Abstract

Most oral injuries are diagnosed by histopathological analysis of a biopsy, which is an invasive procedure and does not give immediate results. On the other hand, Raman spectroscopy is a real time and minimally invasive analytical tool with potential for the diagnosis of diseases. The potential for diagnostics can be improved by data post-processing. Hence, this study aims to evaluate the performance of preprocessing steps and multivariate analysis methods for the classification of normal tissues and pathological oral lesion spectra. A total of 80 spectra acquired from normal and abnormal tissues using optical fiber Raman-based spectroscopy (OFRS) were subjected to PCA preprocessing in the z-scored data set, and the KNN (K-nearest neighbors), J48 (unpruned C4.5 decision tree), RBF (radial basis function), RF (random forest), and MLP (multilayer perceptron) classifiers at WEKA software (Waikato environment for knowledge analysis), after area normalization or maximum intensity normalization. Our results suggest the best classification was achieved by using maximum intensity normalization followed by MLP. Based on these results, software for automated analysis can be generated and validated using larger data sets. This would aid quick comprehension of spectroscopic data and easy diagnosis by medical practitioners in clinical settings.

© 2017 Optical Society of America

Full Article  |  PDF Article

Corrections

Luis Felipe C. S. Carvalho, Marcelo Saito Nogueira, Lázaro P. M. Neto, Tanmoy T. Bhattacharjee, and Airton A. Martin, "Raman spectral post-processing for oral tissue discrimination – a step for an automatized diagnostic system: erratum," Biomed. Opt. Express 9, 649-649 (2018)
https://www.osapublishing.org/boe/abstract.cfm?uri=boe-9-2-649
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References

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    [Crossref] [PubMed]
  4. L. F. Carvalho, T. Dreyer, J. Almeida, and H. Martinho, “Diagnosis of inflammatory lesions by high-wavenumber FT-IR spectroscopy,” in Latin America Optics and Photonics Conference,(Optical Society of America, 2012), LT4A. 3.
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    [Crossref] [PubMed]
  17. L. F. D. C. E. Silva, T. M. Pereira, T. D. Magrini, A. S. R. Cavalcante, H. D. S. Martinho, and J. D. Almeida, “Optical diagnosis of actinic cheilitis by infrared spectroscopy,” Photodiagn. Photodyn. Ther. 16, 27–34 (2016).
  18. F. Bonnier and H. J. Byrne, “Understanding the molecular information contained in principal component analysis of vibrational spectra of biological systems,” Analyst (Lond.) 137(2), 322–332 (2012).
    [Crossref] [PubMed]
  19. M. R. Guerra, C. M. Gallo, G. Mendonça, and G. Silva, “Risco de câncer no Brasil: tendências e estudos epidemiológicos mais recentes,” Rev. Bras. Cancerol. 51, 227–234 (2005).
  20. J. P. Fernandes, V. S. G. Brandão, and A. Lima, “Prevalência de lesões cancerizáveis bucais em indivíduos portadores de alcoolismo,” Rev. Bras. Cancerol. 54, 239–244 (2008).
  21. S. Duraipandian, W. Zheng, J. Ng, J. J. Low, A. Ilancheran, and Z. Huang, “In vivo diagnosis of cervical precancer using Raman spectroscopy and genetic algorithm techniques,” Analyst (Lond.) 136(20), 4328–4336 (2011).
    [Crossref] [PubMed]
  22. H. Lui, J. Zhao, D. McLean, and H. Zeng, “Real-time Raman spectroscopy for in vivo skin cancer diagnosis,” Cancer Res. 72(10), 2491–2500 (2012).
    [Crossref] [PubMed]
  23. A. T. Harris, M. Garg, X. B. Yang, S. E. Fisher, J. Kirkham, D. A. Smith, D. P. Martin-Hirsch, and A. S. High, “Raman spectroscopy and advanced mathematical modelling in the discrimination of human thyroid cell lines,” Head Neck Oncol. 1(1), 38 (2009).
    [Crossref] [PubMed]

2016 (6)

F. L. Cals, S. Koljenović, J. A. Hardillo, R. J. Baatenburg de Jong, T. C. Bakker Schut, and G. J. Puppels, “Development and validation of Raman spectroscopic classification models to discriminate tongue squamous cell carcinoma from non-tumorous tissue,” Oral Oncol. 60, 41–47 (2016).
[Crossref] [PubMed]

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

L. Hou, Y. Shi, G. Jiang, W. Liu, H. Han, Q. Feng, J. Ren, Y. Yuan, Y. Wang, J. Shi, and Z. Zhang, “Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery,” Nanotechnology 27(31), 315105 (2016).
[Crossref] [PubMed]

P.-H. Chen, R. Shimada, S. Yabumoto, H. Okajima, M. Ando, C.-T. Chang, L.-T. Lee, Y.-K. Wong, A. Chiou, and H. O. Hamaguchi, “Automatic and objective oral cancer diagnosis by Raman spectroscopic detection of keratin with multivariate curve resolution analysis,” Sci. Rep. 6(1), 20097 (2016).
[Crossref] [PubMed]

L. F. D. C. E. Silva, T. M. Pereira, T. D. Magrini, A. S. R. Cavalcante, H. D. S. Martinho, and J. D. Almeida, “Optical diagnosis of actinic cheilitis by infrared spectroscopy,” Photodiagn. Photodyn. Ther. 16, 27–34 (2016).

A. Cosci, M. S. Nogueira, S. Pratavieira, A. Takahama, R. S. Azevedo, and C. Kurachi, “Time-resolved fluorescence spectroscopy for clinical diagnosis of actinic cheilitis,” Biomed. Opt. Express 7(10), 4210–4219 (2016).
[Crossref] [PubMed]

2015 (2)

O. Warszawik-Hendzel, M. Olszewska, M. Maj, A. Rakowska, J. Czuwara, and L. Rudnicka, “Non-invasive diagnostic techniques in the diagnosis of squamous cell carcinoma,” J. Dermatol. Case Rep. 9(4), 89–97 (2015).
[Crossref] [PubMed]

L. F. C. Carvalho, F. Bonnier, K. O’Callaghan, J. O’Sullivan, S. Flint, H. J. Byrne, and F. M. Lyng, “Raman micro-spectroscopy for rapid screening of oral squamous cell carcinoma,” Exp. Mol. Pathol. 98(3), 502–509 (2015).
[Crossref] [PubMed]

2014 (1)

2012 (3)

H. Lui, J. Zhao, D. McLean, and H. Zeng, “Real-time Raman spectroscopy for in vivo skin cancer diagnosis,” Cancer Res. 72(10), 2491–2500 (2012).
[Crossref] [PubMed]

S. P. Singh, A. Deshmukh, P. Chaturvedi, and C. Murali Krishna, “In vivo Raman spectroscopic identification of premalignant lesions in oral buccal mucosa,” J. Biomed. Opt. 17(10), 0105002 (2012).
[Crossref] [PubMed]

F. Bonnier and H. J. Byrne, “Understanding the molecular information contained in principal component analysis of vibrational spectra of biological systems,” Analyst (Lond.) 137(2), 322–332 (2012).
[Crossref] [PubMed]

2011 (1)

S. Duraipandian, W. Zheng, J. Ng, J. J. Low, A. Ilancheran, and Z. Huang, “In vivo diagnosis of cervical precancer using Raman spectroscopy and genetic algorithm techniques,” Analyst (Lond.) 136(20), 4328–4336 (2011).
[Crossref] [PubMed]

2010 (1)

L. F. C. S. de Carvalho, R. A. Bitar, E. A. L. Arisawa, A. A. H. Brandão, K. M. Honório, L. A. G. Cabral, A. A. Martin, H. S. Martinho, and J. D. Almeida, “Spectral region optimization for Raman-based optical biopsy of inflammatory lesions,” Photomed. Laser Surg. 28(S1), S111–S117 (2010).
[Crossref] [PubMed]

2009 (1)

A. T. Harris, M. Garg, X. B. Yang, S. E. Fisher, J. Kirkham, D. A. Smith, D. P. Martin-Hirsch, and A. S. High, “Raman spectroscopy and advanced mathematical modelling in the discrimination of human thyroid cell lines,” Head Neck Oncol. 1(1), 38 (2009).
[Crossref] [PubMed]

2008 (2)

J. P. Fernandes, V. S. G. Brandão, and A. Lima, “Prevalência de lesões cancerizáveis bucais em indivíduos portadores de alcoolismo,” Rev. Bras. Cancerol. 54, 239–244 (2008).

C. Kurachi, C. R. Fontana, L. E. Rosa, and V. S. Bagnato, “Fluorescence spectroscopy for the detection of tongue carcinoma—validation in an animal model,” J. Biomed. Opt. 13, 0340182008).

2007 (1)

P. Holmstrup, P. Vedtofte, J. Reibel, and K. Stoltze, “Oral premalignant lesions: is a biopsy reliable?” J. Oral Pathol. Med. 36(5), 262–266 (2007).
[Crossref] [PubMed]

2006 (1)

B. Swinson, W. Jerjes, M. El-Maaytah, P. Norris, and C. Hopper, “Optical techniques in diagnosis of head and neck malignancy,” Oral Oncol. 42(3), 221–228 (2006).
[Crossref] [PubMed]

2005 (1)

M. R. Guerra, C. M. Gallo, G. Mendonça, and G. Silva, “Risco de câncer no Brasil: tendências e estudos epidemiológicos mais recentes,” Rev. Bras. Cancerol. 51, 227–234 (2005).

Almeida, J.

L. F. Carvalho, T. Dreyer, J. Almeida, and H. Martinho, “Diagnosis of inflammatory lesions by high-wavenumber FT-IR spectroscopy,” in Latin America Optics and Photonics Conference,(Optical Society of America, 2012), LT4A. 3.
[Crossref]

Almeida, J. D.

L. F. D. C. E. Silva, T. M. Pereira, T. D. Magrini, A. S. R. Cavalcante, H. D. S. Martinho, and J. D. Almeida, “Optical diagnosis of actinic cheilitis by infrared spectroscopy,” Photodiagn. Photodyn. Ther. 16, 27–34 (2016).

L. F. C. S. de Carvalho, R. A. Bitar, E. A. L. Arisawa, A. A. H. Brandão, K. M. Honório, L. A. G. Cabral, A. A. Martin, H. S. Martinho, and J. D. Almeida, “Spectral region optimization for Raman-based optical biopsy of inflammatory lesions,” Photomed. Laser Surg. 28(S1), S111–S117 (2010).
[Crossref] [PubMed]

Ando, M.

P.-H. Chen, R. Shimada, S. Yabumoto, H. Okajima, M. Ando, C.-T. Chang, L.-T. Lee, Y.-K. Wong, A. Chiou, and H. O. Hamaguchi, “Automatic and objective oral cancer diagnosis by Raman spectroscopic detection of keratin with multivariate curve resolution analysis,” Sci. Rep. 6(1), 20097 (2016).
[Crossref] [PubMed]

Arisawa, E. A. L.

L. F. C. S. de Carvalho, R. A. Bitar, E. A. L. Arisawa, A. A. H. Brandão, K. M. Honório, L. A. G. Cabral, A. A. Martin, H. S. Martinho, and J. D. Almeida, “Spectral region optimization for Raman-based optical biopsy of inflammatory lesions,” Photomed. Laser Surg. 28(S1), S111–S117 (2010).
[Crossref] [PubMed]

Azevedo, R. S.

Baatenburg de Jong, R. J.

F. L. Cals, S. Koljenović, J. A. Hardillo, R. J. Baatenburg de Jong, T. C. Bakker Schut, and G. J. Puppels, “Development and validation of Raman spectroscopic classification models to discriminate tongue squamous cell carcinoma from non-tumorous tissue,” Oral Oncol. 60, 41–47 (2016).
[Crossref] [PubMed]

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

Bagnato, V. S.

C. Kurachi, C. R. Fontana, L. E. Rosa, and V. S. Bagnato, “Fluorescence spectroscopy for the detection of tongue carcinoma—validation in an animal model,” J. Biomed. Opt. 13, 0340182008).

Bakker Schut, T. C.

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

F. L. Cals, S. Koljenović, J. A. Hardillo, R. J. Baatenburg de Jong, T. C. Bakker Schut, and G. J. Puppels, “Development and validation of Raman spectroscopic classification models to discriminate tongue squamous cell carcinoma from non-tumorous tissue,” Oral Oncol. 60, 41–47 (2016).
[Crossref] [PubMed]

Barroso, E. M.

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

Bitar, R. A.

L. F. C. S. de Carvalho, R. A. Bitar, E. A. L. Arisawa, A. A. H. Brandão, K. M. Honório, L. A. G. Cabral, A. A. Martin, H. S. Martinho, and J. D. Almeida, “Spectral region optimization for Raman-based optical biopsy of inflammatory lesions,” Photomed. Laser Surg. 28(S1), S111–S117 (2010).
[Crossref] [PubMed]

Bonnier, F.

L. F. C. Carvalho, F. Bonnier, K. O’Callaghan, J. O’Sullivan, S. Flint, H. J. Byrne, and F. M. Lyng, “Raman micro-spectroscopy for rapid screening of oral squamous cell carcinoma,” Exp. Mol. Pathol. 98(3), 502–509 (2015).
[Crossref] [PubMed]

F. Bonnier and H. J. Byrne, “Understanding the molecular information contained in principal component analysis of vibrational spectra of biological systems,” Analyst (Lond.) 137(2), 322–332 (2012).
[Crossref] [PubMed]

Brandão, A. A. H.

L. F. C. S. de Carvalho, R. A. Bitar, E. A. L. Arisawa, A. A. H. Brandão, K. M. Honório, L. A. G. Cabral, A. A. Martin, H. S. Martinho, and J. D. Almeida, “Spectral region optimization for Raman-based optical biopsy of inflammatory lesions,” Photomed. Laser Surg. 28(S1), S111–S117 (2010).
[Crossref] [PubMed]

Brandão, V. S. G.

J. P. Fernandes, V. S. G. Brandão, and A. Lima, “Prevalência de lesões cancerizáveis bucais em indivíduos portadores de alcoolismo,” Rev. Bras. Cancerol. 54, 239–244 (2008).

Byrne, H. J.

L. F. C. Carvalho, F. Bonnier, K. O’Callaghan, J. O’Sullivan, S. Flint, H. J. Byrne, and F. M. Lyng, “Raman micro-spectroscopy for rapid screening of oral squamous cell carcinoma,” Exp. Mol. Pathol. 98(3), 502–509 (2015).
[Crossref] [PubMed]

F. Bonnier and H. J. Byrne, “Understanding the molecular information contained in principal component analysis of vibrational spectra of biological systems,” Analyst (Lond.) 137(2), 322–332 (2012).
[Crossref] [PubMed]

Cabral, L. A. G.

L. F. C. S. de Carvalho, R. A. Bitar, E. A. L. Arisawa, A. A. H. Brandão, K. M. Honório, L. A. G. Cabral, A. A. Martin, H. S. Martinho, and J. D. Almeida, “Spectral region optimization for Raman-based optical biopsy of inflammatory lesions,” Photomed. Laser Surg. 28(S1), S111–S117 (2010).
[Crossref] [PubMed]

Cals, F. L.

F. L. Cals, S. Koljenović, J. A. Hardillo, R. J. Baatenburg de Jong, T. C. Bakker Schut, and G. J. Puppels, “Development and validation of Raman spectroscopic classification models to discriminate tongue squamous cell carcinoma from non-tumorous tissue,” Oral Oncol. 60, 41–47 (2016).
[Crossref] [PubMed]

Carvalho, L. F.

L. F. Carvalho, T. Dreyer, J. Almeida, and H. Martinho, “Diagnosis of inflammatory lesions by high-wavenumber FT-IR spectroscopy,” in Latin America Optics and Photonics Conference,(Optical Society of America, 2012), LT4A. 3.
[Crossref]

Carvalho, L. F. C.

L. F. C. Carvalho, F. Bonnier, K. O’Callaghan, J. O’Sullivan, S. Flint, H. J. Byrne, and F. M. Lyng, “Raman micro-spectroscopy for rapid screening of oral squamous cell carcinoma,” Exp. Mol. Pathol. 98(3), 502–509 (2015).
[Crossref] [PubMed]

Caspers, P. J.

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

Cavalcante, A. S. R.

L. F. D. C. E. Silva, T. M. Pereira, T. D. Magrini, A. S. R. Cavalcante, H. D. S. Martinho, and J. D. Almeida, “Optical diagnosis of actinic cheilitis by infrared spectroscopy,” Photodiagn. Photodyn. Ther. 16, 27–34 (2016).

Chang, C.-T.

P.-H. Chen, R. Shimada, S. Yabumoto, H. Okajima, M. Ando, C.-T. Chang, L.-T. Lee, Y.-K. Wong, A. Chiou, and H. O. Hamaguchi, “Automatic and objective oral cancer diagnosis by Raman spectroscopic detection of keratin with multivariate curve resolution analysis,” Sci. Rep. 6(1), 20097 (2016).
[Crossref] [PubMed]

Chaturvedi, P.

S. P. Singh, A. Deshmukh, P. Chaturvedi, and C. Murali Krishna, “In vivo Raman spectroscopic identification of premalignant lesions in oral buccal mucosa,” J. Biomed. Opt. 17(10), 0105002 (2012).
[Crossref] [PubMed]

Chen, P.-H.

P.-H. Chen, R. Shimada, S. Yabumoto, H. Okajima, M. Ando, C.-T. Chang, L.-T. Lee, Y.-K. Wong, A. Chiou, and H. O. Hamaguchi, “Automatic and objective oral cancer diagnosis by Raman spectroscopic detection of keratin with multivariate curve resolution analysis,” Sci. Rep. 6(1), 20097 (2016).
[Crossref] [PubMed]

Chiou, A.

P.-H. Chen, R. Shimada, S. Yabumoto, H. Okajima, M. Ando, C.-T. Chang, L.-T. Lee, Y.-K. Wong, A. Chiou, and H. O. Hamaguchi, “Automatic and objective oral cancer diagnosis by Raman spectroscopic detection of keratin with multivariate curve resolution analysis,” Sci. Rep. 6(1), 20097 (2016).
[Crossref] [PubMed]

Cosci, A.

Czuwara, J.

O. Warszawik-Hendzel, M. Olszewska, M. Maj, A. Rakowska, J. Czuwara, and L. Rudnicka, “Non-invasive diagnostic techniques in the diagnosis of squamous cell carcinoma,” J. Dermatol. Case Rep. 9(4), 89–97 (2015).
[Crossref] [PubMed]

de Carvalho, L. F. C. S.

L. F. C. S. de Carvalho, R. A. Bitar, E. A. L. Arisawa, A. A. H. Brandão, K. M. Honório, L. A. G. Cabral, A. A. Martin, H. S. Martinho, and J. D. Almeida, “Spectral region optimization for Raman-based optical biopsy of inflammatory lesions,” Photomed. Laser Surg. 28(S1), S111–S117 (2010).
[Crossref] [PubMed]

Deshmukh, A.

S. P. Singh, A. Deshmukh, P. Chaturvedi, and C. Murali Krishna, “In vivo Raman spectroscopic identification of premalignant lesions in oral buccal mucosa,” J. Biomed. Opt. 17(10), 0105002 (2012).
[Crossref] [PubMed]

Dreyer, T.

L. F. Carvalho, T. Dreyer, J. Almeida, and H. Martinho, “Diagnosis of inflammatory lesions by high-wavenumber FT-IR spectroscopy,” in Latin America Optics and Photonics Conference,(Optical Society of America, 2012), LT4A. 3.
[Crossref]

Duraipandian, S.

S. Duraipandian, W. Zheng, J. Ng, J. J. Low, A. Ilancheran, and Z. Huang, “In vivo diagnosis of cervical precancer using Raman spectroscopy and genetic algorithm techniques,” Analyst (Lond.) 136(20), 4328–4336 (2011).
[Crossref] [PubMed]

El-Maaytah, M.

B. Swinson, W. Jerjes, M. El-Maaytah, P. Norris, and C. Hopper, “Optical techniques in diagnosis of head and neck malignancy,” Oral Oncol. 42(3), 221–228 (2006).
[Crossref] [PubMed]

Feng, Q.

L. Hou, Y. Shi, G. Jiang, W. Liu, H. Han, Q. Feng, J. Ren, Y. Yuan, Y. Wang, J. Shi, and Z. Zhang, “Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery,” Nanotechnology 27(31), 315105 (2016).
[Crossref] [PubMed]

Fernandes, J. P.

J. P. Fernandes, V. S. G. Brandão, and A. Lima, “Prevalência de lesões cancerizáveis bucais em indivíduos portadores de alcoolismo,” Rev. Bras. Cancerol. 54, 239–244 (2008).

Fisher, S. E.

A. T. Harris, M. Garg, X. B. Yang, S. E. Fisher, J. Kirkham, D. A. Smith, D. P. Martin-Hirsch, and A. S. High, “Raman spectroscopy and advanced mathematical modelling in the discrimination of human thyroid cell lines,” Head Neck Oncol. 1(1), 38 (2009).
[Crossref] [PubMed]

Flint, S.

L. F. C. Carvalho, F. Bonnier, K. O’Callaghan, J. O’Sullivan, S. Flint, H. J. Byrne, and F. M. Lyng, “Raman micro-spectroscopy for rapid screening of oral squamous cell carcinoma,” Exp. Mol. Pathol. 98(3), 502–509 (2015).
[Crossref] [PubMed]

Fontana, C. R.

C. Kurachi, C. R. Fontana, L. E. Rosa, and V. S. Bagnato, “Fluorescence spectroscopy for the detection of tongue carcinoma—validation in an animal model,” J. Biomed. Opt. 13, 0340182008).

Gallo, C. M.

M. R. Guerra, C. M. Gallo, G. Mendonça, and G. Silva, “Risco de câncer no Brasil: tendências e estudos epidemiológicos mais recentes,” Rev. Bras. Cancerol. 51, 227–234 (2005).

Garg, M.

A. T. Harris, M. Garg, X. B. Yang, S. E. Fisher, J. Kirkham, D. A. Smith, D. P. Martin-Hirsch, and A. S. High, “Raman spectroscopy and advanced mathematical modelling in the discrimination of human thyroid cell lines,” Head Neck Oncol. 1(1), 38 (2009).
[Crossref] [PubMed]

Guerra, M. R.

M. R. Guerra, C. M. Gallo, G. Mendonça, and G. Silva, “Risco de câncer no Brasil: tendências e estudos epidemiológicos mais recentes,” Rev. Bras. Cancerol. 51, 227–234 (2005).

Hamaguchi, H. O.

P.-H. Chen, R. Shimada, S. Yabumoto, H. Okajima, M. Ando, C.-T. Chang, L.-T. Lee, Y.-K. Wong, A. Chiou, and H. O. Hamaguchi, “Automatic and objective oral cancer diagnosis by Raman spectroscopic detection of keratin with multivariate curve resolution analysis,” Sci. Rep. 6(1), 20097 (2016).
[Crossref] [PubMed]

Han, H.

L. Hou, Y. Shi, G. Jiang, W. Liu, H. Han, Q. Feng, J. Ren, Y. Yuan, Y. Wang, J. Shi, and Z. Zhang, “Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery,” Nanotechnology 27(31), 315105 (2016).
[Crossref] [PubMed]

Hardillo, J. A.

F. L. Cals, S. Koljenović, J. A. Hardillo, R. J. Baatenburg de Jong, T. C. Bakker Schut, and G. J. Puppels, “Development and validation of Raman spectroscopic classification models to discriminate tongue squamous cell carcinoma from non-tumorous tissue,” Oral Oncol. 60, 41–47 (2016).
[Crossref] [PubMed]

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

Harris, A. T.

A. T. Harris, M. Garg, X. B. Yang, S. E. Fisher, J. Kirkham, D. A. Smith, D. P. Martin-Hirsch, and A. S. High, “Raman spectroscopy and advanced mathematical modelling in the discrimination of human thyroid cell lines,” Head Neck Oncol. 1(1), 38 (2009).
[Crossref] [PubMed]

High, A. S.

A. T. Harris, M. Garg, X. B. Yang, S. E. Fisher, J. Kirkham, D. A. Smith, D. P. Martin-Hirsch, and A. S. High, “Raman spectroscopy and advanced mathematical modelling in the discrimination of human thyroid cell lines,” Head Neck Oncol. 1(1), 38 (2009).
[Crossref] [PubMed]

Holmstrup, P.

P. Holmstrup, P. Vedtofte, J. Reibel, and K. Stoltze, “Oral premalignant lesions: is a biopsy reliable?” J. Oral Pathol. Med. 36(5), 262–266 (2007).
[Crossref] [PubMed]

Honório, K. M.

L. F. C. S. de Carvalho, R. A. Bitar, E. A. L. Arisawa, A. A. H. Brandão, K. M. Honório, L. A. G. Cabral, A. A. Martin, H. S. Martinho, and J. D. Almeida, “Spectral region optimization for Raman-based optical biopsy of inflammatory lesions,” Photomed. Laser Surg. 28(S1), S111–S117 (2010).
[Crossref] [PubMed]

Hopper, C.

B. Swinson, W. Jerjes, M. El-Maaytah, P. Norris, and C. Hopper, “Optical techniques in diagnosis of head and neck malignancy,” Oral Oncol. 42(3), 221–228 (2006).
[Crossref] [PubMed]

Hou, L.

L. Hou, Y. Shi, G. Jiang, W. Liu, H. Han, Q. Feng, J. Ren, Y. Yuan, Y. Wang, J. Shi, and Z. Zhang, “Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery,” Nanotechnology 27(31), 315105 (2016).
[Crossref] [PubMed]

Huang, Z.

S. Duraipandian, W. Zheng, J. Ng, J. J. Low, A. Ilancheran, and Z. Huang, “In vivo diagnosis of cervical precancer using Raman spectroscopy and genetic algorithm techniques,” Analyst (Lond.) 136(20), 4328–4336 (2011).
[Crossref] [PubMed]

Ilancheran, A.

S. Duraipandian, W. Zheng, J. Ng, J. J. Low, A. Ilancheran, and Z. Huang, “In vivo diagnosis of cervical precancer using Raman spectroscopy and genetic algorithm techniques,” Analyst (Lond.) 136(20), 4328–4336 (2011).
[Crossref] [PubMed]

Jerjes, W.

B. Swinson, W. Jerjes, M. El-Maaytah, P. Norris, and C. Hopper, “Optical techniques in diagnosis of head and neck malignancy,” Oral Oncol. 42(3), 221–228 (2006).
[Crossref] [PubMed]

Jiang, G.

L. Hou, Y. Shi, G. Jiang, W. Liu, H. Han, Q. Feng, J. Ren, Y. Yuan, Y. Wang, J. Shi, and Z. Zhang, “Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery,” Nanotechnology 27(31), 315105 (2016).
[Crossref] [PubMed]

Kirkham, J.

A. T. Harris, M. Garg, X. B. Yang, S. E. Fisher, J. Kirkham, D. A. Smith, D. P. Martin-Hirsch, and A. S. High, “Raman spectroscopy and advanced mathematical modelling in the discrimination of human thyroid cell lines,” Head Neck Oncol. 1(1), 38 (2009).
[Crossref] [PubMed]

Koljenovic, S.

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

F. L. Cals, S. Koljenović, J. A. Hardillo, R. J. Baatenburg de Jong, T. C. Bakker Schut, and G. J. Puppels, “Development and validation of Raman spectroscopic classification models to discriminate tongue squamous cell carcinoma from non-tumorous tissue,” Oral Oncol. 60, 41–47 (2016).
[Crossref] [PubMed]

Kurachi, C.

Lee, L.-T.

P.-H. Chen, R. Shimada, S. Yabumoto, H. Okajima, M. Ando, C.-T. Chang, L.-T. Lee, Y.-K. Wong, A. Chiou, and H. O. Hamaguchi, “Automatic and objective oral cancer diagnosis by Raman spectroscopic detection of keratin with multivariate curve resolution analysis,” Sci. Rep. 6(1), 20097 (2016).
[Crossref] [PubMed]

Lima, A.

J. P. Fernandes, V. S. G. Brandão, and A. Lima, “Prevalência de lesões cancerizáveis bucais em indivíduos portadores de alcoolismo,” Rev. Bras. Cancerol. 54, 239–244 (2008).

Liu, W.

L. Hou, Y. Shi, G. Jiang, W. Liu, H. Han, Q. Feng, J. Ren, Y. Yuan, Y. Wang, J. Shi, and Z. Zhang, “Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery,” Nanotechnology 27(31), 315105 (2016).
[Crossref] [PubMed]

Low, J. J.

S. Duraipandian, W. Zheng, J. Ng, J. J. Low, A. Ilancheran, and Z. Huang, “In vivo diagnosis of cervical precancer using Raman spectroscopy and genetic algorithm techniques,” Analyst (Lond.) 136(20), 4328–4336 (2011).
[Crossref] [PubMed]

Lui, H.

H. Lui, J. Zhao, D. McLean, and H. Zeng, “Real-time Raman spectroscopy for in vivo skin cancer diagnosis,” Cancer Res. 72(10), 2491–2500 (2012).
[Crossref] [PubMed]

Lyng, F. M.

L. F. C. Carvalho, F. Bonnier, K. O’Callaghan, J. O’Sullivan, S. Flint, H. J. Byrne, and F. M. Lyng, “Raman micro-spectroscopy for rapid screening of oral squamous cell carcinoma,” Exp. Mol. Pathol. 98(3), 502–509 (2015).
[Crossref] [PubMed]

Magrini, T. D.

L. F. D. C. E. Silva, T. M. Pereira, T. D. Magrini, A. S. R. Cavalcante, H. D. S. Martinho, and J. D. Almeida, “Optical diagnosis of actinic cheilitis by infrared spectroscopy,” Photodiagn. Photodyn. Ther. 16, 27–34 (2016).

Maj, M.

O. Warszawik-Hendzel, M. Olszewska, M. Maj, A. Rakowska, J. Czuwara, and L. Rudnicka, “Non-invasive diagnostic techniques in the diagnosis of squamous cell carcinoma,” J. Dermatol. Case Rep. 9(4), 89–97 (2015).
[Crossref] [PubMed]

Martin, A. A.

L. F. C. S. de Carvalho, R. A. Bitar, E. A. L. Arisawa, A. A. H. Brandão, K. M. Honório, L. A. G. Cabral, A. A. Martin, H. S. Martinho, and J. D. Almeida, “Spectral region optimization for Raman-based optical biopsy of inflammatory lesions,” Photomed. Laser Surg. 28(S1), S111–S117 (2010).
[Crossref] [PubMed]

Martin-Hirsch, D. P.

A. T. Harris, M. Garg, X. B. Yang, S. E. Fisher, J. Kirkham, D. A. Smith, D. P. Martin-Hirsch, and A. S. High, “Raman spectroscopy and advanced mathematical modelling in the discrimination of human thyroid cell lines,” Head Neck Oncol. 1(1), 38 (2009).
[Crossref] [PubMed]

Martinho, H.

L. F. Carvalho, T. Dreyer, J. Almeida, and H. Martinho, “Diagnosis of inflammatory lesions by high-wavenumber FT-IR spectroscopy,” in Latin America Optics and Photonics Conference,(Optical Society of America, 2012), LT4A. 3.
[Crossref]

Martinho, H. D. S.

L. F. D. C. E. Silva, T. M. Pereira, T. D. Magrini, A. S. R. Cavalcante, H. D. S. Martinho, and J. D. Almeida, “Optical diagnosis of actinic cheilitis by infrared spectroscopy,” Photodiagn. Photodyn. Ther. 16, 27–34 (2016).

Martinho, H. S.

L. F. C. S. de Carvalho, R. A. Bitar, E. A. L. Arisawa, A. A. H. Brandão, K. M. Honório, L. A. G. Cabral, A. A. Martin, H. S. Martinho, and J. D. Almeida, “Spectral region optimization for Raman-based optical biopsy of inflammatory lesions,” Photomed. Laser Surg. 28(S1), S111–S117 (2010).
[Crossref] [PubMed]

Mast, H.

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

McLean, D.

H. Lui, J. Zhao, D. McLean, and H. Zeng, “Real-time Raman spectroscopy for in vivo skin cancer diagnosis,” Cancer Res. 72(10), 2491–2500 (2012).
[Crossref] [PubMed]

Meeuwis, C. A.

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

Mendonça, G.

M. R. Guerra, C. M. Gallo, G. Mendonça, and G. Silva, “Risco de câncer no Brasil: tendências e estudos epidemiológicos mais recentes,” Rev. Bras. Cancerol. 51, 227–234 (2005).

Moriyama, L. T.

Murali Krishna, C.

S. P. Singh, A. Deshmukh, P. Chaturvedi, and C. Murali Krishna, “In vivo Raman spectroscopic identification of premalignant lesions in oral buccal mucosa,” J. Biomed. Opt. 17(10), 0105002 (2012).
[Crossref] [PubMed]

Ng, J.

S. Duraipandian, W. Zheng, J. Ng, J. J. Low, A. Ilancheran, and Z. Huang, “In vivo diagnosis of cervical precancer using Raman spectroscopy and genetic algorithm techniques,” Analyst (Lond.) 136(20), 4328–4336 (2011).
[Crossref] [PubMed]

Nogueira, M. S.

Noordhoek Hegt, V.

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

Norris, P.

B. Swinson, W. Jerjes, M. El-Maaytah, P. Norris, and C. Hopper, “Optical techniques in diagnosis of head and neck malignancy,” Oral Oncol. 42(3), 221–228 (2006).
[Crossref] [PubMed]

O’Callaghan, K.

L. F. C. Carvalho, F. Bonnier, K. O’Callaghan, J. O’Sullivan, S. Flint, H. J. Byrne, and F. M. Lyng, “Raman micro-spectroscopy for rapid screening of oral squamous cell carcinoma,” Exp. Mol. Pathol. 98(3), 502–509 (2015).
[Crossref] [PubMed]

O’Sullivan, J.

L. F. C. Carvalho, F. Bonnier, K. O’Callaghan, J. O’Sullivan, S. Flint, H. J. Byrne, and F. M. Lyng, “Raman micro-spectroscopy for rapid screening of oral squamous cell carcinoma,” Exp. Mol. Pathol. 98(3), 502–509 (2015).
[Crossref] [PubMed]

Okajima, H.

P.-H. Chen, R. Shimada, S. Yabumoto, H. Okajima, M. Ando, C.-T. Chang, L.-T. Lee, Y.-K. Wong, A. Chiou, and H. O. Hamaguchi, “Automatic and objective oral cancer diagnosis by Raman spectroscopic detection of keratin with multivariate curve resolution analysis,” Sci. Rep. 6(1), 20097 (2016).
[Crossref] [PubMed]

Olszewska, M.

O. Warszawik-Hendzel, M. Olszewska, M. Maj, A. Rakowska, J. Czuwara, and L. Rudnicka, “Non-invasive diagnostic techniques in the diagnosis of squamous cell carcinoma,” J. Dermatol. Case Rep. 9(4), 89–97 (2015).
[Crossref] [PubMed]

Pereira, T. M.

L. F. D. C. E. Silva, T. M. Pereira, T. D. Magrini, A. S. R. Cavalcante, H. D. S. Martinho, and J. D. Almeida, “Optical diagnosis of actinic cheilitis by infrared spectroscopy,” Photodiagn. Photodyn. Ther. 16, 27–34 (2016).

Pires, L.

Pratavieira, S.

Puppels, G. J.

F. L. Cals, S. Koljenović, J. A. Hardillo, R. J. Baatenburg de Jong, T. C. Bakker Schut, and G. J. Puppels, “Development and validation of Raman spectroscopic classification models to discriminate tongue squamous cell carcinoma from non-tumorous tissue,” Oral Oncol. 60, 41–47 (2016).
[Crossref] [PubMed]

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

Rakowska, A.

O. Warszawik-Hendzel, M. Olszewska, M. Maj, A. Rakowska, J. Czuwara, and L. Rudnicka, “Non-invasive diagnostic techniques in the diagnosis of squamous cell carcinoma,” J. Dermatol. Case Rep. 9(4), 89–97 (2015).
[Crossref] [PubMed]

Reibel, J.

P. Holmstrup, P. Vedtofte, J. Reibel, and K. Stoltze, “Oral premalignant lesions: is a biopsy reliable?” J. Oral Pathol. Med. 36(5), 262–266 (2007).
[Crossref] [PubMed]

Ren, J.

L. Hou, Y. Shi, G. Jiang, W. Liu, H. Han, Q. Feng, J. Ren, Y. Yuan, Y. Wang, J. Shi, and Z. Zhang, “Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery,” Nanotechnology 27(31), 315105 (2016).
[Crossref] [PubMed]

Rosa, L. E.

C. Kurachi, C. R. Fontana, L. E. Rosa, and V. S. Bagnato, “Fluorescence spectroscopy for the detection of tongue carcinoma—validation in an animal model,” J. Biomed. Opt. 13, 0340182008).

Rudnicka, L.

O. Warszawik-Hendzel, M. Olszewska, M. Maj, A. Rakowska, J. Czuwara, and L. Rudnicka, “Non-invasive diagnostic techniques in the diagnosis of squamous cell carcinoma,” J. Dermatol. Case Rep. 9(4), 89–97 (2015).
[Crossref] [PubMed]

Sewnaik, A.

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

Shi, J.

L. Hou, Y. Shi, G. Jiang, W. Liu, H. Han, Q. Feng, J. Ren, Y. Yuan, Y. Wang, J. Shi, and Z. Zhang, “Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery,” Nanotechnology 27(31), 315105 (2016).
[Crossref] [PubMed]

Shi, Y.

L. Hou, Y. Shi, G. Jiang, W. Liu, H. Han, Q. Feng, J. Ren, Y. Yuan, Y. Wang, J. Shi, and Z. Zhang, “Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery,” Nanotechnology 27(31), 315105 (2016).
[Crossref] [PubMed]

Shimada, R.

P.-H. Chen, R. Shimada, S. Yabumoto, H. Okajima, M. Ando, C.-T. Chang, L.-T. Lee, Y.-K. Wong, A. Chiou, and H. O. Hamaguchi, “Automatic and objective oral cancer diagnosis by Raman spectroscopic detection of keratin with multivariate curve resolution analysis,” Sci. Rep. 6(1), 20097 (2016).
[Crossref] [PubMed]

Silva, G.

M. R. Guerra, C. M. Gallo, G. Mendonça, and G. Silva, “Risco de câncer no Brasil: tendências e estudos epidemiológicos mais recentes,” Rev. Bras. Cancerol. 51, 227–234 (2005).

Silva, L. F. D. C. E.

L. F. D. C. E. Silva, T. M. Pereira, T. D. Magrini, A. S. R. Cavalcante, H. D. S. Martinho, and J. D. Almeida, “Optical diagnosis of actinic cheilitis by infrared spectroscopy,” Photodiagn. Photodyn. Ther. 16, 27–34 (2016).

Singh, S. P.

S. P. Singh, A. Deshmukh, P. Chaturvedi, and C. Murali Krishna, “In vivo Raman spectroscopic identification of premalignant lesions in oral buccal mucosa,” J. Biomed. Opt. 17(10), 0105002 (2012).
[Crossref] [PubMed]

Smith, D. A.

A. T. Harris, M. Garg, X. B. Yang, S. E. Fisher, J. Kirkham, D. A. Smith, D. P. Martin-Hirsch, and A. S. High, “Raman spectroscopy and advanced mathematical modelling in the discrimination of human thyroid cell lines,” Head Neck Oncol. 1(1), 38 (2009).
[Crossref] [PubMed]

Smits, R. W.

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

Stoltze, K.

P. Holmstrup, P. Vedtofte, J. Reibel, and K. Stoltze, “Oral premalignant lesions: is a biopsy reliable?” J. Oral Pathol. Med. 36(5), 262–266 (2007).
[Crossref] [PubMed]

Swinson, B.

B. Swinson, W. Jerjes, M. El-Maaytah, P. Norris, and C. Hopper, “Optical techniques in diagnosis of head and neck malignancy,” Oral Oncol. 42(3), 221–228 (2006).
[Crossref] [PubMed]

Takahama, A.

Ten Hove, I.

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

van Lanschot, C. G.

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

Vedtofte, P.

P. Holmstrup, P. Vedtofte, J. Reibel, and K. Stoltze, “Oral premalignant lesions: is a biopsy reliable?” J. Oral Pathol. Med. 36(5), 262–266 (2007).
[Crossref] [PubMed]

Verdijk, R.

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

Wang, Y.

L. Hou, Y. Shi, G. Jiang, W. Liu, H. Han, Q. Feng, J. Ren, Y. Yuan, Y. Wang, J. Shi, and Z. Zhang, “Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery,” Nanotechnology 27(31), 315105 (2016).
[Crossref] [PubMed]

Warszawik-Hendzel, O.

O. Warszawik-Hendzel, M. Olszewska, M. Maj, A. Rakowska, J. Czuwara, and L. Rudnicka, “Non-invasive diagnostic techniques in the diagnosis of squamous cell carcinoma,” J. Dermatol. Case Rep. 9(4), 89–97 (2015).
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L. Hou, Y. Shi, G. Jiang, W. Liu, H. Han, Q. Feng, J. Ren, Y. Yuan, Y. Wang, J. Shi, and Z. Zhang, “Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery,” Nanotechnology 27(31), 315105 (2016).
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L. Hou, Y. Shi, G. Jiang, W. Liu, H. Han, Q. Feng, J. Ren, Y. Yuan, Y. Wang, J. Shi, and Z. Zhang, “Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery,” Nanotechnology 27(31), 315105 (2016).
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Analyst (Lond.) (2)

S. Duraipandian, W. Zheng, J. Ng, J. J. Low, A. Ilancheran, and Z. Huang, “In vivo diagnosis of cervical precancer using Raman spectroscopy and genetic algorithm techniques,” Analyst (Lond.) 136(20), 4328–4336 (2011).
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F. Bonnier and H. J. Byrne, “Understanding the molecular information contained in principal component analysis of vibrational spectra of biological systems,” Analyst (Lond.) 137(2), 322–332 (2012).
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Biomed. Opt. Express (2)

Cancer Res. (2)

H. Lui, J. Zhao, D. McLean, and H. Zeng, “Real-time Raman spectroscopy for in vivo skin cancer diagnosis,” Cancer Res. 72(10), 2491–2500 (2012).
[Crossref] [PubMed]

E. M. Barroso, R. W. Smits, C. G. van Lanschot, P. J. Caspers, I. Ten Hove, H. Mast, A. Sewnaik, J. A. Hardillo, C. A. Meeuwis, R. Verdijk, V. Noordhoek Hegt, R. J. Baatenburg de Jong, E. B. Wolvius, T. C. Bakker Schut, S. Koljenović, and G. J. Puppels, “Water concentration analysis by Raman spectroscopy to determine the location of the tumor border in oral cancer surgery,” Cancer Res. 76(20), 5945–5953 (2016).
[Crossref] [PubMed]

Exp. Mol. Pathol. (1)

L. F. C. Carvalho, F. Bonnier, K. O’Callaghan, J. O’Sullivan, S. Flint, H. J. Byrne, and F. M. Lyng, “Raman micro-spectroscopy for rapid screening of oral squamous cell carcinoma,” Exp. Mol. Pathol. 98(3), 502–509 (2015).
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A. T. Harris, M. Garg, X. B. Yang, S. E. Fisher, J. Kirkham, D. A. Smith, D. P. Martin-Hirsch, and A. S. High, “Raman spectroscopy and advanced mathematical modelling in the discrimination of human thyroid cell lines,” Head Neck Oncol. 1(1), 38 (2009).
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J. Biomed. Opt. (2)

S. P. Singh, A. Deshmukh, P. Chaturvedi, and C. Murali Krishna, “In vivo Raman spectroscopic identification of premalignant lesions in oral buccal mucosa,” J. Biomed. Opt. 17(10), 0105002 (2012).
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O. Warszawik-Hendzel, M. Olszewska, M. Maj, A. Rakowska, J. Czuwara, and L. Rudnicka, “Non-invasive diagnostic techniques in the diagnosis of squamous cell carcinoma,” J. Dermatol. Case Rep. 9(4), 89–97 (2015).
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Nanotechnology (1)

L. Hou, Y. Shi, G. Jiang, W. Liu, H. Han, Q. Feng, J. Ren, Y. Yuan, Y. Wang, J. Shi, and Z. Zhang, “Smart nanocomposite hydrogels based on azo crosslinked graphene oxide for oral colon-specific drug delivery,” Nanotechnology 27(31), 315105 (2016).
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F. L. Cals, S. Koljenović, J. A. Hardillo, R. J. Baatenburg de Jong, T. C. Bakker Schut, and G. J. Puppels, “Development and validation of Raman spectroscopic classification models to discriminate tongue squamous cell carcinoma from non-tumorous tissue,” Oral Oncol. 60, 41–47 (2016).
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L. F. C. S. de Carvalho, R. A. Bitar, E. A. L. Arisawa, A. A. H. Brandão, K. M. Honório, L. A. G. Cabral, A. A. Martin, H. S. Martinho, and J. D. Almeida, “Spectral region optimization for Raman-based optical biopsy of inflammatory lesions,” Photomed. Laser Surg. 28(S1), S111–S117 (2010).
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Sci. Rep. (1)

P.-H. Chen, R. Shimada, S. Yabumoto, H. Okajima, M. Ando, C.-T. Chang, L.-T. Lee, Y.-K. Wong, A. Chiou, and H. O. Hamaguchi, “Automatic and objective oral cancer diagnosis by Raman spectroscopic detection of keratin with multivariate curve resolution analysis,” Sci. Rep. 6(1), 20097 (2016).
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S. A. Mian, C. Yorucu, M. S. Ullah, I. U. Rehman, and H. E. Colley, “Raman spectroscopy can discriminate between normal, dysplastic and cancerous oral mucosa: a tissue-engineering approach,” J. Tissue Eng. Regen. Med., published ahead of print doi: 10.1002/term.2234 (2016).

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Figures (5)

Fig. 1
Fig. 1 Mean spectra of pathological and normal tissues for Raman spectra normalized by the intensity maximum of each spectrum (A) and by area of each spectrum (B).

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Fig. 2
Fig. 2 Plot of PC2 loadings for Raman spectra normalized by the intensity maximum or by area. The behavior of loadings is mostly different from 900 cm−1 to 1600 cm−1 range.

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Fig. 3
Fig. 3 Plot of PC3 loadings for Raman spectra normalized by the intensity maximum or by area. The behavior of loadings is mostly different from 900 cm−1 to 1600 cm−1 range.

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Fig. 4
Fig. 4 PCA Scores plot for Raman spectra A) normalized by the area under the spectrum (PC2 x PC5 x PC6) and B) normalized by the intensity maximum (PC2 x PC3 x PC5). Although we do not observe a good discrimination only by using three parameters, we achieved very good values of sensitivity and specificity when using classification methods for twenty one or more parameters.

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Fig. 5
Fig. 5 ROC curves for normal tissue when using A) RSNIM parameters and B) PCA parameters of RSNIM.

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Tables (3)

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Table 1 Types of normalization, parameters and classifiers used for classification, where RSNAS is Raman Spectra Normalized by the Area of Spectrum and RSNIM is Raman Spectra Normalized by the Intensity Maximum

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Table 2 Confusion matrices and the Area Under the Receiver Operating Characteristic curve (AUROC) for the classification of the Raman Spectra Normalized by the Area of Spectrum (RSNAS) and the Raman Spectra Normalized by Intensity Maximum (RSNIM) using the PCA parameters or the full spectrum.

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Table 3 Overall accuracy of the different statistical analyses used in this study

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