Abstract

For cancer patients, treatment selection fundamentally relies on staging, with “under-staging” considered a common problem. Imaging modalities that can complement conventional white-light laparoscopy are needed to detect more accurately small metastatic lesions in patients undergoing operative cancer care. Biopsies from healthy parietal peritoneum and ovarian peritoneal metastases obtained from 8 patients were imaged employing a two-photon laser scanning microscope to generate collagen-second harmonic generation (SHG) and fluorescence images at 755 nm and 900 nm excitation and 460 ± 20 nm and 525 ± 25 nm emission. Forty-one images were analyzed by automated image processing algorithms and statistical textural analysis techniques, namely gray level co-occurrence matrices. Two textural features (contrast and correlation) were employed to describe the spatial intensity variations within the captured images and outcomes were used for discriminant analysis. We found that healthy tissues displayed large variations in contrast and correlation features as a function of distance, corresponding to repetitive, increased local intensity fluctuations. Metastatic tissue images exhibited decreased contrast and correlation related values, representing more uniform intensity patterns and smaller fibers, indicating the destruction of the healthy stroma by the cancerous infiltration. The textural outcomes resulted in high classification accuracy as evaluated quantitatively by discriminant analysis.

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Full Article  |  PDF Article
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References

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    [Crossref]
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    [Crossref]
  21. C. J. Huberty, S. Olejnik, and C. J. Huberty, Applied MANOVA and Discriminant Analysis, 2nd ed., Wiley Series in Probability and Statistics (Wiley-Interscience, 2006), pp. xxxiv.
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    [Crossref]
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    [Crossref]

2018 (1)

S. Cheng, Y. Lu, Y. Li, L. Gao, H. Shen, and K. Song, “Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal mesothelial cells,” Sci. Rep. 8(1), 5863 (2018).
[Crossref]

2016 (2)

D. Pouli, M. Balu, C. A. Alonzo, Z. Liu, K. P. Quinn, F. Rius-Diaz, R. M. Harris, K. M. Kelly, B. J. Tromberg, and I. Georgakoudi, “Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis,” Sci. Transl. Med. 8(367), 367ra169 (2016).
[Crossref]

S. H. Chandrashekhara, G. S. Triveni, and R. Kumar, “Imaging of peritoneal deposits in ovarian cancer: A pictorial review,” World J Radiol 8(5), 513–517 (2016).
[Crossref]

2015 (1)

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

2014 (1)

J. Adur, H. F. Carvalho, C. L. Cesar, and V. H. Casco, “Nonlinear optical microscopy signal processing strategies in cancer,” Cancer Inf. 13, CIN.S12419 (2014).
[Crossref]

2013 (4)

M. A. Karsdal, M. J. Nielsen, J. M. Sand, K. Henriksen, F. Genovese, A. C. Bay-Jensen, V. Smith, J. I. Adamkewicz, C. Christiansen, and D. J. Leeming, “Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure,” Assay Drug Dev. Technol. 11(2), 70–92 (2013).
[Crossref]

P. Amate, C. Huchon, A. L. Dessapt, C. Bensaid, J. Medioni, M. A. Le Frere Belda, A. S. Bats, and F. R. Lecuru, “Ovarian cancer: sites of recurrence,” Int J Gynecol Cancer 23(9), 1590–1596 (2013).
[Crossref]

Y. Kodera, “Gastric cancer with minimal peritoneal metastasis: is this a sign to give up or to treat more aggressively?” Nagoya J Med Sci 75(1–2), 3–10 (2013).

D. G. Ouzounov, D. R. Rivera, W. O. Williams, J. A. Stupinski, T. L. Southard, K. H. Hume, J. Bentley, R. S. Weiss, W. W. Webb, and C. Xu, “Dual modality endomicroscope with optical zoom capability,” Biomed. Opt. Express 4(9), 1494–1503 (2013).
[Crossref]

2012 (5)

T. Schnelldorfer, “Image-enhanced laparoscopy: a promising technology for detection of peritoneal micrometastases,” Surgery 151(3), 345–350 (2012).
[Crossref]

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, W. W. Webb, and C. Xu, “Multifocal multiphoton endoscope,” Opt. Lett. 37(8), 1349–1351 (2012).
[Crossref]

J. Xylas, K. P. Quinn, M. Hunter, and I. Georgakoudi, “Improved Fourier-based characterization of intracellular fractal features,” Opt. Express 20(21), 23442–23455 (2012).
[Crossref]

I. Georgakoudi and K. P. Quinn, “Optical imaging using endogenous contrast to assess metabolic state,” Annu. Rev. Biomed. Eng. 14(1), 351–367 (2012).
[Crossref]

2011 (2)

T. R. Cox and J. T. Erler, “Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer,” Dis. Models Mech. 4(2), 165–178 (2011).
[Crossref]

C. M. Patel, A. Sahdev, and R. H. Reznek, “CT, MRI and PET imaging in peritoneal malignancy,” Cancer Imaging 11(1), 123–139 (2011).
[Crossref]

2010 (1)

E. Lengyel, “Ovarian cancer development and metastasis,” Am. J. Pathol. 177(3), 1053–1064 (2010).
[Crossref]

2005 (1)

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[Crossref]

2002 (1)

T. Ushiki, “Collagen fibers, reticular fibers and elastic fibers. A comprehensive understanding from a morphological viewpoint,” Arch. Histol. Cytol. 65(2), 109–126 (2002).
[Crossref]

2000 (1)

P. T. So, C. Y. Dong, B. R. Masters, and K. M. Berland, “Two-photon excitation fluorescence microscopy,” Annu. Rev. Biomed. Eng. 2(1), 399–429 (2000).
[Crossref]

1973 (1)

R. M. Haralick, K. Shanmugam, and I. Dinstein, “Textural Features for Image Classification,” IEEE Trans. Syst., Man, Cybern. SMC-3(6), 610–621 (1973).
[Crossref]

Adamkewicz, J. I.

M. A. Karsdal, M. J. Nielsen, J. M. Sand, K. Henriksen, F. Genovese, A. C. Bay-Jensen, V. Smith, J. I. Adamkewicz, C. Christiansen, and D. J. Leeming, “Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure,” Assay Drug Dev. Technol. 11(2), 70–92 (2013).
[Crossref]

Adur, J.

J. Adur, H. F. Carvalho, C. L. Cesar, and V. H. Casco, “Nonlinear optical microscopy signal processing strategies in cancer,” Cancer Inf. 13, CIN.S12419 (2014).
[Crossref]

Alonzo, C. A.

D. Pouli, M. Balu, C. A. Alonzo, Z. Liu, K. P. Quinn, F. Rius-Diaz, R. M. Harris, K. M. Kelly, B. J. Tromberg, and I. Georgakoudi, “Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis,” Sci. Transl. Med. 8(367), 367ra169 (2016).
[Crossref]

Amate, P.

P. Amate, C. Huchon, A. L. Dessapt, C. Bensaid, J. Medioni, M. A. Le Frere Belda, A. S. Bats, and F. R. Lecuru, “Ovarian cancer: sites of recurrence,” Int J Gynecol Cancer 23(9), 1590–1596 (2013).
[Crossref]

Balu, M.

D. Pouli, M. Balu, C. A. Alonzo, Z. Liu, K. P. Quinn, F. Rius-Diaz, R. M. Harris, K. M. Kelly, B. J. Tromberg, and I. Georgakoudi, “Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis,” Sci. Transl. Med. 8(367), 367ra169 (2016).
[Crossref]

Batrin, R.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

Bats, A. S.

P. Amate, C. Huchon, A. L. Dessapt, C. Bensaid, J. Medioni, M. A. Le Frere Belda, A. S. Bats, and F. R. Lecuru, “Ovarian cancer: sites of recurrence,” Int J Gynecol Cancer 23(9), 1590–1596 (2013).
[Crossref]

Bay-Jensen, A. C.

M. A. Karsdal, M. J. Nielsen, J. M. Sand, K. Henriksen, F. Genovese, A. C. Bay-Jensen, V. Smith, J. I. Adamkewicz, C. Christiansen, and D. J. Leeming, “Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure,” Assay Drug Dev. Technol. 11(2), 70–92 (2013).
[Crossref]

Bensaid, C.

P. Amate, C. Huchon, A. L. Dessapt, C. Bensaid, J. Medioni, M. A. Le Frere Belda, A. S. Bats, and F. R. Lecuru, “Ovarian cancer: sites of recurrence,” Int J Gynecol Cancer 23(9), 1590–1596 (2013).
[Crossref]

Bentley, J.

Berland, K. M.

P. T. So, C. Y. Dong, B. R. Masters, and K. M. Berland, “Two-photon excitation fluorescence microscopy,” Annu. Rev. Biomed. Eng. 2(1), 399–429 (2000).
[Crossref]

Bourg-Heckly, G.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

Braud, F.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

Brevier, J.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

Brown, C. M.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref]

D. R. Rivera, C. M. Brown, D. G. Ouzounov, W. W. Webb, and C. Xu, “Multifocal multiphoton endoscope,” Opt. Lett. 37(8), 1349–1351 (2012).
[Crossref]

Carvalho, H. F.

J. Adur, H. F. Carvalho, C. L. Cesar, and V. H. Casco, “Nonlinear optical microscopy signal processing strategies in cancer,” Cancer Inf. 13, CIN.S12419 (2014).
[Crossref]

Casco, V. H.

J. Adur, H. F. Carvalho, C. L. Cesar, and V. H. Casco, “Nonlinear optical microscopy signal processing strategies in cancer,” Cancer Inf. 13, CIN.S12419 (2014).
[Crossref]

Cesar, C. L.

J. Adur, H. F. Carvalho, C. L. Cesar, and V. H. Casco, “Nonlinear optical microscopy signal processing strategies in cancer,” Cancer Inf. 13, CIN.S12419 (2014).
[Crossref]

Chandrashekhara, S. H.

S. H. Chandrashekhara, G. S. Triveni, and R. Kumar, “Imaging of peritoneal deposits in ovarian cancer: A pictorial review,” World J Radiol 8(5), 513–517 (2016).
[Crossref]

Cheng, S.

S. Cheng, Y. Lu, Y. Li, L. Gao, H. Shen, and K. Song, “Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal mesothelial cells,” Sci. Rep. 8(1), 5863 (2018).
[Crossref]

Christiansen, C.

M. A. Karsdal, M. J. Nielsen, J. M. Sand, K. Henriksen, F. Genovese, A. C. Bay-Jensen, V. Smith, J. I. Adamkewicz, C. Christiansen, and D. J. Leeming, “Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure,” Assay Drug Dev. Technol. 11(2), 70–92 (2013).
[Crossref]

Cox, T. R.

T. R. Cox and J. T. Erler, “Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer,” Dis. Models Mech. 4(2), 165–178 (2011).
[Crossref]

Denk, W.

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[Crossref]

Dessapt, A. L.

P. Amate, C. Huchon, A. L. Dessapt, C. Bensaid, J. Medioni, M. A. Le Frere Belda, A. S. Bats, and F. R. Lecuru, “Ovarian cancer: sites of recurrence,” Int J Gynecol Cancer 23(9), 1590–1596 (2013).
[Crossref]

Dinstein, I.

R. M. Haralick, K. Shanmugam, and I. Dinstein, “Textural Features for Image Classification,” IEEE Trans. Syst., Man, Cybern. SMC-3(6), 610–621 (1973).
[Crossref]

Dong, C. Y.

P. T. So, C. Y. Dong, B. R. Masters, and K. M. Berland, “Two-photon excitation fluorescence microscopy,” Annu. Rev. Biomed. Eng. 2(1), 399–429 (2000).
[Crossref]

Druilhe, A.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

Ducourthial, G.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

Erler, J. T.

T. R. Cox and J. T. Erler, “Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer,” Dis. Models Mech. 4(2), 165–178 (2011).
[Crossref]

Fabert, M.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

Gao, L.

S. Cheng, Y. Lu, Y. Li, L. Gao, H. Shen, and K. Song, “Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal mesothelial cells,” Sci. Rep. 8(1), 5863 (2018).
[Crossref]

Genovese, F.

M. A. Karsdal, M. J. Nielsen, J. M. Sand, K. Henriksen, F. Genovese, A. C. Bay-Jensen, V. Smith, J. I. Adamkewicz, C. Christiansen, and D. J. Leeming, “Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure,” Assay Drug Dev. Technol. 11(2), 70–92 (2013).
[Crossref]

Georgakoudi, I.

D. Pouli, M. Balu, C. A. Alonzo, Z. Liu, K. P. Quinn, F. Rius-Diaz, R. M. Harris, K. M. Kelly, B. J. Tromberg, and I. Georgakoudi, “Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis,” Sci. Transl. Med. 8(367), 367ra169 (2016).
[Crossref]

I. Georgakoudi and K. P. Quinn, “Optical imaging using endogenous contrast to assess metabolic state,” Annu. Rev. Biomed. Eng. 14(1), 351–367 (2012).
[Crossref]

J. Xylas, K. P. Quinn, M. Hunter, and I. Georgakoudi, “Improved Fourier-based characterization of intracellular fractal features,” Opt. Express 20(21), 23442–23455 (2012).
[Crossref]

Habert, R.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

Hall-Beyer, M.

M. Hall-Beyer, “GLCM Texture: A Tutorial v. 3.0 March 2017,” (2017).

Haralick, R. M.

R. M. Haralick, K. Shanmugam, and I. Dinstein, “Textural Features for Image Classification,” IEEE Trans. Syst., Man, Cybern. SMC-3(6), 610–621 (1973).
[Crossref]

Harris, R. M.

D. Pouli, M. Balu, C. A. Alonzo, Z. Liu, K. P. Quinn, F. Rius-Diaz, R. M. Harris, K. M. Kelly, B. J. Tromberg, and I. Georgakoudi, “Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis,” Sci. Transl. Med. 8(367), 367ra169 (2016).
[Crossref]

Helmchen, F.

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[Crossref]

Henriksen, K.

M. A. Karsdal, M. J. Nielsen, J. M. Sand, K. Henriksen, F. Genovese, A. C. Bay-Jensen, V. Smith, J. I. Adamkewicz, C. Christiansen, and D. J. Leeming, “Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure,” Assay Drug Dev. Technol. 11(2), 70–92 (2013).
[Crossref]

Huberty, C. J.

C. J. Huberty, S. Olejnik, and C. J. Huberty, Applied MANOVA and Discriminant Analysis, 2nd ed., Wiley Series in Probability and Statistics (Wiley-Interscience, 2006), pp. xxxiv.

C. J. Huberty, S. Olejnik, and C. J. Huberty, Applied MANOVA and Discriminant Analysis, 2nd ed., Wiley Series in Probability and Statistics (Wiley-Interscience, 2006), pp. xxxiv.

Huchon, C.

P. Amate, C. Huchon, A. L. Dessapt, C. Bensaid, J. Medioni, M. A. Le Frere Belda, A. S. Bats, and F. R. Lecuru, “Ovarian cancer: sites of recurrence,” Int J Gynecol Cancer 23(9), 1590–1596 (2013).
[Crossref]

Hume, K. H.

Hunter, M.

Karsdal, M. A.

M. A. Karsdal, M. J. Nielsen, J. M. Sand, K. Henriksen, F. Genovese, A. C. Bay-Jensen, V. Smith, J. I. Adamkewicz, C. Christiansen, and D. J. Leeming, “Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure,” Assay Drug Dev. Technol. 11(2), 70–92 (2013).
[Crossref]

Kelly, K. M.

D. Pouli, M. Balu, C. A. Alonzo, Z. Liu, K. P. Quinn, F. Rius-Diaz, R. M. Harris, K. M. Kelly, B. J. Tromberg, and I. Georgakoudi, “Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis,” Sci. Transl. Med. 8(367), 367ra169 (2016).
[Crossref]

Kodera, Y.

Y. Kodera, “Gastric cancer with minimal peritoneal metastasis: is this a sign to give up or to treat more aggressively?” Nagoya J Med Sci 75(1–2), 3–10 (2013).

Kudlinski, A.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

Kumar, R.

S. H. Chandrashekhara, G. S. Triveni, and R. Kumar, “Imaging of peritoneal deposits in ovarian cancer: A pictorial review,” World J Radiol 8(5), 513–517 (2016).
[Crossref]

Le Frere Belda, M. A.

P. Amate, C. Huchon, A. L. Dessapt, C. Bensaid, J. Medioni, M. A. Le Frere Belda, A. S. Bats, and F. R. Lecuru, “Ovarian cancer: sites of recurrence,” Int J Gynecol Cancer 23(9), 1590–1596 (2013).
[Crossref]

Leclerc, P.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

Lecuru, F. R.

P. Amate, C. Huchon, A. L. Dessapt, C. Bensaid, J. Medioni, M. A. Le Frere Belda, A. S. Bats, and F. R. Lecuru, “Ovarian cancer: sites of recurrence,” Int J Gynecol Cancer 23(9), 1590–1596 (2013).
[Crossref]

Leeming, D. J.

M. A. Karsdal, M. J. Nielsen, J. M. Sand, K. Henriksen, F. Genovese, A. C. Bay-Jensen, V. Smith, J. I. Adamkewicz, C. Christiansen, and D. J. Leeming, “Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure,” Assay Drug Dev. Technol. 11(2), 70–92 (2013).
[Crossref]

Lengyel, E.

E. Lengyel, “Ovarian cancer development and metastasis,” Am. J. Pathol. 177(3), 1053–1064 (2010).
[Crossref]

Li, Y.

S. Cheng, Y. Lu, Y. Li, L. Gao, H. Shen, and K. Song, “Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal mesothelial cells,” Sci. Rep. 8(1), 5863 (2018).
[Crossref]

Liu, Z.

D. Pouli, M. Balu, C. A. Alonzo, Z. Liu, K. P. Quinn, F. Rius-Diaz, R. M. Harris, K. M. Kelly, B. J. Tromberg, and I. Georgakoudi, “Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis,” Sci. Transl. Med. 8(367), 367ra169 (2016).
[Crossref]

Louradour, F.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

Lu, Y.

S. Cheng, Y. Lu, Y. Li, L. Gao, H. Shen, and K. Song, “Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal mesothelial cells,” Sci. Rep. 8(1), 5863 (2018).
[Crossref]

Mansuryan, T.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

Masters, B. R.

P. T. So, C. Y. Dong, B. R. Masters, and K. M. Berland, “Two-photon excitation fluorescence microscopy,” Annu. Rev. Biomed. Eng. 2(1), 399–429 (2000).
[Crossref]

Medioni, J.

P. Amate, C. Huchon, A. L. Dessapt, C. Bensaid, J. Medioni, M. A. Le Frere Belda, A. S. Bats, and F. R. Lecuru, “Ovarian cancer: sites of recurrence,” Int J Gynecol Cancer 23(9), 1590–1596 (2013).
[Crossref]

Mohanan, S.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref]

Nielsen, M. J.

M. A. Karsdal, M. J. Nielsen, J. M. Sand, K. Henriksen, F. Genovese, A. C. Bay-Jensen, V. Smith, J. I. Adamkewicz, C. Christiansen, and D. J. Leeming, “Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure,” Assay Drug Dev. Technol. 11(2), 70–92 (2013).
[Crossref]

Olejnik, S.

C. J. Huberty, S. Olejnik, and C. J. Huberty, Applied MANOVA and Discriminant Analysis, 2nd ed., Wiley Series in Probability and Statistics (Wiley-Interscience, 2006), pp. xxxiv.

Ouzounov, D. G.

Patel, C. M.

C. M. Patel, A. Sahdev, and R. H. Reznek, “CT, MRI and PET imaging in peritoneal malignancy,” Cancer Imaging 11(1), 123–139 (2011).
[Crossref]

Pavlova, I.

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref]

Pouli, D.

D. Pouli, M. Balu, C. A. Alonzo, Z. Liu, K. P. Quinn, F. Rius-Diaz, R. M. Harris, K. M. Kelly, B. J. Tromberg, and I. Georgakoudi, “Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis,” Sci. Transl. Med. 8(367), 367ra169 (2016).
[Crossref]

Quinn, K. P.

D. Pouli, M. Balu, C. A. Alonzo, Z. Liu, K. P. Quinn, F. Rius-Diaz, R. M. Harris, K. M. Kelly, B. J. Tromberg, and I. Georgakoudi, “Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis,” Sci. Transl. Med. 8(367), 367ra169 (2016).
[Crossref]

I. Georgakoudi and K. P. Quinn, “Optical imaging using endogenous contrast to assess metabolic state,” Annu. Rev. Biomed. Eng. 14(1), 351–367 (2012).
[Crossref]

J. Xylas, K. P. Quinn, M. Hunter, and I. Georgakoudi, “Improved Fourier-based characterization of intracellular fractal features,” Opt. Express 20(21), 23442–23455 (2012).
[Crossref]

Reznek, R. H.

C. M. Patel, A. Sahdev, and R. H. Reznek, “CT, MRI and PET imaging in peritoneal malignancy,” Cancer Imaging 11(1), 123–139 (2011).
[Crossref]

Rius-Diaz, F.

D. Pouli, M. Balu, C. A. Alonzo, Z. Liu, K. P. Quinn, F. Rius-Diaz, R. M. Harris, K. M. Kelly, B. J. Tromberg, and I. Georgakoudi, “Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis,” Sci. Transl. Med. 8(367), 367ra169 (2016).
[Crossref]

Rivera, D. R.

Sahdev, A.

C. M. Patel, A. Sahdev, and R. H. Reznek, “CT, MRI and PET imaging in peritoneal malignancy,” Cancer Imaging 11(1), 123–139 (2011).
[Crossref]

Sand, J. M.

M. A. Karsdal, M. J. Nielsen, J. M. Sand, K. Henriksen, F. Genovese, A. C. Bay-Jensen, V. Smith, J. I. Adamkewicz, C. Christiansen, and D. J. Leeming, “Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure,” Assay Drug Dev. Technol. 11(2), 70–92 (2013).
[Crossref]

Schnelldorfer, T.

T. Schnelldorfer, “Image-enhanced laparoscopy: a promising technology for detection of peritoneal micrometastases,” Surgery 151(3), 345–350 (2012).
[Crossref]

Shanmugam, K.

R. M. Haralick, K. Shanmugam, and I. Dinstein, “Textural Features for Image Classification,” IEEE Trans. Syst., Man, Cybern. SMC-3(6), 610–621 (1973).
[Crossref]

Shen, H.

S. Cheng, Y. Lu, Y. Li, L. Gao, H. Shen, and K. Song, “Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal mesothelial cells,” Sci. Rep. 8(1), 5863 (2018).
[Crossref]

Smith, V.

M. A. Karsdal, M. J. Nielsen, J. M. Sand, K. Henriksen, F. Genovese, A. C. Bay-Jensen, V. Smith, J. I. Adamkewicz, C. Christiansen, and D. J. Leeming, “Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure,” Assay Drug Dev. Technol. 11(2), 70–92 (2013).
[Crossref]

So, P. T.

P. T. So, C. Y. Dong, B. R. Masters, and K. M. Berland, “Two-photon excitation fluorescence microscopy,” Annu. Rev. Biomed. Eng. 2(1), 399–429 (2000).
[Crossref]

Song, K.

S. Cheng, Y. Lu, Y. Li, L. Gao, H. Shen, and K. Song, “Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal mesothelial cells,” Sci. Rep. 8(1), 5863 (2018).
[Crossref]

Southard, T. L.

Stupinski, J. A.

Thiberville, L.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

Triveni, G. S.

S. H. Chandrashekhara, G. S. Triveni, and R. Kumar, “Imaging of peritoneal deposits in ovarian cancer: A pictorial review,” World J Radiol 8(5), 513–517 (2016).
[Crossref]

Tromberg, B. J.

D. Pouli, M. Balu, C. A. Alonzo, Z. Liu, K. P. Quinn, F. Rius-Diaz, R. M. Harris, K. M. Kelly, B. J. Tromberg, and I. Georgakoudi, “Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis,” Sci. Transl. Med. 8(367), 367ra169 (2016).
[Crossref]

Ushiki, T.

T. Ushiki, “Collagen fibers, reticular fibers and elastic fibers. A comprehensive understanding from a morphological viewpoint,” Arch. Histol. Cytol. 65(2), 109–126 (2002).
[Crossref]

Vever-Bizet, C.

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

Webb, W. W.

Weiss, R. S.

Williams, W. O.

D. G. Ouzounov, D. R. Rivera, W. O. Williams, J. A. Stupinski, T. L. Southard, K. H. Hume, J. Bentley, R. S. Weiss, W. W. Webb, and C. Xu, “Dual modality endomicroscope with optical zoom capability,” Biomed. Opt. Express 4(9), 1494–1503 (2013).
[Crossref]

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref]

Xu, C.

Xylas, J.

Am. J. Pathol. (1)

E. Lengyel, “Ovarian cancer development and metastasis,” Am. J. Pathol. 177(3), 1053–1064 (2010).
[Crossref]

Annu. Rev. Biomed. Eng. (2)

P. T. So, C. Y. Dong, B. R. Masters, and K. M. Berland, “Two-photon excitation fluorescence microscopy,” Annu. Rev. Biomed. Eng. 2(1), 399–429 (2000).
[Crossref]

I. Georgakoudi and K. P. Quinn, “Optical imaging using endogenous contrast to assess metabolic state,” Annu. Rev. Biomed. Eng. 14(1), 351–367 (2012).
[Crossref]

Arch. Histol. Cytol. (1)

T. Ushiki, “Collagen fibers, reticular fibers and elastic fibers. A comprehensive understanding from a morphological viewpoint,” Arch. Histol. Cytol. 65(2), 109–126 (2002).
[Crossref]

Assay Drug Dev. Technol. (1)

M. A. Karsdal, M. J. Nielsen, J. M. Sand, K. Henriksen, F. Genovese, A. C. Bay-Jensen, V. Smith, J. I. Adamkewicz, C. Christiansen, and D. J. Leeming, “Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure,” Assay Drug Dev. Technol. 11(2), 70–92 (2013).
[Crossref]

Biomed. Opt. Express (1)

Cancer Imaging (1)

C. M. Patel, A. Sahdev, and R. H. Reznek, “CT, MRI and PET imaging in peritoneal malignancy,” Cancer Imaging 11(1), 123–139 (2011).
[Crossref]

Cancer Inf. (1)

J. Adur, H. F. Carvalho, C. L. Cesar, and V. H. Casco, “Nonlinear optical microscopy signal processing strategies in cancer,” Cancer Inf. 13, CIN.S12419 (2014).
[Crossref]

Dis. Models Mech. (1)

T. R. Cox and J. T. Erler, “Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer,” Dis. Models Mech. 4(2), 165–178 (2011).
[Crossref]

IEEE Trans. Syst., Man, Cybern. (1)

R. M. Haralick, K. Shanmugam, and I. Dinstein, “Textural Features for Image Classification,” IEEE Trans. Syst., Man, Cybern. SMC-3(6), 610–621 (1973).
[Crossref]

Int J Gynecol Cancer (1)

P. Amate, C. Huchon, A. L. Dessapt, C. Bensaid, J. Medioni, M. A. Le Frere Belda, A. S. Bats, and F. R. Lecuru, “Ovarian cancer: sites of recurrence,” Int J Gynecol Cancer 23(9), 1590–1596 (2013).
[Crossref]

J. Biomed. Opt. (1)

C. M. Brown, D. R. Rivera, I. Pavlova, D. G. Ouzounov, W. O. Williams, S. Mohanan, W. W. Webb, and C. Xu, “In vivo imaging of unstained tissues using a compact and flexible multiphoton microendoscope,” J. Biomed. Opt. 17(4), 040505 (2012).
[Crossref]

Nagoya J Med Sci (1)

Y. Kodera, “Gastric cancer with minimal peritoneal metastasis: is this a sign to give up or to treat more aggressively?” Nagoya J Med Sci 75(1–2), 3–10 (2013).

Nat. Methods (1)

F. Helmchen and W. Denk, “Deep tissue two-photon microscopy,” Nat. Methods 2(12), 932–940 (2005).
[Crossref]

Opt. Express (1)

Opt. Lett. (1)

Sci. Rep. (2)

G. Ducourthial, P. Leclerc, T. Mansuryan, M. Fabert, J. Brevier, R. Habert, F. Braud, R. Batrin, C. Vever-Bizet, G. Bourg-Heckly, L. Thiberville, A. Druilhe, A. Kudlinski, and F. Louradour, “Development of a real-time flexible multiphoton microendoscope for label-free imaging in a live animal,” Sci. Rep. 5(1), 18303 (2015).
[Crossref]

S. Cheng, Y. Lu, Y. Li, L. Gao, H. Shen, and K. Song, “Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal mesothelial cells,” Sci. Rep. 8(1), 5863 (2018).
[Crossref]

Sci. Transl. Med. (1)

D. Pouli, M. Balu, C. A. Alonzo, Z. Liu, K. P. Quinn, F. Rius-Diaz, R. M. Harris, K. M. Kelly, B. J. Tromberg, and I. Georgakoudi, “Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis,” Sci. Transl. Med. 8(367), 367ra169 (2016).
[Crossref]

Surgery (1)

T. Schnelldorfer, “Image-enhanced laparoscopy: a promising technology for detection of peritoneal micrometastases,” Surgery 151(3), 345–350 (2012).
[Crossref]

World J Radiol (1)

S. H. Chandrashekhara, G. S. Triveni, and R. Kumar, “Imaging of peritoneal deposits in ovarian cancer: A pictorial review,” World J Radiol 8(5), 513–517 (2016).
[Crossref]

Other (2)

M. Hall-Beyer, “GLCM Texture: A Tutorial v. 3.0 March 2017,” (2017).

C. J. Huberty, S. Olejnik, and C. J. Huberty, Applied MANOVA and Discriminant Analysis, 2nd ed., Wiley Series in Probability and Statistics (Wiley-Interscience, 2006), pp. xxxiv.

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Figures (6)

Fig. 1.
Fig. 1. Cancer invasion alters tissue component constitution A. Examples of two-photon label-free images capturing SHG (pseudocolored green) and autofluorescence (pseudocolored red) signals for healthy parietal peritoneum and ovarian metastatic tissue. Signal overlay reveals spatial overlap of collagen SHG and fluorescence in healthy tissues, whereas destruction of matrix components by cancerous cellular infiltration is observed in metastasis. Insert in ovarian metastasis fluorescence image highlights the presence of cellular clusters (white arrows), identified by dark nuclei and bright cytoplasmic features. B. Quantification of image area coverage by automated image feature segmentation as shown in A. *denotes significance at a = 0.05 C-D. Examples of histological H&E microscopic images for each tissue group (C-Healthy,D-Metastasis). Black arrows indicate mesothelial surface while red arrows highlight infiltrative cancerous cellular clusters in the metastatic biopsy. Mesothelial cells were not typically recognized in the examined sections.
Fig. 2.
Fig. 2. Automated image contrast texture analysis. A. (top row) SHG and Fluorescence intensity images from healthy and metastatic parietal peritoneum. For all panels of top row, image heat maps reflect varying image intensities. A multicolor image heat map was employed here to better highlight visually the differences between the image intensities. Color and scale bars are the same for all images of the panel. (bottom row) Corresponding polar plots graphically depicting contrast values as a function of angle and distance. Hemi circle center corresponds to contrast values within 1-pixel distance and dotted concentric semicircles represent increasingly distances of 2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 25 pixels (1 pixel ≈1.2 microns). Plot heat maps reflect varying extracted contrast values. Color bars are the same for all plots of bottom row panel B. Mean contrast values averaged over all angles and distances for each tissue group. *denotes significance at a = 0.05
Fig. 3.
Fig. 3. Automated image correlation texture analysis of collagen associated areas. A. (top row) Representative SHG and fluorescence intensity images from healthy and metastatic parietal peritoneum as shown in Fig. 2(a) but processed to contain only collagen-SHG related information. For all panels, image heat maps reflect varying image intensities. Color and scale bars are the same for all images of the panel. (bottom row) Corresponding correlation plots graphically depicting correlation values as a function of increasing distance (1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20 and 25 pixels (1 pixel ≈1.2 microns). Asterisks and blue lines signify for each plot the distance where correlation declines to 50% of its initial value (D50) for this set of images. B. Mean D50 values from analysis of each type of image for the two tissue groups. *denotes significance at a = 0.05
Fig. 4.
Fig. 4. A. Plot of the canonical QDA discriminant scores showing the separation of the healthy (black; N = 8 participants; 30 sampled areas) and diseased metastatic (red; N = 4; 11 sampled areas) tissues, on the basis of the morphological tissue metrics extracted from SHG and Fluorescence image analysis as shown in Fig. 13. Each point represents one sampled area. Outer line ellipses represent 50% of data coverage. Crosses display group means and inner line ellipses indicate 95% confidence intervals for the mean of each tissue group respectively. As the two groups differ significantly, the confidence ellipses do not intersect B. Original classification outcomes presented based on the comparison of the QDA model predictions for the healthy and metastatic disease groups with corresponding histopathological evaluations and extracted accuracy, sensitivity and specificity outcomes.
Fig. 5.
Fig. 5. Automated image analysis steps for isolation of extracellular matrix associated features prior to textural correlation analysis. A. Example of unfiltered intensity image as shown in Fig. 3(a). This image will be utilized for textural contrast analysis B. Segmentation mask identifying ECM collagen positive associated features in green as also shown in Fig. 1(a). C. Segmented areas from raw image after application of segmentation mask. D. Final intensity image as shown in Fig. 3(a), after the automated digital object cloning (DOC) algorithm that utilizes the segmented areas in C. to fill any segmented voids produced by any non-ECM feature removal. This image will be finally utilized for the textural correlation analysis. These analytical steps were commonly used for isolation of the fibrillar collagen SHG-positive image signal in the SHG and fluorescence channels respectively. Scale bar (100 µm) is same for all images of figure and colorbar is same for images A,C and D.
Fig. 6.
Fig. 6. Scatterplot Matrix reporting covariances for each classification group and each pair of covariates. Observations vary differentially across classes and covariate pairs.