Abstract

We evaluate a new hybrid algorithm for determining nuclear morphology using angle-resolved low coherence interferometry (a/LCI) measurements in ex vivo cervical tissue. The algorithm combines Mie theory based and continuous wavelet transform inverse light scattering analysis. The hybrid algorithm was validated and compared to traditional Mie theory based analysis using an ex vivo tissue data set. The hybrid algorithm achieved 100% agreement with pathology in distinguishing dysplastic and non-dysplastic biopsy sites in the pilot study. Significantly, the new algorithm performed over four times faster than traditional Mie theory based analysis.

© 2015 Optical Society of America

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  1. A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
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    [Crossref] [PubMed]
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    [Crossref]
  19. J. W. Pyhtila, H. Ma, A. J. Simnick, A. Chilkoti, and A. Wax, “Analysis of long range correlations due to coherent light scattering from in-vitro cell arrays using angle-resolved low coherence interferometry,” J. Biomed. Opt. 11(3), 034022 (2006).
    [Crossref] [PubMed]
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2014 (1)

2011 (3)

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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

N. Terry, Y. Zhu, J. K. M. Thacker, J. Migaly, C. Guy, C. R. Mantyh, and A. Wax, “Detection of intestinal dysplasia using angle-resolved low coherence interferometry,” J. Biomed. Opt. 16(10), 106002 (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]

2010 (3)

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[Crossref] [PubMed]

M. G. Giacomelli, K. J. Chalut, J. H. Ostrander, and A. Wax, “Review of the Application of T-Matrix Calculations for Determining the Structure of Cell Nuclei With Angle-Resolved Light Scattering Measurements,” IEEE J. Sel. Top. Quantum Electron. 16(4), 900–908 (2010).
[Crossref]

P. Dey, “Cancer nucleus: morphology and beyond,” Diagn. Cytopathol. 38(5), 382–390 (2010).
[PubMed]

2009 (1)

2008 (3)

M. Arbyn, C. Bergeron, P. Klinkhamer, P. Martin-Hirsch, A. G. Siebers, and J. Bulten, “Liquid compared with conventional cervical cytology: A systematic review and meta-analysis,” Obstet. Gynecol. 111(1), 167–177 (2008).
[Crossref] [PubMed]

N. Thekkek and R. Richards-Kortum, “Optical imaging for cervical cancer detection: solutions for a continuing global problem,” Nat. Rev. Cancer 8(9), 725–731 (2008).
[Crossref] [PubMed]

W. J. Brown, J. W. Pyhtila, N. G. Terry, K. J. Chalut, T. A. D’Amico, T. A. Sporn, J. V. Obando, and A. Wax, “Review and recent development of angle-resolved low-coherence interferometry for detection of precancerous cells in human esophageal epithelium,” IEEE J. Sel. Top. Quantum Electron. 14(1), 88–97 (2008).
[Crossref]

2007 (1)

2006 (1)

J. W. Pyhtila, H. Ma, A. J. Simnick, A. Chilkoti, and A. Wax, “Analysis of long range correlations due to coherent light scattering from in-vitro cell arrays using angle-resolved low coherence interferometry,” J. Biomed. Opt. 11(3), 034022 (2006).
[Crossref] [PubMed]

2003 (2)

J. Pyhtila, R. Graf, and A. Wax, “Determining nuclear morphology using an improved angle-resolved low coherence interferometry system,” Opt. Express 11(25), 3473–3484 (2003).
[Crossref] [PubMed]

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

2001 (1)

E. L. Franco, E. Duarte-Franco, and A. Ferenczy, “Cervical cancer: epidemiology, prevention and the role of human papillomavirus infection,” CMAJ 164(7), 1017–1025 (2001).
[PubMed]

1998 (1)

M. F. Mitchell, D. Schottenfeld, G. Tortolero-Luna, S. B. Cantor, and R. Richards-Kortum, “Colposcopy for the diagnosis of squamous intraepithelial lesions: A meta-analysis,” Obstet. Gynecol. 91(4), 626–631 (1998).
[Crossref] [PubMed]

1992 (1)

C. W. Boone, G. J. Kelloff, and V. E. Steele, “Natural history of intraepithelial neoplasia in humans with implications for cancer chemoprevention strategy,” Cancer Res. 52(7), 1651–1659 (1992).
[PubMed]

Amoozegar, C.

Arbyn, M.

M. Arbyn, C. Bergeron, P. Klinkhamer, P. Martin-Hirsch, A. G. Siebers, and J. Bulten, “Liquid compared with conventional cervical cytology: A systematic review and meta-analysis,” Obstet. Gynecol. 111(1), 167–177 (2008).
[Crossref] [PubMed]

Bao, Y. P.

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

Bergeron, C.

M. Arbyn, C. Bergeron, P. Klinkhamer, P. Martin-Hirsch, A. G. Siebers, and J. Bulten, “Liquid compared with conventional cervical cytology: A systematic review and meta-analysis,” Obstet. Gynecol. 111(1), 167–177 (2008).
[Crossref] [PubMed]

Boone, C. W.

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

C. W. Boone, G. J. Kelloff, and V. E. Steele, “Natural history of intraepithelial neoplasia in humans with implications for cancer chemoprevention strategy,” Cancer Res. 52(7), 1651–1659 (1992).
[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,” Gastroenterology 140(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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

W. J. Brown, J. W. Pyhtila, N. G. Terry, K. J. Chalut, T. A. D’Amico, T. A. Sporn, J. V. Obando, and A. Wax, “Review and recent development of angle-resolved low-coherence interferometry for detection of precancerous cells in human esophageal epithelium,” IEEE J. Sel. Top. Quantum Electron. 14(1), 88–97 (2008).
[Crossref]

Bulten, J.

M. Arbyn, C. Bergeron, P. Klinkhamer, P. Martin-Hirsch, A. G. Siebers, and J. Bulten, “Liquid compared with conventional cervical cytology: A systematic review and meta-analysis,” Obstet. Gynecol. 111(1), 167–177 (2008).
[Crossref] [PubMed]

Cagle, A. J.

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[Crossref] [PubMed]

Cantor, S. B.

M. F. Mitchell, D. Schottenfeld, G. Tortolero-Luna, S. B. Cantor, and R. Richards-Kortum, “Colposcopy for the diagnosis of squamous intraepithelial lesions: A meta-analysis,” Obstet. Gynecol. 91(4), 626–631 (1998).
[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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

Chalut, K. J.

M. G. Giacomelli, K. J. Chalut, J. H. Ostrander, and A. Wax, “Review of the Application of T-Matrix Calculations for Determining the Structure of Cell Nuclei With Angle-Resolved Light Scattering Measurements,” IEEE J. Sel. Top. Quantum Electron. 16(4), 900–908 (2010).
[Crossref]

C. Amoozegar, M. G. Giacomelli, J. D. Keener, K. J. Chalut, and A. Wax, “Experimental verification of T-matrix-based inverse light scattering analysis for assessing structure of spheroids as models of cell nuclei,” Appl. Opt. 48(10), D20–D25 (2009).
[Crossref] [PubMed]

W. J. Brown, J. W. Pyhtila, N. G. Terry, K. J. Chalut, T. A. D’Amico, T. A. Sporn, J. V. Obando, and A. Wax, “Review and recent development of angle-resolved low-coherence interferometry for detection of precancerous cells in human esophageal epithelium,” IEEE J. Sel. Top. Quantum Electron. 14(1), 88–97 (2008).
[Crossref]

J. D. Keener, K. J. Chalut, J. W. Pyhtila, and A. Wax, “Application of Mie theory to determine the structure of spheroidal scatterers in biological materials,” Opt. Lett. 32(10), 1326–1328 (2007).
[Crossref] [PubMed]

Chilkoti, A.

J. W. Pyhtila, H. Ma, A. J. Simnick, A. Chilkoti, and A. Wax, “Analysis of long range correlations due to coherent light scattering from in-vitro cell arrays using angle-resolved low coherence interferometry,” J. Biomed. Opt. 11(3), 034022 (2006).
[Crossref] [PubMed]

D’Amico, T. A.

W. J. Brown, J. W. Pyhtila, N. G. Terry, K. J. Chalut, T. A. D’Amico, T. A. Sporn, J. V. Obando, and A. Wax, “Review and recent development of angle-resolved low-coherence interferometry for detection of precancerous cells in human esophageal epithelium,” IEEE J. Sel. Top. Quantum Electron. 14(1), 88–97 (2008).
[Crossref]

Dasari, R. R.

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

Dellon, E. 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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

Dey, P.

P. Dey, “Cancer nucleus: morphology and beyond,” Diagn. Cytopathol. 38(5), 382–390 (2010).
[PubMed]

Drake, T. K.

Duarte-Franco, E.

E. L. Franco, E. Duarte-Franco, and A. Ferenczy, “Cervical cancer: epidemiology, prevention and the role of human papillomavirus infection,” CMAJ 164(7), 1017–1025 (2001).
[PubMed]

Eldridge, W. J.

Feld, M. S.

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

Ferenczy, A.

E. L. Franco, E. Duarte-Franco, and A. Ferenczy, “Cervical cancer: epidemiology, prevention and the role of human papillomavirus infection,” CMAJ 164(7), 1017–1025 (2001).
[PubMed]

Franco, E. L.

E. L. Franco, E. Duarte-Franco, and A. Ferenczy, “Cervical cancer: epidemiology, prevention and the role of human papillomavirus infection,” CMAJ 164(7), 1017–1025 (2001).
[PubMed]

Galanko, 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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

Giacomelli, M. G.

M. G. Giacomelli, K. J. Chalut, J. H. Ostrander, and A. Wax, “Review of the Application of T-Matrix Calculations for Determining the Structure of Cell Nuclei With Angle-Resolved Light Scattering Measurements,” IEEE J. Sel. Top. Quantum Electron. 16(4), 900–908 (2010).
[Crossref]

C. Amoozegar, M. G. Giacomelli, J. D. Keener, K. J. Chalut, and A. Wax, “Experimental verification of T-matrix-based inverse light scattering analysis for assessing structure of spheroids as models of cell nuclei,” Appl. Opt. 48(10), D20–D25 (2009).
[Crossref] [PubMed]

Goldblum, J. R.

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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

Graf, R.

Guy, C.

N. Terry, Y. Zhu, J. K. M. Thacker, J. Migaly, C. Guy, C. R. Mantyh, and A. Wax, “Detection of intestinal dysplasia using angle-resolved low coherence interferometry,” J. Biomed. Opt. 16(10), 106002 (2011).
[Crossref] [PubMed]

Ho, D.

Hu, S. Y.

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[Crossref] [PubMed]

Keener, J. D.

Kelloff, G. J.

C. W. Boone, G. J. Kelloff, and V. E. Steele, “Natural history of intraepithelial neoplasia in humans with implications for cancer chemoprevention strategy,” Cancer Res. 52(7), 1651–1659 (1992).
[PubMed]

Kim, S.

Klinkhamer, P.

M. Arbyn, C. Bergeron, P. Klinkhamer, P. Martin-Hirsch, A. G. Siebers, and J. Bulten, “Liquid compared with conventional cervical cytology: A systematic review and meta-analysis,” Obstet. Gynecol. 111(1), 167–177 (2008).
[Crossref] [PubMed]

Lewis, K.

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[Crossref] [PubMed]

Li, S. M.

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[Crossref] [PubMed]

Lim, J. M.

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[Crossref] [PubMed]

Ma, H.

J. W. Pyhtila, H. Ma, A. J. Simnick, A. Chilkoti, and A. Wax, “Analysis of long range correlations due to coherent light scattering from in-vitro cell arrays using angle-resolved low coherence interferometry,” J. Biomed. Opt. 11(3), 034022 (2006).
[Crossref] [PubMed]

Ma, J. F.

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[Crossref] [PubMed]

Madanick, R. 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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

Mantyh, C. R.

N. Terry, Y. Zhu, J. K. M. Thacker, J. Migaly, C. Guy, C. R. Mantyh, and A. Wax, “Detection of intestinal dysplasia using angle-resolved low coherence interferometry,” J. Biomed. Opt. 16(10), 106002 (2011).
[Crossref] [PubMed]

Martin-Hirsch, P.

M. Arbyn, C. Bergeron, P. Klinkhamer, P. Martin-Hirsch, A. G. Siebers, and J. Bulten, “Liquid compared with conventional cervical cytology: A systematic review and meta-analysis,” Obstet. Gynecol. 111(1), 167–177 (2008).
[Crossref] [PubMed]

Migaly, J.

N. Terry, Y. Zhu, J. K. M. Thacker, J. Migaly, C. Guy, C. R. Mantyh, and A. Wax, “Detection of intestinal dysplasia using angle-resolved low coherence interferometry,” J. Biomed. Opt. 16(10), 106002 (2011).
[Crossref] [PubMed]

Mitchell, M. F.

M. F. Mitchell, D. Schottenfeld, G. Tortolero-Luna, S. B. Cantor, and R. Richards-Kortum, “Colposcopy for the diagnosis of squamous intraepithelial lesions: A meta-analysis,” Obstet. Gynecol. 91(4), 626–631 (1998).
[Crossref] [PubMed]

Müller, M. G.

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

Nines, R.

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

Obando, J. V.

W. J. Brown, J. W. Pyhtila, N. G. Terry, K. J. Chalut, T. A. D’Amico, T. A. Sporn, J. V. Obando, and A. Wax, “Review and recent development of angle-resolved low-coherence interferometry for detection of precancerous cells in human esophageal epithelium,” IEEE J. Sel. Top. Quantum Electron. 14(1), 88–97 (2008).
[Crossref]

Ostrander, J. H.

M. G. Giacomelli, K. J. Chalut, J. H. Ostrander, and A. Wax, “Review of the Application of T-Matrix Calculations for Determining the Structure of Cell Nuclei With Angle-Resolved Light Scattering Measurements,” IEEE J. Sel. Top. Quantum Electron. 16(4), 900–908 (2010).
[Crossref]

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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

Pan, Q. J.

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

Pyhtila, J.

Pyhtila, J. W.

W. J. Brown, J. W. Pyhtila, N. G. Terry, K. J. Chalut, T. A. D’Amico, T. A. Sporn, J. V. Obando, and A. Wax, “Review and recent development of angle-resolved low-coherence interferometry for detection of precancerous cells in human esophageal epithelium,” IEEE J. Sel. Top. Quantum Electron. 14(1), 88–97 (2008).
[Crossref]

J. D. Keener, K. J. Chalut, J. W. Pyhtila, and A. Wax, “Application of Mie theory to determine the structure of spheroidal scatterers in biological materials,” Opt. Lett. 32(10), 1326–1328 (2007).
[Crossref] [PubMed]

J. W. Pyhtila, H. Ma, A. J. Simnick, A. Chilkoti, and A. Wax, “Analysis of long range correlations due to coherent light scattering from in-vitro cell arrays using angle-resolved low coherence interferometry,” J. Biomed. Opt. 11(3), 034022 (2006).
[Crossref] [PubMed]

Qiao, Y. L.

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[Crossref] [PubMed]

Richards-Kortum, R.

N. Thekkek and R. Richards-Kortum, “Optical imaging for cervical cancer detection: solutions for a continuing global problem,” Nat. Rev. Cancer 8(9), 725–731 (2008).
[Crossref] [PubMed]

M. F. Mitchell, D. Schottenfeld, G. Tortolero-Luna, S. B. Cantor, and R. Richards-Kortum, “Colposcopy for the diagnosis of squamous intraepithelial lesions: A meta-analysis,” Obstet. Gynecol. 91(4), 626–631 (1998).
[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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

Schottenfeld, D.

M. F. Mitchell, D. Schottenfeld, G. Tortolero-Luna, S. B. Cantor, and R. Richards-Kortum, “Colposcopy for the diagnosis of squamous intraepithelial lesions: A meta-analysis,” Obstet. Gynecol. 91(4), 626–631 (1998).
[Crossref] [PubMed]

Sellors, J. W.

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[Crossref] [PubMed]

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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

Siebers, A. G.

M. Arbyn, C. Bergeron, P. Klinkhamer, P. Martin-Hirsch, A. G. Siebers, and J. Bulten, “Liquid compared with conventional cervical cytology: A systematic review and meta-analysis,” Obstet. Gynecol. 111(1), 167–177 (2008).
[Crossref] [PubMed]

Simnick, A. J.

J. W. Pyhtila, H. Ma, A. J. Simnick, A. Chilkoti, and A. Wax, “Analysis of long range correlations due to coherent light scattering from in-vitro cell arrays using angle-resolved low coherence interferometry,” J. Biomed. Opt. 11(3), 034022 (2006).
[Crossref] [PubMed]

Song, Y.

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[Crossref] [PubMed]

Sporn, T. A.

W. J. Brown, J. W. Pyhtila, N. G. Terry, K. J. Chalut, T. A. D’Amico, T. A. Sporn, J. V. Obando, and A. Wax, “Review and recent development of angle-resolved low-coherence interferometry for detection of precancerous cells in human esophageal epithelium,” IEEE J. Sel. Top. Quantum Electron. 14(1), 88–97 (2008).
[Crossref]

Steele, V. E.

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

C. W. Boone, G. J. Kelloff, and V. E. Steele, “Natural history of intraepithelial neoplasia in humans with implications for cancer chemoprevention strategy,” Cancer Res. 52(7), 1651–1659 (1992).
[PubMed]

Stoner, G. D.

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

Terry, N.

N. Terry, Y. Zhu, J. K. M. Thacker, J. Migaly, C. Guy, C. R. Mantyh, and A. Wax, “Detection of intestinal dysplasia using angle-resolved low coherence interferometry,” J. Biomed. Opt. 16(10), 106002 (2011).
[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,” Gastroenterology 140(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]

W. J. Brown, J. W. Pyhtila, N. G. Terry, K. J. Chalut, T. A. D’Amico, T. A. Sporn, J. V. Obando, and A. Wax, “Review and recent development of angle-resolved low-coherence interferometry for detection of precancerous cells in human esophageal epithelium,” IEEE J. Sel. Top. Quantum Electron. 14(1), 88–97 (2008).
[Crossref]

Thacker, J. K. M.

N. Terry, Y. Zhu, J. K. M. Thacker, J. Migaly, C. Guy, C. R. Mantyh, and A. Wax, “Detection of intestinal dysplasia using angle-resolved low coherence interferometry,” J. Biomed. Opt. 16(10), 106002 (2011).
[Crossref] [PubMed]

Thekkek, N.

N. Thekkek and R. Richards-Kortum, “Optical imaging for cervical cancer detection: solutions for a continuing global problem,” Nat. Rev. Cancer 8(9), 725–731 (2008).
[Crossref] [PubMed]

Tortolero-Luna, G.

M. F. Mitchell, D. Schottenfeld, G. Tortolero-Luna, S. B. Cantor, and R. Richards-Kortum, “Colposcopy for the diagnosis of squamous intraepithelial lesions: A meta-analysis,” Obstet. Gynecol. 91(4), 626–631 (1998).
[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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

Wax, A.

D. Ho, S. Kim, T. K. Drake, W. J. Eldridge, and A. Wax, “Wavelet transform fast inverse light scattering analysis for size determination of spherical scatterers,” Biomed. Opt. Express 5(10), 3292–3304 (2014).
[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,” Gastroenterology 140(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]

N. Terry, Y. Zhu, J. K. M. Thacker, J. Migaly, C. Guy, C. R. Mantyh, and A. Wax, “Detection of intestinal dysplasia using angle-resolved low coherence interferometry,” J. Biomed. Opt. 16(10), 106002 (2011).
[Crossref] [PubMed]

M. G. Giacomelli, K. J. Chalut, J. H. Ostrander, and A. Wax, “Review of the Application of T-Matrix Calculations for Determining the Structure of Cell Nuclei With Angle-Resolved Light Scattering Measurements,” IEEE J. Sel. Top. Quantum Electron. 16(4), 900–908 (2010).
[Crossref]

C. Amoozegar, M. G. Giacomelli, J. D. Keener, K. J. Chalut, and A. Wax, “Experimental verification of T-matrix-based inverse light scattering analysis for assessing structure of spheroids as models of cell nuclei,” Appl. Opt. 48(10), D20–D25 (2009).
[Crossref] [PubMed]

W. J. Brown, J. W. Pyhtila, N. G. Terry, K. J. Chalut, T. A. D’Amico, T. A. Sporn, J. V. Obando, and A. Wax, “Review and recent development of angle-resolved low-coherence interferometry for detection of precancerous cells in human esophageal epithelium,” IEEE J. Sel. Top. Quantum Electron. 14(1), 88–97 (2008).
[Crossref]

J. D. Keener, K. J. Chalut, J. W. Pyhtila, and A. Wax, “Application of Mie theory to determine the structure of spheroidal scatterers in biological materials,” Opt. Lett. 32(10), 1326–1328 (2007).
[Crossref] [PubMed]

J. W. Pyhtila, H. Ma, A. J. Simnick, A. Chilkoti, and A. Wax, “Analysis of long range correlations due to coherent light scattering from in-vitro cell arrays using angle-resolved low coherence interferometry,” J. Biomed. Opt. 11(3), 034022 (2006).
[Crossref] [PubMed]

J. Pyhtila, R. Graf, and A. Wax, “Determining nuclear morphology using an improved angle-resolved low coherence interferometry system,” Opt. Express 11(25), 3473–3484 (2003).
[Crossref] [PubMed]

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

Woosley, J. 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,” Gastroenterology 140(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]

Yang, C.

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

Zhang, W. H.

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[Crossref] [PubMed]

Zhao, F. H.

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[Crossref] [PubMed]

Zhu, Y.

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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

N. Terry, Y. Zhu, J. K. M. Thacker, J. Migaly, C. Guy, C. R. Mantyh, and A. Wax, “Detection of intestinal dysplasia using angle-resolved low coherence interferometry,” J. Biomed. Opt. 16(10), 106002 (2011).
[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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

Appl. Opt. (1)

Biomed. Opt. Express (1)

Cancer Res. (2)

A. Wax, C. Yang, M. G. Müller, R. Nines, C. W. Boone, V. E. Steele, G. D. Stoner, R. R. Dasari, and M. S. Feld, “In situ detection of neoplastic transformation and chemopreventive effects in rat esophagus epithelium using angle-resolved low-coherence interferometry,” Cancer Res. 63(13), 3556–3559 (2003).
[PubMed]

C. W. Boone, G. J. Kelloff, and V. E. Steele, “Natural history of intraepithelial neoplasia in humans with implications for cancer chemoprevention strategy,” Cancer Res. 52(7), 1651–1659 (1992).
[PubMed]

CMAJ (1)

E. L. Franco, E. Duarte-Franco, and A. Ferenczy, “Cervical cancer: epidemiology, prevention and the role of human papillomavirus infection,” CMAJ 164(7), 1017–1025 (2001).
[PubMed]

Diagn. Cytopathol. (1)

P. Dey, “Cancer nucleus: morphology and beyond,” Diagn. Cytopathol. 38(5), 382–390 (2010).
[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,” Gastroenterology 140(1), 42–50 (2011).
[Crossref] [PubMed]

IEEE J. Sel. Top. Quantum Electron. (2)

M. G. Giacomelli, K. J. Chalut, J. H. Ostrander, and A. Wax, “Review of the Application of T-Matrix Calculations for Determining the Structure of Cell Nuclei With Angle-Resolved Light Scattering Measurements,” IEEE J. Sel. Top. Quantum Electron. 16(4), 900–908 (2010).
[Crossref]

W. J. Brown, J. W. Pyhtila, N. G. Terry, K. J. Chalut, T. A. D’Amico, T. A. Sporn, J. V. Obando, and A. Wax, “Review and recent development of angle-resolved low-coherence interferometry for detection of precancerous cells in human esophageal epithelium,” IEEE J. Sel. Top. Quantum Electron. 14(1), 88–97 (2008).
[Crossref]

Int. J. Cancer (1)

A. J. Cagle, S. Y. Hu, J. W. Sellors, Y. P. Bao, J. M. Lim, S. M. Li, K. Lewis, Y. Song, J. F. Ma, Q. J. Pan, W. H. Zhang, F. H. Zhao, and Y. L. Qiao, “Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid,” Int. J. Cancer 126(1), 156–161 (2010).
[Crossref] [PubMed]

J. Biomed. Opt. (3)

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]

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Figures (9)

Fig. 1
Fig. 1 a/LCI clinical system schematic in a Mach-Zehnder interferometer geometry. The fiber probe tip shows the sample illumination by the PM fiber and scattered light collected through the fiber bundle [17].
Fig. 2
Fig. 2 Average nuclear diameter determined from Mie theory ILSA of a/LCI scans for non-dysplastic (healthy and metaplastic) and dysplastic biopsy sites at varying tissue depths. *indicates significant difference (p < 0.05) between group means.
Fig. 3
Fig. 3 (a) The simulated Mie scattering profile for 9 µm cervical tissue with (b), its corresponding CWT. (c) The CWT energy for varying dilation factor of the CWT within the angular analysis range (dotted black line). The first energy peak (apeak = 25) was used for nuclear diameter determination (pink line). (d) The inverse of the first energy peak (1/apeak = 0.4) is input to the scatterer size lookup line (red) to produce a CWT diameter estimate (d = 9.29).
Fig. 4
Fig. 4 (a) CWT predicted diameter vs. true diameter of simulated scattering profiles for cell nuclei using cervical tissue parameters. (b) Bland-Altman plot of CWT ILSA vs Mie theory ILSA predicted nuclear diameter with the filter cutoff optimized for greatest agreement between the two algorithms.
Fig. 5
Fig. 5 Flowchart of (a) Mie theory based ILSA, (b) CWT based ILSA, and (c) the hybrid fitting algorithm. For the hybrid algorithm, the a/LCI scattering distribution is initially filtered at fMie. Coarse fitting is performed using CWT ILSA to determine the optimal CWT filter cutoff position fCWT and a coarse diameter prediction DCWT. Fine fitting is performed using Mie theory based ILSA within a ± 1 µm range around DCWT.
Fig. 6
Fig. 6 (a) Scatter plot of average nuclear diameter and density for each biopsy site at 200-250 µm depth predicted using Mie theory ILSA. A 10.54 µm decision line separates dysplastic (red) from non-dysplastic (green, orange) sites with 100% sensitivity and 90% specificity. Figure adapted with permission from [20]. (b) Average nuclear diameter for non-dysplastic (healthy + metaplastic) and dysplastic biopsy sites.
Fig. 7
Fig. 7 Bland-Altman plots comparing CWT ILSA and Mie theory ILSA nuclear diameter prediction for the a/LCI distribution filtered at fCWT for (a) individual a/LCI scans and (b) biopsy sites. The 11.75 µm decision line can be drawn for CWT based ILSA diameter prediction for 100% predictive accuracy.
Fig. 8
Fig. 8 (a) Bland-Altman comparison of modified CWT ILSA and Mie theory ILSA nuclear diameter prediction. (b) Mie theory ILSA and hybrid algorithm nuclear diameter prediction for each biopsy site. A 10.54 µm decision line separates dysplastic non-dysplastic sites with 100% sensitivity and 100% specificity for the hybrid algorithm.
Fig. 9
Fig. 9 Relative processing time for Mie theory and Hybrid ILSA algorithms along with the adjusted processing times taking into consideration the rejected scans of both algorithms.

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