Abstract

The progression of breast cancer is known to be affected by stromal cells within the local microenvironment. Here we study the effect of stromal fibroblasts on the in-place motions (motility) of mammary epithelial cells within organoids in 3D co-culture, inferred from the speckle fluctuation spectrum using optical coherence tomography (OCT). In contrast to Brownian motion, mammary cell motions exhibit an inverse-power-law fluctuation spectrum. We introduce two complementary metrics for quantifying fluctuation spectra: the power-law exponent and a novel definition of the motility amplitude, both of which are signal and position independent. We find that the power-law exponent and motility amplitude are positively (p<0.001) and negatively (p<0.01) correlated with the density of stromal cells in 3D co-culture, respectively. We also show how the hyperspectral data can be visualized using these metrics to observe heterogeneity within organoids. This constitutes a simple and powerful tool for detecting and imaging cellular functional changes with OCT.

© 2015 Optical Society of America

Full Article  |  PDF Article

Corrections

16 October 2015: A correction was made to Ref. 2 and Ref. 3.


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References

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2015 (1)

2014 (3)

R. An, D. Merrill, L. Avramova, J. Sturgis, M. Tsiper, J. P. Robinson, J. Turek, and D. D. Nolte, “Phenotypic profiling of Raf inhibitors and mitochondrial toxicity in 3D tissue using biodynamic imaging,” J. Biomol. Screening 19, 526–537 (2014).
[Crossref]

G. Lu and B. Fei, “Medical hyperspectral imaging: a review,” J. Biomed. Opt. 19, 010901 (2014).
[Crossref]

M. Guo, A. J. Ehrlicher, M. H. Jensen, M. Renz, J. R. Moore, R. D. Goldman, J. Lippincott-Schwartz, F. C. Mackintosh, and D. A. Weitz, “Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy,” Cell 158, 822–832 (2014).
[Crossref]

2013 (3)

A. L. Oldenburg, R. K. Chhetri, J. M. Cooper, W.-C. Wu, M. A. Troester, and J. B. Tracy, “Motility-, autocorrelation-, and polarization-sensitive optical coherence tomography discriminates cells and gold nanorods within 3D tissue cultures,” Opt. Lett. 38, 2923–2926 (2013).
[Crossref]

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, “Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography,” J. Cereb. Blood Flow Metab. 33, 819–825 (2013).
[Crossref]

P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, “Role of HGF in epithelial-stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ,” Breast Cancer Res. 15, R82 (2013).

2012 (8)

A. L. Oldenburg, R. K. Chhetri, D. B. Hill, and B. Button, “Monitoring airway mucus flow and ciliary activity with optical coherence tomography,” Biomed. Opt. Express 3, 1978–1992 (2012).
[Crossref]

V. J. Srinivasan, H. Radhakrishnan, E. H. Lo, E. T. Mandeville, J. Y. Jiang, S. Barry, and A. E. Cable, “OCT methods for capillary velocimetry,” Biomed. Opt. Express 3, 612–629 (2012).
[Crossref]

J. Lee, W. Wu, J. Y. Jiang, B. Zhu, and D. A. Boas, “Dynamic light scattering optical coherence tomography,” Opt. Express 20, 22262–22277 (2012).
[Crossref]

D. D. Nolte, R. An, J. Turek, and K. Jeong, “Tissue dynamics spectroscopy for phenotypic profiling of drug effects in three-dimensional culture,” Biomed. Opt. Express 3, 2825–2841 (2012).
[Crossref]

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, “Longitudinal study of mammary epithelial and fibroblast co-cultures using optical coherence tomography reveals morphological hallmarks of pre-malignancy,” PLoS One 7, e49148 (2012).
[Crossref]

K. Tanner, H. Mori, R. Mroue, A. Bruni-Cardoso, and M. J. Bissell, “Coherent angular motion in the establishment of multicellular architecture of glandular tissues,” Proc. Natl. Acad. Sci. 109, 1973–1978 (2012).

M. N. Phadke, L. Pinto, O. Alabi, J. Harter, R. M. Taylor, X. Wu, H. Petersen, S. A. Bass, and C. G. Healey, “Exploring ensemble visualization,” Proc. SPIE 8294, 82940B (2012).

E. A. Booth-Gauthier, T. A. Alcoser, G. Yang, and K. N. Dahl, “Force-induced changes in subnuclear movement and rheology,” Biophys. J. 103, 2423–2431 (2012).

2011 (3)

J. T. Camp, F. Elloumi, E. Roman-Perez, J. Rein, D. A. Stewart, J. C. Harrell, C. M. Perou, and M. A. Troester, “Interactions with fibroblasts are distinct in basal-like and luminal breast cancers,” Mol. Cancer Res. 9, 3–13 (2011).
[Crossref]

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]

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83, 040903 (2011).
[Crossref]

2010 (3)

O. Maller, H. Martinson, and P. Schedin, “Extracellular matrix composition reveals complex and dynamic stromal-epithelial interactions in the mammary gland,” J. Mammary Gland Biol. Neoplasia 15, 301–318 (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]

K. Jeong, J. J. Turek, and D. D. Nolte, “Speckle fluctuation spectroscopy of intracellular motion in living tissue using coherence-domain digital holography,” J. Biomed. Opt. 15, 030514 (2010).
[Crossref]

2007 (5)

N. Burris, K. Schwartz, C. M. Tang, M. S. Jafri, J. Schmitt, M. H. Kwon, O. Toshinaga, J. Gu, J. Brown, E. Brown, R. Pierson, and R. Poston, “Catheter-based infrared light scanner as a tool to assess conduit quality in coronary artery bypass surgery,” J. Thorac. Cardiovasc. Surg. 133, 419–427 (2007).
[Crossref]

K. R. Johnson, J. L. Leight, and V. M. Weaver, “Demystifying the effects of a three-dimensional microenvironment in tissue morphogenesis,” Methods Cell Biol. 83, 547–583 (2007).
[Crossref]

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

R. Sinkus, K. Siegmann, T. Xydeas, M. Tanter, C. Claussen, and M. Fink, “MR elastography of breast lesions: understanding the solid/liquid duality can improve the specificity of contrast-enhanced MR mammography,” Magn. Reson. Med. 58, 1135–1144 (2007).
[Crossref]

R. L. Frederick and J. M. Shaw, “Moving mitochondria: establishing distribution of an essential organelle,” Traffic 8, 1668–1675 (2007).
[Crossref]

2006 (1)

C. T. Jordan, M. L. Guzman, and M. Noble, “Cancer stem cells,” N. Engl. J. Med. 355, 1253–1261 (2006).

2005 (1)

M. J. Paszek, N. Zahir, K. R. Johnson, J. N. Lakins, G. I. Rozenberg, A. Gefen, C. A. Reinhart-King, S. S. Margulies, M. Dembo, D. Boettiger, D. A. Hammer, and V. M. Weaver, “Tensional homeostasis and the malignant phenotype,” Cancer Cell 8, 241–254 (2005).
[Crossref]

2004 (2)

N. Nassif, B. Cense, B. Hyle Park, S. H. Yun, T. C. Chen, B. E. Bouma, G. J. Tearney, and J. F. de Boer, “In vivo human retinal imaging by ultrahigh-speed spectral domain optical coherence tomography,” Opt. Lett. 29, 480–482 (2004).
[Crossref]

W. D. Foulkes, J.-S. Brunet, I. M. Stefansson, O. Straume, P. O. Chappuis, L. R. Bégin, N. Hamel, J. R. Goffin, N. Wong, M. Trudel, L. Kapusta, P. Porter, and L. A. Akslen, “The prognostic implication of the basal-like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) phenotype of BRCA1-related breast cancer,” Cancer Res. 64, 830–835 (2004).
[Crossref]

2003 (2)

J. Debnath, S. K. Muthuswamy, and J. S. Brugge, “Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures,” Methods 30, 256–268 (2003).
[Crossref]

D. L. Marks, A. L. Oldenburg, J. J. Reynolds, and S. A. Boppart, “Digital algorithm for dispersion correction in optical coherence tomography for homogeneous and stratified media,” Appl. Opt. 42, 204–217 (2003).
[Crossref]

2002 (2)

M. Ciccotti and F. Mulargia, “Pernicious effect of physical cutoffs in fractal analysis,” Phys. Rev. E 65, 037201 (2002).
[Crossref]

R. Taylor, “Visualizing multiple fields on the same surface,” IEEE Comput. Graph. Appl. 22, 6–10 (2002).
[Crossref]

2001 (1)

M. J. Bissell and D. Radisky, “Putting tumours in context,” Nat. Rev. Cancer 1, 46–54 (2001).
[Crossref]

2000 (2)

1999 (1)

1998 (1)

1995 (1)

H. Schiessel and A. Blumen, “Mesoscopic pictures of the sol-gel transition: ladder models and fractal networks,” Macromolecules 28, 4013–4019 (1995).
[Crossref]

1992 (1)

O. W. Petersen, L. Rønnov-Jessen, A. R. Howlett, and M. J. Bissell, “Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells,” Proc. Natl Acad. Sci. 89, 9064–9068 (1992).

1988 (1)

P. Bak, C. Tang, and K. Wiesenfeld, “Self-organized criticality,” Phys. Rev. A 38, 364–374 (1988).
[Crossref]

1968 (1)

B. B. Mandelbrot and J. W. Van Ness, “Fractional Brownian motions, fractional noises and applications,” SIAM Rev. 10, 422–437 (1968).
[Crossref]

Akslen, L. A.

W. D. Foulkes, J.-S. Brunet, I. M. Stefansson, O. Straume, P. O. Chappuis, L. R. Bégin, N. Hamel, J. R. Goffin, N. Wong, M. Trudel, L. Kapusta, P. Porter, and L. A. Akslen, “The prognostic implication of the basal-like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) phenotype of BRCA1-related breast cancer,” Cancer Res. 64, 830–835 (2004).
[Crossref]

Alabi, O.

M. N. Phadke, L. Pinto, O. Alabi, J. Harter, R. M. Taylor, X. Wu, H. Petersen, S. A. Bass, and C. G. Healey, “Exploring ensemble visualization,” Proc. SPIE 8294, 82940B (2012).

Alcoser, T. A.

E. A. Booth-Gauthier, T. A. Alcoser, G. Yang, and K. N. Dahl, “Force-induced changes in subnuclear movement and rheology,” Biophys. J. 103, 2423–2431 (2012).

An, R.

Andersen, P. E.

Avramova, L.

R. An, D. Merrill, L. Avramova, J. Sturgis, M. Tsiper, J. P. Robinson, J. Turek, and D. D. Nolte, “Phenotypic profiling of Raf inhibitors and mitochondrial toxicity in 3D tissue using biodynamic imaging,” J. Biomol. Screening 19, 526–537 (2014).
[Crossref]

Ayata, C.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, “Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography,” J. Cereb. Blood Flow Metab. 33, 819–825 (2013).
[Crossref]

Bak, P.

P. Bak, C. Tang, and K. Wiesenfeld, “Self-organized criticality,” Phys. Rev. A 38, 364–374 (1988).
[Crossref]

Barry, S.

Bass, S. A.

M. N. Phadke, L. Pinto, O. Alabi, J. Harter, R. M. Taylor, X. Wu, H. Petersen, S. A. Bass, and C. G. Healey, “Exploring ensemble visualization,” Proc. SPIE 8294, 82940B (2012).

Bégin, L. R.

W. D. Foulkes, J.-S. Brunet, I. M. Stefansson, O. Straume, P. O. Chappuis, L. R. Bégin, N. Hamel, J. R. Goffin, N. Wong, M. Trudel, L. Kapusta, P. Porter, and L. A. Akslen, “The prognostic implication of the basal-like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) phenotype of BRCA1-related breast cancer,” Cancer Res. 64, 830–835 (2004).
[Crossref]

Bissell, M. J.

K. Tanner, H. Mori, R. Mroue, A. Bruni-Cardoso, and M. J. Bissell, “Coherent angular motion in the establishment of multicellular architecture of glandular tissues,” Proc. Natl. Acad. Sci. 109, 1973–1978 (2012).

M. J. Bissell and D. Radisky, “Putting tumours in context,” Nat. Rev. Cancer 1, 46–54 (2001).
[Crossref]

O. W. Petersen, L. Rønnov-Jessen, A. R. Howlett, and M. J. Bissell, “Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells,” Proc. Natl Acad. Sci. 89, 9064–9068 (1992).

Bizheva, K. K.

Blumen, A.

H. Schiessel and A. Blumen, “Mesoscopic pictures of the sol-gel transition: ladder models and fractal networks,” Macromolecules 28, 4013–4019 (1995).
[Crossref]

Boas, D. A.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, “Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography,” J. Cereb. Blood Flow Metab. 33, 819–825 (2013).
[Crossref]

J. Lee, W. Wu, J. Y. Jiang, B. Zhu, and D. A. Boas, “Dynamic light scattering optical coherence tomography,” Opt. Express 20, 22262–22277 (2012).
[Crossref]

D. A. Boas, K. K. Bizheva, and A. M. Siegel, “Using dynamic low-coherence interferometry to image Brownian motion within highly scattering media,” Opt. Lett. 23, 319–321 (1998).
[Crossref]

Boettiger, D.

M. J. Paszek, N. Zahir, K. R. Johnson, J. N. Lakins, G. I. Rozenberg, A. Gefen, C. A. Reinhart-King, S. S. Margulies, M. Dembo, D. Boettiger, D. A. Hammer, and V. M. Weaver, “Tensional homeostasis and the malignant phenotype,” Cancer Cell 8, 241–254 (2005).
[Crossref]

Booth-Gauthier, E. A.

E. A. Booth-Gauthier, T. A. Alcoser, G. Yang, and K. N. Dahl, “Force-induced changes in subnuclear movement and rheology,” Biophys. J. 103, 2423–2431 (2012).

Boppart, S. A.

Bouma, B. E.

Brauer, H. A.

P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, “Role of HGF in epithelial-stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ,” Breast Cancer Res. 15, R82 (2013).

Brown, E.

N. Burris, K. Schwartz, C. M. Tang, M. S. Jafri, J. Schmitt, M. H. Kwon, O. Toshinaga, J. Gu, J. Brown, E. Brown, R. Pierson, and R. Poston, “Catheter-based infrared light scanner as a tool to assess conduit quality in coronary artery bypass surgery,” J. Thorac. Cardiovasc. Surg. 133, 419–427 (2007).
[Crossref]

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N. Burris, K. Schwartz, C. M. Tang, M. S. Jafri, J. Schmitt, M. H. Kwon, O. Toshinaga, J. Gu, J. Brown, E. Brown, R. Pierson, and R. Poston, “Catheter-based infrared light scanner as a tool to assess conduit quality in coronary artery bypass surgery,” J. Thorac. Cardiovasc. Surg. 133, 419–427 (2007).
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J. Debnath, S. K. Muthuswamy, and J. S. Brugge, “Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures,” Methods 30, 256–268 (2003).
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K. Tanner, H. Mori, R. Mroue, A. Bruni-Cardoso, and M. J. Bissell, “Coherent angular motion in the establishment of multicellular architecture of glandular tissues,” Proc. Natl. Acad. Sci. 109, 1973–1978 (2012).

Burris, N.

N. Burris, K. Schwartz, C. M. Tang, M. S. Jafri, J. Schmitt, M. H. Kwon, O. Toshinaga, J. Gu, J. Brown, E. Brown, R. Pierson, and R. Poston, “Catheter-based infrared light scanner as a tool to assess conduit quality in coronary artery bypass surgery,” J. Thorac. Cardiovasc. Surg. 133, 419–427 (2007).
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Cable, A. E.

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J. T. Camp, F. Elloumi, E. Roman-Perez, J. Rein, D. A. Stewart, J. C. Harrell, C. M. Perou, and M. A. Troester, “Interactions with fibroblasts are distinct in basal-like and luminal breast cancers,” Mol. Cancer Res. 9, 3–13 (2011).
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P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, “Role of HGF in epithelial-stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ,” Breast Cancer Res. 15, R82 (2013).

Cense, B.

Chappuis, P. O.

W. D. Foulkes, J.-S. Brunet, I. M. Stefansson, O. Straume, P. O. Chappuis, L. R. Bégin, N. Hamel, J. R. Goffin, N. Wong, M. Trudel, L. Kapusta, P. Porter, and L. A. Akslen, “The prognostic implication of the basal-like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) phenotype of BRCA1-related breast cancer,” Cancer Res. 64, 830–835 (2004).
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Chhetri, R. K.

A. L. Oldenburg, R. K. Chhetri, J. M. Cooper, W.-C. Wu, M. A. Troester, and J. B. Tracy, “Motility-, autocorrelation-, and polarization-sensitive optical coherence tomography discriminates cells and gold nanorods within 3D tissue cultures,” Opt. Lett. 38, 2923–2926 (2013).
[Crossref]

P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, “Role of HGF in epithelial-stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ,” Breast Cancer Res. 15, R82 (2013).

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, “Longitudinal study of mammary epithelial and fibroblast co-cultures using optical coherence tomography reveals morphological hallmarks of pre-malignancy,” PLoS One 7, e49148 (2012).
[Crossref]

A. L. Oldenburg, R. K. Chhetri, D. B. Hill, and B. Button, “Monitoring airway mucus flow and ciliary activity with optical coherence tomography,” Biomed. Opt. Express 3, 1978–1992 (2012).
[Crossref]

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83, 040903 (2011).
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M. Ciccotti and F. Mulargia, “Pernicious effect of physical cutoffs in fractal analysis,” Phys. Rev. E 65, 037201 (2002).
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R. Sinkus, K. Siegmann, T. Xydeas, M. Tanter, C. Claussen, and M. Fink, “MR elastography of breast lesions: understanding the solid/liquid duality can improve the specificity of contrast-enhanced MR mammography,” Magn. Reson. Med. 58, 1135–1144 (2007).
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J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, “Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography,” J. Cereb. Blood Flow Metab. 33, 819–825 (2013).
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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).
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P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, “Role of HGF in epithelial-stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ,” Breast Cancer Res. 15, R82 (2013).

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Debnath, J.

J. Debnath, S. K. Muthuswamy, and J. S. Brugge, “Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures,” Methods 30, 256–268 (2003).
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M. J. Paszek, N. Zahir, K. R. Johnson, J. N. Lakins, G. I. Rozenberg, A. Gefen, C. A. Reinhart-King, S. S. Margulies, M. Dembo, D. Boettiger, D. A. Hammer, and V. M. Weaver, “Tensional homeostasis and the malignant phenotype,” Cancer Cell 8, 241–254 (2005).
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Drezek, R.

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M. Guo, A. J. Ehrlicher, M. H. Jensen, M. Renz, J. R. Moore, R. D. Goldman, J. Lippincott-Schwartz, F. C. Mackintosh, and D. A. Weitz, “Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy,” Cell 158, 822–832 (2014).
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J. T. Camp, F. Elloumi, E. Roman-Perez, J. Rein, D. A. Stewart, J. C. Harrell, C. M. Perou, and M. A. Troester, “Interactions with fibroblasts are distinct in basal-like and luminal breast cancers,” Mol. Cancer Res. 9, 3–13 (2011).
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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).
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G. Lu and B. Fei, “Medical hyperspectral imaging: a review,” J. Biomed. Opt. 19, 010901 (2014).
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R. Sinkus, K. Siegmann, T. Xydeas, M. Tanter, C. Claussen, and M. Fink, “MR elastography of breast lesions: understanding the solid/liquid duality can improve the specificity of contrast-enhanced MR mammography,” Magn. Reson. Med. 58, 1135–1144 (2007).
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W. D. Foulkes, J.-S. Brunet, I. M. Stefansson, O. Straume, P. O. Chappuis, L. R. Bégin, N. Hamel, J. R. Goffin, N. Wong, M. Trudel, L. Kapusta, P. Porter, and L. A. Akslen, “The prognostic implication of the basal-like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) phenotype of BRCA1-related breast cancer,” Cancer Res. 64, 830–835 (2004).
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W. D. Foulkes, J.-S. Brunet, I. M. Stefansson, O. Straume, P. O. Chappuis, L. R. Bégin, N. Hamel, J. R. Goffin, N. Wong, M. Trudel, L. Kapusta, P. Porter, and L. A. Akslen, “The prognostic implication of the basal-like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) phenotype of BRCA1-related breast cancer,” Cancer Res. 64, 830–835 (2004).
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M. Guo, A. J. Ehrlicher, M. H. Jensen, M. Renz, J. R. Moore, R. D. Goldman, J. Lippincott-Schwartz, F. C. Mackintosh, and D. A. Weitz, “Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy,” Cell 158, 822–832 (2014).
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N. Burris, K. Schwartz, C. M. Tang, M. S. Jafri, J. Schmitt, M. H. Kwon, O. Toshinaga, J. Gu, J. Brown, E. Brown, R. Pierson, and R. Poston, “Catheter-based infrared light scanner as a tool to assess conduit quality in coronary artery bypass surgery,” J. Thorac. Cardiovasc. Surg. 133, 419–427 (2007).
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W. D. Foulkes, J.-S. Brunet, I. M. Stefansson, O. Straume, P. O. Chappuis, L. R. Bégin, N. Hamel, J. R. Goffin, N. Wong, M. Trudel, L. Kapusta, P. Porter, and L. A. Akslen, “The prognostic implication of the basal-like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) phenotype of BRCA1-related breast cancer,” Cancer Res. 64, 830–835 (2004).
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M. J. Paszek, N. Zahir, K. R. Johnson, J. N. Lakins, G. I. Rozenberg, A. Gefen, C. A. Reinhart-King, S. S. Margulies, M. Dembo, D. Boettiger, D. A. Hammer, and V. M. Weaver, “Tensional homeostasis and the malignant phenotype,” Cancer Cell 8, 241–254 (2005).
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J. T. Camp, F. Elloumi, E. Roman-Perez, J. Rein, D. A. Stewart, J. C. Harrell, C. M. Perou, and M. A. Troester, “Interactions with fibroblasts are distinct in basal-like and luminal breast cancers,” Mol. Cancer Res. 9, 3–13 (2011).
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O. W. Petersen, L. Rønnov-Jessen, A. R. Howlett, and M. J. Bissell, “Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells,” Proc. Natl Acad. Sci. 89, 9064–9068 (1992).

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N. Burris, K. Schwartz, C. M. Tang, M. S. Jafri, J. Schmitt, M. H. Kwon, O. Toshinaga, J. Gu, J. Brown, E. Brown, R. Pierson, and R. Poston, “Catheter-based infrared light scanner as a tool to assess conduit quality in coronary artery bypass surgery,” J. Thorac. Cardiovasc. Surg. 133, 419–427 (2007).
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M. Guo, A. J. Ehrlicher, M. H. Jensen, M. Renz, J. R. Moore, R. D. Goldman, J. Lippincott-Schwartz, F. C. Mackintosh, and D. A. Weitz, “Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy,” Cell 158, 822–832 (2014).
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Jiang, J. Y.

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K. R. Johnson, J. L. Leight, and V. M. Weaver, “Demystifying the effects of a three-dimensional microenvironment in tissue morphogenesis,” Methods Cell Biol. 83, 547–583 (2007).
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R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83, 040903 (2011).
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Jordan, C. T.

C. T. Jordan, M. L. Guzman, and M. Noble, “Cancer stem cells,” N. Engl. J. Med. 355, 1253–1261 (2006).

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W. D. Foulkes, J.-S. Brunet, I. M. Stefansson, O. Straume, P. O. Chappuis, L. R. Bégin, N. Hamel, J. R. Goffin, N. Wong, M. Trudel, L. Kapusta, P. Porter, and L. A. Akslen, “The prognostic implication of the basal-like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) phenotype of BRCA1-related breast cancer,” Cancer Res. 64, 830–835 (2004).
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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).
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R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83, 040903 (2011).
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N. Burris, K. Schwartz, C. M. Tang, M. S. Jafri, J. Schmitt, M. H. Kwon, O. Toshinaga, J. Gu, J. Brown, E. Brown, R. Pierson, and R. Poston, “Catheter-based infrared light scanner as a tool to assess conduit quality in coronary artery bypass surgery,” J. Thorac. Cardiovasc. Surg. 133, 419–427 (2007).
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M. J. Paszek, N. Zahir, K. R. Johnson, J. N. Lakins, G. I. Rozenberg, A. Gefen, C. A. Reinhart-King, S. S. Margulies, M. Dembo, D. Boettiger, D. A. Hammer, and V. M. Weaver, “Tensional homeostasis and the malignant phenotype,” Cancer Cell 8, 241–254 (2005).
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J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, “Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography,” J. Cereb. Blood Flow Metab. 33, 819–825 (2013).
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K. R. Johnson, J. L. Leight, and V. M. Weaver, “Demystifying the effects of a three-dimensional microenvironment in tissue morphogenesis,” Methods Cell Biol. 83, 547–583 (2007).
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M. Guo, A. J. Ehrlicher, M. H. Jensen, M. Renz, J. R. Moore, R. D. Goldman, J. Lippincott-Schwartz, F. C. Mackintosh, and D. A. Weitz, “Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy,” Cell 158, 822–832 (2014).
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G. Lu and B. Fei, “Medical hyperspectral imaging: a review,” J. Biomed. Opt. 19, 010901 (2014).
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M. Guo, A. J. Ehrlicher, M. H. Jensen, M. Renz, J. R. Moore, R. D. Goldman, J. Lippincott-Schwartz, F. C. Mackintosh, and D. A. Weitz, “Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy,” Cell 158, 822–832 (2014).
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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).
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R. An, D. Merrill, L. Avramova, J. Sturgis, M. Tsiper, J. P. Robinson, J. Turek, and D. D. Nolte, “Phenotypic profiling of Raf inhibitors and mitochondrial toxicity in 3D tissue using biodynamic imaging,” J. Biomol. Screening 19, 526–537 (2014).
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M. Guo, A. J. Ehrlicher, M. H. Jensen, M. Renz, J. R. Moore, R. D. Goldman, J. Lippincott-Schwartz, F. C. Mackintosh, and D. A. Weitz, “Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy,” Cell 158, 822–832 (2014).
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Mroue, R.

K. Tanner, H. Mori, R. Mroue, A. Bruni-Cardoso, and M. J. Bissell, “Coherent angular motion in the establishment of multicellular architecture of glandular tissues,” Proc. Natl. Acad. Sci. 109, 1973–1978 (2012).

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M. Ciccotti and F. Mulargia, “Pernicious effect of physical cutoffs in fractal analysis,” Phys. Rev. E 65, 037201 (2002).
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J. Debnath, S. K. Muthuswamy, and J. S. Brugge, “Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures,” Methods 30, 256–268 (2003).
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C. T. Jordan, M. L. Guzman, and M. Noble, “Cancer stem cells,” N. Engl. J. Med. 355, 1253–1261 (2006).

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R. An, C. Wang, J. Turek, Z. Machaty, and D. D. Nolte, “Biodynamic imaging of live porcine oocytes, zygotes and blastocysts for viability assessment in assisted reproductive technologies,” Biomed. Opt. Express 6, 963–976 (2015).
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R. An, D. Merrill, L. Avramova, J. Sturgis, M. Tsiper, J. P. Robinson, J. Turek, and D. D. Nolte, “Phenotypic profiling of Raf inhibitors and mitochondrial toxicity in 3D tissue using biodynamic imaging,” J. Biomol. Screening 19, 526–537 (2014).
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A. L. Oldenburg, R. K. Chhetri, J. M. Cooper, W.-C. Wu, M. A. Troester, and J. B. Tracy, “Motility-, autocorrelation-, and polarization-sensitive optical coherence tomography discriminates cells and gold nanorods within 3D tissue cultures,” Opt. Lett. 38, 2923–2926 (2013).
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P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, “Role of HGF in epithelial-stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ,” Breast Cancer Res. 15, R82 (2013).

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, “Longitudinal study of mammary epithelial and fibroblast co-cultures using optical coherence tomography reveals morphological hallmarks of pre-malignancy,” PLoS One 7, e49148 (2012).
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A. L. Oldenburg, R. K. Chhetri, D. B. Hill, and B. Button, “Monitoring airway mucus flow and ciliary activity with optical coherence tomography,” Biomed. Opt. Express 3, 1978–1992 (2012).
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R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83, 040903 (2011).
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J. T. Camp, F. Elloumi, E. Roman-Perez, J. Rein, D. A. Stewart, J. C. Harrell, C. M. Perou, and M. A. Troester, “Interactions with fibroblasts are distinct in basal-like and luminal breast cancers,” Mol. Cancer Res. 9, 3–13 (2011).
[Crossref]

Petersen, H.

M. N. Phadke, L. Pinto, O. Alabi, J. Harter, R. M. Taylor, X. Wu, H. Petersen, S. A. Bass, and C. G. Healey, “Exploring ensemble visualization,” Proc. SPIE 8294, 82940B (2012).

Petersen, O. W.

O. W. Petersen, L. Rønnov-Jessen, A. R. Howlett, and M. J. Bissell, “Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells,” Proc. Natl Acad. Sci. 89, 9064–9068 (1992).

Phadke, M. N.

M. N. Phadke, L. Pinto, O. Alabi, J. Harter, R. M. Taylor, X. Wu, H. Petersen, S. A. Bass, and C. G. Healey, “Exploring ensemble visualization,” Proc. SPIE 8294, 82940B (2012).

Phillips, Z. F.

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, “Longitudinal study of mammary epithelial and fibroblast co-cultures using optical coherence tomography reveals morphological hallmarks of pre-malignancy,” PLoS One 7, e49148 (2012).
[Crossref]

Pierson, R.

N. Burris, K. Schwartz, C. M. Tang, M. S. Jafri, J. Schmitt, M. H. Kwon, O. Toshinaga, J. Gu, J. Brown, E. Brown, R. Pierson, and R. Poston, “Catheter-based infrared light scanner as a tool to assess conduit quality in coronary artery bypass surgery,” J. Thorac. Cardiovasc. Surg. 133, 419–427 (2007).
[Crossref]

Pinto, L.

M. N. Phadke, L. Pinto, O. Alabi, J. Harter, R. M. Taylor, X. Wu, H. Petersen, S. A. Bass, and C. G. Healey, “Exploring ensemble visualization,” Proc. SPIE 8294, 82940B (2012).

Pitris, C.

Porter, P.

W. D. Foulkes, J.-S. Brunet, I. M. Stefansson, O. Straume, P. O. Chappuis, L. R. Bégin, N. Hamel, J. R. Goffin, N. Wong, M. Trudel, L. Kapusta, P. Porter, and L. A. Akslen, “The prognostic implication of the basal-like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) phenotype of BRCA1-related breast cancer,” Cancer Res. 64, 830–835 (2004).
[Crossref]

Poston, R.

N. Burris, K. Schwartz, C. M. Tang, M. S. Jafri, J. Schmitt, M. H. Kwon, O. Toshinaga, J. Gu, J. Brown, E. Brown, R. Pierson, and R. Poston, “Catheter-based infrared light scanner as a tool to assess conduit quality in coronary artery bypass surgery,” J. Thorac. Cardiovasc. Surg. 133, 419–427 (2007).
[Crossref]

Radhakrishnan, H.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, “Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography,” J. Cereb. Blood Flow Metab. 33, 819–825 (2013).
[Crossref]

V. J. Srinivasan, H. Radhakrishnan, E. H. Lo, E. T. Mandeville, J. Y. Jiang, S. Barry, and A. E. Cable, “OCT methods for capillary velocimetry,” Biomed. Opt. Express 3, 612–629 (2012).
[Crossref]

Radisky, D.

M. J. Bissell and D. Radisky, “Putting tumours in context,” Nat. Rev. Cancer 1, 46–54 (2001).
[Crossref]

Rein, J.

J. T. Camp, F. Elloumi, E. Roman-Perez, J. Rein, D. A. Stewart, J. C. Harrell, C. M. Perou, and M. A. Troester, “Interactions with fibroblasts are distinct in basal-like and luminal breast cancers,” Mol. Cancer Res. 9, 3–13 (2011).
[Crossref]

Reinhart-King, C. A.

M. J. Paszek, N. Zahir, K. R. Johnson, J. N. Lakins, G. I. Rozenberg, A. Gefen, C. A. Reinhart-King, S. S. Margulies, M. Dembo, D. Boettiger, D. A. Hammer, and V. M. Weaver, “Tensional homeostasis and the malignant phenotype,” Cancer Cell 8, 241–254 (2005).
[Crossref]

Renz, M.

M. Guo, A. J. Ehrlicher, M. H. Jensen, M. Renz, J. R. Moore, R. D. Goldman, J. Lippincott-Schwartz, F. C. Mackintosh, and D. A. Weitz, “Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy,” Cell 158, 822–832 (2014).
[Crossref]

Reynolds, J. J.

Richards-Kortum, R.

Robinson, J. P.

R. An, D. Merrill, L. Avramova, J. Sturgis, M. Tsiper, J. P. Robinson, J. Turek, and D. D. Nolte, “Phenotypic profiling of Raf inhibitors and mitochondrial toxicity in 3D tissue using biodynamic imaging,” J. Biomol. Screening 19, 526–537 (2014).
[Crossref]

Roman-Perez, E.

P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, “Role of HGF in epithelial-stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ,” Breast Cancer Res. 15, R82 (2013).

J. T. Camp, F. Elloumi, E. Roman-Perez, J. Rein, D. A. Stewart, J. C. Harrell, C. M. Perou, and M. A. Troester, “Interactions with fibroblasts are distinct in basal-like and luminal breast cancers,” Mol. Cancer Res. 9, 3–13 (2011).
[Crossref]

Rønnov-Jessen, L.

O. W. Petersen, L. Rønnov-Jessen, A. R. Howlett, and M. J. Bissell, “Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells,” Proc. Natl Acad. Sci. 89, 9064–9068 (1992).

Rozenberg, G. I.

M. J. Paszek, N. Zahir, K. R. Johnson, J. N. Lakins, G. I. Rozenberg, A. Gefen, C. A. Reinhart-King, S. S. Margulies, M. Dembo, D. Boettiger, D. A. Hammer, and V. M. Weaver, “Tensional homeostasis and the malignant phenotype,” Cancer Cell 8, 241–254 (2005).
[Crossref]

Schedin, P.

O. Maller, H. Martinson, and P. Schedin, “Extracellular matrix composition reveals complex and dynamic stromal-epithelial interactions in the mammary gland,” J. Mammary Gland Biol. Neoplasia 15, 301–318 (2010).
[Crossref]

Schiessel, H.

H. Schiessel and A. Blumen, “Mesoscopic pictures of the sol-gel transition: ladder models and fractal networks,” Macromolecules 28, 4013–4019 (1995).
[Crossref]

Schmitt, J.

N. Burris, K. Schwartz, C. M. Tang, M. S. Jafri, J. Schmitt, M. H. Kwon, O. Toshinaga, J. Gu, J. Brown, E. Brown, R. Pierson, and R. Poston, “Catheter-based infrared light scanner as a tool to assess conduit quality in coronary artery bypass surgery,” J. Thorac. Cardiovasc. Surg. 133, 419–427 (2007).
[Crossref]

Schwartz, K.

N. Burris, K. Schwartz, C. M. Tang, M. S. Jafri, J. Schmitt, M. H. Kwon, O. Toshinaga, J. Gu, J. Brown, E. Brown, R. Pierson, and R. Poston, “Catheter-based infrared light scanner as a tool to assess conduit quality in coronary artery bypass surgery,” J. Thorac. Cardiovasc. Surg. 133, 419–427 (2007).
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R. L. Frederick and J. M. Shaw, “Moving mitochondria: establishing distribution of an essential organelle,” Traffic 8, 1668–1675 (2007).
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Siegel, A. M.

Siegmann, K.

R. Sinkus, K. Siegmann, T. Xydeas, M. Tanter, C. Claussen, and M. Fink, “MR elastography of breast lesions: understanding the solid/liquid duality can improve the specificity of contrast-enhanced MR mammography,” Magn. Reson. Med. 58, 1135–1144 (2007).
[Crossref]

Sinkus, R.

R. Sinkus, K. Siegmann, T. Xydeas, M. Tanter, C. Claussen, and M. Fink, “MR elastography of breast lesions: understanding the solid/liquid duality can improve the specificity of contrast-enhanced MR mammography,” Magn. Reson. Med. 58, 1135–1144 (2007).
[Crossref]

Srinivasan, V. J.

Stefansson, I. M.

W. D. Foulkes, J.-S. Brunet, I. M. Stefansson, O. Straume, P. O. Chappuis, L. R. Bégin, N. Hamel, J. R. Goffin, N. Wong, M. Trudel, L. Kapusta, P. Porter, and L. A. Akslen, “The prognostic implication of the basal-like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) phenotype of BRCA1-related breast cancer,” Cancer Res. 64, 830–835 (2004).
[Crossref]

Stepinac, T.

Stewart, D. A.

J. T. Camp, F. Elloumi, E. Roman-Perez, J. Rein, D. A. Stewart, J. C. Harrell, C. M. Perou, and M. A. Troester, “Interactions with fibroblasts are distinct in basal-like and luminal breast cancers,” Mol. Cancer Res. 9, 3–13 (2011).
[Crossref]

Straume, O.

W. D. Foulkes, J.-S. Brunet, I. M. Stefansson, O. Straume, P. O. Chappuis, L. R. Bégin, N. Hamel, J. R. Goffin, N. Wong, M. Trudel, L. Kapusta, P. Porter, and L. A. Akslen, “The prognostic implication of the basal-like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) phenotype of BRCA1-related breast cancer,” Cancer Res. 64, 830–835 (2004).
[Crossref]

Sturgis, J.

R. An, D. Merrill, L. Avramova, J. Sturgis, M. Tsiper, J. P. Robinson, J. Turek, and D. D. Nolte, “Phenotypic profiling of Raf inhibitors and mitochondrial toxicity in 3D tissue using biodynamic imaging,” J. Biomol. Screening 19, 526–537 (2014).
[Crossref]

Tang, C.

P. Bak, C. Tang, and K. Wiesenfeld, “Self-organized criticality,” Phys. Rev. A 38, 364–374 (1988).
[Crossref]

Tang, C. M.

N. Burris, K. Schwartz, C. M. Tang, M. S. Jafri, J. Schmitt, M. H. Kwon, O. Toshinaga, J. Gu, J. Brown, E. Brown, R. Pierson, and R. Poston, “Catheter-based infrared light scanner as a tool to assess conduit quality in coronary artery bypass surgery,” J. Thorac. Cardiovasc. Surg. 133, 419–427 (2007).
[Crossref]

Tanner, K.

K. Tanner, H. Mori, R. Mroue, A. Bruni-Cardoso, and M. J. Bissell, “Coherent angular motion in the establishment of multicellular architecture of glandular tissues,” Proc. Natl. Acad. Sci. 109, 1973–1978 (2012).

Tanter, M.

R. Sinkus, K. Siegmann, T. Xydeas, M. Tanter, C. Claussen, and M. Fink, “MR elastography of breast lesions: understanding the solid/liquid duality can improve the specificity of contrast-enhanced MR mammography,” Magn. Reson. Med. 58, 1135–1144 (2007).
[Crossref]

Taylor, R.

R. Taylor, “Visualizing multiple fields on the same surface,” IEEE Comput. Graph. Appl. 22, 6–10 (2002).
[Crossref]

Taylor, R. M.

M. N. Phadke, L. Pinto, O. Alabi, J. Harter, R. M. Taylor, X. Wu, H. Petersen, S. A. Bass, and C. G. Healey, “Exploring ensemble visualization,” Proc. SPIE 8294, 82940B (2012).

Tearney, G. J.

Thrane, L.

Toshinaga, O.

N. Burris, K. Schwartz, C. M. Tang, M. S. Jafri, J. Schmitt, M. H. Kwon, O. Toshinaga, J. Gu, J. Brown, E. Brown, R. Pierson, and R. Poston, “Catheter-based infrared light scanner as a tool to assess conduit quality in coronary artery bypass surgery,” J. Thorac. Cardiovasc. Surg. 133, 419–427 (2007).
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Tracy, J. B.

A. L. Oldenburg, R. K. Chhetri, J. M. Cooper, W.-C. Wu, M. A. Troester, and J. B. Tracy, “Motility-, autocorrelation-, and polarization-sensitive optical coherence tomography discriminates cells and gold nanorods within 3D tissue cultures,” Opt. Lett. 38, 2923–2926 (2013).
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R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83, 040903 (2011).
[Crossref]

Troester, M. A.

P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, “Role of HGF in epithelial-stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ,” Breast Cancer Res. 15, R82 (2013).

A. L. Oldenburg, R. K. Chhetri, J. M. Cooper, W.-C. Wu, M. A. Troester, and J. B. Tracy, “Motility-, autocorrelation-, and polarization-sensitive optical coherence tomography discriminates cells and gold nanorods within 3D tissue cultures,” Opt. Lett. 38, 2923–2926 (2013).
[Crossref]

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, “Longitudinal study of mammary epithelial and fibroblast co-cultures using optical coherence tomography reveals morphological hallmarks of pre-malignancy,” PLoS One 7, e49148 (2012).
[Crossref]

J. T. Camp, F. Elloumi, E. Roman-Perez, J. Rein, D. A. Stewart, J. C. Harrell, C. M. Perou, and M. A. Troester, “Interactions with fibroblasts are distinct in basal-like and luminal breast cancers,” Mol. Cancer Res. 9, 3–13 (2011).
[Crossref]

Trudel, M.

W. D. Foulkes, J.-S. Brunet, I. M. Stefansson, O. Straume, P. O. Chappuis, L. R. Bégin, N. Hamel, J. R. Goffin, N. Wong, M. Trudel, L. Kapusta, P. Porter, and L. A. Akslen, “The prognostic implication of the basal-like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) phenotype of BRCA1-related breast cancer,” Cancer Res. 64, 830–835 (2004).
[Crossref]

Tsiper, M.

R. An, D. Merrill, L. Avramova, J. Sturgis, M. Tsiper, J. P. Robinson, J. Turek, and D. D. Nolte, “Phenotypic profiling of Raf inhibitors and mitochondrial toxicity in 3D tissue using biodynamic imaging,” J. Biomol. Screening 19, 526–537 (2014).
[Crossref]

Turek, J.

Turek, J. J.

K. Jeong, J. J. Turek, and D. D. Nolte, “Speckle fluctuation spectroscopy of intracellular motion in living tissue using coherence-domain digital holography,” J. Biomed. Opt. 15, 030514 (2010).
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K. Jeong, J. J. Turek, and D. D. Nolte, “Volumetric motility-contrast imaging of tissue response to cytoskeletal anti-cancer drugs,” Opt. Express 15, 14057–14064 (2007).
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B. B. Mandelbrot and J. W. Van Ness, “Fractional Brownian motions, fractional noises and applications,” SIAM Rev. 10, 422–437 (1968).
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Wang, C.

Weaver, V. M.

K. R. Johnson, J. L. Leight, and V. M. Weaver, “Demystifying the effects of a three-dimensional microenvironment in tissue morphogenesis,” Methods Cell Biol. 83, 547–583 (2007).
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M. J. Paszek, N. Zahir, K. R. Johnson, J. N. Lakins, G. I. Rozenberg, A. Gefen, C. A. Reinhart-King, S. S. Margulies, M. Dembo, D. Boettiger, D. A. Hammer, and V. M. Weaver, “Tensional homeostasis and the malignant phenotype,” Cancer Cell 8, 241–254 (2005).
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Weitz, D. A.

M. Guo, A. J. Ehrlicher, M. H. Jensen, M. Renz, J. R. Moore, R. D. Goldman, J. Lippincott-Schwartz, F. C. Mackintosh, and D. A. Weitz, “Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy,” Cell 158, 822–832 (2014).
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Wiesenfeld, K.

P. Bak, C. Tang, and K. Wiesenfeld, “Self-organized criticality,” Phys. Rev. A 38, 364–374 (1988).
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Wong, N.

W. D. Foulkes, J.-S. Brunet, I. M. Stefansson, O. Straume, P. O. Chappuis, L. R. Bégin, N. Hamel, J. R. Goffin, N. Wong, M. Trudel, L. Kapusta, P. Porter, and L. A. Akslen, “The prognostic implication of the basal-like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) phenotype of BRCA1-related breast cancer,” Cancer Res. 64, 830–835 (2004).
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Wu, W.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, “Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography,” J. Cereb. Blood Flow Metab. 33, 819–825 (2013).
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J. Lee, W. Wu, J. Y. Jiang, B. Zhu, and D. A. Boas, “Dynamic light scattering optical coherence tomography,” Opt. Express 20, 22262–22277 (2012).
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Wu, W.-C.

Wu, X.

M. N. Phadke, L. Pinto, O. Alabi, J. Harter, R. M. Taylor, X. Wu, H. Petersen, S. A. Bass, and C. G. Healey, “Exploring ensemble visualization,” Proc. SPIE 8294, 82940B (2012).

Xydeas, T.

R. Sinkus, K. Siegmann, T. Xydeas, M. Tanter, C. Claussen, and M. Fink, “MR elastography of breast lesions: understanding the solid/liquid duality can improve the specificity of contrast-enhanced MR mammography,” Magn. Reson. Med. 58, 1135–1144 (2007).
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E. A. Booth-Gauthier, T. A. Alcoser, G. Yang, and K. N. Dahl, “Force-induced changes in subnuclear movement and rheology,” Biophys. J. 103, 2423–2431 (2012).

Yang, V. X. D.

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).
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Yura, H. T.

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M. J. Paszek, N. Zahir, K. R. Johnson, J. N. Lakins, G. I. Rozenberg, A. Gefen, C. A. Reinhart-King, S. S. Margulies, M. Dembo, D. Boettiger, D. A. Hammer, and V. M. Weaver, “Tensional homeostasis and the malignant phenotype,” Cancer Cell 8, 241–254 (2005).
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Zhu, B.

Appl. Opt. (2)

Biomed. Opt. Express (4)

Biophys. J. (1)

E. A. Booth-Gauthier, T. A. Alcoser, G. Yang, and K. N. Dahl, “Force-induced changes in subnuclear movement and rheology,” Biophys. J. 103, 2423–2431 (2012).

Breast Cancer Res. (1)

P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, “Role of HGF in epithelial-stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ,” Breast Cancer Res. 15, R82 (2013).

Cancer Cell (1)

M. J. Paszek, N. Zahir, K. R. Johnson, J. N. Lakins, G. I. Rozenberg, A. Gefen, C. A. Reinhart-King, S. S. Margulies, M. Dembo, D. Boettiger, D. A. Hammer, and V. M. Weaver, “Tensional homeostasis and the malignant phenotype,” Cancer Cell 8, 241–254 (2005).
[Crossref]

Cancer Res. (1)

W. D. Foulkes, J.-S. Brunet, I. M. Stefansson, O. Straume, P. O. Chappuis, L. R. Bégin, N. Hamel, J. R. Goffin, N. Wong, M. Trudel, L. Kapusta, P. Porter, and L. A. Akslen, “The prognostic implication of the basal-like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) phenotype of BRCA1-related breast cancer,” Cancer Res. 64, 830–835 (2004).
[Crossref]

Cell (1)

M. Guo, A. J. Ehrlicher, M. H. Jensen, M. Renz, J. R. Moore, R. D. Goldman, J. Lippincott-Schwartz, F. C. Mackintosh, and D. A. Weitz, “Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy,” Cell 158, 822–832 (2014).
[Crossref]

IEEE Comput. Graph. Appl. (1)

R. Taylor, “Visualizing multiple fields on the same surface,” IEEE Comput. Graph. Appl. 22, 6–10 (2002).
[Crossref]

J. Biomed. Opt (1)

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]

J. Biomed. Opt. (2)

G. Lu and B. Fei, “Medical hyperspectral imaging: a review,” J. Biomed. Opt. 19, 010901 (2014).
[Crossref]

K. Jeong, J. J. Turek, and D. D. Nolte, “Speckle fluctuation spectroscopy of intracellular motion in living tissue using coherence-domain digital holography,” J. Biomed. Opt. 15, 030514 (2010).
[Crossref]

J. Biomol. Screening (1)

R. An, D. Merrill, L. Avramova, J. Sturgis, M. Tsiper, J. P. Robinson, J. Turek, and D. D. Nolte, “Phenotypic profiling of Raf inhibitors and mitochondrial toxicity in 3D tissue using biodynamic imaging,” J. Biomol. Screening 19, 526–537 (2014).
[Crossref]

J. Cereb. Blood Flow Metab. (1)

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, “Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography,” J. Cereb. Blood Flow Metab. 33, 819–825 (2013).
[Crossref]

J. Mammary Gland Biol. Neoplasia (1)

O. Maller, H. Martinson, and P. Schedin, “Extracellular matrix composition reveals complex and dynamic stromal-epithelial interactions in the mammary gland,” J. Mammary Gland Biol. Neoplasia 15, 301–318 (2010).
[Crossref]

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

J. Thorac. Cardiovasc. Surg. (1)

N. Burris, K. Schwartz, C. M. Tang, M. S. Jafri, J. Schmitt, M. H. Kwon, O. Toshinaga, J. Gu, J. Brown, E. Brown, R. Pierson, and R. Poston, “Catheter-based infrared light scanner as a tool to assess conduit quality in coronary artery bypass surgery,” J. Thorac. Cardiovasc. Surg. 133, 419–427 (2007).
[Crossref]

Macromolecules (1)

H. Schiessel and A. Blumen, “Mesoscopic pictures of the sol-gel transition: ladder models and fractal networks,” Macromolecules 28, 4013–4019 (1995).
[Crossref]

Magn. Reson. Med. (1)

R. Sinkus, K. Siegmann, T. Xydeas, M. Tanter, C. Claussen, and M. Fink, “MR elastography of breast lesions: understanding the solid/liquid duality can improve the specificity of contrast-enhanced MR mammography,” Magn. Reson. Med. 58, 1135–1144 (2007).
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J. Debnath, S. K. Muthuswamy, and J. S. Brugge, “Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures,” Methods 30, 256–268 (2003).
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Methods Cell Biol. (1)

K. R. Johnson, J. L. Leight, and V. M. Weaver, “Demystifying the effects of a three-dimensional microenvironment in tissue morphogenesis,” Methods Cell Biol. 83, 547–583 (2007).
[Crossref]

Mol. Cancer Res. (1)

J. T. Camp, F. Elloumi, E. Roman-Perez, J. Rein, D. A. Stewart, J. C. Harrell, C. M. Perou, and M. A. Troester, “Interactions with fibroblasts are distinct in basal-like and luminal breast cancers,” Mol. Cancer Res. 9, 3–13 (2011).
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N. Engl. J. Med. (1)

C. T. Jordan, M. L. Guzman, and M. Noble, “Cancer stem cells,” N. Engl. J. Med. 355, 1253–1261 (2006).

Nat. Rev. Cancer (1)

M. J. Bissell and D. Radisky, “Putting tumours in context,” Nat. Rev. Cancer 1, 46–54 (2001).
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Opt. Express (3)

Opt. Lett. (4)

Phys. Rev. A (1)

P. Bak, C. Tang, and K. Wiesenfeld, “Self-organized criticality,” Phys. Rev. A 38, 364–374 (1988).
[Crossref]

Phys. Rev. E (2)

M. Ciccotti and F. Mulargia, “Pernicious effect of physical cutoffs in fractal analysis,” Phys. Rev. E 65, 037201 (2002).
[Crossref]

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83, 040903 (2011).
[Crossref]

PLoS One (1)

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, “Longitudinal study of mammary epithelial and fibroblast co-cultures using optical coherence tomography reveals morphological hallmarks of pre-malignancy,” PLoS One 7, e49148 (2012).
[Crossref]

Proc. Natl Acad. Sci. (1)

O. W. Petersen, L. Rønnov-Jessen, A. R. Howlett, and M. J. Bissell, “Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells,” Proc. Natl Acad. Sci. 89, 9064–9068 (1992).

Proc. Natl. Acad. Sci. (1)

K. Tanner, H. Mori, R. Mroue, A. Bruni-Cardoso, and M. J. Bissell, “Coherent angular motion in the establishment of multicellular architecture of glandular tissues,” Proc. Natl. Acad. Sci. 109, 1973–1978 (2012).

Proc. SPIE (1)

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Supplementary Material (3)

NameDescription
» Supplement 1: PDF (1155 KB)      Supplemental document
» Visualization 1: AVI (3338 KB)      Visualization 1
» Visualization 2: AVI (1295 KB)      Visualization 2

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Figures (7)

Fig. 1.
Fig. 1. (a) Example stack-averaged OCT image of four MEC organoids (normal) in 3D co-culture with RMF (seed density 30 , 000 / cm 3 ) at 8 days culture time. See Visualization 1 and Visualization 2 corresponding to panels (b) and (c), respectively, which display 50 frames of the image stack at 23 × real-time. [The pixel intensity in panel (c) was increased 3.4 × for display].
Fig. 2.
Fig. 2. Example of the semi-automated segmentation method (see text for description) applied to a stack-averaged OCT image of MEC organoids (pre-malignant) in 3D co-culture with RMF (seed density 90 , 000 / cm 3 ) at 14 days culture time. Notably, these MEC organoids are significantly less spherical than those shown in Fig. 1 due to the different cell line (pre-malignant versus normal), increased RMF seed density, and increased culture time, consistent with our previous findings on MEC organoid morphology [12]. The challenging MEC organoid shapes are reliably segmented into 10 ROIs in this example using the semi-automated method.
Fig. 3.
Fig. 3. Motility images of the same data as in Fig. 2. (a) Time-averaged OCT image. (b) Motility image obtained using the standard deviation method [Eq. (3)] that exhibits depth-dependent roll-off. (c) Motility image obtained using the modified standard deviation method [Eq. (4)] that omits random noise. Unlike the other methods, this method appears stable with depth with a value of M = 0.24 ± 0.05 (mean ± s.d.) for the 10 ROIs shown in Fig. 2(d). (d) Motility image obtained using the standard deviation with stronger normalization [Eq. (3) numerator and Eq. (4) denominator], which exhibits a depth-dependent increase in M . Also note that an image artifact apparent in panels (b) and (d) (red arrows) is absent from panel (c); this artifact likely arises from a strong specular reflection at the air–liquid interface.
Fig. 4.
Fig. 4. Box-and-whisker plots of the distribution of R 2 values obtained from least-squares fitting to the Lorentzian and inverse-power-law models for all cell culture conditions. Only live cells exhibited a preference for the inverse-power-law model (red arrow). (ECM unfixed n R = 180 , ECM fixed n R = 36 , MEC unfixed n R = 153 , and MEC fixed n R = 33 , where n R is the number of manually selected ROIs of each condition).
Fig. 5.
Fig. 5. α and M of MEC organoids composed of normal or pre-malignant cell lines were quantified before and after fixation. While there is no significant difference between cell lines, both α and M are significantly different between live and fixed cells ( p < 10 10 for all four comparisons). Error bars indicate standard deviation.
Fig. 6.
Fig. 6. Box-and-whisker plots of the distribution of α and M at each fibroblast seed density (for both cell lines and all culture times). As seed density increases, α increases strongly, while M decreases slightly. The bottom panel illustrates inverse-power-law model fittings of the power spectra for representative ROIs seeded with no fibroblasts (blue) compared to 300 μl 1 fibroblasts (purple); the noise constant [ n in Eq. (2)] was subtracted and spectra normalized before plotting to emphasize the effects of α . As shown, a higher value of α indicates the suppression of higher frequencies relative to lower frequencies.
Fig. 7.
Fig. 7. Visualization of motility metrics on the same data as in Figs. 2 and 3, where panels (b) and (c) are close-up views of organoids (yellow arrows) in panel (a). The background gray-scale image indicates M , and α is overlaid as a spherical glyph colored from blue to red to represent fluctuation spectra with more high-frequency or low-frequency components, respectively. Blue or red hollow glyphs indicate α values beyond the scale ( < 1 and > 2 , respectively). The size of the glyph represents R 2 from the power-law fitting, with larger glyphs indicating α values with greater confidence. Yellow contour lines indicate the ROIs determined from segmentation of the time-averaged OCT image.

Tables (3)

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Table 1. Standard Deviation of Motility Metrics in MEC Organoids

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Table 2. Parameter Estimates for Motility Metrics in Co-culturesa

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Table 3. Parameter Estimates for Motility Amplitude According to Eq. (6) in Co-Culturesa

Equations (7)

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S ( f ) = c 0 γ f 2 + γ 2 + n ,
S ( f ) = c 0 f α + n ,
M ( x , z ) = 1 N i = 1 N ( I ( x , z , t i ) I ¯ ( x , z ) ) 2 I ¯ ( x , z ) ,
M ( x , z ) = Γ I ( x , z , Δ t ) I ¯ ( x , z ) 2 I ¯ ( x , z ) ,
( α , M ) = β 0 + β 1 x RMF + β 2 n MEC + β 3 t + β 4 m g ,
M = β 0 + β 1 x RMF + β 2 n MEC + β 3 t + β 5 x RMF n MEC ,
d = ( R 2 ) ( log 10 ( 0.5 ) log 10 ( R 0 2 ) ) ,

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