Abstract

Biodynamic digital holography was used to obtain phenotypic profiles of canine non-Hodgkin B-cell lymphoma biopsies treated with standard-of-care chemotherapy. Biodynamic signatures from the living 3D tissues were extracted using fluctuation spectroscopy from intracellular Doppler light scattering in response to the molecular mechanisms of action of therapeutic drugs that modify a range of internal cellular motions. The standard-of-care to treat B-cell lymphoma in both humans and dogs is a combination CHOP therapy that consists of doxorubicin, prednisolone, cyclophosphamide and vincristine. The proportion of dogs experiencing durable cancer remission following CHOP chemotherapy was 68%, with 13 out of 19 dogs responding favorably to therapy and 6 dogs failing to have progression-free survival times greater than 100 days. Biodynamic signatures were found that correlate with inferior survival times, and biomarker selection was optimized to identify specific Doppler signatures related to chemoresistance. A machine learning classifier was constructed based on feature vector correlations and linear separability in high-dimensional feature space. Hold-out validation predicted patient response to therapy with 84% accuracy. These results point to the potential for biodynamic profiling to contribute to personalized medicine by aiding the selection of chemotherapy for cancer patients.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Full Article  |  PDF Article
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References

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2017 (1)

H. Sun, D. Merrill, R. An, J. Turek, D. Matei, and D. D. Nolte, “Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture,” J. Biomed. Opt. 22(1), 16007 (2017).
[Crossref] [PubMed]

2016 (3)

D. Merrill, R. An, H. Sun, B. Yakubov, D. Matei, J. Turek, and D. Nolte, “Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts,” Sci. Rep. 6(1), 18821 (2016).
[Crossref] [PubMed]

E. J. Hartsough and A. E. Aplin, “Of Mice and Melanoma: PDX System for Modeling Personalized Medicine,” Clin. Cancer Res. 22(7), 1550–1552 (2016).
[Crossref] [PubMed]

R. L. Blackmon, R. Sandhu, B. S. Chapman, P. Casbas-Hernandez, J. B. Tracy, M. A. Troester, and A. L. Oldenburg, “Imaging Extracellular Matrix Remodeling In Vitro by Diffusion-Sensitive Optical Coherence Tomography,” Biophys. J. 110(8), 1858–1868 (2016).
[Crossref] [PubMed]

2015 (3)

G. Farhat, A. Giles, M. C. Kolios, and G. J. Czarnota, “Optical coherence tomography spectral analysis for detecting apoptosis in vitro and in vivo,” J. Biomed. Opt. 20(12), 126001 (2015).
[Crossref] [PubMed]

M. R. Custead, R. An, J. J. Turek, G. E. Moore, D. D. Nolte, and M. O. Childress, “Predictive value of ex vivo biodynamic imaging in determining response to chemotherapy in dogs with spontaneous non-Hodgkin’s lymphomas: a preliminary study,” Converg Sci Phys Oncol 1(1), 015003 (2015).
[Crossref] [PubMed]

D. Merrill, R. An, J. Turek, and D. D. Nolte, “Digital holography of intracellular dynamics to probe tissue physiology,” Appl. Opt. 54(1), A89–A97 (2015).
[Crossref] [PubMed]

2014 (2)

D. Ito, A. M. Frantz, and J. F. Modiano, “Canine lymphoma as a comparative model for human non-Hodgkin lymphoma: recent progress and applications,” Vet. Immunol. Immunopathol. 159(3-4), 192–201 (2014).
[Crossref] [PubMed]

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. Screen. 19(4), 526–537 (2014).
[Crossref] [PubMed]

2013 (4)

J. A. Lee and E. L. Berg, “Neoclassic Drug Discovery: The Case for Lead Generation Using Phenotypic and Functional Approaches,” J. Biomol. Screen. 18(10), 1143–1155 (2013).
[Crossref] [PubMed]

S. Breslin and L. O’Driscoll, “Three-dimensional cell culture: the missing link in drug discovery,” Drug Discov. Today 18(5-6), 240–249 (2013).
[Crossref] [PubMed]

C. Joo and J. F. de Boer, “Field-based dynamic light scattering microscopy: theory and numerical analysis,” Appl. Opt. 52(31), 7618–7628 (2013).
[Crossref] [PubMed]

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(6), 819–825 (2013).
[Crossref] [PubMed]

2012 (1)

2011 (4)

D. D. Nolte, R. An, J. Turek, and K. Jeong, “Tissue Dynamics Spectroscopy for Three-Dimensional Tissue-Based Drug Screening,” J. Lab. Autom. 16(6), 431–442 (2011).
[Crossref] [PubMed]

K. Tamura, T. Mizutani, H. Haga, and K. Kawabata, “Active fluctuation in the cortical cytoskeleton observed by high-speed live-cell scanning probe microscopy,” Acta Biomater. 7(10), 3766–3772 (2011).
[Crossref] [PubMed]

N. T. Elliott and F. Yuan, “A Review of Three-Dimensional In Vitro Tissue Models for Drug Discovery and Transport Studies,” J. Pharm. Sci. 100(1), 59–74 (2011).
[Crossref] [PubMed]

D. D. Nolte, R. An, J. Turek, and K. Jeong, “Holographic tissue dynamics spectroscopy,” J. Biomed. Opt. 16(8), 087004 (2011).
[Crossref] [PubMed]

2010 (4)

D. M. Vail, G. M. Michels, C. Khanna, K. A. Selting, and C. A. London, “Response evaluation criteria for peripheral nodal lymphoma in dogs (v1.0)-a veterinary cooperative oncology group (VCOG) consensus document,” Vet. Comp. Oncol. 8(1), 28–37 (2010).
[Crossref] [PubMed]

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(3), 030514 (2010).
[Crossref] [PubMed]

D. A. Fletcher and R. D. Mullins, “Cell mechanics and the cytoskeleton,” Nature 463(7280), 485–492 (2010).
[Crossref] [PubMed]

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(3), 2858–2871 (2010).
[Crossref] [PubMed]

2009 (3)

Y. Z. Yoon, H. Hong, A. Brown, D. C. Kim, D. J. Kang, V. L. Lew, and P. Cicuta, “Flickering Analysis of Erythrocyte Mechanical Properties: Dependence on Oxygenation Level, Cell Shape, and Hydration Level,” Biophys. J. 97(6), 1606–1615 (2009).
[Crossref] [PubMed]

I. A. Cree, “Chemosensitivity and chemoresistance testing in ovarian cancer,” Curr. Opin. Obstet. Gynecol. 21(1), 39–43 (2009).
[Crossref] [PubMed]

T. Betz, M. Lenz, J.-F. Joanny, and C. Sykes, “ATP-dependent mechanics of red blood cells,” Proc. Natl. Acad. Sci. U.S.A. 106(36), 15320–15325 (2009).
[Crossref] [PubMed]

2008 (3)

X. Nan, P. A. Sims, and X. S. Xie, “Organelle tracking in a living cell with microsecond time resolution and nanometer spatial precision,” ChemPhysChem 9(5), 707–712 (2008).
[Crossref] [PubMed]

J. Evans, W. Gratzer, N. Mohandas, K. Parker, and J. Sleep, “Fluctuations of the red blood cell membrane: Relation to mechanical properties and lack of ATP dependence,” Biophys. J. 94(10), 4134–4144 (2008).
[Crossref] [PubMed]

M. Suissa, C. Place, E. Goillot, and E. Freyssingeas, “Internal dynamics of a living cell nucleus investigated by dynamic light scattering,” Eur Phys J E Soft Matter 26(4), 435–448 (2008).
[Crossref] [PubMed]

2007 (3)

S. Y. Sung, C. L. Hsieh, D. Wu, L. W. Chung, and P. A. Johnstone, “Tumor microenvironment promotes cancer progression, metastasis, and therapeutic resistance,” Curr. Probl. Cancer 31(2), 36–100 (2007).
[Crossref] [PubMed]

V. Racine, M. Sachse, J. Salamero, V. Fraisier, A. Trubuil, and J. B. Sibarita, “Visualization and quantification of vesicle trafficking on a three-dimensional cytoskeleton network in living cells,” J. Microsc. 225(Pt 3), 214–228 (2007).
[Crossref] [PubMed]

K. Jeong, J. J. Turek, and D. D. Nolte, “Imaging Motility Contrast in Digital Holography of Tissue Response to Cytoskeletal Anti-cancer Drugs,” Opt. Express 15(21), 14057–14064 (2007).
[Crossref] [PubMed]

2006 (3)

Z. Yaqoob, J. Fingler, X. Heng, and C. Yang, “Homodyne en face optical coherence tomography,” Opt. Lett. 31(12), 1815–1817 (2006).
[Crossref] [PubMed]

N. A. Brazhe, A. R. Brazhe, A. N. Pavlov, L. A. Erokhova, A. I. Yusipovich, G. V. Maksimov, E. Mosekilde, and O. V. Sosnovtseva, “Unraveling cell processes: interference imaging interwoven with data analysis,” J. Biol. Phys. 32(3-4), 191–208 (2006).
[Crossref] [PubMed]

L. G. Griffith and M. A. Swartz, “Capturing complex 3D tissue physiology in vitro,” Nat. Rev. Mol. Cell Biol. 7(3), 211–224 (2006).
[Crossref] [PubMed]

2002 (1)

L. D. Garrett, D. H. Thamm, R. Chun, R. Dudley, and D. M. Vail, “Evaluation of a 6-month chemotherapy protocol with no maintenance therapy for dogs with lymphoma,” J. Vet. Intern. Med. 16(6), 704–709 (2002).
[Crossref] [PubMed]

2001 (1)

2000 (1)

R. D. Vale and R. A. Milligan, “The way things move: Looking under the hood of molecular motor proteins,” Science 288(5463), 88–95 (2000).
[Crossref] [PubMed]

1999 (2)

B. Trinczek, A. Ebneth, E. M. Mandelkow, and E. Mandelkow, “Tau regulates the attachment/detachment but not the speed of motors in microtubule-dependent transport of single vesicles and organelles,” J. Cell Sci. 112(Pt 14), 2355–2367 (1999).
[PubMed]

E. Cuche, F. Bevilacqua, and C. Depeursinge, “Digital holography for quantitative phase-contrast imaging,” Opt. Lett. 24(5), 291–293 (1999).
[Crossref] [PubMed]

1998 (2)

T. Zhang and I. Yamaguchi, “Three-dimensional microscopy with phase-shifting digital holography,” Opt. Lett. 23(15), 1221–1223 (1998).
[Crossref] [PubMed]

K. K. Bizheva, A. M. Siegel, and D. A. Boas, “Path-length-resolved dynamic light scattering in highly scattering random media: The transition to diffusing wave spectroscopy,” Phys. Rev. E Stat. Phys. Plasmas Fluids Relat. Interdiscip. Topics 58(6), 7664–7667 (1998).
[Crossref]

1997 (1)

1995 (1)

H. Strey, M. Peterson, and E. Sackmann, “Measurement of Erythrocyte Membrane Elasticity by Flicker Eigenmode Decomposition,” Biophys. J. 69(2), 478–488 (1995).
[Crossref] [PubMed]

1992 (3)

A. Zilker, M. Ziegler, and E. Sackmann, “Spectral Analysis of Erythrocyte Flickering in the 0.3-4- Mu-M-1 Regime by Microinterferometry Combined with Fast Image Processing,” Phys. Rev. A 46(12), 7998–8001 (1992).
[Crossref] [PubMed]

M. A. Peterson, H. Strey, and E. Sackmann, “Theoretical and Phase-Contrast Microscopic Eigenmode Analysis of Erythrocyte Flicker - Amplitudes,” J. Phys. II 2(5), 1273–1285 (1992).
[Crossref]

K. J. Karnaky, L. T. Garretson, and R. G. O’Neil, “Video-Enhanced Microscopy of Organelle Movement in an Intact Epithelium,” J. Morphol. 213(1), 21–31 (1992).
[Crossref] [PubMed]

1975 (1)

F. Brochard and J. F. Lennon, “Frequency Spectrum of Flicker Phenomenon in Erythrocytes,” J. Phys. 36(11), 1035–1047 (1975).
[Crossref]

An, R.

H. Sun, D. Merrill, R. An, J. Turek, D. Matei, and D. D. Nolte, “Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture,” J. Biomed. Opt. 22(1), 16007 (2017).
[Crossref] [PubMed]

D. Merrill, R. An, H. Sun, B. Yakubov, D. Matei, J. Turek, and D. Nolte, “Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts,” Sci. Rep. 6(1), 18821 (2016).
[Crossref] [PubMed]

M. R. Custead, R. An, J. J. Turek, G. E. Moore, D. D. Nolte, and M. O. Childress, “Predictive value of ex vivo biodynamic imaging in determining response to chemotherapy in dogs with spontaneous non-Hodgkin’s lymphomas: a preliminary study,” Converg Sci Phys Oncol 1(1), 015003 (2015).
[Crossref] [PubMed]

D. Merrill, R. An, J. Turek, and D. D. Nolte, “Digital holography of intracellular dynamics to probe tissue physiology,” Appl. Opt. 54(1), A89–A97 (2015).
[Crossref] [PubMed]

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. Screen. 19(4), 526–537 (2014).
[Crossref] [PubMed]

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D. D. Nolte, R. An, J. Turek, and K. Jeong, “Tissue Dynamics Spectroscopy for Three-Dimensional Tissue-Based Drug Screening,” J. Lab. Autom. 16(6), 431–442 (2011).
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E. J. Hartsough and A. E. Aplin, “Of Mice and Melanoma: PDX System for Modeling Personalized Medicine,” Clin. Cancer Res. 22(7), 1550–1552 (2016).
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J. A. Lee and E. L. Berg, “Neoclassic Drug Discovery: The Case for Lead Generation Using Phenotypic and Functional Approaches,” J. Biomol. Screen. 18(10), 1143–1155 (2013).
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M. R. Custead, R. An, J. J. Turek, G. E. Moore, D. D. Nolte, and M. O. Childress, “Predictive value of ex vivo biodynamic imaging in determining response to chemotherapy in dogs with spontaneous non-Hodgkin’s lymphomas: a preliminary study,” Converg Sci Phys Oncol 1(1), 015003 (2015).
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G. Farhat, A. Giles, M. C. Kolios, and G. J. Czarnota, “Optical coherence tomography spectral analysis for detecting apoptosis in vitro and in vivo,” J. Biomed. Opt. 20(12), 126001 (2015).
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L. D. Garrett, D. H. Thamm, R. Chun, R. Dudley, and D. M. Vail, “Evaluation of a 6-month chemotherapy protocol with no maintenance therapy for dogs with lymphoma,” J. Vet. Intern. Med. 16(6), 704–709 (2002).
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G. Farhat, A. Giles, M. C. Kolios, and G. J. Czarnota, “Optical coherence tomography spectral analysis for detecting apoptosis in vitro and in vivo,” J. Biomed. Opt. 20(12), 126001 (2015).
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M. Suissa, C. Place, E. Goillot, and E. Freyssingeas, “Internal dynamics of a living cell nucleus investigated by dynamic light scattering,” Eur Phys J E Soft Matter 26(4), 435–448 (2008).
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J. Evans, W. Gratzer, N. Mohandas, K. Parker, and J. Sleep, “Fluctuations of the red blood cell membrane: Relation to mechanical properties and lack of ATP dependence,” Biophys. J. 94(10), 4134–4144 (2008).
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E. J. Hartsough and A. E. Aplin, “Of Mice and Melanoma: PDX System for Modeling Personalized Medicine,” Clin. Cancer Res. 22(7), 1550–1552 (2016).
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Y. Z. Yoon, H. Hong, A. Brown, D. C. Kim, D. J. Kang, V. L. Lew, and P. Cicuta, “Flickering Analysis of Erythrocyte Mechanical Properties: Dependence on Oxygenation Level, Cell Shape, and Hydration Level,” Biophys. J. 97(6), 1606–1615 (2009).
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S. Y. Sung, C. L. Hsieh, D. Wu, L. W. Chung, and P. A. Johnstone, “Tumor microenvironment promotes cancer progression, metastasis, and therapeutic resistance,” Curr. Probl. Cancer 31(2), 36–100 (2007).
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D. Ito, A. M. Frantz, and J. F. Modiano, “Canine lymphoma as a comparative model for human non-Hodgkin lymphoma: recent progress and applications,” Vet. Immunol. Immunopathol. 159(3-4), 192–201 (2014).
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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(11), 2825–2841 (2012).
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D. D. Nolte, R. An, J. Turek, and K. Jeong, “Tissue Dynamics Spectroscopy for Three-Dimensional Tissue-Based Drug Screening,” J. Lab. Autom. 16(6), 431–442 (2011).
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T. Betz, M. Lenz, J.-F. Joanny, and C. Sykes, “ATP-dependent mechanics of red blood cells,” Proc. Natl. Acad. Sci. U.S.A. 106(36), 15320–15325 (2009).
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S. Y. Sung, C. L. Hsieh, D. Wu, L. W. Chung, and P. A. Johnstone, “Tumor microenvironment promotes cancer progression, metastasis, and therapeutic resistance,” Curr. Probl. Cancer 31(2), 36–100 (2007).
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Y. Z. Yoon, H. Hong, A. Brown, D. C. Kim, D. J. Kang, V. L. Lew, and P. Cicuta, “Flickering Analysis of Erythrocyte Mechanical Properties: Dependence on Oxygenation Level, Cell Shape, and Hydration Level,” Biophys. J. 97(6), 1606–1615 (2009).
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K. J. Karnaky, L. T. Garretson, and R. G. O’Neil, “Video-Enhanced Microscopy of Organelle Movement in an Intact Epithelium,” J. Morphol. 213(1), 21–31 (1992).
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K. Tamura, T. Mizutani, H. Haga, and K. Kawabata, “Active fluctuation in the cortical cytoskeleton observed by high-speed live-cell scanning probe microscopy,” Acta Biomater. 7(10), 3766–3772 (2011).
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Y. Z. Yoon, H. Hong, A. Brown, D. C. Kim, D. J. Kang, V. L. Lew, and P. Cicuta, “Flickering Analysis of Erythrocyte Mechanical Properties: Dependence on Oxygenation Level, Cell Shape, and Hydration Level,” Biophys. J. 97(6), 1606–1615 (2009).
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G. Farhat, A. Giles, M. C. Kolios, and G. J. Czarnota, “Optical coherence tomography spectral analysis for detecting apoptosis in vitro and in vivo,” J. Biomed. Opt. 20(12), 126001 (2015).
[Crossref] [PubMed]

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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(6), 819–825 (2013).
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J. A. Lee and E. L. Berg, “Neoclassic Drug Discovery: The Case for Lead Generation Using Phenotypic and Functional Approaches,” J. Biomol. Screen. 18(10), 1143–1155 (2013).
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F. Brochard and J. F. Lennon, “Frequency Spectrum of Flicker Phenomenon in Erythrocytes,” J. Phys. 36(11), 1035–1047 (1975).
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T. Betz, M. Lenz, J.-F. Joanny, and C. Sykes, “ATP-dependent mechanics of red blood cells,” Proc. Natl. Acad. Sci. U.S.A. 106(36), 15320–15325 (2009).
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Y. Z. Yoon, H. Hong, A. Brown, D. C. Kim, D. J. Kang, V. L. Lew, and P. Cicuta, “Flickering Analysis of Erythrocyte Mechanical Properties: Dependence on Oxygenation Level, Cell Shape, and Hydration Level,” Biophys. J. 97(6), 1606–1615 (2009).
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B. Trinczek, A. Ebneth, E. M. Mandelkow, and E. Mandelkow, “Tau regulates the attachment/detachment but not the speed of motors in microtubule-dependent transport of single vesicles and organelles,” J. Cell Sci. 112(Pt 14), 2355–2367 (1999).
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H. Sun, D. Merrill, R. An, J. Turek, D. Matei, and D. D. Nolte, “Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture,” J. Biomed. Opt. 22(1), 16007 (2017).
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D. Merrill, R. An, H. Sun, B. Yakubov, D. Matei, J. Turek, and D. Nolte, “Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts,” Sci. Rep. 6(1), 18821 (2016).
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H. Sun, D. Merrill, R. An, J. Turek, D. Matei, and D. D. Nolte, “Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture,” J. Biomed. Opt. 22(1), 16007 (2017).
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D. Merrill, R. An, H. Sun, B. Yakubov, D. Matei, J. Turek, and D. Nolte, “Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts,” Sci. Rep. 6(1), 18821 (2016).
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D. Merrill, R. An, J. Turek, and D. D. Nolte, “Digital holography of intracellular dynamics to probe tissue physiology,” Appl. Opt. 54(1), A89–A97 (2015).
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D. M. Vail, G. M. Michels, C. Khanna, K. A. Selting, and C. A. London, “Response evaluation criteria for peripheral nodal lymphoma in dogs (v1.0)-a veterinary cooperative oncology group (VCOG) consensus document,” Vet. Comp. Oncol. 8(1), 28–37 (2010).
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K. Tamura, T. Mizutani, H. Haga, and K. Kawabata, “Active fluctuation in the cortical cytoskeleton observed by high-speed live-cell scanning probe microscopy,” Acta Biomater. 7(10), 3766–3772 (2011).
[Crossref] [PubMed]

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D. Ito, A. M. Frantz, and J. F. Modiano, “Canine lymphoma as a comparative model for human non-Hodgkin lymphoma: recent progress and applications,” Vet. Immunol. Immunopathol. 159(3-4), 192–201 (2014).
[Crossref] [PubMed]

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J. Evans, W. Gratzer, N. Mohandas, K. Parker, and J. Sleep, “Fluctuations of the red blood cell membrane: Relation to mechanical properties and lack of ATP dependence,” Biophys. J. 94(10), 4134–4144 (2008).
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M. R. Custead, R. An, J. J. Turek, G. E. Moore, D. D. Nolte, and M. O. Childress, “Predictive value of ex vivo biodynamic imaging in determining response to chemotherapy in dogs with spontaneous non-Hodgkin’s lymphomas: a preliminary study,” Converg Sci Phys Oncol 1(1), 015003 (2015).
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H. Sun, D. Merrill, R. An, J. Turek, D. Matei, and D. D. Nolte, “Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture,” J. Biomed. Opt. 22(1), 16007 (2017).
[Crossref] [PubMed]

M. R. Custead, R. An, J. J. Turek, G. E. Moore, D. D. Nolte, and M. O. Childress, “Predictive value of ex vivo biodynamic imaging in determining response to chemotherapy in dogs with spontaneous non-Hodgkin’s lymphomas: a preliminary study,” Converg Sci Phys Oncol 1(1), 015003 (2015).
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D. Merrill, R. An, J. Turek, and D. D. Nolte, “Digital holography of intracellular dynamics to probe tissue physiology,” Appl. Opt. 54(1), A89–A97 (2015).
[Crossref] [PubMed]

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. Screen. 19(4), 526–537 (2014).
[Crossref] [PubMed]

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(11), 2825–2841 (2012).
[Crossref] [PubMed]

D. D. Nolte, R. An, J. Turek, and K. Jeong, “Holographic tissue dynamics spectroscopy,” J. Biomed. Opt. 16(8), 087004 (2011).
[Crossref] [PubMed]

D. D. Nolte, R. An, J. Turek, and K. Jeong, “Tissue Dynamics Spectroscopy for Three-Dimensional Tissue-Based Drug Screening,” J. Lab. Autom. 16(6), 431–442 (2011).
[Crossref] [PubMed]

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(3), 030514 (2010).
[Crossref] [PubMed]

K. Jeong, J. J. Turek, and D. D. Nolte, “Imaging Motility Contrast in Digital Holography of Tissue Response to Cytoskeletal Anti-cancer Drugs,” Opt. Express 15(21), 14057–14064 (2007).
[Crossref] [PubMed]

O’Driscoll, L.

S. Breslin and L. O’Driscoll, “Three-dimensional cell culture: the missing link in drug discovery,” Drug Discov. Today 18(5-6), 240–249 (2013).
[Crossref] [PubMed]

O’Neil, R. G.

K. J. Karnaky, L. T. Garretson, and R. G. O’Neil, “Video-Enhanced Microscopy of Organelle Movement in an Intact Epithelium,” J. Morphol. 213(1), 21–31 (1992).
[Crossref] [PubMed]

Oldenburg, A. L.

R. L. Blackmon, R. Sandhu, B. S. Chapman, P. Casbas-Hernandez, J. B. Tracy, M. A. Troester, and A. L. Oldenburg, “Imaging Extracellular Matrix Remodeling In Vitro by Diffusion-Sensitive Optical Coherence Tomography,” Biophys. J. 110(8), 1858–1868 (2016).
[Crossref] [PubMed]

Parker, K.

J. Evans, W. Gratzer, N. Mohandas, K. Parker, and J. Sleep, “Fluctuations of the red blood cell membrane: Relation to mechanical properties and lack of ATP dependence,” Biophys. J. 94(10), 4134–4144 (2008).
[Crossref] [PubMed]

Pavlov, A. N.

N. A. Brazhe, A. R. Brazhe, A. N. Pavlov, L. A. Erokhova, A. I. Yusipovich, G. V. Maksimov, E. Mosekilde, and O. V. Sosnovtseva, “Unraveling cell processes: interference imaging interwoven with data analysis,” J. Biol. Phys. 32(3-4), 191–208 (2006).
[Crossref] [PubMed]

Peterson, M.

H. Strey, M. Peterson, and E. Sackmann, “Measurement of Erythrocyte Membrane Elasticity by Flicker Eigenmode Decomposition,” Biophys. J. 69(2), 478–488 (1995).
[Crossref] [PubMed]

Peterson, M. A.

M. A. Peterson, H. Strey, and E. Sackmann, “Theoretical and Phase-Contrast Microscopic Eigenmode Analysis of Erythrocyte Flicker - Amplitudes,” J. Phys. II 2(5), 1273–1285 (1992).
[Crossref]

Place, C.

M. Suissa, C. Place, E. Goillot, and E. Freyssingeas, “Internal dynamics of a living cell nucleus investigated by dynamic light scattering,” Eur Phys J E Soft Matter 26(4), 435–448 (2008).
[Crossref] [PubMed]

Racine, V.

V. Racine, M. Sachse, J. Salamero, V. Fraisier, A. Trubuil, and J. B. Sibarita, “Visualization and quantification of vesicle trafficking on a three-dimensional cytoskeleton network in living cells,” J. Microsc. 225(Pt 3), 214–228 (2007).
[Crossref] [PubMed]

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(6), 819–825 (2013).
[Crossref] [PubMed]

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. Screen. 19(4), 526–537 (2014).
[Crossref] [PubMed]

Sachse, M.

V. Racine, M. Sachse, J. Salamero, V. Fraisier, A. Trubuil, and J. B. Sibarita, “Visualization and quantification of vesicle trafficking on a three-dimensional cytoskeleton network in living cells,” J. Microsc. 225(Pt 3), 214–228 (2007).
[Crossref] [PubMed]

Sackmann, E.

H. Strey, M. Peterson, and E. Sackmann, “Measurement of Erythrocyte Membrane Elasticity by Flicker Eigenmode Decomposition,” Biophys. J. 69(2), 478–488 (1995).
[Crossref] [PubMed]

M. A. Peterson, H. Strey, and E. Sackmann, “Theoretical and Phase-Contrast Microscopic Eigenmode Analysis of Erythrocyte Flicker - Amplitudes,” J. Phys. II 2(5), 1273–1285 (1992).
[Crossref]

A. Zilker, M. Ziegler, and E. Sackmann, “Spectral Analysis of Erythrocyte Flickering in the 0.3-4- Mu-M-1 Regime by Microinterferometry Combined with Fast Image Processing,” Phys. Rev. A 46(12), 7998–8001 (1992).
[Crossref] [PubMed]

Salamero, J.

V. Racine, M. Sachse, J. Salamero, V. Fraisier, A. Trubuil, and J. B. Sibarita, “Visualization and quantification of vesicle trafficking on a three-dimensional cytoskeleton network in living cells,” J. Microsc. 225(Pt 3), 214–228 (2007).
[Crossref] [PubMed]

Sandhu, R.

R. L. Blackmon, R. Sandhu, B. S. Chapman, P. Casbas-Hernandez, J. B. Tracy, M. A. Troester, and A. L. Oldenburg, “Imaging Extracellular Matrix Remodeling In Vitro by Diffusion-Sensitive Optical Coherence Tomography,” Biophys. J. 110(8), 1858–1868 (2016).
[Crossref] [PubMed]

Selting, K. A.

D. M. Vail, G. M. Michels, C. Khanna, K. A. Selting, and C. A. London, “Response evaluation criteria for peripheral nodal lymphoma in dogs (v1.0)-a veterinary cooperative oncology group (VCOG) consensus document,” Vet. Comp. Oncol. 8(1), 28–37 (2010).
[Crossref] [PubMed]

Sibarita, J. B.

V. Racine, M. Sachse, J. Salamero, V. Fraisier, A. Trubuil, and J. B. Sibarita, “Visualization and quantification of vesicle trafficking on a three-dimensional cytoskeleton network in living cells,” J. Microsc. 225(Pt 3), 214–228 (2007).
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K. K. Bizheva, A. M. Siegel, and D. A. Boas, “Path-length-resolved dynamic light scattering in highly scattering random media: The transition to diffusing wave spectroscopy,” Phys. Rev. E Stat. Phys. Plasmas Fluids Relat. Interdiscip. Topics 58(6), 7664–7667 (1998).
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Sims, P. A.

X. Nan, P. A. Sims, and X. S. Xie, “Organelle tracking in a living cell with microsecond time resolution and nanometer spatial precision,” ChemPhysChem 9(5), 707–712 (2008).
[Crossref] [PubMed]

Sleep, J.

J. Evans, W. Gratzer, N. Mohandas, K. Parker, and J. Sleep, “Fluctuations of the red blood cell membrane: Relation to mechanical properties and lack of ATP dependence,” Biophys. J. 94(10), 4134–4144 (2008).
[Crossref] [PubMed]

Sosnovtseva, O. V.

N. A. Brazhe, A. R. Brazhe, A. N. Pavlov, L. A. Erokhova, A. I. Yusipovich, G. V. Maksimov, E. Mosekilde, and O. V. Sosnovtseva, “Unraveling cell processes: interference imaging interwoven with data analysis,” J. Biol. Phys. 32(3-4), 191–208 (2006).
[Crossref] [PubMed]

Stepinac, T.

Strey, H.

H. Strey, M. Peterson, and E. Sackmann, “Measurement of Erythrocyte Membrane Elasticity by Flicker Eigenmode Decomposition,” Biophys. J. 69(2), 478–488 (1995).
[Crossref] [PubMed]

M. A. Peterson, H. Strey, and E. Sackmann, “Theoretical and Phase-Contrast Microscopic Eigenmode Analysis of Erythrocyte Flicker - Amplitudes,” J. Phys. II 2(5), 1273–1285 (1992).
[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. Screen. 19(4), 526–537 (2014).
[Crossref] [PubMed]

Suissa, M.

M. Suissa, C. Place, E. Goillot, and E. Freyssingeas, “Internal dynamics of a living cell nucleus investigated by dynamic light scattering,” Eur Phys J E Soft Matter 26(4), 435–448 (2008).
[Crossref] [PubMed]

Sun, H.

H. Sun, D. Merrill, R. An, J. Turek, D. Matei, and D. D. Nolte, “Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture,” J. Biomed. Opt. 22(1), 16007 (2017).
[Crossref] [PubMed]

D. Merrill, R. An, H. Sun, B. Yakubov, D. Matei, J. Turek, and D. Nolte, “Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts,” Sci. Rep. 6(1), 18821 (2016).
[Crossref] [PubMed]

Sung, S. Y.

S. Y. Sung, C. L. Hsieh, D. Wu, L. W. Chung, and P. A. Johnstone, “Tumor microenvironment promotes cancer progression, metastasis, and therapeutic resistance,” Curr. Probl. Cancer 31(2), 36–100 (2007).
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L. G. Griffith and M. A. Swartz, “Capturing complex 3D tissue physiology in vitro,” Nat. Rev. Mol. Cell Biol. 7(3), 211–224 (2006).
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T. Betz, M. Lenz, J.-F. Joanny, and C. Sykes, “ATP-dependent mechanics of red blood cells,” Proc. Natl. Acad. Sci. U.S.A. 106(36), 15320–15325 (2009).
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K. Tamura, T. Mizutani, H. Haga, and K. Kawabata, “Active fluctuation in the cortical cytoskeleton observed by high-speed live-cell scanning probe microscopy,” Acta Biomater. 7(10), 3766–3772 (2011).
[Crossref] [PubMed]

Thamm, D. H.

L. D. Garrett, D. H. Thamm, R. Chun, R. Dudley, and D. M. Vail, “Evaluation of a 6-month chemotherapy protocol with no maintenance therapy for dogs with lymphoma,” J. Vet. Intern. Med. 16(6), 704–709 (2002).
[Crossref] [PubMed]

Tracy, J. B.

R. L. Blackmon, R. Sandhu, B. S. Chapman, P. Casbas-Hernandez, J. B. Tracy, M. A. Troester, and A. L. Oldenburg, “Imaging Extracellular Matrix Remodeling In Vitro by Diffusion-Sensitive Optical Coherence Tomography,” Biophys. J. 110(8), 1858–1868 (2016).
[Crossref] [PubMed]

Trinczek, B.

B. Trinczek, A. Ebneth, E. M. Mandelkow, and E. Mandelkow, “Tau regulates the attachment/detachment but not the speed of motors in microtubule-dependent transport of single vesicles and organelles,” J. Cell Sci. 112(Pt 14), 2355–2367 (1999).
[PubMed]

Troester, M. A.

R. L. Blackmon, R. Sandhu, B. S. Chapman, P. Casbas-Hernandez, J. B. Tracy, M. A. Troester, and A. L. Oldenburg, “Imaging Extracellular Matrix Remodeling In Vitro by Diffusion-Sensitive Optical Coherence Tomography,” Biophys. J. 110(8), 1858–1868 (2016).
[Crossref] [PubMed]

Trubuil, A.

V. Racine, M. Sachse, J. Salamero, V. Fraisier, A. Trubuil, and J. B. Sibarita, “Visualization and quantification of vesicle trafficking on a three-dimensional cytoskeleton network in living cells,” J. Microsc. 225(Pt 3), 214–228 (2007).
[Crossref] [PubMed]

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. Screen. 19(4), 526–537 (2014).
[Crossref] [PubMed]

Turek, J.

H. Sun, D. Merrill, R. An, J. Turek, D. Matei, and D. D. Nolte, “Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture,” J. Biomed. Opt. 22(1), 16007 (2017).
[Crossref] [PubMed]

D. Merrill, R. An, H. Sun, B. Yakubov, D. Matei, J. Turek, and D. Nolte, “Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts,” Sci. Rep. 6(1), 18821 (2016).
[Crossref] [PubMed]

D. Merrill, R. An, J. Turek, and D. D. Nolte, “Digital holography of intracellular dynamics to probe tissue physiology,” Appl. Opt. 54(1), A89–A97 (2015).
[Crossref] [PubMed]

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. Screen. 19(4), 526–537 (2014).
[Crossref] [PubMed]

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(11), 2825–2841 (2012).
[Crossref] [PubMed]

D. D. Nolte, R. An, J. Turek, and K. Jeong, “Holographic tissue dynamics spectroscopy,” J. Biomed. Opt. 16(8), 087004 (2011).
[Crossref] [PubMed]

D. D. Nolte, R. An, J. Turek, and K. Jeong, “Tissue Dynamics Spectroscopy for Three-Dimensional Tissue-Based Drug Screening,” J. Lab. Autom. 16(6), 431–442 (2011).
[Crossref] [PubMed]

Turek, J. J.

M. R. Custead, R. An, J. J. Turek, G. E. Moore, D. D. Nolte, and M. O. Childress, “Predictive value of ex vivo biodynamic imaging in determining response to chemotherapy in dogs with spontaneous non-Hodgkin’s lymphomas: a preliminary study,” Converg Sci Phys Oncol 1(1), 015003 (2015).
[Crossref] [PubMed]

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(3), 030514 (2010).
[Crossref] [PubMed]

K. Jeong, J. J. Turek, and D. D. Nolte, “Imaging Motility Contrast in Digital Holography of Tissue Response to Cytoskeletal Anti-cancer Drugs,” Opt. Express 15(21), 14057–14064 (2007).
[Crossref] [PubMed]

Vail, D. M.

D. M. Vail, G. M. Michels, C. Khanna, K. A. Selting, and C. A. London, “Response evaluation criteria for peripheral nodal lymphoma in dogs (v1.0)-a veterinary cooperative oncology group (VCOG) consensus document,” Vet. Comp. Oncol. 8(1), 28–37 (2010).
[Crossref] [PubMed]

L. D. Garrett, D. H. Thamm, R. Chun, R. Dudley, and D. M. Vail, “Evaluation of a 6-month chemotherapy protocol with no maintenance therapy for dogs with lymphoma,” J. Vet. Intern. Med. 16(6), 704–709 (2002).
[Crossref] [PubMed]

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R. D. Vale and R. A. Milligan, “The way things move: Looking under the hood of molecular motor proteins,” Science 288(5463), 88–95 (2000).
[Crossref] [PubMed]

Wax, A.

Wu, D.

S. Y. Sung, C. L. Hsieh, D. Wu, L. W. Chung, and P. A. Johnstone, “Tumor microenvironment promotes cancer progression, metastasis, and therapeutic resistance,” Curr. Probl. Cancer 31(2), 36–100 (2007).
[Crossref] [PubMed]

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(6), 819–825 (2013).
[Crossref] [PubMed]

Xie, X. S.

X. Nan, P. A. Sims, and X. S. Xie, “Organelle tracking in a living cell with microsecond time resolution and nanometer spatial precision,” ChemPhysChem 9(5), 707–712 (2008).
[Crossref] [PubMed]

Yakubov, B.

D. Merrill, R. An, H. Sun, B. Yakubov, D. Matei, J. Turek, and D. Nolte, “Intracellular Doppler Signatures of Platinum Sensitivity Captured by Biodynamic Profiling in Ovarian Xenografts,” Sci. Rep. 6(1), 18821 (2016).
[Crossref] [PubMed]

Yamaguchi, I.

Yang, C.

Yaqoob, Z.

Yoon, Y. Z.

Y. Z. Yoon, H. Hong, A. Brown, D. C. Kim, D. J. Kang, V. L. Lew, and P. Cicuta, “Flickering Analysis of Erythrocyte Mechanical Properties: Dependence on Oxygenation Level, Cell Shape, and Hydration Level,” Biophys. J. 97(6), 1606–1615 (2009).
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Yuan, F.

N. T. Elliott and F. Yuan, “A Review of Three-Dimensional In Vitro Tissue Models for Drug Discovery and Transport Studies,” J. Pharm. Sci. 100(1), 59–74 (2011).
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Yusipovich, A. I.

N. A. Brazhe, A. R. Brazhe, A. N. Pavlov, L. A. Erokhova, A. I. Yusipovich, G. V. Maksimov, E. Mosekilde, and O. V. Sosnovtseva, “Unraveling cell processes: interference imaging interwoven with data analysis,” J. Biol. Phys. 32(3-4), 191–208 (2006).
[Crossref] [PubMed]

Zhang, T.

Ziegler, M.

A. Zilker, M. Ziegler, and E. Sackmann, “Spectral Analysis of Erythrocyte Flickering in the 0.3-4- Mu-M-1 Regime by Microinterferometry Combined with Fast Image Processing,” Phys. Rev. A 46(12), 7998–8001 (1992).
[Crossref] [PubMed]

Zilker, A.

A. Zilker, M. Ziegler, and E. Sackmann, “Spectral Analysis of Erythrocyte Flickering in the 0.3-4- Mu-M-1 Regime by Microinterferometry Combined with Fast Image Processing,” Phys. Rev. A 46(12), 7998–8001 (1992).
[Crossref] [PubMed]

Acta Biomater. (1)

K. Tamura, T. Mizutani, H. Haga, and K. Kawabata, “Active fluctuation in the cortical cytoskeleton observed by high-speed live-cell scanning probe microscopy,” Acta Biomater. 7(10), 3766–3772 (2011).
[Crossref] [PubMed]

Appl. Opt. (3)

Biomed. Opt. Express (1)

Biophys. J. (4)

Y. Z. Yoon, H. Hong, A. Brown, D. C. Kim, D. J. Kang, V. L. Lew, and P. Cicuta, “Flickering Analysis of Erythrocyte Mechanical Properties: Dependence on Oxygenation Level, Cell Shape, and Hydration Level,” Biophys. J. 97(6), 1606–1615 (2009).
[Crossref] [PubMed]

J. Evans, W. Gratzer, N. Mohandas, K. Parker, and J. Sleep, “Fluctuations of the red blood cell membrane: Relation to mechanical properties and lack of ATP dependence,” Biophys. J. 94(10), 4134–4144 (2008).
[Crossref] [PubMed]

H. Strey, M. Peterson, and E. Sackmann, “Measurement of Erythrocyte Membrane Elasticity by Flicker Eigenmode Decomposition,” Biophys. J. 69(2), 478–488 (1995).
[Crossref] [PubMed]

R. L. Blackmon, R. Sandhu, B. S. Chapman, P. Casbas-Hernandez, J. B. Tracy, M. A. Troester, and A. L. Oldenburg, “Imaging Extracellular Matrix Remodeling In Vitro by Diffusion-Sensitive Optical Coherence Tomography,” Biophys. J. 110(8), 1858–1868 (2016).
[Crossref] [PubMed]

ChemPhysChem (1)

X. Nan, P. A. Sims, and X. S. Xie, “Organelle tracking in a living cell with microsecond time resolution and nanometer spatial precision,” ChemPhysChem 9(5), 707–712 (2008).
[Crossref] [PubMed]

Clin. Cancer Res. (1)

E. J. Hartsough and A. E. Aplin, “Of Mice and Melanoma: PDX System for Modeling Personalized Medicine,” Clin. Cancer Res. 22(7), 1550–1552 (2016).
[Crossref] [PubMed]

Converg Sci Phys Oncol (1)

M. R. Custead, R. An, J. J. Turek, G. E. Moore, D. D. Nolte, and M. O. Childress, “Predictive value of ex vivo biodynamic imaging in determining response to chemotherapy in dogs with spontaneous non-Hodgkin’s lymphomas: a preliminary study,” Converg Sci Phys Oncol 1(1), 015003 (2015).
[Crossref] [PubMed]

Curr. Opin. Obstet. Gynecol. (1)

I. A. Cree, “Chemosensitivity and chemoresistance testing in ovarian cancer,” Curr. Opin. Obstet. Gynecol. 21(1), 39–43 (2009).
[Crossref] [PubMed]

Curr. Probl. Cancer (1)

S. Y. Sung, C. L. Hsieh, D. Wu, L. W. Chung, and P. A. Johnstone, “Tumor microenvironment promotes cancer progression, metastasis, and therapeutic resistance,” Curr. Probl. Cancer 31(2), 36–100 (2007).
[Crossref] [PubMed]

Drug Discov. Today (1)

S. Breslin and L. O’Driscoll, “Three-dimensional cell culture: the missing link in drug discovery,” Drug Discov. Today 18(5-6), 240–249 (2013).
[Crossref] [PubMed]

Eur Phys J E Soft Matter (1)

M. Suissa, C. Place, E. Goillot, and E. Freyssingeas, “Internal dynamics of a living cell nucleus investigated by dynamic light scattering,” Eur Phys J E Soft Matter 26(4), 435–448 (2008).
[Crossref] [PubMed]

J. Biol. Phys. (1)

N. A. Brazhe, A. R. Brazhe, A. N. Pavlov, L. A. Erokhova, A. I. Yusipovich, G. V. Maksimov, E. Mosekilde, and O. V. Sosnovtseva, “Unraveling cell processes: interference imaging interwoven with data analysis,” J. Biol. Phys. 32(3-4), 191–208 (2006).
[Crossref] [PubMed]

J. Biomed. Opt. (4)

G. Farhat, A. Giles, M. C. Kolios, and G. J. Czarnota, “Optical coherence tomography spectral analysis for detecting apoptosis in vitro and in vivo,” J. Biomed. Opt. 20(12), 126001 (2015).
[Crossref] [PubMed]

H. Sun, D. Merrill, R. An, J. Turek, D. Matei, and D. D. Nolte, “Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture,” J. Biomed. Opt. 22(1), 16007 (2017).
[Crossref] [PubMed]

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(3), 030514 (2010).
[Crossref] [PubMed]

D. D. Nolte, R. An, J. Turek, and K. Jeong, “Holographic tissue dynamics spectroscopy,” J. Biomed. Opt. 16(8), 087004 (2011).
[Crossref] [PubMed]

J. Biomol. Screen. (2)

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. Screen. 19(4), 526–537 (2014).
[Crossref] [PubMed]

J. A. Lee and E. L. Berg, “Neoclassic Drug Discovery: The Case for Lead Generation Using Phenotypic and Functional Approaches,” J. Biomol. Screen. 18(10), 1143–1155 (2013).
[Crossref] [PubMed]

J. Cell Sci. (1)

B. Trinczek, A. Ebneth, E. M. Mandelkow, and E. Mandelkow, “Tau regulates the attachment/detachment but not the speed of motors in microtubule-dependent transport of single vesicles and organelles,” J. Cell Sci. 112(Pt 14), 2355–2367 (1999).
[PubMed]

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(6), 819–825 (2013).
[Crossref] [PubMed]

J. Lab. Autom. (1)

D. D. Nolte, R. An, J. Turek, and K. Jeong, “Tissue Dynamics Spectroscopy for Three-Dimensional Tissue-Based Drug Screening,” J. Lab. Autom. 16(6), 431–442 (2011).
[Crossref] [PubMed]

J. Microsc. (1)

V. Racine, M. Sachse, J. Salamero, V. Fraisier, A. Trubuil, and J. B. Sibarita, “Visualization and quantification of vesicle trafficking on a three-dimensional cytoskeleton network in living cells,” J. Microsc. 225(Pt 3), 214–228 (2007).
[Crossref] [PubMed]

J. Morphol. (1)

K. J. Karnaky, L. T. Garretson, and R. G. O’Neil, “Video-Enhanced Microscopy of Organelle Movement in an Intact Epithelium,” J. Morphol. 213(1), 21–31 (1992).
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Figures (8)

Fig. 1
Fig. 1 (a) Optical system configuration with low-coherence light (SL) and (b) reconstructed images of B-cell Lymphoma of a canine patient. Optical coherence images (OCI) and corresponding motility contrast images (MCI) are shown for baseline and post-dose measurements.
Fig. 2
Fig. 2 (a) A schematic of the spectral contributions from three assumed intracellular processes. The fluctuation spectra separate according to their representative knee frequency, with rheological (cell shape) processes dominating at low frequencies, nuclear and membrane processes at mid frequencies, and organelle dynamics at high frequencies. (b) The data format D(ω, t) of biodynamic spectrograms illustrated for the case of a B-cell lymphoma biopsy responding to 10 μM doxorubicin. The horizontal axis is the mean intracellular speed obtained from v=ω/q. The vertical axis is time. The sample is dosed after a 4-hour baseline.
Fig. 3
Fig. 3 Progression-free survival (PFS) for 19 dogs treated with CHOP. The last two dogs had PFS times greater than 365 days.
Fig. 4
Fig. 4 Raw average spectrograms (top row) and DMSO-subtracted average spectrograms (bottom row). Frequency spans from 0.01 to 10 Hz on the horizontal frequency axis, and from −4 hours to 12 hours on the vertical time axis. The treatment is applied at t = 0 (horizontal line on each spectrogram). The color range is from −70% (blue) to + 70% (red).
Fig. 5
Fig. 5 Average spectrograms for (a) the resistant and (b) the sensitive subsets of the canine patient cohort. A strong phenotypic difference exists for nearly all drugs. The sensitive phenotype displays early apoptotic character (which is a desired chemotherapy outcome) for CHOP, doxorubicin and prednisolone. The responses to vincristine and cyclophosphamide show strong spectral enhancements for the resistant patients. (c) Difference spectrograms for short-PFS relative to long-PFS patient responses. There is overall enhanced higher frequency content in all cases, and a blue-shift of doxorubicin for short-PFS relative to long-PFS.
Fig. 6
Fig. 6 Classifier values for log likelihood and the averaged perceptrons for hold-out validation. TP = 5, TN = 11, FN = 1, FP = 2. Accuracy = 84%.
Fig. 7
Fig. 7 (a) Feature vector matrix for nineteen patients and 9 features (N-Dim = 9) grouped into resistant (short-PFS) and sensitive (long-PFS) groups. The patient sorting order is based on PFS times (see Fig. 3). (b) Similarity matrix for the nineteen patients. Each matrix element is the direction cosine between the two feature vectors. The short-PFS and long-PFS groups cluster into block-diagonal (except for Jul). The color scale is from −1 (blue) to + 1 (red).
Fig. 8
Fig. 8 Similarity network with links that reflect similarities between dogs. The nodes are colored blue (short-PFS) and red (long-PFS). Links are shown for direction cosines greater than 0.3. Nodes representing the average long and short PFS responses are included. Two false positives (Cli and Jo) and one false negative (Jul) are clearly clustered with the opposite groups.

Equations (4)

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S( ω )=FT( A( τ ) )
D( ω,t )=logS( ω,t )log S 0 ( ω )
S 0 ( ω )= 1 4 4 0 S( ω,t )dt
LL= a log 1+ P R ( v a ) 1+ P S ( v a )

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