Nassif, B. Cense, B. Park, M. Pierce, S. Yun, B. Bouma, G. Tearney, T. Chen, and J. F. de Boer, "In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve," Opt. Express 12, 367-376 (2004).
[CrossRef] [PubMed]

J. F. De Boer, S. Srinivas, A. Malekafzali, Z. P. Chen, and J. Nelson, "Imaging thermally damaged tissue by Polarization Sensitive Optical Coherence Tomography," Opt. Express 3, 212-218 (1998).
[CrossRef] [PubMed]

Debnath, J.

J. Debnath and J. S. Brugge, "Modeling glandular epithelial cancers in three-dimensional cultures," Nat. Rev. Cancer 5, 675-88 (2005).
[CrossRef] [PubMed]

J. Debnath, K. Mills, N. Collins, M. Reginato, S. Muthuswamy, and J. Brugge, "The Role of Apoptosis in Creating and Maintaining Luminal Space within Normal and Oncogene-Expressing Mammary Acini," Cell 111, 29-40 (2002).
[CrossRef] [PubMed]

del Carmen, M. G.

M. G. del Carmen, I. Rizvi, Y. Chang, A. C. E. Moor, E. Oliva, M. Sherwood, B. Pogue, and T. Hasan, "Synergism of Epidermal Growth Factor Receptor-Targeted Immunotherapy With Photodynamic Treatment of Ovarian Cancer In Vivo," JNCI 97, 1516-1524 (2005).
[PubMed]

Denk, W.

W. Denk, J. Strickler, and W. Webb, "Two-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990).
[CrossRef] [PubMed]

El-Zaiat, S.

A. Fercher, C. Hitzenberger, G. Kamp, and S. El-Zaiat, "Measurement of intraocular distances by backscattering spectral interferometry," Opt. Commun. 117, 43-48 (1995).
[CrossRef]

Fercher, A.

A. Fercher, C. Hitzenberger, G. Kamp, and S. El-Zaiat, "Measurement of intraocular distances by backscattering spectral interferometry," Opt. Commun. 117, 43-48 (1995).
[CrossRef]

Francis, H.

S. Frisch and H. Francis, "Disruption of epithelial cell-matrix interactions induces apoptosis." J. Cell. Biol. 124, 619-626 (1994).
[CrossRef] [PubMed]

Friedlos, F.

R. Knox, F. Friedlos, D. Lydall, and J. Roberts, "Mechanism of Cytotoxicity of Anticancer Platinum Drugs: Evidence That cis-Diamminedichloroplatinum (II) and cis-Diammine-(1, 1-cyclobutanedicarboxylato) platinum (II) Differ Only in the Kinetics of Their Interaction with DNA," Cancer Research 46, 1972-1979 (1986).
[PubMed]

Frisch, S.

S. Frisch and H. Francis, "Disruption of epithelial cell-matrix interactions induces apoptosis." J. Cell. Biol. 124, 619-626 (1994).
[CrossRef] [PubMed]

Fujimoto, J.

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

Fukumura, D.

R. Jain, L. Munn, and D. Fukumura, "Dissecting tumour pathophysiology using intravital microscopy." Nat. Rev. Cancer 2, 266-76 (2002).
[CrossRef] [PubMed]

Fuller, A. F.

K. L. Molpus, D. Koelliker, L. Atkins, D. T. Kato, J. Buczek-Thomas, A. F. Fuller Jr, and T. Hasan, "Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice," Int. J. Cancer 68, 588-95 (1996).
[CrossRef] [PubMed]

Gorczyca, W.

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos,  et al., "Cytometry in cell necrobiology: Analysis of apoptosis and accidental cell death(necrosis)," Cytometry 27, 1-20 (1997).
[CrossRef] [PubMed]

Gunther, J. R.

Hasan, T.

M. G. del Carmen, I. Rizvi, Y. Chang, A. C. E. Moor, E. Oliva, M. Sherwood, B. Pogue, and T. Hasan, "Synergism of Epidermal Growth Factor Receptor-Targeted Immunotherapy With Photodynamic Treatment of Ovarian Cancer In Vivo," JNCI 97, 1516-1524 (2005).
[PubMed]

K. L. Molpus, D. Koelliker, L. Atkins, D. T. Kato, J. Buczek-Thomas, A. F. Fuller Jr, and T. Hasan, "Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice," Int. J. Cancer 68, 588-95 (1996).
[CrossRef] [PubMed]

Herlyn, M.

K. S. M. Smalley, M. Lioni, and M. Herlyn, "Life isn’t flat: Taking cancer biology to the next dimension," In vitro cell. dev. biol. - Animal 42, 242-247 (2006).
[CrossRef]

Hitzenberger, C.

A. Fercher, C. Hitzenberger, G. Kamp, and S. El-Zaiat, "Measurement of intraocular distances by backscattering spectral interferometry," Opt. Commun. 117, 43-48 (1995).
[CrossRef]

Jain, R.

R. Jain, L. Munn, and D. Fukumura, "Dissecting tumour pathophysiology using intravital microscopy." Nat. Rev. Cancer 2, 266-76 (2002).
[CrossRef] [PubMed]

Jang, I. K.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, and E. Pomerantsev, "Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound," J. Am. Coll. Cardio. 39, 604-609 (2002).
[CrossRef]

Juan, G.

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos,  et al., "Cytometry in cell necrobiology: Analysis of apoptosis and accidental cell death(necrosis)," Cytometry 27, 1-20 (1997).
[CrossRef] [PubMed]

Kamp, G.

A. Fercher, C. Hitzenberger, G. Kamp, and S. El-Zaiat, "Measurement of intraocular distances by backscattering spectral interferometry," Opt. Commun. 117, 43-48 (1995).
[CrossRef]

Kang, D. H.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, and E. Pomerantsev, "Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound," J. Am. Coll. Cardio. 39, 604-609 (2002).
[CrossRef]

Kato, D. T.

K. L. Molpus, D. Koelliker, L. Atkins, D. T. Kato, J. Buczek-Thomas, A. F. Fuller Jr, and T. Hasan, "Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice," Int. J. Cancer 68, 588-95 (1996).
[CrossRef] [PubMed]

Kenny, P. A.

G. Y. Lee, P. A. Kenny, E. H. Lee, and M. J. Bissell, "Three-dimensional culture models of normal and malignant breast epithelial cells," Nature Methods 4, 359-365 (2007).
[CrossRef] [PubMed]

Knox, R.

R. Knox, F. Friedlos, D. Lydall, and J. Roberts, "Mechanism of Cytotoxicity of Anticancer Platinum Drugs: Evidence That cis-Diamminedichloroplatinum (II) and cis-Diammine-(1, 1-cyclobutanedicarboxylato) platinum (II) Differ Only in the Kinetics of Their Interaction with DNA," Cancer Research 46, 1972-1979 (1986).
[PubMed]

Koelliker, D.

K. L. Molpus, D. Koelliker, L. Atkins, D. T. Kato, J. Buczek-Thomas, A. F. Fuller Jr, and T. Hasan, "Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice," Int. J. Cancer 68, 588-95 (1996).
[CrossRef] [PubMed]

Lee, E. H.

G. Y. Lee, P. A. Kenny, E. H. Lee, and M. J. Bissell, "Three-dimensional culture models of normal and malignant breast epithelial cells," Nature Methods 4, 359-365 (2007).
[CrossRef] [PubMed]

Lee, G. Y.

G. Y. Lee, P. A. Kenny, E. H. Lee, and M. J. Bissell, "Three-dimensional culture models of normal and malignant breast epithelial cells," Nature Methods 4, 359-365 (2007).
[CrossRef] [PubMed]

Li, X.

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos,  et al., "Cytometry in cell necrobiology: Analysis of apoptosis and accidental cell death(necrosis)," Cytometry 27, 1-20 (1997).
[CrossRef] [PubMed]

Lioni, M.

K. S. M. Smalley, M. Lioni, and M. Herlyn, "Life isn’t flat: Taking cancer biology to the next dimension," In vitro cell. dev. biol. - Animal 42, 242-247 (2006).
[CrossRef]

Luo, W.

Lydall, D.

R. Knox, F. Friedlos, D. Lydall, and J. Roberts, "Mechanism of Cytotoxicity of Anticancer Platinum Drugs: Evidence That cis-Diamminedichloroplatinum (II) and cis-Diammine-(1, 1-cyclobutanedicarboxylato) platinum (II) Differ Only in the Kinetics of Their Interaction with DNA," Cancer Research 46, 1972-1979 (1986).
[PubMed]

Malekafzali, A.

Marks, D. L.

D. L. Marks and S. A. Boppart, "Nonlinear interferometric vibrational imaging." Phys. Rev. Lett. 92, 123905 (2004).
[CrossRef] [PubMed]

Mills, K.

J. Debnath, K. Mills, N. Collins, M. Reginato, S. Muthuswamy, and J. Brugge, "The Role of Apoptosis in Creating and Maintaining Luminal Space within Normal and Oncogene-Expressing Mammary Acini," Cell 111, 29-40 (2002).
[CrossRef] [PubMed]

Molpus, K. L.

K. L. Molpus, D. Koelliker, L. Atkins, D. T. Kato, J. Buczek-Thomas, A. F. Fuller Jr, and T. Hasan, "Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice," Int. J. Cancer 68, 588-95 (1996).
[CrossRef] [PubMed]

Montell, D.

H. Naora and D. Montell, "Ovarian cancer metastasis: integrating insights from disparate model organisms." Nat. Rev. Cancer 5, 355-366 (2005).
[CrossRef] [PubMed]

Moor, A. C. E.

M. G. del Carmen, I. Rizvi, Y. Chang, A. C. E. Moor, E. Oliva, M. Sherwood, B. Pogue, and T. Hasan, "Synergism of Epidermal Growth Factor Receptor-Targeted Immunotherapy With Photodynamic Treatment of Ovarian Cancer In Vivo," JNCI 97, 1516-1524 (2005).
[PubMed]

Mueller-Klieser, W.

W. Mueller-Klieser, "Three-dimensional cell cultures: from molecular mechanisms to clinical applications," Am. Physiological Soc. 273, 1109-1123 (1997).

Mujat, M.

M. Mujat, B. Park, B. Cense, T. Chen, and J. F. de Boer, "Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination," J. Biomed. Opt. 12, 041205 (2007).
[CrossRef] [PubMed]

Munn, L.

R. Jain, L. Munn, and D. Fukumura, "Dissecting tumour pathophysiology using intravital microscopy." Nat. Rev. Cancer 2, 266-76 (2002).
[CrossRef] [PubMed]

Murakami, T.

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos,  et al., "Cytometry in cell necrobiology: Analysis of apoptosis and accidental cell death(necrosis)," Cytometry 27, 1-20 (1997).
[CrossRef] [PubMed]

Muthuswamy, S.

J. Debnath, K. Mills, N. Collins, M. Reginato, S. Muthuswamy, and J. Brugge, "The Role of Apoptosis in Creating and Maintaining Luminal Space within Normal and Oncogene-Expressing Mammary Acini," Cell 111, 29-40 (2002).
[CrossRef] [PubMed]

Naora, H.

H. Naora and D. Montell, "Ovarian cancer metastasis: integrating insights from disparate model organisms." Nat. Rev. Cancer 5, 355-366 (2005).
[CrossRef] [PubMed]

Nassif, N.

T. Chen, B. Cense, M. Pierce, N. Nassif, B. Park, S. Yun, B. White, B. Bouma, G. Tearney, and J. F. de Boer, "Spectral Domain Optical Coherence Tomography Ultra-high Speed, Ultra-high Resolution Ophthalmic Imaging," Arch. Ophthalmol. 123, 1715-1720 (2005).
[CrossRef] [PubMed]

N. Nassif, B. Cense, B. Park, M. Pierce, S. Yun, B. Bouma, G. Tearney, T. Chen, and J. F. de Boer, "In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve," Opt. Express 12, 367-376 (2004).
[CrossRef] [PubMed]

Nelson, C. M.

C. M. Nelson and M. J. Bissell, "Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer," Annu. Rev. Cell Dev. Biol. 22, 287-309 (2006).
[CrossRef] [PubMed]

Nelson, J.

Nishioka, N. S.

J. M. Poneros, S. Brand, B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, "Diagnosis of Specialized Intestinal Metaplasia by Optical Coherence Tomography," Gastroenterology 120, 7-12 (2001).
[CrossRef] [PubMed]

B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, "High-resolution imaging of the human esophagus and stomach in vivo using optical coherence tomography," Gastrointest. Endosc. 51, 467-474 (1999).
[CrossRef]

Oldenburg, A. L.

Oliva, E.

M. G. del Carmen, I. Rizvi, Y. Chang, A. C. E. Moor, E. Oliva, M. Sherwood, B. Pogue, and T. Hasan, "Synergism of Epidermal Growth Factor Receptor-Targeted Immunotherapy With Photodynamic Treatment of Ovarian Cancer In Vivo," JNCI 97, 1516-1524 (2005).
[PubMed]

Park, B.

M. Mujat, B. Park, B. Cense, T. Chen, and J. F. de Boer, "Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination," J. Biomed. Opt. 12, 041205 (2007).
[CrossRef] [PubMed]

T. Chen, B. Cense, M. Pierce, N. Nassif, B. Park, S. Yun, B. White, B. Bouma, G. Tearney, and J. F. de Boer, "Spectral Domain Optical Coherence Tomography Ultra-high Speed, Ultra-high Resolution Ophthalmic Imaging," Arch. Ophthalmol. 123, 1715-1720 (2005).
[CrossRef] [PubMed]

N. Nassif, B. Cense, B. Park, M. Pierce, S. Yun, B. Bouma, G. Tearney, T. Chen, and J. F. de Boer, "In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve," Opt. Express 12, 367-376 (2004).
[CrossRef] [PubMed]

Park, S. J.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, and E. Pomerantsev, "Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound," J. Am. Coll. Cardio. 39, 604-609 (2002).
[CrossRef]

Park, S. W.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, and E. Pomerantsev, "Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound," J. Am. Coll. Cardio. 39, 604-609 (2002).
[CrossRef]

Pierce, M.

T. Chen, B. Cense, M. Pierce, N. Nassif, B. Park, S. Yun, B. White, B. Bouma, G. Tearney, and J. F. de Boer, "Spectral Domain Optical Coherence Tomography Ultra-high Speed, Ultra-high Resolution Ophthalmic Imaging," Arch. Ophthalmol. 123, 1715-1720 (2005).
[CrossRef] [PubMed]

N. Nassif, B. Cense, B. Park, M. Pierce, S. Yun, B. Bouma, G. Tearney, T. Chen, and J. F. de Boer, "In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve," Opt. Express 12, 367-376 (2004).
[CrossRef] [PubMed]

Pogue, B.

M. G. del Carmen, I. Rizvi, Y. Chang, A. C. E. Moor, E. Oliva, M. Sherwood, B. Pogue, and T. Hasan, "Synergism of Epidermal Growth Factor Receptor-Targeted Immunotherapy With Photodynamic Treatment of Ovarian Cancer In Vivo," JNCI 97, 1516-1524 (2005).
[PubMed]

Pomerantsev, E.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, and E. Pomerantsev, "Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound," J. Am. Coll. Cardio. 39, 604-609 (2002).
[CrossRef]

Poneros, J. M.

J. M. Poneros, S. Brand, B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, "Diagnosis of Specialized Intestinal Metaplasia by Optical Coherence Tomography," Gastroenterology 120, 7-12 (2001).
[CrossRef] [PubMed]

Ralston, T. S.

Reginato, M.

J. Debnath, K. Mills, N. Collins, M. Reginato, S. Muthuswamy, and J. Brugge, "The Role of Apoptosis in Creating and Maintaining Luminal Space within Normal and Oncogene-Expressing Mammary Acini," Cell 111, 29-40 (2002).
[CrossRef] [PubMed]

Rizvi, I.

M. G. del Carmen, I. Rizvi, Y. Chang, A. C. E. Moor, E. Oliva, M. Sherwood, B. Pogue, and T. Hasan, "Synergism of Epidermal Growth Factor Receptor-Targeted Immunotherapy With Photodynamic Treatment of Ovarian Cancer In Vivo," JNCI 97, 1516-1524 (2005).
[PubMed]

Roberts, J.

R. Knox, F. Friedlos, D. Lydall, and J. Roberts, "Mechanism of Cytotoxicity of Anticancer Platinum Drugs: Evidence That cis-Diamminedichloroplatinum (II) and cis-Diammine-(1, 1-cyclobutanedicarboxylato) platinum (II) Differ Only in the Kinetics of Their Interaction with DNA," Cancer Research 46, 1972-1979 (1986).
[PubMed]

Schlendorf, K.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, and E. Pomerantsev, "Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound," J. Am. Coll. Cardio. 39, 604-609 (2002).
[CrossRef]

Seung, K. B.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, and E. Pomerantsev, "Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound," J. Am. Coll. Cardio. 39, 604-609 (2002).
[CrossRef]

Sherwood, M.

M. G. del Carmen, I. Rizvi, Y. Chang, A. C. E. Moor, E. Oliva, M. Sherwood, B. Pogue, and T. Hasan, "Synergism of Epidermal Growth Factor Receptor-Targeted Immunotherapy With Photodynamic Treatment of Ovarian Cancer In Vivo," JNCI 97, 1516-1524 (2005).
[PubMed]

Shishkov, M.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, and E. Pomerantsev, "Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound," J. Am. Coll. Cardio. 39, 604-609 (2002).
[CrossRef]

Smalley, K. S. M.

K. S. M. Smalley, M. Lioni, and M. Herlyn, "Life isn’t flat: Taking cancer biology to the next dimension," In vitro cell. dev. biol. - Animal 42, 242-247 (2006).
[CrossRef]

Srinivas, S.

Strickler, J.

W. Denk, J. Strickler, and W. Webb, "Two-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990).
[CrossRef] [PubMed]

Tan, W.

Tearney, G.

T. Chen, B. Cense, M. Pierce, N. Nassif, B. Park, S. Yun, B. White, B. Bouma, G. Tearney, and J. F. de Boer, "Spectral Domain Optical Coherence Tomography Ultra-high Speed, Ultra-high Resolution Ophthalmic Imaging," Arch. Ophthalmol. 123, 1715-1720 (2005).
[CrossRef] [PubMed]

N. Nassif, B. Cense, B. Park, M. Pierce, S. Yun, B. Bouma, G. Tearney, T. Chen, and J. F. de Boer, "In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve," Opt. Express 12, 367-376 (2004).
[CrossRef] [PubMed]

Tearney, G. J.

J. M. Poneros, S. Brand, B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, "Diagnosis of Specialized Intestinal Metaplasia by Optical Coherence Tomography," Gastroenterology 120, 7-12 (2001).
[CrossRef] [PubMed]

B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, "High-resolution imaging of the human esophagus and stomach in vivo using optical coherence tomography," Gastrointest. Endosc. 51, 467-474 (1999).
[CrossRef]

Traganos, F.

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos,  et al., "Cytometry in cell necrobiology: Analysis of apoptosis and accidental cell death(necrosis)," Cytometry 27, 1-20 (1997).
[CrossRef] [PubMed]

Vinegoni, C.

Webb, W.

W. Denk, J. Strickler, and W. Webb, "Two-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990).
[CrossRef] [PubMed]

White, B.

T. Chen, B. Cense, M. Pierce, N. Nassif, B. Park, S. Yun, B. White, B. Bouma, G. Tearney, and J. F. de Boer, "Spectral Domain Optical Coherence Tomography Ultra-high Speed, Ultra-high Resolution Ophthalmic Imaging," Arch. Ophthalmol. 123, 1715-1720 (2005).
[CrossRef] [PubMed]

Xu, C.

Yun, S.

T. Chen, B. Cense, M. Pierce, N. Nassif, B. Park, S. Yun, B. White, B. Bouma, G. Tearney, and J. F. de Boer, "Spectral Domain Optical Coherence Tomography Ultra-high Speed, Ultra-high Resolution Ophthalmic Imaging," Arch. Ophthalmol. 123, 1715-1720 (2005).
[CrossRef] [PubMed]

N. Nassif, B. Cense, B. Park, M. Pierce, S. Yun, B. Bouma, G. Tearney, T. Chen, and J. F. de Boer, "In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve," Opt. Express 12, 367-376 (2004).
[CrossRef] [PubMed]

Am. Physiological Soc.

W. Mueller-Klieser, "Three-dimensional cell cultures: from molecular mechanisms to clinical applications," Am. Physiological Soc. 273, 1109-1123 (1997).

Annu. Rev. Cell Dev. Biol.

C. M. Nelson and M. J. Bissell, "Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer," Annu. Rev. Cell Dev. Biol. 22, 287-309 (2006).
[CrossRef] [PubMed]

Arch. Ophthalmol.

T. Chen, B. Cense, M. Pierce, N. Nassif, B. Park, S. Yun, B. White, B. Bouma, G. Tearney, and J. F. de Boer, "Spectral Domain Optical Coherence Tomography Ultra-high Speed, Ultra-high Resolution Ophthalmic Imaging," Arch. Ophthalmol. 123, 1715-1720 (2005).
[CrossRef] [PubMed]

Cancer Research

R. Knox, F. Friedlos, D. Lydall, and J. Roberts, "Mechanism of Cytotoxicity of Anticancer Platinum Drugs: Evidence That cis-Diamminedichloroplatinum (II) and cis-Diammine-(1, 1-cyclobutanedicarboxylato) platinum (II) Differ Only in the Kinetics of Their Interaction with DNA," Cancer Research 46, 1972-1979 (1986).
[PubMed]

Cell

J. Debnath, K. Mills, N. Collins, M. Reginato, S. Muthuswamy, and J. Brugge, "The Role of Apoptosis in Creating and Maintaining Luminal Space within Normal and Oncogene-Expressing Mammary Acini," Cell 111, 29-40 (2002).
[CrossRef] [PubMed]

Cytometry

Z. Darzynkiewicz, G. Juan, X. Li, W. Gorczyca, T. Murakami, F. Traganos,  et al., "Cytometry in cell necrobiology: Analysis of apoptosis and accidental cell death(necrosis)," Cytometry 27, 1-20 (1997).
[CrossRef] [PubMed]

Gastroenterology

J. M. Poneros, S. Brand, B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, "Diagnosis of Specialized Intestinal Metaplasia by Optical Coherence Tomography," Gastroenterology 120, 7-12 (2001).
[CrossRef] [PubMed]

Gastrointest. Endosc.

B. E. Bouma, G. J. Tearney, C. C. Compton, and N. S. Nishioka, "High-resolution imaging of the human esophagus and stomach in vivo using optical coherence tomography," Gastrointest. Endosc. 51, 467-474 (1999).
[CrossRef]

In vitro cell. dev. biol. - Animal

K. S. M. Smalley, M. Lioni, and M. Herlyn, "Life isn’t flat: Taking cancer biology to the next dimension," In vitro cell. dev. biol. - Animal 42, 242-247 (2006).
[CrossRef]

Int. J. Cancer

K. L. Molpus, D. Koelliker, L. Atkins, D. T. Kato, J. Buczek-Thomas, A. F. Fuller Jr, and T. Hasan, "Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice," Int. J. Cancer 68, 588-95 (1996).
[CrossRef] [PubMed]

J. Am. Coll. Cardio.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, and E. Pomerantsev, "Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound," J. Am. Coll. Cardio. 39, 604-609 (2002).
[CrossRef]

J. Biomed. Opt.

M. Mujat, B. Park, B. Cense, T. Chen, and J. F. de Boer, "Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination," J. Biomed. Opt. 12, 041205 (2007).
[CrossRef] [PubMed]

J. Cell. Biol.

S. Frisch and H. Francis, "Disruption of epithelial cell-matrix interactions induces apoptosis." J. Cell. Biol. 124, 619-626 (1994).
[CrossRef] [PubMed]

JNCI

M. G. del Carmen, I. Rizvi, Y. Chang, A. C. E. Moor, E. Oliva, M. Sherwood, B. Pogue, and T. Hasan, "Synergism of Epidermal Growth Factor Receptor-Targeted Immunotherapy With Photodynamic Treatment of Ovarian Cancer In Vivo," JNCI 97, 1516-1524 (2005).
[PubMed]

Nat. Rev. Cancer

R. Jain, L. Munn, and D. Fukumura, "Dissecting tumour pathophysiology using intravital microscopy." Nat. Rev. Cancer 2, 266-76 (2002).
[CrossRef] [PubMed]

J. Debnath and J. S. Brugge, "Modeling glandular epithelial cancers in three-dimensional cultures," Nat. Rev. Cancer 5, 675-88 (2005).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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Supplementary Material (6)

» Media 1: MOV (3318 KB)     
» Media 2: MOV (3594 KB)     
» Media 3: MOV (3278 KB)     
» Media 4: MOV (2364 KB)     
» Media 5: MOV (2158 KB)     
» Media 6: MOV (2427 KB)     

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Figures (7)

Fig. 1.
Fig. 1.

Ultrahigh resolution OCT and multiphoton microscopy experimental setup. The output from a Ti: Sapphire laser is either coupled into a fiber interferometer for OCT imaging or selected with a flip mirror towards a pair of dispersion compensating mirrors (DSP) for two-photon microscopy. The sample arm of the interferometer or the reflected dispersion compensated beam was coupled into an inverted beam-scanning microscope. SL, scan lens; TL, tube lens; DM, dichroic mirror; SM, silver mirror; PMT, photomultiplier tube.

Fig. 2.
Fig. 2.

OCT B-scans of acinar growth. After 10 days of growth (a) (Media 1) acini appeared as small, solid structures which continue to grow larger by day 13 (b) (Media 2). Internal structure appeared on day 17 (c) (Media 3) as the acini begin to hollow. By three weeks of growth (d) (Media 4), the developing acini were hollow, luminal structures full of highly scattering, loosely packed bodies. Each B-scan links to a movie showing a transverse scan through a 2 mm x 1mm x 360 μm volume.

Fig. 3.
Fig. 3.

Direct comparison between live OCT images and stained two-photon fluorescence images of ovarian cancer acini at different time points. All images are 4 μm thick projections taken at the acini centers. DAPI appears in blue, while Alexa568-phalloidin labeled actin is shown in red. A Day 13 acinus visualized with OCT (a) and two-photon fluorescence microscopy (d) shows a densely packed cellular structure. The hollow center seen in a day 17 acinus captured by OCT (b) matches the structure visualized using fluorescence staining (e). The thin walls of three-week old acini seen in OCT (c) are revealed to be composed of a layer of cells (f).

Fig. 4.
Fig. 4.

Ovarian cancer acini stained for activated caspase-3 (red) and E-cadherin (green). As a cell-cell adhesion molecule, E-cadherin can be seen outlining cellular contacts throughout the acini. Before acinar hollowing, very few apoptotic cells were observed, and were distributed randomly throughout the acinus volume (a). Following hollowing, cells in the luminal space begin undergo apoptosis (b), leading to the eventual filling of the luminal space with apoptotic bodies.

Fig. 5.
Fig. 5.

(Media 5) Time-lapse OCT movie of acinar growth and development. Two neighboring B-scans were averaged.The movie runs for 92 hours, beginning on day 13 of growth. The camera was run at a rate of 3076 Hz for an integration time of 325 μs per A-line. Volumes were collected continuously, with a full 2 mm × 1 mm × 1.6 mm volume recorded every hour. Three acini are labeled in the figure, here called “A”, “B”, and “C”.

Fig. 6.
Fig. 6.

(Media 6)Time-lapse OCT movie of acinar treatment with CISplatin. Two neighboring B-scans were averaged. The movie runs for 81 hours, beginning on day 13 of growth. The camera was run at a rate of 1081 Hz for an integration time of 925 μs per A-line. Volumes were collected continuously, with a full 2 mm × 1 mm × 1.6 mm volume recorded every 30 minutes.

Fig. 7.
Fig. 7.

CISplatin treated ovarian cancer acini can survive the chemotherapeutic regimen. Two acini from the time-lapse movie in Figure 6 before treatment (a) and after treatment (b), and their z-projections (c), and (d), respectively. Following treatment, both acini display solid, spherical structures (blue circles in (d)) that are revealed to be the surviving acinar cores using the Live/Dead viability assay (e). Viable cells show green fluorescence from cleaved Calcein Green AM, while dead cells are are shown in red, stained by Ethidium bromide. Many of the dead cells seen in (d) were lost during the staining process, resulting in the few dead cells observed in (e).

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