Abstract

We present a quantitative second-harmonic generation (SHG) imaging technique that quantifies the 2D spatial organization of collagen fiber samples under dynamic conditions, as an image is acquired. The technique is demonstrated for both a well-aligned tendon sample and a randomly aligned, sparsely distributed collagen scaffold sample. For a fixed signal-to-noise ratio, we confirm the applicability of this method for various window sizes (pixel areas) as well as with using a gridded overlay map that allows for correlations of fiber orientations within a given image. This work has direct impact to in vivo biological studies by incorporating simultaneous SHG image acquisition and analysis.

© 2013 Optical Society of America

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    [CrossRef] [PubMed]
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2013

T. Y. Lau, H. K. Sangha, E. K. Chien, B. L. McFarlin, A. J. Wagoner Johnson, K. C. Toussaint., “Application of Fourier transform-second-harmonic generation imaging to the rat cervix,” J. Microsc. 251(1), 77–83 (2013).
[CrossRef] [PubMed]

2012

X. Chen, O. Nadiarynkh, S. Plotnikov, P. J. Campagnola, “Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure,” Nat. Protoc. 7(4), 654–669 (2012).
[CrossRef] [PubMed]

R. Ambekar, M. Chittenden, I. Jasiuk, K. C. Toussaint., “Quantitative second-harmonic generation microscopy for imaging porcine cortical bone: Comparison to SEM and its potential to investigate age-related changes,” Bone 50(3), 643–650 (2012).
[CrossRef] [PubMed]

R. Ambekar, T. Y. Lau, M. Walsh, R. Bhargava, K. C. Toussaint., “Quantifying collagen structure in breast biopsies using second-harmonic generation imaging,” Biomed. Opt. Express 3(9), 2021–2035 (2012).
[CrossRef] [PubMed]

T. Y. Lau, R. Ambekar, K. C. Toussaint, “Quantification of collagen fiber organization using three-dimensional Fourier transform-second-harmonic generation imaging,” Opt. Express 20(19), 21821–21832 (2012).
[CrossRef] [PubMed]

2011

P. G. Ellingsen, M. B. Lilledahl, L. M. S. Aas, C. L. Davies, M. Kildemo, “Quantitative characterization of articular cartilage using Mueller matrix imaging and multiphoton microscopy,” J. Biomed. Opt. 16(11), 116002 (2011).
[CrossRef] [PubMed]

M. B. Lilledahl, D. M. Pierce, T. Ricken, G. A. Holzapfel, C. L. Davies, “Structural analysis of articular cartilage using multiphoton microscopy: Input for biomechanical modeling,” IEEE Trans. Med. Imaging 30(9), 1635–1648 (2011).
[CrossRef] [PubMed]

S. H. Huang, C. D. Hsiao, D. S. Lin, C. Y. Chow, C. J. Chang, I. Liau, “Imaging of zebrafish in Vivo with second-harmonic generation reveals shortened sarcomeres associated with myopathy induced by statin,” PLoS ONE 6(9), e24764 (2011).
[CrossRef] [PubMed]

2010

B. E. Cohen, “Biological imaging: Beyond fluorescence,” Nature 467(7314), 407–408 (2010).
[CrossRef] [PubMed]

P. Pantazis, J. Maloney, D. Wu, S. E. Fraser, “Second harmonic generating (SHG) nanoprobes for in vivo imaging,” Proc. Natl. Acad. Sci. U.S.A. 107(33), 14535–14540 (2010).
[CrossRef] [PubMed]

M. Sivaguru, S. Durgam, R. Ambekar, D. Luedtke, G. Fried, A. Stewart, K. C. Toussaint., “Quantitative analysis of collagen fiber organization in injured tendons using Fourier transform-second harmonic generation imaging,” Opt. Express 18(24), 24983–24993 (2010).
[CrossRef] [PubMed]

2009

2008

T. Hompland, A. Erikson, M. Lindgren, T. Lindmo, C. de Lange Davies, “Second-harmonic generation in collagen as a potential cancer diagnostic parameter,” J. Biomed. Opt. 13(5), 054050 (2008).
[CrossRef] [PubMed]

R. LaComb, O. Nadiarnykh, P. J. Campagnola, “Quantitative Second Harmonic Generation Imaging of the Diseased State Osteogenesis Imperfecta: Experiment and Simulation,” Biophys. J. 94(11), 4504–4514 (2008).
[CrossRef] [PubMed]

2007

M. Strupler, A. M. Pena, M. Hernest, P. L. Tharaux, J. L. Martin, E. Beaurepaire, M. C. Schanne-Klein, “Second harmonic imaging and scoring of collagen in fibrotic tissues,” Opt. Express 15(7), 4054–4065 (2007).
[CrossRef] [PubMed]

F. Tiaho, G. Recher, D. Rouède, “Estimation of helical angles of myosin and collagen by second harmonic generation imaging microscopy,” Opt. Express 15(19), 12286–12295 (2007).
[CrossRef] [PubMed]

M. B. Lilledahl, O. A. Haugen, C. de Lange Davies, L. O. Svaasand, “Characterization of vulnerable plaques by multiphoton microscopy,” J. Biomed. Opt. 12(4), 044005 (2007).
[CrossRef] [PubMed]

C. B. Raub, V. Suresh, T. Krasieva, J. Lyubovitsky, J. D. Mih, A. J. Putnam, B. J. Tromberg, S. C. George, “Noninvasive Assessment of Collagen Gel Microstructure and Mechanics Using Multiphoton Microscopy,” Biophys. J. 92(6), 2212–2222 (2007).
[CrossRef] [PubMed]

2006

2003

D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

P. J. Campagnola, 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]

1989

S. Tokutake, Y. Imanishi, M. Sisido, “Efficiency of Second Harmonic Generation from Amino Acids, Peptides, and Polypeptides Carrying Polarizable Aromatic Groups,” Mol. Cryst. Liq. Cryst. (Phila. Pa.) 170, 245–257 (1989).

1986

1978

J. N. Gannaway, C. J. R. Sheppard, “Second-harmonic imaging in the scanning optical microscope,” Opt. Quantum Electron. 10(5), 435–439 (1978).
[CrossRef]

1974

R. Hellwarth, P. Christensen, “Nonlinear optical microscopic examination of structure in polycrystalline ZnSe,” Opt. Commun. 12(3), 318–322 (1974).
[CrossRef]

1961

P. A. Franken, A. E. Hill, C. W. Peters, G. Weinreich, “Generation of Optical Harmonics,” Phys. Rev. Lett. 7(4), 118–119 (1961).
[CrossRef]

Aas, L. M. S.

P. G. Ellingsen, M. B. Lilledahl, L. M. S. Aas, C. L. Davies, M. Kildemo, “Quantitative characterization of articular cartilage using Mueller matrix imaging and multiphoton microscopy,” J. Biomed. Opt. 16(11), 116002 (2011).
[CrossRef] [PubMed]

Ambekar, R.

Beaurepaire, E.

Bhargava, R.

Campagnola, P. J.

X. Chen, O. Nadiarynkh, S. Plotnikov, P. J. Campagnola, “Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure,” Nat. Protoc. 7(4), 654–669 (2012).
[CrossRef] [PubMed]

R. LaComb, O. Nadiarnykh, P. J. Campagnola, “Quantitative Second Harmonic Generation Imaging of the Diseased State Osteogenesis Imperfecta: Experiment and Simulation,” Biophys. J. 94(11), 4504–4514 (2008).
[CrossRef] [PubMed]

P. J. Campagnola, 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]

Chang, C. J.

S. H. Huang, C. D. Hsiao, D. S. Lin, C. Y. Chow, C. J. Chang, I. Liau, “Imaging of zebrafish in Vivo with second-harmonic generation reveals shortened sarcomeres associated with myopathy induced by statin,” PLoS ONE 6(9), e24764 (2011).
[CrossRef] [PubMed]

Chen, X.

X. Chen, O. Nadiarynkh, S. Plotnikov, P. J. Campagnola, “Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure,” Nat. Protoc. 7(4), 654–669 (2012).
[CrossRef] [PubMed]

Chien, E. K.

T. Y. Lau, H. K. Sangha, E. K. Chien, B. L. McFarlin, A. J. Wagoner Johnson, K. C. Toussaint., “Application of Fourier transform-second-harmonic generation imaging to the rat cervix,” J. Microsc. 251(1), 77–83 (2013).
[CrossRef] [PubMed]

Chittenden, M.

R. Ambekar, M. Chittenden, I. Jasiuk, K. C. Toussaint., “Quantitative second-harmonic generation microscopy for imaging porcine cortical bone: Comparison to SEM and its potential to investigate age-related changes,” Bone 50(3), 643–650 (2012).
[CrossRef] [PubMed]

Chow, C. Y.

S. H. Huang, C. D. Hsiao, D. S. Lin, C. Y. Chow, C. J. Chang, I. Liau, “Imaging of zebrafish in Vivo with second-harmonic generation reveals shortened sarcomeres associated with myopathy induced by statin,” PLoS ONE 6(9), e24764 (2011).
[CrossRef] [PubMed]

Christensen, P.

R. Hellwarth, P. Christensen, “Nonlinear optical microscopic examination of structure in polycrystalline ZnSe,” Opt. Commun. 12(3), 318–322 (1974).
[CrossRef]

Cohen, B. E.

B. E. Cohen, “Biological imaging: Beyond fluorescence,” Nature 467(7314), 407–408 (2010).
[CrossRef] [PubMed]

Davies, C. L.

P. G. Ellingsen, M. B. Lilledahl, L. M. S. Aas, C. L. Davies, M. Kildemo, “Quantitative characterization of articular cartilage using Mueller matrix imaging and multiphoton microscopy,” J. Biomed. Opt. 16(11), 116002 (2011).
[CrossRef] [PubMed]

M. B. Lilledahl, D. M. Pierce, T. Ricken, G. A. Holzapfel, C. L. Davies, “Structural analysis of articular cartilage using multiphoton microscopy: Input for biomechanical modeling,” IEEE Trans. Med. Imaging 30(9), 1635–1648 (2011).
[CrossRef] [PubMed]

de Lange Davies, C.

T. Hompland, A. Erikson, M. Lindgren, T. Lindmo, C. de Lange Davies, “Second-harmonic generation in collagen as a potential cancer diagnostic parameter,” J. Biomed. Opt. 13(5), 054050 (2008).
[CrossRef] [PubMed]

M. B. Lilledahl, O. A. Haugen, C. de Lange Davies, L. O. Svaasand, “Characterization of vulnerable plaques by multiphoton microscopy,” J. Biomed. Opt. 12(4), 044005 (2007).
[CrossRef] [PubMed]

Débarre, D.

Deutsch, M.

Dombeck, D. A.

D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

Durgam, S.

Ellingsen, P. G.

P. G. Ellingsen, M. B. Lilledahl, L. M. S. Aas, C. L. Davies, M. Kildemo, “Quantitative characterization of articular cartilage using Mueller matrix imaging and multiphoton microscopy,” J. Biomed. Opt. 16(11), 116002 (2011).
[CrossRef] [PubMed]

Erikson, A.

T. Hompland, A. Erikson, M. Lindgren, T. Lindmo, C. de Lange Davies, “Second-harmonic generation in collagen as a potential cancer diagnostic parameter,” J. Biomed. Opt. 13(5), 054050 (2008).
[CrossRef] [PubMed]

Franken, P. A.

P. A. Franken, A. E. Hill, C. W. Peters, G. Weinreich, “Generation of Optical Harmonics,” Phys. Rev. Lett. 7(4), 118–119 (1961).
[CrossRef]

Fraser, S. E.

P. Pantazis, J. Maloney, D. Wu, S. E. Fraser, “Second harmonic generating (SHG) nanoprobes for in vivo imaging,” Proc. Natl. Acad. Sci. U.S.A. 107(33), 14535–14540 (2010).
[CrossRef] [PubMed]

Freund, I.

Fried, G.

Gannaway, J. N.

J. N. Gannaway, C. J. R. Sheppard, “Second-harmonic imaging in the scanning optical microscope,” Opt. Quantum Electron. 10(5), 435–439 (1978).
[CrossRef]

George, S. C.

C. B. Raub, V. Suresh, T. Krasieva, J. Lyubovitsky, J. D. Mih, A. J. Putnam, B. J. Tromberg, S. C. George, “Noninvasive Assessment of Collagen Gel Microstructure and Mechanics Using Multiphoton Microscopy,” Biophys. J. 92(6), 2212–2222 (2007).
[CrossRef] [PubMed]

Haugen, O. A.

M. B. Lilledahl, O. A. Haugen, C. de Lange Davies, L. O. Svaasand, “Characterization of vulnerable plaques by multiphoton microscopy,” J. Biomed. Opt. 12(4), 044005 (2007).
[CrossRef] [PubMed]

Hellwarth, R.

R. Hellwarth, P. Christensen, “Nonlinear optical microscopic examination of structure in polycrystalline ZnSe,” Opt. Commun. 12(3), 318–322 (1974).
[CrossRef]

Hernest, M.

Hill, A. E.

P. A. Franken, A. E. Hill, C. W. Peters, G. Weinreich, “Generation of Optical Harmonics,” Phys. Rev. Lett. 7(4), 118–119 (1961).
[CrossRef]

Holzapfel, G. A.

M. B. Lilledahl, D. M. Pierce, T. Ricken, G. A. Holzapfel, C. L. Davies, “Structural analysis of articular cartilage using multiphoton microscopy: Input for biomechanical modeling,” IEEE Trans. Med. Imaging 30(9), 1635–1648 (2011).
[CrossRef] [PubMed]

Hompland, T.

T. Hompland, A. Erikson, M. Lindgren, T. Lindmo, C. de Lange Davies, “Second-harmonic generation in collagen as a potential cancer diagnostic parameter,” J. Biomed. Opt. 13(5), 054050 (2008).
[CrossRef] [PubMed]

Hsiao, C. D.

S. H. Huang, C. D. Hsiao, D. S. Lin, C. Y. Chow, C. J. Chang, I. Liau, “Imaging of zebrafish in Vivo with second-harmonic generation reveals shortened sarcomeres associated with myopathy induced by statin,” PLoS ONE 6(9), e24764 (2011).
[CrossRef] [PubMed]

Huang, S. H.

S. H. Huang, C. D. Hsiao, D. S. Lin, C. Y. Chow, C. J. Chang, I. Liau, “Imaging of zebrafish in Vivo with second-harmonic generation reveals shortened sarcomeres associated with myopathy induced by statin,” PLoS ONE 6(9), e24764 (2011).
[CrossRef] [PubMed]

Hyman, B. T.

D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

Imanishi, Y.

S. Tokutake, Y. Imanishi, M. Sisido, “Efficiency of Second Harmonic Generation from Amino Acids, Peptides, and Polypeptides Carrying Polarizable Aromatic Groups,” Mol. Cryst. Liq. Cryst. (Phila. Pa.) 170, 245–257 (1989).

Ingelsson, M.

D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

Jasiuk, I.

R. Ambekar, M. Chittenden, I. Jasiuk, K. C. Toussaint., “Quantitative second-harmonic generation microscopy for imaging porcine cortical bone: Comparison to SEM and its potential to investigate age-related changes,” Bone 50(3), 643–650 (2012).
[CrossRef] [PubMed]

Joffre, M.

Kasischke, K. A.

D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

Kildemo, M.

P. G. Ellingsen, M. B. Lilledahl, L. M. S. Aas, C. L. Davies, M. Kildemo, “Quantitative characterization of articular cartilage using Mueller matrix imaging and multiphoton microscopy,” J. Biomed. Opt. 16(11), 116002 (2011).
[CrossRef] [PubMed]

Krasieva, T.

C. B. Raub, V. Suresh, T. Krasieva, J. Lyubovitsky, J. D. Mih, A. J. Putnam, B. J. Tromberg, S. C. George, “Noninvasive Assessment of Collagen Gel Microstructure and Mechanics Using Multiphoton Microscopy,” Biophys. J. 92(6), 2212–2222 (2007).
[CrossRef] [PubMed]

LaComb, R.

R. LaComb, O. Nadiarnykh, P. J. Campagnola, “Quantitative Second Harmonic Generation Imaging of the Diseased State Osteogenesis Imperfecta: Experiment and Simulation,” Biophys. J. 94(11), 4504–4514 (2008).
[CrossRef] [PubMed]

Lau, T. Y.

Leithem, S.

Liau, I.

S. H. Huang, C. D. Hsiao, D. S. Lin, C. Y. Chow, C. J. Chang, I. Liau, “Imaging of zebrafish in Vivo with second-harmonic generation reveals shortened sarcomeres associated with myopathy induced by statin,” PLoS ONE 6(9), e24764 (2011).
[CrossRef] [PubMed]

Lilledahl, M. B.

M. B. Lilledahl, D. M. Pierce, T. Ricken, G. A. Holzapfel, C. L. Davies, “Structural analysis of articular cartilage using multiphoton microscopy: Input for biomechanical modeling,” IEEE Trans. Med. Imaging 30(9), 1635–1648 (2011).
[CrossRef] [PubMed]

P. G. Ellingsen, M. B. Lilledahl, L. M. S. Aas, C. L. Davies, M. Kildemo, “Quantitative characterization of articular cartilage using Mueller matrix imaging and multiphoton microscopy,” J. Biomed. Opt. 16(11), 116002 (2011).
[CrossRef] [PubMed]

M. B. Lilledahl, O. A. Haugen, C. de Lange Davies, L. O. Svaasand, “Characterization of vulnerable plaques by multiphoton microscopy,” J. Biomed. Opt. 12(4), 044005 (2007).
[CrossRef] [PubMed]

Lin, D. S.

S. H. Huang, C. D. Hsiao, D. S. Lin, C. Y. Chow, C. J. Chang, I. Liau, “Imaging of zebrafish in Vivo with second-harmonic generation reveals shortened sarcomeres associated with myopathy induced by statin,” PLoS ONE 6(9), e24764 (2011).
[CrossRef] [PubMed]

Lindgren, M.

T. Hompland, A. Erikson, M. Lindgren, T. Lindmo, C. de Lange Davies, “Second-harmonic generation in collagen as a potential cancer diagnostic parameter,” J. Biomed. Opt. 13(5), 054050 (2008).
[CrossRef] [PubMed]

Lindmo, T.

T. Hompland, A. Erikson, M. Lindgren, T. Lindmo, C. de Lange Davies, “Second-harmonic generation in collagen as a potential cancer diagnostic parameter,” J. Biomed. Opt. 13(5), 054050 (2008).
[CrossRef] [PubMed]

Loew, L. M.

P. J. Campagnola, 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]

Luedtke, D.

Lyubovitsky, J.

C. B. Raub, V. Suresh, T. Krasieva, J. Lyubovitsky, J. D. Mih, A. J. Putnam, B. J. Tromberg, S. C. George, “Noninvasive Assessment of Collagen Gel Microstructure and Mechanics Using Multiphoton Microscopy,” Biophys. J. 92(6), 2212–2222 (2007).
[CrossRef] [PubMed]

Maloney, J.

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[CrossRef] [PubMed]

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McFarlin, B. L.

T. Y. Lau, H. K. Sangha, E. K. Chien, B. L. McFarlin, A. J. Wagoner Johnson, K. C. Toussaint., “Application of Fourier transform-second-harmonic generation imaging to the rat cervix,” J. Microsc. 251(1), 77–83 (2013).
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R. LaComb, O. Nadiarnykh, P. J. Campagnola, “Quantitative Second Harmonic Generation Imaging of the Diseased State Osteogenesis Imperfecta: Experiment and Simulation,” Biophys. J. 94(11), 4504–4514 (2008).
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Nadiarynkh, O.

X. Chen, O. Nadiarynkh, S. Plotnikov, P. J. Campagnola, “Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure,” Nat. Protoc. 7(4), 654–669 (2012).
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Ogilvie, J. P.

Pantazis, P.

P. Pantazis, J. Maloney, D. Wu, S. E. Fraser, “Second harmonic generating (SHG) nanoprobes for in vivo imaging,” Proc. Natl. Acad. Sci. U.S.A. 107(33), 14535–14540 (2010).
[CrossRef] [PubMed]

Pena, A. M.

Peters, C. W.

P. A. Franken, A. E. Hill, C. W. Peters, G. Weinreich, “Generation of Optical Harmonics,” Phys. Rev. Lett. 7(4), 118–119 (1961).
[CrossRef]

Pierce, D. M.

M. B. Lilledahl, D. M. Pierce, T. Ricken, G. A. Holzapfel, C. L. Davies, “Structural analysis of articular cartilage using multiphoton microscopy: Input for biomechanical modeling,” IEEE Trans. Med. Imaging 30(9), 1635–1648 (2011).
[CrossRef] [PubMed]

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X. Chen, O. Nadiarynkh, S. Plotnikov, P. J. Campagnola, “Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure,” Nat. Protoc. 7(4), 654–669 (2012).
[CrossRef] [PubMed]

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C. B. Raub, V. Suresh, T. Krasieva, J. Lyubovitsky, J. D. Mih, A. J. Putnam, B. J. Tromberg, S. C. George, “Noninvasive Assessment of Collagen Gel Microstructure and Mechanics Using Multiphoton Microscopy,” Biophys. J. 92(6), 2212–2222 (2007).
[CrossRef] [PubMed]

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Rao, R. A. R.

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C. B. Raub, V. Suresh, T. Krasieva, J. Lyubovitsky, J. D. Mih, A. J. Putnam, B. J. Tromberg, S. C. George, “Noninvasive Assessment of Collagen Gel Microstructure and Mechanics Using Multiphoton Microscopy,” Biophys. J. 92(6), 2212–2222 (2007).
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Recher, G.

Ricken, T.

M. B. Lilledahl, D. M. Pierce, T. Ricken, G. A. Holzapfel, C. L. Davies, “Structural analysis of articular cartilage using multiphoton microscopy: Input for biomechanical modeling,” IEEE Trans. Med. Imaging 30(9), 1635–1648 (2011).
[CrossRef] [PubMed]

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Sangha, H. K.

T. Y. Lau, H. K. Sangha, E. K. Chien, B. L. McFarlin, A. J. Wagoner Johnson, K. C. Toussaint., “Application of Fourier transform-second-harmonic generation imaging to the rat cervix,” J. Microsc. 251(1), 77–83 (2013).
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[CrossRef]

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S. Tokutake, Y. Imanishi, M. Sisido, “Efficiency of Second Harmonic Generation from Amino Acids, Peptides, and Polypeptides Carrying Polarizable Aromatic Groups,” Mol. Cryst. Liq. Cryst. (Phila. Pa.) 170, 245–257 (1989).

Sivaguru, M.

Solinas, X.

Stewart, A.

Strupler, M.

Suresh, V.

C. B. Raub, V. Suresh, T. Krasieva, J. Lyubovitsky, J. D. Mih, A. J. Putnam, B. J. Tromberg, S. C. George, “Noninvasive Assessment of Collagen Gel Microstructure and Mechanics Using Multiphoton Microscopy,” Biophys. J. 92(6), 2212–2222 (2007).
[CrossRef] [PubMed]

Svaasand, L. O.

M. B. Lilledahl, O. A. Haugen, C. de Lange Davies, L. O. Svaasand, “Characterization of vulnerable plaques by multiphoton microscopy,” J. Biomed. Opt. 12(4), 044005 (2007).
[CrossRef] [PubMed]

Tharaux, P. L.

Tiaho, F.

Tokutake, S.

S. Tokutake, Y. Imanishi, M. Sisido, “Efficiency of Second Harmonic Generation from Amino Acids, Peptides, and Polypeptides Carrying Polarizable Aromatic Groups,” Mol. Cryst. Liq. Cryst. (Phila. Pa.) 170, 245–257 (1989).

Toussaint, K. C.

T. Y. Lau, H. K. Sangha, E. K. Chien, B. L. McFarlin, A. J. Wagoner Johnson, K. C. Toussaint., “Application of Fourier transform-second-harmonic generation imaging to the rat cervix,” J. Microsc. 251(1), 77–83 (2013).
[CrossRef] [PubMed]

R. Ambekar, T. Y. Lau, M. Walsh, R. Bhargava, K. C. Toussaint., “Quantifying collagen structure in breast biopsies using second-harmonic generation imaging,” Biomed. Opt. Express 3(9), 2021–2035 (2012).
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M. Sivaguru, S. Durgam, R. Ambekar, D. Luedtke, G. Fried, A. Stewart, K. C. Toussaint., “Quantitative analysis of collagen fiber organization in injured tendons using Fourier transform-second harmonic generation imaging,” Opt. Express 18(24), 24983–24993 (2010).
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R. A. Rao, M. R. Mehta, K. C. Toussaint., “Fourier transform-second-harmonic generation imaging of biological tissues,” Opt. Express 17(17), 14534–14542 (2009).
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C. B. Raub, V. Suresh, T. Krasieva, J. Lyubovitsky, J. D. Mih, A. J. Putnam, B. J. Tromberg, S. C. George, “Noninvasive Assessment of Collagen Gel Microstructure and Mechanics Using Multiphoton Microscopy,” Biophys. J. 92(6), 2212–2222 (2007).
[CrossRef] [PubMed]

Vishwasrao, H. D.

D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

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T. Y. Lau, H. K. Sangha, E. K. Chien, B. L. McFarlin, A. J. Wagoner Johnson, K. C. Toussaint., “Application of Fourier transform-second-harmonic generation imaging to the rat cervix,” J. Microsc. 251(1), 77–83 (2013).
[CrossRef] [PubMed]

Walsh, M.

Webb, W. W.

D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

Weinreich, G.

P. A. Franken, A. E. Hill, C. W. Peters, G. Weinreich, “Generation of Optical Harmonics,” Phys. Rev. Lett. 7(4), 118–119 (1961).
[CrossRef]

Wu, D.

P. Pantazis, J. Maloney, D. Wu, S. E. Fraser, “Second harmonic generating (SHG) nanoprobes for in vivo imaging,” Proc. Natl. Acad. Sci. U.S.A. 107(33), 14535–14540 (2010).
[CrossRef] [PubMed]

Biomed. Opt. Express

Biophys. J.

C. B. Raub, V. Suresh, T. Krasieva, J. Lyubovitsky, J. D. Mih, A. J. Putnam, B. J. Tromberg, S. C. George, “Noninvasive Assessment of Collagen Gel Microstructure and Mechanics Using Multiphoton Microscopy,” Biophys. J. 92(6), 2212–2222 (2007).
[CrossRef] [PubMed]

R. LaComb, O. Nadiarnykh, P. J. Campagnola, “Quantitative Second Harmonic Generation Imaging of the Diseased State Osteogenesis Imperfecta: Experiment and Simulation,” Biophys. J. 94(11), 4504–4514 (2008).
[CrossRef] [PubMed]

Bone

R. Ambekar, M. Chittenden, I. Jasiuk, K. C. Toussaint., “Quantitative second-harmonic generation microscopy for imaging porcine cortical bone: Comparison to SEM and its potential to investigate age-related changes,” Bone 50(3), 643–650 (2012).
[CrossRef] [PubMed]

IEEE Trans. Med. Imaging

M. B. Lilledahl, D. M. Pierce, T. Ricken, G. A. Holzapfel, C. L. Davies, “Structural analysis of articular cartilage using multiphoton microscopy: Input for biomechanical modeling,” IEEE Trans. Med. Imaging 30(9), 1635–1648 (2011).
[CrossRef] [PubMed]

J. Biomed. Opt.

M. B. Lilledahl, O. A. Haugen, C. de Lange Davies, L. O. Svaasand, “Characterization of vulnerable plaques by multiphoton microscopy,” J. Biomed. Opt. 12(4), 044005 (2007).
[CrossRef] [PubMed]

T. Hompland, A. Erikson, M. Lindgren, T. Lindmo, C. de Lange Davies, “Second-harmonic generation in collagen as a potential cancer diagnostic parameter,” J. Biomed. Opt. 13(5), 054050 (2008).
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J. Microsc.

T. Y. Lau, H. K. Sangha, E. K. Chien, B. L. McFarlin, A. J. Wagoner Johnson, K. C. Toussaint., “Application of Fourier transform-second-harmonic generation imaging to the rat cervix,” J. Microsc. 251(1), 77–83 (2013).
[CrossRef] [PubMed]

Mol. Cryst. Liq. Cryst. (Phila. Pa.)

S. Tokutake, Y. Imanishi, M. Sisido, “Efficiency of Second Harmonic Generation from Amino Acids, Peptides, and Polypeptides Carrying Polarizable Aromatic Groups,” Mol. Cryst. Liq. Cryst. (Phila. Pa.) 170, 245–257 (1989).

Nat. Biotechnol.

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

X. Chen, O. Nadiarynkh, S. Plotnikov, P. J. Campagnola, “Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure,” Nat. Protoc. 7(4), 654–669 (2012).
[CrossRef] [PubMed]

Nature

B. E. Cohen, “Biological imaging: Beyond fluorescence,” Nature 467(7314), 407–408 (2010).
[CrossRef] [PubMed]

Opt. Commun.

R. Hellwarth, P. Christensen, “Nonlinear optical microscopic examination of structure in polycrystalline ZnSe,” Opt. Commun. 12(3), 318–322 (1974).
[CrossRef]

Opt. Express

Opt. Lett.

Opt. Quantum Electron.

J. N. Gannaway, C. J. R. Sheppard, “Second-harmonic imaging in the scanning optical microscope,” Opt. Quantum Electron. 10(5), 435–439 (1978).
[CrossRef]

Phys. Rev. Lett.

P. A. Franken, A. E. Hill, C. W. Peters, G. Weinreich, “Generation of Optical Harmonics,” Phys. Rev. Lett. 7(4), 118–119 (1961).
[CrossRef]

PLoS ONE

S. H. Huang, C. D. Hsiao, D. S. Lin, C. Y. Chow, C. J. Chang, I. Liau, “Imaging of zebrafish in Vivo with second-harmonic generation reveals shortened sarcomeres associated with myopathy induced by statin,” PLoS ONE 6(9), e24764 (2011).
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Proc. Natl. Acad. Sci. U.S.A.

P. Pantazis, J. Maloney, D. Wu, S. E. Fraser, “Second harmonic generating (SHG) nanoprobes for in vivo imaging,” Proc. Natl. Acad. Sci. U.S.A. 107(33), 14535–14540 (2010).
[CrossRef] [PubMed]

D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, W. W. Webb, “Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy,” Proc. Natl. Acad. Sci. U.S.A. 100(12), 7081–7086 (2003).
[CrossRef] [PubMed]

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R. Gonzalez and R. Woods, Digital Image Processing (3rd Edition) (Prentice Hall, 2007).

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Supplementary Material (4)

» Media 1: MP4 (2197 KB)     
» Media 2: MP4 (1744 KB)     
» Media 3: MP4 (1651 KB)     
» Media 4: MP4 (2339 KB)     

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Figures (5)

Fig. 1
Fig. 1

(a) Schematic of the experimental setup used and (b) an example SHG image of stained tendon sample with associated circular histogram (top right) and FFT spectrum (bottom right). See text for details.

Fig. 2
Fig. 2

SHG images of (a) tendon and (b) collagen scaffold fibers for various pixel areas and a fixed SNR of 7. The corresponding pixel areas are: (i) 120 x 120 (ii) 240 x 240 (iii) 360 x 360 and (iv) 512 x 512 pixels. The same scale applies to all images. (c) The acquisition time for each image area is plotted against the pixel area.

Fig. 3
Fig. 3

SHG images of stage-scanned (a) tendon (Media 1) and (b) collagen scaffold fibers (Media 2) at different locations shown in top left corner. The lateral coordinates for each image, relative to the initial (0, 0), are provided in the bottom right hand corner for each frame. The same scale applies to all images. See text for additional details.

Fig. 4
Fig. 4

SHG images of collagen scaffold fiber formation (Media 3) at different times in (i)10 (ii)11.4 (iii)11.6 (iv)12.2 minutes. The same scale applies to all images.

Fig. 5
Fig. 5

SHG images of breast tissue samples (Media 4) at different cores corresponding to (a) malignant (b) healthy tissues. The same scale applies to all images.

Tables (1)

Tables Icon

Table 1 Image processing time for various image sizes.

Metrics