Abstract

In this study, we demonstrated the feasibility of using a handheld optical coherence tomography (OCT) for in vivo visualizations of the microstructural and microvascular features of various oral mucosal types. To scan arbitrary locations of the oral mucosa, a scanning probe was developed, composed of a probe body fabricated by a 3D printer, miniaturized two-axis galvanometer, relay lenses, and reflective prism. With a 3D printing technique, the probe weight and the system volume were greatly reduced, enabling the effective improvement of imaging artifacts from unconscious motion and system complexity. Additionally, in our design, the distal end of the probe can be switched to fit various oral conditions, and the optical parameters of the probe, such as the transverse resolution, working distance, and probe length can be easily varied. The results showed that the epithelium and lamina propria layers, as well as the fungiform papilla and salivary gland, were differentiated. Moreover, various microcirculation features at different mucosal sites were identified that are potentially effective indicators for the diagnosis of premalignant lesions. The demonstrated results indicate that the developed OCT system is a promising tool for noninvasive imaging of oral mucosae.

© 2017 Optical Society of America

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References

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2017 (1)

2016 (1)

2015 (2)

A. M. Lee, L. Cahill, K. Liu, C. MacAulay, C. Poh, and P. Lane, “Wide-field in vivo oral OCT imaging,” Biomed. Opt. Express 6(7), 2664–2674 (2015).
[PubMed]

R. L. Siegel, K. D. Miller, and A. Jemal, “Cancer statistics, 2015,” CA Cancer J. Clin. 65(1), 5–29 (2015).
[PubMed]

2014 (6)

M. T. Tsai and M. C. Chan, “Simultaneous 0.8, 1.0, and 1.3 μm multispectral and common-path broadband source for optical coherence tomography,” Opt. Lett. 39(4), 865–868 (2014).
[PubMed]

D. Nankivil, A. H. Dhalla, N. Gahm, K. Shia, S. Farsiu, and J. A. Izatt, “Coherence revival multiplexed, buffered swept source optical coherence tomography: 400 kHz imaging with a 100 kHz source,” Opt. Lett. 39(13), 3740–3743 (2014).
[PubMed]

W. J. Choi and R. K. Wang, “In vivo imaging of functional microvasculature within tissue beds of oral and nasal cavities by swept-source optical coherence tomography with a forward/side-viewing probe,” Biomed. Opt. Express 5(8), 2620–2634 (2014).
[PubMed]

H. Pahlevaninezhad, A. M. Lee, T. Shaipanich, R. Raizada, L. Cahill, G. Hohert, V. X. Yang, S. Lam, C. MacAulay, and P. Lane, “A high-efficiency fiber-based imaging system for co-registered autofluorescence and optical coherence tomography,” Biomed. Opt. Express 5(9), 2978–2987 (2014).
[PubMed]

J. M. Jabbour, J. L. Bentley, B. H. Malik, J. Nemechek, J. Warda, R. Cuenca, S. Cheng, J. A. Jo, and K. C. Maitland, “Reflectance confocal endomicroscope with optical axial scanning for in vivo imaging of the oral mucosa,” Biomed. Opt. Express 5(11), 3781–3791 (2014).
[PubMed]

C. H. Yang, M. T. Tsai, S. C. Shen, C. Y. Ng, and S. M. Jung, “Feasibility of ablative fractional laser-assisted drug delivery with optical coherence tomography,” Biomed. Opt. Express 5(11), 3949–3959 (2014).
[PubMed]

2013 (6)

R. Djaberi, J. D. Schuijf, E. J. de Koning, D. C. Wijewickrama, A. M. Pereira, J. W. Smit, L. J. Kroft, Ad. Roos, J. J. Bax, T. J. Rabelink, and J. W. Jukema, “Non-invasive assessment of microcirculation by sidestream dark field imaging as a marker of coronary artery disease in diabetes,” Diab. Vasc. Dis. Res. 10(2), 123–134 (2013).
[PubMed]

E. A. Naumova, T. Dierkes, J. Sprang, and W. H. Arnold, “The oral mucosal surface and blood vessels,” Head Face Med. 9, 8 (2013).
[PubMed]

M. S. Mahmud, D. W. Cadotte, B. Vuong, C. Sun, T. W. Luk, A. Mariampillai, and V. X. Yang, “Review of speckle and phase variance optical coherence tomography to visualize microvascular networks,” J. Biomed. Opt. 18(5), 50901 (2013).
[PubMed]

I. Grulkowski, J. J. Liu, B. Potsaid, V. Jayaraman, J. Jiang, J. G. Fujimoto, and A. E. Cable, “High-precision, high-accuracy ultralong-range swept-source optical coherence tomography using vertical cavity surface emitting laser light source,” Opt. Lett. 38(5), 673–675 (2013).
[PubMed]

H. Fatakdawala, S. Poti, F. Zhou, Y. Sun, J. Bec, J. Liu, D. R. Yankelevich, S. P. Tinling, R. F. Gandour-Edwards, D. G. Farwell, and L. Marcu, “Multimodal in vivo imaging of oral cancer using fluorescence lifetime, photoacoustic and ultrasound techniques,” Biomed. Opt. Express 4(9), 1724–1741 (2013).
[PubMed]

C. D. Lu, M. F. Kraus, B. Potsaid, J. J. Liu, W. Choi, V. Jayaraman, A. E. Cable, J. Hornegger, J. S. Duker, and J. G. Fujimoto, “Handheld ultrahigh speed swept source optical coherence tomography instrument using a MEMS scanning mirror,” Biomed. Opt. Express 5(1), 293–311 (2013).
[PubMed]

2012 (4)

B. Davoudi, A. Lindenmaier, B. A. Standish, G. Allo, K. Bizheva, and A. Vitkin, “Noninvasive in vivo structural and vascular imaging of human oral tissues with spectral domain optical coherence tomography,” Biomed. Opt. Express 3(5), 826–839 (2012).
[PubMed]

R. Cernat, T. S. Tatla, J. Pang, P. J. Tadrous, A. Bradu, G. Dobre, G. Gelikonov, V. Gelikonov, and A. G. Podoleanu, “Dual instrument for in vivo and ex vivo OCT imaging in an ENT department,” Biomed. Opt. Express 3(12), 3346–3356 (2012).
[PubMed]

G. A. Scardina and P. Messina, “Oral microcirculation in post-menopause: a possible correlation with periodontitis,” Gerodontology 29(2), e1045–e1051 (2012).
[PubMed]

M. R. Tsai, D. B. Shieh, P. J. Lou, C. F. Lin, and C. K. Sun, “Characterization of oral squamous cell carcinoma based on higher-harmonic generation microscopy,” J. Biophotonics 5(5-6), 415–424 (2012).
[PubMed]

2011 (6)

A. G. Ammer, K. E. Hayes, K. H. Martin, L. Zhang, G. A. Spirou, and S. A. Weed, “Multi-photon imaging of tumor cell invasion in an orthotopic mouse model of oral squamous cell carcinoma,” J. Vis. Exp. 53, e2941 (2011).

E. Jonathan, J. Enfield, and M. J. Leahy, “Correlation mapping method for generating microcirculation morphology from optical coherence tomography (OCT) intensity images,” J. Biophotonics 4(9), 583–587 (2011).
[PubMed]

J. Enfield, E. Jonathan, and M. Leahy, “In vivo imaging of the microcirculation of the volar forearm using correlation mapping optical coherence tomography (cmOCT),” Biomed. Opt. Express 2(5), 1184–1193 (2011).
[PubMed]

G. Liu, L. Chou, W. Jia, W. Qi, B. Choi, and Z. Chen, “Intensity-based modified Doppler variance algorithm: application to phase instable and phase stable optical coherence tomography systems,” Opt. Express 19(12), 11429–11440 (2011).
[PubMed]

L. An, P. Li, T. T. Shen, and R. Wang, “High speed spectral domain optical coherence tomography for retinal imaging at 500,000 A‑lines per second,” Biomed. Opt. Express 2(10), 2770–2783 (2011).
[PubMed]

W. Jung, J. Kim, M. Jeon, E. J. Chaney, C. N. Stewart, and S. A. Boppart, “Handheld optical coherence tomography scanner for primary care diagnostics,” IEEE Trans. Biomed. Eng. 58(3), 741–744 (2011).
[PubMed]

2010 (2)

2008 (3)

2006 (1)

J. M. Ridgway, W. B. Armstrong, S. Guo, U. Mahmood, J. Su, R. P. Jackson, T. Shibuya, R. L. Crumley, M. Gu, Z. Chen, and B. J. Wong, “In vivo optical coherence tomography of the human oral cavity and oropharynx,” Arch. Otolaryngol. Head Neck Surg. 132(10), 1074–1081 (2006).
[PubMed]

2005 (2)

W. Jung, J. Zhang, J. Chung, P. Wilder-Smith, M. Brenner, J. S. Nelson, and Z. Chen, “Advances in oral cancer detection using optical coherence tomography,” IEEE J. Sel. Top. Quantum Electron. 11(4), 811–817 (2005).

P. Wilder-Smith, T. Krasieva, W. G. Jung, J. Zhang, Z. Chen, K. Osann, and B. Tromberg, “Noninvasive imaging of oral premalignancy and malignancy,” J. Biomed. Opt. 10(5), 051601 (2005).
[PubMed]

2004 (1)

P. Wilder-Smith, W. G. Jung, M. Brenner, K. Osann, H. Beydoun, D. Messadi, and Z. Chen, “In vivo optical coherence tomography for the diagnosis of oral malignancy,” Lasers Surg. Med. 35(4), 269–275 (2004).
[PubMed]

2003 (1)

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal Microscopy for Real-Time Detection of Oral Cavity Neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

2002 (1)

2001 (2)

C. A. Squier and M. J. Kremer, “Biology of Oral Mucosa and Esophagus,” J. Natl. Cancer Inst. Monogr. 2001(29), 7–15 (2001).
[PubMed]

M. Lingen, E. M. Sturgis, and M. S. Kies, “Squamous cell carcinoma of the head and neck in nonsmokers: clinical and biologic characteristics and implications for management,” Curr. Opin. Oncol. 13(3), 176–182 (2001).
[PubMed]

2000 (1)

G. W. Gynther, B. Rozell, and A. Heimdahl, “Direct oral microscopy and its value in diagnosing mucosal lesions: A pilot study,” Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 90(2), 164–170 (2000).
[PubMed]

1997 (1)

L. L. Gleich, P. W. Biddinger, F. D. Duperier, and J. L. Gluckman, “Tumor angiogenesis as a prognostic indicator in T2-T4 oral cavity squamous cell carcinoma: A clinical-pathologic correlation,” Head Neck 19(4), 276–280 (1997).
[PubMed]

1996 (1)

L. L. Gleich, P. W. Biddinger, Z. P. Pavelic, and J. L. Gluckman, “Tumor angiogenesis in T1 oral cavity squamous cell carcinoma: Role in predicting tumor aggressiveness,” Head Neck 18(4), 343–346 (1996).
[PubMed]

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[PubMed]

1988 (1)

S. Silverman., “Early diagnosis of oral cancer,” Cancer 62(8Suppl), 1796–1799 (1988).
[PubMed]

Alizadeh-Naderi, R.

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal Microscopy for Real-Time Detection of Oral Cavity Neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

Allo, G.

Ammer, A. G.

A. G. Ammer, K. E. Hayes, K. H. Martin, L. Zhang, G. A. Spirou, and S. A. Weed, “Multi-photon imaging of tumor cell invasion in an orthotopic mouse model of oral squamous cell carcinoma,” J. Vis. Exp. 53, e2941 (2011).

An, L.

Armstrong, W. B.

J. M. Ridgway, W. B. Armstrong, S. Guo, U. Mahmood, J. Su, R. P. Jackson, T. Shibuya, R. L. Crumley, M. Gu, Z. Chen, and B. J. Wong, “In vivo optical coherence tomography of the human oral cavity and oropharynx,” Arch. Otolaryngol. Head Neck Surg. 132(10), 1074–1081 (2006).
[PubMed]

Arnold, W. H.

E. A. Naumova, T. Dierkes, J. Sprang, and W. H. Arnold, “The oral mucosal surface and blood vessels,” Head Face Med. 9, 8 (2013).
[PubMed]

Bax, J. J.

R. Djaberi, J. D. Schuijf, E. J. de Koning, D. C. Wijewickrama, A. M. Pereira, J. W. Smit, L. J. Kroft, Ad. Roos, J. J. Bax, T. J. Rabelink, and J. W. Jukema, “Non-invasive assessment of microcirculation by sidestream dark field imaging as a marker of coronary artery disease in diabetes,” Diab. Vasc. Dis. Res. 10(2), 123–134 (2013).
[PubMed]

Bec, J.

Bentley, J. L.

Beydoun, H.

P. Wilder-Smith, W. G. Jung, M. Brenner, K. Osann, H. Beydoun, D. Messadi, and Z. Chen, “In vivo optical coherence tomography for the diagnosis of oral malignancy,” Lasers Surg. Med. 35(4), 269–275 (2004).
[PubMed]

Biddinger, P. W.

L. L. Gleich, P. W. Biddinger, F. D. Duperier, and J. L. Gluckman, “Tumor angiogenesis as a prognostic indicator in T2-T4 oral cavity squamous cell carcinoma: A clinical-pathologic correlation,” Head Neck 19(4), 276–280 (1997).
[PubMed]

L. L. Gleich, P. W. Biddinger, Z. P. Pavelic, and J. L. Gluckman, “Tumor angiogenesis in T1 oral cavity squamous cell carcinoma: Role in predicting tumor aggressiveness,” Head Neck 18(4), 343–346 (1996).
[PubMed]

Bizheva, K.

Boppart, S. A.

W. Jung, J. Kim, M. Jeon, E. J. Chaney, C. N. Stewart, and S. A. Boppart, “Handheld optical coherence tomography scanner for primary care diagnostics,” IEEE Trans. Biomed. Eng. 58(3), 741–744 (2011).
[PubMed]

Bradu, A.

Brenner, M.

W. Jung, J. Zhang, J. Chung, P. Wilder-Smith, M. Brenner, J. S. Nelson, and Z. Chen, “Advances in oral cancer detection using optical coherence tomography,” IEEE J. Sel. Top. Quantum Electron. 11(4), 811–817 (2005).

P. Wilder-Smith, W. G. Jung, M. Brenner, K. Osann, H. Beydoun, D. Messadi, and Z. Chen, “In vivo optical coherence tomography for the diagnosis of oral malignancy,” Lasers Surg. Med. 35(4), 269–275 (2004).
[PubMed]

Cable, A.

Cable, A. E.

Cadotte, D. W.

M. S. Mahmud, D. W. Cadotte, B. Vuong, C. Sun, T. W. Luk, A. Mariampillai, and V. X. Yang, “Review of speckle and phase variance optical coherence tomography to visualize microvascular networks,” J. Biomed. Opt. 18(5), 50901 (2013).
[PubMed]

Cahill, L.

Campbell, J. P.

Cernat, R.

Chan, M. C.

Chaney, E. J.

W. Jung, J. Kim, M. Jeon, E. J. Chaney, C. N. Stewart, and S. A. Boppart, “Handheld optical coherence tomography scanner for primary care diagnostics,” IEEE Trans. Biomed. Eng. 58(3), 741–744 (2011).
[PubMed]

Chang, C. C.

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[PubMed]

Chen, H. M.

Chen, Z.

G. Liu, L. Chou, W. Jia, W. Qi, B. Choi, and Z. Chen, “Intensity-based modified Doppler variance algorithm: application to phase instable and phase stable optical coherence tomography systems,” Opt. Express 19(12), 11429–11440 (2011).
[PubMed]

J. M. Ridgway, W. B. Armstrong, S. Guo, U. Mahmood, J. Su, R. P. Jackson, T. Shibuya, R. L. Crumley, M. Gu, Z. Chen, and B. J. Wong, “In vivo optical coherence tomography of the human oral cavity and oropharynx,” Arch. Otolaryngol. Head Neck Surg. 132(10), 1074–1081 (2006).
[PubMed]

P. Wilder-Smith, T. Krasieva, W. G. Jung, J. Zhang, Z. Chen, K. Osann, and B. Tromberg, “Noninvasive imaging of oral premalignancy and malignancy,” J. Biomed. Opt. 10(5), 051601 (2005).
[PubMed]

W. Jung, J. Zhang, J. Chung, P. Wilder-Smith, M. Brenner, J. S. Nelson, and Z. Chen, “Advances in oral cancer detection using optical coherence tomography,” IEEE J. Sel. Top. Quantum Electron. 11(4), 811–817 (2005).

P. Wilder-Smith, W. G. Jung, M. Brenner, K. Osann, H. Beydoun, D. Messadi, and Z. Chen, “In vivo optical coherence tomography for the diagnosis of oral malignancy,” Lasers Surg. Med. 35(4), 269–275 (2004).
[PubMed]

Z. Ding, Y. Zhao, H. Ren, J. Nelson, and Z. Chen, “Real-time phase-resolved optical coherence tomography and optical Doppler tomography,” Opt. Express 10(5), 236–245 (2002).
[PubMed]

Cheng, S.

Chiang, C. P.

M. T. Tsai, H. C. Lee, C. K. Lee, C. H. Yu, H. M. Chen, C. P. Chiang, C. C. Chang, Y. M. Wang, and C. C. Yang, “Effective indicators for diagnosis of oral cancer using optical coherence tomography,” Opt. Express 16(20), 15847–15862 (2008).
[PubMed]

M. T. Tsai, H. C. Lee, C. W. Lu, Y. M. Wang, C. K. Lee, C. C. Yang, and C. P. Chiang, “Delineation of an oral cancer lesion with swept-source optical coherence tomography,” J. Biomed. Opt. 13(4), 044012 (2008).
[PubMed]

Choi, B.

Choi, W.

Choi, W. J.

Chou, L.

Chung, J.

W. Jung, J. Zhang, J. Chung, P. Wilder-Smith, M. Brenner, J. S. Nelson, and Z. Chen, “Advances in oral cancer detection using optical coherence tomography,” IEEE J. Sel. Top. Quantum Electron. 11(4), 811–817 (2005).

Clark, A. L.

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal Microscopy for Real-Time Detection of Oral Cavity Neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

Collier, T. G.

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal Microscopy for Real-Time Detection of Oral Cavity Neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

Crumley, R. L.

J. M. Ridgway, W. B. Armstrong, S. Guo, U. Mahmood, J. Su, R. P. Jackson, T. Shibuya, R. L. Crumley, M. Gu, Z. Chen, and B. J. Wong, “In vivo optical coherence tomography of the human oral cavity and oropharynx,” Arch. Otolaryngol. Head Neck Surg. 132(10), 1074–1081 (2006).
[PubMed]

Cuenca, R.

Davoudi, B.

de Koning, E. J.

R. Djaberi, J. D. Schuijf, E. J. de Koning, D. C. Wijewickrama, A. M. Pereira, J. W. Smit, L. J. Kroft, Ad. Roos, J. J. Bax, T. J. Rabelink, and J. W. Jukema, “Non-invasive assessment of microcirculation by sidestream dark field imaging as a marker of coronary artery disease in diabetes,” Diab. Vasc. Dis. Res. 10(2), 123–134 (2013).
[PubMed]

Dhalla, A. H.

Dierkes, T.

E. A. Naumova, T. Dierkes, J. Sprang, and W. H. Arnold, “The oral mucosal surface and blood vessels,” Head Face Med. 9, 8 (2013).
[PubMed]

Ding, Z.

Djaberi, R.

R. Djaberi, J. D. Schuijf, E. J. de Koning, D. C. Wijewickrama, A. M. Pereira, J. W. Smit, L. J. Kroft, Ad. Roos, J. J. Bax, T. J. Rabelink, and J. W. Jukema, “Non-invasive assessment of microcirculation by sidestream dark field imaging as a marker of coronary artery disease in diabetes,” Diab. Vasc. Dis. Res. 10(2), 123–134 (2013).
[PubMed]

Dobre, G.

Duker, J. S.

Duperier, F. D.

L. L. Gleich, P. W. Biddinger, F. D. Duperier, and J. L. Gluckman, “Tumor angiogenesis as a prognostic indicator in T2-T4 oral cavity squamous cell carcinoma: A clinical-pathologic correlation,” Head Neck 19(4), 276–280 (1997).
[PubMed]

El-Naggar, A. K.

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal Microscopy for Real-Time Detection of Oral Cavity Neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

Enfield, J.

E. Jonathan, J. Enfield, and M. J. Leahy, “Correlation mapping method for generating microcirculation morphology from optical coherence tomography (OCT) intensity images,” J. Biophotonics 4(9), 583–587 (2011).
[PubMed]

J. Enfield, E. Jonathan, and M. Leahy, “In vivo imaging of the microcirculation of the volar forearm using correlation mapping optical coherence tomography (cmOCT),” Biomed. Opt. Express 2(5), 1184–1193 (2011).
[PubMed]

Farsiu, S.

Farwell, D. G.

Fatakdawala, H.

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[PubMed]

Francis, P.

Fujimoto, J. G.

Gahm, N.

Gandour-Edwards, R. F.

Gelikonov, G.

Gelikonov, V.

Gillenwater, A. M.

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal Microscopy for Real-Time Detection of Oral Cavity Neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

Gleich, L. L.

L. L. Gleich, P. W. Biddinger, F. D. Duperier, and J. L. Gluckman, “Tumor angiogenesis as a prognostic indicator in T2-T4 oral cavity squamous cell carcinoma: A clinical-pathologic correlation,” Head Neck 19(4), 276–280 (1997).
[PubMed]

L. L. Gleich, P. W. Biddinger, Z. P. Pavelic, and J. L. Gluckman, “Tumor angiogenesis in T1 oral cavity squamous cell carcinoma: Role in predicting tumor aggressiveness,” Head Neck 18(4), 343–346 (1996).
[PubMed]

Gluckman, J. L.

L. L. Gleich, P. W. Biddinger, F. D. Duperier, and J. L. Gluckman, “Tumor angiogenesis as a prognostic indicator in T2-T4 oral cavity squamous cell carcinoma: A clinical-pathologic correlation,” Head Neck 19(4), 276–280 (1997).
[PubMed]

L. L. Gleich, P. W. Biddinger, Z. P. Pavelic, and J. L. Gluckman, “Tumor angiogenesis in T1 oral cavity squamous cell carcinoma: Role in predicting tumor aggressiveness,” Head Neck 18(4), 343–346 (1996).
[PubMed]

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[PubMed]

Grulkowski, I.

Gu, M.

J. M. Ridgway, W. B. Armstrong, S. Guo, U. Mahmood, J. Su, R. P. Jackson, T. Shibuya, R. L. Crumley, M. Gu, Z. Chen, and B. J. Wong, “In vivo optical coherence tomography of the human oral cavity and oropharynx,” Arch. Otolaryngol. Head Neck Surg. 132(10), 1074–1081 (2006).
[PubMed]

Guo, S.

J. M. Ridgway, W. B. Armstrong, S. Guo, U. Mahmood, J. Su, R. P. Jackson, T. Shibuya, R. L. Crumley, M. Gu, Z. Chen, and B. J. Wong, “In vivo optical coherence tomography of the human oral cavity and oropharynx,” Arch. Otolaryngol. Head Neck Surg. 132(10), 1074–1081 (2006).
[PubMed]

Gynther, G. W.

G. W. Gynther, B. Rozell, and A. Heimdahl, “Direct oral microscopy and its value in diagnosing mucosal lesions: A pilot study,” Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 90(2), 164–170 (2000).
[PubMed]

Hayes, K. E.

A. G. Ammer, K. E. Hayes, K. H. Martin, L. Zhang, G. A. Spirou, and S. A. Weed, “Multi-photon imaging of tumor cell invasion in an orthotopic mouse model of oral squamous cell carcinoma,” J. Vis. Exp. 53, e2941 (2011).

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[PubMed]

Heimdahl, A.

G. W. Gynther, B. Rozell, and A. Heimdahl, “Direct oral microscopy and its value in diagnosing mucosal lesions: A pilot study,” Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 90(2), 164–170 (2000).
[PubMed]

Hohert, G.

Hornegger, J.

Huang, D.

J. Yang, L. Liu, J. P. Campbell, D. Huang, and G. Liu, “Handheld optical coherence tomography angiography,” Biomed. Opt. Express 8(4), 2287–2300 (2017).
[PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[PubMed]

Izatt, J. A.

Jabbour, J. M.

Jackson, R. P.

J. M. Ridgway, W. B. Armstrong, S. Guo, U. Mahmood, J. Su, R. P. Jackson, T. Shibuya, R. L. Crumley, M. Gu, Z. Chen, and B. J. Wong, “In vivo optical coherence tomography of the human oral cavity and oropharynx,” Arch. Otolaryngol. Head Neck Surg. 132(10), 1074–1081 (2006).
[PubMed]

Jayaraman, V.

Jemal, A.

R. L. Siegel, K. D. Miller, and A. Jemal, “Cancer statistics, 2015,” CA Cancer J. Clin. 65(1), 5–29 (2015).
[PubMed]

Jeon, M.

W. Jung, J. Kim, M. Jeon, E. J. Chaney, C. N. Stewart, and S. A. Boppart, “Handheld optical coherence tomography scanner for primary care diagnostics,” IEEE Trans. Biomed. Eng. 58(3), 741–744 (2011).
[PubMed]

Jia, W.

Jiang, J.

Jo, J. A.

Jonathan, E.

J. Enfield, E. Jonathan, and M. Leahy, “In vivo imaging of the microcirculation of the volar forearm using correlation mapping optical coherence tomography (cmOCT),” Biomed. Opt. Express 2(5), 1184–1193 (2011).
[PubMed]

E. Jonathan, J. Enfield, and M. J. Leahy, “Correlation mapping method for generating microcirculation morphology from optical coherence tomography (OCT) intensity images,” J. Biophotonics 4(9), 583–587 (2011).
[PubMed]

Jukema, J. W.

R. Djaberi, J. D. Schuijf, E. J. de Koning, D. C. Wijewickrama, A. M. Pereira, J. W. Smit, L. J. Kroft, Ad. Roos, J. J. Bax, T. J. Rabelink, and J. W. Jukema, “Non-invasive assessment of microcirculation by sidestream dark field imaging as a marker of coronary artery disease in diabetes,” Diab. Vasc. Dis. Res. 10(2), 123–134 (2013).
[PubMed]

Jung, S. M.

Jung, W.

W. Jung, J. Kim, M. Jeon, E. J. Chaney, C. N. Stewart, and S. A. Boppart, “Handheld optical coherence tomography scanner for primary care diagnostics,” IEEE Trans. Biomed. Eng. 58(3), 741–744 (2011).
[PubMed]

W. Jung, J. Zhang, J. Chung, P. Wilder-Smith, M. Brenner, J. S. Nelson, and Z. Chen, “Advances in oral cancer detection using optical coherence tomography,” IEEE J. Sel. Top. Quantum Electron. 11(4), 811–817 (2005).

Jung, W. G.

P. Wilder-Smith, T. Krasieva, W. G. Jung, J. Zhang, Z. Chen, K. Osann, and B. Tromberg, “Noninvasive imaging of oral premalignancy and malignancy,” J. Biomed. Opt. 10(5), 051601 (2005).
[PubMed]

P. Wilder-Smith, W. G. Jung, M. Brenner, K. Osann, H. Beydoun, D. Messadi, and Z. Chen, “In vivo optical coherence tomography for the diagnosis of oral malignancy,” Lasers Surg. Med. 35(4), 269–275 (2004).
[PubMed]

Khurana, M.

Kies, M. S.

M. Lingen, E. M. Sturgis, and M. S. Kies, “Squamous cell carcinoma of the head and neck in nonsmokers: clinical and biologic characteristics and implications for management,” Curr. Opin. Oncol. 13(3), 176–182 (2001).
[PubMed]

Kim, J.

W. Jung, J. Kim, M. Jeon, E. J. Chaney, C. N. Stewart, and S. A. Boppart, “Handheld optical coherence tomography scanner for primary care diagnostics,” IEEE Trans. Biomed. Eng. 58(3), 741–744 (2011).
[PubMed]

Krasieva, T.

P. Wilder-Smith, T. Krasieva, W. G. Jung, J. Zhang, Z. Chen, K. Osann, and B. Tromberg, “Noninvasive imaging of oral premalignancy and malignancy,” J. Biomed. Opt. 10(5), 051601 (2005).
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Kraus, M. F.

Kremer, M. J.

C. A. Squier and M. J. Kremer, “Biology of Oral Mucosa and Esophagus,” J. Natl. Cancer Inst. Monogr. 2001(29), 7–15 (2001).
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Kroft, L. J.

R. Djaberi, J. D. Schuijf, E. J. de Koning, D. C. Wijewickrama, A. M. Pereira, J. W. Smit, L. J. Kroft, Ad. Roos, J. J. Bax, T. J. Rabelink, and J. W. Jukema, “Non-invasive assessment of microcirculation by sidestream dark field imaging as a marker of coronary artery disease in diabetes,” Diab. Vasc. Dis. Res. 10(2), 123–134 (2013).
[PubMed]

Lam, S.

Lane, P.

Leahy, M.

Leahy, M. J.

E. Jonathan, J. Enfield, and M. J. Leahy, “Correlation mapping method for generating microcirculation morphology from optical coherence tomography (OCT) intensity images,” J. Biophotonics 4(9), 583–587 (2011).
[PubMed]

Lee, A. M.

Lee, C. K.

M. T. Tsai, H. C. Lee, C. K. Lee, C. H. Yu, H. M. Chen, C. P. Chiang, C. C. Chang, Y. M. Wang, and C. C. Yang, “Effective indicators for diagnosis of oral cancer using optical coherence tomography,” Opt. Express 16(20), 15847–15862 (2008).
[PubMed]

M. T. Tsai, H. C. Lee, C. W. Lu, Y. M. Wang, C. K. Lee, C. C. Yang, and C. P. Chiang, “Delineation of an oral cancer lesion with swept-source optical coherence tomography,” J. Biomed. Opt. 13(4), 044012 (2008).
[PubMed]

Lee, H. C.

M. T. Tsai, H. C. Lee, C. W. Lu, Y. M. Wang, C. K. Lee, C. C. Yang, and C. P. Chiang, “Delineation of an oral cancer lesion with swept-source optical coherence tomography,” J. Biomed. Opt. 13(4), 044012 (2008).
[PubMed]

M. T. Tsai, H. C. Lee, C. K. Lee, C. H. Yu, H. M. Chen, C. P. Chiang, C. C. Chang, Y. M. Wang, and C. C. Yang, “Effective indicators for diagnosis of oral cancer using optical coherence tomography,” Opt. Express 16(20), 15847–15862 (2008).
[PubMed]

Leung, M. K.

Li, P.

Lin, C. F.

M. R. Tsai, D. B. Shieh, P. J. Lou, C. F. Lin, and C. K. Sun, “Characterization of oral squamous cell carcinoma based on higher-harmonic generation microscopy,” J. Biophotonics 5(5-6), 415–424 (2012).
[PubMed]

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[PubMed]

Lindenmaier, A.

Lingen, M.

M. Lingen, E. M. Sturgis, and M. S. Kies, “Squamous cell carcinoma of the head and neck in nonsmokers: clinical and biologic characteristics and implications for management,” Curr. Opin. Oncol. 13(3), 176–182 (2001).
[PubMed]

Liu, G.

Liu, H. L.

Liu, J.

Liu, J. J.

Liu, K.

Liu, L.

Liu, Y. H.

Lou, P. J.

M. R. Tsai, D. B. Shieh, P. J. Lou, C. F. Lin, and C. K. Sun, “Characterization of oral squamous cell carcinoma based on higher-harmonic generation microscopy,” J. Biophotonics 5(5-6), 415–424 (2012).
[PubMed]

Lu, C. D.

Lu, C. W.

M. T. Tsai, H. C. Lee, C. W. Lu, Y. M. Wang, C. K. Lee, C. C. Yang, and C. P. Chiang, “Delineation of an oral cancer lesion with swept-source optical coherence tomography,” J. Biomed. Opt. 13(4), 044012 (2008).
[PubMed]

Luk, T. W.

M. S. Mahmud, D. W. Cadotte, B. Vuong, C. Sun, T. W. Luk, A. Mariampillai, and V. X. Yang, “Review of speckle and phase variance optical coherence tomography to visualize microvascular networks,” J. Biomed. Opt. 18(5), 50901 (2013).
[PubMed]

MacAulay, C.

Mahmood, U.

J. M. Ridgway, W. B. Armstrong, S. Guo, U. Mahmood, J. Su, R. P. Jackson, T. Shibuya, R. L. Crumley, M. Gu, Z. Chen, and B. J. Wong, “In vivo optical coherence tomography of the human oral cavity and oropharynx,” Arch. Otolaryngol. Head Neck Surg. 132(10), 1074–1081 (2006).
[PubMed]

Mahmud, M. S.

M. S. Mahmud, D. W. Cadotte, B. Vuong, C. Sun, T. W. Luk, A. Mariampillai, and V. X. Yang, “Review of speckle and phase variance optical coherence tomography to visualize microvascular networks,” J. Biomed. Opt. 18(5), 50901 (2013).
[PubMed]

Maitland, K. C.

Malik, B. H.

Marcu, L.

Mariampillai, A.

M. S. Mahmud, D. W. Cadotte, B. Vuong, C. Sun, T. W. Luk, A. Mariampillai, and V. X. Yang, “Review of speckle and phase variance optical coherence tomography to visualize microvascular networks,” J. Biomed. Opt. 18(5), 50901 (2013).
[PubMed]

A. Mariampillai, B. A. Standish, E. H. Moriyama, M. Khurana, N. R. Munce, M. K. Leung, J. Jiang, A. Cable, B. C. Wilson, I. A. Vitkin, and V. X. Yang, “Speckle variance detection of microvasculature using swept-source optical coherence tomography,” Opt. Lett. 33(13), 1530–1532 (2008).
[PubMed]

Martin, K. H.

A. G. Ammer, K. E. Hayes, K. H. Martin, L. Zhang, G. A. Spirou, and S. A. Weed, “Multi-photon imaging of tumor cell invasion in an orthotopic mouse model of oral squamous cell carcinoma,” J. Vis. Exp. 53, e2941 (2011).

Messadi, D.

P. Wilder-Smith, W. G. Jung, M. Brenner, K. Osann, H. Beydoun, D. Messadi, and Z. Chen, “In vivo optical coherence tomography for the diagnosis of oral malignancy,” Lasers Surg. Med. 35(4), 269–275 (2004).
[PubMed]

Messina, P.

G. A. Scardina and P. Messina, “Oral microcirculation in post-menopause: a possible correlation with periodontitis,” Gerodontology 29(2), e1045–e1051 (2012).
[PubMed]

Miller, K. D.

R. L. Siegel, K. D. Miller, and A. Jemal, “Cancer statistics, 2015,” CA Cancer J. Clin. 65(1), 5–29 (2015).
[PubMed]

Moriyama, E. H.

Munce, N. R.

Nankivil, D.

Naumova, E. A.

E. A. Naumova, T. Dierkes, J. Sprang, and W. H. Arnold, “The oral mucosal surface and blood vessels,” Head Face Med. 9, 8 (2013).
[PubMed]

Nelson, J.

Nelson, J. S.

W. Jung, J. Zhang, J. Chung, P. Wilder-Smith, M. Brenner, J. S. Nelson, and Z. Chen, “Advances in oral cancer detection using optical coherence tomography,” IEEE J. Sel. Top. Quantum Electron. 11(4), 811–817 (2005).

Nemechek, J.

Ng, C. Y.

Osann, K.

P. Wilder-Smith, T. Krasieva, W. G. Jung, J. Zhang, Z. Chen, K. Osann, and B. Tromberg, “Noninvasive imaging of oral premalignancy and malignancy,” J. Biomed. Opt. 10(5), 051601 (2005).
[PubMed]

P. Wilder-Smith, W. G. Jung, M. Brenner, K. Osann, H. Beydoun, D. Messadi, and Z. Chen, “In vivo optical coherence tomography for the diagnosis of oral malignancy,” Lasers Surg. Med. 35(4), 269–275 (2004).
[PubMed]

Pahlevaninezhad, H.

Pang, J.

Pavelic, Z. P.

L. L. Gleich, P. W. Biddinger, Z. P. Pavelic, and J. L. Gluckman, “Tumor angiogenesis in T1 oral cavity squamous cell carcinoma: Role in predicting tumor aggressiveness,” Head Neck 18(4), 343–346 (1996).
[PubMed]

Pereira, A. M.

R. Djaberi, J. D. Schuijf, E. J. de Koning, D. C. Wijewickrama, A. M. Pereira, J. W. Smit, L. J. Kroft, Ad. Roos, J. J. Bax, T. J. Rabelink, and J. W. Jukema, “Non-invasive assessment of microcirculation by sidestream dark field imaging as a marker of coronary artery disease in diabetes,” Diab. Vasc. Dis. Res. 10(2), 123–134 (2013).
[PubMed]

Podoleanu, A. G.

Poh, C.

Poti, S.

Potsaid, B.

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[PubMed]

Qi, W.

Qin, J.

Rabelink, T. J.

R. Djaberi, J. D. Schuijf, E. J. de Koning, D. C. Wijewickrama, A. M. Pereira, J. W. Smit, L. J. Kroft, Ad. Roos, J. J. Bax, T. J. Rabelink, and J. W. Jukema, “Non-invasive assessment of microcirculation by sidestream dark field imaging as a marker of coronary artery disease in diabetes,” Diab. Vasc. Dis. Res. 10(2), 123–134 (2013).
[PubMed]

Raizada, R.

Ren, H.

Richards-Kortum, R. R.

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal Microscopy for Real-Time Detection of Oral Cavity Neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

Ridgway, J. M.

J. M. Ridgway, W. B. Armstrong, S. Guo, U. Mahmood, J. Su, R. P. Jackson, T. Shibuya, R. L. Crumley, M. Gu, Z. Chen, and B. J. Wong, “In vivo optical coherence tomography of the human oral cavity and oropharynx,” Arch. Otolaryngol. Head Neck Surg. 132(10), 1074–1081 (2006).
[PubMed]

Roos, Ad.

R. Djaberi, J. D. Schuijf, E. J. de Koning, D. C. Wijewickrama, A. M. Pereira, J. W. Smit, L. J. Kroft, Ad. Roos, J. J. Bax, T. J. Rabelink, and J. W. Jukema, “Non-invasive assessment of microcirculation by sidestream dark field imaging as a marker of coronary artery disease in diabetes,” Diab. Vasc. Dis. Res. 10(2), 123–134 (2013).
[PubMed]

Rozell, B.

G. W. Gynther, B. Rozell, and A. Heimdahl, “Direct oral microscopy and its value in diagnosing mucosal lesions: A pilot study,” Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 90(2), 164–170 (2000).
[PubMed]

Scardina, G. A.

G. A. Scardina and P. Messina, “Oral microcirculation in post-menopause: a possible correlation with periodontitis,” Gerodontology 29(2), e1045–e1051 (2012).
[PubMed]

Schuijf, J. D.

R. Djaberi, J. D. Schuijf, E. J. de Koning, D. C. Wijewickrama, A. M. Pereira, J. W. Smit, L. J. Kroft, Ad. Roos, J. J. Bax, T. J. Rabelink, and J. W. Jukema, “Non-invasive assessment of microcirculation by sidestream dark field imaging as a marker of coronary artery disease in diabetes,” Diab. Vasc. Dis. Res. 10(2), 123–134 (2013).
[PubMed]

Schuman, J. S.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[PubMed]

Shaipanich, T.

Shen, S. C.

Shen, T. T.

Shia, K.

Shibuya, T.

J. M. Ridgway, W. B. Armstrong, S. Guo, U. Mahmood, J. Su, R. P. Jackson, T. Shibuya, R. L. Crumley, M. Gu, Z. Chen, and B. J. Wong, “In vivo optical coherence tomography of the human oral cavity and oropharynx,” Arch. Otolaryngol. Head Neck Surg. 132(10), 1074–1081 (2006).
[PubMed]

Shieh, D. B.

M. R. Tsai, D. B. Shieh, P. J. Lou, C. F. Lin, and C. K. Sun, “Characterization of oral squamous cell carcinoma based on higher-harmonic generation microscopy,” J. Biophotonics 5(5-6), 415–424 (2012).
[PubMed]

Siegel, R. L.

R. L. Siegel, K. D. Miller, and A. Jemal, “Cancer statistics, 2015,” CA Cancer J. Clin. 65(1), 5–29 (2015).
[PubMed]

Silverman, S.

S. Silverman., “Early diagnosis of oral cancer,” Cancer 62(8Suppl), 1796–1799 (1988).
[PubMed]

Smit, J. W.

R. Djaberi, J. D. Schuijf, E. J. de Koning, D. C. Wijewickrama, A. M. Pereira, J. W. Smit, L. J. Kroft, Ad. Roos, J. J. Bax, T. J. Rabelink, and J. W. Jukema, “Non-invasive assessment of microcirculation by sidestream dark field imaging as a marker of coronary artery disease in diabetes,” Diab. Vasc. Dis. Res. 10(2), 123–134 (2013).
[PubMed]

Spirou, G. A.

A. G. Ammer, K. E. Hayes, K. H. Martin, L. Zhang, G. A. Spirou, and S. A. Weed, “Multi-photon imaging of tumor cell invasion in an orthotopic mouse model of oral squamous cell carcinoma,” J. Vis. Exp. 53, e2941 (2011).

Sprang, J.

E. A. Naumova, T. Dierkes, J. Sprang, and W. H. Arnold, “The oral mucosal surface and blood vessels,” Head Face Med. 9, 8 (2013).
[PubMed]

Squier, C. A.

C. A. Squier and M. J. Kremer, “Biology of Oral Mucosa and Esophagus,” J. Natl. Cancer Inst. Monogr. 2001(29), 7–15 (2001).
[PubMed]

Standish, B. A.

Stewart, C. N.

W. Jung, J. Kim, M. Jeon, E. J. Chaney, C. N. Stewart, and S. A. Boppart, “Handheld optical coherence tomography scanner for primary care diagnostics,” IEEE Trans. Biomed. Eng. 58(3), 741–744 (2011).
[PubMed]

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[PubMed]

Sturgis, E. M.

M. Lingen, E. M. Sturgis, and M. S. Kies, “Squamous cell carcinoma of the head and neck in nonsmokers: clinical and biologic characteristics and implications for management,” Curr. Opin. Oncol. 13(3), 176–182 (2001).
[PubMed]

Su, J.

J. M. Ridgway, W. B. Armstrong, S. Guo, U. Mahmood, J. Su, R. P. Jackson, T. Shibuya, R. L. Crumley, M. Gu, Z. Chen, and B. J. Wong, “In vivo optical coherence tomography of the human oral cavity and oropharynx,” Arch. Otolaryngol. Head Neck Surg. 132(10), 1074–1081 (2006).
[PubMed]

Sun, C.

M. S. Mahmud, D. W. Cadotte, B. Vuong, C. Sun, T. W. Luk, A. Mariampillai, and V. X. Yang, “Review of speckle and phase variance optical coherence tomography to visualize microvascular networks,” J. Biomed. Opt. 18(5), 50901 (2013).
[PubMed]

Sun, C. K.

M. R. Tsai, D. B. Shieh, P. J. Lou, C. F. Lin, and C. K. Sun, “Characterization of oral squamous cell carcinoma based on higher-harmonic generation microscopy,” J. Biophotonics 5(5-6), 415–424 (2012).
[PubMed]

Sun, Y.

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[PubMed]

Tadrous, P. J.

Tatla, T. S.

Tinling, S. P.

Tromberg, B.

P. Wilder-Smith, T. Krasieva, W. G. Jung, J. Zhang, Z. Chen, K. Osann, and B. Tromberg, “Noninvasive imaging of oral premalignancy and malignancy,” J. Biomed. Opt. 10(5), 051601 (2005).
[PubMed]

Tsai, M. R.

M. R. Tsai, D. B. Shieh, P. J. Lou, C. F. Lin, and C. K. Sun, “Characterization of oral squamous cell carcinoma based on higher-harmonic generation microscopy,” J. Biophotonics 5(5-6), 415–424 (2012).
[PubMed]

Tsai, M. T.

Vitkin, A.

Vitkin, I. A.

Vuong, B.

M. S. Mahmud, D. W. Cadotte, B. Vuong, C. Sun, T. W. Luk, A. Mariampillai, and V. X. Yang, “Review of speckle and phase variance optical coherence tomography to visualize microvascular networks,” J. Biomed. Opt. 18(5), 50901 (2013).
[PubMed]

Wang, R.

Wang, R. K.

Wang, Y. M.

M. T. Tsai, H. C. Lee, C. K. Lee, C. H. Yu, H. M. Chen, C. P. Chiang, C. C. Chang, Y. M. Wang, and C. C. Yang, “Effective indicators for diagnosis of oral cancer using optical coherence tomography,” Opt. Express 16(20), 15847–15862 (2008).
[PubMed]

M. T. Tsai, H. C. Lee, C. W. Lu, Y. M. Wang, C. K. Lee, C. C. Yang, and C. P. Chiang, “Delineation of an oral cancer lesion with swept-source optical coherence tomography,” J. Biomed. Opt. 13(4), 044012 (2008).
[PubMed]

Warda, J.

Weed, S. A.

A. G. Ammer, K. E. Hayes, K. H. Martin, L. Zhang, G. A. Spirou, and S. A. Weed, “Multi-photon imaging of tumor cell invasion in an orthotopic mouse model of oral squamous cell carcinoma,” J. Vis. Exp. 53, e2941 (2011).

Wei, K. C.

Wijewickrama, D. C.

R. Djaberi, J. D. Schuijf, E. J. de Koning, D. C. Wijewickrama, A. M. Pereira, J. W. Smit, L. J. Kroft, Ad. Roos, J. J. Bax, T. J. Rabelink, and J. W. Jukema, “Non-invasive assessment of microcirculation by sidestream dark field imaging as a marker of coronary artery disease in diabetes,” Diab. Vasc. Dis. Res. 10(2), 123–134 (2013).
[PubMed]

Wilder-Smith, P.

W. Jung, J. Zhang, J. Chung, P. Wilder-Smith, M. Brenner, J. S. Nelson, and Z. Chen, “Advances in oral cancer detection using optical coherence tomography,” IEEE J. Sel. Top. Quantum Electron. 11(4), 811–817 (2005).

P. Wilder-Smith, T. Krasieva, W. G. Jung, J. Zhang, Z. Chen, K. Osann, and B. Tromberg, “Noninvasive imaging of oral premalignancy and malignancy,” J. Biomed. Opt. 10(5), 051601 (2005).
[PubMed]

P. Wilder-Smith, W. G. Jung, M. Brenner, K. Osann, H. Beydoun, D. Messadi, and Z. Chen, “In vivo optical coherence tomography for the diagnosis of oral malignancy,” Lasers Surg. Med. 35(4), 269–275 (2004).
[PubMed]

Wilson, B. C.

Wilson, D. J.

Wong, B. J.

J. M. Ridgway, W. B. Armstrong, S. Guo, U. Mahmood, J. Su, R. P. Jackson, T. Shibuya, R. L. Crumley, M. Gu, Z. Chen, and B. J. Wong, “In vivo optical coherence tomography of the human oral cavity and oropharynx,” Arch. Otolaryngol. Head Neck Surg. 132(10), 1074–1081 (2006).
[PubMed]

Yang, C. C.

M. T. Tsai, H. C. Lee, C. W. Lu, Y. M. Wang, C. K. Lee, C. C. Yang, and C. P. Chiang, “Delineation of an oral cancer lesion with swept-source optical coherence tomography,” J. Biomed. Opt. 13(4), 044012 (2008).
[PubMed]

M. T. Tsai, H. C. Lee, C. K. Lee, C. H. Yu, H. M. Chen, C. P. Chiang, C. C. Chang, Y. M. Wang, and C. C. Yang, “Effective indicators for diagnosis of oral cancer using optical coherence tomography,” Opt. Express 16(20), 15847–15862 (2008).
[PubMed]

Yang, C. H.

Yang, J.

Yang, V. X.

Yankelevich, D. R.

Yeh, C. K.

Yu, C. H.

Zhang, J.

W. Jung, J. Zhang, J. Chung, P. Wilder-Smith, M. Brenner, J. S. Nelson, and Z. Chen, “Advances in oral cancer detection using optical coherence tomography,” IEEE J. Sel. Top. Quantum Electron. 11(4), 811–817 (2005).

P. Wilder-Smith, T. Krasieva, W. G. Jung, J. Zhang, Z. Chen, K. Osann, and B. Tromberg, “Noninvasive imaging of oral premalignancy and malignancy,” J. Biomed. Opt. 10(5), 051601 (2005).
[PubMed]

Zhang, J. W.

Zhang, L.

A. G. Ammer, K. E. Hayes, K. H. Martin, L. Zhang, G. A. Spirou, and S. A. Weed, “Multi-photon imaging of tumor cell invasion in an orthotopic mouse model of oral squamous cell carcinoma,” J. Vis. Exp. 53, e2941 (2011).

Zhao, Y.

Zhou, F.

Arch. Otolaryngol. Head Neck Surg. (1)

J. M. Ridgway, W. B. Armstrong, S. Guo, U. Mahmood, J. Su, R. P. Jackson, T. Shibuya, R. L. Crumley, M. Gu, Z. Chen, and B. J. Wong, “In vivo optical coherence tomography of the human oral cavity and oropharynx,” Arch. Otolaryngol. Head Neck Surg. 132(10), 1074–1081 (2006).
[PubMed]

Biomed. Opt. Express (12)

L. An, P. Li, T. T. Shen, and R. Wang, “High speed spectral domain optical coherence tomography for retinal imaging at 500,000 A‑lines per second,” Biomed. Opt. Express 2(10), 2770–2783 (2011).
[PubMed]

B. Davoudi, A. Lindenmaier, B. A. Standish, G. Allo, K. Bizheva, and A. Vitkin, “Noninvasive in vivo structural and vascular imaging of human oral tissues with spectral domain optical coherence tomography,” Biomed. Opt. Express 3(5), 826–839 (2012).
[PubMed]

R. Cernat, T. S. Tatla, J. Pang, P. J. Tadrous, A. Bradu, G. Dobre, G. Gelikonov, V. Gelikonov, and A. G. Podoleanu, “Dual instrument for in vivo and ex vivo OCT imaging in an ENT department,” Biomed. Opt. Express 3(12), 3346–3356 (2012).
[PubMed]

H. Fatakdawala, S. Poti, F. Zhou, Y. Sun, J. Bec, J. Liu, D. R. Yankelevich, S. P. Tinling, R. F. Gandour-Edwards, D. G. Farwell, and L. Marcu, “Multimodal in vivo imaging of oral cancer using fluorescence lifetime, photoacoustic and ultrasound techniques,” Biomed. Opt. Express 4(9), 1724–1741 (2013).
[PubMed]

C. D. Lu, M. F. Kraus, B. Potsaid, J. J. Liu, W. Choi, V. Jayaraman, A. E. Cable, J. Hornegger, J. S. Duker, and J. G. Fujimoto, “Handheld ultrahigh speed swept source optical coherence tomography instrument using a MEMS scanning mirror,” Biomed. Opt. Express 5(1), 293–311 (2013).
[PubMed]

W. J. Choi and R. K. Wang, “In vivo imaging of functional microvasculature within tissue beds of oral and nasal cavities by swept-source optical coherence tomography with a forward/side-viewing probe,” Biomed. Opt. Express 5(8), 2620–2634 (2014).
[PubMed]

H. Pahlevaninezhad, A. M. Lee, T. Shaipanich, R. Raizada, L. Cahill, G. Hohert, V. X. Yang, S. Lam, C. MacAulay, and P. Lane, “A high-efficiency fiber-based imaging system for co-registered autofluorescence and optical coherence tomography,” Biomed. Opt. Express 5(9), 2978–2987 (2014).
[PubMed]

J. M. Jabbour, J. L. Bentley, B. H. Malik, J. Nemechek, J. Warda, R. Cuenca, S. Cheng, J. A. Jo, and K. C. Maitland, “Reflectance confocal endomicroscope with optical axial scanning for in vivo imaging of the oral mucosa,” Biomed. Opt. Express 5(11), 3781–3791 (2014).
[PubMed]

C. H. Yang, M. T. Tsai, S. C. Shen, C. Y. Ng, and S. M. Jung, “Feasibility of ablative fractional laser-assisted drug delivery with optical coherence tomography,” Biomed. Opt. Express 5(11), 3949–3959 (2014).
[PubMed]

A. M. Lee, L. Cahill, K. Liu, C. MacAulay, C. Poh, and P. Lane, “Wide-field in vivo oral OCT imaging,” Biomed. Opt. Express 6(7), 2664–2674 (2015).
[PubMed]

J. Enfield, E. Jonathan, and M. Leahy, “In vivo imaging of the microcirculation of the volar forearm using correlation mapping optical coherence tomography (cmOCT),” Biomed. Opt. Express 2(5), 1184–1193 (2011).
[PubMed]

J. Yang, L. Liu, J. P. Campbell, D. Huang, and G. Liu, “Handheld optical coherence tomography angiography,” Biomed. Opt. Express 8(4), 2287–2300 (2017).
[PubMed]

CA Cancer J. Clin. (1)

R. L. Siegel, K. D. Miller, and A. Jemal, “Cancer statistics, 2015,” CA Cancer J. Clin. 65(1), 5–29 (2015).
[PubMed]

Cancer (1)

S. Silverman., “Early diagnosis of oral cancer,” Cancer 62(8Suppl), 1796–1799 (1988).
[PubMed]

Clin. Cancer Res. (1)

A. L. Clark, A. M. Gillenwater, T. G. Collier, R. Alizadeh-Naderi, A. K. El-Naggar, and R. R. Richards-Kortum, “Confocal Microscopy for Real-Time Detection of Oral Cavity Neoplasia,” Clin. Cancer Res. 9(13), 4714–4721 (2003).
[PubMed]

Curr. Opin. Oncol. (1)

M. Lingen, E. M. Sturgis, and M. S. Kies, “Squamous cell carcinoma of the head and neck in nonsmokers: clinical and biologic characteristics and implications for management,” Curr. Opin. Oncol. 13(3), 176–182 (2001).
[PubMed]

Diab. Vasc. Dis. Res. (1)

R. Djaberi, J. D. Schuijf, E. J. de Koning, D. C. Wijewickrama, A. M. Pereira, J. W. Smit, L. J. Kroft, Ad. Roos, J. J. Bax, T. J. Rabelink, and J. W. Jukema, “Non-invasive assessment of microcirculation by sidestream dark field imaging as a marker of coronary artery disease in diabetes,” Diab. Vasc. Dis. Res. 10(2), 123–134 (2013).
[PubMed]

Gerodontology (1)

G. A. Scardina and P. Messina, “Oral microcirculation in post-menopause: a possible correlation with periodontitis,” Gerodontology 29(2), e1045–e1051 (2012).
[PubMed]

Head Face Med. (1)

E. A. Naumova, T. Dierkes, J. Sprang, and W. H. Arnold, “The oral mucosal surface and blood vessels,” Head Face Med. 9, 8 (2013).
[PubMed]

Head Neck (2)

L. L. Gleich, P. W. Biddinger, Z. P. Pavelic, and J. L. Gluckman, “Tumor angiogenesis in T1 oral cavity squamous cell carcinoma: Role in predicting tumor aggressiveness,” Head Neck 18(4), 343–346 (1996).
[PubMed]

L. L. Gleich, P. W. Biddinger, F. D. Duperier, and J. L. Gluckman, “Tumor angiogenesis as a prognostic indicator in T2-T4 oral cavity squamous cell carcinoma: A clinical-pathologic correlation,” Head Neck 19(4), 276–280 (1997).
[PubMed]

IEEE J. Sel. Top. Quantum Electron. (1)

W. Jung, J. Zhang, J. Chung, P. Wilder-Smith, M. Brenner, J. S. Nelson, and Z. Chen, “Advances in oral cancer detection using optical coherence tomography,” IEEE J. Sel. Top. Quantum Electron. 11(4), 811–817 (2005).

IEEE Trans. Biomed. Eng. (1)

W. Jung, J. Kim, M. Jeon, E. J. Chaney, C. N. Stewart, and S. A. Boppart, “Handheld optical coherence tomography scanner for primary care diagnostics,” IEEE Trans. Biomed. Eng. 58(3), 741–744 (2011).
[PubMed]

J. Biomed. Opt. (3)

M. S. Mahmud, D. W. Cadotte, B. Vuong, C. Sun, T. W. Luk, A. Mariampillai, and V. X. Yang, “Review of speckle and phase variance optical coherence tomography to visualize microvascular networks,” J. Biomed. Opt. 18(5), 50901 (2013).
[PubMed]

P. Wilder-Smith, T. Krasieva, W. G. Jung, J. Zhang, Z. Chen, K. Osann, and B. Tromberg, “Noninvasive imaging of oral premalignancy and malignancy,” J. Biomed. Opt. 10(5), 051601 (2005).
[PubMed]

M. T. Tsai, H. C. Lee, C. W. Lu, Y. M. Wang, C. K. Lee, C. C. Yang, and C. P. Chiang, “Delineation of an oral cancer lesion with swept-source optical coherence tomography,” J. Biomed. Opt. 13(4), 044012 (2008).
[PubMed]

J. Biophotonics (2)

E. Jonathan, J. Enfield, and M. J. Leahy, “Correlation mapping method for generating microcirculation morphology from optical coherence tomography (OCT) intensity images,” J. Biophotonics 4(9), 583–587 (2011).
[PubMed]

M. R. Tsai, D. B. Shieh, P. J. Lou, C. F. Lin, and C. K. Sun, “Characterization of oral squamous cell carcinoma based on higher-harmonic generation microscopy,” J. Biophotonics 5(5-6), 415–424 (2012).
[PubMed]

J. Natl. Cancer Inst. Monogr. (1)

C. A. Squier and M. J. Kremer, “Biology of Oral Mucosa and Esophagus,” J. Natl. Cancer Inst. Monogr. 2001(29), 7–15 (2001).
[PubMed]

J. Vis. Exp. (1)

A. G. Ammer, K. E. Hayes, K. H. Martin, L. Zhang, G. A. Spirou, and S. A. Weed, “Multi-photon imaging of tumor cell invasion in an orthotopic mouse model of oral squamous cell carcinoma,” J. Vis. Exp. 53, e2941 (2011).

Lasers Surg. Med. (1)

P. Wilder-Smith, W. G. Jung, M. Brenner, K. Osann, H. Beydoun, D. Messadi, and Z. Chen, “In vivo optical coherence tomography for the diagnosis of oral malignancy,” Lasers Surg. Med. 35(4), 269–275 (2004).
[PubMed]

Opt. Express (4)

Opt. Lett. (6)

Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. (1)

G. W. Gynther, B. Rozell, and A. Heimdahl, “Direct oral microscopy and its value in diagnosing mucosal lesions: A pilot study,” Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 90(2), 164–170 (2000).
[PubMed]

Science (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[PubMed]

Other (1)

B. Neville, D. D. Damm, C. Allen, and J. Bouquot, Oral and Maxillofacial Pathology. 3rd Edition. (Saunders, 2008).

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Figures (8)

Fig. 1
Fig. 1 Design of a handheld probe for oral cavity scanning. (a) Optical path of the probe simulated by Zemax; (b) assembly of the handheld probe; (c) size of probe; (d) probe picture. Col: collimator, Galvo: galvanometer, AC: achromatic lens, and RP: right-angle prism mirror.
Fig. 2
Fig. 2 Schematic diagram of the SS-OCT system. SS: swept-source, CIR: circulator, FC: fiber coupler, DC: dispersion compensator, M: mirror, BD: balanced detector, DAQ: data acquisition board, and PC: personal computer.
Fig. 3
Fig. 3 In vivo OCT images of the upper lip obtained from a healthy 24-year-old male including a (a) 2D image, (b) 3D image, and (c)–(h) projection-view angiographies obtained at varying depths of 300–310, 350–360, 400–410, 450–460, 500–510, and 300–600 μm, respectively, beneath the lip surface. E: epidermis, LP: lamina propria, and SG: salivary gland. The scale bar in (a) represents 500 μm. The yellow arrows indicate the twists of capillaries.
Fig. 4
Fig. 4 Estimated results of (a) the averaged vessel diameters and (b) the vessel densities of Fig. 3(c)-3(g).
Fig. 5
Fig. 5 In vivo OCT images of the right buccal mucosa obtained from a healthy 25-year-old female including a (a) 2D image, (b) 3D image, and (c)–(h) projection-view angiographies obtained at varying depths of 250–260, 300–310, 350–360, 400–410, 450–460, and 250–500 μm, respectively, beneath the buccal surface. E: epidermis, LP: lamina propria, and SG: salivary gland. The scale bar in (a) represents 500 μm.
Fig. 6
Fig. 6 In vivo OCT images of the ventral surface of a tongue obtained from a 25-year-old male including a (a) 2D image, (b) 3D image, and (c)–(h) projection-view angiographies obtained at the various depths of 250–260, 300–310, 350–360, 400–410, 450–460, and 250–500 μm beneath the tongue surface. E: epidermis, LP: lamina propria, and MF: muscle fiber. The scale bar in (a) represents 500 μm.
Fig. 7
Fig. 7 In vivo OCT images of gingival mucosa obtained from a 24-year-old female including a (a) 2D image, (b) 3D image, and (c)–(h) projection-view angiographies obtained at the various depths of 250–260, 300–310, 350–360, 400–410, 450–460, and 250–500 μm beneath the tissue surface. E: epidermis, LP: lamina propria, and PM: plastic membrane. The scale bar in (a) represents 500 μm.
Fig. 8
Fig. 8 In vivo OCT images of the dorsal surface of a tongue obtained from a 24-year-old male volunteer including a (a) 2D image, (b) 3D image, (c) top-view of 3D image, and (d)–(g) angiographies obtained at the various depths of 200–250, 250–300, 300–350, 350–400, and 200–400 μm beneath the tissue surface. E: epidermis, LP: lamina propria, and FP: fungiform papilla. The scale bar in (a) represents 500 μm in length. The yellow arrows indicate the dense twists of vessels beneath the epithelium.

Equations (1)

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Corr(x,z)= i=1 m j=1 n [ I A (x+i,z+j) I A ¯ ][ I B (x+i,z+j) I B ¯ ] i=1 m j=1 n [ I A (x+i,z+j) I A ¯ ] 2 i=1 m j=1 n [ I B (x+i,z+j) I B ¯ ] 2

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