Abstract

The microscopic structural origins of optical properties in biological media are still not fully understood. Better understanding these origins can serve to improve the utility of existing techniques and facilitate the discovery of other novel techniques. We propose a novel analysis technique using electron microscopy (EM) to calculate optical properties of specific biological structures. This method is demonstrated with images of human epithelial colon cell nuclei. The spectrum of anisotropy factor g, the phase function and the shape factor D of the nuclei are calculated. The results show strong agreement with an independent study. This method provides a new way to extract the true phase function of biological samples and provides an independent validation for optical property measurement techniques.

© 2016 Optical Society of America

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2015 (3)

A. J. Radosevich, N. N. Mutyal, A. Eshein, T.-Q. Nguyen, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, J. Van Dam, V. Backman, and H. K. Roy, “Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal Lesions,” Clin. Cancer Res. 21(19), 4347–4355 (2015).
[Crossref] [PubMed]

N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, S. Upadhye, A. Koons, M. Gonzalez-Haba Ruiz, H. K. Roy, and V. Backman, “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44(5), 735–741 (2015).
[Crossref] [PubMed]

A. J. Radosevich, A. Eshein, T. Q. Nguyen, and V. Backman, “Subdiffusion reflectance spectroscopy to measure tissue ultrastructure and microvasculature: model and inverse algorithm,” J. Biomed. Opt. 20(9), 097002 (2015).
[Crossref] [PubMed]

2014 (4)

J. Yi, A. J. Radosevich, Y. Stypula-Cyrus, N. N. Mutyal, S. M. Azarin, E. Horcher, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Spatially resolved optical and ultrastructural properties of colorectal and pancreatic field carcinogenesis observed by inverse spectroscopic optical coherence tomography,” J. Biomed. Opt. 19(3), 036013 (2014).
[Crossref] [PubMed]

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14(1), 189 (2014).
[Crossref] [PubMed]

J. S. Kim and I. Szleifer, “Crowding-induced formation and structural alteration of nuclear compartments: insights from computer simulations,” Int. Rev. Cell Mol. Biol. 307, 73–108 (2014).
[Crossref] [PubMed]

K. W. Calabro and I. J. Bigio, “Influence of the phase function in generalized diffuse reflectance models: review of current formalisms and novel observations,” J. Biomed. Opt. 19(7), 075005 (2014).
[Crossref] [PubMed]

2013 (6)

T. Tan, A. Taflove, and V. Backman, “Single realization stochastic FDTD for weak scattering waves in biological random media,” IEEE Trans. Antenn. Propag. 61(2), 818–828 (2013).
[Crossref] [PubMed]

J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling Light Scattering in Tissue as Continuous Random Media Using a Versatile Refractive Index Correlation Function,” IEEE J. Sel. Top. Quantum Electron. 20(2), 7000514 (2013).
[PubMed]

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18(9), 097002 (2013).
[Crossref] [PubMed]

J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling Light Scattering in Tissue as Continuous Random Media Using a Versatile Refractive Index Correlation Function,” IEEE J. Sel. Top. Quantum Electron. 20(2), 7000514 (2013).
[PubMed]

J. Yi, A. J. Radosevich, J. D. Rogers, S. C. Norris, I. R. Çapoğlu, A. Taflove, and V. Backman, “Can OCT be sensitive to nanoscale structural alterations in biological tissue?” Opt. Express 21(7), 9043–9059 (2013).
[Crossref] [PubMed]

V. Backman and H. K. Roy, “Advances in biophotonics detection of field carcinogenesis for colon cancer risk stratification,” J. Cancer 4(3), 251–261 (2013).
[Crossref] [PubMed]

2012 (2)

2011 (1)

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

2009 (4)

A. Bancaud, S. Huet, N. Daigle, J. Mozziconacci, J. Beaudouin, and J. Ellenberg, “Molecular crowding affects diffusion and binding of nuclear proteins in heterochromatin and reveals the fractal organization of chromatin,” EMBO J. 28(24), 3785–3798 (2009).
[Crossref] [PubMed]

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res. 69(13), 5357–5363 (2009).
[Crossref] [PubMed]

İ. R. Capoğlu, J. D. Rogers, A. Taflove, and V. Backman, “Accuracy of the Born approximation in calculating the scattering coefficient of biological continuous random media,” Opt. Lett. 34(17), 2679–2681 (2009).
[Crossref] [PubMed]

J. D. Rogers, İ. R. Capoğlu, and V. Backman, “Nonscalar elastic light scattering from continuous random media in the Born approximation,” Opt. Lett. 34(12), 1891–1893 (2009).
[Crossref] [PubMed]

2007 (1)

2006 (2)

T. Binzoni, T. Leung, A. Gandjbakhche, D. Rüfenacht, and D. Delpy, “The use of the Henyey–Greenstein phase function in Monte Carlo simulations in biomedical optics,” Phys. Med. Biol. 51(17), 313 (2006).

H. K. Roy, Y. L. Kim, Y. Liu, R. K. Wali, M. J. Goldberg, V. Turzhitsky, J. Horwitz, and V. Backman, “Risk stratification of colon carcinogenesis through enhanced backscattering spectroscopy analysis of the uninvolved colonic mucosa,” Clin. Cancer Res. 12(3), 961–968 (2006).
[Crossref] [PubMed]

2005 (5)

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, and V. Backman, “Low-coherent backscattering spectroscopy for tissue characterization,” Appl. Opt. 44(3), 366–377 (2005).
[Crossref] [PubMed]

Y. L. Kim, Y. Liu, V. M. Turzhitsky, R. K. Wali, H. K. Roy, and V. Backman, “Depth-resolved low-coherence enhanced backscattering,” Opt. Lett. 30(7), 741–743 (2005).
[Crossref] [PubMed]

T. C. Zhu, J. C. Finlay, and S. M. Hahn, “Determination of the distribution of light, optical properties, drug concentration, and tissue oxygenation in-vivo in human prostate during motexafin lutetium-mediated photodynamic therapy,” J. Photochem. Photobiol. B 79(3), 231–241 (2005).
[Crossref] [PubMed]

M. Xu and R. R. Alfano, “Fractal mechanisms of light scattering in biological tissue and cells,” Opt. Lett. 30(22), 3051–3053 (2005).
[Crossref] [PubMed]

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

2004 (1)

2000 (1)

J.-R. Daban, “Physical constraints in the condensation of eukaryotic chromosomes. Local concentration of DNA versus linear packing ratio in higher order chromatin structures,” Biochemistry 39(14), 3861–3866 (2000).
[Crossref] [PubMed]

1999 (3)

W. Drexler, U. Morgner, F. X. Kärtner, C. Pitris, S. A. Boppart, X. D. Li, E. P. Ippen, and J. G. Fujimoto, “In vivo ultrahigh-resolution optical coherence tomography,” Opt. Lett. 24(17), 1221–1223 (1999).
[Crossref] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” Selected Topics in Quantum Electronics, IEEE Journal of 5(4), 1019–1026 (1999).
[Crossref]

R. M. Doornbos, R. Lang, M. C. Aalders, F. W. Cross, and H. J. Sterenborg, “The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy,” Phys. Med. Biol. 44(4), 967–981 (1999).
[Crossref] [PubMed]

1998 (3)

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, “Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution,” Phys. Rev. Lett. 80(3), 627–630 (1998).
[Crossref]

M. Hammer, D. Schweitzer, B. Michel, E. Thamm, and A. Kolb, “Single scattering by red blood cells,” Appl. Opt. 37(31), 7410–7418 (1998).
[Crossref] [PubMed]

J. R. Mourant, J. P. Freyer, A. H. Hielscher, A. A. Eick, D. Shen, and T. M. Johnson, “Mechanisms of light scattering from biological cells relevant to noninvasive optical-tissue diagnostics,” Appl. Opt. 37(16), 3586–3593 (1998).
[Crossref] [PubMed]

1997 (3)

1996 (1)

1994 (1)

P. A. Penczek, R. A. Grassucci, and J. Frank, “The ribosome at improved resolution: new techniques for merging and orientation refinement in 3D cryo-electron microscopy of biological particles,” Ultramicroscopy 53(3), 251–270 (1994).
[Crossref] [PubMed]

1993 (2)

B. Bohrmann, M. Haider, and E. Kellenberger, “Concentration evaluation of chromatin in unstained resin-embedded sections by means of low-dose ratio-contrast imaging in STEM,” Ultramicroscopy 49(1-4), 235–251 (1993).
[Crossref] [PubMed]

J. W. Pickering, S. A. Prahl, N. van Wieringen, J. F. Beek, H. J. Sterenborg, and M. J. van Gemert, “Double-integrating-sphere system for measuring the optical properties of tissue,” Appl. Opt. 32(4), 399–410 (1993).
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1992 (1)

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12(5), 510–519 (1992).
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1990 (2)

B. C. Wilson and S. L. Jacques, “Optical reflectance and transmittance of tissues: principles and applications,” Quantum Electronics, IEEE Journal of 26(12), 2186–2199 (1990).
[Crossref]

W.-F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990).
[Crossref]

1989 (1)

1986 (1)

B. C. Wilson and M. S. Patterson, “The physics of photodynamic therapy,” Phys. Med. Biol. 31(4), 327–360 (1986).
[Crossref] [PubMed]

1985 (1)

B. H. Johnston and A. Rich, “Chemical probes of DNA conformation: detection of Z-DNA at nucleotide resolution,” Cell 42(3), 713–724 (1985).
[Crossref] [PubMed]

1984 (1)

M. Adrian, J. Dubochet, J. Lepault, and A. W. McDowall, “Cryo-electron microscopy of viruses,” Nature 53, 32–36 (1984).

1982 (1)

E. Lukasova, F. Jelen, and E. Palecek, “Electrochemistry of osmium nucleic-acid complexes-a probe for single-stranded and distorted double-stranded regions in DNA,” Gen. Physiol. Biophys. 1, 53–70 (1982).

1976 (1)

J. Mandarino, “The Gladstone-Dale relationship. Part I: derivation of new constants,” Can. Mineral. 14, 498–502 (1976).

1955 (1)

J. A. Jacquez and H. F. Kuppenheim, “Theory of the integrating sphere,” JOSA 45(6), 460–466 (1955).
[Crossref]

1954 (1)

H. Davies, M. Wilkins, J. Chayen, and L. La Cour, “The use of the interference microscope to determine dry mass in living cells and as a quantitative cytochemical method,” Q. J. Microsc. Sci. 3, 271–304 (1954).

Aalders, M. C.

R. M. Doornbos, R. Lang, M. C. Aalders, F. W. Cross, and H. J. Sterenborg, “The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy,” Phys. Med. Biol. 44(4), 967–981 (1999).
[Crossref] [PubMed]

Adrian, M.

M. Adrian, J. Dubochet, J. Lepault, and A. W. McDowall, “Cryo-electron microscopy of viruses,” Nature 53, 32–36 (1984).

Alfano, R. R.

Allman, B. E.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

Anderson, E. R.

Azarin, S. M.

J. Yi, A. J. Radosevich, Y. Stypula-Cyrus, N. N. Mutyal, S. M. Azarin, E. Horcher, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Spatially resolved optical and ultrastructural properties of colorectal and pancreatic field carcinogenesis observed by inverse spectroscopic optical coherence tomography,” J. Biomed. Opt. 19(3), 036013 (2014).
[Crossref] [PubMed]

Backman, V.

A. J. Radosevich, A. Eshein, T. Q. Nguyen, and V. Backman, “Subdiffusion reflectance spectroscopy to measure tissue ultrastructure and microvasculature: model and inverse algorithm,” J. Biomed. Opt. 20(9), 097002 (2015).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, A. Eshein, T.-Q. Nguyen, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, J. Van Dam, V. Backman, and H. K. Roy, “Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal Lesions,” Clin. Cancer Res. 21(19), 4347–4355 (2015).
[Crossref] [PubMed]

N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, S. Upadhye, A. Koons, M. Gonzalez-Haba Ruiz, H. K. Roy, and V. Backman, “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44(5), 735–741 (2015).
[Crossref] [PubMed]

J. Yi, A. J. Radosevich, Y. Stypula-Cyrus, N. N. Mutyal, S. M. Azarin, E. Horcher, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Spatially resolved optical and ultrastructural properties of colorectal and pancreatic field carcinogenesis observed by inverse spectroscopic optical coherence tomography,” J. Biomed. Opt. 19(3), 036013 (2014).
[Crossref] [PubMed]

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14(1), 189 (2014).
[Crossref] [PubMed]

J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling Light Scattering in Tissue as Continuous Random Media Using a Versatile Refractive Index Correlation Function,” IEEE J. Sel. Top. Quantum Electron. 20(2), 7000514 (2013).
[PubMed]

T. Tan, A. Taflove, and V. Backman, “Single realization stochastic FDTD for weak scattering waves in biological random media,” IEEE Trans. Antenn. Propag. 61(2), 818–828 (2013).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18(9), 097002 (2013).
[Crossref] [PubMed]

J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling Light Scattering in Tissue as Continuous Random Media Using a Versatile Refractive Index Correlation Function,” IEEE J. Sel. Top. Quantum Electron. 20(2), 7000514 (2013).
[PubMed]

V. Backman and H. K. Roy, “Advances in biophotonics detection of field carcinogenesis for colon cancer risk stratification,” J. Cancer 4(3), 251–261 (2013).
[Crossref] [PubMed]

J. Yi, A. J. Radosevich, J. D. Rogers, S. C. Norris, I. R. Çapoğlu, A. Taflove, and V. Backman, “Can OCT be sensitive to nanoscale structural alterations in biological tissue?” Opt. Express 21(7), 9043–9059 (2013).
[Crossref] [PubMed]

J. Yi and V. Backman, “Imaging a full set of optical scattering properties of biological tissue by inverse spectroscopic optical coherence tomography,” Opt. Lett. 37(21), 4443–4445 (2012).
[Crossref] [PubMed]

A. J. Radosevich, J. Yi, J. D. Rogers, and V. Backman, “Structural length-scale sensitivities of reflectance measurements in continuous random media under the Born approximation,” Opt. Lett. 37(24), 5220–5222 (2012).
[Crossref] [PubMed]

İ. R. Capoğlu, J. D. Rogers, A. Taflove, and V. Backman, “Accuracy of the Born approximation in calculating the scattering coefficient of biological continuous random media,” Opt. Lett. 34(17), 2679–2681 (2009).
[Crossref] [PubMed]

J. D. Rogers, İ. R. Capoğlu, and V. Backman, “Nonscalar elastic light scattering from continuous random media in the Born approximation,” Opt. Lett. 34(12), 1891–1893 (2009).
[Crossref] [PubMed]

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res. 69(13), 5357–5363 (2009).
[Crossref] [PubMed]

H. K. Roy, Y. L. Kim, Y. Liu, R. K. Wali, M. J. Goldberg, V. Turzhitsky, J. Horwitz, and V. Backman, “Risk stratification of colon carcinogenesis through enhanced backscattering spectroscopy analysis of the uninvolved colonic mucosa,” Clin. Cancer Res. 12(3), 961–968 (2006).
[Crossref] [PubMed]

Y. L. Kim, Y. Liu, V. M. Turzhitsky, R. K. Wali, H. K. Roy, and V. Backman, “Depth-resolved low-coherence enhanced backscattering,” Opt. Lett. 30(7), 741–743 (2005).
[Crossref] [PubMed]

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, and V. Backman, “Low-coherent backscattering spectroscopy for tissue characterization,” Appl. Opt. 44(3), 366–377 (2005).
[Crossref] [PubMed]

Y. L. Kim, Y. Liu, V. M. Turzhitsky, H. K. Roy, R. K. Wali, and V. Backman, “Coherent backscattering spectroscopy,” Opt. Lett. 29(16), 1906–1908 (2004).
[Crossref] [PubMed]

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” Selected Topics in Quantum Electronics, IEEE Journal of 5(4), 1019–1026 (1999).
[Crossref]

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, “Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution,” Phys. Rev. Lett. 80(3), 627–630 (1998).
[Crossref]

Badizadegan, K.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” Selected Topics in Quantum Electronics, IEEE Journal of 5(4), 1019–1026 (1999).
[Crossref]

Bajaj, S.

N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, S. Upadhye, A. Koons, M. Gonzalez-Haba Ruiz, H. K. Roy, and V. Backman, “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44(5), 735–741 (2015).
[Crossref] [PubMed]

J. Yi, A. J. Radosevich, Y. Stypula-Cyrus, N. N. Mutyal, S. M. Azarin, E. Horcher, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Spatially resolved optical and ultrastructural properties of colorectal and pancreatic field carcinogenesis observed by inverse spectroscopic optical coherence tomography,” J. Biomed. Opt. 19(3), 036013 (2014).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18(9), 097002 (2013).
[Crossref] [PubMed]

Bancaud, A.

A. Bancaud, S. Huet, N. Daigle, J. Mozziconacci, J. Beaudouin, and J. Ellenberg, “Molecular crowding affects diffusion and binding of nuclear proteins in heterochromatin and reveals the fractal organization of chromatin,” EMBO J. 28(24), 3785–3798 (2009).
[Crossref] [PubMed]

Barer, R.

R. Barer and S. Tkaczyk, “Refractive index of concentrated protein solutions,” (1954).
[Crossref]

Beaudouin, J.

A. Bancaud, S. Huet, N. Daigle, J. Mozziconacci, J. Beaudouin, and J. Ellenberg, “Molecular crowding affects diffusion and binding of nuclear proteins in heterochromatin and reveals the fractal organization of chromatin,” EMBO J. 28(24), 3785–3798 (2009).
[Crossref] [PubMed]

Beek, J. F.

Bellair, C. J.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

Bianchi, L. K.

A. J. Radosevich, N. N. Mutyal, A. Eshein, T.-Q. Nguyen, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, J. Van Dam, V. Backman, and H. K. Roy, “Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal Lesions,” Clin. Cancer Res. 21(19), 4347–4355 (2015).
[Crossref] [PubMed]

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14(1), 189 (2014).
[Crossref] [PubMed]

J. Yi, A. J. Radosevich, Y. Stypula-Cyrus, N. N. Mutyal, S. M. Azarin, E. Horcher, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Spatially resolved optical and ultrastructural properties of colorectal and pancreatic field carcinogenesis observed by inverse spectroscopic optical coherence tomography,” J. Biomed. Opt. 19(3), 036013 (2014).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18(9), 097002 (2013).
[Crossref] [PubMed]

Bigio, I. J.

K. W. Calabro and I. J. Bigio, “Influence of the phase function in generalized diffuse reflectance models: review of current formalisms and novel observations,” J. Biomed. Opt. 19(7), 075005 (2014).
[Crossref] [PubMed]

J. R. Mourant, T. Fuselier, J. Boyer, T. M. Johnson, and I. J. Bigio, “Predictions and measurements of scattering and absorption over broad wavelength ranges in tissue phantoms,” Appl. Opt. 36(4), 949–957 (1997).
[Crossref] [PubMed]

Binzoni, T.

T. Binzoni, T. Leung, A. Gandjbakhche, D. Rüfenacht, and D. Delpy, “The use of the Henyey–Greenstein phase function in Monte Carlo simulations in biomedical optics,” Phys. Med. Biol. 51(17), 313 (2006).

Bogojevic, A.

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res. 69(13), 5357–5363 (2009).
[Crossref] [PubMed]

Bohrmann, B.

B. Bohrmann, M. Haider, and E. Kellenberger, “Concentration evaluation of chromatin in unstained resin-embedded sections by means of low-dose ratio-contrast imaging in STEM,” Ultramicroscopy 49(1-4), 235–251 (1993).
[Crossref] [PubMed]

Boppart, S. A.

Bouma, B. E.

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

Boyer, J.

Brand, R. E.

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res. 69(13), 5357–5363 (2009).
[Crossref] [PubMed]

Brenner, M.

Calabro, K. W.

K. W. Calabro and I. J. Bigio, “Influence of the phase function in generalized diffuse reflectance models: review of current formalisms and novel observations,” J. Biomed. Opt. 19(7), 075005 (2014).
[Crossref] [PubMed]

Capoglu, I. R.

Çapoglu, I. R.

Chance, B.

Chang, J. S.

H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res. 69(13), 5357–5363 (2009).
[Crossref] [PubMed]

Chayen, J.

H. Davies, M. Wilkins, J. Chayen, and L. La Cour, “The use of the interference microscope to determine dry mass in living cells and as a quantitative cytochemical method,” Q. J. Microsc. Sci. 3, 271–304 (1954).

Cheong, W.-F.

W.-F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26(12), 2166–2185 (1990).
[Crossref]

Cherkezyan, L.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14(1), 189 (2014).
[Crossref] [PubMed]

Coquoz, O.

Crawford, J. M.

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, “Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution,” Phys. Rev. Lett. 80(3), 627–630 (1998).
[Crossref]

Cross, F. W.

R. M. Doornbos, R. Lang, M. C. Aalders, F. W. Cross, and H. J. Sterenborg, “The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy,” Phys. Med. Biol. 44(4), 967–981 (1999).
[Crossref] [PubMed]

Curl, C. L.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

Daban, J.-R.

J.-R. Daban, “Physical constraints in the condensation of eukaryotic chromosomes. Local concentration of DNA versus linear packing ratio in higher order chromatin structures,” Biochemistry 39(14), 3861–3866 (2000).
[Crossref] [PubMed]

Daigle, N.

A. Bancaud, S. Huet, N. Daigle, J. Mozziconacci, J. Beaudouin, and J. Ellenberg, “Molecular crowding affects diffusion and binding of nuclear proteins in heterochromatin and reveals the fractal organization of chromatin,” EMBO J. 28(24), 3785–3798 (2009).
[Crossref] [PubMed]

Dasari, R. R.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” Selected Topics in Quantum Electronics, IEEE Journal of 5(4), 1019–1026 (1999).
[Crossref]

Davies, H.

H. Davies, M. Wilkins, J. Chayen, and L. La Cour, “The use of the interference microscope to determine dry mass in living cells and as a quantitative cytochemical method,” Q. J. Microsc. Sci. 3, 271–304 (1954).

Dela Cruz, M.

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14(1), 189 (2014).
[Crossref] [PubMed]

Delbridge, L. M.

C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

Delpy, D.

T. Binzoni, T. Leung, A. Gandjbakhche, D. Rüfenacht, and D. Delpy, “The use of the Henyey–Greenstein phase function in Monte Carlo simulations in biomedical optics,” Phys. Med. Biol. 51(17), 313 (2006).

Doornbos, R. M.

R. M. Doornbos, R. Lang, M. C. Aalders, F. W. Cross, and H. J. Sterenborg, “The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy,” Phys. Med. Biol. 44(4), 967–981 (1999).
[Crossref] [PubMed]

Drexler, W.

Dubochet, J.

M. Adrian, J. Dubochet, J. Lepault, and A. W. McDowall, “Cryo-electron microscopy of viruses,” Nature 53, 32–36 (1984).

Eick, A. A.

Ellenberg, J.

A. Bancaud, S. Huet, N. Daigle, J. Mozziconacci, J. Beaudouin, and J. Ellenberg, “Molecular crowding affects diffusion and binding of nuclear proteins in heterochromatin and reveals the fractal organization of chromatin,” EMBO J. 28(24), 3785–3798 (2009).
[Crossref] [PubMed]

Eshein, A.

A. J. Radosevich, A. Eshein, T. Q. Nguyen, and V. Backman, “Subdiffusion reflectance spectroscopy to measure tissue ultrastructure and microvasculature: model and inverse algorithm,” J. Biomed. Opt. 20(9), 097002 (2015).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, A. Eshein, T.-Q. Nguyen, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, J. Van Dam, V. Backman, and H. K. Roy, “Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal Lesions,” Clin. Cancer Res. 21(19), 4347–4355 (2015).
[Crossref] [PubMed]

N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, S. Upadhye, A. Koons, M. Gonzalez-Haba Ruiz, H. K. Roy, and V. Backman, “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44(5), 735–741 (2015).
[Crossref] [PubMed]

Feld, M. S.

V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” Selected Topics in Quantum Electronics, IEEE Journal of 5(4), 1019–1026 (1999).
[Crossref]

L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, “Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution,” Phys. Rev. Lett. 80(3), 627–630 (1998).
[Crossref]

Finlay, J. C.

T. C. Zhu, J. C. Finlay, and S. M. Hahn, “Determination of the distribution of light, optical properties, drug concentration, and tissue oxygenation in-vivo in human prostate during motexafin lutetium-mediated photodynamic therapy,” J. Photochem. Photobiol. B 79(3), 231–241 (2005).
[Crossref] [PubMed]

Fishkin, J. B.

Flock, S. T.

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12(5), 510–519 (1992).
[Crossref] [PubMed]

Frank, J.

P. A. Penczek, R. A. Grassucci, and J. Frank, “The ribosome at improved resolution: new techniques for merging and orientation refinement in 3D cryo-electron microscopy of biological particles,” Ultramicroscopy 53(3), 251–270 (1994).
[Crossref] [PubMed]

Freyer, J. P.

Fujimoto, J. G.

Fuselier, T.

Gandjbakhche, A.

T. Binzoni, T. Leung, A. Gandjbakhche, D. Rüfenacht, and D. Delpy, “The use of the Henyey–Greenstein phase function in Monte Carlo simulations in biomedical optics,” Phys. Med. Biol. 51(17), 313 (2006).

Gardecki, J. A.

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

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H. K. Roy, Y. L. Kim, Y. Liu, R. K. Wali, M. J. Goldberg, V. Turzhitsky, J. Horwitz, and V. Backman, “Risk stratification of colon carcinogenesis through enhanced backscattering spectroscopy analysis of the uninvolved colonic mucosa,” Clin. Cancer Res. 12(3), 961–968 (2006).
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N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, S. Upadhye, A. Koons, M. Gonzalez-Haba Ruiz, H. K. Roy, and V. Backman, “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44(5), 735–741 (2015).
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L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, “Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution,” Phys. Rev. Lett. 80(3), 627–630 (1998).
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J. Yi, A. J. Radosevich, Y. Stypula-Cyrus, N. N. Mutyal, S. M. Azarin, E. Horcher, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Spatially resolved optical and ultrastructural properties of colorectal and pancreatic field carcinogenesis observed by inverse spectroscopic optical coherence tomography,” J. Biomed. Opt. 19(3), 036013 (2014).
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A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18(9), 097002 (2013).
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A. J. Radosevich, A. Eshein, T. Q. Nguyen, and V. Backman, “Subdiffusion reflectance spectroscopy to measure tissue ultrastructure and microvasculature: model and inverse algorithm,” J. Biomed. Opt. 20(9), 097002 (2015).
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[Crossref] [PubMed]

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L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, “Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution,” Phys. Rev. Lett. 80(3), 627–630 (1998).
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P. A. Penczek, R. A. Grassucci, and J. Frank, “The ribosome at improved resolution: new techniques for merging and orientation refinement in 3D cryo-electron microscopy of biological particles,” Ultramicroscopy 53(3), 251–270 (1994).
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L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, “Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution,” Phys. Rev. Lett. 80(3), 627–630 (1998).
[Crossref]

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V. Backman, R. Gurjar, K. Badizadegan, I. Itzkan, R. R. Dasari, L. T. Perelman, and M. S. Feld, “Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ,” Selected Topics in Quantum Electronics, IEEE Journal of 5(4), 1019–1026 (1999).
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Radosevich, A. J.

A. J. Radosevich, A. Eshein, T. Q. Nguyen, and V. Backman, “Subdiffusion reflectance spectroscopy to measure tissue ultrastructure and microvasculature: model and inverse algorithm,” J. Biomed. Opt. 20(9), 097002 (2015).
[Crossref] [PubMed]

N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, S. Upadhye, A. Koons, M. Gonzalez-Haba Ruiz, H. K. Roy, and V. Backman, “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44(5), 735–741 (2015).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, A. Eshein, T.-Q. Nguyen, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, J. Van Dam, V. Backman, and H. K. Roy, “Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal Lesions,” Clin. Cancer Res. 21(19), 4347–4355 (2015).
[Crossref] [PubMed]

J. Yi, A. J. Radosevich, Y. Stypula-Cyrus, N. N. Mutyal, S. M. Azarin, E. Horcher, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Spatially resolved optical and ultrastructural properties of colorectal and pancreatic field carcinogenesis observed by inverse spectroscopic optical coherence tomography,” J. Biomed. Opt. 19(3), 036013 (2014).
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J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling Light Scattering in Tissue as Continuous Random Media Using a Versatile Refractive Index Correlation Function,” IEEE J. Sel. Top. Quantum Electron. 20(2), 7000514 (2013).
[PubMed]

J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling Light Scattering in Tissue as Continuous Random Media Using a Versatile Refractive Index Correlation Function,” IEEE J. Sel. Top. Quantum Electron. 20(2), 7000514 (2013).
[PubMed]

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18(9), 097002 (2013).
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J. Yi, A. J. Radosevich, J. D. Rogers, S. C. Norris, I. R. Çapoğlu, A. Taflove, and V. Backman, “Can OCT be sensitive to nanoscale structural alterations in biological tissue?” Opt. Express 21(7), 9043–9059 (2013).
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A. J. Radosevich, J. Yi, J. D. Rogers, and V. Backman, “Structural length-scale sensitivities of reflectance measurements in continuous random media under the Born approximation,” Opt. Lett. 37(24), 5220–5222 (2012).
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H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res. 69(13), 5357–5363 (2009).
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A. J. Radosevich, N. N. Mutyal, A. Eshein, T.-Q. Nguyen, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, J. Van Dam, V. Backman, and H. K. Roy, “Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal Lesions,” Clin. Cancer Res. 21(19), 4347–4355 (2015).
[Crossref] [PubMed]

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B. H. Johnston and A. Rich, “Chemical probes of DNA conformation: detection of Z-DNA at nucleotide resolution,” Cell 42(3), 713–724 (1985).
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C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
[Crossref] [PubMed]

Rogers, J. D.

A. J. Radosevich, N. N. Mutyal, A. Eshein, T.-Q. Nguyen, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, J. Van Dam, V. Backman, and H. K. Roy, “Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal Lesions,” Clin. Cancer Res. 21(19), 4347–4355 (2015).
[Crossref] [PubMed]

N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, S. Upadhye, A. Koons, M. Gonzalez-Haba Ruiz, H. K. Roy, and V. Backman, “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44(5), 735–741 (2015).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18(9), 097002 (2013).
[Crossref] [PubMed]

J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling Light Scattering in Tissue as Continuous Random Media Using a Versatile Refractive Index Correlation Function,” IEEE J. Sel. Top. Quantum Electron. 20(2), 7000514 (2013).
[PubMed]

J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling Light Scattering in Tissue as Continuous Random Media Using a Versatile Refractive Index Correlation Function,” IEEE J. Sel. Top. Quantum Electron. 20(2), 7000514 (2013).
[PubMed]

J. Yi, A. J. Radosevich, J. D. Rogers, S. C. Norris, I. R. Çapoğlu, A. Taflove, and V. Backman, “Can OCT be sensitive to nanoscale structural alterations in biological tissue?” Opt. Express 21(7), 9043–9059 (2013).
[Crossref] [PubMed]

A. J. Radosevich, J. Yi, J. D. Rogers, and V. Backman, “Structural length-scale sensitivities of reflectance measurements in continuous random media under the Born approximation,” Opt. Lett. 37(24), 5220–5222 (2012).
[Crossref] [PubMed]

J. D. Rogers, İ. R. Capoğlu, and V. Backman, “Nonscalar elastic light scattering from continuous random media in the Born approximation,” Opt. Lett. 34(12), 1891–1893 (2009).
[Crossref] [PubMed]

İ. R. Capoğlu, J. D. Rogers, A. Taflove, and V. Backman, “Accuracy of the Born approximation in calculating the scattering coefficient of biological continuous random media,” Opt. Lett. 34(17), 2679–2681 (2009).
[Crossref] [PubMed]

Roy, H. K.

N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, S. Upadhye, A. Koons, M. Gonzalez-Haba Ruiz, H. K. Roy, and V. Backman, “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44(5), 735–741 (2015).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, A. Eshein, T.-Q. Nguyen, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, J. Van Dam, V. Backman, and H. K. Roy, “Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal Lesions,” Clin. Cancer Res. 21(19), 4347–4355 (2015).
[Crossref] [PubMed]

J. Yi, A. J. Radosevich, Y. Stypula-Cyrus, N. N. Mutyal, S. M. Azarin, E. Horcher, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Spatially resolved optical and ultrastructural properties of colorectal and pancreatic field carcinogenesis observed by inverse spectroscopic optical coherence tomography,” J. Biomed. Opt. 19(3), 036013 (2014).
[Crossref] [PubMed]

L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14(1), 189 (2014).
[Crossref] [PubMed]

A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18(9), 097002 (2013).
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V. Backman and H. K. Roy, “Advances in biophotonics detection of field carcinogenesis for colon cancer risk stratification,” J. Cancer 4(3), 251–261 (2013).
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H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res. 69(13), 5357–5363 (2009).
[Crossref] [PubMed]

H. K. Roy, Y. L. Kim, Y. Liu, R. K. Wali, M. J. Goldberg, V. Turzhitsky, J. Horwitz, and V. Backman, “Risk stratification of colon carcinogenesis through enhanced backscattering spectroscopy analysis of the uninvolved colonic mucosa,” Clin. Cancer Res. 12(3), 961–968 (2006).
[Crossref] [PubMed]

Y. L. Kim, Y. Liu, R. K. Wali, H. K. Roy, and V. Backman, “Low-coherent backscattering spectroscopy for tissue characterization,” Appl. Opt. 44(3), 366–377 (2005).
[Crossref] [PubMed]

Y. L. Kim, Y. Liu, V. M. Turzhitsky, R. K. Wali, H. K. Roy, and V. Backman, “Depth-resolved low-coherence enhanced backscattering,” Opt. Lett. 30(7), 741–743 (2005).
[Crossref] [PubMed]

Y. L. Kim, Y. Liu, V. M. Turzhitsky, H. K. Roy, R. K. Wali, and V. Backman, “Coherent backscattering spectroscopy,” Opt. Lett. 29(16), 1906–1908 (2004).
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T. Binzoni, T. Leung, A. Gandjbakhche, D. Rüfenacht, and D. Delpy, “The use of the Henyey–Greenstein phase function in Monte Carlo simulations in biomedical optics,” Phys. Med. Biol. 51(17), 313 (2006).

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Schweitzer, D.

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L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, “Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution,” Phys. Rev. Lett. 80(3), 627–630 (1998).
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L. Perelman, V. Backman, M. Wallace, G. Zonios, R. Manoharan, A. Nusrat, S. Shields, M. Seiler, C. Lima, T. Hamano, I. Itzkan, J. Van Dam, J. M. Crawford, and M. S. Feld, “Observation of periodic fine structure in reflectance from biological tissue: a new technique for measuring nuclear size distribution,” Phys. Rev. Lett. 80(3), 627–630 (1998).
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N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, S. Upadhye, A. Koons, M. Gonzalez-Haba Ruiz, H. K. Roy, and V. Backman, “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44(5), 735–741 (2015).
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S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12(5), 510–519 (1992).
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C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. Delbridge, “Refractive index measurement in viable cells using quantitative phase-amplitude microscopy and confocal microscopy,” Cytometry A 65(1), 88–92 (2005).
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H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res. 69(13), 5357–5363 (2009).
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J. Yi, A. J. Radosevich, Y. Stypula-Cyrus, N. N. Mutyal, S. M. Azarin, E. Horcher, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Spatially resolved optical and ultrastructural properties of colorectal and pancreatic field carcinogenesis observed by inverse spectroscopic optical coherence tomography,” J. Biomed. Opt. 19(3), 036013 (2014).
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L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14(1), 189 (2014).
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L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14(1), 189 (2014).
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H. Subramanian, H. K. Roy, P. Pradhan, M. J. Goldberg, J. Muldoon, R. E. Brand, C. Sturgis, T. Hensing, D. Ray, A. Bogojevic, J. Mohammed, J. S. Chang, and V. Backman, “Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy,” Cancer Res. 69(13), 5357–5363 (2009).
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H. K. Roy, Y. L. Kim, Y. Liu, R. K. Wali, M. J. Goldberg, V. Turzhitsky, J. Horwitz, and V. Backman, “Risk stratification of colon carcinogenesis through enhanced backscattering spectroscopy analysis of the uninvolved colonic mucosa,” Clin. Cancer Res. 12(3), 961–968 (2006).
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Upadhye, S.

N. N. Mutyal, A. J. Radosevich, S. Bajaj, V. Konda, U. D. Siddiqui, I. Waxman, M. J. Goldberg, J. D. Rogers, B. Gould, A. Eshein, S. Upadhye, A. Koons, M. Gonzalez-Haba Ruiz, H. K. Roy, and V. Backman, “In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa,” Pancreas 44(5), 735–741 (2015).
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A. J. Radosevich, N. N. Mutyal, A. Eshein, T.-Q. Nguyen, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, J. Van Dam, V. Backman, and H. K. Roy, “Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal Lesions,” Clin. Cancer Res. 21(19), 4347–4355 (2015).
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J. W. Pickering, S. A. Prahl, N. van Wieringen, J. F. Beek, H. J. Sterenborg, and M. J. van Gemert, “Double-integrating-sphere system for measuring the optical properties of tissue,” Appl. Opt. 32(4), 399–410 (1993).
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L. Cherkezyan, Y. Stypula-Cyrus, H. Subramanian, C. White, M. Dela Cruz, R. K. Wali, M. J. Goldberg, L. K. Bianchi, H. K. Roy, and V. Backman, “Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study,” BMC Cancer 14(1), 189 (2014).
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A. J. Radosevich, N. N. Mutyal, A. Eshein, T.-Q. Nguyen, B. Gould, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, E. F. Yen, V. Konda, D. K. Rex, J. Van Dam, V. Backman, and H. K. Roy, “Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal Lesions,” Clin. Cancer Res. 21(19), 4347–4355 (2015).
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J. Yi, A. J. Radosevich, Y. Stypula-Cyrus, N. N. Mutyal, S. M. Azarin, E. Horcher, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Spatially resolved optical and ultrastructural properties of colorectal and pancreatic field carcinogenesis observed by inverse spectroscopic optical coherence tomography,” J. Biomed. Opt. 19(3), 036013 (2014).
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J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling Light Scattering in Tissue as Continuous Random Media Using a Versatile Refractive Index Correlation Function,” IEEE J. Sel. Top. Quantum Electron. 20(2), 7000514 (2013).
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J. D. Rogers, A. J. Radosevich, J. Yi, and V. Backman, “Modeling Light Scattering in Tissue as Continuous Random Media Using a Versatile Refractive Index Correlation Function,” IEEE J. Sel. Top. Quantum Electron. 20(2), 7000514 (2013).
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A. J. Radosevich, N. N. Mutyal, J. Yi, Y. Stypula-Cyrus, J. D. Rogers, M. J. Goldberg, L. K. Bianchi, S. Bajaj, H. K. Roy, and V. Backman, “Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy,” J. Biomed. Opt. 18(9), 097002 (2013).
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J. Yi, A. J. Radosevich, J. D. Rogers, S. C. Norris, I. R. Çapoğlu, A. Taflove, and V. Backman, “Can OCT be sensitive to nanoscale structural alterations in biological tissue?” Opt. Express 21(7), 9043–9059 (2013).
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A. J. Radosevich, J. Yi, J. D. Rogers, and V. Backman, “Structural length-scale sensitivities of reflectance measurements in continuous random media under the Born approximation,” Opt. Lett. 37(24), 5220–5222 (2012).
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J. Yi and V. Backman, “Imaging a full set of optical scattering properties of biological tissue by inverse spectroscopic optical coherence tomography,” Opt. Lett. 37(21), 4443–4445 (2012).
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J. W. Pickering, S. A. Prahl, N. van Wieringen, J. F. Beek, H. J. Sterenborg, and M. J. van Gemert, “Double-integrating-sphere system for measuring the optical properties of tissue,” Appl. Opt. 32(4), 399–410 (1993).
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Figures (5)

Fig. 1
Fig. 1

Nuclei in a TEM image. (a) is the original TEM image of the biopsy. (b) is the selected nucleus in TEM image. (c) is the cropped out nucleus. The background of the image is taken as uniform cytoplasm. (d) is the nuclear refractive index distribution n(x,y) after binarization. The refractive index is 1.35 for euchromatin, 1.36 for cytoplasm and 1.39 for heterochromatin. The scale bar in (a) is 2μm , the scale bar in (b-c) is 2.5 μm .

Fig. 2
Fig. 2

Extracting   B n ( r d ) from 2D images. (a) is an example of numerically generated random media. (b) shows the difference between   B n ( r d ) from 3D random media and 2D random media. (c) shows the B n 2D ( r d ) from 2D slides of random media converge to   B n ( r d ) from 3D RM. (d) is one example of RM with biological parameters of the nuclei TEM images. (e) shows the R2 between   B n ( r d ) and N averaged B n 2D ( r d ) . This result shows that when N10 , R2 between   B n ( r d ) and   B n ( r d ) from averaging over N B n 2D ( r d ) is larger than 99% and the difference is negligible. (f) is an example of   B n ( r d ) after averaging over 10 B n 2D ( r d ) of nuclei TEM images(RI represents refractive index).

Fig. 3
Fig. 3

Results for the autocorrelation function, spectrum of g and the phase function for control sample and AA sample. (a) is the B n ( r d ) from control data set and AA data set. (b) shows the phase functions calculated from TEM images. Phase functions are calculated at λ 0 =700nm (c) shows the spectrum of g for the range of λ between 500nm to 700nm.

Fig. 4
Fig. 4

Results of the optical property calculated from colon cell nuclei TEM images, compared with ISOCT result.’*’ indicates the p-value is smaller than 0.05. The result from TEM image shows significant difference in g and D between control data set and AA set. Compared with ISOCT measurement, the TEM method shows the same trend between control and AA for g and D. In the case of D, the values between two methods match with each other within 5%.

Fig. 5
Fig. 5

The comparison of the phase functions from TEM images (The solid lines) and the HG relation (The dash lines). Both phase functions are calculated at λ 0 =700nm

Equations (15)

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n( r )= n water +αρ( r )
B n ( r d )= v n Δ ( r ) n Δ ( r r d )d r 3
Φ s ( k s )= 1 2 π 2 0 B n ( r d )[ sin( k s r d ) k s r d ]d r d
σ( θ,ϕ,k )=2π ( n cyt k ) 4 ( 1 sin 2 θ cos 2 ϕ ) Φ s ( k s )
σ( θ,k )=2π ( n cyt k ) 4 ( 1+ cos 2 θ ) Φ s ( k s )
g(k)= 1 1 cosθσ ( cosθ,k )dcosθ 1 1 σ ( cosθ,k )dcosθ
l s * ( k )= 1 1 1 σ( cosθ,k )dcosθ( 1g(k) )
l s * ( k ) k D4 ,D4
B n ( r d )= A n ( r d l n ) D3 2 K D3 2 ( r d l n )
B n ( Δx,Δy )= Δn( x,y )Δn( xΔx,yΔy )dxdy = F 1 { | F{ Δn( x,y ) } | 2 }
B n 2D ( r d )= B n ( Δx,Δy ) dθ= B n ( r d cosθ, r d sinθ ) dθ
P TEM (θ)= A 0 σ(θ,2π/ λ 0 )
0 2π { 0 π P TEM (θ)sin( θ )dθ }dϕ=1
log( l s * (k))=(D4)logk+C
P HG (θ)= 1 4π 1 g 2 [1+ g 2 2gcos(θ)] 3/2

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