Abstract

Holographic optical coherence imaging is an en face form of optical coherence tomography that uses low-coherence digital holography as a coherence gate to select light from a chosen depth inside scattering tissue. By acquiring successive holograms at a high camera frame rate at a fixed depth, dynamic speckle provides information concerning dynamic light scattering from intracellular motility. Motility contrast imaging (MCI) uses living motion as a label-free and functional biomarker. MCI provides a new form of viability assay and also is applicable for proliferation and cytotoxicity assays. The results presented here demonstrate that low-coherence digital holography can extract viability information from biologically relevant three-dimensional (3D) tissue based on multicellular tumor spheroids by moving beyond the format of two-dimensional cell culture used for conventional high-content analysis. This paper also demonstrates the use of MCI for chemosensitivity assays on tumor exgrafts of excised ovarian cancer tumors responding to standard-of-care cisplatin chemotherapy. This ex vivo application extends the applicability of MCI beyond 3D tissue culture grown in vitro.

© 2012 Optical Society of America

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    [CrossRef]

2011

G. Farhat, A. Mariampillai, V. X. D. Yang, G. J. Czarnota, and M. C. Kolios, “Detecting apoptosis using dynamic light scattering with optical coherence tomography,” J. Biomed. Opt. 16, 070505 (2011).
[CrossRef]

Z. Wang, L. Millet, V. Chan, H. Ding, M. U. Gillette, R. Bashir, and G. Popescu, “Label-free intracellular transport measured by spatial light interference microscopy,” J. Biomed. Opt. 16, 026019 (2011).
[CrossRef]

E. Oikonomou, M. Koc, V. Sourkova, L. Andera, and A. Pintzas, “Selective BRAFV600E inhibitor PLX4720, requires TRAIL assistance to overcome oncogenic PIK3CA resistance,” Plos One 6, e21632 (2011).
[CrossRef]

W. De Roock, V. De Vriendt, N. Normanno, F. Ciardiello, and S. Tejpar, “KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer,” Lancet Oncol. 12, 594–603 (2011).
[CrossRef]

E. Vakiani and D. B. Solit, “KRAS and BRAF: drug targets and predictive biomarkers,” J. Pathol. 223, 220–230 (2011).
[CrossRef]

M. Markman, “Counterpoint: chemosensitivity assays for recurrent ovarian cancer,” J. Natl. Compr. Cancer Network 9, 121–124 (2011).

2010

T. J. Herzog, T. C. Krivak, A. N. Fader, and R. L. Coleman, “Chemosensitivity testing with ChemoFx and overall survival in primary ovarian cancer,” Am. J. Obstet. Gynecol. 203, 68.e1–68.e6 (2010).
[CrossRef]

V. Guarneri, F. Piacentini, E. Barbieri, and P. F. Conte, “Achievements and unmet needs in the management of advanced ovarian cancer,” Gynecol. Oncol. 117, 152–158 (2010).
[CrossRef]

C. Joo, C. L. Evans, T. Stepinac, T. Hasan, and J. F. de Boer, “Diffusive and directional intracellular dynamics measured by field-based dynamic light scattering,” Opt. Express 18, 2858–2871 (2010).
[CrossRef]

L. T. K. Jin, Y. Shen, K. He, Z. Xu, and G. Li, “Patient-derived human tumour tissue xenografts in immunodeficient mice: a systematic review,” Clin. Trans. Oncol. 12, 473–480 (2010).
[CrossRef]

H. M. F. Hirschhaeuser, C. Dittfeld, J. West, W. Mueller-Klieser, and L. A. Kunz-Schughart, “Multicellular tumor spheroids: an underestimated tool is catching up again,” J. Biotechnol. 148, 3–15 (2010).
[CrossRef]

T. Durduran, R. Choe, W. B. Baker, and A. G. Yodh, “Diffuse optics for tissue monitoring and tomography,” Rep. Prog. Phys. 73, 076701 (2010).
[CrossRef]

2009

P.C. De Witt Hamer, S. Leenstra, C. J. Van Noorden, and A. H. Zwinderman, “Organotypic glioma spheroids for screening of experimental therapies: how many spheroids and sections are required?” Cytometry Part A 75, 528–534 (2009).
[CrossRef]

T. T. Chang and M. Hughes-Fulford, “Monolayer and spheroid culture of human liver hepatocellular carcinoma cell line cells demonstrate distinct global gene expression patterns and functional phenotypes,” Tissue Eng. A 15, 559–567 (2009).
[CrossRef]

I. A. Cree, “Chemosensitivity and chemoresistance testing in ovarian cancer,” Curr. Opin. Obstet. Gynecol. 21, 39–43 (2009).
[CrossRef]

2008

H. Neubauer, M. Stefanova, E. Solomayer, C. Meisner, M. Zwirner, D. Wallwiener, and T. Fehm, “Predicting resistance to chemotherapy with the ATP tumor chemosensitivity assay in primary ovarian cancer,” Anticancer Res. 28, 949–955 (2008).
[CrossRef]

N. A. L. Cody, M. Zietarska, A. Filali-Mouhim, D. M. Provencher, A. M. Mes-Masson, and P. N. Tonin, “Influence of monolayer, spheroid, and tumor growth conditions on chromosome 3 gene expression in tumorigenic epithelial ovarian cancer cell lines,” BMC Med. Genom. 1, 34 (2008).
[CrossRef]

I. Serebriiskii, R. Castello-Cros, A. Lamb, E. A. Golemis, and E. Cukierman, “Fibroblast-derived 3D matrix differentially regulates the growth and drug-responsiveness of human cancer cells,” Matrix biol. 27, 573–585 (2008).
[CrossRef]

L. David, V. Dulong, D. Le Cerf, L. Cazin, M. Lamacz, and J. P. Vannier, “Hyaluronan hydrogel: an appropriate three-dimensional model for evaluation of anticancer drug sensitivity,” Acta Biomater. 4, 256–263 (2008).
[CrossRef]

2007

L. Gaedtke, L. Thoenes, C. Culmsee, B. Mayer, and E. Wagner, “Proteomic analysis reveals differences in protein expression in spheroid versus monolayer cultures of low-passage colon carcinoma cells,” J. Proteome Res. 6, 4111–4118 (2007).
[CrossRef]

M. Zietarska, C. M. Maugard, A. Filali-Mouhim, M. Alam-Fahmy, P. N. Tonin, D. M. Provencher, and A. M. Mes-Masson, “Molecular description of a 3D in vitro model for the study of epithelial ovarian cancer (EOC),” Mol. Carcinog. 46, 872–885 (2007).
[CrossRef]

M. Shimada, Y. Yamashita, S. Tanaka, K. Shirabe, K. Nakazawa, H. Ijima, R. Sakiyama, J. Fukuda, K. Funatsu, and K. Sugimachi, “Characteristic gene expression induced by polyurethane foam/spheroid culture of hepatoma cell line, Hep G2 as a promising cell source for bioartificial liver,” Hepatogastroenterology 54, 814–820 (2007).

K. Dardousis, C. Voolstra, M. Roengvoraphoj, A. Sekandarzad, S. Mesghenna, J. Winkler, Y. Ko, J. Hescheler, and A. Sachinidis, “Identification of differentially expressed genes involved in the formation of multicellular tumor spheroids by HT-29 colon carcinoma cells,” Molec. Ther. 15, 94–102 (2007).
[CrossRef]

F. Pampaloni, E. G. Reynaud, and E. H. K. Stelzer, “The third dimension bridges the gap between cell culture and live tissue,” Nat. Rev. Mol. Cell Biol. 8, 839–845 (2007).
[CrossRef]

J. J. T. K. Jeong and D. D. Nolte, “Volumetric motility-contrast imaging of tissue response to cytoskeletal anti-cancer drugs,” Opt. Express 15, 14057–14064 (2007).
[CrossRef]

M. Satpathy, L. Cao, R. Pincheira, R. Emerson, R. Bigsby, H. Nakshatri, and D. Matei, “Enhanced peritoneal ovarian tumor dissemination by tissue transglutaminase,” Cancer Res. 67, 7194–7202 (2007).
[CrossRef]

K. Jeong, J. J. Turek, and D. D. Nolte, “Fourier-domain digital holographic optical coherence imaging of living tissue,” Appl. Opt. 46, 4999–5008 (2007).
[CrossRef]

2006

O. J. Becher and E. C. Holland, “Genetically engineered models have advantages over xenografts for preclinical studies,” Cancer Res. 66, 3355–3359 (2006).
[CrossRef]

P. J. Keller, F. Pampaloni, and E. H. K. Stelzer, “Life sciences require the third dimension,” Curr. Opin. Cell Biol. 18, 117–124 (2006).
[CrossRef]

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. Anim. 42, 242–247 (2006).
[CrossRef]

2005

M. Suggitt and M. C. Bibby, “50 years of preclinical anticancer drug screening: empirical to target-driven approaches,” Clin. Cancer Res. 11, 971–981 (2005).

K. Jeong, L. Peng, J. J. Turek, M. R. Melloch, and D. D. Nolte, “Fourier-domain holographic optical coherence imaging of tumor spheroids and mouse eye,” Appl. Opt. 44, 1798–1805 (2005).
[CrossRef]

2004

P. Yu, M. Mustata, L. L. Peng, J. J. Turek, M. R. Melloch, P. M. W. French, and D. D. Nolte, “Holographic optical coherence imaging of rat osteogenic sarcoma tumor spheroids,” Appl. Opt. 43, 4862–4873 (2004).
[CrossRef]

K. Jeong, L. Peng, D. D. Nolte, and M. R. Melloch, “Fourier-domain holography in photorefractive quantum-well films,” Appl. Opt. 43, 3802–3811 (2004).
[CrossRef]

L. A. Kunz-Schughart, J. P. Freyer, F. Hofstaedter, and R. Ebner, “The use of 3-D cultures for high-throughput screening: the multicellular spheroid model,” J. Biomol. Sceening 9, 273–285 (2004).
[CrossRef]

T. J. Shaw, M. K. Senterman, K. Dawson, C. A. Crane, and B. C. Vanderhyden, “Characterization of intraperitoneal, orthotopic, and metastatic xenograft models of human ovarian cancer,” Molec. Ther. 10, 013 (2004).
[CrossRef]

Y. Yamashita, M. Shimada, N. Harimoto, S. Tanaka, K. Shirabe, H. Ijima, K. Nakazawa, J. Fukuda, K. Funatsu, and Y. Maehara, “cDNA microarray analysis in hepatocyte differentiation in Huh 7 cells,” Cell transplantation 13, 793–799 (2004).
[CrossRef]

2003

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography—principles and applications,” Rep. Prog. Phys. 66, 239–303 (2003).
[CrossRef]

M. A. Choma, M. V. Sarunic, C. H. Yang, and J. A. Izatt, “Sensitivity advantage of swept source and Fourier domain optical coherence tomography,” Opt. Express 11, 2183–2189 (2003).
[CrossRef]

N. Iftimia, B. E. Bouma, and G. J. Tearney, “Speckle reduction in optical coherence tomography by ‘path length encoded’ angular compounding,” J. Biomed. Opt. 8, 260–263 (2003).
[CrossRef]

A. Wax, C. Yang, and J. A. Izatt, “Fourier-domain low-coherence interferometry for light-scattering spectroscopy,” Opt. Lett. 28, 1230–1232 (2003).
[CrossRef]

L. A. Hazlehurst, T. H. Landowski, and W. S. Dalton, “Role of the tumor microenvironment in mediating de novo resistance to drugs and physiological mediators of cell death,” Oncogene 22, 7396–7402 (2003).
[CrossRef]

P. Yu, M. Mustata, J. J. Turek, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83, 575–577 (2003).
[CrossRef]

2002

T. Jacks and R. A. Weinberg, “Taking the study of cancer cell survival to a new dimension,” Cell 111, 923–925 (2002).
[CrossRef]

J. Poland, P. Sinha, A. Siegert, M. Schnolzer, U. Korf, and S. Hauptmann, “Comparison of protein expression profiles between monolayer and spheroid cell culture of HT-29 cells revealed fragmentation of CK18 in three-dimensional cell culture,” Electrophoresis 23, 1174–1184 (2002).
[CrossRef]

2001

E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, “Taking cell-matrix adhesions to the third dimension,” Science 294, 1708–1712 (2001).
[CrossRef]

2000

M. Bashkansky and J. Reintjes, “Statistics and reduction of speckle in optical coherence tomography,” Opt. Lett. 25, 545–547 (2000).
[CrossRef]

L. A. Kunz-Schughart, J. Doetsch, W. Mueller-Klieser, K. Groebe, F. Hofstaedter, and R. Ebner, “Proliferative activity and tumorigenic conversion: impact on cellular metabolism in 3-D culture,” Am. J. Physiol. Cell Physiol. 278, C765–C780 (2000).

1999

J. M. Schmitt, S. H. Xiang, and K. M. Yung, “Speckle in optical coherence tomography,” J. Biomed. Opt. 4, 95–105 (1999).
[CrossRef]

J. M. Schmitt, “Optical coherence tomography (OCT): a review,” IEEE J. Sel. Top. Quantum Electron. 5, 1205–1215 (1999).
[CrossRef]

1998

R. Hamamoto, K. Yamada, M. Kamihira, and S. Iijima, “Differentiation and proliferation of primary rat hepatocytes cultured as spheroids,” J. Biochem. Microbiol. Technol. Eng. 124, 972–979 (1998).
[CrossRef]

G. Hamilton, “Multicellular spheroids as an in vitro tumor mode,” Cancer Lett. 131, 29–34 (1998).
[CrossRef]

1997

L. de Ridder, “Autologous confrontation of brain tumor derived spheroids with human dermal spheroids,” Anticancer Res. 17, 4119–4120 (1997).

G. Maret, “Diffusing-wave spectroscopy,” Curr. Opin. Colloid Interf. Sci. 2, 251–257 (1997).
[CrossRef]

A. Frankel, R. Buckman, and R. S. Kerbel, “Abrogation of taxol-induced G2-M arrest and apoptosis in human ovarian cancer cells grown as multicellular tumor spheroids,” Cancer Res. 57, 2388–2393 (1997).

1996

K. Groebe ang W. Mueller-Klieser, “On the relation between size of necrosis and diameter of tumor spheroids,” Int. J. Radiat. Oncol. Biol. Phys. 34, 395–401 (1996).
[CrossRef]

P. Hargrave, P. W. Nicholson, D. T. Delpy, and M. Firbank, “Optical properties of multicellular tumor spheroids,” Phys. Med. Biol. 41, 1067–1072 (1996).
[CrossRef]

1995

D. A. Boas, L. E. Campbell, and A. G. Yodh, “Scattering and imaging with diffusing temporal field correlations,” Phys. Rev. Lett. 75, 1855–1858 (1995).
[CrossRef]

1994

R. L. Dougherty, B. J. Ackerson, N. M. Reguigui, F. Dorrinowkoorani, and U. Nobbmann, “Correlation transfer—development and application,” J. Quant. Spectrosc. Radiat. Transfer 52, 713–727 (1994).
[CrossRef]

1993

R. Parker, I. Dimery, M. Dabholkar, J. Vionnet, and E. Reed, “Platinum-DNA adduct in head and neck-cancer patients receiving cisplatin and carboplatin chemotherapy,” Int. J. Oncol. 3, 331–335 (1993).

1992

B. J. Ackerson, R. L. Dougherty, N. M. Reguigui, and U. Nobbmann, “Correlation transfer—application of radiative-transfer solution methods to photon-correlation problems,” J. Thermophys. Heat Transfer 6, 577–588 (1992).
[CrossRef]

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. Puliafto, and J. G. Fujimoto, “Optical coherence tomography,” Science 254, 1178–1181 (1991).
[CrossRef]

R. J. Parker, A. Eastman, F. Bostick-Bruton, and E. Reed, “Acquired cisplatin resistance in human ovarian-cancer cell is associated with enhanced repair of cisplatin-DNA lesions and reduced drug accumulation,” J. Clin. Invest. 87, 772–777 (1991).
[CrossRef]

1988

D. J. Pine, D. A. Weitz, P. M. Chaikin, and E. Herbolzheimer, “Diffusing-wave spectroscopy,” Phys. Rev. Lett. 60, 1134–1137 (1988).
[CrossRef]

1977

A. A. Yunis, “Human pancreatic carcinoma (MIA PaCa-2) in continuous culture: sensitivity to asparaginase,” Int. J. Cancer 19, 128–135 (1977).
[CrossRef]

1970

R. M. Sutherland, W. R. Inch, J. A. McCredie, and J. Kruuv, “A multicomponent radiation survival curve using an in vitro tumor model,” Int. J. Radiat. Biol. Relat. Stud. Phys., Chem. Med. 18, 491–495 (1970).
[CrossRef]

1969

J. Rygaard and C. O. Povlsen, “Heterotransplantation of a human malignant tumour to ‘nude’ mice,” Acta Pathol. Microbiol. Scand. 77, 758–760 (1969).
[CrossRef]

Ackerson, B. J.

R. L. Dougherty, B. J. Ackerson, N. M. Reguigui, F. Dorrinowkoorani, and U. Nobbmann, “Correlation transfer—development and application,” J. Quant. Spectrosc. Radiat. Transfer 52, 713–727 (1994).
[CrossRef]

B. J. Ackerson, R. L. Dougherty, N. M. Reguigui, and U. Nobbmann, “Correlation transfer—application of radiative-transfer solution methods to photon-correlation problems,” J. Thermophys. Heat Transfer 6, 577–588 (1992).
[CrossRef]

Alam-Fahmy, M.

M. Zietarska, C. M. Maugard, A. Filali-Mouhim, M. Alam-Fahmy, P. N. Tonin, D. M. Provencher, and A. M. Mes-Masson, “Molecular description of a 3D in vitro model for the study of epithelial ovarian cancer (EOC),” Mol. Carcinog. 46, 872–885 (2007).
[CrossRef]

Andera, L.

E. Oikonomou, M. Koc, V. Sourkova, L. Andera, and A. Pintzas, “Selective BRAFV600E inhibitor PLX4720, requires TRAIL assistance to overcome oncogenic PIK3CA resistance,” Plos One 6, e21632 (2011).
[CrossRef]

Baker, W. B.

T. Durduran, R. Choe, W. B. Baker, and A. G. Yodh, “Diffuse optics for tissue monitoring and tomography,” Rep. Prog. Phys. 73, 076701 (2010).
[CrossRef]

Barbieri, E.

V. Guarneri, F. Piacentini, E. Barbieri, and P. F. Conte, “Achievements and unmet needs in the management of advanced ovarian cancer,” Gynecol. Oncol. 117, 152–158 (2010).
[CrossRef]

Bashir, R.

Z. Wang, L. Millet, V. Chan, H. Ding, M. U. Gillette, R. Bashir, and G. Popescu, “Label-free intracellular transport measured by spatial light interference microscopy,” J. Biomed. Opt. 16, 026019 (2011).
[CrossRef]

Bashkansky, M.

Becher, O. J.

O. J. Becher and E. C. Holland, “Genetically engineered models have advantages over xenografts for preclinical studies,” Cancer Res. 66, 3355–3359 (2006).
[CrossRef]

Bibby, M. C.

M. Suggitt and M. C. Bibby, “50 years of preclinical anticancer drug screening: empirical to target-driven approaches,” Clin. Cancer Res. 11, 971–981 (2005).

Bigsby, R.

M. Satpathy, L. Cao, R. Pincheira, R. Emerson, R. Bigsby, H. Nakshatri, and D. Matei, “Enhanced peritoneal ovarian tumor dissemination by tissue transglutaminase,” Cancer Res. 67, 7194–7202 (2007).
[CrossRef]

Boas, D. A.

D. A. Boas, L. E. Campbell, and A. G. Yodh, “Scattering and imaging with diffusing temporal field correlations,” Phys. Rev. Lett. 75, 1855–1858 (1995).
[CrossRef]

Bostick-Bruton, F.

R. J. Parker, A. Eastman, F. Bostick-Bruton, and E. Reed, “Acquired cisplatin resistance in human ovarian-cancer cell is associated with enhanced repair of cisplatin-DNA lesions and reduced drug accumulation,” J. Clin. Invest. 87, 772–777 (1991).
[CrossRef]

Bouma, B. E.

N. Iftimia, B. E. Bouma, and G. J. Tearney, “Speckle reduction in optical coherence tomography by ‘path length encoded’ angular compounding,” J. Biomed. Opt. 8, 260–263 (2003).
[CrossRef]

Buckman, R.

A. Frankel, R. Buckman, and R. S. Kerbel, “Abrogation of taxol-induced G2-M arrest and apoptosis in human ovarian cancer cells grown as multicellular tumor spheroids,” Cancer Res. 57, 2388–2393 (1997).

Burger, A. M.

H. H. Fiebig and A. M. Burger, “Human tumor xenografts and explants,” in Tumor Models in Cancer Research, B. A. Teicher, ed. (Humana, 2001), pp. 113–137.

Campbell, L. E.

D. A. Boas, L. E. Campbell, and A. G. Yodh, “Scattering and imaging with diffusing temporal field correlations,” Phys. Rev. Lett. 75, 1855–1858 (1995).
[CrossRef]

Cao, L.

M. Satpathy, L. Cao, R. Pincheira, R. Emerson, R. Bigsby, H. Nakshatri, and D. Matei, “Enhanced peritoneal ovarian tumor dissemination by tissue transglutaminase,” Cancer Res. 67, 7194–7202 (2007).
[CrossRef]

Castello-Cros, R.

I. Serebriiskii, R. Castello-Cros, A. Lamb, E. A. Golemis, and E. Cukierman, “Fibroblast-derived 3D matrix differentially regulates the growth and drug-responsiveness of human cancer cells,” Matrix biol. 27, 573–585 (2008).
[CrossRef]

Cazin, L.

L. David, V. Dulong, D. Le Cerf, L. Cazin, M. Lamacz, and J. P. Vannier, “Hyaluronan hydrogel: an appropriate three-dimensional model for evaluation of anticancer drug sensitivity,” Acta Biomater. 4, 256–263 (2008).
[CrossRef]

Chaikin, P. M.

D. J. Pine, D. A. Weitz, P. M. Chaikin, and E. Herbolzheimer, “Diffusing-wave spectroscopy,” Phys. Rev. Lett. 60, 1134–1137 (1988).
[CrossRef]

Chan, V.

Z. Wang, L. Millet, V. Chan, H. Ding, M. U. Gillette, R. Bashir, and G. Popescu, “Label-free intracellular transport measured by spatial light interference microscopy,” J. Biomed. Opt. 16, 026019 (2011).
[CrossRef]

Chang, T. T.

T. T. Chang and M. Hughes-Fulford, “Monolayer and spheroid culture of human liver hepatocellular carcinoma cell line cells demonstrate distinct global gene expression patterns and functional phenotypes,” Tissue Eng. A 15, 559–567 (2009).
[CrossRef]

Chang, W.

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. Puliafto, and J. G. Fujimoto, “Optical coherence tomography,” Science 254, 1178–1181 (1991).
[CrossRef]

Choe, R.

T. Durduran, R. Choe, W. B. Baker, and A. G. Yodh, “Diffuse optics for tissue monitoring and tomography,” Rep. Prog. Phys. 73, 076701 (2010).
[CrossRef]

Choma, M. A.

Ciardiello, F.

W. De Roock, V. De Vriendt, N. Normanno, F. Ciardiello, and S. Tejpar, “KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer,” Lancet Oncol. 12, 594–603 (2011).
[CrossRef]

Cody, N. A. L.

N. A. L. Cody, M. Zietarska, A. Filali-Mouhim, D. M. Provencher, A. M. Mes-Masson, and P. N. Tonin, “Influence of monolayer, spheroid, and tumor growth conditions on chromosome 3 gene expression in tumorigenic epithelial ovarian cancer cell lines,” BMC Med. Genom. 1, 34 (2008).
[CrossRef]

Coleman, R. L.

T. J. Herzog, T. C. Krivak, A. N. Fader, and R. L. Coleman, “Chemosensitivity testing with ChemoFx and overall survival in primary ovarian cancer,” Am. J. Obstet. Gynecol. 203, 68.e1–68.e6 (2010).
[CrossRef]

Conte, P. F.

V. Guarneri, F. Piacentini, E. Barbieri, and P. F. Conte, “Achievements and unmet needs in the management of advanced ovarian cancer,” Gynecol. Oncol. 117, 152–158 (2010).
[CrossRef]

Crane, C. A.

T. J. Shaw, M. K. Senterman, K. Dawson, C. A. Crane, and B. C. Vanderhyden, “Characterization of intraperitoneal, orthotopic, and metastatic xenograft models of human ovarian cancer,” Molec. Ther. 10, 013 (2004).
[CrossRef]

Cree, I. A.

I. A. Cree, “Chemosensitivity and chemoresistance testing in ovarian cancer,” Curr. Opin. Obstet. Gynecol. 21, 39–43 (2009).
[CrossRef]

Cukierman, E.

I. Serebriiskii, R. Castello-Cros, A. Lamb, E. A. Golemis, and E. Cukierman, “Fibroblast-derived 3D matrix differentially regulates the growth and drug-responsiveness of human cancer cells,” Matrix biol. 27, 573–585 (2008).
[CrossRef]

E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, “Taking cell-matrix adhesions to the third dimension,” Science 294, 1708–1712 (2001).
[CrossRef]

Culmsee, C.

L. Gaedtke, L. Thoenes, C. Culmsee, B. Mayer, and E. Wagner, “Proteomic analysis reveals differences in protein expression in spheroid versus monolayer cultures of low-passage colon carcinoma cells,” J. Proteome Res. 6, 4111–4118 (2007).
[CrossRef]

Czarnota, G. J.

G. Farhat, A. Mariampillai, V. X. D. Yang, G. J. Czarnota, and M. C. Kolios, “Detecting apoptosis using dynamic light scattering with optical coherence tomography,” J. Biomed. Opt. 16, 070505 (2011).
[CrossRef]

Dabholkar, M.

R. Parker, I. Dimery, M. Dabholkar, J. Vionnet, and E. Reed, “Platinum-DNA adduct in head and neck-cancer patients receiving cisplatin and carboplatin chemotherapy,” Int. J. Oncol. 3, 331–335 (1993).

Dalton, W. S.

L. A. Hazlehurst, T. H. Landowski, and W. S. Dalton, “Role of the tumor microenvironment in mediating de novo resistance to drugs and physiological mediators of cell death,” Oncogene 22, 7396–7402 (2003).
[CrossRef]

Dardousis, K.

K. Dardousis, C. Voolstra, M. Roengvoraphoj, A. Sekandarzad, S. Mesghenna, J. Winkler, Y. Ko, J. Hescheler, and A. Sachinidis, “Identification of differentially expressed genes involved in the formation of multicellular tumor spheroids by HT-29 colon carcinoma cells,” Molec. Ther. 15, 94–102 (2007).
[CrossRef]

David, L.

L. David, V. Dulong, D. Le Cerf, L. Cazin, M. Lamacz, and J. P. Vannier, “Hyaluronan hydrogel: an appropriate three-dimensional model for evaluation of anticancer drug sensitivity,” Acta Biomater. 4, 256–263 (2008).
[CrossRef]

Dawson, K.

T. J. Shaw, M. K. Senterman, K. Dawson, C. A. Crane, and B. C. Vanderhyden, “Characterization of intraperitoneal, orthotopic, and metastatic xenograft models of human ovarian cancer,” Molec. Ther. 10, 013 (2004).
[CrossRef]

de Boer, J. F.

de Ridder, L.

L. de Ridder, “Autologous confrontation of brain tumor derived spheroids with human dermal spheroids,” Anticancer Res. 17, 4119–4120 (1997).

De Roock, W.

W. De Roock, V. De Vriendt, N. Normanno, F. Ciardiello, and S. Tejpar, “KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer,” Lancet Oncol. 12, 594–603 (2011).
[CrossRef]

De Vriendt, V.

W. De Roock, V. De Vriendt, N. Normanno, F. Ciardiello, and S. Tejpar, “KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer,” Lancet Oncol. 12, 594–603 (2011).
[CrossRef]

De Witt Hamer, P.C.

P.C. De Witt Hamer, S. Leenstra, C. J. Van Noorden, and A. H. Zwinderman, “Organotypic glioma spheroids for screening of experimental therapies: how many spheroids and sections are required?” Cytometry Part A 75, 528–534 (2009).
[CrossRef]

Delpy, D. T.

P. Hargrave, P. W. Nicholson, D. T. Delpy, and M. Firbank, “Optical properties of multicellular tumor spheroids,” Phys. Med. Biol. 41, 1067–1072 (1996).
[CrossRef]

Dimery, I.

R. Parker, I. Dimery, M. Dabholkar, J. Vionnet, and E. Reed, “Platinum-DNA adduct in head and neck-cancer patients receiving cisplatin and carboplatin chemotherapy,” Int. J. Oncol. 3, 331–335 (1993).

Ding, H.

Z. Wang, L. Millet, V. Chan, H. Ding, M. U. Gillette, R. Bashir, and G. Popescu, “Label-free intracellular transport measured by spatial light interference microscopy,” J. Biomed. Opt. 16, 026019 (2011).
[CrossRef]

Dittfeld, C.

H. M. F. Hirschhaeuser, C. Dittfeld, J. West, W. Mueller-Klieser, and L. A. Kunz-Schughart, “Multicellular tumor spheroids: an underestimated tool is catching up again,” J. Biotechnol. 148, 3–15 (2010).
[CrossRef]

Doetsch, J.

L. A. Kunz-Schughart, J. Doetsch, W. Mueller-Klieser, K. Groebe, F. Hofstaedter, and R. Ebner, “Proliferative activity and tumorigenic conversion: impact on cellular metabolism in 3-D culture,” Am. J. Physiol. Cell Physiol. 278, C765–C780 (2000).

Dorrinowkoorani, F.

R. L. Dougherty, B. J. Ackerson, N. M. Reguigui, F. Dorrinowkoorani, and U. Nobbmann, “Correlation transfer—development and application,” J. Quant. Spectrosc. Radiat. Transfer 52, 713–727 (1994).
[CrossRef]

Dougherty, R. L.

R. L. Dougherty, B. J. Ackerson, N. M. Reguigui, F. Dorrinowkoorani, and U. Nobbmann, “Correlation transfer—development and application,” J. Quant. Spectrosc. Radiat. Transfer 52, 713–727 (1994).
[CrossRef]

B. J. Ackerson, R. L. Dougherty, N. M. Reguigui, and U. Nobbmann, “Correlation transfer—application of radiative-transfer solution methods to photon-correlation problems,” J. Thermophys. Heat Transfer 6, 577–588 (1992).
[CrossRef]

Drexler, W.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography—principles and applications,” Rep. Prog. Phys. 66, 239–303 (2003).
[CrossRef]

Dulong, V.

L. David, V. Dulong, D. Le Cerf, L. Cazin, M. Lamacz, and J. P. Vannier, “Hyaluronan hydrogel: an appropriate three-dimensional model for evaluation of anticancer drug sensitivity,” Acta Biomater. 4, 256–263 (2008).
[CrossRef]

Durduran, T.

T. Durduran, R. Choe, W. B. Baker, and A. G. Yodh, “Diffuse optics for tissue monitoring and tomography,” Rep. Prog. Phys. 73, 076701 (2010).
[CrossRef]

Eastman, A.

R. J. Parker, A. Eastman, F. Bostick-Bruton, and E. Reed, “Acquired cisplatin resistance in human ovarian-cancer cell is associated with enhanced repair of cisplatin-DNA lesions and reduced drug accumulation,” J. Clin. Invest. 87, 772–777 (1991).
[CrossRef]

Ebner, R.

L. A. Kunz-Schughart, J. P. Freyer, F. Hofstaedter, and R. Ebner, “The use of 3-D cultures for high-throughput screening: the multicellular spheroid model,” J. Biomol. Sceening 9, 273–285 (2004).
[CrossRef]

L. A. Kunz-Schughart, J. Doetsch, W. Mueller-Klieser, K. Groebe, F. Hofstaedter, and R. Ebner, “Proliferative activity and tumorigenic conversion: impact on cellular metabolism in 3-D culture,” Am. J. Physiol. Cell Physiol. 278, C765–C780 (2000).

Emerson, R.

M. Satpathy, L. Cao, R. Pincheira, R. Emerson, R. Bigsby, H. Nakshatri, and D. Matei, “Enhanced peritoneal ovarian tumor dissemination by tissue transglutaminase,” Cancer Res. 67, 7194–7202 (2007).
[CrossRef]

Evans, C. L.

Fader, A. N.

T. J. Herzog, T. C. Krivak, A. N. Fader, and R. L. Coleman, “Chemosensitivity testing with ChemoFx and overall survival in primary ovarian cancer,” Am. J. Obstet. Gynecol. 203, 68.e1–68.e6 (2010).
[CrossRef]

Farhat, G.

G. Farhat, A. Mariampillai, V. X. D. Yang, G. J. Czarnota, and M. C. Kolios, “Detecting apoptosis using dynamic light scattering with optical coherence tomography,” J. Biomed. Opt. 16, 070505 (2011).
[CrossRef]

Fehm, T.

H. Neubauer, M. Stefanova, E. Solomayer, C. Meisner, M. Zwirner, D. Wallwiener, and T. Fehm, “Predicting resistance to chemotherapy with the ATP tumor chemosensitivity assay in primary ovarian cancer,” Anticancer Res. 28, 949–955 (2008).
[CrossRef]

Fercher, A. F.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography—principles and applications,” Rep. Prog. Phys. 66, 239–303 (2003).
[CrossRef]

Fiebig, H. H.

H. H. Fiebig and A. M. Burger, “Human tumor xenografts and explants,” in Tumor Models in Cancer Research, B. A. Teicher, ed. (Humana, 2001), pp. 113–137.

Filali-Mouhim, A.

N. A. L. Cody, M. Zietarska, A. Filali-Mouhim, D. M. Provencher, A. M. Mes-Masson, and P. N. Tonin, “Influence of monolayer, spheroid, and tumor growth conditions on chromosome 3 gene expression in tumorigenic epithelial ovarian cancer cell lines,” BMC Med. Genom. 1, 34 (2008).
[CrossRef]

M. Zietarska, C. M. Maugard, A. Filali-Mouhim, M. Alam-Fahmy, P. N. Tonin, D. M. Provencher, and A. M. Mes-Masson, “Molecular description of a 3D in vitro model for the study of epithelial ovarian cancer (EOC),” Mol. Carcinog. 46, 872–885 (2007).
[CrossRef]

Firbank, M.

P. Hargrave, P. W. Nicholson, D. T. Delpy, and M. Firbank, “Optical properties of multicellular tumor spheroids,” Phys. Med. Biol. 41, 1067–1072 (1996).
[CrossRef]

Flotte, T.

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. Puliafto, and J. G. Fujimoto, “Optical coherence tomography,” Science 254, 1178–1181 (1991).
[CrossRef]

Frankel, A.

A. Frankel, R. Buckman, and R. S. Kerbel, “Abrogation of taxol-induced G2-M arrest and apoptosis in human ovarian cancer cells grown as multicellular tumor spheroids,” Cancer Res. 57, 2388–2393 (1997).

French, P. M. W.

P. Yu, M. Mustata, L. L. Peng, J. J. Turek, M. R. Melloch, P. M. W. French, and D. D. Nolte, “Holographic optical coherence imaging of rat osteogenic sarcoma tumor spheroids,” Appl. Opt. 43, 4862–4873 (2004).
[CrossRef]

P. Yu, M. Mustata, J. J. Turek, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83, 575–577 (2003).
[CrossRef]

Freyer, J. P.

L. A. Kunz-Schughart, J. P. Freyer, F. Hofstaedter, and R. Ebner, “The use of 3-D cultures for high-throughput screening: the multicellular spheroid model,” J. Biomol. Sceening 9, 273–285 (2004).
[CrossRef]

Fujimoto, J. 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. Puliafto, and J. G. Fujimoto, “Optical coherence tomography,” Science 254, 1178–1181 (1991).
[CrossRef]

Fukuda, J.

M. Shimada, Y. Yamashita, S. Tanaka, K. Shirabe, K. Nakazawa, H. Ijima, R. Sakiyama, J. Fukuda, K. Funatsu, and K. Sugimachi, “Characteristic gene expression induced by polyurethane foam/spheroid culture of hepatoma cell line, Hep G2 as a promising cell source for bioartificial liver,” Hepatogastroenterology 54, 814–820 (2007).

Y. Yamashita, M. Shimada, N. Harimoto, S. Tanaka, K. Shirabe, H. Ijima, K. Nakazawa, J. Fukuda, K. Funatsu, and Y. Maehara, “cDNA microarray analysis in hepatocyte differentiation in Huh 7 cells,” Cell transplantation 13, 793–799 (2004).
[CrossRef]

Funatsu, K.

M. Shimada, Y. Yamashita, S. Tanaka, K. Shirabe, K. Nakazawa, H. Ijima, R. Sakiyama, J. Fukuda, K. Funatsu, and K. Sugimachi, “Characteristic gene expression induced by polyurethane foam/spheroid culture of hepatoma cell line, Hep G2 as a promising cell source for bioartificial liver,” Hepatogastroenterology 54, 814–820 (2007).

Y. Yamashita, M. Shimada, N. Harimoto, S. Tanaka, K. Shirabe, H. Ijima, K. Nakazawa, J. Fukuda, K. Funatsu, and Y. Maehara, “cDNA microarray analysis in hepatocyte differentiation in Huh 7 cells,” Cell transplantation 13, 793–799 (2004).
[CrossRef]

Gaedtke, L.

L. Gaedtke, L. Thoenes, C. Culmsee, B. Mayer, and E. Wagner, “Proteomic analysis reveals differences in protein expression in spheroid versus monolayer cultures of low-passage colon carcinoma cells,” J. Proteome Res. 6, 4111–4118 (2007).
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Gillette, M. U.

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Figures (8)

Fig. 1.
Fig. 1.

Principle of digital holographic motility contrast imaging (DHMCI) on multicellular tumor spheroids. The biological sample is located at the image plane of lens L1. The backscattered light from the sample is Fourier transformed by L1 and interferes with the reference beam on the CCD chip. The speckle hologram is recorded on the Fourier plane with a 2° crossing angel with the reference beam. Note examples of (a) raw digital hologram, (b) reconstructed image, (c) MCI image. O.A., optical axis; I.P., image plane; L1, lens; BS, beam splitter; CCD, charge-coupled device.

Fig. 2.
Fig. 2.

Selected motility contrast images of UMR-106, HT-29, DLD-1, and PaCa-2 MTS samples. The color represents the motility metric (NSD) on a scale from 0% to 100%. Red means indicates the intracellular motility is active. The PaCa-2 and DLD-1 cell lines are highly aggressive and proliferative, resulting in high motility metrics relative to UMR-106 and HT-29. The shape of PaCa-2 and DLD-1 MTSs is usually not very regular, while the shape of UMR-106 and HT-29 is more like a spheroid.

Fig. 3.
Fig. 3.

Distribution of motility metric values (NSD) for spheroids from four cell lines (UMR-106, HT-29, DLD-1, and PaCa-2). The fit curves are skewed normal distributions. The y axis is the distribution number, and the x axis is the NSD value. The PaCa-2 and DLD-1 cell lines are highly proliferative relative to the HT-29 and UMR lines. The UMR and HT lines form compact spheroids. The DLD line forms small compact spheroids that tend to clump together. The PaCa-2 line forms a loose aggregation and has the biggest NSD with the smallest diversity.

Fig. 4.
Fig. 4.

DHMCI image of UMR-106 tumor spheroids: (a) small tumor spheroid that survived from the CO2 imbalance, (b), (c) normal tumor spheroids. After surviving from the CO2 imbalance, the small tumor spheroid grew a necrotic core area, and the spheroid shape is uncommon as well. In contrast, the normal small tumor spheroid has no core area and has a spheroid shape. The large tumor shows the typical size when MTSs begin to form a necrotic core.

Fig. 5.
Fig. 5.

(a)–(c) Histograms of NSD values of UMR spheroids in a bioreactor; the y axis is the number of tumor spheroids, and the x axis is the NSD range. The refreshing of growth medium stopped at day 1. (d) Distribution of motility metric values (NSD) for healthy UMR spheroids (right), and for spheroids 2 days after CO2 was shut off in the bioreactor (left). The fit curves are skewed normal distributions.

Fig. 6.
Fig. 6.

Motility contrast maps of (a) A2780 and (b) A2780-CP70 xenografts. The average NSD values are 0.70 and 0.83, respectively. The platinum-resistant A2780-CP70 is more aggressive than the parent A2780 line and has a higher NSD value.

Fig. 7.
Fig. 7.

Holographic motility contrast image of A2780 tumor-normal tissue margin. The margin is discernible with high motility contrast because the NSD of normal tissue is smaller than the NSD of A2780.

Fig. 8.
Fig. 8.

Motility metric (NSD) of ovarian cancer tumor xenografts responding to 20 μM cisplatin. The x-axis is time (minutes), and the y-axis is NSD value. The sensitive tumor is A2780, while the insensitive tumor A2780-CP70. Both tumor tissues begin with higher motility than normal mouse tissue. The cisplatin was added at time t=0. The NSD of A2780 dropped quickly, and after 8 h it dropped to 0.1. The NSD of the insensitive tumor A2780-CP70 remained constant during the 9 h period.

Equations (4)

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

FT(IH)=FT(|ψR|2)+FT(|ψOF|2)+FT(ψR*ψOF)+FT(ψOF*ψR)=F1+F2+F3+F4,
F3(vx,vy)=iλfψR0exp(i4πfλ)ψO(λfvx+λfvx0,λfvy+λfvy0),
F4(vx,vy)=iλfψR0exp(i4πfλ)ψO*(λfvx+λfvx0,λfvy+λfvy0),
MC(x,y,z,t)=[IIτ]2Iτ,

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