Abstract

In this study, we propose a low-cost cross-polarized dark field microscopy system for in vivo vascular imaging to detect head and neck cancer. A simple-to-use Gabor-filter-based image processing technique was developed to objectively and automatically quantify several important vascular features, including tortuosity, length, diameter and area fraction, from vascular images. Simulations were performed to evaluate the accuracies of vessel segmentation and feature extraction for our algorithm. Sensitivity and specificity for vessel segmentation of the Gabor masks both remained above 80% at all contrast levels when compared to gold-standard masks. Errors for vascular feature extraction were under 5%. Moreover, vascular contrast and vessel diameter were identified to be the two primary factors which affected the segmentation accuracies. After our algorithm was validated, we monitored the blood vessels in an inducible hamster cheek pouch carcinogen model over 17 weeks and quantified vascular features during carcinogenesis. A significant increase in vascular tortuosity and a significant decrease in vessel length were observed during carcinogenesis.

© 2016 Optical Society of America

Full Article  |  PDF Article
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References

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  1. NIH, “ https://costprojections.cancer.gov/graph.php ,” (2010).
  2. J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D. M. Parkin, D. Forman, and F. Bray, “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” Int. J. Cancer 136(5), E359–E386 (2015).
    [Crossref] [PubMed]
  3. “Winning the Battle Against Head and Neck Cancer” (Seattle Cancer Care Alliance), retrieved http://www.seattlecca.org/diseases/head-neck-cancer-survival-rates.cfm .
  4. J. Folkman, D. M. Long, and F. F. Becker, “Growth and Metastasis of Tumor in Organ Culture,” Cancer 16(4), 453–467 (1963).
    [Crossref] [PubMed]
  5. M. J. Folkman, D. M. Long, and F. F. Becker, “Tumor growth in organ culture,” Surg. Forum 13, 81–83 (1962).
    [PubMed]
  6. M. Sathyakumar, G. Sriram, T. Saraswathi, and B. Sivapathasundharam, “Immunohistochemical evaluation of mast cells and vascular endothelial proliferation in oral precancerous lesion-leukoplakia,” J. Oral Maxillofac. Pathol. 16(3), 343–348 (2012).
    [Crossref] [PubMed]
  7. Y. Jin, G. L. Tipoe, F. H. White, and L. Yang, “A quantitative investigation of immunocytochemically stained blood vessels in normal, benign, premalignant and malignant human oral cheek epithelium,” Virchows Arch. 427(2), 145–151 (1995).
    [PubMed]
  8. V. T. C. Chang, P. S. Cartwright, S. M. Bean, G. M. Palmer, R. C. Bentley, and N. Ramanujam, “Quantitative Physiology of the Precancerous Cervix in Vivo Through Optical Spectroscopy,” Neoplasia 11(4), 325–332 (2009).
    [Crossref] [PubMed]
  9. R. H. Farnsworth, M. Lackmann, M. G. Achen, and S. A. Stacker, “Vascular remodeling in cancer,” Oncogene 33(27), 3496–3505 (2014).
    [Crossref] [PubMed]
  10. C. Blatter, J. Weingast, A. Alex, B. Grajciar, W. Wieser, W. Drexler, R. Huber, and R. A. Leitgeb, “In situ structural and microangiographic assessment of human skin lesions with high-speed OCT,” Biomed. Opt. Express 3(10), 2636–2646 (2012).
    [Crossref] [PubMed]
  11. R. Reif and R. K. Wang, “Label-free imaging of blood vessel morphology with capillary resolution using optical microangiography,” Quant. Imaging Med. Surg. 2(3), 207–212 (2012).
    [PubMed]
  12. E. M. C. Hillman, A. Devor, A. K. Dunn, and D. A. Boas, “Laminar optical tomography: high-resolution 3D functional imaging of superficial tissues - art. no. 61431M,” P Soc Photo-Opt Ins 6143, M1431–M1431 (2006).
  13. H. Sherman, S. Klausner, and W. A. Cook, “Incident dark-field illumination: a new method for microcirculatory study,” Angiology 22(5), 295–303 (1971).
    [Crossref] [PubMed]
  14. K. R. Mathura, G. J. Bouma, and C. Ince, “Abnormal microcirculation in brain tumours during surgery,” Lancet 358(9294), 1698–1699 (2001).
    [Crossref] [PubMed]
  15. F. Feldchtein, V. Gelikonov, R. Iksanov, G. Gelikonov, R. Kuranov, A. Sergeev, N. Gladkova, M. Ourutina, D. Reitze, and J. Warren, “In vivo OCT imaging of hard and soft tissue of the oral cavity,” Opt. Express 3(6), 239–250 (1998).
    [Crossref] [PubMed]
  16. S. F. Chen, C. W. Lu, Y. M. Wang, M. T. Tsai, and C. C. Yang, “In vivo OCT imaging of the oral cavity tissue by use of a probe,” 2005 Pacific Rim Conference on Lasers and Electro-Optics, 198–199 (2005).
  17. P. K. Upputuri, K. Sivasubramanian, C. S. K. Mark, and M. Pramanik, “Recent Developments in Vascular Imaging Techniques in Tissue Engineering and Regenerative Medicine,” BioMed Res. Int. 2015, 783983 (2015).
    [Crossref] [PubMed]
  18. W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, “Orthogonal polarization spectral imaging: A new method for study of the microcirculation,” Nat. Med. 5(10), 1209–1212 (1999).
    [Crossref] [PubMed]
  19. M. Heger, J. Beek, K. Stenback, D. Faber, M. van Gemert, and C. Ince, “Darkfield orthogonal polarized spectral imaging for studying endovascular laser-tissue interactions in vivo - a preliminary study,” Opt. Express 13(3), 702–715 (2005).
    [Crossref] [PubMed]
  20. S. Andrejevic, J. F. Savary, C. Fontolliet, P. Monnier, and H. van Den Bergh, “7,12-Dimethylbenz[a]anthracene-induced ‘early’ squamous cell carcinoma in the Golden Syrian hamster: Evaluation of an animal model and comparison with ‘early’ forms of human squamous cell carcinoma in the upper aero-digestive tract,” Int. J. Exp. Pathol. 77(1), 7–14 (1996).
    [Crossref] [PubMed]
  21. X. Liu, Y. Huang, and J. U. Kang, “Dark-field illuminated reflectance fiber bundle endoscopic microscope,” J. Biomed. Opt. 16(4), 046003 (2011).
    [Crossref] [PubMed]
  22. S. Preibisch, S. Saalfeld, and P. Tomancak, “Globally optimal stitching of tiled 3D microscopic image acquisitions,” Bioinformatics 25(11), 1463–1465 (2009).
    [Crossref] [PubMed]
  23. R. Estrada, C. Tomasi, M. T. Cabrera, D. K. Wallace, S. F. Freedman, and S. Farsiu, “Exploratory Dijkstra forest based automatic vessel segmentation: applications in video indirect ophthalmoscopy (VIO),” Biomed. Opt. Express 3(2), 327–339 (2012).
    [Crossref] [PubMed]
  24. F. Farokhian and H. Demirel, “Blood Vessels Detection and Segmentation in Retina using Gabor Filters,” 2013 10th International Conference on High Capacity Optical Networks and Enabling Technologies (Honet-Cns), 104–108 (2013).
    [Crossref]
  25. S. K. Kuri and M. R. Hossain, “Automated Retinal Blood Vessels Extraction Using Optimized Gabor Filter,” 2014 International Conference on Informatics, Electronics & Vision (Iciev) (2014).
    [Crossref]
  26. M. Nandy and M. Banerjee, “Retinal Vessel Segmentation Using Gabor Filter and Artificial Neural Network,” Proc Int Conf Emerg, 157–160 (2012).
    [Crossref]
  27. C. Heneghan, J. Flynn, M. O’Keefe, and M. Cahill, “Characterization of changes in blood vessel width and tortuosity in retinopathy of prematurity using image analysis,” Med. Image Anal. 6(4), 407–429 (2002).
    [Crossref] [PubMed]
  28. X. R. Bao, X. Ge, L. H. She, and S. Zhang, “Segmentation of retinal blood vessels based on cake filter,” BioMed Res. Int. 2015, 137024 (2015).
    [Crossref] [PubMed]
  29. J. V. K. Saumitra Kumar Kuri, “Automated Segmentation of Retinal Blood Vessels using Optimized Gabor Filter with Local Entropy Thresholding,” Int. J. Comput. Appl. 114, 37–42 (2015).
  30. S. Goel, D. G. Duda, L. Xu, L. L. Munn, Y. Boucher, D. Fukumura, and R. K. Jain, “Normalization of the Vasculature for Treatment of Cancer and Other Diseases,” Physiol. Rev. 91(3), 1071–1121 (2011).
    [Crossref] [PubMed]
  31. C. Y. Li, S. Shan, Q. Huang, R. D. Braun, J. Lanzen, K. Hu, P. Lin, and M. W. Dewhirst, “Initial stages of tumor cell-induced angiogenesis: Evaluation via skin window chambers in rodent models,” J. Natl. Cancer Inst. 92(2), 143–147 (2000).
    [Crossref] [PubMed]
  32. L. Conroy, R. S. DaCosta, and I. A. Vitkin, “Quantifying tissue microvasculature with speckle variance optical coherence tomography,” Opt. Lett. 37(15), 3180–3182 (2012).
    [Crossref] [PubMed]
  33. S. E. Shelton, Y. Z. Lee, M. Lee, E. Cherin, F. S. Foster, S. R. Aylward, and P. A. Dayton, “Quantification of Microvascular Tortuosity during Tumor Evolution Using Acoustic Angiography,” Ultrasound Med. Biol. 41(7), 1896–1904 (2015).
    [Crossref] [PubMed]
  34. A. G. Lurie, M. Tatematsu, T. Nakatsuka, R. M. Rippey, and N. Ito, “Anatomical and Functional Vascular Changes in Hamster Cheek Pouch during Carcinogenesis Induced by 7, 12-Dimethylbenz(a)Anthracene,” Cancer Res. 43(12 Pt 1), 5986–5994 (1983).
    [PubMed]
  35. P. T. Goedhart, M. Khalilzada, R. Bezemer, J. Merza, and C. Ince, “Sidestream Dark Field (SDF) imaging: a novel stroboscopic LED ring-based imaging modality for clinical assessment of the microcirculation,” Opt. Express 15(23), 15101–15114 (2007).
    [Crossref] [PubMed]
  36. F. Farahmand, K. Eftekhari, V. Modarresi, M. Najafi-Sani, A. Khodadad, and F. Motamed, “Comparing Oral Route Paraffin Oil versus Rectal Route for Disimpaction in Children with Chronic Constipation; a Randomized Control Trial,” Iran. J. Pediatr. 20(3), 291–296 (2010).
    [PubMed]
  37. A. L. Harris, “Hypoxia--A key regulatory factor in tumour growth,” Nat. Rev. Cancer 2(1), 38–47 (2002).
    [Crossref] [PubMed]
  38. F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
    [Crossref] [PubMed]
  39. F. Hu, K. Vishwanath, J. Lo, A. Erkanli, C. Mulvey, W. T. Lee, and N. Ramanujam, “Rapid Determination of Oxygen Saturation and Vascularity for Cancer Detection,” PLoS One 8(12), e82977 (2013).
    [Crossref] [PubMed]
  40. J. Y. Lo, J. Q. Brown, S. Dhar, B. Yu, G. M. Palmer, N. M. Jokerst, and N. Ramanujam, “Wavelength Optimization for Quantitative Spectral Imaging of Breast Tumor Margins,” PLoS One 8(4), e61767 (2013).
    [Crossref] [PubMed]
  41. M. Khalilzada, K. Dogan, C. Ince, and J. Stam, “Sublingual Microvascular Changes in Patients With Cerebral Small Vessel Disease,” Stroke 42(7), 2071–2073 (2011).
    [Crossref] [PubMed]

2015 (5)

J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D. M. Parkin, D. Forman, and F. Bray, “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” Int. J. Cancer 136(5), E359–E386 (2015).
[Crossref] [PubMed]

P. K. Upputuri, K. Sivasubramanian, C. S. K. Mark, and M. Pramanik, “Recent Developments in Vascular Imaging Techniques in Tissue Engineering and Regenerative Medicine,” BioMed Res. Int. 2015, 783983 (2015).
[Crossref] [PubMed]

X. R. Bao, X. Ge, L. H. She, and S. Zhang, “Segmentation of retinal blood vessels based on cake filter,” BioMed Res. Int. 2015, 137024 (2015).
[Crossref] [PubMed]

J. V. K. Saumitra Kumar Kuri, “Automated Segmentation of Retinal Blood Vessels using Optimized Gabor Filter with Local Entropy Thresholding,” Int. J. Comput. Appl. 114, 37–42 (2015).

S. E. Shelton, Y. Z. Lee, M. Lee, E. Cherin, F. S. Foster, S. R. Aylward, and P. A. Dayton, “Quantification of Microvascular Tortuosity during Tumor Evolution Using Acoustic Angiography,” Ultrasound Med. Biol. 41(7), 1896–1904 (2015).
[Crossref] [PubMed]

2014 (2)

F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
[Crossref] [PubMed]

R. H. Farnsworth, M. Lackmann, M. G. Achen, and S. A. Stacker, “Vascular remodeling in cancer,” Oncogene 33(27), 3496–3505 (2014).
[Crossref] [PubMed]

2013 (2)

F. Hu, K. Vishwanath, J. Lo, A. Erkanli, C. Mulvey, W. T. Lee, and N. Ramanujam, “Rapid Determination of Oxygen Saturation and Vascularity for Cancer Detection,” PLoS One 8(12), e82977 (2013).
[Crossref] [PubMed]

J. Y. Lo, J. Q. Brown, S. Dhar, B. Yu, G. M. Palmer, N. M. Jokerst, and N. Ramanujam, “Wavelength Optimization for Quantitative Spectral Imaging of Breast Tumor Margins,” PLoS One 8(4), e61767 (2013).
[Crossref] [PubMed]

2012 (5)

2011 (3)

X. Liu, Y. Huang, and J. U. Kang, “Dark-field illuminated reflectance fiber bundle endoscopic microscope,” J. Biomed. Opt. 16(4), 046003 (2011).
[Crossref] [PubMed]

S. Goel, D. G. Duda, L. Xu, L. L. Munn, Y. Boucher, D. Fukumura, and R. K. Jain, “Normalization of the Vasculature for Treatment of Cancer and Other Diseases,” Physiol. Rev. 91(3), 1071–1121 (2011).
[Crossref] [PubMed]

M. Khalilzada, K. Dogan, C. Ince, and J. Stam, “Sublingual Microvascular Changes in Patients With Cerebral Small Vessel Disease,” Stroke 42(7), 2071–2073 (2011).
[Crossref] [PubMed]

2010 (1)

F. Farahmand, K. Eftekhari, V. Modarresi, M. Najafi-Sani, A. Khodadad, and F. Motamed, “Comparing Oral Route Paraffin Oil versus Rectal Route for Disimpaction in Children with Chronic Constipation; a Randomized Control Trial,” Iran. J. Pediatr. 20(3), 291–296 (2010).
[PubMed]

2009 (2)

V. T. C. Chang, P. S. Cartwright, S. M. Bean, G. M. Palmer, R. C. Bentley, and N. Ramanujam, “Quantitative Physiology of the Precancerous Cervix in Vivo Through Optical Spectroscopy,” Neoplasia 11(4), 325–332 (2009).
[Crossref] [PubMed]

S. Preibisch, S. Saalfeld, and P. Tomancak, “Globally optimal stitching of tiled 3D microscopic image acquisitions,” Bioinformatics 25(11), 1463–1465 (2009).
[Crossref] [PubMed]

2007 (1)

2005 (1)

2002 (2)

C. Heneghan, J. Flynn, M. O’Keefe, and M. Cahill, “Characterization of changes in blood vessel width and tortuosity in retinopathy of prematurity using image analysis,” Med. Image Anal. 6(4), 407–429 (2002).
[Crossref] [PubMed]

A. L. Harris, “Hypoxia--A key regulatory factor in tumour growth,” Nat. Rev. Cancer 2(1), 38–47 (2002).
[Crossref] [PubMed]

2001 (1)

K. R. Mathura, G. J. Bouma, and C. Ince, “Abnormal microcirculation in brain tumours during surgery,” Lancet 358(9294), 1698–1699 (2001).
[Crossref] [PubMed]

2000 (1)

C. Y. Li, S. Shan, Q. Huang, R. D. Braun, J. Lanzen, K. Hu, P. Lin, and M. W. Dewhirst, “Initial stages of tumor cell-induced angiogenesis: Evaluation via skin window chambers in rodent models,” J. Natl. Cancer Inst. 92(2), 143–147 (2000).
[Crossref] [PubMed]

1999 (1)

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, “Orthogonal polarization spectral imaging: A new method for study of the microcirculation,” Nat. Med. 5(10), 1209–1212 (1999).
[Crossref] [PubMed]

1998 (1)

1996 (1)

S. Andrejevic, J. F. Savary, C. Fontolliet, P. Monnier, and H. van Den Bergh, “7,12-Dimethylbenz[a]anthracene-induced ‘early’ squamous cell carcinoma in the Golden Syrian hamster: Evaluation of an animal model and comparison with ‘early’ forms of human squamous cell carcinoma in the upper aero-digestive tract,” Int. J. Exp. Pathol. 77(1), 7–14 (1996).
[Crossref] [PubMed]

1995 (1)

Y. Jin, G. L. Tipoe, F. H. White, and L. Yang, “A quantitative investigation of immunocytochemically stained blood vessels in normal, benign, premalignant and malignant human oral cheek epithelium,” Virchows Arch. 427(2), 145–151 (1995).
[PubMed]

1983 (1)

A. G. Lurie, M. Tatematsu, T. Nakatsuka, R. M. Rippey, and N. Ito, “Anatomical and Functional Vascular Changes in Hamster Cheek Pouch during Carcinogenesis Induced by 7, 12-Dimethylbenz(a)Anthracene,” Cancer Res. 43(12 Pt 1), 5986–5994 (1983).
[PubMed]

1971 (1)

H. Sherman, S. Klausner, and W. A. Cook, “Incident dark-field illumination: a new method for microcirculatory study,” Angiology 22(5), 295–303 (1971).
[Crossref] [PubMed]

1963 (1)

J. Folkman, D. M. Long, and F. F. Becker, “Growth and Metastasis of Tumor in Organ Culture,” Cancer 16(4), 453–467 (1963).
[Crossref] [PubMed]

1962 (1)

M. J. Folkman, D. M. Long, and F. F. Becker, “Tumor growth in organ culture,” Surg. Forum 13, 81–83 (1962).
[PubMed]

Achen, M. G.

R. H. Farnsworth, M. Lackmann, M. G. Achen, and S. A. Stacker, “Vascular remodeling in cancer,” Oncogene 33(27), 3496–3505 (2014).
[Crossref] [PubMed]

Afshari, H. R.

F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
[Crossref] [PubMed]

Alex, A.

Andrejevic, S.

S. Andrejevic, J. F. Savary, C. Fontolliet, P. Monnier, and H. van Den Bergh, “7,12-Dimethylbenz[a]anthracene-induced ‘early’ squamous cell carcinoma in the Golden Syrian hamster: Evaluation of an animal model and comparison with ‘early’ forms of human squamous cell carcinoma in the upper aero-digestive tract,” Int. J. Exp. Pathol. 77(1), 7–14 (1996).
[Crossref] [PubMed]

Aylward, S. R.

S. E. Shelton, Y. Z. Lee, M. Lee, E. Cherin, F. S. Foster, S. R. Aylward, and P. A. Dayton, “Quantification of Microvascular Tortuosity during Tumor Evolution Using Acoustic Angiography,” Ultrasound Med. Biol. 41(7), 1896–1904 (2015).
[Crossref] [PubMed]

Banerjee, M.

M. Nandy and M. Banerjee, “Retinal Vessel Segmentation Using Gabor Filter and Artificial Neural Network,” Proc Int Conf Emerg, 157–160 (2012).
[Crossref]

Bao, X. R.

X. R. Bao, X. Ge, L. H. She, and S. Zhang, “Segmentation of retinal blood vessels based on cake filter,” BioMed Res. Int. 2015, 137024 (2015).
[Crossref] [PubMed]

Bean, S. M.

V. T. C. Chang, P. S. Cartwright, S. M. Bean, G. M. Palmer, R. C. Bentley, and N. Ramanujam, “Quantitative Physiology of the Precancerous Cervix in Vivo Through Optical Spectroscopy,” Neoplasia 11(4), 325–332 (2009).
[Crossref] [PubMed]

Becker, F. F.

J. Folkman, D. M. Long, and F. F. Becker, “Growth and Metastasis of Tumor in Organ Culture,” Cancer 16(4), 453–467 (1963).
[Crossref] [PubMed]

M. J. Folkman, D. M. Long, and F. F. Becker, “Tumor growth in organ culture,” Surg. Forum 13, 81–83 (1962).
[PubMed]

Beek, J.

Bentley, R. C.

V. T. C. Chang, P. S. Cartwright, S. M. Bean, G. M. Palmer, R. C. Bentley, and N. Ramanujam, “Quantitative Physiology of the Precancerous Cervix in Vivo Through Optical Spectroscopy,” Neoplasia 11(4), 325–332 (2009).
[Crossref] [PubMed]

Bezemer, R.

Blatter, C.

Boucher, Y.

S. Goel, D. G. Duda, L. Xu, L. L. Munn, Y. Boucher, D. Fukumura, and R. K. Jain, “Normalization of the Vasculature for Treatment of Cancer and Other Diseases,” Physiol. Rev. 91(3), 1071–1121 (2011).
[Crossref] [PubMed]

Bouma, G. J.

K. R. Mathura, G. J. Bouma, and C. Ince, “Abnormal microcirculation in brain tumours during surgery,” Lancet 358(9294), 1698–1699 (2001).
[Crossref] [PubMed]

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, “Orthogonal polarization spectral imaging: A new method for study of the microcirculation,” Nat. Med. 5(10), 1209–1212 (1999).
[Crossref] [PubMed]

Braun, R. D.

C. Y. Li, S. Shan, Q. Huang, R. D. Braun, J. Lanzen, K. Hu, P. Lin, and M. W. Dewhirst, “Initial stages of tumor cell-induced angiogenesis: Evaluation via skin window chambers in rodent models,” J. Natl. Cancer Inst. 92(2), 143–147 (2000).
[Crossref] [PubMed]

Bray, F.

J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D. M. Parkin, D. Forman, and F. Bray, “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” Int. J. Cancer 136(5), E359–E386 (2015).
[Crossref] [PubMed]

Brown, J. Q.

J. Y. Lo, J. Q. Brown, S. Dhar, B. Yu, G. M. Palmer, N. M. Jokerst, and N. Ramanujam, “Wavelength Optimization for Quantitative Spectral Imaging of Breast Tumor Margins,” PLoS One 8(4), e61767 (2013).
[Crossref] [PubMed]

Cabrera, M. T.

Cahill, M.

C. Heneghan, J. Flynn, M. O’Keefe, and M. Cahill, “Characterization of changes in blood vessel width and tortuosity in retinopathy of prematurity using image analysis,” Med. Image Anal. 6(4), 407–429 (2002).
[Crossref] [PubMed]

Cartwright, P. S.

V. T. C. Chang, P. S. Cartwright, S. M. Bean, G. M. Palmer, R. C. Bentley, and N. Ramanujam, “Quantitative Physiology of the Precancerous Cervix in Vivo Through Optical Spectroscopy,” Neoplasia 11(4), 325–332 (2009).
[Crossref] [PubMed]

Chang, V. T. C.

V. T. C. Chang, P. S. Cartwright, S. M. Bean, G. M. Palmer, R. C. Bentley, and N. Ramanujam, “Quantitative Physiology of the Precancerous Cervix in Vivo Through Optical Spectroscopy,” Neoplasia 11(4), 325–332 (2009).
[Crossref] [PubMed]

Chen, S. F.

S. F. Chen, C. W. Lu, Y. M. Wang, M. T. Tsai, and C. C. Yang, “In vivo OCT imaging of the oral cavity tissue by use of a probe,” 2005 Pacific Rim Conference on Lasers and Electro-Optics, 198–199 (2005).

Cherin, E.

S. E. Shelton, Y. Z. Lee, M. Lee, E. Cherin, F. S. Foster, S. R. Aylward, and P. A. Dayton, “Quantification of Microvascular Tortuosity during Tumor Evolution Using Acoustic Angiography,” Ultrasound Med. Biol. 41(7), 1896–1904 (2015).
[Crossref] [PubMed]

Conroy, L.

Cook, W. A.

H. Sherman, S. Klausner, and W. A. Cook, “Incident dark-field illumination: a new method for microcirculatory study,” Angiology 22(5), 295–303 (1971).
[Crossref] [PubMed]

DaCosta, R. S.

Dayton, P. A.

S. E. Shelton, Y. Z. Lee, M. Lee, E. Cherin, F. S. Foster, S. R. Aylward, and P. A. Dayton, “Quantification of Microvascular Tortuosity during Tumor Evolution Using Acoustic Angiography,” Ultrasound Med. Biol. 41(7), 1896–1904 (2015).
[Crossref] [PubMed]

Dewhirst, M. W.

C. Y. Li, S. Shan, Q. Huang, R. D. Braun, J. Lanzen, K. Hu, P. Lin, and M. W. Dewhirst, “Initial stages of tumor cell-induced angiogenesis: Evaluation via skin window chambers in rodent models,” J. Natl. Cancer Inst. 92(2), 143–147 (2000).
[Crossref] [PubMed]

Dhar, S.

J. Y. Lo, J. Q. Brown, S. Dhar, B. Yu, G. M. Palmer, N. M. Jokerst, and N. Ramanujam, “Wavelength Optimization for Quantitative Spectral Imaging of Breast Tumor Margins,” PLoS One 8(4), e61767 (2013).
[Crossref] [PubMed]

Dikshit, R.

J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D. M. Parkin, D. Forman, and F. Bray, “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” Int. J. Cancer 136(5), E359–E386 (2015).
[Crossref] [PubMed]

Dogan, K.

M. Khalilzada, K. Dogan, C. Ince, and J. Stam, “Sublingual Microvascular Changes in Patients With Cerebral Small Vessel Disease,” Stroke 42(7), 2071–2073 (2011).
[Crossref] [PubMed]

Drexler, W.

Duda, D. G.

S. Goel, D. G. Duda, L. Xu, L. L. Munn, Y. Boucher, D. Fukumura, and R. K. Jain, “Normalization of the Vasculature for Treatment of Cancer and Other Diseases,” Physiol. Rev. 91(3), 1071–1121 (2011).
[Crossref] [PubMed]

Eftekhari, K.

F. Farahmand, K. Eftekhari, V. Modarresi, M. Najafi-Sani, A. Khodadad, and F. Motamed, “Comparing Oral Route Paraffin Oil versus Rectal Route for Disimpaction in Children with Chronic Constipation; a Randomized Control Trial,” Iran. J. Pediatr. 20(3), 291–296 (2010).
[PubMed]

Erkanli, A.

F. Hu, K. Vishwanath, J. Lo, A. Erkanli, C. Mulvey, W. T. Lee, and N. Ramanujam, “Rapid Determination of Oxygen Saturation and Vascularity for Cancer Detection,” PLoS One 8(12), e82977 (2013).
[Crossref] [PubMed]

Esclamado, R. M.

F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
[Crossref] [PubMed]

Eser, S.

J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D. M. Parkin, D. Forman, and F. Bray, “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” Int. J. Cancer 136(5), E359–E386 (2015).
[Crossref] [PubMed]

Estrada, R.

Faber, D.

Farahmand, F.

F. Farahmand, K. Eftekhari, V. Modarresi, M. Najafi-Sani, A. Khodadad, and F. Motamed, “Comparing Oral Route Paraffin Oil versus Rectal Route for Disimpaction in Children with Chronic Constipation; a Randomized Control Trial,” Iran. J. Pediatr. 20(3), 291–296 (2010).
[PubMed]

Farnsworth, R. H.

R. H. Farnsworth, M. Lackmann, M. G. Achen, and S. A. Stacker, “Vascular remodeling in cancer,” Oncogene 33(27), 3496–3505 (2014).
[Crossref] [PubMed]

Farsiu, S.

Feldchtein, F.

Ferlay, J.

J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D. M. Parkin, D. Forman, and F. Bray, “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” Int. J. Cancer 136(5), E359–E386 (2015).
[Crossref] [PubMed]

Fisher, S.

F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
[Crossref] [PubMed]

Flynn, J.

C. Heneghan, J. Flynn, M. O’Keefe, and M. Cahill, “Characterization of changes in blood vessel width and tortuosity in retinopathy of prematurity using image analysis,” Med. Image Anal. 6(4), 407–429 (2002).
[Crossref] [PubMed]

Folkman, J.

J. Folkman, D. M. Long, and F. F. Becker, “Growth and Metastasis of Tumor in Organ Culture,” Cancer 16(4), 453–467 (1963).
[Crossref] [PubMed]

Folkman, M. J.

M. J. Folkman, D. M. Long, and F. F. Becker, “Tumor growth in organ culture,” Surg. Forum 13, 81–83 (1962).
[PubMed]

Fontolliet, C.

S. Andrejevic, J. F. Savary, C. Fontolliet, P. Monnier, and H. van Den Bergh, “7,12-Dimethylbenz[a]anthracene-induced ‘early’ squamous cell carcinoma in the Golden Syrian hamster: Evaluation of an animal model and comparison with ‘early’ forms of human squamous cell carcinoma in the upper aero-digestive tract,” Int. J. Exp. Pathol. 77(1), 7–14 (1996).
[Crossref] [PubMed]

Forman, D.

J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D. M. Parkin, D. Forman, and F. Bray, “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” Int. J. Cancer 136(5), E359–E386 (2015).
[Crossref] [PubMed]

Foster, F. S.

S. E. Shelton, Y. Z. Lee, M. Lee, E. Cherin, F. S. Foster, S. R. Aylward, and P. A. Dayton, “Quantification of Microvascular Tortuosity during Tumor Evolution Using Acoustic Angiography,” Ultrasound Med. Biol. 41(7), 1896–1904 (2015).
[Crossref] [PubMed]

Freedman, S. F.

Fukumura, D.

S. Goel, D. G. Duda, L. Xu, L. L. Munn, Y. Boucher, D. Fukumura, and R. K. Jain, “Normalization of the Vasculature for Treatment of Cancer and Other Diseases,” Physiol. Rev. 91(3), 1071–1121 (2011).
[Crossref] [PubMed]

Ge, X.

X. R. Bao, X. Ge, L. H. She, and S. Zhang, “Segmentation of retinal blood vessels based on cake filter,” BioMed Res. Int. 2015, 137024 (2015).
[Crossref] [PubMed]

Gelikonov, G.

Gelikonov, V.

Gladkova, N.

Goedhart, P. T.

Goel, S.

S. Goel, D. G. Duda, L. Xu, L. L. Munn, Y. Boucher, D. Fukumura, and R. K. Jain, “Normalization of the Vasculature for Treatment of Cancer and Other Diseases,” Physiol. Rev. 91(3), 1071–1121 (2011).
[Crossref] [PubMed]

Grajciar, B.

Groner, W.

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, “Orthogonal polarization spectral imaging: A new method for study of the microcirculation,” Nat. Med. 5(10), 1209–1212 (1999).
[Crossref] [PubMed]

Harris, A. G.

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, “Orthogonal polarization spectral imaging: A new method for study of the microcirculation,” Nat. Med. 5(10), 1209–1212 (1999).
[Crossref] [PubMed]

Harris, A. L.

A. L. Harris, “Hypoxia--A key regulatory factor in tumour growth,” Nat. Rev. Cancer 2(1), 38–47 (2002).
[Crossref] [PubMed]

Heger, M.

Heneghan, C.

C. Heneghan, J. Flynn, M. O’Keefe, and M. Cahill, “Characterization of changes in blood vessel width and tortuosity in retinopathy of prematurity using image analysis,” Med. Image Anal. 6(4), 407–429 (2002).
[Crossref] [PubMed]

Hossain, M. R.

S. K. Kuri and M. R. Hossain, “Automated Retinal Blood Vessels Extraction Using Optimized Gabor Filter,” 2014 International Conference on Informatics, Electronics & Vision (Iciev) (2014).
[Crossref]

Hu, F.

F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
[Crossref] [PubMed]

F. Hu, K. Vishwanath, J. Lo, A. Erkanli, C. Mulvey, W. T. Lee, and N. Ramanujam, “Rapid Determination of Oxygen Saturation and Vascularity for Cancer Detection,” PLoS One 8(12), e82977 (2013).
[Crossref] [PubMed]

Hu, K.

C. Y. Li, S. Shan, Q. Huang, R. D. Braun, J. Lanzen, K. Hu, P. Lin, and M. W. Dewhirst, “Initial stages of tumor cell-induced angiogenesis: Evaluation via skin window chambers in rodent models,” J. Natl. Cancer Inst. 92(2), 143–147 (2000).
[Crossref] [PubMed]

Huang, Q.

C. Y. Li, S. Shan, Q. Huang, R. D. Braun, J. Lanzen, K. Hu, P. Lin, and M. W. Dewhirst, “Initial stages of tumor cell-induced angiogenesis: Evaluation via skin window chambers in rodent models,” J. Natl. Cancer Inst. 92(2), 143–147 (2000).
[Crossref] [PubMed]

Huang, Y.

X. Liu, Y. Huang, and J. U. Kang, “Dark-field illuminated reflectance fiber bundle endoscopic microscope,” J. Biomed. Opt. 16(4), 046003 (2011).
[Crossref] [PubMed]

Huber, R.

Iksanov, R.

Ince, C.

M. Khalilzada, K. Dogan, C. Ince, and J. Stam, “Sublingual Microvascular Changes in Patients With Cerebral Small Vessel Disease,” Stroke 42(7), 2071–2073 (2011).
[Crossref] [PubMed]

P. T. Goedhart, M. Khalilzada, R. Bezemer, J. Merza, and C. Ince, “Sidestream Dark Field (SDF) imaging: a novel stroboscopic LED ring-based imaging modality for clinical assessment of the microcirculation,” Opt. Express 15(23), 15101–15114 (2007).
[Crossref] [PubMed]

M. Heger, J. Beek, K. Stenback, D. Faber, M. van Gemert, and C. Ince, “Darkfield orthogonal polarized spectral imaging for studying endovascular laser-tissue interactions in vivo - a preliminary study,” Opt. Express 13(3), 702–715 (2005).
[Crossref] [PubMed]

K. R. Mathura, G. J. Bouma, and C. Ince, “Abnormal microcirculation in brain tumours during surgery,” Lancet 358(9294), 1698–1699 (2001).
[Crossref] [PubMed]

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, “Orthogonal polarization spectral imaging: A new method for study of the microcirculation,” Nat. Med. 5(10), 1209–1212 (1999).
[Crossref] [PubMed]

Ito, N.

A. G. Lurie, M. Tatematsu, T. Nakatsuka, R. M. Rippey, and N. Ito, “Anatomical and Functional Vascular Changes in Hamster Cheek Pouch during Carcinogenesis Induced by 7, 12-Dimethylbenz(a)Anthracene,” Cancer Res. 43(12 Pt 1), 5986–5994 (1983).
[PubMed]

Jain, R. K.

S. Goel, D. G. Duda, L. Xu, L. L. Munn, Y. Boucher, D. Fukumura, and R. K. Jain, “Normalization of the Vasculature for Treatment of Cancer and Other Diseases,” Physiol. Rev. 91(3), 1071–1121 (2011).
[Crossref] [PubMed]

Jin, Y.

Y. Jin, G. L. Tipoe, F. H. White, and L. Yang, “A quantitative investigation of immunocytochemically stained blood vessels in normal, benign, premalignant and malignant human oral cheek epithelium,” Virchows Arch. 427(2), 145–151 (1995).
[PubMed]

Jokerst, N. M.

J. Y. Lo, J. Q. Brown, S. Dhar, B. Yu, G. M. Palmer, N. M. Jokerst, and N. Ramanujam, “Wavelength Optimization for Quantitative Spectral Imaging of Breast Tumor Margins,” PLoS One 8(4), e61767 (2013).
[Crossref] [PubMed]

Kang, J. U.

X. Liu, Y. Huang, and J. U. Kang, “Dark-field illuminated reflectance fiber bundle endoscopic microscope,” J. Biomed. Opt. 16(4), 046003 (2011).
[Crossref] [PubMed]

Khalilzada, M.

Khodadad, A.

F. Farahmand, K. Eftekhari, V. Modarresi, M. Najafi-Sani, A. Khodadad, and F. Motamed, “Comparing Oral Route Paraffin Oil versus Rectal Route for Disimpaction in Children with Chronic Constipation; a Randomized Control Trial,” Iran. J. Pediatr. 20(3), 291–296 (2010).
[PubMed]

Klausner, S.

H. Sherman, S. Klausner, and W. A. Cook, “Incident dark-field illumination: a new method for microcirculatory study,” Angiology 22(5), 295–303 (1971).
[Crossref] [PubMed]

Kuranov, R.

Kuri, S. K.

S. K. Kuri and M. R. Hossain, “Automated Retinal Blood Vessels Extraction Using Optimized Gabor Filter,” 2014 International Conference on Informatics, Electronics & Vision (Iciev) (2014).
[Crossref]

Lackmann, M.

R. H. Farnsworth, M. Lackmann, M. G. Achen, and S. A. Stacker, “Vascular remodeling in cancer,” Oncogene 33(27), 3496–3505 (2014).
[Crossref] [PubMed]

Lanzen, J.

C. Y. Li, S. Shan, Q. Huang, R. D. Braun, J. Lanzen, K. Hu, P. Lin, and M. W. Dewhirst, “Initial stages of tumor cell-induced angiogenesis: Evaluation via skin window chambers in rodent models,” J. Natl. Cancer Inst. 92(2), 143–147 (2000).
[Crossref] [PubMed]

Lee, M.

S. E. Shelton, Y. Z. Lee, M. Lee, E. Cherin, F. S. Foster, S. R. Aylward, and P. A. Dayton, “Quantification of Microvascular Tortuosity during Tumor Evolution Using Acoustic Angiography,” Ultrasound Med. Biol. 41(7), 1896–1904 (2015).
[Crossref] [PubMed]

Lee, W. T.

F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
[Crossref] [PubMed]

F. Hu, K. Vishwanath, J. Lo, A. Erkanli, C. Mulvey, W. T. Lee, and N. Ramanujam, “Rapid Determination of Oxygen Saturation and Vascularity for Cancer Detection,” PLoS One 8(12), e82977 (2013).
[Crossref] [PubMed]

Lee, Y. Z.

S. E. Shelton, Y. Z. Lee, M. Lee, E. Cherin, F. S. Foster, S. R. Aylward, and P. A. Dayton, “Quantification of Microvascular Tortuosity during Tumor Evolution Using Acoustic Angiography,” Ultrasound Med. Biol. 41(7), 1896–1904 (2015).
[Crossref] [PubMed]

Leitgeb, R. A.

Li, C. Y.

C. Y. Li, S. Shan, Q. Huang, R. D. Braun, J. Lanzen, K. Hu, P. Lin, and M. W. Dewhirst, “Initial stages of tumor cell-induced angiogenesis: Evaluation via skin window chambers in rodent models,” J. Natl. Cancer Inst. 92(2), 143–147 (2000).
[Crossref] [PubMed]

Lin, P.

C. Y. Li, S. Shan, Q. Huang, R. D. Braun, J. Lanzen, K. Hu, P. Lin, and M. W. Dewhirst, “Initial stages of tumor cell-induced angiogenesis: Evaluation via skin window chambers in rodent models,” J. Natl. Cancer Inst. 92(2), 143–147 (2000).
[Crossref] [PubMed]

Liu, X.

X. Liu, Y. Huang, and J. U. Kang, “Dark-field illuminated reflectance fiber bundle endoscopic microscope,” J. Biomed. Opt. 16(4), 046003 (2011).
[Crossref] [PubMed]

Lo, J.

F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
[Crossref] [PubMed]

F. Hu, K. Vishwanath, J. Lo, A. Erkanli, C. Mulvey, W. T. Lee, and N. Ramanujam, “Rapid Determination of Oxygen Saturation and Vascularity for Cancer Detection,” PLoS One 8(12), e82977 (2013).
[Crossref] [PubMed]

Lo, J. Y.

J. Y. Lo, J. Q. Brown, S. Dhar, B. Yu, G. M. Palmer, N. M. Jokerst, and N. Ramanujam, “Wavelength Optimization for Quantitative Spectral Imaging of Breast Tumor Margins,” PLoS One 8(4), e61767 (2013).
[Crossref] [PubMed]

Long, D. M.

J. Folkman, D. M. Long, and F. F. Becker, “Growth and Metastasis of Tumor in Organ Culture,” Cancer 16(4), 453–467 (1963).
[Crossref] [PubMed]

M. J. Folkman, D. M. Long, and F. F. Becker, “Tumor growth in organ culture,” Surg. Forum 13, 81–83 (1962).
[PubMed]

Lu, C. W.

S. F. Chen, C. W. Lu, Y. M. Wang, M. T. Tsai, and C. C. Yang, “In vivo OCT imaging of the oral cavity tissue by use of a probe,” 2005 Pacific Rim Conference on Lasers and Electro-Optics, 198–199 (2005).

Lurie, A. G.

A. G. Lurie, M. Tatematsu, T. Nakatsuka, R. M. Rippey, and N. Ito, “Anatomical and Functional Vascular Changes in Hamster Cheek Pouch during Carcinogenesis Induced by 7, 12-Dimethylbenz(a)Anthracene,” Cancer Res. 43(12 Pt 1), 5986–5994 (1983).
[PubMed]

Mark, C. S. K.

P. K. Upputuri, K. Sivasubramanian, C. S. K. Mark, and M. Pramanik, “Recent Developments in Vascular Imaging Techniques in Tissue Engineering and Regenerative Medicine,” BioMed Res. Int. 2015, 783983 (2015).
[Crossref] [PubMed]

Mathers, C.

J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D. M. Parkin, D. Forman, and F. Bray, “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” Int. J. Cancer 136(5), E359–E386 (2015).
[Crossref] [PubMed]

Mathura, K. R.

K. R. Mathura, G. J. Bouma, and C. Ince, “Abnormal microcirculation in brain tumours during surgery,” Lancet 358(9294), 1698–1699 (2001).
[Crossref] [PubMed]

Merza, J.

Messmer, K.

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, “Orthogonal polarization spectral imaging: A new method for study of the microcirculation,” Nat. Med. 5(10), 1209–1212 (1999).
[Crossref] [PubMed]

Modarresi, V.

F. Farahmand, K. Eftekhari, V. Modarresi, M. Najafi-Sani, A. Khodadad, and F. Motamed, “Comparing Oral Route Paraffin Oil versus Rectal Route for Disimpaction in Children with Chronic Constipation; a Randomized Control Trial,” Iran. J. Pediatr. 20(3), 291–296 (2010).
[PubMed]

Monnier, P.

S. Andrejevic, J. F. Savary, C. Fontolliet, P. Monnier, and H. van Den Bergh, “7,12-Dimethylbenz[a]anthracene-induced ‘early’ squamous cell carcinoma in the Golden Syrian hamster: Evaluation of an animal model and comparison with ‘early’ forms of human squamous cell carcinoma in the upper aero-digestive tract,” Int. J. Exp. Pathol. 77(1), 7–14 (1996).
[Crossref] [PubMed]

Motamed, F.

F. Farahmand, K. Eftekhari, V. Modarresi, M. Najafi-Sani, A. Khodadad, and F. Motamed, “Comparing Oral Route Paraffin Oil versus Rectal Route for Disimpaction in Children with Chronic Constipation; a Randomized Control Trial,” Iran. J. Pediatr. 20(3), 291–296 (2010).
[PubMed]

Mulvey, C.

F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
[Crossref] [PubMed]

F. Hu, K. Vishwanath, J. Lo, A. Erkanli, C. Mulvey, W. T. Lee, and N. Ramanujam, “Rapid Determination of Oxygen Saturation and Vascularity for Cancer Detection,” PLoS One 8(12), e82977 (2013).
[Crossref] [PubMed]

Munn, L. L.

S. Goel, D. G. Duda, L. Xu, L. L. Munn, Y. Boucher, D. Fukumura, and R. K. Jain, “Normalization of the Vasculature for Treatment of Cancer and Other Diseases,” Physiol. Rev. 91(3), 1071–1121 (2011).
[Crossref] [PubMed]

Nadeau, R. G.

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, “Orthogonal polarization spectral imaging: A new method for study of the microcirculation,” Nat. Med. 5(10), 1209–1212 (1999).
[Crossref] [PubMed]

Najafi-Sani, M.

F. Farahmand, K. Eftekhari, V. Modarresi, M. Najafi-Sani, A. Khodadad, and F. Motamed, “Comparing Oral Route Paraffin Oil versus Rectal Route for Disimpaction in Children with Chronic Constipation; a Randomized Control Trial,” Iran. J. Pediatr. 20(3), 291–296 (2010).
[PubMed]

Nakatsuka, T.

A. G. Lurie, M. Tatematsu, T. Nakatsuka, R. M. Rippey, and N. Ito, “Anatomical and Functional Vascular Changes in Hamster Cheek Pouch during Carcinogenesis Induced by 7, 12-Dimethylbenz(a)Anthracene,” Cancer Res. 43(12 Pt 1), 5986–5994 (1983).
[PubMed]

Nandy, M.

M. Nandy and M. Banerjee, “Retinal Vessel Segmentation Using Gabor Filter and Artificial Neural Network,” Proc Int Conf Emerg, 157–160 (2012).
[Crossref]

O’Keefe, M.

C. Heneghan, J. Flynn, M. O’Keefe, and M. Cahill, “Characterization of changes in blood vessel width and tortuosity in retinopathy of prematurity using image analysis,” Med. Image Anal. 6(4), 407–429 (2002).
[Crossref] [PubMed]

Ourutina, M.

Palmer, G. M.

J. Y. Lo, J. Q. Brown, S. Dhar, B. Yu, G. M. Palmer, N. M. Jokerst, and N. Ramanujam, “Wavelength Optimization for Quantitative Spectral Imaging of Breast Tumor Margins,” PLoS One 8(4), e61767 (2013).
[Crossref] [PubMed]

V. T. C. Chang, P. S. Cartwright, S. M. Bean, G. M. Palmer, R. C. Bentley, and N. Ramanujam, “Quantitative Physiology of the Precancerous Cervix in Vivo Through Optical Spectroscopy,” Neoplasia 11(4), 325–332 (2009).
[Crossref] [PubMed]

Parkin, D. M.

J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D. M. Parkin, D. Forman, and F. Bray, “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” Int. J. Cancer 136(5), E359–E386 (2015).
[Crossref] [PubMed]

Pramanik, M.

P. K. Upputuri, K. Sivasubramanian, C. S. K. Mark, and M. Pramanik, “Recent Developments in Vascular Imaging Techniques in Tissue Engineering and Regenerative Medicine,” BioMed Res. Int. 2015, 783983 (2015).
[Crossref] [PubMed]

Preibisch, S.

S. Preibisch, S. Saalfeld, and P. Tomancak, “Globally optimal stitching of tiled 3D microscopic image acquisitions,” Bioinformatics 25(11), 1463–1465 (2009).
[Crossref] [PubMed]

Puscas, L.

F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
[Crossref] [PubMed]

Ramanujam, N.

F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
[Crossref] [PubMed]

F. Hu, K. Vishwanath, J. Lo, A. Erkanli, C. Mulvey, W. T. Lee, and N. Ramanujam, “Rapid Determination of Oxygen Saturation and Vascularity for Cancer Detection,” PLoS One 8(12), e82977 (2013).
[Crossref] [PubMed]

J. Y. Lo, J. Q. Brown, S. Dhar, B. Yu, G. M. Palmer, N. M. Jokerst, and N. Ramanujam, “Wavelength Optimization for Quantitative Spectral Imaging of Breast Tumor Margins,” PLoS One 8(4), e61767 (2013).
[Crossref] [PubMed]

V. T. C. Chang, P. S. Cartwright, S. M. Bean, G. M. Palmer, R. C. Bentley, and N. Ramanujam, “Quantitative Physiology of the Precancerous Cervix in Vivo Through Optical Spectroscopy,” Neoplasia 11(4), 325–332 (2009).
[Crossref] [PubMed]

Rebelo, M.

J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D. M. Parkin, D. Forman, and F. Bray, “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” Int. J. Cancer 136(5), E359–E386 (2015).
[Crossref] [PubMed]

Reif, R.

R. Reif and R. K. Wang, “Label-free imaging of blood vessel morphology with capillary resolution using optical microangiography,” Quant. Imaging Med. Surg. 2(3), 207–212 (2012).
[PubMed]

Reitze, D.

Rippey, R. M.

A. G. Lurie, M. Tatematsu, T. Nakatsuka, R. M. Rippey, and N. Ito, “Anatomical and Functional Vascular Changes in Hamster Cheek Pouch during Carcinogenesis Induced by 7, 12-Dimethylbenz(a)Anthracene,” Cancer Res. 43(12 Pt 1), 5986–5994 (1983).
[PubMed]

Saalfeld, S.

S. Preibisch, S. Saalfeld, and P. Tomancak, “Globally optimal stitching of tiled 3D microscopic image acquisitions,” Bioinformatics 25(11), 1463–1465 (2009).
[Crossref] [PubMed]

Saraswathi, T.

M. Sathyakumar, G. Sriram, T. Saraswathi, and B. Sivapathasundharam, “Immunohistochemical evaluation of mast cells and vascular endothelial proliferation in oral precancerous lesion-leukoplakia,” J. Oral Maxillofac. Pathol. 16(3), 343–348 (2012).
[Crossref] [PubMed]

Sathyakumar, M.

M. Sathyakumar, G. Sriram, T. Saraswathi, and B. Sivapathasundharam, “Immunohistochemical evaluation of mast cells and vascular endothelial proliferation in oral precancerous lesion-leukoplakia,” J. Oral Maxillofac. Pathol. 16(3), 343–348 (2012).
[Crossref] [PubMed]

Saumitra Kumar Kuri, J. V. K.

J. V. K. Saumitra Kumar Kuri, “Automated Segmentation of Retinal Blood Vessels using Optimized Gabor Filter with Local Entropy Thresholding,” Int. J. Comput. Appl. 114, 37–42 (2015).

Savary, J. F.

S. Andrejevic, J. F. Savary, C. Fontolliet, P. Monnier, and H. van Den Bergh, “7,12-Dimethylbenz[a]anthracene-induced ‘early’ squamous cell carcinoma in the Golden Syrian hamster: Evaluation of an animal model and comparison with ‘early’ forms of human squamous cell carcinoma in the upper aero-digestive tract,” Int. J. Exp. Pathol. 77(1), 7–14 (1996).
[Crossref] [PubMed]

Scher, R.

F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
[Crossref] [PubMed]

Sergeev, A.

Shan, S.

C. Y. Li, S. Shan, Q. Huang, R. D. Braun, J. Lanzen, K. Hu, P. Lin, and M. W. Dewhirst, “Initial stages of tumor cell-induced angiogenesis: Evaluation via skin window chambers in rodent models,” J. Natl. Cancer Inst. 92(2), 143–147 (2000).
[Crossref] [PubMed]

She, L. H.

X. R. Bao, X. Ge, L. H. She, and S. Zhang, “Segmentation of retinal blood vessels based on cake filter,” BioMed Res. Int. 2015, 137024 (2015).
[Crossref] [PubMed]

Shelton, S. E.

S. E. Shelton, Y. Z. Lee, M. Lee, E. Cherin, F. S. Foster, S. R. Aylward, and P. A. Dayton, “Quantification of Microvascular Tortuosity during Tumor Evolution Using Acoustic Angiography,” Ultrasound Med. Biol. 41(7), 1896–1904 (2015).
[Crossref] [PubMed]

Sherman, H.

H. Sherman, S. Klausner, and W. A. Cook, “Incident dark-field illumination: a new method for microcirculatory study,” Angiology 22(5), 295–303 (1971).
[Crossref] [PubMed]

Sivapathasundharam, B.

M. Sathyakumar, G. Sriram, T. Saraswathi, and B. Sivapathasundharam, “Immunohistochemical evaluation of mast cells and vascular endothelial proliferation in oral precancerous lesion-leukoplakia,” J. Oral Maxillofac. Pathol. 16(3), 343–348 (2012).
[Crossref] [PubMed]

Sivasubramanian, K.

P. K. Upputuri, K. Sivasubramanian, C. S. K. Mark, and M. Pramanik, “Recent Developments in Vascular Imaging Techniques in Tissue Engineering and Regenerative Medicine,” BioMed Res. Int. 2015, 783983 (2015).
[Crossref] [PubMed]

Soerjomataram, I.

J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D. M. Parkin, D. Forman, and F. Bray, “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” Int. J. Cancer 136(5), E359–E386 (2015).
[Crossref] [PubMed]

Sriram, G.

M. Sathyakumar, G. Sriram, T. Saraswathi, and B. Sivapathasundharam, “Immunohistochemical evaluation of mast cells and vascular endothelial proliferation in oral precancerous lesion-leukoplakia,” J. Oral Maxillofac. Pathol. 16(3), 343–348 (2012).
[Crossref] [PubMed]

Stacker, S. A.

R. H. Farnsworth, M. Lackmann, M. G. Achen, and S. A. Stacker, “Vascular remodeling in cancer,” Oncogene 33(27), 3496–3505 (2014).
[Crossref] [PubMed]

Stam, J.

M. Khalilzada, K. Dogan, C. Ince, and J. Stam, “Sublingual Microvascular Changes in Patients With Cerebral Small Vessel Disease,” Stroke 42(7), 2071–2073 (2011).
[Crossref] [PubMed]

Stenback, K.

Tatematsu, M.

A. G. Lurie, M. Tatematsu, T. Nakatsuka, R. M. Rippey, and N. Ito, “Anatomical and Functional Vascular Changes in Hamster Cheek Pouch during Carcinogenesis Induced by 7, 12-Dimethylbenz(a)Anthracene,” Cancer Res. 43(12 Pt 1), 5986–5994 (1983).
[PubMed]

Tipoe, G. L.

Y. Jin, G. L. Tipoe, F. H. White, and L. Yang, “A quantitative investigation of immunocytochemically stained blood vessels in normal, benign, premalignant and malignant human oral cheek epithelium,” Virchows Arch. 427(2), 145–151 (1995).
[PubMed]

Tomancak, P.

S. Preibisch, S. Saalfeld, and P. Tomancak, “Globally optimal stitching of tiled 3D microscopic image acquisitions,” Bioinformatics 25(11), 1463–1465 (2009).
[Crossref] [PubMed]

Tomasi, C.

Tsai, M. T.

S. F. Chen, C. W. Lu, Y. M. Wang, M. T. Tsai, and C. C. Yang, “In vivo OCT imaging of the oral cavity tissue by use of a probe,” 2005 Pacific Rim Conference on Lasers and Electro-Optics, 198–199 (2005).

Upputuri, P. K.

P. K. Upputuri, K. Sivasubramanian, C. S. K. Mark, and M. Pramanik, “Recent Developments in Vascular Imaging Techniques in Tissue Engineering and Regenerative Medicine,” BioMed Res. Int. 2015, 783983 (2015).
[Crossref] [PubMed]

van Den Bergh, H.

S. Andrejevic, J. F. Savary, C. Fontolliet, P. Monnier, and H. van Den Bergh, “7,12-Dimethylbenz[a]anthracene-induced ‘early’ squamous cell carcinoma in the Golden Syrian hamster: Evaluation of an animal model and comparison with ‘early’ forms of human squamous cell carcinoma in the upper aero-digestive tract,” Int. J. Exp. Pathol. 77(1), 7–14 (1996).
[Crossref] [PubMed]

van Gemert, M.

Vishwanath, K.

F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
[Crossref] [PubMed]

F. Hu, K. Vishwanath, J. Lo, A. Erkanli, C. Mulvey, W. T. Lee, and N. Ramanujam, “Rapid Determination of Oxygen Saturation and Vascularity for Cancer Detection,” PLoS One 8(12), e82977 (2013).
[Crossref] [PubMed]

Vitkin, I. A.

Wallace, D. K.

Wang, R. K.

R. Reif and R. K. Wang, “Label-free imaging of blood vessel morphology with capillary resolution using optical microangiography,” Quant. Imaging Med. Surg. 2(3), 207–212 (2012).
[PubMed]

Wang, Y. M.

S. F. Chen, C. W. Lu, Y. M. Wang, M. T. Tsai, and C. C. Yang, “In vivo OCT imaging of the oral cavity tissue by use of a probe,” 2005 Pacific Rim Conference on Lasers and Electro-Optics, 198–199 (2005).

Warren, J.

Weingast, J.

White, F. H.

Y. Jin, G. L. Tipoe, F. H. White, and L. Yang, “A quantitative investigation of immunocytochemically stained blood vessels in normal, benign, premalignant and malignant human oral cheek epithelium,” Virchows Arch. 427(2), 145–151 (1995).
[PubMed]

Wieser, W.

Winkelman, J. W.

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, “Orthogonal polarization spectral imaging: A new method for study of the microcirculation,” Nat. Med. 5(10), 1209–1212 (1999).
[Crossref] [PubMed]

Wolfgang Beumer, H.

F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
[Crossref] [PubMed]

Xu, L.

S. Goel, D. G. Duda, L. Xu, L. L. Munn, Y. Boucher, D. Fukumura, and R. K. Jain, “Normalization of the Vasculature for Treatment of Cancer and Other Diseases,” Physiol. Rev. 91(3), 1071–1121 (2011).
[Crossref] [PubMed]

Yang, C. C.

S. F. Chen, C. W. Lu, Y. M. Wang, M. T. Tsai, and C. C. Yang, “In vivo OCT imaging of the oral cavity tissue by use of a probe,” 2005 Pacific Rim Conference on Lasers and Electro-Optics, 198–199 (2005).

Yang, L.

Y. Jin, G. L. Tipoe, F. H. White, and L. Yang, “A quantitative investigation of immunocytochemically stained blood vessels in normal, benign, premalignant and malignant human oral cheek epithelium,” Virchows Arch. 427(2), 145–151 (1995).
[PubMed]

Yu, B.

J. Y. Lo, J. Q. Brown, S. Dhar, B. Yu, G. M. Palmer, N. M. Jokerst, and N. Ramanujam, “Wavelength Optimization for Quantitative Spectral Imaging of Breast Tumor Margins,” PLoS One 8(4), e61767 (2013).
[Crossref] [PubMed]

Zhang, S.

X. R. Bao, X. Ge, L. H. She, and S. Zhang, “Segmentation of retinal blood vessels based on cake filter,” BioMed Res. Int. 2015, 137024 (2015).
[Crossref] [PubMed]

Angiology (1)

H. Sherman, S. Klausner, and W. A. Cook, “Incident dark-field illumination: a new method for microcirculatory study,” Angiology 22(5), 295–303 (1971).
[Crossref] [PubMed]

Bioinformatics (1)

S. Preibisch, S. Saalfeld, and P. Tomancak, “Globally optimal stitching of tiled 3D microscopic image acquisitions,” Bioinformatics 25(11), 1463–1465 (2009).
[Crossref] [PubMed]

BioMed Res. Int. (2)

X. R. Bao, X. Ge, L. H. She, and S. Zhang, “Segmentation of retinal blood vessels based on cake filter,” BioMed Res. Int. 2015, 137024 (2015).
[Crossref] [PubMed]

P. K. Upputuri, K. Sivasubramanian, C. S. K. Mark, and M. Pramanik, “Recent Developments in Vascular Imaging Techniques in Tissue Engineering and Regenerative Medicine,” BioMed Res. Int. 2015, 783983 (2015).
[Crossref] [PubMed]

Biomed. Opt. Express (2)

Cancer (1)

J. Folkman, D. M. Long, and F. F. Becker, “Growth and Metastasis of Tumor in Organ Culture,” Cancer 16(4), 453–467 (1963).
[Crossref] [PubMed]

Cancer Res. (1)

A. G. Lurie, M. Tatematsu, T. Nakatsuka, R. M. Rippey, and N. Ito, “Anatomical and Functional Vascular Changes in Hamster Cheek Pouch during Carcinogenesis Induced by 7, 12-Dimethylbenz(a)Anthracene,” Cancer Res. 43(12 Pt 1), 5986–5994 (1983).
[PubMed]

Int. J. Cancer (1)

J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D. M. Parkin, D. Forman, and F. Bray, “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” Int. J. Cancer 136(5), E359–E386 (2015).
[Crossref] [PubMed]

Int. J. Comput. Appl. (1)

J. V. K. Saumitra Kumar Kuri, “Automated Segmentation of Retinal Blood Vessels using Optimized Gabor Filter with Local Entropy Thresholding,” Int. J. Comput. Appl. 114, 37–42 (2015).

Int. J. Exp. Pathol. (1)

S. Andrejevic, J. F. Savary, C. Fontolliet, P. Monnier, and H. van Den Bergh, “7,12-Dimethylbenz[a]anthracene-induced ‘early’ squamous cell carcinoma in the Golden Syrian hamster: Evaluation of an animal model and comparison with ‘early’ forms of human squamous cell carcinoma in the upper aero-digestive tract,” Int. J. Exp. Pathol. 77(1), 7–14 (1996).
[Crossref] [PubMed]

Iran. J. Pediatr. (1)

F. Farahmand, K. Eftekhari, V. Modarresi, M. Najafi-Sani, A. Khodadad, and F. Motamed, “Comparing Oral Route Paraffin Oil versus Rectal Route for Disimpaction in Children with Chronic Constipation; a Randomized Control Trial,” Iran. J. Pediatr. 20(3), 291–296 (2010).
[PubMed]

J. Biomed. Opt. (1)

X. Liu, Y. Huang, and J. U. Kang, “Dark-field illuminated reflectance fiber bundle endoscopic microscope,” J. Biomed. Opt. 16(4), 046003 (2011).
[Crossref] [PubMed]

J. Natl. Cancer Inst. (1)

C. Y. Li, S. Shan, Q. Huang, R. D. Braun, J. Lanzen, K. Hu, P. Lin, and M. W. Dewhirst, “Initial stages of tumor cell-induced angiogenesis: Evaluation via skin window chambers in rodent models,” J. Natl. Cancer Inst. 92(2), 143–147 (2000).
[Crossref] [PubMed]

J. Oral Maxillofac. Pathol. (1)

M. Sathyakumar, G. Sriram, T. Saraswathi, and B. Sivapathasundharam, “Immunohistochemical evaluation of mast cells and vascular endothelial proliferation in oral precancerous lesion-leukoplakia,” J. Oral Maxillofac. Pathol. 16(3), 343–348 (2012).
[Crossref] [PubMed]

Lancet (1)

K. R. Mathura, G. J. Bouma, and C. Ince, “Abnormal microcirculation in brain tumours during surgery,” Lancet 358(9294), 1698–1699 (2001).
[Crossref] [PubMed]

Med. Image Anal. (1)

C. Heneghan, J. Flynn, M. O’Keefe, and M. Cahill, “Characterization of changes in blood vessel width and tortuosity in retinopathy of prematurity using image analysis,” Med. Image Anal. 6(4), 407–429 (2002).
[Crossref] [PubMed]

Nat. Med. (1)

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, “Orthogonal polarization spectral imaging: A new method for study of the microcirculation,” Nat. Med. 5(10), 1209–1212 (1999).
[Crossref] [PubMed]

Nat. Rev. Cancer (1)

A. L. Harris, “Hypoxia--A key regulatory factor in tumour growth,” Nat. Rev. Cancer 2(1), 38–47 (2002).
[Crossref] [PubMed]

Neoplasia (1)

V. T. C. Chang, P. S. Cartwright, S. M. Bean, G. M. Palmer, R. C. Bentley, and N. Ramanujam, “Quantitative Physiology of the Precancerous Cervix in Vivo Through Optical Spectroscopy,” Neoplasia 11(4), 325–332 (2009).
[Crossref] [PubMed]

Oncogene (1)

R. H. Farnsworth, M. Lackmann, M. G. Achen, and S. A. Stacker, “Vascular remodeling in cancer,” Oncogene 33(27), 3496–3505 (2014).
[Crossref] [PubMed]

Opt. Express (3)

Opt. Lett. (1)

Oral Oncol. (1)

F. Hu, K. Vishwanath, H. Wolfgang Beumer, L. Puscas, H. R. Afshari, R. M. Esclamado, R. Scher, S. Fisher, J. Lo, C. Mulvey, N. Ramanujam, and W. T. Lee, “Assessment of the sensitivity and specificity of tissue-specific-based and anatomical-based optical biomarkers for rapid detection of human head and neck squamous cell carcinoma,” Oral Oncol. 50(9), 848–856 (2014).
[Crossref] [PubMed]

Physiol. Rev. (1)

S. Goel, D. G. Duda, L. Xu, L. L. Munn, Y. Boucher, D. Fukumura, and R. K. Jain, “Normalization of the Vasculature for Treatment of Cancer and Other Diseases,” Physiol. Rev. 91(3), 1071–1121 (2011).
[Crossref] [PubMed]

PLoS One (2)

F. Hu, K. Vishwanath, J. Lo, A. Erkanli, C. Mulvey, W. T. Lee, and N. Ramanujam, “Rapid Determination of Oxygen Saturation and Vascularity for Cancer Detection,” PLoS One 8(12), e82977 (2013).
[Crossref] [PubMed]

J. Y. Lo, J. Q. Brown, S. Dhar, B. Yu, G. M. Palmer, N. M. Jokerst, and N. Ramanujam, “Wavelength Optimization for Quantitative Spectral Imaging of Breast Tumor Margins,” PLoS One 8(4), e61767 (2013).
[Crossref] [PubMed]

Quant. Imaging Med. Surg. (1)

R. Reif and R. K. Wang, “Label-free imaging of blood vessel morphology with capillary resolution using optical microangiography,” Quant. Imaging Med. Surg. 2(3), 207–212 (2012).
[PubMed]

Stroke (1)

M. Khalilzada, K. Dogan, C. Ince, and J. Stam, “Sublingual Microvascular Changes in Patients With Cerebral Small Vessel Disease,” Stroke 42(7), 2071–2073 (2011).
[Crossref] [PubMed]

Surg. Forum (1)

M. J. Folkman, D. M. Long, and F. F. Becker, “Tumor growth in organ culture,” Surg. Forum 13, 81–83 (1962).
[PubMed]

Ultrasound Med. Biol. (1)

S. E. Shelton, Y. Z. Lee, M. Lee, E. Cherin, F. S. Foster, S. R. Aylward, and P. A. Dayton, “Quantification of Microvascular Tortuosity during Tumor Evolution Using Acoustic Angiography,” Ultrasound Med. Biol. 41(7), 1896–1904 (2015).
[Crossref] [PubMed]

Virchows Arch. (1)

Y. Jin, G. L. Tipoe, F. H. White, and L. Yang, “A quantitative investigation of immunocytochemically stained blood vessels in normal, benign, premalignant and malignant human oral cheek epithelium,” Virchows Arch. 427(2), 145–151 (1995).
[PubMed]

Other (7)

“Winning the Battle Against Head and Neck Cancer” (Seattle Cancer Care Alliance), retrieved http://www.seattlecca.org/diseases/head-neck-cancer-survival-rates.cfm .

E. M. C. Hillman, A. Devor, A. K. Dunn, and D. A. Boas, “Laminar optical tomography: high-resolution 3D functional imaging of superficial tissues - art. no. 61431M,” P Soc Photo-Opt Ins 6143, M1431–M1431 (2006).

S. F. Chen, C. W. Lu, Y. M. Wang, M. T. Tsai, and C. C. Yang, “In vivo OCT imaging of the oral cavity tissue by use of a probe,” 2005 Pacific Rim Conference on Lasers and Electro-Optics, 198–199 (2005).

NIH, “ https://costprojections.cancer.gov/graph.php ,” (2010).

F. Farokhian and H. Demirel, “Blood Vessels Detection and Segmentation in Retina using Gabor Filters,” 2013 10th International Conference on High Capacity Optical Networks and Enabling Technologies (Honet-Cns), 104–108 (2013).
[Crossref]

S. K. Kuri and M. R. Hossain, “Automated Retinal Blood Vessels Extraction Using Optimized Gabor Filter,” 2014 International Conference on Informatics, Electronics & Vision (Iciev) (2014).
[Crossref]

M. Nandy and M. Banerjee, “Retinal Vessel Segmentation Using Gabor Filter and Artificial Neural Network,” Proc Int Conf Emerg, 157–160 (2012).
[Crossref]

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Figures (7)

Fig. 1
Fig. 1 Schematic of the dark field microscope system and the measured resolution. The key components in the cross-polarized dark field microscopy system are the stop and iris, which are 8mm and 6mm, respectively. They remove specular reflectance while maintaining high contrast for the detected diffuse reflectance. Cross polarized imaging was achieved by placing a polarizer in the illumination channel and an analyzer in the collection channel. The power spectrum is shown. The measured resolution is 3.1 µm. The measured field of view is 1.5 mm by 1 mm.
Fig. 2
Fig. 2 Timeline and endpoints for the hamster study design. To demonstrate the ability of our dark field system to monitor in vivo vascular changes during carcinogenesis in an inducible cancer model, non-invasive cross-polarized dark field (CPDF) images were obtained from hamster cheek pouches at week 12, 14 and 17 after treatment with dimethylbenz[a]anthracene (DMBA). Biopsies were obtained at week 17 from the sites that were imaged to confirm the induction of cancer.
Fig. 3
Fig. 3 Representative images of the steps to obtain a Gabor mask from the raw images and the representative time course reverse G/R images obtained during the study. (A) A 3 by 3 image mosaic was obtained and stitched. The Gabor algorithm was applied to the reverse G/R image to obtain the Gabor mask. (B) The images depict the progression of a single cheek pouch from week 12 to week 17 of mineral oil or DMBA treatment. Pathology was confirmed for the image site at week 17. Pathology was not available at week 12 and 14 at the image sites since biopsy would damage the tissues and might alter our observation. (C) The corresponding Gabor masks are also shown. SCC: squamous cell carcinoma.
Fig. 4
Fig. 4 Gabor filter vascular segmentation accuracy is affected by vascular contrast. (A) Vascular images with varying levels of vascular contrast were simulated. Vascular contrast was defined as the difference between the average intensity in the vascular area and the average intensity in the non-vascular area. A total of 10 randomly selected hamster cheek pouches images (N = 4 for control from week 12, N = 2 for DMBA treated cheek pouch from week 12, 14 and 17 respectively) were used for the simulation. Representative simulated images and their corresponding validation are shown. The Gabor filter was used to segment the vasculature in the simulated images. The segmented masks were compared to the original gold-standard mask. True positive (TP), false negative (FN) and false positive (FP) pixels are identified and color-coded. (B) The computed sensitivities and specificities for varying vascular contrast. Sensitivity increased with vascular contrast and specificity remained above 90% in the simulations. Error bars show standard error.
Fig. 5
Fig. 5 The Gabor algorithm overestimated the vascular diameter of the small vessels. (A) Simulated vascular images with different diameters and tortuosities. (B) Gabor masks derived from the simulated vascular images. (C) Tortuosity, diameter and length were computed from the Gabor masks. Gabor algorithm overestimated the vascular diameter more than 50% when the vascular diameter were 20 µm. The errors of the extracted diameters were within 6% when the expected diameters were 200 or 400 µm. The errors of the extracted tortuosity and length were all within 5% when the expected diameters were 20, 200 or 400 µm. Dash lines show the 5% and −5% boundaries.
Fig. 6
Fig. 6 Gabor algorithm segments the vasculature with high accuracies. (A) A total of 10 randomly selected hamster cheek pouches images (N = 4 for control from week 12, N = 2 for DMBA treated cheek pouch from week 12, 14 and 17 respectively) were used to validate the Gabor masks. Ten manually traced masks were used to validate the Gabor masks. The manually traced masks served as the gold standard. The sensitivity and specificity for identifying the vasculature were computed for each selected image. (B) Vascular contrast was computed using the manually traced mask. Contrast was defined as the difference between the average intensity in the vascular area and non-vascular area. Contrast vs. sensitivity and specificity are shown. Sensitivity increased with contrast while specificity remained above 80% for the 10 selected images. Note the highest contrast computed from the selected image is less than 0.3. TP: true positive, FN: false negative, FP: false positive.
Fig. 7
Fig. 7 Vascular tortuosity, length, area fraction and diameter were computed from DMBA treated and control cheek pouches during the study. Significant changes in vascular tortuosity and length were observed during DMBA treatment (Friedman test). DMBA treated cheek pouches demonstrated significantly different trends compared to the vascular features in the control cheek pouches during the study. In addition, Wilcoxon sign-rank tests were performed between the extracted vascular features from the DMBA treated and control cheek pouches at week 17.Tortuosity and length in the DMBA treated cheek pouches was significant higher and lower than the control cheeks at week 17. Red bars indicate the means.

Tables (3)

Tables Icon

Table 1 Estimated cost for the critical components of optical coherence tomography, laminar optical tomography and cross-polarized dark field microscopy.

Tables Icon

Table 2 Definition of true positive, true negative, false positive and false negative for vessel classification.

Tables Icon

Table 3 Average sensitivity, specificity and contrast from the selected images.

Metrics