Abstract

Multimodal spectral imaging (MSI) based on auto-fluorescence imaging and Raman micro-spectroscopy was used to detect basal cell carcinoma (BCC) in tissue specimens excised during Mohs micrographic surgery. In this study, the MSI algorithm was optimized to maximize the diagnosis accuracy while minimizing the number of Raman spectra: the segmentation of the auto-fluorescence images was optimized according to the type of BCC, sampling points for Raman spectroscopy were generated based on auto-fluorescence intensity variance and segment area, additional Raman spectra were acquired when performance of the segmentation algorithm was sub-optimal. The results indicate that accurate diagnosis can be achieved with a sampling density of ~2,000 Raman spectra/cm2, based on sampling points generated by the MSI algorithms. The key benefit of MSI is that diagnosis of BCC is obtained based on intrinsic chemical contrast of the tissue, within time scales similar to frozen-section histopathology, but without requiring laborious sample preparation and subjective interpretation of stained frozen-sections.

© 2014 Optical Society of America

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2014 (3)

S. V. Mohan and A. L. S. Chang, “Advanced Basal Cell Carcinoma: Epidemiology and Therapeutic Innovations,” Curr. Dermatol. Rep. 3(1), 40–45 (2014).
[Crossref] [PubMed]

E. van Loo, K. Mosterd, G. A. M. Krekels, M. H. Roozeboom, J. U. Ostertag, C. D. Dirksen, P. M. Steijlen, H. A. Neumann, P. J. Nelemans, and N. W. J. Kelleners-Smeets, “Surgical excision versus Mohs’ micrographic surgery for basal cell carcinoma of the face: A randomised clinical trial with 10year follow-up,” Eur. J. Cancer 50(17), 3011–3020 (2014).
[Crossref] [PubMed]

K. Kong, F. Zaabar, E. Rakha, I. Ellis, A. Koloydenko, and I. Notingher, “Towards intra-operative diagnosis of tumours during breast conserving surgery by selective-sampling Raman micro-spectroscopy,” Phys. Med. Biol. 59(20), 6141–6152 (2014).
[Crossref] [PubMed]

2013 (1)

K. Kong, C. J. Rowlands, S. Varma, W. Perkins, I. H. Leach, A. A. Koloydenko, H. C. Williams, and I. Notingher, “Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 110(38), 15189–15194 (2013).
[Crossref] [PubMed]

2012 (2)

C. J. Rowlands, S. Varma, W. Perkins, I. Leach, H. Williams, and I. Notingher, “Rapid acquisition of Raman spectral maps through minimal sampling: applications in tissue imaging,” J. Biophotonics 5(3), 220–229 (2012).
[Crossref] [PubMed]

J. M. Baxter, A. N. Patel, and S. Varma, “Facial basal cell carcinoma,” BMJ 345(aug21 2), e5342 (2012).
[Crossref] [PubMed]

2009 (1)

M. Larraona-Puy, A. Ghita, A. Zoladek, W. Perkins, S. Varma, I. H. Leach, A. A. Koloydenko, H. Williams, and I. Notingher, “Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma,” J. Biomed. Opt. 14(5), 054031 (2009).
[Crossref] [PubMed]

2008 (1)

C. A. Lieber, S. K. Majumder, D. L. Ellis, D. D. Billheimer, and A. Mahadevan-Jansen, “In vivo nonmelanoma skin cancer diagnosis using Raman microspectroscopy,” Lasers Surg. Med. 40(7), 461–467 (2008).
[Crossref] [PubMed]

2005 (2)

R. J. O’Callaghan and D. R. Bull, “Combined morphological-spectral unsupervised image segmentation,” IEEE Trans. Image Process. 14(1), 49–62 (2005).
[Crossref] [PubMed]

I. W. Selesnick, R. G. Baraniuk, and N. G. Kingsbury, “The dual-tree complex wavelet transform,” IEEE Signal Process. Mag. 22(6), 123–151 (2005).
[Crossref]

2002 (1)

A. Nijssen, T. C. Bakker Schut, F. Heule, P. J. Caspers, D. P. Hayes, M. H. A. Neumann, and G. J. Puppels, “Discriminating Basal Cell Carcinoma from its Surrounding Tissue by Raman Spectroscopy,” J. Invest. Dermatol. 119(1), 64–69 (2002).
[Crossref] [PubMed]

1997 (1)

M. Gniadecka, H. C. Wulf, N. N. Mortensen, O. F. Nielsen, and D. H. Christensen, “Diagnosis of Basal Cell Carcinoma by Raman Spectroscopy,” J. Raman Spectrosc. 28, 125–129 (1997).

Bakker Schut, T. C.

A. Nijssen, T. C. Bakker Schut, F. Heule, P. J. Caspers, D. P. Hayes, M. H. A. Neumann, and G. J. Puppels, “Discriminating Basal Cell Carcinoma from its Surrounding Tissue by Raman Spectroscopy,” J. Invest. Dermatol. 119(1), 64–69 (2002).
[Crossref] [PubMed]

Baraniuk, R. G.

I. W. Selesnick, R. G. Baraniuk, and N. G. Kingsbury, “The dual-tree complex wavelet transform,” IEEE Signal Process. Mag. 22(6), 123–151 (2005).
[Crossref]

Baxter, J. M.

J. M. Baxter, A. N. Patel, and S. Varma, “Facial basal cell carcinoma,” BMJ 345(aug21 2), e5342 (2012).
[Crossref] [PubMed]

Billheimer, D. D.

C. A. Lieber, S. K. Majumder, D. L. Ellis, D. D. Billheimer, and A. Mahadevan-Jansen, “In vivo nonmelanoma skin cancer diagnosis using Raman microspectroscopy,” Lasers Surg. Med. 40(7), 461–467 (2008).
[Crossref] [PubMed]

Bull, D. R.

R. J. O’Callaghan and D. R. Bull, “Combined morphological-spectral unsupervised image segmentation,” IEEE Trans. Image Process. 14(1), 49–62 (2005).
[Crossref] [PubMed]

Caspers, P. J.

A. Nijssen, T. C. Bakker Schut, F. Heule, P. J. Caspers, D. P. Hayes, M. H. A. Neumann, and G. J. Puppels, “Discriminating Basal Cell Carcinoma from its Surrounding Tissue by Raman Spectroscopy,” J. Invest. Dermatol. 119(1), 64–69 (2002).
[Crossref] [PubMed]

Chang, A. L. S.

S. V. Mohan and A. L. S. Chang, “Advanced Basal Cell Carcinoma: Epidemiology and Therapeutic Innovations,” Curr. Dermatol. Rep. 3(1), 40–45 (2014).
[Crossref] [PubMed]

Christensen, D. H.

M. Gniadecka, H. C. Wulf, N. N. Mortensen, O. F. Nielsen, and D. H. Christensen, “Diagnosis of Basal Cell Carcinoma by Raman Spectroscopy,” J. Raman Spectrosc. 28, 125–129 (1997).

Dirksen, C. D.

E. van Loo, K. Mosterd, G. A. M. Krekels, M. H. Roozeboom, J. U. Ostertag, C. D. Dirksen, P. M. Steijlen, H. A. Neumann, P. J. Nelemans, and N. W. J. Kelleners-Smeets, “Surgical excision versus Mohs’ micrographic surgery for basal cell carcinoma of the face: A randomised clinical trial with 10year follow-up,” Eur. J. Cancer 50(17), 3011–3020 (2014).
[Crossref] [PubMed]

Ellis, D. L.

C. A. Lieber, S. K. Majumder, D. L. Ellis, D. D. Billheimer, and A. Mahadevan-Jansen, “In vivo nonmelanoma skin cancer diagnosis using Raman microspectroscopy,” Lasers Surg. Med. 40(7), 461–467 (2008).
[Crossref] [PubMed]

Ellis, I.

K. Kong, F. Zaabar, E. Rakha, I. Ellis, A. Koloydenko, and I. Notingher, “Towards intra-operative diagnosis of tumours during breast conserving surgery by selective-sampling Raman micro-spectroscopy,” Phys. Med. Biol. 59(20), 6141–6152 (2014).
[Crossref] [PubMed]

Ghita, A.

M. Larraona-Puy, A. Ghita, A. Zoladek, W. Perkins, S. Varma, I. H. Leach, A. A. Koloydenko, H. Williams, and I. Notingher, “Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma,” J. Biomed. Opt. 14(5), 054031 (2009).
[Crossref] [PubMed]

Gniadecka, M.

M. Gniadecka, H. C. Wulf, N. N. Mortensen, O. F. Nielsen, and D. H. Christensen, “Diagnosis of Basal Cell Carcinoma by Raman Spectroscopy,” J. Raman Spectrosc. 28, 125–129 (1997).

Hayes, D. P.

A. Nijssen, T. C. Bakker Schut, F. Heule, P. J. Caspers, D. P. Hayes, M. H. A. Neumann, and G. J. Puppels, “Discriminating Basal Cell Carcinoma from its Surrounding Tissue by Raman Spectroscopy,” J. Invest. Dermatol. 119(1), 64–69 (2002).
[Crossref] [PubMed]

Heule, F.

A. Nijssen, T. C. Bakker Schut, F. Heule, P. J. Caspers, D. P. Hayes, M. H. A. Neumann, and G. J. Puppels, “Discriminating Basal Cell Carcinoma from its Surrounding Tissue by Raman Spectroscopy,” J. Invest. Dermatol. 119(1), 64–69 (2002).
[Crossref] [PubMed]

Kelleners-Smeets, N. W. J.

E. van Loo, K. Mosterd, G. A. M. Krekels, M. H. Roozeboom, J. U. Ostertag, C. D. Dirksen, P. M. Steijlen, H. A. Neumann, P. J. Nelemans, and N. W. J. Kelleners-Smeets, “Surgical excision versus Mohs’ micrographic surgery for basal cell carcinoma of the face: A randomised clinical trial with 10year follow-up,” Eur. J. Cancer 50(17), 3011–3020 (2014).
[Crossref] [PubMed]

Kingsbury, N. G.

I. W. Selesnick, R. G. Baraniuk, and N. G. Kingsbury, “The dual-tree complex wavelet transform,” IEEE Signal Process. Mag. 22(6), 123–151 (2005).
[Crossref]

Koloydenko, A.

K. Kong, F. Zaabar, E. Rakha, I. Ellis, A. Koloydenko, and I. Notingher, “Towards intra-operative diagnosis of tumours during breast conserving surgery by selective-sampling Raman micro-spectroscopy,” Phys. Med. Biol. 59(20), 6141–6152 (2014).
[Crossref] [PubMed]

Koloydenko, A. A.

K. Kong, C. J. Rowlands, S. Varma, W. Perkins, I. H. Leach, A. A. Koloydenko, H. C. Williams, and I. Notingher, “Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 110(38), 15189–15194 (2013).
[Crossref] [PubMed]

M. Larraona-Puy, A. Ghita, A. Zoladek, W. Perkins, S. Varma, I. H. Leach, A. A. Koloydenko, H. Williams, and I. Notingher, “Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma,” J. Biomed. Opt. 14(5), 054031 (2009).
[Crossref] [PubMed]

Kong, K.

K. Kong, F. Zaabar, E. Rakha, I. Ellis, A. Koloydenko, and I. Notingher, “Towards intra-operative diagnosis of tumours during breast conserving surgery by selective-sampling Raman micro-spectroscopy,” Phys. Med. Biol. 59(20), 6141–6152 (2014).
[Crossref] [PubMed]

K. Kong, C. J. Rowlands, S. Varma, W. Perkins, I. H. Leach, A. A. Koloydenko, H. C. Williams, and I. Notingher, “Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 110(38), 15189–15194 (2013).
[Crossref] [PubMed]

Krekels, G. A. M.

E. van Loo, K. Mosterd, G. A. M. Krekels, M. H. Roozeboom, J. U. Ostertag, C. D. Dirksen, P. M. Steijlen, H. A. Neumann, P. J. Nelemans, and N. W. J. Kelleners-Smeets, “Surgical excision versus Mohs’ micrographic surgery for basal cell carcinoma of the face: A randomised clinical trial with 10year follow-up,” Eur. J. Cancer 50(17), 3011–3020 (2014).
[Crossref] [PubMed]

Larraona-Puy, M.

M. Larraona-Puy, A. Ghita, A. Zoladek, W. Perkins, S. Varma, I. H. Leach, A. A. Koloydenko, H. Williams, and I. Notingher, “Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma,” J. Biomed. Opt. 14(5), 054031 (2009).
[Crossref] [PubMed]

Leach, I.

C. J. Rowlands, S. Varma, W. Perkins, I. Leach, H. Williams, and I. Notingher, “Rapid acquisition of Raman spectral maps through minimal sampling: applications in tissue imaging,” J. Biophotonics 5(3), 220–229 (2012).
[Crossref] [PubMed]

Leach, I. H.

K. Kong, C. J. Rowlands, S. Varma, W. Perkins, I. H. Leach, A. A. Koloydenko, H. C. Williams, and I. Notingher, “Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 110(38), 15189–15194 (2013).
[Crossref] [PubMed]

M. Larraona-Puy, A. Ghita, A. Zoladek, W. Perkins, S. Varma, I. H. Leach, A. A. Koloydenko, H. Williams, and I. Notingher, “Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma,” J. Biomed. Opt. 14(5), 054031 (2009).
[Crossref] [PubMed]

Lieber, C. A.

C. A. Lieber, S. K. Majumder, D. L. Ellis, D. D. Billheimer, and A. Mahadevan-Jansen, “In vivo nonmelanoma skin cancer diagnosis using Raman microspectroscopy,” Lasers Surg. Med. 40(7), 461–467 (2008).
[Crossref] [PubMed]

Mahadevan-Jansen, A.

C. A. Lieber, S. K. Majumder, D. L. Ellis, D. D. Billheimer, and A. Mahadevan-Jansen, “In vivo nonmelanoma skin cancer diagnosis using Raman microspectroscopy,” Lasers Surg. Med. 40(7), 461–467 (2008).
[Crossref] [PubMed]

Majumder, S. K.

C. A. Lieber, S. K. Majumder, D. L. Ellis, D. D. Billheimer, and A. Mahadevan-Jansen, “In vivo nonmelanoma skin cancer diagnosis using Raman microspectroscopy,” Lasers Surg. Med. 40(7), 461–467 (2008).
[Crossref] [PubMed]

Mohan, S. V.

S. V. Mohan and A. L. S. Chang, “Advanced Basal Cell Carcinoma: Epidemiology and Therapeutic Innovations,” Curr. Dermatol. Rep. 3(1), 40–45 (2014).
[Crossref] [PubMed]

Mortensen, N. N.

M. Gniadecka, H. C. Wulf, N. N. Mortensen, O. F. Nielsen, and D. H. Christensen, “Diagnosis of Basal Cell Carcinoma by Raman Spectroscopy,” J. Raman Spectrosc. 28, 125–129 (1997).

Mosterd, K.

E. van Loo, K. Mosterd, G. A. M. Krekels, M. H. Roozeboom, J. U. Ostertag, C. D. Dirksen, P. M. Steijlen, H. A. Neumann, P. J. Nelemans, and N. W. J. Kelleners-Smeets, “Surgical excision versus Mohs’ micrographic surgery for basal cell carcinoma of the face: A randomised clinical trial with 10year follow-up,” Eur. J. Cancer 50(17), 3011–3020 (2014).
[Crossref] [PubMed]

Nelemans, P. J.

E. van Loo, K. Mosterd, G. A. M. Krekels, M. H. Roozeboom, J. U. Ostertag, C. D. Dirksen, P. M. Steijlen, H. A. Neumann, P. J. Nelemans, and N. W. J. Kelleners-Smeets, “Surgical excision versus Mohs’ micrographic surgery for basal cell carcinoma of the face: A randomised clinical trial with 10year follow-up,” Eur. J. Cancer 50(17), 3011–3020 (2014).
[Crossref] [PubMed]

Neumann, H. A.

E. van Loo, K. Mosterd, G. A. M. Krekels, M. H. Roozeboom, J. U. Ostertag, C. D. Dirksen, P. M. Steijlen, H. A. Neumann, P. J. Nelemans, and N. W. J. Kelleners-Smeets, “Surgical excision versus Mohs’ micrographic surgery for basal cell carcinoma of the face: A randomised clinical trial with 10year follow-up,” Eur. J. Cancer 50(17), 3011–3020 (2014).
[Crossref] [PubMed]

Neumann, M. H. A.

A. Nijssen, T. C. Bakker Schut, F. Heule, P. J. Caspers, D. P. Hayes, M. H. A. Neumann, and G. J. Puppels, “Discriminating Basal Cell Carcinoma from its Surrounding Tissue by Raman Spectroscopy,” J. Invest. Dermatol. 119(1), 64–69 (2002).
[Crossref] [PubMed]

Nielsen, O. F.

M. Gniadecka, H. C. Wulf, N. N. Mortensen, O. F. Nielsen, and D. H. Christensen, “Diagnosis of Basal Cell Carcinoma by Raman Spectroscopy,” J. Raman Spectrosc. 28, 125–129 (1997).

Nijssen, A.

A. Nijssen, T. C. Bakker Schut, F. Heule, P. J. Caspers, D. P. Hayes, M. H. A. Neumann, and G. J. Puppels, “Discriminating Basal Cell Carcinoma from its Surrounding Tissue by Raman Spectroscopy,” J. Invest. Dermatol. 119(1), 64–69 (2002).
[Crossref] [PubMed]

Notingher, I.

K. Kong, F. Zaabar, E. Rakha, I. Ellis, A. Koloydenko, and I. Notingher, “Towards intra-operative diagnosis of tumours during breast conserving surgery by selective-sampling Raman micro-spectroscopy,” Phys. Med. Biol. 59(20), 6141–6152 (2014).
[Crossref] [PubMed]

K. Kong, C. J. Rowlands, S. Varma, W. Perkins, I. H. Leach, A. A. Koloydenko, H. C. Williams, and I. Notingher, “Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 110(38), 15189–15194 (2013).
[Crossref] [PubMed]

C. J. Rowlands, S. Varma, W. Perkins, I. Leach, H. Williams, and I. Notingher, “Rapid acquisition of Raman spectral maps through minimal sampling: applications in tissue imaging,” J. Biophotonics 5(3), 220–229 (2012).
[Crossref] [PubMed]

M. Larraona-Puy, A. Ghita, A. Zoladek, W. Perkins, S. Varma, I. H. Leach, A. A. Koloydenko, H. Williams, and I. Notingher, “Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma,” J. Biomed. Opt. 14(5), 054031 (2009).
[Crossref] [PubMed]

O’Callaghan, R. J.

R. J. O’Callaghan and D. R. Bull, “Combined morphological-spectral unsupervised image segmentation,” IEEE Trans. Image Process. 14(1), 49–62 (2005).
[Crossref] [PubMed]

Ostertag, J. U.

E. van Loo, K. Mosterd, G. A. M. Krekels, M. H. Roozeboom, J. U. Ostertag, C. D. Dirksen, P. M. Steijlen, H. A. Neumann, P. J. Nelemans, and N. W. J. Kelleners-Smeets, “Surgical excision versus Mohs’ micrographic surgery for basal cell carcinoma of the face: A randomised clinical trial with 10year follow-up,” Eur. J. Cancer 50(17), 3011–3020 (2014).
[Crossref] [PubMed]

Patel, A. N.

J. M. Baxter, A. N. Patel, and S. Varma, “Facial basal cell carcinoma,” BMJ 345(aug21 2), e5342 (2012).
[Crossref] [PubMed]

Perkins, W.

K. Kong, C. J. Rowlands, S. Varma, W. Perkins, I. H. Leach, A. A. Koloydenko, H. C. Williams, and I. Notingher, “Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 110(38), 15189–15194 (2013).
[Crossref] [PubMed]

C. J. Rowlands, S. Varma, W. Perkins, I. Leach, H. Williams, and I. Notingher, “Rapid acquisition of Raman spectral maps through minimal sampling: applications in tissue imaging,” J. Biophotonics 5(3), 220–229 (2012).
[Crossref] [PubMed]

M. Larraona-Puy, A. Ghita, A. Zoladek, W. Perkins, S. Varma, I. H. Leach, A. A. Koloydenko, H. Williams, and I. Notingher, “Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma,” J. Biomed. Opt. 14(5), 054031 (2009).
[Crossref] [PubMed]

Puppels, G. J.

A. Nijssen, T. C. Bakker Schut, F. Heule, P. J. Caspers, D. P. Hayes, M. H. A. Neumann, and G. J. Puppels, “Discriminating Basal Cell Carcinoma from its Surrounding Tissue by Raman Spectroscopy,” J. Invest. Dermatol. 119(1), 64–69 (2002).
[Crossref] [PubMed]

Rakha, E.

K. Kong, F. Zaabar, E. Rakha, I. Ellis, A. Koloydenko, and I. Notingher, “Towards intra-operative diagnosis of tumours during breast conserving surgery by selective-sampling Raman micro-spectroscopy,” Phys. Med. Biol. 59(20), 6141–6152 (2014).
[Crossref] [PubMed]

Roozeboom, M. H.

E. van Loo, K. Mosterd, G. A. M. Krekels, M. H. Roozeboom, J. U. Ostertag, C. D. Dirksen, P. M. Steijlen, H. A. Neumann, P. J. Nelemans, and N. W. J. Kelleners-Smeets, “Surgical excision versus Mohs’ micrographic surgery for basal cell carcinoma of the face: A randomised clinical trial with 10year follow-up,” Eur. J. Cancer 50(17), 3011–3020 (2014).
[Crossref] [PubMed]

Rowlands, C. J.

K. Kong, C. J. Rowlands, S. Varma, W. Perkins, I. H. Leach, A. A. Koloydenko, H. C. Williams, and I. Notingher, “Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 110(38), 15189–15194 (2013).
[Crossref] [PubMed]

C. J. Rowlands, S. Varma, W. Perkins, I. Leach, H. Williams, and I. Notingher, “Rapid acquisition of Raman spectral maps through minimal sampling: applications in tissue imaging,” J. Biophotonics 5(3), 220–229 (2012).
[Crossref] [PubMed]

Selesnick, I. W.

I. W. Selesnick, R. G. Baraniuk, and N. G. Kingsbury, “The dual-tree complex wavelet transform,” IEEE Signal Process. Mag. 22(6), 123–151 (2005).
[Crossref]

Steijlen, P. M.

E. van Loo, K. Mosterd, G. A. M. Krekels, M. H. Roozeboom, J. U. Ostertag, C. D. Dirksen, P. M. Steijlen, H. A. Neumann, P. J. Nelemans, and N. W. J. Kelleners-Smeets, “Surgical excision versus Mohs’ micrographic surgery for basal cell carcinoma of the face: A randomised clinical trial with 10year follow-up,” Eur. J. Cancer 50(17), 3011–3020 (2014).
[Crossref] [PubMed]

van Loo, E.

E. van Loo, K. Mosterd, G. A. M. Krekels, M. H. Roozeboom, J. U. Ostertag, C. D. Dirksen, P. M. Steijlen, H. A. Neumann, P. J. Nelemans, and N. W. J. Kelleners-Smeets, “Surgical excision versus Mohs’ micrographic surgery for basal cell carcinoma of the face: A randomised clinical trial with 10year follow-up,” Eur. J. Cancer 50(17), 3011–3020 (2014).
[Crossref] [PubMed]

Varma, S.

K. Kong, C. J. Rowlands, S. Varma, W. Perkins, I. H. Leach, A. A. Koloydenko, H. C. Williams, and I. Notingher, “Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 110(38), 15189–15194 (2013).
[Crossref] [PubMed]

C. J. Rowlands, S. Varma, W. Perkins, I. Leach, H. Williams, and I. Notingher, “Rapid acquisition of Raman spectral maps through minimal sampling: applications in tissue imaging,” J. Biophotonics 5(3), 220–229 (2012).
[Crossref] [PubMed]

J. M. Baxter, A. N. Patel, and S. Varma, “Facial basal cell carcinoma,” BMJ 345(aug21 2), e5342 (2012).
[Crossref] [PubMed]

M. Larraona-Puy, A. Ghita, A. Zoladek, W. Perkins, S. Varma, I. H. Leach, A. A. Koloydenko, H. Williams, and I. Notingher, “Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma,” J. Biomed. Opt. 14(5), 054031 (2009).
[Crossref] [PubMed]

Williams, H.

C. J. Rowlands, S. Varma, W. Perkins, I. Leach, H. Williams, and I. Notingher, “Rapid acquisition of Raman spectral maps through minimal sampling: applications in tissue imaging,” J. Biophotonics 5(3), 220–229 (2012).
[Crossref] [PubMed]

M. Larraona-Puy, A. Ghita, A. Zoladek, W. Perkins, S. Varma, I. H. Leach, A. A. Koloydenko, H. Williams, and I. Notingher, “Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma,” J. Biomed. Opt. 14(5), 054031 (2009).
[Crossref] [PubMed]

Williams, H. C.

K. Kong, C. J. Rowlands, S. Varma, W. Perkins, I. H. Leach, A. A. Koloydenko, H. C. Williams, and I. Notingher, “Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 110(38), 15189–15194 (2013).
[Crossref] [PubMed]

Wulf, H. C.

M. Gniadecka, H. C. Wulf, N. N. Mortensen, O. F. Nielsen, and D. H. Christensen, “Diagnosis of Basal Cell Carcinoma by Raman Spectroscopy,” J. Raman Spectrosc. 28, 125–129 (1997).

Zaabar, F.

K. Kong, F. Zaabar, E. Rakha, I. Ellis, A. Koloydenko, and I. Notingher, “Towards intra-operative diagnosis of tumours during breast conserving surgery by selective-sampling Raman micro-spectroscopy,” Phys. Med. Biol. 59(20), 6141–6152 (2014).
[Crossref] [PubMed]

Zoladek, A.

M. Larraona-Puy, A. Ghita, A. Zoladek, W. Perkins, S. Varma, I. H. Leach, A. A. Koloydenko, H. Williams, and I. Notingher, “Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma,” J. Biomed. Opt. 14(5), 054031 (2009).
[Crossref] [PubMed]

BMJ (1)

J. M. Baxter, A. N. Patel, and S. Varma, “Facial basal cell carcinoma,” BMJ 345(aug21 2), e5342 (2012).
[Crossref] [PubMed]

Curr. Dermatol. Rep. (1)

S. V. Mohan and A. L. S. Chang, “Advanced Basal Cell Carcinoma: Epidemiology and Therapeutic Innovations,” Curr. Dermatol. Rep. 3(1), 40–45 (2014).
[Crossref] [PubMed]

Eur. J. Cancer (1)

E. van Loo, K. Mosterd, G. A. M. Krekels, M. H. Roozeboom, J. U. Ostertag, C. D. Dirksen, P. M. Steijlen, H. A. Neumann, P. J. Nelemans, and N. W. J. Kelleners-Smeets, “Surgical excision versus Mohs’ micrographic surgery for basal cell carcinoma of the face: A randomised clinical trial with 10year follow-up,” Eur. J. Cancer 50(17), 3011–3020 (2014).
[Crossref] [PubMed]

IEEE Signal Process. Mag. (1)

I. W. Selesnick, R. G. Baraniuk, and N. G. Kingsbury, “The dual-tree complex wavelet transform,” IEEE Signal Process. Mag. 22(6), 123–151 (2005).
[Crossref]

IEEE Trans. Image Process. (1)

R. J. O’Callaghan and D. R. Bull, “Combined morphological-spectral unsupervised image segmentation,” IEEE Trans. Image Process. 14(1), 49–62 (2005).
[Crossref] [PubMed]

J. Biomed. Opt. (1)

M. Larraona-Puy, A. Ghita, A. Zoladek, W. Perkins, S. Varma, I. H. Leach, A. A. Koloydenko, H. Williams, and I. Notingher, “Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma,” J. Biomed. Opt. 14(5), 054031 (2009).
[Crossref] [PubMed]

J. Biophotonics (1)

C. J. Rowlands, S. Varma, W. Perkins, I. Leach, H. Williams, and I. Notingher, “Rapid acquisition of Raman spectral maps through minimal sampling: applications in tissue imaging,” J. Biophotonics 5(3), 220–229 (2012).
[Crossref] [PubMed]

J. Invest. Dermatol. (1)

A. Nijssen, T. C. Bakker Schut, F. Heule, P. J. Caspers, D. P. Hayes, M. H. A. Neumann, and G. J. Puppels, “Discriminating Basal Cell Carcinoma from its Surrounding Tissue by Raman Spectroscopy,” J. Invest. Dermatol. 119(1), 64–69 (2002).
[Crossref] [PubMed]

J. Raman Spectrosc. (1)

M. Gniadecka, H. C. Wulf, N. N. Mortensen, O. F. Nielsen, and D. H. Christensen, “Diagnosis of Basal Cell Carcinoma by Raman Spectroscopy,” J. Raman Spectrosc. 28, 125–129 (1997).

Lasers Surg. Med. (1)

C. A. Lieber, S. K. Majumder, D. L. Ellis, D. D. Billheimer, and A. Mahadevan-Jansen, “In vivo nonmelanoma skin cancer diagnosis using Raman microspectroscopy,” Lasers Surg. Med. 40(7), 461–467 (2008).
[Crossref] [PubMed]

Phys. Med. Biol. (1)

K. Kong, F. Zaabar, E. Rakha, I. Ellis, A. Koloydenko, and I. Notingher, “Towards intra-operative diagnosis of tumours during breast conserving surgery by selective-sampling Raman micro-spectroscopy,” Phys. Med. Biol. 59(20), 6141–6152 (2014).
[Crossref] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (1)

K. Kong, C. J. Rowlands, S. Varma, W. Perkins, I. H. Leach, A. A. Koloydenko, H. C. Williams, and I. Notingher, “Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy,” Proc. Natl. Acad. Sci. U.S.A. 110(38), 15189–15194 (2013).
[Crossref] [PubMed]

Other (3)

National Collaborating Centre for Cancer, “Improving Outcomes for People with Skin Tumors including Melanoma (update): The Management of Low-risk Basal Cell Carcinomas in the Community,” http://www.nice.org.uk/guidance/csgstim/evidence/improving-outcomes-for-people-with-skin-tumours-including-melanoma-update-the-management-of-lowrisk-basal-cell-carcinomas-in-the-community-2010-partial-guidance-update2 .

R. C. Gonzalez and R. E. Woods, Digital Image Processing (Prentice Hall, 2007).

V. P. S. Naidu, “Multi modal image segmentation,” http://www.mathworks.co.uk/matlabcentral/fileexchange/28418-multi-modal-image-segmentation .

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Figures (7)

Fig. 1
Fig. 1 (a) Schematic flowchart of the MSI algorithm based on auto-fluorescence imaging (AF) and Raman spectroscopy. (b) Flow chart for the segmentation algorithm for the AF intensity images of skin tissue.
Fig. 2
Fig. 2 Segmentation of auto-fluorescence intensity (AF) images for skin samples with large nodular BCC (tumours larger than 1mm). r: radius of disk structuring element used for the morphological processing of AF images. Color code for segmented images: red = tumor regions (diagnostic provided by histopathology - for clarity not all tumors are highlighted), white = segment containing residual tumor, green = segments with AF intensity above threshold, gray = segment without tumor. Nseg = the number of segments.
Fig. 3
Fig. 3 Segmentation of auto-fluorescence intensity (AF) images for skin samples with nodular, micro-nodular and superficial BCC with tumour sizes within 300-1000 μm. r: radius of disk structuring element used for the morphological processing of AF images. Color code for segmented images: red = tumor regions (diagnostic provided by histopathology - for clarity not all tumors are highlighted), white = segment containing residual tumor, green = segments with AF intensity above threshold, gray = segment without tumor. Symbols “o” indicate segments for which the tumour accounted for more than half of the segment area, and “*” segments that can be observed clearly in the AF but the tumour accounted for less than a quarter of the segmentation area. . Nseg = the number of segments.
Fig. 4
Fig. 4 Segmentation of auto-fluorescence intensity (AF) images for skin samples with small BCC (morphemic/infiltrative BCC). r: radius of disk structuring element used for the morphological processing of tissue AF image. Color code for segmented images: red = tumor regions (diagnostic provided by histopathology) (for clarity not all tumors are highlighted), white = segment containing residual tumor, green = segments with AF intensity above threshold, gray = segment without tumor. Nseg = the number of segments.
Fig. 5
Fig. 5 Generation of sampling points for Raman spectropscopy based on AF intensity images for two tissue samples. (a), (f) AF images, (b), (g) the intensity variance maps for the segmented AF images (gray scale) with estimated sampling points (cyan), segment-boundary (orange) and segments AF intensity above threshold (green). (c), (h): H&E-stained skin tissue image with BCC highlights in red. (d), (e) and (i), (j): zoom-in images of the red square region in (b) and (g). In (e) and (j), BCCs are additionally highlighted in red. For both skin tissue samples, the segmentation function optimized for large BCC was applied with Nmin = 2 and σsampling = 2,000 spectra cm−2.
Fig. 6
Fig. 6 Evaluation of the MSI algorithms for nodular and superficial BCC (tumors larger than 300 μm). H&E-stained adjacent section is included for comparison. Tissue size: (a) 4 mm × 4 mm and (b) 3 mm × 3 mm.
Fig. 7
Fig. 7 Evaluation of the MSI algorithms for morphoeic/infiltrative BCC (tumors smaller than 300 μm). H&E-stained adjacent section is included for comparison. Tissue size: (a) 4 mm × 4 mm and (b) 2 mm × 2 mm.

Equations (1)

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N sampling ( i )= N min + Var( i )×Area (i) i=1 k [ Var( i )×Area(i) ] × N rest  , 

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