Abstract

Point-scanning reflectance confocal microscopes continue to be successfully translated for detection of skin cancer. Line-scanning, with the use of a single scanner and a linear-array detector, offers a potentially smaller, simpler and lower cost alternative approach, to accelerate widespread dissemination into the clinic. However, translation will require an understanding of imaging performance deep within scattering and aberrating human tissues. We report the results of an investigation of the performance of a full-pupil line-scanning reflectance confocal microscope in human skin and oral mucosa, in terms of resolution, optical sectioning, contrast, signal-to-noise ratio, imaging and the effect of speckle noise.

© 2011 OSA

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2010

A. Scope, U. Mahmood, D. S. Gareau, M. Kenkre, J. A. Lieb, K. S. Nehal, and M. Rajadhyaksha, “In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins,” Br. J. Dermatol. 163(6), 1218–1228 (2010).
[CrossRef] [PubMed]

P. Guitera, G. Pellacani, K. A. Crotty, R. A. Scolyer, L. X. Li, S. Bassoli, M. Vinceti, H. Rabinovitz, C. Longo, and S. W. Menzies, “The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face,” J. Invest. Dermatol. 130(8), 2080–2091 (2010).
[CrossRef] [PubMed]

2009

A. A. Tanbakuchi, A. R. Rouse, J. A. Udovich, K. D. Hatch, and A. F. Gmitro, “Clinical confocal microlaparoscope for real-time in vivo optical biopsies,” J. Biomed. Opt. 14(4), 044030 (2009).
[CrossRef] [PubMed]

D. S. Gareau, J. K. Karen, S. W. Dusza, M. Tudisco, K. S. Nehal, and M. Rajadhyaksha, “Sensitivity and specificity for detecting basal cell carcinomas in Mohs excisions with confocal fluorescence mosaicing microscopy,” J. Biomed. Opt. 14(3), 034012 (2009).
[CrossRef] [PubMed]

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, “Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy,” Br. J. Dermatol. 160(6), 1242–1250 (2009).
[CrossRef] [PubMed]

P. Guitera, G. Pellacani, C. Longo, S. Seidenari, M. Avramidis, and S. W. Menzies, “In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions,” J. Invest. Dermatol. 129(1), 131–138 (2009).
[CrossRef] [PubMed]

D. S. Gareau, S. Abeytunge, and M. Rajadhyaksha, “Line-scanning reflectance confocal microscopy of human skin: comparison of full-pupil and divided-pupil configurations,” Opt. Lett. 34(20), 3235–3237 (2009).
[CrossRef] [PubMed]

2008

A. Gerger, R. Hofmann-Wellenhof, U. Langsenlehner, E. Richtig, S. Koller, W. Weger, V. Ahlgrimm-Siess, M. Horn, H. Samonigg, and J. Smolle, “In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images,” Br. J. Dermatol. 158(2), 329–333 (2008).
[CrossRef] [PubMed]

2007

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[PubMed]

P. J. Dwyer, C. A. DiMarzio, and M. Rajadhyaksha, “Confocal theta line-scanning microscope for imaging human tissues,” Appl. Opt. 46(10), 1843–1851 (2007).
[CrossRef] [PubMed]

2006

R. Wolleschensky, B. Zimmermann, and M. Kempe, “High-speed confocal fluorescence imaging with a novel line scanning microscope,” J. Biomed. Opt. 11(6), 064011 (2006).
[CrossRef] [PubMed]

2005

K. B. Im, S. Han, H. Park, D. Kim, and B. M. Kim, “Simple high-speed confocal line-scanning microscope,” Opt. Express 13(13), 5151–5156 (2005).
[CrossRef] [PubMed]

C. S. Chen, M. Elias, K. Busam, M. Rajadhyaksha, and A. A. Marghoob, “Multimodal in vivo optical imaging, including confocal microscopy, facilitates presurgical margin mapping for clinically complex lentigo maligna melanoma,” Br. J. Dermatol. 153(5), 1031–1036 (2005).
[CrossRef] [PubMed]

2004

S. Nori, F. Rius-Díaz, J. Cuevas, M. Goldgeier, P. Jaen, A. Torres, and S. G. González, “Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study,” J. Am. Acad. Dermatol. 51(6), 923–930 (2004).
[CrossRef] [PubMed]

D. X. Hammer, “Hand-held digital line-scanning laser ophthalmoscope (LSLO),” Proc. SPIE 5314, 161–169 (2004).
[CrossRef]

1999

1992

G. Brakenhoff and K. Visscher, “Scanning mirror microscope with optical sectioning characteristics: applications in ophthalmology,” J. Microsc. 165, 139–146 (1992).

1987

1985

1980

Abeytunge, S.

Ahlgrimm-Siess, V.

A. Gerger, R. Hofmann-Wellenhof, U. Langsenlehner, E. Richtig, S. Koller, W. Weger, V. Ahlgrimm-Siess, M. Horn, H. Samonigg, and J. Smolle, “In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images,” Br. J. Dermatol. 158(2), 329–333 (2008).
[CrossRef] [PubMed]

Avramidis, M.

P. Guitera, G. Pellacani, C. Longo, S. Seidenari, M. Avramidis, and S. W. Menzies, “In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions,” J. Invest. Dermatol. 129(1), 131–138 (2009).
[CrossRef] [PubMed]

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[PubMed]

Bassoli, S.

P. Guitera, G. Pellacani, K. A. Crotty, R. A. Scolyer, L. X. Li, S. Bassoli, M. Vinceti, H. Rabinovitz, C. Longo, and S. W. Menzies, “The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face,” J. Invest. Dermatol. 130(8), 2080–2091 (2010).
[CrossRef] [PubMed]

Brakenhoff, G.

G. Brakenhoff and K. Visscher, “Scanning mirror microscope with optical sectioning characteristics: applications in ophthalmology,” J. Microsc. 165, 139–146 (1992).

Busam, K.

C. S. Chen, M. Elias, K. Busam, M. Rajadhyaksha, and A. A. Marghoob, “Multimodal in vivo optical imaging, including confocal microscopy, facilitates presurgical margin mapping for clinically complex lentigo maligna melanoma,” Br. J. Dermatol. 153(5), 1031–1036 (2005).
[CrossRef] [PubMed]

Carlini, A. R.

Chen, C. S.

C. S. Chen, M. Elias, K. Busam, M. Rajadhyaksha, and A. A. Marghoob, “Multimodal in vivo optical imaging, including confocal microscopy, facilitates presurgical margin mapping for clinically complex lentigo maligna melanoma,” Br. J. Dermatol. 153(5), 1031–1036 (2005).
[CrossRef] [PubMed]

Crimmins, T. R.

Crotty, K. A.

P. Guitera, G. Pellacani, K. A. Crotty, R. A. Scolyer, L. X. Li, S. Bassoli, M. Vinceti, H. Rabinovitz, C. Longo, and S. W. Menzies, “The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face,” J. Invest. Dermatol. 130(8), 2080–2091 (2010).
[CrossRef] [PubMed]

Cuevas, J.

S. Nori, F. Rius-Díaz, J. Cuevas, M. Goldgeier, P. Jaen, A. Torres, and S. G. González, “Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study,” J. Am. Acad. Dermatol. 51(6), 923–930 (2004).
[CrossRef] [PubMed]

DiMarzio, C. A.

Donaldson, L.

Dusza, S. W.

D. S. Gareau, J. K. Karen, S. W. Dusza, M. Tudisco, K. S. Nehal, and M. Rajadhyaksha, “Sensitivity and specificity for detecting basal cell carcinomas in Mohs excisions with confocal fluorescence mosaicing microscopy,” J. Biomed. Opt. 14(3), 034012 (2009).
[CrossRef] [PubMed]

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, “Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy,” Br. J. Dermatol. 160(6), 1242–1250 (2009).
[CrossRef] [PubMed]

Dwyer, P. J.

Elias, M.

C. S. Chen, M. Elias, K. Busam, M. Rajadhyaksha, and A. A. Marghoob, “Multimodal in vivo optical imaging, including confocal microscopy, facilitates presurgical margin mapping for clinically complex lentigo maligna melanoma,” Br. J. Dermatol. 153(5), 1031–1036 (2005).
[CrossRef] [PubMed]

Gareau, D. S.

A. Scope, U. Mahmood, D. S. Gareau, M. Kenkre, J. A. Lieb, K. S. Nehal, and M. Rajadhyaksha, “In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins,” Br. J. Dermatol. 163(6), 1218–1228 (2010).
[CrossRef] [PubMed]

D. S. Gareau, J. K. Karen, S. W. Dusza, M. Tudisco, K. S. Nehal, and M. Rajadhyaksha, “Sensitivity and specificity for detecting basal cell carcinomas in Mohs excisions with confocal fluorescence mosaicing microscopy,” J. Biomed. Opt. 14(3), 034012 (2009).
[CrossRef] [PubMed]

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, “Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy,” Br. J. Dermatol. 160(6), 1242–1250 (2009).
[CrossRef] [PubMed]

D. S. Gareau, S. Abeytunge, and M. Rajadhyaksha, “Line-scanning reflectance confocal microscopy of human skin: comparison of full-pupil and divided-pupil configurations,” Opt. Lett. 34(20), 3235–3237 (2009).
[CrossRef] [PubMed]

Gerger, A.

A. Gerger, R. Hofmann-Wellenhof, U. Langsenlehner, E. Richtig, S. Koller, W. Weger, V. Ahlgrimm-Siess, M. Horn, H. Samonigg, and J. Smolle, “In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images,” Br. J. Dermatol. 158(2), 329–333 (2008).
[CrossRef] [PubMed]

Gmitro, A. F.

A. A. Tanbakuchi, A. R. Rouse, J. A. Udovich, K. D. Hatch, and A. F. Gmitro, “Clinical confocal microlaparoscope for real-time in vivo optical biopsies,” J. Biomed. Opt. 14(4), 044030 (2009).
[CrossRef] [PubMed]

Y. S. Sabharwal, A. R. Rouse, L. Donaldson, M. F. Hopkins, and A. F. Gmitro, “Slit-scanning confocal microendoscope for high-resolution in vivo imaging,” Appl. Opt. 38(34), 7133–7144 (1999).
[CrossRef] [PubMed]

Goldgeier, M.

S. Nori, F. Rius-Díaz, J. Cuevas, M. Goldgeier, P. Jaen, A. Torres, and S. G. González, “Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study,” J. Am. Acad. Dermatol. 51(6), 923–930 (2004).
[CrossRef] [PubMed]

González, S. G.

S. Nori, F. Rius-Díaz, J. Cuevas, M. Goldgeier, P. Jaen, A. Torres, and S. G. González, “Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study,” J. Am. Acad. Dermatol. 51(6), 923–930 (2004).
[CrossRef] [PubMed]

Guitera, P.

P. Guitera, G. Pellacani, K. A. Crotty, R. A. Scolyer, L. X. Li, S. Bassoli, M. Vinceti, H. Rabinovitz, C. Longo, and S. W. Menzies, “The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face,” J. Invest. Dermatol. 130(8), 2080–2091 (2010).
[CrossRef] [PubMed]

P. Guitera, G. Pellacani, C. Longo, S. Seidenari, M. Avramidis, and S. W. Menzies, “In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions,” J. Invest. Dermatol. 129(1), 131–138 (2009).
[CrossRef] [PubMed]

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[PubMed]

Hammer, D. X.

D. X. Hammer, “Hand-held digital line-scanning laser ophthalmoscope (LSLO),” Proc. SPIE 5314, 161–169 (2004).
[CrossRef]

Han, S.

Hatch, K. D.

A. A. Tanbakuchi, A. R. Rouse, J. A. Udovich, K. D. Hatch, and A. F. Gmitro, “Clinical confocal microlaparoscope for real-time in vivo optical biopsies,” J. Biomed. Opt. 14(4), 044030 (2009).
[CrossRef] [PubMed]

Hofmann-Wellenhof, R.

A. Gerger, R. Hofmann-Wellenhof, U. Langsenlehner, E. Richtig, S. Koller, W. Weger, V. Ahlgrimm-Siess, M. Horn, H. Samonigg, and J. Smolle, “In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images,” Br. J. Dermatol. 158(2), 329–333 (2008).
[CrossRef] [PubMed]

Hopkins, M. F.

Horn, M.

A. Gerger, R. Hofmann-Wellenhof, U. Langsenlehner, E. Richtig, S. Koller, W. Weger, V. Ahlgrimm-Siess, M. Horn, H. Samonigg, and J. Smolle, “In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images,” Br. J. Dermatol. 158(2), 329–333 (2008).
[CrossRef] [PubMed]

Im, K. B.

Jaen, P.

S. Nori, F. Rius-Díaz, J. Cuevas, M. Goldgeier, P. Jaen, A. Torres, and S. G. González, “Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study,” J. Am. Acad. Dermatol. 51(6), 923–930 (2004).
[CrossRef] [PubMed]

Karen, J. K.

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, “Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy,” Br. J. Dermatol. 160(6), 1242–1250 (2009).
[CrossRef] [PubMed]

D. S. Gareau, J. K. Karen, S. W. Dusza, M. Tudisco, K. S. Nehal, and M. Rajadhyaksha, “Sensitivity and specificity for detecting basal cell carcinomas in Mohs excisions with confocal fluorescence mosaicing microscopy,” J. Biomed. Opt. 14(3), 034012 (2009).
[CrossRef] [PubMed]

Kempe, M.

R. Wolleschensky, B. Zimmermann, and M. Kempe, “High-speed confocal fluorescence imaging with a novel line scanning microscope,” J. Biomed. Opt. 11(6), 064011 (2006).
[CrossRef] [PubMed]

Kenkre, M.

A. Scope, U. Mahmood, D. S. Gareau, M. Kenkre, J. A. Lieb, K. S. Nehal, and M. Rajadhyaksha, “In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins,” Br. J. Dermatol. 163(6), 1218–1228 (2010).
[CrossRef] [PubMed]

Kim, B. M.

Kim, D.

Koester, C. J.

Koller, S.

A. Gerger, R. Hofmann-Wellenhof, U. Langsenlehner, E. Richtig, S. Koller, W. Weger, V. Ahlgrimm-Siess, M. Horn, H. Samonigg, and J. Smolle, “In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images,” Br. J. Dermatol. 158(2), 329–333 (2008).
[CrossRef] [PubMed]

Langsenlehner, U.

A. Gerger, R. Hofmann-Wellenhof, U. Langsenlehner, E. Richtig, S. Koller, W. Weger, V. Ahlgrimm-Siess, M. Horn, H. Samonigg, and J. Smolle, “In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images,” Br. J. Dermatol. 158(2), 329–333 (2008).
[CrossRef] [PubMed]

Li, L. X.

P. Guitera, G. Pellacani, K. A. Crotty, R. A. Scolyer, L. X. Li, S. Bassoli, M. Vinceti, H. Rabinovitz, C. Longo, and S. W. Menzies, “The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face,” J. Invest. Dermatol. 130(8), 2080–2091 (2010).
[CrossRef] [PubMed]

Lieb, J. A.

A. Scope, U. Mahmood, D. S. Gareau, M. Kenkre, J. A. Lieb, K. S. Nehal, and M. Rajadhyaksha, “In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins,” Br. J. Dermatol. 163(6), 1218–1228 (2010).
[CrossRef] [PubMed]

Longo, C.

P. Guitera, G. Pellacani, K. A. Crotty, R. A. Scolyer, L. X. Li, S. Bassoli, M. Vinceti, H. Rabinovitz, C. Longo, and S. W. Menzies, “The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face,” J. Invest. Dermatol. 130(8), 2080–2091 (2010).
[CrossRef] [PubMed]

P. Guitera, G. Pellacani, C. Longo, S. Seidenari, M. Avramidis, and S. W. Menzies, “In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions,” J. Invest. Dermatol. 129(1), 131–138 (2009).
[CrossRef] [PubMed]

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[PubMed]

Mahmood, U.

A. Scope, U. Mahmood, D. S. Gareau, M. Kenkre, J. A. Lieb, K. S. Nehal, and M. Rajadhyaksha, “In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins,” Br. J. Dermatol. 163(6), 1218–1228 (2010).
[CrossRef] [PubMed]

Marghoob, A. A.

C. S. Chen, M. Elias, K. Busam, M. Rajadhyaksha, and A. A. Marghoob, “Multimodal in vivo optical imaging, including confocal microscopy, facilitates presurgical margin mapping for clinically complex lentigo maligna melanoma,” Br. J. Dermatol. 153(5), 1031–1036 (2005).
[CrossRef] [PubMed]

Menzies, S.

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[PubMed]

Menzies, S. W.

P. Guitera, G. Pellacani, K. A. Crotty, R. A. Scolyer, L. X. Li, S. Bassoli, M. Vinceti, H. Rabinovitz, C. Longo, and S. W. Menzies, “The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face,” J. Invest. Dermatol. 130(8), 2080–2091 (2010).
[CrossRef] [PubMed]

P. Guitera, G. Pellacani, C. Longo, S. Seidenari, M. Avramidis, and S. W. Menzies, “In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions,” J. Invest. Dermatol. 129(1), 131–138 (2009).
[CrossRef] [PubMed]

Nehal, K. S.

A. Scope, U. Mahmood, D. S. Gareau, M. Kenkre, J. A. Lieb, K. S. Nehal, and M. Rajadhyaksha, “In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins,” Br. J. Dermatol. 163(6), 1218–1228 (2010).
[CrossRef] [PubMed]

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, “Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy,” Br. J. Dermatol. 160(6), 1242–1250 (2009).
[CrossRef] [PubMed]

D. S. Gareau, J. K. Karen, S. W. Dusza, M. Tudisco, K. S. Nehal, and M. Rajadhyaksha, “Sensitivity and specificity for detecting basal cell carcinomas in Mohs excisions with confocal fluorescence mosaicing microscopy,” J. Biomed. Opt. 14(3), 034012 (2009).
[CrossRef] [PubMed]

Nori, S.

S. Nori, F. Rius-Díaz, J. Cuevas, M. Goldgeier, P. Jaen, A. Torres, and S. G. González, “Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study,” J. Am. Acad. Dermatol. 51(6), 923–930 (2004).
[CrossRef] [PubMed]

Park, H.

Pellacani, G.

P. Guitera, G. Pellacani, K. A. Crotty, R. A. Scolyer, L. X. Li, S. Bassoli, M. Vinceti, H. Rabinovitz, C. Longo, and S. W. Menzies, “The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face,” J. Invest. Dermatol. 130(8), 2080–2091 (2010).
[CrossRef] [PubMed]

P. Guitera, G. Pellacani, C. Longo, S. Seidenari, M. Avramidis, and S. W. Menzies, “In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions,” J. Invest. Dermatol. 129(1), 131–138 (2009).
[CrossRef] [PubMed]

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[PubMed]

Rabinovitz, H.

P. Guitera, G. Pellacani, K. A. Crotty, R. A. Scolyer, L. X. Li, S. Bassoli, M. Vinceti, H. Rabinovitz, C. Longo, and S. W. Menzies, “The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face,” J. Invest. Dermatol. 130(8), 2080–2091 (2010).
[CrossRef] [PubMed]

Rajadhyaksha, M.

A. Scope, U. Mahmood, D. S. Gareau, M. Kenkre, J. A. Lieb, K. S. Nehal, and M. Rajadhyaksha, “In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins,” Br. J. Dermatol. 163(6), 1218–1228 (2010).
[CrossRef] [PubMed]

D. S. Gareau, J. K. Karen, S. W. Dusza, M. Tudisco, K. S. Nehal, and M. Rajadhyaksha, “Sensitivity and specificity for detecting basal cell carcinomas in Mohs excisions with confocal fluorescence mosaicing microscopy,” J. Biomed. Opt. 14(3), 034012 (2009).
[CrossRef] [PubMed]

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, “Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy,” Br. J. Dermatol. 160(6), 1242–1250 (2009).
[CrossRef] [PubMed]

D. S. Gareau, S. Abeytunge, and M. Rajadhyaksha, “Line-scanning reflectance confocal microscopy of human skin: comparison of full-pupil and divided-pupil configurations,” Opt. Lett. 34(20), 3235–3237 (2009).
[CrossRef] [PubMed]

P. J. Dwyer, C. A. DiMarzio, and M. Rajadhyaksha, “Confocal theta line-scanning microscope for imaging human tissues,” Appl. Opt. 46(10), 1843–1851 (2007).
[CrossRef] [PubMed]

C. S. Chen, M. Elias, K. Busam, M. Rajadhyaksha, and A. A. Marghoob, “Multimodal in vivo optical imaging, including confocal microscopy, facilitates presurgical margin mapping for clinically complex lentigo maligna melanoma,” Br. J. Dermatol. 153(5), 1031–1036 (2005).
[CrossRef] [PubMed]

Richtig, E.

A. Gerger, R. Hofmann-Wellenhof, U. Langsenlehner, E. Richtig, S. Koller, W. Weger, V. Ahlgrimm-Siess, M. Horn, H. Samonigg, and J. Smolle, “In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images,” Br. J. Dermatol. 158(2), 329–333 (2008).
[CrossRef] [PubMed]

Rius-Díaz, F.

S. Nori, F. Rius-Díaz, J. Cuevas, M. Goldgeier, P. Jaen, A. Torres, and S. G. González, “Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study,” J. Am. Acad. Dermatol. 51(6), 923–930 (2004).
[CrossRef] [PubMed]

Rouse, A. R.

A. A. Tanbakuchi, A. R. Rouse, J. A. Udovich, K. D. Hatch, and A. F. Gmitro, “Clinical confocal microlaparoscope for real-time in vivo optical biopsies,” J. Biomed. Opt. 14(4), 044030 (2009).
[CrossRef] [PubMed]

Y. S. Sabharwal, A. R. Rouse, L. Donaldson, M. F. Hopkins, and A. F. Gmitro, “Slit-scanning confocal microendoscope for high-resolution in vivo imaging,” Appl. Opt. 38(34), 7133–7144 (1999).
[CrossRef] [PubMed]

Sabharwal, Y. S.

Samonigg, H.

A. Gerger, R. Hofmann-Wellenhof, U. Langsenlehner, E. Richtig, S. Koller, W. Weger, V. Ahlgrimm-Siess, M. Horn, H. Samonigg, and J. Smolle, “In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images,” Br. J. Dermatol. 158(2), 329–333 (2008).
[CrossRef] [PubMed]

Scolyer, R. A.

P. Guitera, G. Pellacani, K. A. Crotty, R. A. Scolyer, L. X. Li, S. Bassoli, M. Vinceti, H. Rabinovitz, C. Longo, and S. W. Menzies, “The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face,” J. Invest. Dermatol. 130(8), 2080–2091 (2010).
[CrossRef] [PubMed]

Scope, A.

A. Scope, U. Mahmood, D. S. Gareau, M. Kenkre, J. A. Lieb, K. S. Nehal, and M. Rajadhyaksha, “In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins,” Br. J. Dermatol. 163(6), 1218–1228 (2010).
[CrossRef] [PubMed]

Seidenari, S.

P. Guitera, G. Pellacani, C. Longo, S. Seidenari, M. Avramidis, and S. W. Menzies, “In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions,” J. Invest. Dermatol. 129(1), 131–138 (2009).
[CrossRef] [PubMed]

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[PubMed]

Smolle, J.

A. Gerger, R. Hofmann-Wellenhof, U. Langsenlehner, E. Richtig, S. Koller, W. Weger, V. Ahlgrimm-Siess, M. Horn, H. Samonigg, and J. Smolle, “In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images,” Br. J. Dermatol. 158(2), 329–333 (2008).
[CrossRef] [PubMed]

Tanbakuchi, A. A.

A. A. Tanbakuchi, A. R. Rouse, J. A. Udovich, K. D. Hatch, and A. F. Gmitro, “Clinical confocal microlaparoscope for real-time in vivo optical biopsies,” J. Biomed. Opt. 14(4), 044030 (2009).
[CrossRef] [PubMed]

Torres, A.

S. Nori, F. Rius-Díaz, J. Cuevas, M. Goldgeier, P. Jaen, A. Torres, and S. G. González, “Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study,” J. Am. Acad. Dermatol. 51(6), 923–930 (2004).
[CrossRef] [PubMed]

Tudisco, M.

D. S. Gareau, J. K. Karen, S. W. Dusza, M. Tudisco, K. S. Nehal, and M. Rajadhyaksha, “Sensitivity and specificity for detecting basal cell carcinomas in Mohs excisions with confocal fluorescence mosaicing microscopy,” J. Biomed. Opt. 14(3), 034012 (2009).
[CrossRef] [PubMed]

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, “Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy,” Br. J. Dermatol. 160(6), 1242–1250 (2009).
[CrossRef] [PubMed]

Udovich, J. A.

A. A. Tanbakuchi, A. R. Rouse, J. A. Udovich, K. D. Hatch, and A. F. Gmitro, “Clinical confocal microlaparoscope for real-time in vivo optical biopsies,” J. Biomed. Opt. 14(4), 044030 (2009).
[CrossRef] [PubMed]

Vinceti, M.

P. Guitera, G. Pellacani, K. A. Crotty, R. A. Scolyer, L. X. Li, S. Bassoli, M. Vinceti, H. Rabinovitz, C. Longo, and S. W. Menzies, “The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face,” J. Invest. Dermatol. 130(8), 2080–2091 (2010).
[CrossRef] [PubMed]

Visscher, K.

G. Brakenhoff and K. Visscher, “Scanning mirror microscope with optical sectioning characteristics: applications in ophthalmology,” J. Microsc. 165, 139–146 (1992).

Weger, W.

A. Gerger, R. Hofmann-Wellenhof, U. Langsenlehner, E. Richtig, S. Koller, W. Weger, V. Ahlgrimm-Siess, M. Horn, H. Samonigg, and J. Smolle, “In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images,” Br. J. Dermatol. 158(2), 329–333 (2008).
[CrossRef] [PubMed]

Wilson, T.

Wolleschensky, R.

R. Wolleschensky, B. Zimmermann, and M. Kempe, “High-speed confocal fluorescence imaging with a novel line scanning microscope,” J. Biomed. Opt. 11(6), 064011 (2006).
[CrossRef] [PubMed]

Zimmermann, B.

R. Wolleschensky, B. Zimmermann, and M. Kempe, “High-speed confocal fluorescence imaging with a novel line scanning microscope,” J. Biomed. Opt. 11(6), 064011 (2006).
[CrossRef] [PubMed]

Appl. Opt.

Br. J. Dermatol.

J. K. Karen, D. S. Gareau, S. W. Dusza, M. Tudisco, M. Rajadhyaksha, and K. S. Nehal, “Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy,” Br. J. Dermatol. 160(6), 1242–1250 (2009).
[CrossRef] [PubMed]

A. Scope, U. Mahmood, D. S. Gareau, M. Kenkre, J. A. Lieb, K. S. Nehal, and M. Rajadhyaksha, “In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins,” Br. J. Dermatol. 163(6), 1218–1228 (2010).
[CrossRef] [PubMed]

C. S. Chen, M. Elias, K. Busam, M. Rajadhyaksha, and A. A. Marghoob, “Multimodal in vivo optical imaging, including confocal microscopy, facilitates presurgical margin mapping for clinically complex lentigo maligna melanoma,” Br. J. Dermatol. 153(5), 1031–1036 (2005).
[CrossRef] [PubMed]

A. Gerger, R. Hofmann-Wellenhof, U. Langsenlehner, E. Richtig, S. Koller, W. Weger, V. Ahlgrimm-Siess, M. Horn, H. Samonigg, and J. Smolle, “In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images,” Br. J. Dermatol. 158(2), 329–333 (2008).
[CrossRef] [PubMed]

J. Am. Acad. Dermatol.

S. Nori, F. Rius-Díaz, J. Cuevas, M. Goldgeier, P. Jaen, A. Torres, and S. G. González, “Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study,” J. Am. Acad. Dermatol. 51(6), 923–930 (2004).
[CrossRef] [PubMed]

J. Biomed. Opt.

D. S. Gareau, J. K. Karen, S. W. Dusza, M. Tudisco, K. S. Nehal, and M. Rajadhyaksha, “Sensitivity and specificity for detecting basal cell carcinomas in Mohs excisions with confocal fluorescence mosaicing microscopy,” J. Biomed. Opt. 14(3), 034012 (2009).
[CrossRef] [PubMed]

R. Wolleschensky, B. Zimmermann, and M. Kempe, “High-speed confocal fluorescence imaging with a novel line scanning microscope,” J. Biomed. Opt. 11(6), 064011 (2006).
[CrossRef] [PubMed]

A. A. Tanbakuchi, A. R. Rouse, J. A. Udovich, K. D. Hatch, and A. F. Gmitro, “Clinical confocal microlaparoscope for real-time in vivo optical biopsies,” J. Biomed. Opt. 14(4), 044030 (2009).
[CrossRef] [PubMed]

J. Invest. Dermatol.

P. Guitera, G. Pellacani, K. A. Crotty, R. A. Scolyer, L. X. Li, S. Bassoli, M. Vinceti, H. Rabinovitz, C. Longo, and S. W. Menzies, “The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face,” J. Invest. Dermatol. 130(8), 2080–2091 (2010).
[CrossRef] [PubMed]

G. Pellacani, P. Guitera, C. Longo, M. Avramidis, S. Seidenari, and S. Menzies, “The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions,” J. Invest. Dermatol. 127(12), 2759–2765 (2007).
[PubMed]

P. Guitera, G. Pellacani, C. Longo, S. Seidenari, M. Avramidis, and S. W. Menzies, “In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions,” J. Invest. Dermatol. 129(1), 131–138 (2009).
[CrossRef] [PubMed]

J. Microsc.

G. Brakenhoff and K. Visscher, “Scanning mirror microscope with optical sectioning characteristics: applications in ophthalmology,” J. Microsc. 165, 139–146 (1992).

Opt. Express

Opt. Lett.

Proc. SPIE

D. X. Hammer, “Hand-held digital line-scanning laser ophthalmoscope (LSLO),” Proc. SPIE 5314, 161–169 (2004).
[CrossRef]

Other

S. G. Gonzalez, M. Gill, and A. C. Halpern, eds., Reflectance Confocal Microscopy of Cutaneous Tumors—An Atlas with Clinical, Dermoscopic and Histological Correlations (Informa Healthcare, London, 2008).

S. L. Jacques, “Polarized light imaging of biological tissues,” in Handbook of Biomedical Optics, D. Boas, C. Pitris, and N. Ramanujam, eds. (CRC Press, Boca Raton, FL, 2011), pp. 649–669.

Supplementary Material (2)

» Media 1: AVI (3684 KB)     
» Media 2: AVI (2790 KB)     

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Figures (10)

Fig. 1
Fig. 1

Optical layout. The blue line shows the path in the plane of the page and the red line shows the path in the perpendicular plane. The cylinder lens focuses the collimated beam into a line in the back focal plane of the objective, which is Fourier-transformed into a perpendicularly-oriented line in the object plane in the tissue. A mirror mounted on a galvanometric scanner sweeps the line across the object plane in the tissue. A polarizing beam splitter and quarter wave plate (QWP) remove back reflections from the optics.

Fig. 2
Fig. 2

Signal flow architecture for the FPGA-based electronics in our line-scanning confocal microscope.

Fig. 3
Fig. 3

(A) Sources of noise in detection system. Pattern noise is the most significant source of noise. (B) Signal-to-noise ratio in the detection system. SNR levels off at one-quarter well, with a maximum SNR of 33, as limited by pattern noise.

Fig. 4
Fig. 4

The FWHM of the axial response with increasing slit diameter in the line-scanning experiments (LS Exp) and increasing pinhole diameter in the point scanning theory (PS Theory). The experimental results in the line-scanning system are compared to the theoretical results for a point scanning system [22].

Fig. 5
Fig. 5

(A) Axial response (AR) measurements for varying detector-slit widths. Slit widths of 5, 10, 25 and 50 μm were used, corresponding to Airy units of 0.27, 0.54, 1.34, and 2.68. (B) AR measurements through full-thickness of human epidermis with detector-slit widths of 5 μm and 25 μm. These are compared to the nominal AR at the same slit width. (C) Five AR plots with plates of varying thickness behind the objective lens. Plate thicknesses of 40 μm, 170 μm, 1 mm and 3.5 mm were used. All measurements were taken with a 10 μm slit in place. (D) Four AR plots for various displacements of the focused line from the BFP of the objective lens. Displacements of +5, 0, −5 and −15 mm were used. (E) Axial response on a logarithmic scale for detector slit width of 25 μm with and without epidermis. Tails of axial response contribute to loss of contrast in imaging.

Fig. 6
Fig. 6

Images of human epidermis in vivo. (A) Granular layer, (B) spinous layer, (C) basal layer.

Fig. 7
Fig. 7

Frame from video clip (Media 1) of human epidermis in vivo.

Fig. 8
Fig. 8

Images of human oral mucosa in vivo. (A) Superficial layer, (B) epithelial layer, (C) capillaries.

Fig. 9
Fig. 9

Frame from a video clip (Media 2) of human oral mucosa in vivo.

Fig. 10
Fig. 10

Comparison of speckle index. (A) Speckle index is plotted for different configurations. The two-frame averaging reduces speckle as compared to that in single frames. The increase in slit width from 50 μm to 125 μm produces the best reduction in speckle noise. The use of the 50/50 beam splitter in place of the PBS and QWP does not significantly change the speckle noise in the system. (B) Single frame image using a PBS and a 50 μm slit. (C) Two frame average using PBS and 50 μm slit. (D) Single frame image using PBS and a 125 μm slit. (E) Single frame image using 50/50 BS and 50 μm slit.

Equations (1)

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s = 1 M 2 m , n = 2 M 1 σ ( m , n ) μ ( m , n ) .

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