Abstract

Second-harmonic generation (SHG) imaging is combined with coherent anti-Stokes Raman scattering (CARS) microscopy to follow the process of optical clearing in human skin ex vivo using dimethyl sulfoxide (DMSO) as the optical clearing agent. SHG imaging revealed that DMSO introduces morphological changes to the collagen I matrix. By carefully measuring the dynamic tissue attenuation of the coherent nonlinear signal, using CARS reference signals during the clearing process, it is found that DMSO reduces the overall SHG response from dermal collagen. Evidence is provided for a role of DMSO in compromising the structure of collagen fibers, associated with a reduction of the tissue’s scattering properties.

© 2009 Optical Society of America

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  26. R. LaComb, O. Nadiarnykh, and P. J. Campagnola, “Quantitative second harmonic generation imaging of the diseased state osteogenesis imperfecta: experiment and simulation,” Biophys. J. 94, 4504-4515 (2008).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]

2008 (3)

R. LaComb, O. Nadiarnykh, S. Carey, and P. J. Campagnola, “Quantitative second harmonic generation imaging and modeling of the optical clearing mechanism in striated muscle and tendon,” J. Biomed. Opt. 13, 021109 (2008).
[CrossRef] [PubMed]

R. LaComb, O. Nadiarnykh, S. S. Townsend, and P. J. Campagnola, “Phase matching considerations in second-harmonic generation from tissues: effects on emission directionality, conversion efficiency, and observed morphology,” Opt. Commun. 281, 1823-1832 (2008).
[CrossRef]

R. LaComb, O. Nadiarnykh, and P. J. Campagnola, “Quantitative second harmonic generation imaging of the diseased state osteogenesis imperfecta: experiment and simulation,” Biophys. J. 94, 4504-4515 (2008).
[CrossRef] [PubMed]

2007 (4)

2006 (2)

S. Plotnikov, V. Junaja, A. B. Isaacson, W. A. Mohler, and P. J. Campagnola, “Optical clearing for improved contrast in second harmonic generation imaging of skeletal muscle,” Biophys. J. 90, 328-339 (2006).
[CrossRef]

J. Hirshburg, B. Choi, J. S. Nelson, and A. T. Yeh, “Collagen solubility correlates with skin optical clearing,” J Biomed. Opt. 11, 040501 (2006).
[CrossRef] [PubMed]

2005 (6)

B. Choi, L. Tsu, E. Chen, T. S. Ishak, S. M. Iskandar, S. Chess, and J. S. Nelson, “Determination of chemical agent optical clearing potential using in vitro human skin,” Lasers Surg. Med. 36, 72-75 (2005).
[CrossRef] [PubMed]

R. Cicchi and F. S. Pavone, “Contrast and depth enhancement in two-photon microscopy of human skin ex vivo by use of optical clearing agents,” Opt. Express 13, 2337-2344 (2005).
[CrossRef] [PubMed]

V. V. Tuchin, “Optical clearing of tissues and blood using the immersion method,” J. Phys. D 38, 2497-2518 (2005).
[CrossRef]

A. M. Pena, T. Boulesteix, T. Dartigalongue, and M. C. Schanne-Klein, “Chiroptical effects in the second harmonic signal of collagens I and IV,” J. Am. Chem. Soc. 127, 10314-10322 (2005).
[CrossRef] [PubMed]

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côte, C. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering (CARS) microscopy,” Proc. Natl. Acad Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef] [PubMed]

R. M. Williams, W. R. Zipfel, and W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88, 1377-1386 (2005).
[CrossRef]

2004 (1)

Y. He and R. K. Wang, “Dynamic optical clearing effect of tissue impregnated with hyperosmotic agents and studied with optical coherence tomography,” J. Biomed. Opt. 9, 200-206 (2004).
[CrossRef] [PubMed]

2003 (4)

A. T. Yeh, J. S. Nelson, and B. J. Tromberg, “Reversible dissociation of collagen in tissues,” J. Invest. Dermatol. 121, 1332-1335 (2003).
[CrossRef] [PubMed]

X. Xu and R. K. Wang, “The role of water desorption on optical clearing of biotissue: Studied with near infrared reflectance spectroscopy,” Med. Phys. 30, 1246-1253 (2003).
[CrossRef] [PubMed]

R. K. Wang, X., Y. He, and J. B. Elder, “Investigation of optical clearing of gastric tissue immersed with hyperosmotic agents,” IEEE J. Sel. Top. Quantum Electron. 9, 234-242 (2003).
[CrossRef]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

2002 (1)

2001 (2)

R. K. Wang, X. Xu, V. V. Tuchin, and J. B. Elder, “Concurrent enhancement of imaging depth and contrast for optical coherence tomography by hyperosmotic agents,” J. Opt. Soc. Am. B 18, 948-953 (2001).
[CrossRef]

G. Vargas, K. F. Chan, S. L. Thomsen, and A. J. Welch, “Use of osmotically active agents to alter optical properties of tissue: effects on the detected fluorescence signal measured through skin,” Lasers Surg. Med. 29, 213-220 (2001).
[CrossRef] [PubMed]

1999 (1)

G. Vargas, E. K. Chan, J. K. Barton, H. G. Rylander, and A. J. Welch, “Use of an agent to reduce scattering in skin,” Lasers Surg. Med. 24, 133-141 (1999).
[CrossRef] [PubMed]

1997 (1)

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2, 401-417 (1997).
[CrossRef]

1992 (1)

F. Cansell, D. Fabre, and J. P. Petitet, “Raman spectroscopy of DMSO and DMSO-H2O mixtures (32 mol % of DMSO) up to 20 GPa,” Physica B 182, 195-200 (1992).
[CrossRef]

1991 (1)

G. F. Odland, “Structure of the Skin,” in Physiology, Biochemistry and Molecular Biology of the Skin (Oxford University Press, 1991), pp. 3-62.

1983 (1)

L. Leonardi, A. Ruggeri, N. Roveri, A. Bigi, and E. Reale, “Light microscopy, electron microscopy, and x-ray diffraction analysis of glycerinated collagen fibers,” J. Ultrastruct. Res. 85, 228-237 (1983).
[CrossRef] [PubMed]

Barton, J. K.

G. Vargas, E. K. Chan, J. K. Barton, H. G. Rylander, and A. J. Welch, “Use of an agent to reduce scattering in skin,” Lasers Surg. Med. 24, 133-141 (1999).
[CrossRef] [PubMed]

Bigi, A.

L. Leonardi, A. Ruggeri, N. Roveri, A. Bigi, and E. Reale, “Light microscopy, electron microscopy, and x-ray diffraction analysis of glycerinated collagen fibers,” J. Ultrastruct. Res. 85, 228-237 (1983).
[CrossRef] [PubMed]

Boulesteix, T.

A. M. Pena, T. Boulesteix, T. Dartigalongue, and M. C. Schanne-Klein, “Chiroptical effects in the second harmonic signal of collagens I and IV,” J. Am. Chem. Soc. 127, 10314-10322 (2005).
[CrossRef] [PubMed]

Campagnola, P. J.

R. LaComb, O. Nadiarnykh, and P. J. Campagnola, “Quantitative second harmonic generation imaging of the diseased state osteogenesis imperfecta: experiment and simulation,” Biophys. J. 94, 4504-4515 (2008).
[CrossRef] [PubMed]

R. LaComb, O. Nadiarnykh, S. S. Townsend, and P. J. Campagnola, “Phase matching considerations in second-harmonic generation from tissues: effects on emission directionality, conversion efficiency, and observed morphology,” Opt. Commun. 281, 1823-1832 (2008).
[CrossRef]

R. LaComb, O. Nadiarnykh, S. Carey, and P. J. Campagnola, “Quantitative second harmonic generation imaging and modeling of the optical clearing mechanism in striated muscle and tendon,” J. Biomed. Opt. 13, 021109 (2008).
[CrossRef] [PubMed]

O. Nadiarnykh, R. B. LaComb, and P. J. Campagnola, “Coherent and incoherent SHG in fibrillar cellulose matrices,” Opt. Express 15, 3348-3360 (2007).
[CrossRef] [PubMed]

S. Plotnikov, V. Junaja, A. B. Isaacson, W. A. Mohler, and P. J. Campagnola, “Optical clearing for improved contrast in second harmonic generation imaging of skeletal muscle,” Biophys. J. 90, 328-339 (2006).
[CrossRef]

Cansell, F.

F. Cansell, D. Fabre, and J. P. Petitet, “Raman spectroscopy of DMSO and DMSO-H2O mixtures (32 mol % of DMSO) up to 20 GPa,” Physica B 182, 195-200 (1992).
[CrossRef]

Carey, S.

R. LaComb, O. Nadiarnykh, S. Carey, and P. J. Campagnola, “Quantitative second harmonic generation imaging and modeling of the optical clearing mechanism in striated muscle and tendon,” J. Biomed. Opt. 13, 021109 (2008).
[CrossRef] [PubMed]

Chan, E. K.

G. Vargas, E. K. Chan, J. K. Barton, H. G. Rylander, and A. J. Welch, “Use of an agent to reduce scattering in skin,” Lasers Surg. Med. 24, 133-141 (1999).
[CrossRef] [PubMed]

Chan, K. F.

G. Vargas, K. F. Chan, S. L. Thomsen, and A. J. Welch, “Use of osmotically active agents to alter optical properties of tissue: effects on the detected fluorescence signal measured through skin,” Lasers Surg. Med. 29, 213-220 (2001).
[CrossRef] [PubMed]

Chan, M. C.

Chen, E.

B. Choi, L. Tsu, E. Chen, T. S. Ishak, S. M. Iskandar, S. Chess, and J. S. Nelson, “Determination of chemical agent optical clearing potential using in vitro human skin,” Lasers Surg. Med. 36, 72-75 (2005).
[CrossRef] [PubMed]

Chen, Y. C.

Cheng, J. X.

Chess, S.

B. Choi, L. Tsu, E. Chen, T. S. Ishak, S. M. Iskandar, S. Chess, and J. S. Nelson, “Determination of chemical agent optical clearing potential using in vitro human skin,” Lasers Surg. Med. 36, 72-75 (2005).
[CrossRef] [PubMed]

Choi, B.

J. Hirshburg, B. Choi, J. S. Nelson, and A. T. Yeh, “Collagen solubility correlates with skin optical clearing,” J Biomed. Opt. 11, 040501 (2006).
[CrossRef] [PubMed]

B. Choi, L. Tsu, E. Chen, T. S. Ishak, S. M. Iskandar, S. Chess, and J. S. Nelson, “Determination of chemical agent optical clearing potential using in vitro human skin,” Lasers Surg. Med. 36, 72-75 (2005).
[CrossRef] [PubMed]

Christie, R.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

Chu, S. W.

Cicchi, R.

Côte, D.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côte, C. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering (CARS) microscopy,” Proc. Natl. Acad Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Dartigalongue, T.

A. M. Pena, T. Boulesteix, T. Dartigalongue, and M. C. Schanne-Klein, “Chiroptical effects in the second harmonic signal of collagens I and IV,” J. Am. Chem. Soc. 127, 10314-10322 (2005).
[CrossRef] [PubMed]

Elder, J. B.

R. K. Wang, X., Y. He, and J. B. Elder, “Investigation of optical clearing of gastric tissue immersed with hyperosmotic agents,” IEEE J. Sel. Top. Quantum Electron. 9, 234-242 (2003).
[CrossRef]

R. K. Wang, X. Xu, V. V. Tuchin, and J. B. Elder, “Concurrent enhancement of imaging depth and contrast for optical coherence tomography by hyperosmotic agents,” J. Opt. Soc. Am. B 18, 948-953 (2001).
[CrossRef]

Evans, C. L.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côte, C. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering (CARS) microscopy,” Proc. Natl. Acad Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Fabre, D.

F. Cansell, D. Fabre, and J. P. Petitet, “Raman spectroscopy of DMSO and DMSO-H2O mixtures (32 mol % of DMSO) up to 20 GPa,” Physica B 182, 195-200 (1992).
[CrossRef]

He, Y.

Y. He and R. K. Wang, “Dynamic optical clearing effect of tissue impregnated with hyperosmotic agents and studied with optical coherence tomography,” J. Biomed. Opt. 9, 200-206 (2004).
[CrossRef] [PubMed]

R. K. Wang, X., Y. He, and J. B. Elder, “Investigation of optical clearing of gastric tissue immersed with hyperosmotic agents,” IEEE J. Sel. Top. Quantum Electron. 9, 234-242 (2003).
[CrossRef]

Hirshburg, J.

J. Hirshburg, B. Choi, J. S. Nelson, and A. T. Yeh, “Collagen solubility correlates with skin optical clearing,” J Biomed. Opt. 11, 040501 (2006).
[CrossRef] [PubMed]

Hsiao, I. C.

Hyman, B. T.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

Isaacson, A. B.

S. Plotnikov, V. Junaja, A. B. Isaacson, W. A. Mohler, and P. J. Campagnola, “Optical clearing for improved contrast in second harmonic generation imaging of skeletal muscle,” Biophys. J. 90, 328-339 (2006).
[CrossRef]

Ishak, T. S.

B. Choi, L. Tsu, E. Chen, T. S. Ishak, S. M. Iskandar, S. Chess, and J. S. Nelson, “Determination of chemical agent optical clearing potential using in vitro human skin,” Lasers Surg. Med. 36, 72-75 (2005).
[CrossRef] [PubMed]

Iskandar, S. M.

B. Choi, L. Tsu, E. Chen, T. S. Ishak, S. M. Iskandar, S. Chess, and J. S. Nelson, “Determination of chemical agent optical clearing potential using in vitro human skin,” Lasers Surg. Med. 36, 72-75 (2005).
[CrossRef] [PubMed]

Junaja, V.

S. Plotnikov, V. Junaja, A. B. Isaacson, W. A. Mohler, and P. J. Campagnola, “Optical clearing for improved contrast in second harmonic generation imaging of skeletal muscle,” Biophys. J. 90, 328-339 (2006).
[CrossRef]

Kon, I. L.

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2, 401-417 (1997).
[CrossRef]

LaComb, R.

R. LaComb, O. Nadiarnykh, S. Carey, and P. J. Campagnola, “Quantitative second harmonic generation imaging and modeling of the optical clearing mechanism in striated muscle and tendon,” J. Biomed. Opt. 13, 021109 (2008).
[CrossRef] [PubMed]

R. LaComb, O. Nadiarnykh, S. S. Townsend, and P. J. Campagnola, “Phase matching considerations in second-harmonic generation from tissues: effects on emission directionality, conversion efficiency, and observed morphology,” Opt. Commun. 281, 1823-1832 (2008).
[CrossRef]

R. LaComb, O. Nadiarnykh, and P. J. Campagnola, “Quantitative second harmonic generation imaging of the diseased state osteogenesis imperfecta: experiment and simulation,” Biophys. J. 94, 4504-4515 (2008).
[CrossRef] [PubMed]

LaComb, R. B.

Légaré, F.

F. Légaré, C. Pfeffer, and B. R. Olsen, “The role of backscattering in SHG tissue imaging,” Biophys. J. 93, 1312-1320(2007).
[CrossRef] [PubMed]

Leonardi, L.

L. Leonardi, A. Ruggeri, N. Roveri, A. Bigi, and E. Reale, “Light microscopy, electron microscopy, and x-ray diffraction analysis of glycerinated collagen fibers,” J. Ultrastruct. Res. 85, 228-237 (1983).
[CrossRef] [PubMed]

Lin, B. L.

Lin, C.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côte, C. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering (CARS) microscopy,” Proc. Natl. Acad Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Lin, C. H.

Maksimova, I. L.

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2, 401-417 (1997).
[CrossRef]

Mavlutov, A. H.

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2, 401-417 (1997).
[CrossRef]

Mishin, A. A.

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2, 401-417 (1997).
[CrossRef]

Mohler, W. A.

S. Plotnikov, V. Junaja, A. B. Isaacson, W. A. Mohler, and P. J. Campagnola, “Optical clearing for improved contrast in second harmonic generation imaging of skeletal muscle,” Biophys. J. 90, 328-339 (2006).
[CrossRef]

Nadiarnykh, O.

R. LaComb, O. Nadiarnykh, S. Carey, and P. J. Campagnola, “Quantitative second harmonic generation imaging and modeling of the optical clearing mechanism in striated muscle and tendon,” J. Biomed. Opt. 13, 021109 (2008).
[CrossRef] [PubMed]

R. LaComb, O. Nadiarnykh, and P. J. Campagnola, “Quantitative second harmonic generation imaging of the diseased state osteogenesis imperfecta: experiment and simulation,” Biophys. J. 94, 4504-4515 (2008).
[CrossRef] [PubMed]

R. LaComb, O. Nadiarnykh, S. S. Townsend, and P. J. Campagnola, “Phase matching considerations in second-harmonic generation from tissues: effects on emission directionality, conversion efficiency, and observed morphology,” Opt. Commun. 281, 1823-1832 (2008).
[CrossRef]

O. Nadiarnykh, R. B. LaComb, and P. J. Campagnola, “Coherent and incoherent SHG in fibrillar cellulose matrices,” Opt. Express 15, 3348-3360 (2007).
[CrossRef] [PubMed]

Nelson, J. S.

J. Hirshburg, B. Choi, J. S. Nelson, and A. T. Yeh, “Collagen solubility correlates with skin optical clearing,” J Biomed. Opt. 11, 040501 (2006).
[CrossRef] [PubMed]

B. Choi, L. Tsu, E. Chen, T. S. Ishak, S. M. Iskandar, S. Chess, and J. S. Nelson, “Determination of chemical agent optical clearing potential using in vitro human skin,” Lasers Surg. Med. 36, 72-75 (2005).
[CrossRef] [PubMed]

A. T. Yeh, J. S. Nelson, and B. J. Tromberg, “Reversible dissociation of collagen in tissues,” J. Invest. Dermatol. 121, 1332-1335 (2003).
[CrossRef] [PubMed]

Nikitin, A. Y.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

Odland, G. F.

G. F. Odland, “Structure of the Skin,” in Physiology, Biochemistry and Molecular Biology of the Skin (Oxford University Press, 1991), pp. 3-62.

Olsen, B. R.

F. Légaré, C. Pfeffer, and B. R. Olsen, “The role of backscattering in SHG tissue imaging,” Biophys. J. 93, 1312-1320(2007).
[CrossRef] [PubMed]

Pavone, F. S.

Pena, A. M.

A. M. Pena, T. Boulesteix, T. Dartigalongue, and M. C. Schanne-Klein, “Chiroptical effects in the second harmonic signal of collagens I and IV,” J. Am. Chem. Soc. 127, 10314-10322 (2005).
[CrossRef] [PubMed]

Petitet, J. P.

F. Cansell, D. Fabre, and J. P. Petitet, “Raman spectroscopy of DMSO and DMSO-H2O mixtures (32 mol % of DMSO) up to 20 GPa,” Physica B 182, 195-200 (1992).
[CrossRef]

Pfeffer, C.

F. Légaré, C. Pfeffer, and B. R. Olsen, “The role of backscattering in SHG tissue imaging,” Biophys. J. 93, 1312-1320(2007).
[CrossRef] [PubMed]

Plotnikov, S.

S. Plotnikov, V. Junaja, A. B. Isaacson, W. A. Mohler, and P. J. Campagnola, “Optical clearing for improved contrast in second harmonic generation imaging of skeletal muscle,” Biophys. J. 90, 328-339 (2006).
[CrossRef]

Potma, E. O.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côte, C. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering (CARS) microscopy,” Proc. Natl. Acad Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Puoris'haag, M.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côte, C. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering (CARS) microscopy,” Proc. Natl. Acad Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Reale, E.

L. Leonardi, A. Ruggeri, N. Roveri, A. Bigi, and E. Reale, “Light microscopy, electron microscopy, and x-ray diffraction analysis of glycerinated collagen fibers,” J. Ultrastruct. Res. 85, 228-237 (1983).
[CrossRef] [PubMed]

Roveri, N.

L. Leonardi, A. Ruggeri, N. Roveri, A. Bigi, and E. Reale, “Light microscopy, electron microscopy, and x-ray diffraction analysis of glycerinated collagen fibers,” J. Ultrastruct. Res. 85, 228-237 (1983).
[CrossRef] [PubMed]

Ruggeri, A.

L. Leonardi, A. Ruggeri, N. Roveri, A. Bigi, and E. Reale, “Light microscopy, electron microscopy, and x-ray diffraction analysis of glycerinated collagen fibers,” J. Ultrastruct. Res. 85, 228-237 (1983).
[CrossRef] [PubMed]

Rylander, H. G.

G. Vargas, E. K. Chan, J. K. Barton, H. G. Rylander, and A. J. Welch, “Use of an agent to reduce scattering in skin,” Lasers Surg. Med. 24, 133-141 (1999).
[CrossRef] [PubMed]

Schanne-Klein, M. C.

A. M. Pena, T. Boulesteix, T. Dartigalongue, and M. C. Schanne-Klein, “Chiroptical effects in the second harmonic signal of collagens I and IV,” J. Am. Chem. Soc. 127, 10314-10322 (2005).
[CrossRef] [PubMed]

Sun, C. K.

Thomsen, S. L.

G. Vargas, K. F. Chan, S. L. Thomsen, and A. J. Welch, “Use of osmotically active agents to alter optical properties of tissue: effects on the detected fluorescence signal measured through skin,” Lasers Surg. Med. 29, 213-220 (2001).
[CrossRef] [PubMed]

Townsend, S. S.

R. LaComb, O. Nadiarnykh, S. S. Townsend, and P. J. Campagnola, “Phase matching considerations in second-harmonic generation from tissues: effects on emission directionality, conversion efficiency, and observed morphology,” Opt. Commun. 281, 1823-1832 (2008).
[CrossRef]

Tromberg, B. J.

A. T. Yeh, J. S. Nelson, and B. J. Tromberg, “Reversible dissociation of collagen in tissues,” J. Invest. Dermatol. 121, 1332-1335 (2003).
[CrossRef] [PubMed]

Tsai, S. P.

Tsu, L.

B. Choi, L. Tsu, E. Chen, T. S. Ishak, S. M. Iskandar, S. Chess, and J. S. Nelson, “Determination of chemical agent optical clearing potential using in vitro human skin,” Lasers Surg. Med. 36, 72-75 (2005).
[CrossRef] [PubMed]

Tuchin, V.

V. Tuchin, Tissue Optics (SPIE Press, 2007).
[CrossRef]

Tuchin, V. V.

V. V. Tuchin, “Optical clearing of tissues and blood using the immersion method,” J. Phys. D 38, 2497-2518 (2005).
[CrossRef]

R. K. Wang, X. Xu, V. V. Tuchin, and J. B. Elder, “Concurrent enhancement of imaging depth and contrast for optical coherence tomography by hyperosmotic agents,” J. Opt. Soc. Am. B 18, 948-953 (2001).
[CrossRef]

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2, 401-417 (1997).
[CrossRef]

Vargas, G.

G. Vargas, K. F. Chan, S. L. Thomsen, and A. J. Welch, “Use of osmotically active agents to alter optical properties of tissue: effects on the detected fluorescence signal measured through skin,” Lasers Surg. Med. 29, 213-220 (2001).
[CrossRef] [PubMed]

G. Vargas, E. K. Chan, J. K. Barton, H. G. Rylander, and A. J. Welch, “Use of an agent to reduce scattering in skin,” Lasers Surg. Med. 24, 133-141 (1999).
[CrossRef] [PubMed]

Volkmer, A.

Wang, R. K.

Y. He and R. K. Wang, “Dynamic optical clearing effect of tissue impregnated with hyperosmotic agents and studied with optical coherence tomography,” J. Biomed. Opt. 9, 200-206 (2004).
[CrossRef] [PubMed]

X. Xu and R. K. Wang, “The role of water desorption on optical clearing of biotissue: Studied with near infrared reflectance spectroscopy,” Med. Phys. 30, 1246-1253 (2003).
[CrossRef] [PubMed]

R. K. Wang, X., Y. He, and J. B. Elder, “Investigation of optical clearing of gastric tissue immersed with hyperosmotic agents,” IEEE J. Sel. Top. Quantum Electron. 9, 234-242 (2003).
[CrossRef]

R. K. Wang, X. Xu, V. V. Tuchin, and J. B. Elder, “Concurrent enhancement of imaging depth and contrast for optical coherence tomography by hyperosmotic agents,” J. Opt. Soc. Am. B 18, 948-953 (2001).
[CrossRef]

Webb, W. W.

R. M. Williams, W. R. Zipfel, and W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88, 1377-1386 (2005).
[CrossRef]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

Welch, A. J.

G. Vargas, K. F. Chan, S. L. Thomsen, and A. J. Welch, “Use of osmotically active agents to alter optical properties of tissue: effects on the detected fluorescence signal measured through skin,” Lasers Surg. Med. 29, 213-220 (2001).
[CrossRef] [PubMed]

G. Vargas, E. K. Chan, J. K. Barton, H. G. Rylander, and A. J. Welch, “Use of an agent to reduce scattering in skin,” Lasers Surg. Med. 24, 133-141 (1999).
[CrossRef] [PubMed]

Williams, R. M.

R. M. Williams, W. R. Zipfel, and W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88, 1377-1386 (2005).
[CrossRef]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

Xie, X. S.

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côte, C. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering (CARS) microscopy,” Proc. Natl. Acad Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef] [PubMed]

J. X. Cheng, A. Volkmer, and X. S. Xie, “Theoretical and experimental characterization of coherent anti-Stokes Raman scattering microscopy,” J. Opt. Soc. Am. B 19, 1363-1375(2002).
[CrossRef]

Xu, X.

X. Xu and R. K. Wang, “The role of water desorption on optical clearing of biotissue: Studied with near infrared reflectance spectroscopy,” Med. Phys. 30, 1246-1253 (2003).
[CrossRef] [PubMed]

R. K. Wang, X. Xu, V. V. Tuchin, and J. B. Elder, “Concurrent enhancement of imaging depth and contrast for optical coherence tomography by hyperosmotic agents,” J. Opt. Soc. Am. B 18, 948-953 (2001).
[CrossRef]

Yeh, A. T.

J. Hirshburg, B. Choi, J. S. Nelson, and A. T. Yeh, “Collagen solubility correlates with skin optical clearing,” J Biomed. Opt. 11, 040501 (2006).
[CrossRef] [PubMed]

A. T. Yeh, J. S. Nelson, and B. J. Tromberg, “Reversible dissociation of collagen in tissues,” J. Invest. Dermatol. 121, 1332-1335 (2003).
[CrossRef] [PubMed]

Zimnyakov, D. A.

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2, 401-417 (1997).
[CrossRef]

Zipfel, W. R.

R. M. Williams, W. R. Zipfel, and W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88, 1377-1386 (2005).
[CrossRef]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

Biophys. J. (4)

S. Plotnikov, V. Junaja, A. B. Isaacson, W. A. Mohler, and P. J. Campagnola, “Optical clearing for improved contrast in second harmonic generation imaging of skeletal muscle,” Biophys. J. 90, 328-339 (2006).
[CrossRef]

F. Légaré, C. Pfeffer, and B. R. Olsen, “The role of backscattering in SHG tissue imaging,” Biophys. J. 93, 1312-1320(2007).
[CrossRef] [PubMed]

R. M. Williams, W. R. Zipfel, and W. W. Webb, “Interpreting second-harmonic generation images of collagen I fibrils,” Biophys. J. 88, 1377-1386 (2005).
[CrossRef]

R. LaComb, O. Nadiarnykh, and P. J. Campagnola, “Quantitative second harmonic generation imaging of the diseased state osteogenesis imperfecta: experiment and simulation,” Biophys. J. 94, 4504-4515 (2008).
[CrossRef] [PubMed]

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

R. K. Wang, X., Y. He, and J. B. Elder, “Investigation of optical clearing of gastric tissue immersed with hyperosmotic agents,” IEEE J. Sel. Top. Quantum Electron. 9, 234-242 (2003).
[CrossRef]

J Biomed. Opt. (1)

J. Hirshburg, B. Choi, J. S. Nelson, and A. T. Yeh, “Collagen solubility correlates with skin optical clearing,” J Biomed. Opt. 11, 040501 (2006).
[CrossRef] [PubMed]

J. Am. Chem. Soc. (1)

A. M. Pena, T. Boulesteix, T. Dartigalongue, and M. C. Schanne-Klein, “Chiroptical effects in the second harmonic signal of collagens I and IV,” J. Am. Chem. Soc. 127, 10314-10322 (2005).
[CrossRef] [PubMed]

J. Biomed. Opt. (3)

R. LaComb, O. Nadiarnykh, S. Carey, and P. J. Campagnola, “Quantitative second harmonic generation imaging and modeling of the optical clearing mechanism in striated muscle and tendon,” J. Biomed. Opt. 13, 021109 (2008).
[CrossRef] [PubMed]

Y. He and R. K. Wang, “Dynamic optical clearing effect of tissue impregnated with hyperosmotic agents and studied with optical coherence tomography,” J. Biomed. Opt. 9, 200-206 (2004).
[CrossRef] [PubMed]

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2, 401-417 (1997).
[CrossRef]

J. Invest. Dermatol. (1)

A. T. Yeh, J. S. Nelson, and B. J. Tromberg, “Reversible dissociation of collagen in tissues,” J. Invest. Dermatol. 121, 1332-1335 (2003).
[CrossRef] [PubMed]

J. Opt. Soc. Am. B (2)

J. Phys. D (1)

V. V. Tuchin, “Optical clearing of tissues and blood using the immersion method,” J. Phys. D 38, 2497-2518 (2005).
[CrossRef]

J. Ultrastruct. Res. (1)

L. Leonardi, A. Ruggeri, N. Roveri, A. Bigi, and E. Reale, “Light microscopy, electron microscopy, and x-ray diffraction analysis of glycerinated collagen fibers,” J. Ultrastruct. Res. 85, 228-237 (1983).
[CrossRef] [PubMed]

Lasers Surg. Med. (3)

G. Vargas, K. F. Chan, S. L. Thomsen, and A. J. Welch, “Use of osmotically active agents to alter optical properties of tissue: effects on the detected fluorescence signal measured through skin,” Lasers Surg. Med. 29, 213-220 (2001).
[CrossRef] [PubMed]

B. Choi, L. Tsu, E. Chen, T. S. Ishak, S. M. Iskandar, S. Chess, and J. S. Nelson, “Determination of chemical agent optical clearing potential using in vitro human skin,” Lasers Surg. Med. 36, 72-75 (2005).
[CrossRef] [PubMed]

G. Vargas, E. K. Chan, J. K. Barton, H. G. Rylander, and A. J. Welch, “Use of an agent to reduce scattering in skin,” Lasers Surg. Med. 24, 133-141 (1999).
[CrossRef] [PubMed]

Med. Phys. (1)

X. Xu and R. K. Wang, “The role of water desorption on optical clearing of biotissue: Studied with near infrared reflectance spectroscopy,” Med. Phys. 30, 1246-1253 (2003).
[CrossRef] [PubMed]

Opt. Commun. (1)

R. LaComb, O. Nadiarnykh, S. S. Townsend, and P. J. Campagnola, “Phase matching considerations in second-harmonic generation from tissues: effects on emission directionality, conversion efficiency, and observed morphology,” Opt. Commun. 281, 1823-1832 (2008).
[CrossRef]

Opt. Express (3)

Physica B (1)

F. Cansell, D. Fabre, and J. P. Petitet, “Raman spectroscopy of DMSO and DMSO-H2O mixtures (32 mol % of DMSO) up to 20 GPa,” Physica B 182, 195-200 (1992).
[CrossRef]

Proc. Natl. Acad Sci. U.S.A. (1)

C. L. Evans, E. O. Potma, M. Puoris'haag, D. Côte, C. Lin, and X. S. Xie, “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering (CARS) microscopy,” Proc. Natl. Acad Sci. U.S.A. 102, 16807-16812 (2005).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (1)

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A. 100, 7075-7080 (2003).
[CrossRef] [PubMed]

Other (2)

G. F. Odland, “Structure of the Skin,” in Physiology, Biochemistry and Molecular Biology of the Skin (Oxford University Press, 1991), pp. 3-62.

V. Tuchin, Tissue Optics (SPIE Press, 2007).
[CrossRef]

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Figures (7)

Fig. 1
Fig. 1

Raman spectra of DMSO:water mixtures for different volume fractions of DMSO. The inset shows the shift of the center frequency of the CH 3 symmetric stretch vibration for different mole fractions of DMSO in water.

Fig. 2
Fig. 2

CARS of DMSO for different volume fractions in water. (a) CARS spectra for different v / v % of DMSO in water. (b) Relative CARS intensity at 2913 cm 1 for increasing volume fractions of DMSO in water.

Fig. 3
Fig. 3

CARS signal at 2913 cm 1 during skin optical clearing with DMSO. (a) F-CARS and E-CARS signals as a function of time after application of the clearing agent. The transmitted pump light ( 812.2 nm ) is also shown. (b) Extracted transmittance of CARS radiation in the tissue and local concentration of the clearing agent during the optical clearing process.

Fig. 4
Fig. 4

Comparison of the tissue attenuation coefficient at the SHG wavelength ( 406 nm ) and at the CARS wavelength ( 656 nm ) measured at different levels of optical clearing. The solid line is a linear fit, which is used to correlate the CARS transmittance to the SHG transmittance.

Fig. 5
Fig. 5

SHG images of dermal collagen (a) before and (b) after 3 h of immersion with DMSO . The scale bar is 50 μm .

Fig. 6
Fig. 6

Variation of SHG, F-CARS, and E-CARS signals during skin optical clearing (a). The extracted transmittance of the CARS radiation, along with the derived transmittance for the SHG light, is given in (b).

Fig. 7
Fig. 7

CARS transmittance and SHG response as a function of DMSO concentration. (a) CARS transmittance for different concentrations of DMSO. (b) Extracted SHG signal as a function of DMSO concentration. The oscillatory trend observed at higher concentrations relates to long-term laser fluctuations rather than changes in the SHG response.

Equations (4)

Equations on this page are rendered with MathJax. Learn more.

S as F = f F S as ( c ) e g as L ,
S as E = f E S as ( c ) [ 1 e g as L ] ,
e g as L = [ f F f E S as E S as F + 1 ] 1 .
S 2 ω F = f F S 2 ω ( r ) e g 2 ω L ,

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