Abstract

High spatial and temporal resolutions are important advantages of optical imaging over other modalities. The recently developed spatial overlap modulation (SPOM) microscopy enables high resolution imaging by spatial modulation of double-beam overlap. However, SPOM suffers from bad temporal resolution and high system complexity. In this paper, we re-formulate the SPOM resolution theory and develop Virtual SPOM (vSPOM) microscopy. By one-way oversampling and convolution with differential filters, vSPOM not only realizes the same factor of spatial resolution improvement as SPOM, but overcome SPOM’s major drawbacks. We demonstrated vSPOM on in vivo clinical images and find that the Gabor filter, which represents two-beam vSPOM, is the most effective among all vSPOM filters. The development of vSPOM enables easy incorporation of SPOM into any imaging system, and extends the use of SPOM to real-time in vivo applications.

© 2013 Optical Society of America

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2013

2012

2011

2010

S.-H. Chia, T.-M. Liu, A. A. Ivanov, A. B. Fedotov, A. M. Zheltikov, M.-R. Tsai, M.-C. Chan, C.-H. Yu, and C.-K. Sun, “A sub-100 fs self-starting Cr:forsterite laser generating 1.4 W output power,” Opt. Express18(23), 24085–24091 (2010).
[CrossRef] [PubMed]

S.-Y. Chen, S.-U. Chen, H.-Y. Wu, W.-J. Lee, Y.-H. Liao, and C.-K. Sun, “In vivo virtual biopsy of human skin by using noninvasive higher harmonic generation microscopy,” IEEE J. Sel. Top. Quantum Electron.16(3), 478–492 (2010).
[CrossRef]

2009

2008

N. Chen, C. H. Wong, and C. J. Sheppard, “Focal modulation microscopy,” Opt. Express16(23), 18764–18769 (2008).
[CrossRef] [PubMed]

C.-S. Hsieh, C.-Y. Ko, S.-Y. Chen, T.-M. Liu, J.-S. Wu, C. H. Hu, and C.-K. Sun, “In vivo long-term continuous observation of gene expression in zebrafish embryo nerve systems by using harmonic generation microscopy and morphant technology,” J. Biomed. Opt.13(6), 064041 (2008).
[CrossRef] [PubMed]

O. L. Muskens, P. Billaud, M. Broyer, N. Del Fatti, and F. Vallée, “Optical extinction spectrum of a single metal nanoparticle: Quantitative characterization of a particle and of its local environment,” Phys. Rev. B78(20), 205410 (2008).
[CrossRef]

2006

2005

2004

C. K. Sun, S. W. Chu, S. Y. Chen, T. H. Tsai, T. M. Liu, C. Y. Lin, and H. J. Tsai, “Higher harmonic generation microscopy for developmental biology,” J. Struct. Biol.147(1), 19–30 (2004).
[CrossRef] [PubMed]

A. Arbouet, D. Christofilos, N. Del Fatti, F. Vallée, J. R. Huntzinger, L. Arnaud, P. Billaud, and M. Broyer, “Direct measurement of the single-metal-cluster optical absorption,” Phys. Rev. Lett.93(12), 127401 (2004).
[CrossRef] [PubMed]

2003

P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol.21(11), 1356–1360 (2003).
[CrossRef] [PubMed]

2001

J. Squier and M. Muller, “High resolution nonlinear microscopy: A review of sources and methods for achieving optimal imaging,” Rev. Sci. Instrum.72(7), 2855–2867 (2001).
[CrossRef]

M. Sticker, C. K. Hitzenberger, R. Leitgeb, and A. F. Fercher, “Quantitative differential phase measurement and imaging in transparent and turbid media by optical coherence tomography,” Opt. Lett.26(8), 518–520 (2001).
[CrossRef] [PubMed]

1999

1998

O. Nestares, R. Navarro, and J. Portilla, “Efficient spatial-domain implementation of a multiscale image representation based on gabor functions,” J. Electron. Imaging7(1), 166–173 (1998).
[CrossRef]

E. D. Salmon and P. Tran, “High-resolution video-enhanced differential interference contrast (VE-DIC) light microscopy,” Methods Cell Biol.56, 153–184 (1998).
[CrossRef] [PubMed]

1991

A. K. Jain and F. Farrokhnia, “Unsupervised texture segmentation using Gabor filters,” Pattern Recognit.24(12), 1167–1186 (1991).
[CrossRef]

1990

B. Chitprasert and K. R. Rao, “Discrete cosine transform filtering,” Signal Process.19(3), 233–245 (1990).
[CrossRef]

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
[CrossRef] [PubMed]

1989

G. E. Sotak and K. L. Boyer, “The Laplacian-of-Gaussian kernel: a formal analysis and design procedure for fast, accurate convolution and full-frame output,” Comput. Vision Graphics Image Process.48(2), 147–189 (1989).
[CrossRef]

1987

R. A. Young, “The Gaussian derivative model for spatial vision: I. Retinal mechanisms,” Spat. Vis.2(4), 273–293 (1987).
[CrossRef] [PubMed]

J. P. Jones and L. A. Palmer, “An evaluation of the two-dimensional Gabor filter model of simple receptive fields in cat striate cortex,” J. Neurophysiol.58(6), 1233–1258 (1987).
[PubMed]

1985

1981

D. V. Cicchetti and S. A. Sparrow, “Developing criteria for establishing interrater reliability of specific items: applications to assessment of adaptive behavior,” Am. J. Ment. Defic.86(2), 127–137 (1981).
[PubMed]

1979

N. Otsu, “A threshold selection method from gray-level histograms,” IEEE Trans. Syst. Man Cybern.9(1), 62–66 (1979).
[CrossRef]

1969

R. D. Allen, G. B. David, and G. Nomarski, “The zeiss-Nomarski differential interference equipment for transmitted-light microscopy,” Z. Wiss. Mikrosk.69(4), 193–221 (1969).
[PubMed]

1965

J. W. Cooley and J. W. Tukey, “An algorithm for the machine calculation of complex Fourier series,” Math. Comput.19(90), 297–301 (1965).
[CrossRef]

Allen, R. D.

R. D. Allen, G. B. David, and G. Nomarski, “The zeiss-Nomarski differential interference equipment for transmitted-light microscopy,” Z. Wiss. Mikrosk.69(4), 193–221 (1969).
[PubMed]

Arbouet, A.

A. Arbouet, D. Christofilos, N. Del Fatti, F. Vallée, J. R. Huntzinger, L. Arnaud, P. Billaud, and M. Broyer, “Direct measurement of the single-metal-cluster optical absorption,” Phys. Rev. Lett.93(12), 127401 (2004).
[CrossRef] [PubMed]

Arnaud, L.

A. Arbouet, D. Christofilos, N. Del Fatti, F. Vallée, J. R. Huntzinger, L. Arnaud, P. Billaud, and M. Broyer, “Direct measurement of the single-metal-cluster optical absorption,” Phys. Rev. Lett.93(12), 127401 (2004).
[CrossRef] [PubMed]

Billaud, P.

O. L. Muskens, P. Billaud, M. Broyer, N. Del Fatti, and F. Vallée, “Optical extinction spectrum of a single metal nanoparticle: Quantitative characterization of a particle and of its local environment,” Phys. Rev. B78(20), 205410 (2008).
[CrossRef]

A. Arbouet, D. Christofilos, N. Del Fatti, F. Vallée, J. R. Huntzinger, L. Arnaud, P. Billaud, and M. Broyer, “Direct measurement of the single-metal-cluster optical absorption,” Phys. Rev. Lett.93(12), 127401 (2004).
[CrossRef] [PubMed]

Boyer, K. L.

G. E. Sotak and K. L. Boyer, “The Laplacian-of-Gaussian kernel: a formal analysis and design procedure for fast, accurate convolution and full-frame output,” Comput. Vision Graphics Image Process.48(2), 147–189 (1989).
[CrossRef]

Broyer, M.

O. L. Muskens, P. Billaud, M. Broyer, N. Del Fatti, and F. Vallée, “Optical extinction spectrum of a single metal nanoparticle: Quantitative characterization of a particle and of its local environment,” Phys. Rev. B78(20), 205410 (2008).
[CrossRef]

A. Arbouet, D. Christofilos, N. Del Fatti, F. Vallée, J. R. Huntzinger, L. Arnaud, P. Billaud, and M. Broyer, “Direct measurement of the single-metal-cluster optical absorption,” Phys. Rev. Lett.93(12), 127401 (2004).
[CrossRef] [PubMed]

Campagnola, P. J.

P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol.21(11), 1356–1360 (2003).
[CrossRef] [PubMed]

Carter, R.

Chan, M.-C.

Chen, N.

Chen, S. Y.

T.-H. Tsai, C. Y. Lin, H. J. Tsai, S. Y. Chen, S. P. Tai, K. H. Lin, and C.-K. Sun, “Biomolecular imaging based on far-red fluorescent protein with a high two-photon excitation action cross section,” Opt. Lett.31(7), 930–932 (2006).
[CrossRef] [PubMed]

C. K. Sun, S. W. Chu, S. Y. Chen, T. H. Tsai, T. M. Liu, C. Y. Lin, and H. J. Tsai, “Higher harmonic generation microscopy for developmental biology,” J. Struct. Biol.147(1), 19–30 (2004).
[CrossRef] [PubMed]

Chen, S.-U.

S.-Y. Chen, S.-U. Chen, H.-Y. Wu, W.-J. Lee, Y.-H. Liao, and C.-K. Sun, “In vivo virtual biopsy of human skin by using noninvasive higher harmonic generation microscopy,” IEEE J. Sel. Top. Quantum Electron.16(3), 478–492 (2010).
[CrossRef]

Chen, S.-Y.

Y.-H. Liao, S.-Y. Chen, S.-Y. Chou, P.-H. Wang, M.-R. Tsai, and C.-K. Sun, “Determination of chronological aging parameters in epidermal keratinocytes by in vivo harmonic generation microscopy,” Biomed. Opt. Express4(1), 77–88 (2013).
[CrossRef] [PubMed]

M.-R. Tsai, S.-Y. Chen, D.-B. Shieh, P.-J. Lou, and C.-K. Sun, “In vivo optical virtual biopsy of human oral mucosa with harmonic generation microscopy,” Biomed. Opt. Express2(8), 2317–2328 (2011).
[CrossRef] [PubMed]

S.-Y. Chen, S.-U. Chen, H.-Y. Wu, W.-J. Lee, Y.-H. Liao, and C.-K. Sun, “In vivo virtual biopsy of human skin by using noninvasive higher harmonic generation microscopy,” IEEE J. Sel. Top. Quantum Electron.16(3), 478–492 (2010).
[CrossRef]

S.-Y. Chen, H.-Y. Wu, and C.-K. Sun, “In vivo harmonic generation biopsy of human skin,” J. Biomed. Opt.14(6), 060505 (2009).
[CrossRef] [PubMed]

C.-S. Hsieh, C.-Y. Ko, S.-Y. Chen, T.-M. Liu, J.-S. Wu, C. H. Hu, and C.-K. Sun, “In vivo long-term continuous observation of gene expression in zebrafish embryo nerve systems by using harmonic generation microscopy and morphant technology,” J. Biomed. Opt.13(6), 064041 (2008).
[CrossRef] [PubMed]

Chia, S.-H.

Chitprasert, B.

B. Chitprasert and K. R. Rao, “Discrete cosine transform filtering,” Signal Process.19(3), 233–245 (1990).
[CrossRef]

Chong, S. P.

Chou, S.-Y.

Christofilos, D.

A. Arbouet, D. Christofilos, N. Del Fatti, F. Vallée, J. R. Huntzinger, L. Arnaud, P. Billaud, and M. Broyer, “Direct measurement of the single-metal-cluster optical absorption,” Phys. Rev. Lett.93(12), 127401 (2004).
[CrossRef] [PubMed]

Chu, S. W.

C. K. Sun, S. W. Chu, S. Y. Chen, T. H. Tsai, T. M. Liu, C. Y. Lin, and H. J. Tsai, “Higher harmonic generation microscopy for developmental biology,” J. Struct. Biol.147(1), 19–30 (2004).
[CrossRef] [PubMed]

Cicchetti, D. V.

D. V. Cicchetti and S. A. Sparrow, “Developing criteria for establishing interrater reliability of specific items: applications to assessment of adaptive behavior,” Am. J. Ment. Defic.86(2), 127–137 (1981).
[PubMed]

Cooley, J. W.

J. W. Cooley and J. W. Tukey, “An algorithm for the machine calculation of complex Fourier series,” Math. Comput.19(90), 297–301 (1965).
[CrossRef]

Daugman, J. G.

David, G. B.

R. D. Allen, G. B. David, and G. Nomarski, “The zeiss-Nomarski differential interference equipment for transmitted-light microscopy,” Z. Wiss. Mikrosk.69(4), 193–221 (1969).
[PubMed]

Del Fatti, N.

O. L. Muskens, P. Billaud, M. Broyer, N. Del Fatti, and F. Vallée, “Optical extinction spectrum of a single metal nanoparticle: Quantitative characterization of a particle and of its local environment,” Phys. Rev. B78(20), 205410 (2008).
[CrossRef]

A. Arbouet, D. Christofilos, N. Del Fatti, F. Vallée, J. R. Huntzinger, L. Arnaud, P. Billaud, and M. Broyer, “Direct measurement of the single-metal-cluster optical absorption,” Phys. Rev. Lett.93(12), 127401 (2004).
[CrossRef] [PubMed]

Denk, W.

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Elliott, T. J.

Fairbairn, N.

Farrokhnia, F.

A. K. Jain and F. Farrokhnia, “Unsupervised texture segmentation using Gabor filters,” Pattern Recognit.24(12), 1167–1186 (1991).
[CrossRef]

Fedotov, A. B.

Fercher, A. F.

Fernandes, R.

Hitzenberger, C. K.

Hsieh, C.-S.

C.-S. Hsieh, C.-Y. Ko, S.-Y. Chen, T.-M. Liu, J.-S. Wu, C. H. Hu, and C.-K. Sun, “In vivo long-term continuous observation of gene expression in zebrafish embryo nerve systems by using harmonic generation microscopy and morphant technology,” J. Biomed. Opt.13(6), 064041 (2008).
[CrossRef] [PubMed]

Hu, C. H.

C.-S. Hsieh, C.-Y. Ko, S.-Y. Chen, T.-M. Liu, J.-S. Wu, C. H. Hu, and C.-K. Sun, “In vivo long-term continuous observation of gene expression in zebrafish embryo nerve systems by using harmonic generation microscopy and morphant technology,” J. Biomed. Opt.13(6), 064041 (2008).
[CrossRef] [PubMed]

Huang, H.-Y.

Huntzinger, J. R.

A. Arbouet, D. Christofilos, N. Del Fatti, F. Vallée, J. R. Huntzinger, L. Arnaud, P. Billaud, and M. Broyer, “Direct measurement of the single-metal-cluster optical absorption,” Phys. Rev. Lett.93(12), 127401 (2004).
[CrossRef] [PubMed]

Isobe, K.

Ivanov, A. A.

Jain, A. K.

A. K. Jain and F. Farrokhnia, “Unsupervised texture segmentation using Gabor filters,” Pattern Recognit.24(12), 1167–1186 (1991).
[CrossRef]

Jones, J. P.

J. P. Jones and L. A. Palmer, “An evaluation of the two-dimensional Gabor filter model of simple receptive fields in cat striate cortex,” J. Neurophysiol.58(6), 1233–1258 (1987).
[PubMed]

Kanaras, A. G.

Kawano, H.

Ko, C.-Y.

C.-S. Hsieh, C.-Y. Ko, S.-Y. Chen, T.-M. Liu, J.-S. Wu, C. H. Hu, and C.-K. Sun, “In vivo long-term continuous observation of gene expression in zebrafish embryo nerve systems by using harmonic generation microscopy and morphant technology,” J. Biomed. Opt.13(6), 064041 (2008).
[CrossRef] [PubMed]

Kumagai, A.

Lee, W.-J.

S.-Y. Chen, S.-U. Chen, H.-Y. Wu, W.-J. Lee, Y.-H. Liao, and C.-K. Sun, “In vivo virtual biopsy of human skin by using noninvasive higher harmonic generation microscopy,” IEEE J. Sel. Top. Quantum Electron.16(3), 478–492 (2010).
[CrossRef]

S.-P. Tai, T.-H. Tsai, W.-J. Lee, D.-B. Shieh, Y.-H. Liao, H.-Y. Huang, K. Zhang, H.-L. Liu, and C.-K. Sun, “Optical biopsy of fixed human skin with backward-collected optical harmonics signals,” Opt. Express13(20), 8231–8242 (2005).
[CrossRef] [PubMed]

Leitgeb, R.

Leray, A.

Liao, Y.-H.

Light, R. A.

Lin, C. Y.

T.-H. Tsai, C. Y. Lin, H. J. Tsai, S. Y. Chen, S. P. Tai, K. H. Lin, and C.-K. Sun, “Biomolecular imaging based on far-red fluorescent protein with a high two-photon excitation action cross section,” Opt. Lett.31(7), 930–932 (2006).
[CrossRef] [PubMed]

C. K. Sun, S. W. Chu, S. Y. Chen, T. H. Tsai, T. M. Liu, C. Y. Lin, and H. J. Tsai, “Higher harmonic generation microscopy for developmental biology,” J. Struct. Biol.147(1), 19–30 (2004).
[CrossRef] [PubMed]

Lin, K. H.

Liu, H.-L.

Liu, T. M.

C. K. Sun, S. W. Chu, S. Y. Chen, T. H. Tsai, T. M. Liu, C. Y. Lin, and H. J. Tsai, “Higher harmonic generation microscopy for developmental biology,” J. Struct. Biol.147(1), 19–30 (2004).
[CrossRef] [PubMed]

Liu, T.-M.

S.-H. Chia, T.-M. Liu, A. A. Ivanov, A. B. Fedotov, A. M. Zheltikov, M.-R. Tsai, M.-C. Chan, C.-H. Yu, and C.-K. Sun, “A sub-100 fs self-starting Cr:forsterite laser generating 1.4 W output power,” Opt. Express18(23), 24085–24091 (2010).
[CrossRef] [PubMed]

C.-S. Hsieh, C.-Y. Ko, S.-Y. Chen, T.-M. Liu, J.-S. Wu, C. H. Hu, and C.-K. Sun, “In vivo long-term continuous observation of gene expression in zebrafish embryo nerve systems by using harmonic generation microscopy and morphant technology,” J. Biomed. Opt.13(6), 064041 (2008).
[CrossRef] [PubMed]

Loew, L. M.

P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol.21(11), 1356–1360 (2003).
[CrossRef] [PubMed]

Lou, P.-J.

Mertz, J.

Midorikawa, K.

Miyawaki, A.

Mizuno, H.

Muller, M.

J. Squier and M. Muller, “High resolution nonlinear microscopy: A review of sources and methods for achieving optimal imaging,” Rev. Sci. Instrum.72(7), 2855–2867 (2001).
[CrossRef]

Muskens, O. L.

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Navarro, R.

O. Nestares, R. Navarro, and J. Portilla, “Efficient spatial-domain implementation of a multiscale image representation based on gabor functions,” J. Electron. Imaging7(1), 166–173 (1998).
[CrossRef]

Nestares, O.

O. Nestares, R. Navarro, and J. Portilla, “Efficient spatial-domain implementation of a multiscale image representation based on gabor functions,” J. Electron. Imaging7(1), 166–173 (1998).
[CrossRef]

Nomarski, G.

R. D. Allen, G. B. David, and G. Nomarski, “The zeiss-Nomarski differential interference equipment for transmitted-light microscopy,” Z. Wiss. Mikrosk.69(4), 193–221 (1969).
[PubMed]

Otsu, N.

N. Otsu, “A threshold selection method from gray-level histograms,” IEEE Trans. Syst. Man Cybern.9(1), 62–66 (1979).
[CrossRef]

Palmer, L. A.

J. P. Jones and L. A. Palmer, “An evaluation of the two-dimensional Gabor filter model of simple receptive fields in cat striate cortex,” J. Neurophysiol.58(6), 1233–1258 (1987).
[PubMed]

Pitter, M. C.

Portilla, J.

O. Nestares, R. Navarro, and J. Portilla, “Efficient spatial-domain implementation of a multiscale image representation based on gabor functions,” J. Electron. Imaging7(1), 166–173 (1998).
[CrossRef]

Rao, K. R.

B. Chitprasert and K. R. Rao, “Discrete cosine transform filtering,” Signal Process.19(3), 233–245 (1990).
[CrossRef]

Salmon, E. D.

E. D. Salmon and P. Tran, “High-resolution video-enhanced differential interference contrast (VE-DIC) light microscopy,” Methods Cell Biol.56, 153–184 (1998).
[CrossRef] [PubMed]

Sheppard, C. J.

Shieh, D.-B.

Sibarita, J. B.

J. B. Sibarita, “Deconvolution microscopy,” Adv. Biochem. Eng. Biotechnol.95, 201–243 (2005).
[CrossRef] [PubMed]

Somekh, M. G.

Sotak, G. E.

G. E. Sotak and K. L. Boyer, “The Laplacian-of-Gaussian kernel: a formal analysis and design procedure for fast, accurate convolution and full-frame output,” Comput. Vision Graphics Image Process.48(2), 147–189 (1989).
[CrossRef]

Sparrow, S. A.

D. V. Cicchetti and S. A. Sparrow, “Developing criteria for establishing interrater reliability of specific items: applications to assessment of adaptive behavior,” Am. J. Ment. Defic.86(2), 127–137 (1981).
[PubMed]

Squier, J.

J. Squier and M. Muller, “High resolution nonlinear microscopy: A review of sources and methods for achieving optimal imaging,” Rev. Sci. Instrum.72(7), 2855–2867 (2001).
[CrossRef]

Sticker, M.

Strickler, J. H.

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Suda, A.

Sun, C. K.

C. K. Sun, S. W. Chu, S. Y. Chen, T. H. Tsai, T. M. Liu, C. Y. Lin, and H. J. Tsai, “Higher harmonic generation microscopy for developmental biology,” J. Struct. Biol.147(1), 19–30 (2004).
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Sun, C.-K.

Y.-H. Liao, S.-Y. Chen, S.-Y. Chou, P.-H. Wang, M.-R. Tsai, and C.-K. Sun, “Determination of chronological aging parameters in epidermal keratinocytes by in vivo harmonic generation microscopy,” Biomed. Opt. Express4(1), 77–88 (2013).
[CrossRef] [PubMed]

M.-R. Tsai, S.-Y. Chen, D.-B. Shieh, P.-J. Lou, and C.-K. Sun, “In vivo optical virtual biopsy of human oral mucosa with harmonic generation microscopy,” Biomed. Opt. Express2(8), 2317–2328 (2011).
[CrossRef] [PubMed]

S.-H. Chia, T.-M. Liu, A. A. Ivanov, A. B. Fedotov, A. M. Zheltikov, M.-R. Tsai, M.-C. Chan, C.-H. Yu, and C.-K. Sun, “A sub-100 fs self-starting Cr:forsterite laser generating 1.4 W output power,” Opt. Express18(23), 24085–24091 (2010).
[CrossRef] [PubMed]

S.-Y. Chen, S.-U. Chen, H.-Y. Wu, W.-J. Lee, Y.-H. Liao, and C.-K. Sun, “In vivo virtual biopsy of human skin by using noninvasive higher harmonic generation microscopy,” IEEE J. Sel. Top. Quantum Electron.16(3), 478–492 (2010).
[CrossRef]

S.-Y. Chen, H.-Y. Wu, and C.-K. Sun, “In vivo harmonic generation biopsy of human skin,” J. Biomed. Opt.14(6), 060505 (2009).
[CrossRef] [PubMed]

C.-S. Hsieh, C.-Y. Ko, S.-Y. Chen, T.-M. Liu, J.-S. Wu, C. H. Hu, and C.-K. Sun, “In vivo long-term continuous observation of gene expression in zebrafish embryo nerve systems by using harmonic generation microscopy and morphant technology,” J. Biomed. Opt.13(6), 064041 (2008).
[CrossRef] [PubMed]

T.-H. Tsai, C. Y. Lin, H. J. Tsai, S. Y. Chen, S. P. Tai, K. H. Lin, and C.-K. Sun, “Biomolecular imaging based on far-red fluorescent protein with a high two-photon excitation action cross section,” Opt. Lett.31(7), 930–932 (2006).
[CrossRef] [PubMed]

S.-P. Tai, T.-H. Tsai, W.-J. Lee, D.-B. Shieh, Y.-H. Liao, H.-Y. Huang, K. Zhang, H.-L. Liu, and C.-K. Sun, “Optical biopsy of fixed human skin with backward-collected optical harmonics signals,” Opt. Express13(20), 8231–8242 (2005).
[CrossRef] [PubMed]

Tai, S. P.

Tai, S.-P.

Takeda, T.

Tran, P.

E. D. Salmon and P. Tran, “High-resolution video-enhanced differential interference contrast (VE-DIC) light microscopy,” Methods Cell Biol.56, 153–184 (1998).
[CrossRef] [PubMed]

Tsai, H. J.

T.-H. Tsai, C. Y. Lin, H. J. Tsai, S. Y. Chen, S. P. Tai, K. H. Lin, and C.-K. Sun, “Biomolecular imaging based on far-red fluorescent protein with a high two-photon excitation action cross section,” Opt. Lett.31(7), 930–932 (2006).
[CrossRef] [PubMed]

C. K. Sun, S. W. Chu, S. Y. Chen, T. H. Tsai, T. M. Liu, C. Y. Lin, and H. J. Tsai, “Higher harmonic generation microscopy for developmental biology,” J. Struct. Biol.147(1), 19–30 (2004).
[CrossRef] [PubMed]

Tsai, M.-R.

Tsai, T. H.

C. K. Sun, S. W. Chu, S. Y. Chen, T. H. Tsai, T. M. Liu, C. Y. Lin, and H. J. Tsai, “Higher harmonic generation microscopy for developmental biology,” J. Struct. Biol.147(1), 19–30 (2004).
[CrossRef] [PubMed]

Tsai, T.-H.

Tukey, J. W.

J. W. Cooley and J. W. Tukey, “An algorithm for the machine calculation of complex Fourier series,” Math. Comput.19(90), 297–301 (1965).
[CrossRef]

Vallée, F.

O. L. Muskens, P. Billaud, M. Broyer, N. Del Fatti, and F. Vallée, “Optical extinction spectrum of a single metal nanoparticle: Quantitative characterization of a particle and of its local environment,” Phys. Rev. B78(20), 205410 (2008).
[CrossRef]

A. Arbouet, D. Christofilos, N. Del Fatti, F. Vallée, J. R. Huntzinger, L. Arnaud, P. Billaud, and M. Broyer, “Direct measurement of the single-metal-cluster optical absorption,” Phys. Rev. Lett.93(12), 127401 (2004).
[CrossRef] [PubMed]

Wang, P.-H.

Webb, W. W.

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Wong, C. H.

Wu, H.-Y.

S.-Y. Chen, S.-U. Chen, H.-Y. Wu, W.-J. Lee, Y.-H. Liao, and C.-K. Sun, “In vivo virtual biopsy of human skin by using noninvasive higher harmonic generation microscopy,” IEEE J. Sel. Top. Quantum Electron.16(3), 478–492 (2010).
[CrossRef]

S.-Y. Chen, H.-Y. Wu, and C.-K. Sun, “In vivo harmonic generation biopsy of human skin,” J. Biomed. Opt.14(6), 060505 (2009).
[CrossRef] [PubMed]

Wu, J.-S.

C.-S. Hsieh, C.-Y. Ko, S.-Y. Chen, T.-M. Liu, J.-S. Wu, C. H. Hu, and C.-K. Sun, “In vivo long-term continuous observation of gene expression in zebrafish embryo nerve systems by using harmonic generation microscopy and morphant technology,” J. Biomed. Opt.13(6), 064041 (2008).
[CrossRef] [PubMed]

Young, R. A.

R. A. Young, “The Gaussian derivative model for spatial vision: I. Retinal mechanisms,” Spat. Vis.2(4), 273–293 (1987).
[CrossRef] [PubMed]

Yu, C.-H.

Zhang, K.

Zheltikov, A. M.

Adv. Biochem. Eng. Biotechnol.

J. B. Sibarita, “Deconvolution microscopy,” Adv. Biochem. Eng. Biotechnol.95, 201–243 (2005).
[CrossRef] [PubMed]

Am. J. Ment. Defic.

D. V. Cicchetti and S. A. Sparrow, “Developing criteria for establishing interrater reliability of specific items: applications to assessment of adaptive behavior,” Am. J. Ment. Defic.86(2), 127–137 (1981).
[PubMed]

Appl. Opt.

Biomed. Opt. Express

Comput. Vision Graphics Image Process.

G. E. Sotak and K. L. Boyer, “The Laplacian-of-Gaussian kernel: a formal analysis and design procedure for fast, accurate convolution and full-frame output,” Comput. Vision Graphics Image Process.48(2), 147–189 (1989).
[CrossRef]

IEEE J. Sel. Top. Quantum Electron.

S.-Y. Chen, S.-U. Chen, H.-Y. Wu, W.-J. Lee, Y.-H. Liao, and C.-K. Sun, “In vivo virtual biopsy of human skin by using noninvasive higher harmonic generation microscopy,” IEEE J. Sel. Top. Quantum Electron.16(3), 478–492 (2010).
[CrossRef]

IEEE Trans. Syst. Man Cybern.

N. Otsu, “A threshold selection method from gray-level histograms,” IEEE Trans. Syst. Man Cybern.9(1), 62–66 (1979).
[CrossRef]

J. Biomed. Opt.

C.-S. Hsieh, C.-Y. Ko, S.-Y. Chen, T.-M. Liu, J.-S. Wu, C. H. Hu, and C.-K. Sun, “In vivo long-term continuous observation of gene expression in zebrafish embryo nerve systems by using harmonic generation microscopy and morphant technology,” J. Biomed. Opt.13(6), 064041 (2008).
[CrossRef] [PubMed]

S.-Y. Chen, H.-Y. Wu, and C.-K. Sun, “In vivo harmonic generation biopsy of human skin,” J. Biomed. Opt.14(6), 060505 (2009).
[CrossRef] [PubMed]

J. Electron. Imaging

O. Nestares, R. Navarro, and J. Portilla, “Efficient spatial-domain implementation of a multiscale image representation based on gabor functions,” J. Electron. Imaging7(1), 166–173 (1998).
[CrossRef]

J. Neurophysiol.

J. P. Jones and L. A. Palmer, “An evaluation of the two-dimensional Gabor filter model of simple receptive fields in cat striate cortex,” J. Neurophysiol.58(6), 1233–1258 (1987).
[PubMed]

J. Opt. Soc. Am. A

J. Struct. Biol.

C. K. Sun, S. W. Chu, S. Y. Chen, T. H. Tsai, T. M. Liu, C. Y. Lin, and H. J. Tsai, “Higher harmonic generation microscopy for developmental biology,” J. Struct. Biol.147(1), 19–30 (2004).
[CrossRef] [PubMed]

Math. Comput.

J. W. Cooley and J. W. Tukey, “An algorithm for the machine calculation of complex Fourier series,” Math. Comput.19(90), 297–301 (1965).
[CrossRef]

Methods Cell Biol.

E. D. Salmon and P. Tran, “High-resolution video-enhanced differential interference contrast (VE-DIC) light microscopy,” Methods Cell Biol.56, 153–184 (1998).
[CrossRef] [PubMed]

Nat. Biotechnol.

P. J. Campagnola and L. M. Loew, “Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms,” Nat. Biotechnol.21(11), 1356–1360 (2003).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Pattern Recognit.

A. K. Jain and F. Farrokhnia, “Unsupervised texture segmentation using Gabor filters,” Pattern Recognit.24(12), 1167–1186 (1991).
[CrossRef]

Phys. Rev. B

O. L. Muskens, P. Billaud, M. Broyer, N. Del Fatti, and F. Vallée, “Optical extinction spectrum of a single metal nanoparticle: Quantitative characterization of a particle and of its local environment,” Phys. Rev. B78(20), 205410 (2008).
[CrossRef]

Phys. Rev. Lett.

A. Arbouet, D. Christofilos, N. Del Fatti, F. Vallée, J. R. Huntzinger, L. Arnaud, P. Billaud, and M. Broyer, “Direct measurement of the single-metal-cluster optical absorption,” Phys. Rev. Lett.93(12), 127401 (2004).
[CrossRef] [PubMed]

Rev. Sci. Instrum.

J. Squier and M. Muller, “High resolution nonlinear microscopy: A review of sources and methods for achieving optimal imaging,” Rev. Sci. Instrum.72(7), 2855–2867 (2001).
[CrossRef]

Science

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science248(4951), 73–76 (1990).
[CrossRef] [PubMed]

Signal Process.

B. Chitprasert and K. R. Rao, “Discrete cosine transform filtering,” Signal Process.19(3), 233–245 (1990).
[CrossRef]

Spat. Vis.

R. A. Young, “The Gaussian derivative model for spatial vision: I. Retinal mechanisms,” Spat. Vis.2(4), 273–293 (1987).
[CrossRef] [PubMed]

Z. Wiss. Mikrosk.

R. D. Allen, G. B. David, and G. Nomarski, “The zeiss-Nomarski differential interference equipment for transmitted-light microscopy,” Z. Wiss. Mikrosk.69(4), 193–221 (1969).
[PubMed]

Other

W. Lang, “Nomarski differential interference-contrast microscopy,” Oberkochen, Carl Zeiss, 11–18 (1982).

R. W. Boyd, Nonlinear Optics (Academic, 2003), Chap. 2.

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Figures (10)

Fig. 1
Fig. 1

Double-beam SPOM. (a) The overlap volume caused by the presence of fixed beam is equivalent to convolution with Gaussian (b) Interaction volume profile. The convolution of two Gaussian functions remains to be Gaussian. Even though we illustrate the idea in 1D, the concepts hold in 2D image as well.

Fig. 2
Fig. 2

1D sampling pattern comparison between oversampling and SPOM. Arrows point to the scanning direction. The dash-line represents the central line of the pixel. (a) Traditional oversampling. Only one sample is taken at each location. (b) Conventional SPOM. At each pixel a beam scans back and forth and takes each sample multiple times. The projections of the red dots on horizontal axis are the center locations of sample points. SPOM does not provide any more information about the object than oversampling.

Fig. 3
Fig. 3

Spatial modulation effect of single-beam vSPOM. (a) Object line profile. Only a single spike is present to describe the impulse response of vSPOM process. (b) vSPOM line profile. Two spikes are present to simulate the back-and-forth SPOM sampling.

Fig. 4
Fig. 4

vSPOM procedure. First we take an oversampled image of the object with nonlinear microscopy. Then we applied any filter from vSPOM filter bank on the oversampled image to obtain vSPOM images.

Fig. 5
Fig. 5

vSPOM filter bank. All the responses are normalized to set their maximum to unity. The vertical axes have arbitrary unit, while the unit of horizontal axes is pixel. (a) Gabor filter to simulate demodulation at 2f for double Gaussian beam; (b) Cosine filter to simulate demodulation at 2f for single beam; (c) LoG filter, 2nd derivative in x and y; (d) Radial derivative filter, 2nd derivative in radial direction.

Fig. 6
Fig. 6

Resolution measurement algorithm. First we subtracted background and smoothed it. Then we binarized the image with Otsu threshold. Thirdly, we evaluated the area and compactness of each CC to determine if we should keep it. Finally, we used these CCs as a mask to evaluate the smoothed image. Within each CC, we thresholded at the half maximum value to obtain the FWHM area, from which we calculated the radius of each CC.

Fig. 7
Fig. 7

Resolution measurement results. (Top) zoom-in view of fluorescent microspheres. Note the smaller fluorescent microsphere size in filtered images. (Bottom) Histograms of fluorescent microsphere diameter.

Fig. 8
Fig. 8

Fluorescent microsphere resolvability study. (Left) Original and smoothed TPEF images for comparison. (Middle and Right) vSPOM images widely separated the fluorescent microspheres.

Fig. 9
Fig. 9

Collagen fiber resolvability study. (Left) Original and smoothed SHG images for comparison. (Middle and Right) vSPOM images widely separated collagen fibers.

Fig. 10
Fig. 10

In vivo vSPOM. (Top) SHG image and associated VSPOM results. (Bottom) THG image and associated VSPOM results

Tables (1)

Tables Icon

Table 1 vSPOM filter comparison

Metrics