Abstract

With a video-rate third harmonic generation (THG) microscopy system, we imaged the micro-circulation beneath the human skin without labeling. Not only the speed of circulation but also the morpho-hydrodynamics of blood cells can be analyzed. Lacking of nuclei, red blood cells (RBCs) shows typical parachute-like and hollow-core morphology under THG microscopy. Quite different from RBCs, every now and then, round and granule rich blood cells with strong THG contrast appear in circulation. The corresponding volume densities in blood, evaluated from their frequencies of appearance and the velocity of circulation, fall within the physiological range of human white blood cell counts.

© 2012 OSA

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, and E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med.1(9), 970–972 (1995).
    [CrossRef] [PubMed]
  2. M. Rajadhyaksha, S. González, J. M. Zavislan, R. R. Anderson, and R. H. Webb, “In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology,” J. Invest. Dermatol.113(3), 293–303 (1999).
    [CrossRef] [PubMed]
  3. G. J. Tearney, R. H. Webb, and B. E. Bouma, “Spectrally encoded confocal microscopy,” Opt. Lett.23(15), 1152–1154 (1998).
    [CrossRef] [PubMed]
  4. L. Golan, D. Yeheskely-Hayon, L. Minai, E. J. Dann, and D. Yelin, “Noninvasive imaging of flowing blood cells using label-free spectrally encoded flow cytometry,” Biomed. Opt. Express3(6), 1455–1464 (2012).
    [CrossRef] [PubMed]
  5. L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
    [CrossRef] [PubMed]
  6. K. König, A. Ehlers, F. Stracke, and I. Riemann, “In vivo drug screening in human skin using femtosecond laser multiphoton tomography,” Skin Pharmacol. Physiol.19(2), 78–88 (2006).
    [CrossRef] [PubMed]
  7. J. Paoli, M. Smedh, A.-M. Wennberg, and M. B. Ericson, “Multiphoton laser scanning microscopy on non-melanoma skin cancer: morphologic features for future non-invasive diagnostics,” J. Invest. Dermatol.128(5), 1248–1255 (2008).
    [CrossRef] [PubMed]
  8. 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]
  9. 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]
  10. S.-H. Chia, C.-H. Yu, C.-H. Lin, N.-C. Cheng, T.-M. Liu, M.-C. Chan, I.-H. Chen, and C.-K. Sun, “Miniaturized video-rate epi-third-harmonic-generation fiber-microscope,” Opt. Express18(16), 17382–17391 (2010).
    [CrossRef] [PubMed]
  11. 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]
  12. B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science330(6009), 1368–1370 (2010).
    [CrossRef] [PubMed]
  13. J. Squier, M. Muller, G. Brakenhoff, and K. R. Wilson, “Third harmonic generation microscopy,” Opt. Express3(9), 315–324 (1998).
    [CrossRef] [PubMed]
  14. D. Yelin and Y. Silberberg, “Laser scanning third-harmonic-generation microscopy in biology,” Opt. Express5(8), 169–175 (1999).
    [CrossRef] [PubMed]
  15. S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, H.-J. Tsai, and C.-K. Sun, “In vivo developmental biology study using noninvasive multi-harmonic generation microscopy,” Opt. Express11(23), 3093–3099 (2003).
    [CrossRef] [PubMed]
  16. N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (2010).
    [CrossRef] [PubMed]
  17. D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein, and E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods3(1), 47–53 (2006).
    [CrossRef] [PubMed]
  18. R. D. Schaller, J. C. Johnson, and R. J. Saykally, “Nonlinear chemical imaging microscopy: near-field third harmonic generation imaging of human red blood cells,” Anal. Chem.72(21), 5361–5364 (2000).
    [CrossRef] [PubMed]
  19. R. Skalak and P.-I. Branemark, “Deformation of red blood cells in capillaries,” Science164(3880), 717–719 (1969).
    [CrossRef] [PubMed]
  20. B. Kaoui, G. Biros, and C. Misbah, “Why do red blood cells have asymmetric shapes even in a symmetric flow?” Phys. Rev. Lett.103(18), 188101 (2009).
    [CrossRef] [PubMed]
  21. D. Kobat, N. G. Horton, and C. Xu, “In vivo two-photon microscopy to 1.6-mm depth in mouse cortex,” J. Biomed. Opt.16(10), 106014 (2011).
    [CrossRef] [PubMed]
  22. C.-K. Tsai, Y.-S. Chen, P.-C. Wu, T.-Y. Hsieh, H.-W. Liu, C.-Y. Yeh, W.-L. Lin, J.-S. Chia, and T.-M. Liu, “Imaging granularity of leukocytes with third harmonic generation microscopy,” Biomed. Opt. Express3(9), 2234–2243 (2012).
    [CrossRef]
  23. S. S. Gorthi and E. Schonbrun, “Phase imaging flow cytometry using a focus-stack collecting microscope,” Opt. Lett.37(4), 707–709 (2012).
    [CrossRef] [PubMed]
  24. M. N. Hart and A. G. Loeffler, Introduction to Human Disease (Jones & Bartlett Learning, 2012), pp 130.

2012 (3)

2011 (3)

D. Kobat, N. G. Horton, and C. Xu, “In vivo two-photon microscopy to 1.6-mm depth in mouse cortex,” J. Biomed. Opt.16(10), 106014 (2011).
[CrossRef] [PubMed]

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
[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]

2010 (4)

B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science330(6009), 1368–1370 (2010).
[CrossRef] [PubMed]

S.-H. Chia, C.-H. Yu, C.-H. Lin, N.-C. Cheng, T.-M. Liu, M.-C. Chan, I.-H. Chen, and C.-K. Sun, “Miniaturized video-rate epi-third-harmonic-generation fiber-microscope,” Opt. Express18(16), 17382–17391 (2010).
[CrossRef] [PubMed]

N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (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 (2)

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]

B. Kaoui, G. Biros, and C. Misbah, “Why do red blood cells have asymmetric shapes even in a symmetric flow?” Phys. Rev. Lett.103(18), 188101 (2009).
[CrossRef] [PubMed]

2008 (1)

J. Paoli, M. Smedh, A.-M. Wennberg, and M. B. Ericson, “Multiphoton laser scanning microscopy on non-melanoma skin cancer: morphologic features for future non-invasive diagnostics,” J. Invest. Dermatol.128(5), 1248–1255 (2008).
[CrossRef] [PubMed]

2006 (2)

K. König, A. Ehlers, F. Stracke, and I. Riemann, “In vivo drug screening in human skin using femtosecond laser multiphoton tomography,” Skin Pharmacol. Physiol.19(2), 78–88 (2006).
[CrossRef] [PubMed]

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein, and E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods3(1), 47–53 (2006).
[CrossRef] [PubMed]

2003 (1)

2000 (1)

R. D. Schaller, J. C. Johnson, and R. J. Saykally, “Nonlinear chemical imaging microscopy: near-field third harmonic generation imaging of human red blood cells,” Anal. Chem.72(21), 5361–5364 (2000).
[CrossRef] [PubMed]

1999 (2)

D. Yelin and Y. Silberberg, “Laser scanning third-harmonic-generation microscopy in biology,” Opt. Express5(8), 169–175 (1999).
[CrossRef] [PubMed]

M. Rajadhyaksha, S. González, J. M. Zavislan, R. R. Anderson, and R. H. Webb, “In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology,” J. Invest. Dermatol.113(3), 293–303 (1999).
[CrossRef] [PubMed]

1998 (2)

1995 (1)

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, and E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med.1(9), 970–972 (1995).
[CrossRef] [PubMed]

1969 (1)

R. Skalak and P.-I. Branemark, “Deformation of red blood cells in capillaries,” Science164(3880), 717–719 (1969).
[CrossRef] [PubMed]

Anderson, R. R.

M. Rajadhyaksha, S. González, J. M. Zavislan, R. R. Anderson, and R. H. Webb, “In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology,” J. Invest. Dermatol.113(3), 293–303 (1999).
[CrossRef] [PubMed]

Beaurepaire, E.

N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (2010).
[CrossRef] [PubMed]

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein, and E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods3(1), 47–53 (2006).
[CrossRef] [PubMed]

Biros, G.

B. Kaoui, G. Biros, and C. Misbah, “Why do red blood cells have asymmetric shapes even in a symmetric flow?” Phys. Rev. Lett.103(18), 188101 (2009).
[CrossRef] [PubMed]

Boppart, S. A.

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, and E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med.1(9), 970–972 (1995).
[CrossRef] [PubMed]

Bouma, B.

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, and E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med.1(9), 970–972 (1995).
[CrossRef] [PubMed]

Bouma, B. E.

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
[CrossRef] [PubMed]

G. J. Tearney, R. H. Webb, and B. E. Bouma, “Spectrally encoded confocal microscopy,” Opt. Lett.23(15), 1152–1154 (1998).
[CrossRef] [PubMed]

Bourgine, P.

N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (2010).
[CrossRef] [PubMed]

Brakenhoff, G.

Branemark, P.-I.

R. Skalak and P.-I. Branemark, “Deformation of red blood cells in capillaries,” Science164(3880), 717–719 (1969).
[CrossRef] [PubMed]

Brezinski, M. E.

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, and E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med.1(9), 970–972 (1995).
[CrossRef] [PubMed]

Chan, M.-C.

Chen, I.-H.

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.

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]

S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, H.-J. Tsai, and C.-K. Sun, “In vivo developmental biology study using noninvasive multi-harmonic generation microscopy,” Opt. Express11(23), 3093–3099 (2003).
[CrossRef] [PubMed]

Chen, Y.-S.

Cheng, N.-C.

Chia, J.-S.

Chia, S.-H.

Chu, S.-W.

Combettes, L.

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein, and E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods3(1), 47–53 (2006).
[CrossRef] [PubMed]

Dann, E. J.

Débarre, D.

N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (2010).
[CrossRef] [PubMed]

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein, and E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods3(1), 47–53 (2006).
[CrossRef] [PubMed]

Duloquin, L.

N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (2010).
[CrossRef] [PubMed]

Ehlers, A.

K. König, A. Ehlers, F. Stracke, and I. Riemann, “In vivo drug screening in human skin using femtosecond laser multiphoton tomography,” Skin Pharmacol. Physiol.19(2), 78–88 (2006).
[CrossRef] [PubMed]

Ericson, M. B.

J. Paoli, M. Smedh, A.-M. Wennberg, and M. B. Ericson, “Multiphoton laser scanning microscopy on non-melanoma skin cancer: morphologic features for future non-invasive diagnostics,” J. Invest. Dermatol.128(5), 1248–1255 (2008).
[CrossRef] [PubMed]

Fabre, A.

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein, and E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods3(1), 47–53 (2006).
[CrossRef] [PubMed]

Faure, E.

N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (2010).
[CrossRef] [PubMed]

Freudiger, C. W.

B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science330(6009), 1368–1370 (2010).
[CrossRef] [PubMed]

Fujimoto, J. G.

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, and E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med.1(9), 970–972 (1995).
[CrossRef] [PubMed]

Gardecki, J. A.

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
[CrossRef] [PubMed]

Golan, L.

González, S.

M. Rajadhyaksha, S. González, J. M. Zavislan, R. R. Anderson, and R. H. Webb, “In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology,” J. Invest. Dermatol.113(3), 293–303 (1999).
[CrossRef] [PubMed]

Gorthi, S. S.

Hee, M. R.

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, and E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med.1(9), 970–972 (1995).
[CrossRef] [PubMed]

Holtom, G. R.

B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science330(6009), 1368–1370 (2010).
[CrossRef] [PubMed]

Horton, N. G.

D. Kobat, N. G. Horton, and C. Xu, “In vivo two-photon microscopy to 1.6-mm depth in mouse cortex,” J. Biomed. Opt.16(10), 106014 (2011).
[CrossRef] [PubMed]

Hsieh, T.-Y.

Johnson, J. C.

R. D. Schaller, J. C. Johnson, and R. J. Saykally, “Nonlinear chemical imaging microscopy: near-field third harmonic generation imaging of human red blood cells,” Anal. Chem.72(21), 5361–5364 (2000).
[CrossRef] [PubMed]

Kaoui, B.

B. Kaoui, G. Biros, and C. Misbah, “Why do red blood cells have asymmetric shapes even in a symmetric flow?” Phys. Rev. Lett.103(18), 188101 (2009).
[CrossRef] [PubMed]

Kobat, D.

D. Kobat, N. G. Horton, and C. Xu, “In vivo two-photon microscopy to 1.6-mm depth in mouse cortex,” J. Biomed. Opt.16(10), 106014 (2011).
[CrossRef] [PubMed]

König, K.

K. König, A. Ehlers, F. Stracke, and I. Riemann, “In vivo drug screening in human skin using femtosecond laser multiphoton tomography,” Skin Pharmacol. Physiol.19(2), 78–88 (2006).
[CrossRef] [PubMed]

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]

Liao, Y.-H.

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]

Lin, C.-H.

Lin, C.-Y.

Lin, W.-L.

Liu, H.-W.

Liu, L.

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
[CrossRef] [PubMed]

Liu, T.-M.

Lou, P.-J.

Luengo-Oroz, M. A.

N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (2010).
[CrossRef] [PubMed]

Minai, L.

Misbah, C.

B. Kaoui, G. Biros, and C. Misbah, “Why do red blood cells have asymmetric shapes even in a symmetric flow?” Phys. Rev. Lett.103(18), 188101 (2009).
[CrossRef] [PubMed]

Muller, M.

Nadkarni, S. K.

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
[CrossRef] [PubMed]

Olivier, N.

N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (2010).
[CrossRef] [PubMed]

Paoli, J.

J. Paoli, M. Smedh, A.-M. Wennberg, and M. B. Ericson, “Multiphoton laser scanning microscopy on non-melanoma skin cancer: morphologic features for future non-invasive diagnostics,” J. Invest. Dermatol.128(5), 1248–1255 (2008).
[CrossRef] [PubMed]

Pena, A.-M.

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein, and E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods3(1), 47–53 (2006).
[CrossRef] [PubMed]

Peyriéras, N.

N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (2010).
[CrossRef] [PubMed]

Rajadhyaksha, M.

M. Rajadhyaksha, S. González, J. M. Zavislan, R. R. Anderson, and R. H. Webb, “In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology,” J. Invest. Dermatol.113(3), 293–303 (1999).
[CrossRef] [PubMed]

Reichman, J.

B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science330(6009), 1368–1370 (2010).
[CrossRef] [PubMed]

Riemann, I.

K. König, A. Ehlers, F. Stracke, and I. Riemann, “In vivo drug screening in human skin using femtosecond laser multiphoton tomography,” Skin Pharmacol. Physiol.19(2), 78–88 (2006).
[CrossRef] [PubMed]

Saar, B. G.

B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science330(6009), 1368–1370 (2010).
[CrossRef] [PubMed]

Santos, A.

N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (2010).
[CrossRef] [PubMed]

Savy, T.

N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (2010).
[CrossRef] [PubMed]

Saykally, R. J.

R. D. Schaller, J. C. Johnson, and R. J. Saykally, “Nonlinear chemical imaging microscopy: near-field third harmonic generation imaging of human red blood cells,” Anal. Chem.72(21), 5361–5364 (2000).
[CrossRef] [PubMed]

Schaller, R. D.

R. D. Schaller, J. C. Johnson, and R. J. Saykally, “Nonlinear chemical imaging microscopy: near-field third harmonic generation imaging of human red blood cells,” Anal. Chem.72(21), 5361–5364 (2000).
[CrossRef] [PubMed]

Schanne-Klein, M.-C.

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein, and E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods3(1), 47–53 (2006).
[CrossRef] [PubMed]

Schonbrun, E.

Shieh, D.-B.

Silberberg, Y.

Skalak, R.

R. Skalak and P.-I. Branemark, “Deformation of red blood cells in capillaries,” Science164(3880), 717–719 (1969).
[CrossRef] [PubMed]

Smedh, M.

J. Paoli, M. Smedh, A.-M. Wennberg, and M. B. Ericson, “Multiphoton laser scanning microscopy on non-melanoma skin cancer: morphologic features for future non-invasive diagnostics,” J. Invest. Dermatol.128(5), 1248–1255 (2008).
[CrossRef] [PubMed]

Solinas, X.

N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (2010).
[CrossRef] [PubMed]

Southern, J. F.

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, and E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med.1(9), 970–972 (1995).
[CrossRef] [PubMed]

Squier, J.

Stanley, C. M.

B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science330(6009), 1368–1370 (2010).
[CrossRef] [PubMed]

Stracke, F.

K. König, A. Ehlers, F. Stracke, and I. Riemann, “In vivo drug screening in human skin using femtosecond laser multiphoton tomography,” Skin Pharmacol. Physiol.19(2), 78–88 (2006).
[CrossRef] [PubMed]

Sun, C.-K.

Supatto, W.

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein, and E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods3(1), 47–53 (2006).
[CrossRef] [PubMed]

Swanson, E. A.

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, and E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med.1(9), 970–972 (1995).
[CrossRef] [PubMed]

Tearney, G. J.

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
[CrossRef] [PubMed]

G. J. Tearney, R. H. Webb, and B. E. Bouma, “Spectrally encoded confocal microscopy,” Opt. Lett.23(15), 1152–1154 (1998).
[CrossRef] [PubMed]

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, and E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med.1(9), 970–972 (1995).
[CrossRef] [PubMed]

Tordjmann, T.

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein, and E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods3(1), 47–53 (2006).
[CrossRef] [PubMed]

Toussaint, J. D.

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
[CrossRef] [PubMed]

Tsai, C.-K.

Tsai, H.-J.

Tsai, M.-R.

Tsai, T.-H.

Veilleux, I.

N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (2010).
[CrossRef] [PubMed]

Webb, R. H.

M. Rajadhyaksha, S. González, J. M. Zavislan, R. R. Anderson, and R. H. Webb, “In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology,” J. Invest. Dermatol.113(3), 293–303 (1999).
[CrossRef] [PubMed]

G. J. Tearney, R. H. Webb, and B. E. Bouma, “Spectrally encoded confocal microscopy,” Opt. Lett.23(15), 1152–1154 (1998).
[CrossRef] [PubMed]

Wennberg, A.-M.

J. Paoli, M. Smedh, A.-M. Wennberg, and M. B. Ericson, “Multiphoton laser scanning microscopy on non-melanoma skin cancer: morphologic features for future non-invasive diagnostics,” J. Invest. Dermatol.128(5), 1248–1255 (2008).
[CrossRef] [PubMed]

Wilson, K. R.

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, P.-C.

Xie, X. S.

B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science330(6009), 1368–1370 (2010).
[CrossRef] [PubMed]

Xu, C.

D. Kobat, N. G. Horton, and C. Xu, “In vivo two-photon microscopy to 1.6-mm depth in mouse cortex,” J. Biomed. Opt.16(10), 106014 (2011).
[CrossRef] [PubMed]

Yagi, Y.

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
[CrossRef] [PubMed]

Yeh, C.-Y.

Yeheskely-Hayon, D.

Yelin, D.

Yu, C.-H.

Zavislan, J. M.

M. Rajadhyaksha, S. González, J. M. Zavislan, R. R. Anderson, and R. H. Webb, “In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology,” J. Invest. Dermatol.113(3), 293–303 (1999).
[CrossRef] [PubMed]

Anal. Chem. (1)

R. D. Schaller, J. C. Johnson, and R. J. Saykally, “Nonlinear chemical imaging microscopy: near-field third harmonic generation imaging of human red blood cells,” Anal. Chem.72(21), 5361–5364 (2000).
[CrossRef] [PubMed]

Biomed. Opt. Express (3)

IEEE J. Sel. Top. Quantum Electron. (1)

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]

J. Biomed. Opt. (2)

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]

D. Kobat, N. G. Horton, and C. Xu, “In vivo two-photon microscopy to 1.6-mm depth in mouse cortex,” J. Biomed. Opt.16(10), 106014 (2011).
[CrossRef] [PubMed]

J. Invest. Dermatol. (2)

J. Paoli, M. Smedh, A.-M. Wennberg, and M. B. Ericson, “Multiphoton laser scanning microscopy on non-melanoma skin cancer: morphologic features for future non-invasive diagnostics,” J. Invest. Dermatol.128(5), 1248–1255 (2008).
[CrossRef] [PubMed]

M. Rajadhyaksha, S. González, J. M. Zavislan, R. R. Anderson, and R. H. Webb, “In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology,” J. Invest. Dermatol.113(3), 293–303 (1999).
[CrossRef] [PubMed]

Nat. Med. (2)

L. Liu, J. A. Gardecki, S. K. Nadkarni, J. D. Toussaint, Y. Yagi, B. E. Bouma, and G. J. Tearney, “Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography,” Nat. Med.17(8), 1010–1014 (2011).
[CrossRef] [PubMed]

J. G. Fujimoto, M. E. Brezinski, G. J. Tearney, S. A. Boppart, B. Bouma, M. R. Hee, J. F. Southern, and E. A. Swanson, “Optical biopsy and imaging using optical coherence tomography,” Nat. Med.1(9), 970–972 (1995).
[CrossRef] [PubMed]

Nat. Methods (1)

D. Débarre, W. Supatto, A.-M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M.-C. Schanne-Klein, and E. Beaurepaire, “Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy,” Nat. Methods3(1), 47–53 (2006).
[CrossRef] [PubMed]

Opt. Express (4)

Opt. Lett. (2)

Phys. Rev. Lett. (1)

B. Kaoui, G. Biros, and C. Misbah, “Why do red blood cells have asymmetric shapes even in a symmetric flow?” Phys. Rev. Lett.103(18), 188101 (2009).
[CrossRef] [PubMed]

Science (3)

N. Olivier, M. A. Luengo-Oroz, L. Duloquin, E. Faure, T. Savy, I. Veilleux, X. Solinas, D. Débarre, P. Bourgine, A. Santos, N. Peyriéras, and E. Beaurepaire, “Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy,” Science329(5994), 967–971 (2010).
[CrossRef] [PubMed]

B. G. Saar, C. W. Freudiger, J. Reichman, C. M. Stanley, G. R. Holtom, and X. S. Xie, “Video-rate molecular imaging in vivo with stimulated Raman scattering,” Science330(6009), 1368–1370 (2010).
[CrossRef] [PubMed]

R. Skalak and P.-I. Branemark, “Deformation of red blood cells in capillaries,” Science164(3880), 717–719 (1969).
[CrossRef] [PubMed]

Skin Pharmacol. Physiol. (1)

K. König, A. Ehlers, F. Stracke, and I. Riemann, “In vivo drug screening in human skin using femtosecond laser multiphoton tomography,” Skin Pharmacol. Physiol.19(2), 78–88 (2006).
[CrossRef] [PubMed]

Other (1)

M. N. Hart and A. G. Loeffler, Introduction to Human Disease (Jones & Bartlett Learning, 2012), pp 130.

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (4)

Fig. 1
Fig. 1

The schematic diagram of the video-rate third harmonic generation (THG) microscopy system with a commercial inverted microscope (DMI 3000 M, Leica). DBS: Dichroic beam splitter; CGF: Colored glass filter; PMT: Photomultiplier tube.

Fig. 2
Fig. 2

(a) In vivo THG microscopy of human capillary (outlined by yellow dashed lines) in dermal papilla (DP) surrounded by basal cells (BC). Average vessel diameter is 7.5μm. (b) Next few frames of THG images observed a round and bright blood cells (indicated with white arrows). Fields of view: 85 × 85μm.

Fig. 3
Fig. 3

In vivo THG images of 15 round blood cells captured within 4-minutes of recording in human capillary. Average diameter of human capillary is 7.5 μm. Fields of view: 24 × 42μm.

Fig. 4
Fig. 4

Consecutive THG images of round blood cells moving in human blood capillary. Fields of view: 85 × 85μm. The moving distance between (b) and (c) of round cell is 5.89μm.

Metrics