Abstract

Evaluation of suspicious skin lesions by dermatologists is usually accomplished using white light examination and direct punch or surgical biopsy. However, these techniques can be imprecise for estimating a lesion’s margin or level of dermal invasion when planning surgical resection. Laminar optical tomography (LOT) is an imaging technique capable of acquiring depth-sensitive information within scattering tissues. Here, we explore whether LOT data can be used to predict the depth and thickness of pigmented lesions using a range of simulations and phantom models. We then compare these results to LOT data acquired on normal and malignant skin lesions in vivo.

© 2012 OSA

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2010 (2)

H. W. Rogers, M. A. Weinstock, A. R. Harris, M. R. Hinckley, S. R. Feldman, A. B. Fleischer, and B. M. Coldiron, “Incidence estimate of nonmelanoma skin cancer in the United States, 2006,” Arch. Dermatol.146(3), 283–287 (2010).
[CrossRef] [PubMed]

S. A. Burgess, D. Ratner, B. R. Chen, and E. M. C. Hillman, “Fiber-optic and articulating arm implementations of laminar optical tomography for clinical applications,” Biomed. Opt. Express1(3), 780–790 (2010).
[CrossRef] [PubMed]

2009 (2)

B. Yuan, S. A. Burgess, A. Iranmahboob, M. B. Bouchard, N. Lehrer, C. Bordier, and E. M. Hillman, “A system for high-resolution depth-resolved optical imaging of fluorescence and absorption contrast,” Rev. Sci. Instrum.80(4), 043706 (2009).
[CrossRef] [PubMed]

S. D. Konecky, A. Mazhar, D. Cuccia, A. J. Durkin, J. C. Schotland, and B. J. Tromberg, “Quantitative optical tomography of sub-surface heterogeneities using spatially modulated structured light,” Opt. Express17(17), 14780–14790 (2009).
[CrossRef] [PubMed]

2008 (1)

2007 (2)

J. A. Neville, E. Welch, and D. J. Leffell, “Management of nonmelanoma skin cancer in 2007,” Nat. Clin. Pract. Oncol.4(8), 462–469 (2007).
[CrossRef] [PubMed]

M. E. Dawn, A. G. Dawn, and S. J. Miller, “Mohs surgery for the treatment of melanoma in situ: a review,” Dermatol. Surg.33(4), 395–402 (2007).
[CrossRef] [PubMed]

2006 (1)

A. Gerger, S. Koller, W. Weger, E. Richtig, H. Kerl, H. Samonigg, P. Krippl, and J. Smolle, “Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors,” Cancer107(1), 193–200 (2006).
[CrossRef] [PubMed]

2005 (1)

J. Feit, W. Kempf, H. Jedlicková, and G. Burg, “Hypertext atlas of dermatopathology with expert system for epithelial tumors of the skin,” J. Cutan. Pathol.32(6), 433–437 (2005).
[CrossRef] [PubMed]

2004 (2)

2003 (2)

E. Eisenberg, “Frozen section examination of the margins for resection of squamous cell carcinoma of the lower lip,” J. Oral Maxillofac. Surg.61(8), 895–897 (2003).
[CrossRef]

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab.23(8), 911–924 (2003).
[CrossRef] [PubMed]

2002 (4)

J. G. A. M. de Visscher, P. J. J. Gooris, A. Vermey, and J. L. N. Roodenburg, “Surgical margins for resection of squamous cell carcinoma of the lower lip,” Int. J. Oral Maxillofac. Surg.31(2), 154–157 (2002).
[CrossRef] [PubMed]

R. S. Batra and L. C. Kelley, “Predictors of extensive subclinical spread in nonmelanoma skin cancer treated with Mohs micrographic surgery,” Arch. Dermatol.138(8), 1043–1051 (2002).
[CrossRef] [PubMed]

I. V. Meglinski and S. J. Matcher, “Quantitative assessment of skin layers absorption and skin reflectance spectra simulation in the visible and near-infrared spectral regions,” Physiol. Meas.23(4), 741–753 (2002).
[CrossRef] [PubMed]

H. Kittler, H. Pehamberger, K. Wolff, and M. Binder, “Diagnostic accuracy of dermoscopy,” Lancet Oncol.3(3), 159–165 (2002).
[CrossRef] [PubMed]

2001 (2)

G. Argenziano and H. P. Soyer, “Dermoscopy of pigmented skin lesions—a valuable tool for early diagnosis of melanoma,” Lancet Oncol.2(7), 443–449 (2001).
[CrossRef] [PubMed]

C. M. Balch, S. J. Soong, T. Smith, M. I. Ross, M. M. Urist, C. P. Karakousis, W. J. Temple, M. C. Mihm, R. L. Barnhill, W. R. Jewell, H. J. Wanebo, and R. Desmond, “Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas,” Ann. Surg. Oncol.8(2), 101–108 (2001).
[PubMed]

2000 (1)

1998 (2)

1997 (1)

J. A. Zitelli, C. Brown, and B. H. Hanusa, “Mohs micrographic surgery for the treatment of primary cutaneous melanoma,” J. Am. Acad. Dermatol.37(2), 236–245 (1997).
[CrossRef] [PubMed]

1996 (1)

C. P. Karakousis, C. M. Balch, M. M. Urist, M. M. Ross, T. J. Smith, and A. A. Bartolucci, “Local recurrence in malignant melanoma: long-term results of the multiinstitutional randomized surgical trial,” Ann. Surg. Oncol.3(5), 446–452 (1996).
[CrossRef] [PubMed]

1995 (3)

M. G. O’Rourke and C. Bourke, “Recommended width of excision for primary malignant melanoma,” World J. Surg.19(3), 343–345 (1995).
[CrossRef] [PubMed]

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol.104(6), 946–952 (1995).
[CrossRef] [PubMed]

L. Wang, S. L. Jacques, and L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Meth. Prog. Bio.47(2), 131–146 (1995).
[CrossRef]

1990 (1)

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron.26(12), 2166–2185 (1990).
[CrossRef]

1973 (1)

J. T. Whitton and J. D. Everall, “The thickness of the epidermis,” Br. J. Dermatol.89(5), 467–476 (1973).
[CrossRef] [PubMed]

Anderson, R. R.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol.104(6), 946–952 (1995).
[CrossRef] [PubMed]

Argenziano, G.

G. Argenziano and H. P. Soyer, “Dermoscopy of pigmented skin lesions—a valuable tool for early diagnosis of melanoma,” Lancet Oncol.2(7), 443–449 (2001).
[CrossRef] [PubMed]

Balch, C. M.

C. M. Balch, S. J. Soong, T. Smith, M. I. Ross, M. M. Urist, C. P. Karakousis, W. J. Temple, M. C. Mihm, R. L. Barnhill, W. R. Jewell, H. J. Wanebo, and R. Desmond, “Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas,” Ann. Surg. Oncol.8(2), 101–108 (2001).
[PubMed]

C. P. Karakousis, C. M. Balch, M. M. Urist, M. M. Ross, T. J. Smith, and A. A. Bartolucci, “Local recurrence in malignant melanoma: long-term results of the multiinstitutional randomized surgical trial,” Ann. Surg. Oncol.3(5), 446–452 (1996).
[CrossRef] [PubMed]

Barnhill, R. L.

C. M. Balch, S. J. Soong, T. Smith, M. I. Ross, M. M. Urist, C. P. Karakousis, W. J. Temple, M. C. Mihm, R. L. Barnhill, W. R. Jewell, H. J. Wanebo, and R. Desmond, “Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas,” Ann. Surg. Oncol.8(2), 101–108 (2001).
[PubMed]

Bartolucci, A. A.

C. P. Karakousis, C. M. Balch, M. M. Urist, M. M. Ross, T. J. Smith, and A. A. Bartolucci, “Local recurrence in malignant melanoma: long-term results of the multiinstitutional randomized surgical trial,” Ann. Surg. Oncol.3(5), 446–452 (1996).
[CrossRef] [PubMed]

Batra, R. S.

R. S. Batra and L. C. Kelley, “Predictors of extensive subclinical spread in nonmelanoma skin cancer treated with Mohs micrographic surgery,” Arch. Dermatol.138(8), 1043–1051 (2002).
[CrossRef] [PubMed]

Binder, M.

H. Kittler, H. Pehamberger, K. Wolff, and M. Binder, “Diagnostic accuracy of dermoscopy,” Lancet Oncol.3(3), 159–165 (2002).
[CrossRef] [PubMed]

Boas, D. A.

Bordier, C.

B. Yuan, S. A. Burgess, A. Iranmahboob, M. B. Bouchard, N. Lehrer, C. Bordier, and E. M. Hillman, “A system for high-resolution depth-resolved optical imaging of fluorescence and absorption contrast,” Rev. Sci. Instrum.80(4), 043706 (2009).
[CrossRef] [PubMed]

Bouchard, M. B.

B. Yuan, S. A. Burgess, A. Iranmahboob, M. B. Bouchard, N. Lehrer, C. Bordier, and E. M. Hillman, “A system for high-resolution depth-resolved optical imaging of fluorescence and absorption contrast,” Rev. Sci. Instrum.80(4), 043706 (2009).
[CrossRef] [PubMed]

S. A. Burgess, M. B. Bouchard, B. Yuan, and E. M. C. Hillman, “Simultaneous multiwavelength laminar optical tomography,” Opt. Lett.33(22), 2710–2712 (2008).
[CrossRef] [PubMed]

Bourke, C.

M. G. O’Rourke and C. Bourke, “Recommended width of excision for primary malignant melanoma,” World J. Surg.19(3), 343–345 (1995).
[CrossRef] [PubMed]

Brown, C.

J. A. Zitelli, C. Brown, and B. H. Hanusa, “Mohs micrographic surgery for the treatment of primary cutaneous melanoma,” J. Am. Acad. Dermatol.37(2), 236–245 (1997).
[CrossRef] [PubMed]

Burg, G.

J. Feit, W. Kempf, H. Jedlicková, and G. Burg, “Hypertext atlas of dermatopathology with expert system for epithelial tumors of the skin,” J. Cutan. Pathol.32(6), 433–437 (2005).
[CrossRef] [PubMed]

Burgess, S. A.

Chen, B. R.

Cheong, W. F.

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron.26(12), 2166–2185 (1990).
[CrossRef]

Cheung, C.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab.23(8), 911–924 (2003).
[CrossRef] [PubMed]

Coldiron, B. M.

H. W. Rogers, M. A. Weinstock, A. R. Harris, M. R. Hinckley, S. R. Feldman, A. B. Fleischer, and B. M. Coldiron, “Incidence estimate of nonmelanoma skin cancer in the United States, 2006,” Arch. Dermatol.146(3), 283–287 (2010).
[CrossRef] [PubMed]

Cook, J.

J. Cook, “Surgical margins for resection of primary cutaneous melanoma,” Clin. Dermatol.22(3), 228–233 (2004).
[CrossRef] [PubMed]

J. Cook and J. A. Zitelli, “Mohs micrographic surgery: a cost analysis,” J. Am. Acad. Dermatol.39(5), 698–703 (1998).
[CrossRef] [PubMed]

Cuccia, D.

Culver, J. P.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab.23(8), 911–924 (2003).
[CrossRef] [PubMed]

Dale, A. M.

Dawn, A. G.

M. E. Dawn, A. G. Dawn, and S. J. Miller, “Mohs surgery for the treatment of melanoma in situ: a review,” Dermatol. Surg.33(4), 395–402 (2007).
[CrossRef] [PubMed]

Dawn, M. E.

M. E. Dawn, A. G. Dawn, and S. J. Miller, “Mohs surgery for the treatment of melanoma in situ: a review,” Dermatol. Surg.33(4), 395–402 (2007).
[CrossRef] [PubMed]

de Visscher, J. G. A. M.

J. G. A. M. de Visscher, P. J. J. Gooris, A. Vermey, and J. L. N. Roodenburg, “Surgical margins for resection of squamous cell carcinoma of the lower lip,” Int. J. Oral Maxillofac. Surg.31(2), 154–157 (2002).
[CrossRef] [PubMed]

Desmond, R.

C. M. Balch, S. J. Soong, T. Smith, M. I. Ross, M. M. Urist, C. P. Karakousis, W. J. Temple, M. C. Mihm, R. L. Barnhill, W. R. Jewell, H. J. Wanebo, and R. Desmond, “Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas,” Ann. Surg. Oncol.8(2), 101–108 (2001).
[PubMed]

Dunn, A. K.

Durduran, T.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab.23(8), 911–924 (2003).
[CrossRef] [PubMed]

Durkin, A. J.

Eisenberg, E.

E. Eisenberg, “Frozen section examination of the margins for resection of squamous cell carcinoma of the lower lip,” J. Oral Maxillofac. Surg.61(8), 895–897 (2003).
[CrossRef]

Esterowitz, D.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol.104(6), 946–952 (1995).
[CrossRef] [PubMed]

Everall, J. D.

J. T. Whitton and J. D. Everall, “The thickness of the epidermis,” Br. J. Dermatol.89(5), 467–476 (1973).
[CrossRef] [PubMed]

Feit, J.

J. Feit, W. Kempf, H. Jedlicková, and G. Burg, “Hypertext atlas of dermatopathology with expert system for epithelial tumors of the skin,” J. Cutan. Pathol.32(6), 433–437 (2005).
[CrossRef] [PubMed]

Feldman, S. R.

H. W. Rogers, M. A. Weinstock, A. R. Harris, M. R. Hinckley, S. R. Feldman, A. B. Fleischer, and B. M. Coldiron, “Incidence estimate of nonmelanoma skin cancer in the United States, 2006,” Arch. Dermatol.146(3), 283–287 (2010).
[CrossRef] [PubMed]

Fleischer, A. B.

H. W. Rogers, M. A. Weinstock, A. R. Harris, M. R. Hinckley, S. R. Feldman, A. B. Fleischer, and B. M. Coldiron, “Incidence estimate of nonmelanoma skin cancer in the United States, 2006,” Arch. Dermatol.146(3), 283–287 (2010).
[CrossRef] [PubMed]

Furuya, D.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab.23(8), 911–924 (2003).
[CrossRef] [PubMed]

Gerger, A.

A. Gerger, S. Koller, W. Weger, E. Richtig, H. Kerl, H. Samonigg, P. Krippl, and J. Smolle, “Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors,” Cancer107(1), 193–200 (2006).
[CrossRef] [PubMed]

Gooris, P. J. J.

J. G. A. M. de Visscher, P. J. J. Gooris, A. Vermey, and J. L. N. Roodenburg, “Surgical margins for resection of squamous cell carcinoma of the lower lip,” Int. J. Oral Maxillofac. Surg.31(2), 154–157 (2002).
[CrossRef] [PubMed]

Greenberg, J. H.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab.23(8), 911–924 (2003).
[CrossRef] [PubMed]

Grossman, M.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol.104(6), 946–952 (1995).
[CrossRef] [PubMed]

Hanusa, B. H.

J. A. Zitelli, C. Brown, and B. H. Hanusa, “Mohs micrographic surgery for the treatment of primary cutaneous melanoma,” J. Am. Acad. Dermatol.37(2), 236–245 (1997).
[CrossRef] [PubMed]

Harris, A. R.

H. W. Rogers, M. A. Weinstock, A. R. Harris, M. R. Hinckley, S. R. Feldman, A. B. Fleischer, and B. M. Coldiron, “Incidence estimate of nonmelanoma skin cancer in the United States, 2006,” Arch. Dermatol.146(3), 283–287 (2010).
[CrossRef] [PubMed]

Hillman, E. M.

B. Yuan, S. A. Burgess, A. Iranmahboob, M. B. Bouchard, N. Lehrer, C. Bordier, and E. M. Hillman, “A system for high-resolution depth-resolved optical imaging of fluorescence and absorption contrast,” Rev. Sci. Instrum.80(4), 043706 (2009).
[CrossRef] [PubMed]

Hillman, E. M. C.

Hinckley, M. R.

H. W. Rogers, M. A. Weinstock, A. R. Harris, M. R. Hinckley, S. R. Feldman, A. B. Fleischer, and B. M. Coldiron, “Incidence estimate of nonmelanoma skin cancer in the United States, 2006,” Arch. Dermatol.146(3), 283–287 (2010).
[CrossRef] [PubMed]

Iranmahboob, A.

B. Yuan, S. A. Burgess, A. Iranmahboob, M. B. Bouchard, N. Lehrer, C. Bordier, and E. M. Hillman, “A system for high-resolution depth-resolved optical imaging of fluorescence and absorption contrast,” Rev. Sci. Instrum.80(4), 043706 (2009).
[CrossRef] [PubMed]

Jacques, S. L.

L. Wang, S. L. Jacques, and L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Meth. Prog. Bio.47(2), 131–146 (1995).
[CrossRef]

Jedlicková, H.

J. Feit, W. Kempf, H. Jedlicková, and G. Burg, “Hypertext atlas of dermatopathology with expert system for epithelial tumors of the skin,” J. Cutan. Pathol.32(6), 433–437 (2005).
[CrossRef] [PubMed]

Jewell, W. R.

C. M. Balch, S. J. Soong, T. Smith, M. I. Ross, M. M. Urist, C. P. Karakousis, W. J. Temple, M. C. Mihm, R. L. Barnhill, W. R. Jewell, H. J. Wanebo, and R. Desmond, “Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas,” Ann. Surg. Oncol.8(2), 101–108 (2001).
[PubMed]

Karakousis, C. P.

C. M. Balch, S. J. Soong, T. Smith, M. I. Ross, M. M. Urist, C. P. Karakousis, W. J. Temple, M. C. Mihm, R. L. Barnhill, W. R. Jewell, H. J. Wanebo, and R. Desmond, “Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas,” Ann. Surg. Oncol.8(2), 101–108 (2001).
[PubMed]

C. P. Karakousis, C. M. Balch, M. M. Urist, M. M. Ross, T. J. Smith, and A. A. Bartolucci, “Local recurrence in malignant melanoma: long-term results of the multiinstitutional randomized surgical trial,” Ann. Surg. Oncol.3(5), 446–452 (1996).
[CrossRef] [PubMed]

Kelley, L. C.

R. S. Batra and L. C. Kelley, “Predictors of extensive subclinical spread in nonmelanoma skin cancer treated with Mohs micrographic surgery,” Arch. Dermatol.138(8), 1043–1051 (2002).
[CrossRef] [PubMed]

Kempf, W.

J. Feit, W. Kempf, H. Jedlicková, and G. Burg, “Hypertext atlas of dermatopathology with expert system for epithelial tumors of the skin,” J. Cutan. Pathol.32(6), 433–437 (2005).
[CrossRef] [PubMed]

Kerl, H.

A. Gerger, S. Koller, W. Weger, E. Richtig, H. Kerl, H. Samonigg, P. Krippl, and J. Smolle, “Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors,” Cancer107(1), 193–200 (2006).
[CrossRef] [PubMed]

Kittler, H.

H. Kittler, H. Pehamberger, K. Wolff, and M. Binder, “Diagnostic accuracy of dermoscopy,” Lancet Oncol.3(3), 159–165 (2002).
[CrossRef] [PubMed]

Koller, S.

A. Gerger, S. Koller, W. Weger, E. Richtig, H. Kerl, H. Samonigg, P. Krippl, and J. Smolle, “Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors,” Cancer107(1), 193–200 (2006).
[CrossRef] [PubMed]

Konecky, S. D.

Krippl, P.

A. Gerger, S. Koller, W. Weger, E. Richtig, H. Kerl, H. Samonigg, P. Krippl, and J. Smolle, “Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors,” Cancer107(1), 193–200 (2006).
[CrossRef] [PubMed]

Leffell, D. J.

J. A. Neville, E. Welch, and D. J. Leffell, “Management of nonmelanoma skin cancer in 2007,” Nat. Clin. Pract. Oncol.4(8), 462–469 (2007).
[CrossRef] [PubMed]

Lehrer, N.

B. Yuan, S. A. Burgess, A. Iranmahboob, M. B. Bouchard, N. Lehrer, C. Bordier, and E. M. Hillman, “A system for high-resolution depth-resolved optical imaging of fluorescence and absorption contrast,” Rev. Sci. Instrum.80(4), 043706 (2009).
[CrossRef] [PubMed]

Matcher, S. J.

I. V. Meglinski and S. J. Matcher, “Quantitative assessment of skin layers absorption and skin reflectance spectra simulation in the visible and near-infrared spectral regions,” Physiol. Meas.23(4), 741–753 (2002).
[CrossRef] [PubMed]

Mazhar, A.

Meglinski, I. V.

I. V. Meglinski and S. J. Matcher, “Quantitative assessment of skin layers absorption and skin reflectance spectra simulation in the visible and near-infrared spectral regions,” Physiol. Meas.23(4), 741–753 (2002).
[CrossRef] [PubMed]

Mihm, M. C.

C. M. Balch, S. J. Soong, T. Smith, M. I. Ross, M. M. Urist, C. P. Karakousis, W. J. Temple, M. C. Mihm, R. L. Barnhill, W. R. Jewell, H. J. Wanebo, and R. Desmond, “Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas,” Ann. Surg. Oncol.8(2), 101–108 (2001).
[PubMed]

Miller, S. J.

M. E. Dawn, A. G. Dawn, and S. J. Miller, “Mohs surgery for the treatment of melanoma in situ: a review,” Dermatol. Surg.33(4), 395–402 (2007).
[CrossRef] [PubMed]

Neville, J. A.

J. A. Neville, E. Welch, and D. J. Leffell, “Management of nonmelanoma skin cancer in 2007,” Nat. Clin. Pract. Oncol.4(8), 462–469 (2007).
[CrossRef] [PubMed]

O’Rourke, M. G.

M. G. O’Rourke and C. Bourke, “Recommended width of excision for primary malignant melanoma,” World J. Surg.19(3), 343–345 (1995).
[CrossRef] [PubMed]

Pehamberger, H.

H. Kittler, H. Pehamberger, K. Wolff, and M. Binder, “Diagnostic accuracy of dermoscopy,” Lancet Oncol.3(3), 159–165 (2002).
[CrossRef] [PubMed]

Prahl, S. A.

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron.26(12), 2166–2185 (1990).
[CrossRef]

Rajadhyaksha, M.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol.104(6), 946–952 (1995).
[CrossRef] [PubMed]

Ratner, D.

Richards-Kortum, R.

Richtig, E.

A. Gerger, S. Koller, W. Weger, E. Richtig, H. Kerl, H. Samonigg, P. Krippl, and J. Smolle, “Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors,” Cancer107(1), 193–200 (2006).
[CrossRef] [PubMed]

Rogers, H. W.

H. W. Rogers, M. A. Weinstock, A. R. Harris, M. R. Hinckley, S. R. Feldman, A. B. Fleischer, and B. M. Coldiron, “Incidence estimate of nonmelanoma skin cancer in the United States, 2006,” Arch. Dermatol.146(3), 283–287 (2010).
[CrossRef] [PubMed]

Roodenburg, J. L. N.

J. G. A. M. de Visscher, P. J. J. Gooris, A. Vermey, and J. L. N. Roodenburg, “Surgical margins for resection of squamous cell carcinoma of the lower lip,” Int. J. Oral Maxillofac. Surg.31(2), 154–157 (2002).
[CrossRef] [PubMed]

Ross, M. I.

C. M. Balch, S. J. Soong, T. Smith, M. I. Ross, M. M. Urist, C. P. Karakousis, W. J. Temple, M. C. Mihm, R. L. Barnhill, W. R. Jewell, H. J. Wanebo, and R. Desmond, “Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas,” Ann. Surg. Oncol.8(2), 101–108 (2001).
[PubMed]

Ross, M. M.

C. P. Karakousis, C. M. Balch, M. M. Urist, M. M. Ross, T. J. Smith, and A. A. Bartolucci, “Local recurrence in malignant melanoma: long-term results of the multiinstitutional randomized surgical trial,” Ann. Surg. Oncol.3(5), 446–452 (1996).
[CrossRef] [PubMed]

Samonigg, H.

A. Gerger, S. Koller, W. Weger, E. Richtig, H. Kerl, H. Samonigg, P. Krippl, and J. Smolle, “Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors,” Cancer107(1), 193–200 (2006).
[CrossRef] [PubMed]

Schotland, J. C.

Smith, T.

C. M. Balch, S. J. Soong, T. Smith, M. I. Ross, M. M. Urist, C. P. Karakousis, W. J. Temple, M. C. Mihm, R. L. Barnhill, W. R. Jewell, H. J. Wanebo, and R. Desmond, “Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas,” Ann. Surg. Oncol.8(2), 101–108 (2001).
[PubMed]

Smith, T. J.

C. P. Karakousis, C. M. Balch, M. M. Urist, M. M. Ross, T. J. Smith, and A. A. Bartolucci, “Local recurrence in malignant melanoma: long-term results of the multiinstitutional randomized surgical trial,” Ann. Surg. Oncol.3(5), 446–452 (1996).
[CrossRef] [PubMed]

Smithpeter, C. L.

Smolle, J.

A. Gerger, S. Koller, W. Weger, E. Richtig, H. Kerl, H. Samonigg, P. Krippl, and J. Smolle, “Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors,” Cancer107(1), 193–200 (2006).
[CrossRef] [PubMed]

Soong, S. J.

C. M. Balch, S. J. Soong, T. Smith, M. I. Ross, M. M. Urist, C. P. Karakousis, W. J. Temple, M. C. Mihm, R. L. Barnhill, W. R. Jewell, H. J. Wanebo, and R. Desmond, “Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas,” Ann. Surg. Oncol.8(2), 101–108 (2001).
[PubMed]

Soyer, H. P.

G. Argenziano and H. P. Soyer, “Dermoscopy of pigmented skin lesions—a valuable tool for early diagnosis of melanoma,” Lancet Oncol.2(7), 443–449 (2001).
[CrossRef] [PubMed]

Temple, W. J.

C. M. Balch, S. J. Soong, T. Smith, M. I. Ross, M. M. Urist, C. P. Karakousis, W. J. Temple, M. C. Mihm, R. L. Barnhill, W. R. Jewell, H. J. Wanebo, and R. Desmond, “Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas,” Ann. Surg. Oncol.8(2), 101–108 (2001).
[PubMed]

Tromberg, B. J.

Urist, M. M.

C. M. Balch, S. J. Soong, T. Smith, M. I. Ross, M. M. Urist, C. P. Karakousis, W. J. Temple, M. C. Mihm, R. L. Barnhill, W. R. Jewell, H. J. Wanebo, and R. Desmond, “Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas,” Ann. Surg. Oncol.8(2), 101–108 (2001).
[PubMed]

C. P. Karakousis, C. M. Balch, M. M. Urist, M. M. Ross, T. J. Smith, and A. A. Bartolucci, “Local recurrence in malignant melanoma: long-term results of the multiinstitutional randomized surgical trial,” Ann. Surg. Oncol.3(5), 446–452 (1996).
[CrossRef] [PubMed]

Vermey, A.

J. G. A. M. de Visscher, P. J. J. Gooris, A. Vermey, and J. L. N. Roodenburg, “Surgical margins for resection of squamous cell carcinoma of the lower lip,” Int. J. Oral Maxillofac. Surg.31(2), 154–157 (2002).
[CrossRef] [PubMed]

Wanebo, H. J.

C. M. Balch, S. J. Soong, T. Smith, M. I. Ross, M. M. Urist, C. P. Karakousis, W. J. Temple, M. C. Mihm, R. L. Barnhill, W. R. Jewell, H. J. Wanebo, and R. Desmond, “Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas,” Ann. Surg. Oncol.8(2), 101–108 (2001).
[PubMed]

Wang, L.

L. Wang, S. L. Jacques, and L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Meth. Prog. Bio.47(2), 131–146 (1995).
[CrossRef]

Webb, R. H.

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol.104(6), 946–952 (1995).
[CrossRef] [PubMed]

Weger, W.

A. Gerger, S. Koller, W. Weger, E. Richtig, H. Kerl, H. Samonigg, P. Krippl, and J. Smolle, “Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors,” Cancer107(1), 193–200 (2006).
[CrossRef] [PubMed]

Weinstock, M. A.

H. W. Rogers, M. A. Weinstock, A. R. Harris, M. R. Hinckley, S. R. Feldman, A. B. Fleischer, and B. M. Coldiron, “Incidence estimate of nonmelanoma skin cancer in the United States, 2006,” Arch. Dermatol.146(3), 283–287 (2010).
[CrossRef] [PubMed]

Welch, A. J.

C. L. Smithpeter, A. K. Dunn, A. J. Welch, and R. Richards-Kortum, “Penetration depth limits of in vivo confocal reflectance imaging,” Appl. Opt.37(13), 2749–2754 (1998).
[CrossRef] [PubMed]

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron.26(12), 2166–2185 (1990).
[CrossRef]

Welch, E.

J. A. Neville, E. Welch, and D. J. Leffell, “Management of nonmelanoma skin cancer in 2007,” Nat. Clin. Pract. Oncol.4(8), 462–469 (2007).
[CrossRef] [PubMed]

Whitton, J. T.

J. T. Whitton and J. D. Everall, “The thickness of the epidermis,” Br. J. Dermatol.89(5), 467–476 (1973).
[CrossRef] [PubMed]

Wolff, K.

H. Kittler, H. Pehamberger, K. Wolff, and M. Binder, “Diagnostic accuracy of dermoscopy,” Lancet Oncol.3(3), 159–165 (2002).
[CrossRef] [PubMed]

Yodh, A. G.

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab.23(8), 911–924 (2003).
[CrossRef] [PubMed]

Yuan, B.

B. Yuan, S. A. Burgess, A. Iranmahboob, M. B. Bouchard, N. Lehrer, C. Bordier, and E. M. Hillman, “A system for high-resolution depth-resolved optical imaging of fluorescence and absorption contrast,” Rev. Sci. Instrum.80(4), 043706 (2009).
[CrossRef] [PubMed]

S. A. Burgess, M. B. Bouchard, B. Yuan, and E. M. C. Hillman, “Simultaneous multiwavelength laminar optical tomography,” Opt. Lett.33(22), 2710–2712 (2008).
[CrossRef] [PubMed]

Zheng, L.

L. Wang, S. L. Jacques, and L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Meth. Prog. Bio.47(2), 131–146 (1995).
[CrossRef]

Zitelli, J. A.

J. Cook and J. A. Zitelli, “Mohs micrographic surgery: a cost analysis,” J. Am. Acad. Dermatol.39(5), 698–703 (1998).
[CrossRef] [PubMed]

J. A. Zitelli, C. Brown, and B. H. Hanusa, “Mohs micrographic surgery for the treatment of primary cutaneous melanoma,” J. Am. Acad. Dermatol.37(2), 236–245 (1997).
[CrossRef] [PubMed]

Ann. Surg. Oncol. (2)

C. P. Karakousis, C. M. Balch, M. M. Urist, M. M. Ross, T. J. Smith, and A. A. Bartolucci, “Local recurrence in malignant melanoma: long-term results of the multiinstitutional randomized surgical trial,” Ann. Surg. Oncol.3(5), 446–452 (1996).
[CrossRef] [PubMed]

C. M. Balch, S. J. Soong, T. Smith, M. I. Ross, M. M. Urist, C. P. Karakousis, W. J. Temple, M. C. Mihm, R. L. Barnhill, W. R. Jewell, H. J. Wanebo, and R. Desmond, “Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas,” Ann. Surg. Oncol.8(2), 101–108 (2001).
[PubMed]

Appl. Opt. (1)

Arch. Dermatol. (2)

H. W. Rogers, M. A. Weinstock, A. R. Harris, M. R. Hinckley, S. R. Feldman, A. B. Fleischer, and B. M. Coldiron, “Incidence estimate of nonmelanoma skin cancer in the United States, 2006,” Arch. Dermatol.146(3), 283–287 (2010).
[CrossRef] [PubMed]

R. S. Batra and L. C. Kelley, “Predictors of extensive subclinical spread in nonmelanoma skin cancer treated with Mohs micrographic surgery,” Arch. Dermatol.138(8), 1043–1051 (2002).
[CrossRef] [PubMed]

Biomed. Opt. Express (1)

Br. J. Dermatol. (1)

J. T. Whitton and J. D. Everall, “The thickness of the epidermis,” Br. J. Dermatol.89(5), 467–476 (1973).
[CrossRef] [PubMed]

Cancer (1)

A. Gerger, S. Koller, W. Weger, E. Richtig, H. Kerl, H. Samonigg, P. Krippl, and J. Smolle, “Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors,” Cancer107(1), 193–200 (2006).
[CrossRef] [PubMed]

Clin. Dermatol. (1)

J. Cook, “Surgical margins for resection of primary cutaneous melanoma,” Clin. Dermatol.22(3), 228–233 (2004).
[CrossRef] [PubMed]

Comput. Meth. Prog. Bio. (1)

L. Wang, S. L. Jacques, and L. Zheng, “MCML—Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Meth. Prog. Bio.47(2), 131–146 (1995).
[CrossRef]

Dermatol. Surg. (1)

M. E. Dawn, A. G. Dawn, and S. J. Miller, “Mohs surgery for the treatment of melanoma in situ: a review,” Dermatol. Surg.33(4), 395–402 (2007).
[CrossRef] [PubMed]

IEEE J. Quantum Electron. (1)

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron.26(12), 2166–2185 (1990).
[CrossRef]

Int. J. Oral Maxillofac. Surg. (1)

J. G. A. M. de Visscher, P. J. J. Gooris, A. Vermey, and J. L. N. Roodenburg, “Surgical margins for resection of squamous cell carcinoma of the lower lip,” Int. J. Oral Maxillofac. Surg.31(2), 154–157 (2002).
[CrossRef] [PubMed]

J. Am. Acad. Dermatol. (2)

J. Cook and J. A. Zitelli, “Mohs micrographic surgery: a cost analysis,” J. Am. Acad. Dermatol.39(5), 698–703 (1998).
[CrossRef] [PubMed]

J. A. Zitelli, C. Brown, and B. H. Hanusa, “Mohs micrographic surgery for the treatment of primary cutaneous melanoma,” J. Am. Acad. Dermatol.37(2), 236–245 (1997).
[CrossRef] [PubMed]

J. Cereb. Blood Flow Metab. (1)

J. P. Culver, T. Durduran, D. Furuya, C. Cheung, J. H. Greenberg, and A. G. Yodh, “Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia,” J. Cereb. Blood Flow Metab.23(8), 911–924 (2003).
[CrossRef] [PubMed]

J. Cutan. Pathol. (1)

J. Feit, W. Kempf, H. Jedlicková, and G. Burg, “Hypertext atlas of dermatopathology with expert system for epithelial tumors of the skin,” J. Cutan. Pathol.32(6), 433–437 (2005).
[CrossRef] [PubMed]

J. Invest. Dermatol. (1)

M. Rajadhyaksha, M. Grossman, D. Esterowitz, R. H. Webb, and R. R. Anderson, “In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast,” J. Invest. Dermatol.104(6), 946–952 (1995).
[CrossRef] [PubMed]

J. Oral Maxillofac. Surg. (1)

E. Eisenberg, “Frozen section examination of the margins for resection of squamous cell carcinoma of the lower lip,” J. Oral Maxillofac. Surg.61(8), 895–897 (2003).
[CrossRef]

Lancet Oncol. (2)

G. Argenziano and H. P. Soyer, “Dermoscopy of pigmented skin lesions—a valuable tool for early diagnosis of melanoma,” Lancet Oncol.2(7), 443–449 (2001).
[CrossRef] [PubMed]

H. Kittler, H. Pehamberger, K. Wolff, and M. Binder, “Diagnostic accuracy of dermoscopy,” Lancet Oncol.3(3), 159–165 (2002).
[CrossRef] [PubMed]

Nat. Clin. Pract. Oncol. (1)

J. A. Neville, E. Welch, and D. J. Leffell, “Management of nonmelanoma skin cancer in 2007,” Nat. Clin. Pract. Oncol.4(8), 462–469 (2007).
[CrossRef] [PubMed]

Opt. Express (1)

Opt. Lett. (3)

Physiol. Meas. (1)

I. V. Meglinski and S. J. Matcher, “Quantitative assessment of skin layers absorption and skin reflectance spectra simulation in the visible and near-infrared spectral regions,” Physiol. Meas.23(4), 741–753 (2002).
[CrossRef] [PubMed]

Rev. Sci. Instrum. (1)

B. Yuan, S. A. Burgess, A. Iranmahboob, M. B. Bouchard, N. Lehrer, C. Bordier, and E. M. Hillman, “A system for high-resolution depth-resolved optical imaging of fluorescence and absorption contrast,” Rev. Sci. Instrum.80(4), 043706 (2009).
[CrossRef] [PubMed]

World J. Surg. (1)

M. G. O’Rourke and C. Bourke, “Recommended width of excision for primary malignant melanoma,” World J. Surg.19(3), 343–345 (1995).
[CrossRef] [PubMed]

Other (1)

N. A. Howlader, N. M. Krapcho, N. Neyman, R. Aminou, S. F. Altekruse, C. L. Kosary, J. Ruhl, Z. Tatalovich, H. Cho, A. Mariotto, M. P. Eisner, D. R. Lewis, H. S. Chen, E. J. Feuer, and K. A. Cronin, eds., SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations), (National Cancer Institute, Bethesda, MD, 2012).

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Figures (5)

Fig. 1
Fig. 1

Schematic diagram of Laminar Optical Tomography system. lower inset: illustration of offset detector geometry and average photon pathways in tissue (blue arcs). Note that wider detector offsets yield deeper average photon migration pathways. Upper inset: Monte Carlo-derived depth sensitivity of LOT measurements at four source-detector offset positions for optical properties approximating skin (normalized to 1 for each offset).

Fig. 2
Fig. 2

Phantom and modeling results. (a) White light photograph of depth-varying optical phantom with the depth of each inclusion indicated. (b) Raw LOT phantom data inclusions of different depths displayed as differential contrast (ΔS/So). (c) and (f) Illustrations of depth-varying and thickness varying optical phantoms, respectively. (d) and (g) Differential contrast measured data (solid lines) and Monte Carlo simulation predictions (dashed lines) for lesions of different depths and thicknesses. Error bars show standard deviations of 15 repeated scans. Power law fits to experimental LOT data are also shown. RMS errors of these fits range from 0.0256 to 0.0666. (e) and (h) plots showing Monte Carlo-derived isolines of power law fit parameters ‘a’ and ‘b’ (y = axb), for various thickness and depths of inclusion. Triangles show results of the power law fits for phantom measurements from (d) and (g) respectively and agree well with phantom parameters. We note that compression of ‘thickness’ isolines at higher “a” values is a result of ΔS/So values approaching 1, corresponding to very little light reaching detectors. This is an intrinsic detection limit of LOT, since if light cannot reach the detector, it cannot distinguish between lesions of increasing thickness beyond that threshold.

Fig. 3
Fig. 3

Effects of background scattering properties on fit parameters. Filled circle represents the predicted fit parameters for an inclusion at the specified depth and thickness in (left) our phantom model (μa = 0.2 mm−1, μs = 4.0 mm−1, and g = 0.8) and (right) in our skin-like model (μa = 0.2 mm−1, μs = 45 mm−1 (100 micron thick epidermis) and μs = 30 mm−1 (dermis) and g = 0.8). The colored triangles represent fit results when the background scattering coefficient is increased by 10% (upward pointing triangles) or decreased by 10% (downward pointing triangles). While the absolute prediction for each location changes somewhat, the trends related to relative depth and thickness are retained.

Fig. 4
Fig. 4

LOT measurements of benign melanocytic nevi. (a),(d) White light images of Compound and Junctional nevi respectively. (b),(e) Raw LOT image (source-detector separation = 0.25mm) showing reference region (white box) and measurement region (red or blue box) for differential contrast calculation. (c),(f) Representative hematoxylin and eosin (H&E) histopathology images of junctional and compound nevi (40X) [28]. Scale bars approximately 100 microns. Arrowheads demonstrate location of melanocytes. Note that melanocytes in the compound nevus extend deep into the dermis, while melanocytes in the junctional nevus are limited to a thin region at the dermal – epidermal junction. (g), (h) LOT differential contrast and plot of fit parameters. Error bars show standard deviations of 15 repeated scans. RMS error of fit was 0.0096 and 0.0266 for the compound and junctional cases, respectively. Fit results are consistent with the compound nevus being substantially thicker than the junctional nevus, with both lesions being superficial.

Fig. 5
Fig. 5

Clinical squamous cell carcinoma. (a),(b) White light and LOT image at 0.20mm source-detector separation (inset) of squamous cell carcinoma lesion (metric ruler at left for scale). Yellow dashed line indicates approximate location of histopathology section from superior (S) to inferior (I) margins. (c) 532 nm LOT image showing regions of interest selected for differential contrast measurement. White box = reference region, Blue and green boxes = regions of interest. Red box = normal region. (d) Raw LOT frames taken at 532nm and RGB merged data for 5 source-detector (s-d) separations. Anomalous red structures are highlighted by yellow arrows (and black arrows in (b)). Note that the pink circles in wider separations are a specular reflection caused by the variable position of the articulating arm between imaging and calibration scans [21]. (e),(f) Plots of differential contrast and fit parameters of regions in (c). Error bars show standard deviations of 15 repeated scans. RMS error of fit for the red, green, and blue ROIs were 0.0462, 0.0528, and 0.0622, respectively. Note that the blue and green regions appear to be deeper than the red region (which is off scale to the left, implying a very superficial source of contrast). (g) H&E histopathology section from yellow dashed line. Scale bar 200 microns. Red arrowheads show increased subsurface blood accumulation, black arrowheads show adjacent aggregates of dysplastic keratinocytes.

Equations (4)

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M s,d =  E s,d L s g d ( S s,d +  R s,d +  D d )
DI s,d =  E s,d L s g d ( R s,d +  D d )
Mo s,d =  E s,d L s g d ( So s,d +  R s,d +  D d )
ΔS/So = ( MMo ) / ( Mo  DI )

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