Abstract

High-resolution imaging in turbid media has been limited by the intrinsic compromise between the gating efficiency (removal of multiply-scattered light background) and signal strength in the existing optical gating techniques. This leads to shallow depths due to the weak ballistic signal, and/or degraded resolution due to the strong multiply-scattering background – the well-known trade-off between resolution and imaging depth in scattering samples. In this work, we employ a nonlinear optics based optical parametric amplifier (OPA) to address this challenge. We demonstrate that both the imaging depth and the spatial resolution in turbid media can be enhanced simultaneously by the OPA, which provides a high level of signal gain as well as an inherent nonlinear optical gate. This technology shifts the nonlinear interaction to an optical crystal placed in the detection arm (image plane), rather than in the sample, which can be used to exploit the benefits given by the high-order parametric process and the use of an intense laser field. The coherent process makes the OPA potentially useful as a general-purpose optical amplifier applicable to a wide range of optical imaging techniques.

© 2014 Optical Society of America

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References

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2012 (1)

N. V. Corzo, A. M. Marino, K. M. Jones, and P. D. Lett, “Noiseless optical amplifier operating on hundreds of spatial modes,” Phys. Rev. Lett. 109(4), 043602 (2012).
[Crossref] [PubMed]

2011 (2)

W. Min, C. W. Freudiger, S. J. Lu, and X. S. Xie, “Coherent nonlinear optical imaging: beyond fluorescence microscopy,” Annu. Rev. Phys. Chem. 62(1), 507–530 (2011).
[Crossref] [PubMed]

P. M. Vaughan and R. Trebino, “Optical-parametric-amplification imaging of complex objects,” Opt. Express 19(9), 8920–8929 (2011).
[Crossref] [PubMed]

2010 (4)

A. Bassi, D. Brida, C. D’Andrea, G. Valentini, R. Cubeddu, S. De Silvestri, and G. Cerullo, “Time-gated optical projection tomography,” Opt. Lett. 35(16), 2732–2734 (2010).
[Crossref] [PubMed]

P. D. Chowdary, Z. Jiang, E. J. Chaney, W. A. Benalcazar, D. L. Marks, M. Gruebele, and S. A. Boppart, “Molecular histopathology by spectrally reconstructed nonlinear interferometric vibrational imaging,” Cancer Res. 70(23), 9562–9569 (2010).
[Crossref] [PubMed]

V. Ntziachristos, “Going deeper than microscopy: the optical imaging frontier in biology,” Nat. Methods 7(8), 603–614 (2010).
[Crossref] [PubMed]

D. Brida, C. Manzoni, G. Cirmi, M. Marangoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Few-optical-cycle pulses tunable from the visible to the mid-infrared by optical parametric amplifiers,” J. Opt. 12(1), 013001 (2010).
[Crossref]

2009 (2)

2008 (2)

E. Lantz and F. Devaux, “Parametric amplification of images: From time gating to noiseless amplification,” IEEE J. Sel. Top. Quantum Electron. 14(3), 635–647 (2008).
[Crossref]

D. Brida, G. Cirmi, C. Manzoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Sub-two-cycle light pulses at 1.6 μm from an optical parametric amplifier,” Opt. Lett. 33(7), 741–743 (2008).
[Crossref] [PubMed]

2007 (1)

2005 (1)

P. Fita, Y. Stepanenko, and C. Radzewicz, “Femtosecond transient fluorescence spectrometer based on parametric amplification,” Appl. Phys. Lett. 86(2), 021909 (2005).
[Crossref]

2004 (1)

2003 (4)

S. Radic, C. J. McKinstrie, R. M. Jopson, J. C. Centanni, Q. Lin, and G. P. Agrawal, “Record performance of parametric amplifier constructed with highly nonlinear fibre,” Electron. Lett. 39(11), 838–839 (2003).
[Crossref]

G. Cerullo and S. De Silvestri, “Ultrafast optical parametric amplifiers,” Rev. Sci. Instrum. 74(1), 1–18 (2003).
[Crossref]

C. Dunsby and P. M. W. French, “Techniques for depth-resolved imaging through turbid media including coherence-gated imaging,” J. Phys. D Appl. Phys. 36(14), R207–R227 (2003).
[Crossref]

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

2001 (1)

A. Hopt and E. Neher, “Highly nonlinear photodamage in two-photon fluorescence microscopy,” Biophys. J. 80(4), 2029–2036 (2001).
[Crossref] [PubMed]

1999 (5)

1998 (1)

1997 (1)

1995 (1)

1994 (2)

1993 (1)

1992 (1)

1991 (4)

S. Kimura and T. Wilson, “Confocal scanning optical microscope using single-mode fiber for signal detection,” Appl. Opt. 30(16), 2143–2150 (1991).
[Crossref] [PubMed]

M. Gu, C. J. R. Sheppard, and X. Gan, “Image-formation in a fiberoptic confocal scanning microscope,” J. Opt. Soc. Am. A 8(11), 1755–1761 (1991).
[Crossref]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

L. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, “Ballistic 2-d imaging through scattering walls using an ultrafast optical kerr gate,” Science 253(5021), 769–771 (1991).
[Crossref] [PubMed]

1990 (2)

W. Denk, J. H. Strickler, and W. W. Webb, “2-Photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[Crossref] [PubMed]

C. J. R. Sheppard and M. Gu, “Image formation in two-photon fluorescence microscopy,” Optik (Stuttg.) 86, 3 (1990).

1987 (1)

1986 (2)

1982 (1)

C. M. Caves, “Quantum limits on noise in linear-amplifiers,” Phys. Rev. D Part. Fields 26(8), 1817–1839 (1982).
[Crossref]

1979 (1)

R. A. Baumgartner and R. L. Byer, “Optical parametric amplification,” IEEE J. Quantum Electron. 15(6), 432–444 (1979).
[Crossref]

Abram, I.

Agrawal, G. P.

S. Radic, C. J. McKinstrie, R. M. Jopson, J. C. Centanni, Q. Lin, and G. P. Agrawal, “Record performance of parametric amplifier constructed with highly nonlinear fibre,” Electron. Lett. 39(11), 838–839 (2003).
[Crossref]

Alfano, R. R.

L. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, “Ballistic 2-d imaging through scattering walls using an ultrafast optical kerr gate,” Science 253(5021), 769–771 (1991).
[Crossref] [PubMed]

Alonzi, B.

Andrekson, P. A.

Bassi, A.

Bates, M.

B. Huang, M. Bates, and X. W. Zhuang, “Super-resolution fluorescence microscopy,” Annu. Rev. Biochem. 78(1), 993–1016 (2009).
[Crossref] [PubMed]

Baumgartner, R. A.

R. A. Baumgartner and R. L. Byer, “Optical parametric amplification,” IEEE J. Quantum Electron. 15(6), 432–444 (1979).
[Crossref]

Becker, T. W.

Benalcazar, W. A.

P. D. Chowdary, Z. Jiang, E. J. Chaney, W. A. Benalcazar, D. L. Marks, M. Gruebele, and S. A. Boppart, “Molecular histopathology by spectrally reconstructed nonlinear interferometric vibrational imaging,” Cancer Res. 70(23), 9562–9569 (2010).
[Crossref] [PubMed]

Bonner, R. F.

Bonora, S.

D. Brida, C. Manzoni, G. Cirmi, M. Marangoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Few-optical-cycle pulses tunable from the visible to the mid-infrared by optical parametric amplifiers,” J. Opt. 12(1), 013001 (2010).
[Crossref]

D. Brida, G. Cirmi, C. Manzoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Sub-two-cycle light pulses at 1.6 μm from an optical parametric amplifier,” Opt. Lett. 33(7), 741–743 (2008).
[Crossref] [PubMed]

Boppart, S. A.

P. D. Chowdary, Z. Jiang, E. J. Chaney, W. A. Benalcazar, D. L. Marks, M. Gruebele, and S. A. Boppart, “Molecular histopathology by spectrally reconstructed nonlinear interferometric vibrational imaging,” Cancer Res. 70(23), 9562–9569 (2010).
[Crossref] [PubMed]

Brida, D.

Brun, A.

Byer, R. L.

R. A. Baumgartner and R. L. Byer, “Optical parametric amplification,” IEEE J. Quantum Electron. 15(6), 432–444 (1979).
[Crossref]

Campagnola, P. J.

P. J. Campagnola, M. D. Wei, A. Lewis, and L. M. Loew, “High-resolution nonlinear optical imaging of live cells by second harmonic generation,” Biophys. J. 77(6), 3341–3349 (1999).
[Crossref] [PubMed]

Carlini, A. R.

Caves, C. M.

C. M. Caves, “Quantum limits on noise in linear-amplifiers,” Phys. Rev. D Part. Fields 26(8), 1817–1839 (1982).
[Crossref]

Centanni, J. C.

S. Radic, C. J. McKinstrie, R. M. Jopson, J. C. Centanni, Q. Lin, and G. P. Agrawal, “Record performance of parametric amplifier constructed with highly nonlinear fibre,” Electron. Lett. 39(11), 838–839 (2003).
[Crossref]

Cerullo, G.

A. Bassi, D. Brida, C. D’Andrea, G. Valentini, R. Cubeddu, S. De Silvestri, and G. Cerullo, “Time-gated optical projection tomography,” Opt. Lett. 35(16), 2732–2734 (2010).
[Crossref] [PubMed]

D. Brida, C. Manzoni, G. Cirmi, M. Marangoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Few-optical-cycle pulses tunable from the visible to the mid-infrared by optical parametric amplifiers,” J. Opt. 12(1), 013001 (2010).
[Crossref]

D. Brida, G. Cirmi, C. Manzoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Sub-two-cycle light pulses at 1.6 μm from an optical parametric amplifier,” Opt. Lett. 33(7), 741–743 (2008).
[Crossref] [PubMed]

G. Cerullo and S. De Silvestri, “Ultrafast optical parametric amplifiers,” Rev. Sci. Instrum. 74(1), 1–18 (2003).
[Crossref]

Chaney, E. J.

P. D. Chowdary, Z. Jiang, E. J. Chaney, W. A. Benalcazar, D. L. Marks, M. Gruebele, and S. A. Boppart, “Molecular histopathology by spectrally reconstructed nonlinear interferometric vibrational imaging,” Cancer Res. 70(23), 9562–9569 (2010).
[Crossref] [PubMed]

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Chen, X. H.

Chou, C. H.

Chowdary, P. D.

P. D. Chowdary, Z. Jiang, E. J. Chaney, W. A. Benalcazar, D. L. Marks, M. Gruebele, and S. A. Boppart, “Molecular histopathology by spectrally reconstructed nonlinear interferometric vibrational imaging,” Cancer Res. 70(23), 9562–9569 (2010).
[Crossref] [PubMed]

Chu, S. W.

Chui, H. C.

Cirmi, G.

D. Brida, C. Manzoni, G. Cirmi, M. Marangoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Few-optical-cycle pulses tunable from the visible to the mid-infrared by optical parametric amplifiers,” J. Opt. 12(1), 013001 (2010).
[Crossref]

D. Brida, G. Cirmi, C. Manzoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Sub-two-cycle light pulses at 1.6 μm from an optical parametric amplifier,” Opt. Lett. 33(7), 741–743 (2008).
[Crossref] [PubMed]

Corle, T. R.

Corzo, N. V.

N. V. Corzo, A. M. Marino, K. M. Jones, and P. D. Lett, “Noiseless optical amplifier operating on hundreds of spatial modes,” Phys. Rev. Lett. 109(4), 043602 (2012).
[Crossref] [PubMed]

Cubeddu, R.

D’Andrea, C.

De Silvestri, S.

Denk, W.

W. Denk, J. H. Strickler, and W. W. Webb, “2-Photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[Crossref] [PubMed]

Devaux, F.

E. Lantz and F. Devaux, “Parametric amplification of images: From time gating to noiseless amplification,” IEEE J. Sel. Top. Quantum Electron. 14(3), 635–647 (2008).
[Crossref]

G. Le Tolguenec, F. Devaux, and E. Lantz, “Two-dimensional time-resolved direct imaging through thick biological tissues: A new step toward noninvasive medical imaging,” Opt. Lett. 24(15), 1047–1049 (1999).
[Crossref] [PubMed]

Dorn, P.

Dunn, M. H.

M. H. Dunn and M. Ebrahimzadeh, “Parametric generation of tunable light from continuous-wave to femtosecond pulses,” Science 286(5444), 1513–1517 (1999).
[Crossref] [PubMed]

Dunsby, C.

C. Dunsby and P. M. W. French, “Techniques for depth-resolved imaging through turbid media including coherence-gated imaging,” J. Phys. D Appl. Phys. 36(14), R207–R227 (2003).
[Crossref]

Ebrahimzadeh, M.

M. H. Dunn and M. Ebrahimzadeh, “Parametric generation of tunable light from continuous-wave to femtosecond pulses,” Science 286(5444), 1513–1517 (1999).
[Crossref] [PubMed]

Fischer, P.

Fita, P.

P. Fita, Y. Stepanenko, and C. Radzewicz, “Femtosecond transient fluorescence spectrometer based on parametric amplification,” Appl. Phys. Lett. 86(2), 021909 (2005).
[Crossref]

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

French, P. M. W.

C. Dunsby and P. M. W. French, “Techniques for depth-resolved imaging through turbid media including coherence-gated imaging,” J. Phys. D Appl. Phys. 36(14), R207–R227 (2003).
[Crossref]

Freudiger, C. W.

W. Min, C. W. Freudiger, S. J. Lu, and X. S. Xie, “Coherent nonlinear optical imaging: beyond fluorescence microscopy,” Annu. Rev. Phys. Chem. 62(1), 507–530 (2011).
[Crossref] [PubMed]

Fujimoto, J. G.

Gan, X.

Gan, X. S.

Gandjbakhche, A. H.

Genack, A. Z.

Georges, P.

Grangier, P.

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Gruebele, M.

P. D. Chowdary, Z. Jiang, E. J. Chaney, W. A. Benalcazar, D. L. Marks, M. Gruebele, and S. A. Boppart, “Molecular histopathology by spectrally reconstructed nonlinear interferometric vibrational imaging,” Cancer Res. 70(23), 9562–9569 (2010).
[Crossref] [PubMed]

Gu, M.

Halbhuber, K. J.

Han, X. F.

Hedekvist, P. O.

Hee, M. R.

J. A. Izatt, M. R. Hee, G. M. Owen, E. A. Swanson, and J. G. Fujimoto, “Optical coherence microscopy in scattering media,” Opt. Lett. 19(8), 590–592 (1994).
[Crossref] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Ho, P. P.

L. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, “Ballistic 2-d imaging through scattering walls using an ultrafast optical kerr gate,” Science 253(5021), 769–771 (1991).
[Crossref] [PubMed]

Hopt, A.

A. Hopt and E. Neher, “Highly nonlinear photodamage in two-photon fluorescence microscopy,” Biophys. J. 80(4), 2029–2036 (2001).
[Crossref] [PubMed]

Huang, B.

B. Huang, M. Bates, and X. W. Zhuang, “Super-resolution fluorescence microscopy,” Annu. Rev. Biochem. 78(1), 993–1016 (2009).
[Crossref] [PubMed]

Huang, C. H.

Huang, D.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Ippen, E. P.

Izatt, J. A.

Jiang, Z.

P. D. Chowdary, Z. Jiang, E. J. Chaney, W. A. Benalcazar, D. L. Marks, M. Gruebele, and S. A. Boppart, “Molecular histopathology by spectrally reconstructed nonlinear interferometric vibrational imaging,” Cancer Res. 70(23), 9562–9569 (2010).
[Crossref] [PubMed]

Jones, K. M.

N. V. Corzo, A. M. Marino, K. M. Jones, and P. D. Lett, “Noiseless optical amplifier operating on hundreds of spatial modes,” Phys. Rev. Lett. 109(4), 043602 (2012).
[Crossref] [PubMed]

Jopson, R. M.

S. Radic, C. J. McKinstrie, R. M. Jopson, J. C. Centanni, Q. Lin, and G. P. Agrawal, “Record performance of parametric amplifier constructed with highly nonlinear fibre,” Electron. Lett. 39(11), 838–839 (2003).
[Crossref]

Karlsson, M.

Kempe, M.

Kimura, S.

Kino, G. S.

Knight, J. C.

Knüttel, A.

König, K.

Kylemark, P.

Lantz, E.

E. Lantz and F. Devaux, “Parametric amplification of images: From time gating to noiseless amplification,” IEEE J. Sel. Top. Quantum Electron. 14(3), 635–647 (2008).
[Crossref]

G. Le Tolguenec, F. Devaux, and E. Lantz, “Two-dimensional time-resolved direct imaging through thick biological tissues: A new step toward noninvasive medical imaging,” Opt. Lett. 24(15), 1047–1049 (1999).
[Crossref] [PubMed]

Le Tolguenec, G.

Lépine, T.

Lett, P. D.

N. V. Corzo, A. M. Marino, K. M. Jones, and P. D. Lett, “Noiseless optical amplifier operating on hundreds of spatial modes,” Phys. Rev. Lett. 109(4), 043602 (2012).
[Crossref] [PubMed]

Levenson, J. A.

Lewis, A.

P. J. Campagnola, M. D. Wei, A. Lewis, and L. M. Loew, “High-resolution nonlinear optical imaging of live cells by second harmonic generation,” Biophys. J. 77(6), 3341–3349 (1999).
[Crossref] [PubMed]

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Lin, Q.

S. Radic, C. J. McKinstrie, R. M. Jopson, J. C. Centanni, Q. Lin, and G. P. Agrawal, “Record performance of parametric amplifier constructed with highly nonlinear fibre,” Electron. Lett. 39(11), 838–839 (2003).
[Crossref]

Lin, Y. Y.

Liu, C.

L. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, “Ballistic 2-d imaging through scattering walls using an ultrafast optical kerr gate,” Science 253(5021), 769–771 (1991).
[Crossref] [PubMed]

Liu, H. L.

Liu, J. M.

Loew, L. M.

P. J. Campagnola, M. D. Wei, A. Lewis, and L. M. Loew, “High-resolution nonlinear optical imaging of live cells by second harmonic generation,” Biophys. J. 77(6), 3341–3349 (1999).
[Crossref] [PubMed]

Lu, S. J.

W. Min, C. W. Freudiger, S. J. Lu, and X. S. Xie, “Coherent nonlinear optical imaging: beyond fluorescence microscopy,” Annu. Rev. Phys. Chem. 62(1), 507–530 (2011).
[Crossref] [PubMed]

Maitland, D. J.

Manzoni, C.

D. Brida, C. Manzoni, G. Cirmi, M. Marangoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Few-optical-cycle pulses tunable from the visible to the mid-infrared by optical parametric amplifiers,” J. Opt. 12(1), 013001 (2010).
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D. Brida, G. Cirmi, C. Manzoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Sub-two-cycle light pulses at 1.6 μm from an optical parametric amplifier,” Opt. Lett. 33(7), 741–743 (2008).
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Marangoni, M.

D. Brida, C. Manzoni, G. Cirmi, M. Marangoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Few-optical-cycle pulses tunable from the visible to the mid-infrared by optical parametric amplifiers,” J. Opt. 12(1), 013001 (2010).
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Margolis, R.

Marino, A. M.

N. V. Corzo, A. M. Marino, K. M. Jones, and P. D. Lett, “Noiseless optical amplifier operating on hundreds of spatial modes,” Phys. Rev. Lett. 109(4), 043602 (2012).
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Marks, D. L.

P. D. Chowdary, Z. Jiang, E. J. Chaney, W. A. Benalcazar, D. L. Marks, M. Gruebele, and S. A. Boppart, “Molecular histopathology by spectrally reconstructed nonlinear interferometric vibrational imaging,” Cancer Res. 70(23), 9562–9569 (2010).
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McKinstrie, C. J.

S. Radic, C. J. McKinstrie, R. M. Jopson, J. C. Centanni, Q. Lin, and G. P. Agrawal, “Record performance of parametric amplifier constructed with highly nonlinear fibre,” Electron. Lett. 39(11), 838–839 (2003).
[Crossref]

Min, W.

W. Min, C. W. Freudiger, S. J. Lu, and X. S. Xie, “Coherent nonlinear optical imaging: beyond fluorescence microscopy,” Annu. Rev. Phys. Chem. 62(1), 507–530 (2011).
[Crossref] [PubMed]

Neher, E.

A. Hopt and E. Neher, “Highly nonlinear photodamage in two-photon fluorescence microscopy,” Biophys. J. 80(4), 2029–2036 (2001).
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V. Ntziachristos, “Going deeper than microscopy: the optical imaging frontier in biology,” Nat. Methods 7(8), 603–614 (2010).
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Oseroff, A.

Owen, G. M.

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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J. G. Fujimoto, S. De Silvestri, E. P. Ippen, C. A. Puliafito, R. Margolis, and A. Oseroff, “Femtosecond optical ranging in biological systems,” Opt. Lett. 11(3), 150–152 (1986).
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S. Radic, C. J. McKinstrie, R. M. Jopson, J. C. Centanni, Q. Lin, and G. P. Agrawal, “Record performance of parametric amplifier constructed with highly nonlinear fibre,” Electron. Lett. 39(11), 838–839 (2003).
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Radzewicz, C.

P. Fita, Y. Stepanenko, and C. Radzewicz, “Femtosecond transient fluorescence spectrometer based on parametric amplification,” Appl. Phys. Lett. 86(2), 021909 (2005).
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Riemann, I.

Rivera, T.

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Sankaran, V.

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D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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P. Fita, Y. Stepanenko, and C. Radzewicz, “Femtosecond transient fluorescence spectrometer based on parametric amplification,” Appl. Phys. Lett. 86(2), 021909 (2005).
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Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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J. A. Izatt, M. R. Hee, G. M. Owen, E. A. Swanson, and J. G. Fujimoto, “Optical coherence microscopy in scattering media,” Opt. Lett. 19(8), 590–592 (1994).
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D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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D. Brida, C. Manzoni, G. Cirmi, M. Marangoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Few-optical-cycle pulses tunable from the visible to the mid-infrared by optical parametric amplifiers,” J. Opt. 12(1), 013001 (2010).
[Crossref]

D. Brida, G. Cirmi, C. Manzoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Sub-two-cycle light pulses at 1.6 μm from an optical parametric amplifier,” Opt. Lett. 33(7), 741–743 (2008).
[Crossref] [PubMed]

Walsh, J. T.

Wang, L.

L. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, “Ballistic 2-d imaging through scattering walls using an ultrafast optical kerr gate,” Science 253(5021), 769–771 (1991).
[Crossref] [PubMed]

Watson, J.

Webb, W. W.

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

W. Denk, J. H. Strickler, and W. W. Webb, “2-Photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
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Wei, M. D.

P. J. Campagnola, M. D. Wei, A. Lewis, and L. M. Loew, “High-resolution nonlinear optical imaging of live cells by second harmonic generation,” Biophys. J. 77(6), 3341–3349 (1999).
[Crossref] [PubMed]

Weng, Y. X.

Williams, R. M.

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

Wilson, T.

Xie, X. S.

W. Min, C. W. Freudiger, S. J. Lu, and X. S. Xie, “Coherent nonlinear optical imaging: beyond fluorescence microscopy,” Annu. Rev. Phys. Chem. 62(1), 507–530 (2011).
[Crossref] [PubMed]

Yadlowsky, M.

Zhang, G.

L. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, “Ballistic 2-d imaging through scattering walls using an ultrafast optical kerr gate,” Science 253(5021), 769–771 (1991).
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Zhuang, X. W.

B. Huang, M. Bates, and X. W. Zhuang, “Super-resolution fluorescence microscopy,” Annu. Rev. Biochem. 78(1), 993–1016 (2009).
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W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
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Annu. Rev. Biochem. (1)

B. Huang, M. Bates, and X. W. Zhuang, “Super-resolution fluorescence microscopy,” Annu. Rev. Biochem. 78(1), 993–1016 (2009).
[Crossref] [PubMed]

Annu. Rev. Phys. Chem. (1)

W. Min, C. W. Freudiger, S. J. Lu, and X. S. Xie, “Coherent nonlinear optical imaging: beyond fluorescence microscopy,” Annu. Rev. Phys. Chem. 62(1), 507–530 (2011).
[Crossref] [PubMed]

Appl. Opt. (3)

Appl. Phys. Lett. (1)

P. Fita, Y. Stepanenko, and C. Radzewicz, “Femtosecond transient fluorescence spectrometer based on parametric amplification,” Appl. Phys. Lett. 86(2), 021909 (2005).
[Crossref]

Biophys. J. (2)

P. J. Campagnola, M. D. Wei, A. Lewis, and L. M. Loew, “High-resolution nonlinear optical imaging of live cells by second harmonic generation,” Biophys. J. 77(6), 3341–3349 (1999).
[Crossref] [PubMed]

A. Hopt and E. Neher, “Highly nonlinear photodamage in two-photon fluorescence microscopy,” Biophys. J. 80(4), 2029–2036 (2001).
[Crossref] [PubMed]

Cancer Res. (1)

P. D. Chowdary, Z. Jiang, E. J. Chaney, W. A. Benalcazar, D. L. Marks, M. Gruebele, and S. A. Boppart, “Molecular histopathology by spectrally reconstructed nonlinear interferometric vibrational imaging,” Cancer Res. 70(23), 9562–9569 (2010).
[Crossref] [PubMed]

Electron. Lett. (1)

S. Radic, C. J. McKinstrie, R. M. Jopson, J. C. Centanni, Q. Lin, and G. P. Agrawal, “Record performance of parametric amplifier constructed with highly nonlinear fibre,” Electron. Lett. 39(11), 838–839 (2003).
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IEEE J. Quantum Electron. (1)

R. A. Baumgartner and R. L. Byer, “Optical parametric amplification,” IEEE J. Quantum Electron. 15(6), 432–444 (1979).
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IEEE J. Sel. Top. Quantum Electron. (1)

E. Lantz and F. Devaux, “Parametric amplification of images: From time gating to noiseless amplification,” IEEE J. Sel. Top. Quantum Electron. 14(3), 635–647 (2008).
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J. Lightwave Technol. (1)

J. Opt. (1)

D. Brida, C. Manzoni, G. Cirmi, M. Marangoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Few-optical-cycle pulses tunable from the visible to the mid-infrared by optical parametric amplifiers,” J. Opt. 12(1), 013001 (2010).
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J. Opt. Soc. Am. A (4)

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C. Dunsby and P. M. W. French, “Techniques for depth-resolved imaging through turbid media including coherence-gated imaging,” J. Phys. D Appl. Phys. 36(14), R207–R227 (2003).
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Nat. Biotechnol. (1)

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
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Nat. Methods (1)

V. Ntziachristos, “Going deeper than microscopy: the optical imaging frontier in biology,” Nat. Methods 7(8), 603–614 (2010).
[Crossref] [PubMed]

Opt. Express (2)

Opt. Lett. (9)

A. Bassi, D. Brida, C. D’Andrea, G. Valentini, R. Cubeddu, S. De Silvestri, and G. Cerullo, “Time-gated optical projection tomography,” Opt. Lett. 35(16), 2732–2734 (2010).
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D. Brida, G. Cirmi, C. Manzoni, S. Bonora, P. Villoresi, S. De Silvestri, and G. Cerullo, “Sub-two-cycle light pulses at 1.6 μm from an optical parametric amplifier,” Opt. Lett. 33(7), 741–743 (2008).
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J. G. Fujimoto, S. De Silvestri, E. P. Ippen, C. A. Puliafito, R. Margolis, and A. Oseroff, “Femtosecond optical ranging in biological systems,” Opt. Lett. 11(3), 150–152 (1986).
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G. Le Tolguenec, F. Devaux, and E. Lantz, “Two-dimensional time-resolved direct imaging through thick biological tissues: A new step toward noninvasive medical imaging,” Opt. Lett. 24(15), 1047–1049 (1999).
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Optik (Stuttg.) (1)

C. J. R. Sheppard and M. Gu, “Image formation in two-photon fluorescence microscopy,” Optik (Stuttg.) 86, 3 (1990).

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N. V. Corzo, A. M. Marino, K. M. Jones, and P. D. Lett, “Noiseless optical amplifier operating on hundreds of spatial modes,” Phys. Rev. Lett. 109(4), 043602 (2012).
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G. Cerullo and S. De Silvestri, “Ultrafast optical parametric amplifiers,” Rev. Sci. Instrum. 74(1), 1–18 (2003).
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Science (4)

M. H. Dunn and M. Ebrahimzadeh, “Parametric generation of tunable light from continuous-wave to femtosecond pulses,” Science 286(5444), 1513–1517 (1999).
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D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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W. Denk, J. H. Strickler, and W. W. Webb, “2-Photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
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J. A. Fujimoto and D. Farkas, Biomedical Optical Imaging, (Oxford University Press, 2009).

P. Torok and F. J. Kao, Optical Imaging and Microscopy, (Springer, 2007).

P. Sebban, Waves and imaging through Complex Media, (Kluwer Academic Publishers, 2001).

J. B. Pawley, Handbook of Biological Confocal Microscopy, (Springer, 2006).

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Figures (8)

Fig. 1
Fig. 1 Confocal effect of the OPA. (a) Geometry of the signal beam focus in the crystal. (b) Calculated signal beam profiles before (at z = d / 2 ) and after (at z = d / 2 ) the amplification. (c) Calculated diameter of the OPA virtual pinhole ( d v p ) at different pump intensities. (d) Calculated signal strengths of the amplified signal beam at different pump intensities.
Fig. 2
Fig. 2 Schematic of the OPA setup for optical imaging. BBO: beta-barium borate crystal; BPF: band-pass filter; BS: beam splitter; DC: dichroic mirror; DL: delay line; NA: numerical aperture; NDF: neutral density filter; SA: sapphire crystal; SHG: second harmonic generation.
Fig. 3
Fig. 3 OPA gain and imaging. (a) Supercontinuum spectra measured without (pink) and with (blue) the presence of the OPA pump. (b) Supercontinuum spectra measured without amplification (signal) and with the OPA tuned to three different central wavelengths (620 nm, 637 nm, and 660 nm). (c-e) Reflection-mode images of onion skin obtained based on reflected signals with (c) and without (d and e) the OPA gain. The same incident power (76 nW) was used for (c) and (d), and increased (290 × higher) power (22 µW) was used for (e), respectively. A 0.5 NA objective was used to acquire all of the images. Intensities of the images (c-e) were normalized. The scale bar in (d) represents 100 µm, and applies to all images.
Fig. 4
Fig. 4 Time sequences (1.0 s) of signals reflected from a silver mirror placed at the focal plane of a 0.25 NA objective. (a) Unamplified (pink) and OPA-amplified (blue) signals, and the noise floor (black), with an incident power of 8 nW. (b) Unamplified signals with an incident power of 14 µW (approximately 1800 times higher than that used for the measurements in (a). The measurements were each averaged 50 times.
Fig. 5
Fig. 5 Confocal effects of the OPA imaging. (a) Axial point-spread-functions of different imaging modes measured by translating a silver mirror along the axial beam direction through the focus. Solid curve, OPA imaging; dashed curve, conventional confocal imaging; dotted curve, conventional reflectance imaging. (b-e) Images of sub-resolution (50 nm) nanoparticles (TiO2) embedded in a polydimethylsiloxane (PDMS) gel obtained in OPA imaging mode (b and c) and conventional reflection mode geometry (d and e). The imaging planes are 100 µm and 400 µm below the surface of the gel for images (b and d), and (c and e), respectively. An objective of 0.65 NA was used to focus light into the sample for all the images. Intensities of the images were normalized. The yellow box insets in the lower left corner of each image are magnified images of the yellow box regions in the upper right corner of each image. (f and g)Three-dimensional renderings of the images in the yellow box insets in (c) and (e), respectively, showing the improved (narrowed) point-spread-functions following OPA imaging. The scale bars in (b) represent 100 µm, and apply to all images.
Fig. 6
Fig. 6 OPA imaging and nonlinear confocal gating in scattering media. (a) Images of a USAF resolution target obtained in OPA imaging mode (top row) and in conventional confocal mode (bottom row) when an increasing number of lens paper sheets were placed on top of the sample to serve as scattering media. In each image, the larger central yellow rectangular inset shows a zoomed image of the smallest line group (a width of 2.19 µm for each bar in element 6 of group 7) located within the smaller yellow rectangular box region to the right. All images are intensity normalized. The scale bar in the lower right image represents 50 µm, and applies to all the images in (a). (b and c) Three-dimensional renderings of the images in the central yellow rectangular insets acquired when imaging the resolution target through 2 sheets of lens paper. (d) Axial point spread functions measured by translating a silver mirror along the axial beam direction and through the focus for OPA (solid curve) and conventional confocal (dashed curve) imaging geometries. Two sheets of lens paper were placed on top of the sample to serve as scattering media.
Fig. 7
Fig. 7 Measurements of attenuation of ballistic photons by lens paper. (a) Plot of the power of ballistic light versus number of sheets of lens paper. (b) Photograph of the far-field pattern of transmitted light through three sheets of lens paper. The bright spot at the center of the image (arrow) is the ballistic light pattern.
Fig. 8
Fig. 8 Imaging of fresh rat muscle tissue at different depths below the surface. (a) Images obtained via OPA imaging. (b) Images obtained via conventional confocal imaging. In both the OPA and confocal imaging modes, the optical signal for image formation was coupled into a single-mode fiber with core size of 3.7 µm by a 10 × objective. An incident power of 16 µW was used for obtaining of all the images. Measured optical signals were attenuated by 180 and 6.5 times for the first two images (captured at 40 µm and 120 µm depths, respectively) obtained in the OPA mode (A) to be similar to the corresponding images shown without the OPA gain (b). An objective of 0.5 NA was used for all the images. The pseudo colormap was set to span from 0% to 97% of the signal levels present in each image. The scale bar represents 100 µm, and applies to all the images. (c) Signal strengths averaged over the full field-of-view of each images at different depths obtained with the OPA (circles) and conventional confocal (diamonds) imaging modes.

Equations (3)

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I s 1 4 I s 0 exp ( 2 L γ I p ) ,
I j ( r , z ) = I 0 , s ( ω 0 , s ω s ( z ) ) 2 exp ( 2 r 2 ω s 2 ( z ) ) ,
I s ( r , z ) = 1 4 z = d / 2 z = d / 2 d z I 0 , s ( ω 0 , s ω s ( z ) ) 2 exp ( 4 z γ r 2 I p ( r , z ) ω s 2 ( z ) ) ,

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