Abstract

We use an extensive set of quantitative histopathology data to construct realistic three-dimensional models of normal and dysplastic cervical cell nuclei at different epithelial depths. We then employ the finite-difference time-domain method to numerically simulate the light scattering response of these representative models as a function of the polar and azimuthal scattering angles. The results indicate that intensity and shape metrics computed from two-dimensional scattering patterns can be used to distinguish between different diagnostic categories. Our numerical study also suggests that different epithelial layers and angular ranges need to be considered separately to fully exploit the diagnostic potential of two-dimensional light scattering measurements.

© 2014 Optical Society of America

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2013 (4)

2012 (2)

O. C. Marina, C. K. Sanders, and J. R. Mourant, “Correlating light scattering with internal cellular structures,” Biomed. Opt. Express3(2), 296–312 (2012).
[CrossRef] [PubMed]

C. MacAulay, C. F. Poh, M. Guillaud, P. M. Williams, D. M. Laronde, L. Zhang, and M. P. Rosin, “High throughput image cytometry for detection of suspicious lesions in the oral cavity,” J. Biomed. Opt.17(8), 086004 (2012).
[CrossRef] [PubMed]

2011 (5)

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

S. Uttam, R. K. Bista, D. J. Hartman, R. E. Brand, and Y. Liu, “Correction of stain variations in nuclear refractive index of clinical histology specimens,” J. Biomed. Opt.16(11), 116013 (2011).
[CrossRef] [PubMed]

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt.16(1), 011003 (2011).
[CrossRef] [PubMed]

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

Y. L. Pan, M. J. Berg, S. S. Zhang, H. Noh, H. Cao, R. K. Chang, and G. Videen, “Measurement and autocorrelation analysis of two-dimensional light-scattering patterns from living cells for label-free classification,” Cytometry A79A(4), 284–292 (2011).
[CrossRef] [PubMed]

2010 (3)

2009 (1)

2008 (2)

M. Xu, T. T. Wu, and J. Y. Qu, “Unified Mie and fractal scattering by cells and experimental study on application in optical characterization of cellular and subcellular structures,” J. Biomed. Opt.13(2), 024015 (2008).
[CrossRef] [PubMed]

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

2007 (5)

2006 (2)

2005 (1)

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, “Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling,” Biophys. J.88(4), 2929–2938 (2005).
[CrossRef] [PubMed]

2004 (2)

M. Guillaud, D. Cox, K. Adler-Storthz, A. Malpica, G. Staerkel, J. Matisic, D. Van Niekerk, N. Poulin, M. Follen, and C. MacAulay, “Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus,” Cytometry A60A(1), 81–89 (2004).
[CrossRef] [PubMed]

X. Li, Z. Chen, A. Taflove, and V. Backman, “Equiphase-sphere approximation for light scattering by stochastically inhomogeneous microparticles,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.70(5), 056610 (2004).
[CrossRef] [PubMed]

2003 (3)

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt.8(1), 7–16 (2003).
[CrossRef] [PubMed]

D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, and R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt.8(3), 484–494 (2003).
[CrossRef] [PubMed]

A. K. Popp, M. T. Valentine, P. D. Kaplan, and D. A. Weitz, “Microscopic origin of light scattering in tissue,” Appl. Opt.42(16), 2871–2880 (2003).
[CrossRef] [PubMed]

1999 (1)

1998 (1)

1996 (1)

Adler-Storthz, K.

M. Guillaud, D. Cox, K. Adler-Storthz, A. Malpica, G. Staerkel, J. Matisic, D. Van Niekerk, N. Poulin, M. Follen, and C. MacAulay, “Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus,” Cytometry A60A(1), 81–89 (2004).
[CrossRef] [PubMed]

Ahn, S. G.

Alexandrov, S.

Arifler, D.

D. Arifler, I. Pavlova, A. Gillenwater, and R. Richards-Kortum, “Light scattering from collagen fiber networks: micro-optical properties of normal and neoplastic stroma,” Biophys. J.92(9), 3260–3274 (2007).
[CrossRef] [PubMed]

D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, and R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt.8(3), 484–494 (2003).
[CrossRef] [PubMed]

Backhouse, C.

Backman, V.

J. Yi, A. J. Radosevich, J. D. Rogers, S. C. P. Norris, I. R. Çapoğlu, A. Taflove, and V. Backman, “Can OCT be sensitive to nanoscale structural alterations in biological tissue?” Opt. Express21(7), 9043–9059 (2013).
[CrossRef] [PubMed]

X. Li, Z. Chen, A. Taflove, and V. Backman, “Equiphase-sphere approximation for light scattering by stochastically inhomogeneous microparticles,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.70(5), 056610 (2004).
[CrossRef] [PubMed]

Badizadegan, K.

Bakkenist, C. J.

S. Uttam, R. K. Bista, K. Staton, S. Alexandrov, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Investigation of depth-resolved nanoscale structural changes in regulated cell proliferation and chromatin decondensation,” Biomed. Opt. Express4(4), 596–613 (2013).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

Bennett, A.

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

Berg, M. J.

Y. L. Pan, M. J. Berg, S. S. Zhang, H. Noh, H. Cao, R. K. Chang, and G. Videen, “Measurement and autocorrelation analysis of two-dimensional light-scattering patterns from living cells for label-free classification,” Cytometry A79A(4), 284–292 (2011).
[CrossRef] [PubMed]

Best-Popescu, C.

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

Bigelow, C. E.

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, “Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling,” Biophys. J.88(4), 2929–2938 (2005).
[CrossRef] [PubMed]

Bista, R. K.

S. Uttam, R. K. Bista, K. Staton, S. Alexandrov, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Investigation of depth-resolved nanoscale structural changes in regulated cell proliferation and chromatin decondensation,” Biomed. Opt. Express4(4), 596–613 (2013).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

S. Uttam, R. K. Bista, D. J. Hartman, R. E. Brand, and Y. Liu, “Correction of stain variations in nuclear refractive index of clinical histology specimens,” J. Biomed. Opt.16(11), 116013 (2011).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. Qiu, W. E. Khalbuss, L. Zhang, R. E. Brand, and Y. Liu, “An insight into statistical refractive index properties of cell internal structure via low-coherence statistical amplitude microscopy,” Opt. Express18(21), 21950–21958 (2010).
[CrossRef] [PubMed]

Boiko, I.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt.8(1), 7–16 (2003).
[CrossRef] [PubMed]

Brand, R. E.

S. Uttam, R. K. Bista, K. Staton, S. Alexandrov, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Investigation of depth-resolved nanoscale structural changes in regulated cell proliferation and chromatin decondensation,” Biomed. Opt. Express4(4), 596–613 (2013).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

S. Uttam, R. K. Bista, D. J. Hartman, R. E. Brand, and Y. Liu, “Correction of stain variations in nuclear refractive index of clinical histology specimens,” J. Biomed. Opt.16(11), 116013 (2011).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. Qiu, W. E. Khalbuss, L. Zhang, R. E. Brand, and Y. Liu, “An insight into statistical refractive index properties of cell internal structure via low-coherence statistical amplitude microscopy,” Opt. Express18(21), 21950–21958 (2010).
[CrossRef] [PubMed]

Bright, S.

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

Brown, W. J.

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

Calkins, D. J.

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, “Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling,” Biophys. J.88(4), 2929–2938 (2005).
[CrossRef] [PubMed]

Cao, H.

Y. L. Pan, M. J. Berg, S. S. Zhang, H. Noh, H. Cao, R. K. Chang, and G. Videen, “Measurement and autocorrelation analysis of two-dimensional light-scattering patterns from living cells for label-free classification,” Cytometry A79A(4), 284–292 (2011).
[CrossRef] [PubMed]

Capjack, C.

Çapoglu, I. R.

Carpenter, S.

Carraro, A.

D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, and R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt.8(3), 484–494 (2003).
[CrossRef] [PubMed]

Carretta, E.

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

Chang, C. H.

J. W. Su, W. C. Hsu, C. Y. Chou, C. H. Chang, and K. B. Sung, “Digital holographic microtomography for high-resolution refractive index mapping of live cells,” J. Biophotonics6(5), 416–424 (2013).
[CrossRef] [PubMed]

Chang, R. K.

Y. L. Pan, M. J. Berg, S. S. Zhang, H. Noh, H. Cao, R. K. Chang, and G. Videen, “Measurement and autocorrelation analysis of two-dimensional light-scattering patterns from living cells for label-free classification,” Cytometry A79A(4), 284–292 (2011).
[CrossRef] [PubMed]

Chen, Z.

X. Li, Z. Chen, A. Taflove, and V. Backman, “Equiphase-sphere approximation for light scattering by stochastically inhomogeneous microparticles,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.70(5), 056610 (2004).
[CrossRef] [PubMed]

Choi, S.

S. Uttam, R. K. Bista, K. Staton, S. Alexandrov, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Investigation of depth-resolved nanoscale structural changes in regulated cell proliferation and chromatin decondensation,” Biomed. Opt. Express4(4), 596–613 (2013).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

Choi, W.

Choi, W. J.

Chou, C. Y.

J. W. Su, W. C. Hsu, C. Y. Chou, C. H. Chang, and K. B. Sung, “Digital holographic microtomography for high-resolution refractive index mapping of live cells,” J. Biophotonics6(5), 416–424 (2013).
[CrossRef] [PubMed]

Collier, T.

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt.8(1), 7–16 (2003).
[CrossRef] [PubMed]

Cox, D.

M. Guillaud, D. Cox, K. Adler-Storthz, A. Malpica, G. Staerkel, J. Matisic, D. Van Niekerk, N. Poulin, M. Follen, and C. MacAulay, “Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus,” Cytometry A60A(1), 81–89 (2004).
[CrossRef] [PubMed]

Dasari, R. R.

Deflores, L.

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
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N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
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R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt.8(1), 7–16 (2003).
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R. Drezek, A. Dunn, and R. Richards-Kortum, “Light scattering from cells: finite-difference time-domain simulations and goniometric measurements,” Appl. Opt.38(16), 3651–3661 (1999).
[CrossRef] [PubMed]

Dunn, A.

Eick, A. A.

Fang-Yen, C.

Feld, M. S.

Follen, M.

M. Guillaud, D. Cox, K. Adler-Storthz, A. Malpica, G. Staerkel, J. Matisic, D. Van Niekerk, N. Poulin, M. Follen, and C. MacAulay, “Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus,” Cytometry A60A(1), 81–89 (2004).
[CrossRef] [PubMed]

D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, and R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt.8(3), 484–494 (2003).
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R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt.8(1), 7–16 (2003).
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J. D. Wilson, B. R. Giesselman, S. Mitra, and T. H. Foster, “Lysosome-damage-induced scattering changes coincide with release of cytochrome c,” Opt. Lett.32(17), 2517–2519 (2007).
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Fulghum, S. F.

Galanko, J.

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Gebhart, S. C.

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
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Giesselman, B. R.

Gillenwater, A.

D. Arifler, I. Pavlova, A. Gillenwater, and R. Richards-Kortum, “Light scattering from collagen fiber networks: micro-optical properties of normal and neoplastic stroma,” Biophys. J.92(9), 3260–3274 (2007).
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N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
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C. MacAulay, C. F. Poh, M. Guillaud, P. M. Williams, D. M. Laronde, L. Zhang, and M. P. Rosin, “High throughput image cytometry for detection of suspicious lesions in the oral cavity,” J. Biomed. Opt.17(8), 086004 (2012).
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M. Guillaud, D. Cox, K. Adler-Storthz, A. Malpica, G. Staerkel, J. Matisic, D. Van Niekerk, N. Poulin, M. Follen, and C. MacAulay, “Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus,” Cytometry A60A(1), 81–89 (2004).
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D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, and R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt.8(3), 484–494 (2003).
[CrossRef] [PubMed]

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt.8(1), 7–16 (2003).
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S. Uttam, R. K. Bista, K. Staton, S. Alexandrov, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Investigation of depth-resolved nanoscale structural changes in regulated cell proliferation and chromatin decondensation,” Biomed. Opt. Express4(4), 596–613 (2013).
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R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
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S. Uttam, R. K. Bista, D. J. Hartman, R. E. Brand, and Y. Liu, “Correction of stain variations in nuclear refractive index of clinical histology specimens,” J. Biomed. Opt.16(11), 116013 (2011).
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Hsu, W. C.

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Ikeda, T.

Jeon, D. I.

Johnson, T. M.

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Khalbuss, W. E.

Kim, S.

Kumar, G.

Laronde, D. M.

C. MacAulay, C. F. Poh, M. Guillaud, P. M. Williams, D. M. Laronde, L. Zhang, and M. P. Rosin, “High throughput image cytometry for detection of suspicious lesions in the oral cavity,” J. Biomed. Opt.17(8), 086004 (2012).
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Lau, C.

Lee, B. H.

Lee, J.

Li, X.

X. Li, Z. Chen, A. Taflove, and V. Backman, “Equiphase-sphere approximation for light scattering by stochastically inhomogeneous microparticles,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.70(5), 056610 (2004).
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Liu, Y.

S. Uttam, R. K. Bista, K. Staton, S. Alexandrov, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Investigation of depth-resolved nanoscale structural changes in regulated cell proliferation and chromatin decondensation,” Biomed. Opt. Express4(4), 596–613 (2013).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

S. Uttam, R. K. Bista, D. J. Hartman, R. E. Brand, and Y. Liu, “Correction of stain variations in nuclear refractive index of clinical histology specimens,” J. Biomed. Opt.16(11), 116013 (2011).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. Qiu, W. E. Khalbuss, L. Zhang, R. E. Brand, and Y. Liu, “An insight into statistical refractive index properties of cell internal structure via low-coherence statistical amplitude microscopy,” Opt. Express18(21), 21950–21958 (2010).
[CrossRef] [PubMed]

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G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods4(9), 717–719 (2007).
[CrossRef] [PubMed]

N. Lue, G. Popescu, T. Ikeda, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Live cell refractometry using microfluidic devices,” Opt. Lett.31(18), 2759–2761 (2006).
[CrossRef] [PubMed]

MacAulay, C.

C. MacAulay, C. F. Poh, M. Guillaud, P. M. Williams, D. M. Laronde, L. Zhang, and M. P. Rosin, “High throughput image cytometry for detection of suspicious lesions in the oral cavity,” J. Biomed. Opt.17(8), 086004 (2012).
[CrossRef] [PubMed]

M. Guillaud, D. Cox, K. Adler-Storthz, A. Malpica, G. Staerkel, J. Matisic, D. Van Niekerk, N. Poulin, M. Follen, and C. MacAulay, “Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus,” Cytometry A60A(1), 81–89 (2004).
[CrossRef] [PubMed]

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt.8(1), 7–16 (2003).
[CrossRef] [PubMed]

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N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

Malpica, A.

M. Guillaud, D. Cox, K. Adler-Storthz, A. Malpica, G. Staerkel, J. Matisic, D. Van Niekerk, N. Poulin, M. Follen, and C. MacAulay, “Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus,” Cytometry A60A(1), 81–89 (2004).
[CrossRef] [PubMed]

D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, and R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt.8(3), 484–494 (2003).
[CrossRef] [PubMed]

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt.8(1), 7–16 (2003).
[CrossRef] [PubMed]

Marina, O. C.

Matisic, J.

M. Guillaud, D. Cox, K. Adler-Storthz, A. Malpica, G. Staerkel, J. Matisic, D. Van Niekerk, N. Poulin, M. Follen, and C. MacAulay, “Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus,” Cytometry A60A(1), 81–89 (2004).
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Mitra, S.

Mourant, J. R.

Noh, H.

Y. L. Pan, M. J. Berg, S. S. Zhang, H. Noh, H. Cao, R. K. Chang, and G. Videen, “Measurement and autocorrelation analysis of two-dimensional light-scattering patterns from living cells for label-free classification,” Cytometry A79A(4), 284–292 (2011).
[CrossRef] [PubMed]

Norris, S. C. P.

Oh, S.

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods4(9), 717–719 (2007).
[CrossRef] [PubMed]

Overholt, B. F.

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
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Y. L. Pan, M. J. Berg, S. S. Zhang, H. Noh, H. Cao, R. K. Chang, and G. Videen, “Measurement and autocorrelation analysis of two-dimensional light-scattering patterns from living cells for label-free classification,” Cytometry A79A(4), 284–292 (2011).
[CrossRef] [PubMed]

Panjehpour, M.

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

Park, Y.

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

Pavlova, I.

D. Arifler, I. Pavlova, A. Gillenwater, and R. Richards-Kortum, “Light scattering from collagen fiber networks: micro-optical properties of normal and neoplastic stroma,” Biophys. J.92(9), 3260–3274 (2007).
[CrossRef] [PubMed]

Poh, C. F.

C. MacAulay, C. F. Poh, M. Guillaud, P. M. Williams, D. M. Laronde, L. Zhang, and M. P. Rosin, “High throughput image cytometry for detection of suspicious lesions in the oral cavity,” J. Biomed. Opt.17(8), 086004 (2012).
[CrossRef] [PubMed]

Popescu, G.

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

N. Lue, G. Popescu, T. Ikeda, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Live cell refractometry using microfluidic devices,” Opt. Lett.31(18), 2759–2761 (2006).
[CrossRef] [PubMed]

Popp, A. K.

Poulin, N.

M. Guillaud, D. Cox, K. Adler-Storthz, A. Malpica, G. Staerkel, J. Matisic, D. Van Niekerk, N. Poulin, M. Follen, and C. MacAulay, “Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus,” Cytometry A60A(1), 81–89 (2004).
[CrossRef] [PubMed]

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Qiu, W.

Qu, J. Y.

M. Xu, T. T. Wu, and J. Y. Qu, “Unified Mie and fractal scattering by cells and experimental study on application in optical characterization of cellular and subcellular structures,” J. Biomed. Opt.13(2), 024015 (2008).
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Radosevich, A. J.

Ramachandran, J.

Richards-Kortum, R.

D. Arifler, I. Pavlova, A. Gillenwater, and R. Richards-Kortum, “Light scattering from collagen fiber networks: micro-optical properties of normal and neoplastic stroma,” Biophys. J.92(9), 3260–3274 (2007).
[CrossRef] [PubMed]

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt.8(1), 7–16 (2003).
[CrossRef] [PubMed]

D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, and R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt.8(3), 484–494 (2003).
[CrossRef] [PubMed]

R. Drezek, A. Dunn, and R. Richards-Kortum, “Light scattering from cells: finite-difference time-domain simulations and goniometric measurements,” Appl. Opt.38(16), 3651–3661 (1999).
[CrossRef] [PubMed]

Rinehart, M. T.

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

Rogers, J. D.

Rosin, M. P.

C. MacAulay, C. F. Poh, M. Guillaud, P. M. Williams, D. M. Laronde, L. Zhang, and M. P. Rosin, “High throughput image cytometry for detection of suspicious lesions in the oral cavity,” J. Biomed. Opt.17(8), 086004 (2012).
[CrossRef] [PubMed]

Rozmus, W.

Sanders, C. K.

Schmitt, J. M.

Shaheen, N. J.

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt.16(1), 011003 (2011).
[CrossRef] [PubMed]

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

Shen, D.

Staerkel, G.

M. Guillaud, D. Cox, K. Adler-Storthz, A. Malpica, G. Staerkel, J. Matisic, D. Van Niekerk, N. Poulin, M. Follen, and C. MacAulay, “Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus,” Cytometry A60A(1), 81–89 (2004).
[CrossRef] [PubMed]

Staton, K.

S. Uttam, R. K. Bista, K. Staton, S. Alexandrov, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Investigation of depth-resolved nanoscale structural changes in regulated cell proliferation and chromatin decondensation,” Biomed. Opt. Express4(4), 596–613 (2013).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

Su, J. W.

J. W. Su, W. C. Hsu, C. Y. Chou, C. H. Chang, and K. B. Sung, “Digital holographic microtomography for high-resolution refractive index mapping of live cells,” J. Biophotonics6(5), 416–424 (2013).
[CrossRef] [PubMed]

Su, X. T.

Sung, K. B.

J. W. Su, W. C. Hsu, C. Y. Chou, C. H. Chang, and K. B. Sung, “Digital holographic microtomography for high-resolution refractive index mapping of live cells,” J. Biophotonics6(5), 416–424 (2013).
[CrossRef] [PubMed]

Sung, Y.

Taflove, A.

J. Yi, A. J. Radosevich, J. D. Rogers, S. C. P. Norris, I. R. Çapoğlu, A. Taflove, and V. Backman, “Can OCT be sensitive to nanoscale structural alterations in biological tissue?” Opt. Express21(7), 9043–9059 (2013).
[CrossRef] [PubMed]

X. Li, Z. Chen, A. Taflove, and V. Backman, “Equiphase-sphere approximation for light scattering by stochastically inhomogeneous microparticles,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.70(5), 056610 (2004).
[CrossRef] [PubMed]

Terry, N. G.

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt.16(1), 011003 (2011).
[CrossRef] [PubMed]

Trembath, D.

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

Tunnell, J. W.

Uttam, S.

S. Uttam, R. K. Bista, K. Staton, S. Alexandrov, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Investigation of depth-resolved nanoscale structural changes in regulated cell proliferation and chromatin decondensation,” Biomed. Opt. Express4(4), 596–613 (2013).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

S. Uttam, R. K. Bista, D. J. Hartman, R. E. Brand, and Y. Liu, “Correction of stain variations in nuclear refractive index of clinical histology specimens,” J. Biomed. Opt.16(11), 116013 (2011).
[CrossRef] [PubMed]

Valentine, M. T.

Van Niekerk, D.

M. Guillaud, D. Cox, K. Adler-Storthz, A. Malpica, G. Staerkel, J. Matisic, D. Van Niekerk, N. Poulin, M. Follen, and C. MacAulay, “Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus,” Cytometry A60A(1), 81–89 (2004).
[CrossRef] [PubMed]

Videen, G.

Y. L. Pan, M. J. Berg, S. S. Zhang, H. Noh, H. Cao, R. K. Chang, and G. Videen, “Measurement and autocorrelation analysis of two-dimensional light-scattering patterns from living cells for label-free classification,” Cytometry A79A(4), 284–292 (2011).
[CrossRef] [PubMed]

Wang, P.

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. Qiu, W. E. Khalbuss, L. Zhang, R. E. Brand, and Y. Liu, “An insight into statistical refractive index properties of cell internal structure via low-coherence statistical amplitude microscopy,” Opt. Express18(21), 21950–21958 (2010).
[CrossRef] [PubMed]

Wax, A.

S. K. Yarmoska, S. Kim, T. E. Matthews, and A. Wax, “A scattering phantom for observing long range order with two-dimensional angle-resolved low-coherence Interferometry,” Biomed. Opt. Express4(9), 1742–1748 (2013).
[CrossRef] [PubMed]

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt.16(1), 011003 (2011).
[CrossRef] [PubMed]

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

M. Giacomelli, Y. Zhu, J. Lee, and A. Wax, “Size and shape determination of spheroidal scatterers using two-dimensional angle resolved scattering,” Opt. Express18(14), 14616–14626 (2010).
[CrossRef] [PubMed]

Weitz, D. A.

Williams, P. M.

C. MacAulay, C. F. Poh, M. Guillaud, P. M. Williams, D. M. Laronde, L. Zhang, and M. P. Rosin, “High throughput image cytometry for detection of suspicious lesions in the oral cavity,” J. Biomed. Opt.17(8), 086004 (2012).
[CrossRef] [PubMed]

Wilson, J. D.

J. D. Wilson, B. R. Giesselman, S. Mitra, and T. H. Foster, “Lysosome-damage-induced scattering changes coincide with release of cytochrome c,” Opt. Lett.32(17), 2517–2519 (2007).
[CrossRef] [PubMed]

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, “Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling,” Biophys. J.88(4), 2929–2938 (2005).
[CrossRef] [PubMed]

Woosley, J. T.

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt.16(1), 011003 (2011).
[CrossRef] [PubMed]

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

Wu, T. T.

M. Xu, T. T. Wu, and J. Y. Qu, “Unified Mie and fractal scattering by cells and experimental study on application in optical characterization of cellular and subcellular structures,” J. Biomed. Opt.13(2), 024015 (2008).
[CrossRef] [PubMed]

Xu, M.

M. Xu, T. T. Wu, and J. Y. Qu, “Unified Mie and fractal scattering by cells and experimental study on application in optical characterization of cellular and subcellular structures,” J. Biomed. Opt.13(2), 024015 (2008).
[CrossRef] [PubMed]

Yarmoska, S. K.

Yi, J.

Yoon, J. H.

Yu, C. C.

Zhang, L.

C. MacAulay, C. F. Poh, M. Guillaud, P. M. Williams, D. M. Laronde, L. Zhang, and M. P. Rosin, “High throughput image cytometry for detection of suspicious lesions in the oral cavity,” J. Biomed. Opt.17(8), 086004 (2012).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. Qiu, W. E. Khalbuss, L. Zhang, R. E. Brand, and Y. Liu, “An insight into statistical refractive index properties of cell internal structure via low-coherence statistical amplitude microscopy,” Opt. Express18(21), 21950–21958 (2010).
[CrossRef] [PubMed]

Zhang, S. S.

Y. L. Pan, M. J. Berg, S. S. Zhang, H. Noh, H. Cao, R. K. Chang, and G. Videen, “Measurement and autocorrelation analysis of two-dimensional light-scattering patterns from living cells for label-free classification,” Cytometry A79A(4), 284–292 (2011).
[CrossRef] [PubMed]

Zhu, Y.

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt.16(1), 011003 (2011).
[CrossRef] [PubMed]

M. Giacomelli, Y. Zhu, J. Lee, and A. Wax, “Size and shape determination of spheroidal scatterers using two-dimensional angle resolved scattering,” Opt. Express18(14), 14616–14626 (2010).
[CrossRef] [PubMed]

Ziefle, C. G.

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

Am. J. Physiol. Cell Physiol. (1)

G. Popescu, Y. Park, N. Lue, C. Best-Popescu, L. Deflores, R. R. Dasari, M. S. Feld, and K. Badizadegan, “Optical imaging of cell mass and growth dynamics,” Am. J. Physiol. Cell Physiol.295(2), C538–C544 (2008).
[CrossRef] [PubMed]

Appl. Opt. (3)

Biomed. Opt. Express (3)

Biophys. J. (2)

J. D. Wilson, C. E. Bigelow, D. J. Calkins, and T. H. Foster, “Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling,” Biophys. J.88(4), 2929–2938 (2005).
[CrossRef] [PubMed]

D. Arifler, I. Pavlova, A. Gillenwater, and R. Richards-Kortum, “Light scattering from collagen fiber networks: micro-optical properties of normal and neoplastic stroma,” Biophys. J.92(9), 3260–3274 (2007).
[CrossRef] [PubMed]

Cytometry A (2)

Y. L. Pan, M. J. Berg, S. S. Zhang, H. Noh, H. Cao, R. K. Chang, and G. Videen, “Measurement and autocorrelation analysis of two-dimensional light-scattering patterns from living cells for label-free classification,” Cytometry A79A(4), 284–292 (2011).
[CrossRef] [PubMed]

M. Guillaud, D. Cox, K. Adler-Storthz, A. Malpica, G. Staerkel, J. Matisic, D. Van Niekerk, N. Poulin, M. Follen, and C. MacAulay, “Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus,” Cytometry A60A(1), 81–89 (2004).
[CrossRef] [PubMed]

Gastroenterology (1)

N. G. Terry, Y. Zhu, M. T. Rinehart, W. J. Brown, S. C. Gebhart, S. Bright, E. Carretta, C. G. Ziefle, M. Panjehpour, J. Galanko, R. D. Madanick, E. S. Dellon, D. Trembath, A. Bennett, J. R. Goldblum, B. F. Overholt, J. T. Woosley, N. J. Shaheen, and A. Wax, “Detection of dysplasia in Barrett’s esophagus with in vivo depth-resolved nuclear morphology measurements,” Gastroenterology140(1), 42–50 (2011).
[CrossRef] [PubMed]

J. Biomed. Opt. (7)

M. Xu, T. T. Wu, and J. Y. Qu, “Unified Mie and fractal scattering by cells and experimental study on application in optical characterization of cellular and subcellular structures,” J. Biomed. Opt.13(2), 024015 (2008).
[CrossRef] [PubMed]

R. K. Bista, S. Uttam, P. Wang, K. Staton, S. Choi, C. J. Bakkenist, D. J. Hartman, R. E. Brand, and Y. Liu, “Quantification of nanoscale nuclear refractive index changes during the cell cycle,” J. Biomed. Opt.16(7), 070503 (2011).
[CrossRef] [PubMed]

S. Uttam, R. K. Bista, D. J. Hartman, R. E. Brand, and Y. Liu, “Correction of stain variations in nuclear refractive index of clinical histology specimens,” J. Biomed. Opt.16(11), 116013 (2011).
[CrossRef] [PubMed]

R. Drezek, M. Guillaud, T. Collier, I. Boiko, A. Malpica, C. MacAulay, M. Follen, and R. Richards-Kortum, “Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture,” J. Biomed. Opt.8(1), 7–16 (2003).
[CrossRef] [PubMed]

D. Arifler, M. Guillaud, A. Carraro, A. Malpica, M. Follen, and R. Richards-Kortum, “Light scattering from normal and dysplastic cervical cells at different epithelial depths: finite-difference time-domain modeling with a perfectly matched layer boundary condition,” J. Biomed. Opt.8(3), 484–494 (2003).
[CrossRef] [PubMed]

C. MacAulay, C. F. Poh, M. Guillaud, P. M. Williams, D. M. Laronde, L. Zhang, and M. P. Rosin, “High throughput image cytometry for detection of suspicious lesions in the oral cavity,” J. Biomed. Opt.17(8), 086004 (2012).
[CrossRef] [PubMed]

Y. Zhu, N. G. Terry, J. T. Woosley, N. J. Shaheen, and A. Wax, “Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology,” J. Biomed. Opt.16(1), 011003 (2011).
[CrossRef] [PubMed]

J. Biophotonics (1)

J. W. Su, W. C. Hsu, C. Y. Chou, C. H. Chang, and K. B. Sung, “Digital holographic microtomography for high-resolution refractive index mapping of live cells,” J. Biophotonics6(5), 416–424 (2013).
[CrossRef] [PubMed]

Nat. Methods (1)

W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, “Tomographic phase microscopy,” Nat. Methods4(9), 717–719 (2007).
[CrossRef] [PubMed]

Opt. Express (7)

J. Yi, A. J. Radosevich, J. D. Rogers, S. C. P. Norris, I. R. Çapoğlu, A. Taflove, and V. Backman, “Can OCT be sensitive to nanoscale structural alterations in biological tissue?” Opt. Express21(7), 9043–9059 (2013).
[CrossRef] [PubMed]

M. Kalashnikov, W. Choi, C. C. Yu, Y. Sung, R. R. Dasari, K. Badizadegan, and M. S. Feld, “Assessing light scattering of intracellular organelles in single intact living cells,” Opt. Express17(22), 19674–19681 (2009).
[CrossRef] [PubMed]

M. Giacomelli, Y. Zhu, J. Lee, and A. Wax, “Size and shape determination of spheroidal scatterers using two-dimensional angle resolved scattering,” Opt. Express18(14), 14616–14626 (2010).
[CrossRef] [PubMed]

P. Wang, R. K. Bista, W. Qiu, W. E. Khalbuss, L. Zhang, R. E. Brand, and Y. Liu, “An insight into statistical refractive index properties of cell internal structure via low-coherence statistical amplitude microscopy,” Opt. Express18(21), 21950–21958 (2010).
[CrossRef] [PubMed]

W. J. Choi, D. I. Jeon, S. G. Ahn, J. H. Yoon, S. Kim, and B. H. Lee, “Full-field optical coherence microscopy for identifying live cancer cells by quantitative measurement of refractive index distribution,” Opt. Express18(22), 23285–23295 (2010).
[CrossRef] [PubMed]

J. Ramachandran, T. M. Powers, S. Carpenter, A. Garcia-Lopez, J. P. Freyer, and J. R. Mourant, “Light scattering and microarchitectural differences between tumorigenic and non-tumorigenic cell models of tissue,” Opt. Express15(7), 4039–4053 (2007).
[CrossRef] [PubMed]

X. T. Su, C. Capjack, W. Rozmus, and C. Backhouse, “2D light scattering patterns of mitochondria in single cells,” Opt. Express15(17), 10562–10575 (2007).
[CrossRef] [PubMed]

Opt. Lett. (4)

Phys. Rev. E Stat. Nonlin. Soft Matter Phys. (1)

X. Li, Z. Chen, A. Taflove, and V. Backman, “Equiphase-sphere approximation for light scattering by stochastically inhomogeneous microparticles,” Phys. Rev. E Stat. Nonlin. Soft Matter Phys.70(5), 056610 (2004).
[CrossRef] [PubMed]

Other (2)

A. Taflove and S. C. Hagness, Computational Electrodynamics: The Finite-Difference Time-Domain Method (Artech House, Norwood, 2005).

D. Arifler, “Reflectance-based optical diagnosis of epithelial pre-cancer: modeling spectroscopic measurements, fiber-optic probe design considerations, and analysis of tissue micro-optical properties,” Ph.D. Dissertation, The University of Texas at Austin (2005).

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Figures (8)

Fig. 1
Fig. 1

Main stages involved in extraction of layer-specific nuclear features from quantitative histopathology images. Four different epithelial layers considered are basal, parabasal, intermediate, and superficial; the basal layer is the innermost layer, whereas the superficial layer is closest to the tissue surface.

Fig. 2
Fig. 2

FDTD simulation geometry for an x-polarized incident wave. The polar scattering angle θ is defined to be the angle between the incident and scattered light directions, whereas the azimuthal scattering angle ϕ is defined to be the angle between the incident light polarization direction and the scattering plane.

Fig. 3
Fig. 3

Sample images of basal, parabasal, intermediate, and superficial nuclei that are representative of four diagnostic categories, namely normal or negative for dysplasia, mild dysplasia, moderate dysplasia, and severe dysplasia or CIS. Each pixel shown is 0.34 × 0.34 μm2.

Fig. 4
Fig. 4

Sample two-dimensional scattering patterns of basal, parabasal, intermediate, and superficial nuclei that are representative of four diagnostic categories, namely normal or negative for dysplasia, mild dysplasia, moderate dysplasia, and severe dysplasia or CIS. Simulation results are plotted on a log scale where the maximum value is normalized to zero for each layer and diagnostic category.

Fig. 5
Fig. 5

Integrated absolute intensity computed from two-dimensional scattering patterns of cervical cell nuclei. Four angular ranges are considered separately: (a) θ = 0°-180° and ϕ = 0°-360°, (b) θ = 0°-40° and ϕ = 0°-360° corresponding to forward scattering, (c) θ = 40°-140° and ϕ = 0°-360° corresponding to side scattering, and (d) θ = 140°-180° and ϕ = 0°-360° corresponding to backscattering.

Fig. 6
Fig. 6

Integrated normalized intensity computed from two-dimensional scattering patterns of cervical cell nuclei. Four angular ranges are considered separately: (a) θ = 0°-180° and ϕ = 0°-360°, (b) θ = 0°-40° and ϕ = 0°-360° corresponding to forward scattering, (c) θ = 40°-140° and ϕ = 0°-360° corresponding to side scattering, and (d) θ = 140°-180° and ϕ = 0°-360° corresponding to backscattering.

Fig. 7
Fig. 7

Number of regional maxima in two-dimensional scattering patterns of cervical cell nuclei. Four angular ranges are considered separately: (a) θ = 0°-180° and ϕ = 0°-360°, (b) θ = 0°-40° and ϕ = 0°-360° corresponding to forward scattering, (c) θ = 40°-140° and ϕ = 0°-360° corresponding to side scattering, and (d) θ = 140°-180° and ϕ = 0°-360° corresponding to backscattering.

Fig. 8
Fig. 8

Average correlation for two-dimensional scattering patterns of cervical cell nuclei. Four angular ranges are considered separately: (a) θ = 0°-180° and ϕ = 0°-360°, (b) θ = 0°-40° and ϕ = 0°-360° corresponding to forward scattering, (c) θ = 40°-140° and ϕ = 0°-360° corresponding to side scattering, and (d) θ = 140°-180° and ϕ = 0°-360° corresponding to backscattering.

Tables (2)

Tables Icon

Table 1 Breakdown of 66 nuclear models constructed for electromagnetic simulations. The numbers in parentheses indicate the number of nuclei analyzed to construct each model.

Tables Icon

Table 2 Nuclear features averaged over the entire image set.

Equations (2)

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OD(i,j)=log I B -logI(i,j),
OD ¯ = (i,j)A OD(i,j) c norm | A | ,

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