Abstract

Polarization responses in Second Harmonic Generation (SHG) imaging microscopy are a valuable method to quantify aspects of tissue structure, and may be a means to differentiate normal and diseased tissues. Due to multiple scattering, the polarization data is lost in turbid tissues. Here we investigate if this information can be retained through the use of optical clearing which greatly reduces the scattering coefficient and increases the corresponding mean free path. To this end, we have measured the SHG intensity as a function of laser polarization and the SHG signal anisotropy in murine tendon and striated muscle over a depth range of 200 microns. We find that the laser polarization is highly randomized in the uncleared tissues at depths corresponding to only 2-3 scattering collisions (50-10 microns). This depolarization of the laser is also reflected in the randomized anisotropy of the SHG signal as it is created over a range of polarization states. In strong contrast, both polarization signatures are significantly retained through ~200 microns of tissue thickness following treatment with 50% glycerol. Moreover, the measured polarization responses for both tendon and striated muscle are consistent with the extent of reduction of the respective scattering coefficients upon clearing. We suggest the method will be applicable to SHG imaging of connective disorders as well as cancer through several hundred microns of extracellular matrix.

© 2009 Optical Society of America

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    [CrossRef] [PubMed]
  2. R. Lacomb, O. Nadiarnykh, and P. J. Campagnola, "Quantitative SHG imaging of the diseased state Osteogenesis Imperfecta: Experiment and Simulation," Biophys J 94, 4104- (2008).
    [CrossRef]
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    [CrossRef] [PubMed]
  4. E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
    [CrossRef] [PubMed]
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    [CrossRef]
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    [CrossRef] [PubMed]
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  20. X. Q. Xu, L. F. Yu, and Z. P. Chen, "Optical clearing of flowing blood using dextrans with spectral domain optical coherence tomography," J. Biomed. Opt. 13, 021107 (2008).
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    [CrossRef] [PubMed]
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    [CrossRef]
  23. E. A. Genina, A. N. Bashkatov, Y. P. Sinichkin, and V. V. Tuchin, "Optical clearing of the eye sclera in vivo caused by glucose," Quantum Electron. 36, 1119-1124 (2006).
    [CrossRef]
  24. M. G. Ghosn, E. F. Carbajal, N. A. Befrui, V. V. Tuchin, and K. V. Larin, "Differential permeability rate and percent clearing of glucose in different regions in rabbit sclera," J. Biomed. Opt. 13, 021110 (2008).
    [CrossRef] [PubMed]
  25. M. V. Schulmerich, J. H. Cole, K. A. Dooley, M. D. Morris, J. M. Kreider, and S. A. Goldstein, "Optical clearing in transcutaneous Raman spectroscopy of murine cortical bone tissue," J. Biomed. Opt. 13, 021108 (2008).
    [CrossRef] [PubMed]
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    [CrossRef]
  27. V. V. Tuchin, "Optical clearing of tissues and blood using the immersion method," J. Phys D 38, 2497-2518 (2005).
    [CrossRef]
  28. R. LaComb, O. Nadiarnykh, S. Carey, and P. J. Campagnola, "Quantitative SHG imaging and modeling of the optical clearing mechanism in striated muscle and tendon," J. Biomed. Opt. 13, 021109 (2008).
    [CrossRef] [PubMed]
  29. A. T. Yeh and J. Hirshburg, "Molecular interactions of exogenous chemical agents with collagen--implications for tissue optical clearing," J Biomed. Opt. 11, 014003 (2006).
    [CrossRef] [PubMed]
  30. 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]
  31. O. Nadiarnykh, R. B. LaComb, P. J. Campagnola, and W. A. Mohler, "Coherent and incoherent SHG in fibrillar cellulose matrices," Opt. Express 15, 3348-3360 (2007).
    [CrossRef] [PubMed]
  32. X. Wang and L. V. Wang, "Propagation of polarized light in birefringent turbid media: a Monte Carlo study," J. Biomed. Opt. 7, 279-290 (2002).
    [CrossRef] [PubMed]
  33. P. Stoller, B.-M. Kim, A. M. Rubinchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J.Biomed. Opt. 7, 205-214 (2001).
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    [CrossRef]
  35. R. K. K. Wang, X. Q. Xu, Y. H. He, and J. B. Elder, "Investigation of optical clearing of gastric tissue immersed with hyperosmotic agents," IEEE J. Select. Top. Quantum Electron. 9, 234-242 (2003).
    [CrossRef]
  36. J. Yoon, T. Son, E. H. Choi, B. Choi, J. S. Nelson, and B. Jung, "Enhancement of optical skin clearing efficacy using a microneedle roller," J. Biomed. Opt. 13, 021103 (2008).
    [CrossRef] [PubMed]

2008 (9)

R. Lacomb, O. Nadiarnykh, and P. J. Campagnola, "Quantitative SHG imaging of the diseased state Osteogenesis Imperfecta: Experiment and Simulation," Biophys J 94, 4104- (2008).
[CrossRef]

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

J. Y. Jiang, M. Boese, P. Turner, and R. K. K. Wang, "Penetration kinetics of dimethyl sulphoxide and glycerol in dynamic optical clearing of porcine skin tissue in vitro studied by Fourier transform infrared spectroscopic imaging," J. Biomed. Opt. 13, 021105 (2008).
[CrossRef] [PubMed]

X. Q. Xu, L. F. Yu, and Z. P. Chen, "Optical clearing of flowing blood using dextrans with spectral domain optical coherence tomography," J. Biomed. Opt. 13, 021107 (2008).
[CrossRef] [PubMed]

M. G. Ghosn, E. F. Carbajal, N. A. Befrui, V. V. Tuchin, and K. V. Larin, "Differential permeability rate and percent clearing of glucose in different regions in rabbit sclera," J. Biomed. Opt. 13, 021110 (2008).
[CrossRef] [PubMed]

M. V. Schulmerich, J. H. Cole, K. A. Dooley, M. D. Morris, J. M. Kreider, and S. A. Goldstein, "Optical clearing in transcutaneous Raman spectroscopy of murine cortical bone tissue," J. Biomed. Opt. 13, 021108 (2008).
[CrossRef] [PubMed]

R. LaComb, O. Nadiarnykh, S. Carey, and P. J. Campagnola, "Quantitative SHG 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]

J. Yoon, T. Son, E. H. Choi, B. Choi, J. S. Nelson, and B. Jung, "Enhancement of optical skin clearing efficacy using a microneedle roller," J. Biomed. Opt. 13, 021103 (2008).
[CrossRef] [PubMed]

2007 (4)

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

O. Nadiarnykh, S. Plotnikov, W. A. Mohler, I. Kalajzic, D. Redford-Badwal, and P. J. Campagnola, "Second Harmonic Generation imaging microscopy studies of Osteogenesis Imperfecta," J. Biomed. Opt. 12, 051805 (2007).
[CrossRef] [PubMed]

R. Cicchi, D. Massi, S. Sestini, P. Carli, V. De Giorgi, T. Lotti, and F. S. Pavone, "Multidimensional non-linear laser imaging of Basal Cell Carcinoma," Opt. Express 15, 10135-10148 (2007).
[CrossRef] [PubMed]

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, "In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12, 024014 (2007).
[CrossRef] [PubMed]

2006 (7)

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, "Characterization of the Myosin-based source for second-harmonic generation from muscle sarcomeres," Biophys J. 90, 693-703 (2006).
[CrossRef]

P. P. Provenzano, K. W. Eliceiri, J. M. Campbell, D. R. Inman, J. G. White, and P. J. Keely, "Collagen reorganization at the tumor-stromal interface facilitates local invasion," BMC Med. 4, 38 (2006).
[CrossRef] [PubMed]

S. J. Lin, S. H. Jee, C. J. Kuo, R. J. Wu, W. C. Lin, J. S. Chen, Y. H. Liao, C. J. Hsu, T. F. Tsai, Y. F. Chen, and C. Y. Dong, "Discrimination of basal cell carcinoma from normal dermal stroma by quantitative multiphoton imaging," Opt. Lett. 31, 2756-2758 (2006).
[CrossRef] [PubMed]

E. A. Genina, A. N. Bashkatov, Y. P. Sinichkin, and V. V. Tuchin, "Optical clearing of the eye sclera in vivo caused by glucose," Quantum Electron. 36, 1119-1124 (2006).
[CrossRef]

A. T. Yeh and J. Hirshburg, "Molecular interactions of exogenous chemical agents with collagen--implications for tissue optical clearing," J Biomed. Opt. 11, 014003 (2006).
[CrossRef] [PubMed]

S. Plotnikov, V. Juneja, 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]

C. E. Bigelow and T. H. Foster, "Confocal fluorescence polarization microscopy in turbid media: effects of scattering-induced depolarization," J. Opt. Soc. Am. A 23, 2932-2943 (2006).
[CrossRef]

2005 (1)

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

2004 (3)

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

M. H. Khan, B. Choi, S. Chess, K. M. Kelly, J. McCullough, and J. S. Nelson, "Optical clearing of in vivo human skin: Implications for light-based diagnostic imaging and therapeutics," Lasers Surg. Med. 34, 83-85 (2004).
[CrossRef] [PubMed]

M. Khan, B. Choi, S. Chess, J. McCullough, K. Kelly, and J. S. Nelson, "The use of topically applied chemical agents for optical clearing of skin to improve diagnostics and laser therapeutic applications," Lasers Surg. Med., 34, 407-13 (2004).

2003 (4)

A. N. Bashkatov, E. A. Genina, Y. P. Sinichkin, V. I. Kochubey, N. A. Lakodina, and V. V. Tuchin, "Glucose and mannitol diffusion in human dura mater," Biophys. J. 85, 3310-3318 (2003).
[CrossRef] [PubMed]

X. Q. Xu, R. K. Wang, and J. B. Elder, "Optical clearing effect on gastric tissues immersed with biocompatible chemical agents investigated by near infrared reflectance spectroscopy," J. Phys. D 36, 1707-1713 (2003).
[CrossRef]

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef] [PubMed]

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

2002 (3)

X. Wang and L. V. Wang, "Propagation of polarized light in birefringent turbid media: a Monte Carlo study," J. Biomed. Opt. 7, 279-290 (2002).
[CrossRef] [PubMed]

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).
[CrossRef]

V. V. Tuchin, X. Q. Xu, and R. K. Wang, "Dynamic optical coherence tomography in studies of optical clearing, sedimentation, and aggregation of immersed blood," Appl. Opt. 41, 258-271 (2002).
[CrossRef] [PubMed]

2001 (3)

1999 (1)

G. Vargas, E. K. Chan, J. K. Barton, H. G. Rylander, 3rd, and A. J. Welch, "Use of an agent to reduce scattering in skin," Lasers Surg. Med. 24, 133-141 (1999).
[CrossRef] [PubMed]

Adams, D.

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

Barton, J. K.

G. Vargas, E. K. Chan, J. K. Barton, H. G. Rylander, 3rd, and A. J. Welch, "Use of an agent to reduce scattering in skin," Lasers Surg. Med. 24, 133-141 (1999).
[CrossRef] [PubMed]

Bashkatov, A. N.

E. A. Genina, A. N. Bashkatov, Y. P. Sinichkin, and V. V. Tuchin, "Optical clearing of the eye sclera in vivo caused by glucose," Quantum Electron. 36, 1119-1124 (2006).
[CrossRef]

A. N. Bashkatov, E. A. Genina, Y. P. Sinichkin, V. I. Kochubey, N. A. Lakodina, and V. V. Tuchin, "Glucose and mannitol diffusion in human dura mater," Biophys. J. 85, 3310-3318 (2003).
[CrossRef] [PubMed]

Befrui, N. A.

M. G. Ghosn, E. F. Carbajal, N. A. Befrui, V. V. Tuchin, and K. V. Larin, "Differential permeability rate and percent clearing of glucose in different regions in rabbit sclera," J. Biomed. Opt. 13, 021110 (2008).
[CrossRef] [PubMed]

Bigelow, C. E.

Bird, D. K.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, "In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12, 024014 (2007).
[CrossRef] [PubMed]

Boese, M.

J. Y. Jiang, M. Boese, P. Turner, and R. K. K. Wang, "Penetration kinetics of dimethyl sulphoxide and glycerol in dynamic optical clearing of porcine skin tissue in vitro studied by Fourier transform infrared spectroscopic imaging," J. Biomed. Opt. 13, 021105 (2008).
[CrossRef] [PubMed]

Boucher, Y.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef] [PubMed]

Brown, E.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef] [PubMed]

Campagnola, P. J.

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

R. Lacomb, O. Nadiarnykh, and P. J. Campagnola, "Quantitative SHG imaging of the diseased state Osteogenesis Imperfecta: Experiment and Simulation," Biophys J 94, 4104- (2008).
[CrossRef]

R. LaComb, O. Nadiarnykh, S. Carey, and P. J. Campagnola, "Quantitative SHG 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]

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

O. Nadiarnykh, S. Plotnikov, W. A. Mohler, I. Kalajzic, D. Redford-Badwal, and P. J. Campagnola, "Second Harmonic Generation imaging microscopy studies of Osteogenesis Imperfecta," J. Biomed. Opt. 12, 051805 (2007).
[CrossRef] [PubMed]

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, "Characterization of the Myosin-based source for second-harmonic generation from muscle sarcomeres," Biophys J. 90, 693-703 (2006).
[CrossRef]

S. Plotnikov, V. Juneja, 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]

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).
[CrossRef]

Campbell, J. M.

P. P. Provenzano, K. W. Eliceiri, J. M. Campbell, D. R. Inman, J. G. White, and P. J. Keely, "Collagen reorganization at the tumor-stromal interface facilitates local invasion," BMC Med. 4, 38 (2006).
[CrossRef] [PubMed]

Carbajal, E. F.

M. G. Ghosn, E. F. Carbajal, N. A. Befrui, V. V. Tuchin, and K. V. Larin, "Differential permeability rate and percent clearing of glucose in different regions in rabbit sclera," J. Biomed. Opt. 13, 021110 (2008).
[CrossRef] [PubMed]

Carey, S.

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

Carli, P.

Chan, E. K.

G. Vargas, E. K. Chan, J. K. Barton, H. G. Rylander, 3rd, and A. J. Welch, "Use of an agent to reduce scattering in skin," Lasers Surg. Med. 24, 133-141 (1999).
[CrossRef] [PubMed]

Chen, J. S.

Chen, S.-Y.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Chen, Y. F.

Chen, Y.-C.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Chen, Z. P.

X. Q. Xu, L. F. Yu, and Z. P. Chen, "Optical clearing of flowing blood using dextrans with spectral domain optical coherence tomography," J. Biomed. Opt. 13, 021107 (2008).
[CrossRef] [PubMed]

Chern, G.-W.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Chess, S.

M. H. Khan, B. Choi, S. Chess, K. M. Kelly, J. McCullough, and J. S. Nelson, "Optical clearing of in vivo human skin: Implications for light-based diagnostic imaging and therapeutics," Lasers Surg. Med. 34, 83-85 (2004).
[CrossRef] [PubMed]

M. Khan, B. Choi, S. Chess, J. McCullough, K. Kelly, and J. S. Nelson, "The use of topically applied chemical agents for optical clearing of skin to improve diagnostics and laser therapeutic applications," Lasers Surg. Med., 34, 407-13 (2004).

Choi, B.

J. Yoon, T. Son, E. H. Choi, B. Choi, J. S. Nelson, and B. Jung, "Enhancement of optical skin clearing efficacy using a microneedle roller," J. Biomed. Opt. 13, 021103 (2008).
[CrossRef] [PubMed]

M. Khan, B. Choi, S. Chess, J. McCullough, K. Kelly, and J. S. Nelson, "The use of topically applied chemical agents for optical clearing of skin to improve diagnostics and laser therapeutic applications," Lasers Surg. Med., 34, 407-13 (2004).

M. H. Khan, B. Choi, S. Chess, K. M. Kelly, J. McCullough, and J. S. Nelson, "Optical clearing of in vivo human skin: Implications for light-based diagnostic imaging and therapeutics," Lasers Surg. Med. 34, 83-85 (2004).
[CrossRef] [PubMed]

Choi, E. H.

J. Yoon, T. Son, E. H. Choi, B. Choi, J. S. Nelson, and B. Jung, "Enhancement of optical skin clearing efficacy using a microneedle roller," J. Biomed. Opt. 13, 021103 (2008).
[CrossRef] [PubMed]

Chu, S.-W.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Cicchi, R.

Cole, J. H.

M. V. Schulmerich, J. H. Cole, K. A. Dooley, M. D. Morris, J. M. Kreider, and S. A. Goldstein, "Optical clearing in transcutaneous Raman spectroscopy of murine cortical bone tissue," J. Biomed. Opt. 13, 021108 (2008).
[CrossRef] [PubMed]

Da Silva, L. B.

P. Stoller, B.-M. Kim, A. M. Rubinchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J.Biomed. Opt. 7, 205-214 (2001).
[CrossRef]

Dauser, D.

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

De Giorgi, V.

diTomaso, E.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef] [PubMed]

Dong, C. Y.

Dooley, K. A.

M. V. Schulmerich, J. H. Cole, K. A. Dooley, M. D. Morris, J. M. Kreider, and S. A. Goldstein, "Optical clearing in transcutaneous Raman spectroscopy of murine cortical bone tissue," J. Biomed. Opt. 13, 021108 (2008).
[CrossRef] [PubMed]

Dougherty, R.

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

Eickhoff, J.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, "In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12, 024014 (2007).
[CrossRef] [PubMed]

Elder, J. B.

X. Q. Xu, R. K. Wang, and J. B. Elder, "Optical clearing effect on gastric tissues immersed with biocompatible chemical agents investigated by near infrared reflectance spectroscopy," J. Phys. D 36, 1707-1713 (2003).
[CrossRef]

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

Eliceiri, K. W.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, "In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12, 024014 (2007).
[CrossRef] [PubMed]

P. P. Provenzano, K. W. Eliceiri, J. M. Campbell, D. R. Inman, J. G. White, and P. J. Keely, "Collagen reorganization at the tumor-stromal interface facilitates local invasion," BMC Med. 4, 38 (2006).
[CrossRef] [PubMed]

Foster, T. H.

Gendron-Fitzpatrick, A.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, "In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12, 024014 (2007).
[CrossRef] [PubMed]

Genina, E. A.

E. A. Genina, A. N. Bashkatov, Y. P. Sinichkin, and V. V. Tuchin, "Optical clearing of the eye sclera in vivo caused by glucose," Quantum Electron. 36, 1119-1124 (2006).
[CrossRef]

A. N. Bashkatov, E. A. Genina, Y. P. Sinichkin, V. I. Kochubey, N. A. Lakodina, and V. V. Tuchin, "Glucose and mannitol diffusion in human dura mater," Biophys. J. 85, 3310-3318 (2003).
[CrossRef] [PubMed]

Ghosn, M. G.

M. G. Ghosn, E. F. Carbajal, N. A. Befrui, V. V. Tuchin, and K. V. Larin, "Differential permeability rate and percent clearing of glucose in different regions in rabbit sclera," J. Biomed. Opt. 13, 021110 (2008).
[CrossRef] [PubMed]

Goldstein, S. A.

M. V. Schulmerich, J. H. Cole, K. A. Dooley, M. D. Morris, J. M. Kreider, and S. A. Goldstein, "Optical clearing in transcutaneous Raman spectroscopy of murine cortical bone tissue," J. Biomed. Opt. 13, 021108 (2008).
[CrossRef] [PubMed]

He, Y. H.

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

Hirshburg, J.

A. T. Yeh and J. Hirshburg, "Molecular interactions of exogenous chemical agents with collagen--implications for tissue optical clearing," J Biomed. Opt. 11, 014003 (2006).
[CrossRef] [PubMed]

Hoppe, P. E.

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).
[CrossRef]

Hsu, C. J.

Inman, D. R.

P. P. Provenzano, K. W. Eliceiri, J. M. Campbell, D. R. Inman, J. G. White, and P. J. Keely, "Collagen reorganization at the tumor-stromal interface facilitates local invasion," BMC Med. 4, 38 (2006).
[CrossRef] [PubMed]

Isaacson, A. B.

S. Plotnikov, V. Juneja, 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]

Jain, R. K.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef] [PubMed]

Jee, S. H.

Jiang, J. Y.

J. Y. Jiang, M. Boese, P. Turner, and R. K. K. Wang, "Penetration kinetics of dimethyl sulphoxide and glycerol in dynamic optical clearing of porcine skin tissue in vitro studied by Fourier transform infrared spectroscopic imaging," J. Biomed. Opt. 13, 021105 (2008).
[CrossRef] [PubMed]

Joseph, C.

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

Juneja, V.

S. Plotnikov, V. Juneja, 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]

Jung, B.

J. Yoon, T. Son, E. H. Choi, B. Choi, J. S. Nelson, and B. Jung, "Enhancement of optical skin clearing efficacy using a microneedle roller," J. Biomed. Opt. 13, 021103 (2008).
[CrossRef] [PubMed]

Kalajzic, I.

O. Nadiarnykh, S. Plotnikov, W. A. Mohler, I. Kalajzic, D. Redford-Badwal, and P. J. Campagnola, "Second Harmonic Generation imaging microscopy studies of Osteogenesis Imperfecta," J. Biomed. Opt. 12, 051805 (2007).
[CrossRef] [PubMed]

Keely, P. J.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, "In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12, 024014 (2007).
[CrossRef] [PubMed]

P. P. Provenzano, K. W. Eliceiri, J. M. Campbell, D. R. Inman, J. G. White, and P. J. Keely, "Collagen reorganization at the tumor-stromal interface facilitates local invasion," BMC Med. 4, 38 (2006).
[CrossRef] [PubMed]

Keller, J. B.

Kelly, K.

M. Khan, B. Choi, S. Chess, J. McCullough, K. Kelly, and J. S. Nelson, "The use of topically applied chemical agents for optical clearing of skin to improve diagnostics and laser therapeutic applications," Lasers Surg. Med., 34, 407-13 (2004).

Kelly, K. M.

M. H. Khan, B. Choi, S. Chess, K. M. Kelly, J. McCullough, and J. S. Nelson, "Optical clearing of in vivo human skin: Implications for light-based diagnostic imaging and therapeutics," Lasers Surg. Med. 34, 83-85 (2004).
[CrossRef] [PubMed]

Kenny, A.

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

Khan, M.

M. Khan, B. Choi, S. Chess, J. McCullough, K. Kelly, and J. S. Nelson, "The use of topically applied chemical agents for optical clearing of skin to improve diagnostics and laser therapeutic applications," Lasers Surg. Med., 34, 407-13 (2004).

Khan, M. H.

M. H. Khan, B. Choi, S. Chess, K. M. Kelly, J. McCullough, and J. S. Nelson, "Optical clearing of in vivo human skin: Implications for light-based diagnostic imaging and therapeutics," Lasers Surg. Med. 34, 83-85 (2004).
[CrossRef] [PubMed]

Kiang, Y.-W.

Kim, B.-M.

P. Stoller, B.-M. Kim, A. M. Rubinchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J.Biomed. Opt. 7, 205-214 (2001).
[CrossRef]

Kochubey, V. I.

A. N. Bashkatov, E. A. Genina, Y. P. Sinichkin, V. I. Kochubey, N. A. Lakodina, and V. V. Tuchin, "Glucose and mannitol diffusion in human dura mater," Biophys. J. 85, 3310-3318 (2003).
[CrossRef] [PubMed]

Kreider, J. M.

M. V. Schulmerich, J. H. Cole, K. A. Dooley, M. D. Morris, J. M. Kreider, and S. A. Goldstein, "Optical clearing in transcutaneous Raman spectroscopy of murine cortical bone tissue," J. Biomed. Opt. 13, 021108 (2008).
[CrossRef] [PubMed]

Kuchel, G. A.

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

Kuo, C. J.

Lacomb, R.

R. Lacomb, O. Nadiarnykh, and P. J. Campagnola, "Quantitative SHG imaging of the diseased state Osteogenesis Imperfecta: Experiment and Simulation," Biophys J 94, 4104- (2008).
[CrossRef]

R. LaComb, O. Nadiarnykh, S. Carey, and P. J. Campagnola, "Quantitative SHG 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]

LaComb, R. B.

Lakodina, N. A.

A. N. Bashkatov, E. A. Genina, Y. P. Sinichkin, V. I. Kochubey, N. A. Lakodina, and V. V. Tuchin, "Glucose and mannitol diffusion in human dura mater," Biophys. J. 85, 3310-3318 (2003).
[CrossRef] [PubMed]

Larin, K. V.

M. G. Ghosn, E. F. Carbajal, N. A. Befrui, V. V. Tuchin, and K. V. Larin, "Differential permeability rate and percent clearing of glucose in different regions in rabbit sclera," J. Biomed. Opt. 13, 021110 (2008).
[CrossRef] [PubMed]

Liao, Y. H.

Lin, B.-L.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Lin, S. J.

Lin, W. C.

Lotti, T.

Malone, C. J.

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).
[CrossRef]

Massi, D.

McCullough, J.

M. H. Khan, B. Choi, S. Chess, K. M. Kelly, J. McCullough, and J. S. Nelson, "Optical clearing of in vivo human skin: Implications for light-based diagnostic imaging and therapeutics," Lasers Surg. Med. 34, 83-85 (2004).
[CrossRef] [PubMed]

M. Khan, B. Choi, S. Chess, J. McCullough, K. Kelly, and J. S. Nelson, "The use of topically applied chemical agents for optical clearing of skin to improve diagnostics and laser therapeutic applications," Lasers Surg. Med., 34, 407-13 (2004).

McKee, T.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef] [PubMed]

Millard, A. C.

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, "Characterization of the Myosin-based source for second-harmonic generation from muscle sarcomeres," Biophys J. 90, 693-703 (2006).
[CrossRef]

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).
[CrossRef]

Mohler, W. A.

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

O. Nadiarnykh, S. Plotnikov, W. A. Mohler, I. Kalajzic, D. Redford-Badwal, and P. J. Campagnola, "Second Harmonic Generation imaging microscopy studies of Osteogenesis Imperfecta," J. Biomed. Opt. 12, 051805 (2007).
[CrossRef] [PubMed]

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

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, "Characterization of the Myosin-based source for second-harmonic generation from muscle sarcomeres," Biophys J. 90, 693-703 (2006).
[CrossRef]

S. Plotnikov, V. Juneja, 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]

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).
[CrossRef]

Morris, M. D.

M. V. Schulmerich, J. H. Cole, K. A. Dooley, M. D. Morris, J. M. Kreider, and S. A. Goldstein, "Optical clearing in transcutaneous Raman spectroscopy of murine cortical bone tissue," J. Biomed. Opt. 13, 021108 (2008).
[CrossRef] [PubMed]

Moscoso, M.

Nadiarnykh, O.

R. Lacomb, O. Nadiarnykh, and P. J. Campagnola, "Quantitative SHG imaging of the diseased state Osteogenesis Imperfecta: Experiment and Simulation," Biophys J 94, 4104- (2008).
[CrossRef]

R. LaComb, O. Nadiarnykh, S. Carey, and P. J. Campagnola, "Quantitative SHG 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]

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

O. Nadiarnykh, S. Plotnikov, W. A. Mohler, I. Kalajzic, D. Redford-Badwal, and P. J. Campagnola, "Second Harmonic Generation imaging microscopy studies of Osteogenesis Imperfecta," J. Biomed. Opt. 12, 051805 (2007).
[CrossRef] [PubMed]

Nelson, J. S.

J. Yoon, T. Son, E. H. Choi, B. Choi, J. S. Nelson, and B. Jung, "Enhancement of optical skin clearing efficacy using a microneedle roller," J. Biomed. Opt. 13, 021103 (2008).
[CrossRef] [PubMed]

M. Khan, B. Choi, S. Chess, J. McCullough, K. Kelly, and J. S. Nelson, "The use of topically applied chemical agents for optical clearing of skin to improve diagnostics and laser therapeutic applications," Lasers Surg. Med., 34, 407-13 (2004).

M. H. Khan, B. Choi, S. Chess, K. M. Kelly, J. McCullough, and J. S. Nelson, "Optical clearing of in vivo human skin: Implications for light-based diagnostic imaging and therapeutics," Lasers Surg. Med. 34, 83-85 (2004).
[CrossRef] [PubMed]

Papanicolaou, G.

Pavone, F. S.

Pilbeam, C.

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

Plotnikov, S.

O. Nadiarnykh, S. Plotnikov, W. A. Mohler, I. Kalajzic, D. Redford-Badwal, and P. J. Campagnola, "Second Harmonic Generation imaging microscopy studies of Osteogenesis Imperfecta," J. Biomed. Opt. 12, 051805 (2007).
[CrossRef] [PubMed]

S. Plotnikov, V. Juneja, 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]

Plotnikov, S. V.

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, "Characterization of the Myosin-based source for second-harmonic generation from muscle sarcomeres," Biophys J. 90, 693-703 (2006).
[CrossRef]

Pluen, A.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef] [PubMed]

Provenzano, P. P.

P. P. Provenzano, K. W. Eliceiri, J. M. Campbell, D. R. Inman, J. G. White, and P. J. Keely, "Collagen reorganization at the tumor-stromal interface facilitates local invasion," BMC Med. 4, 38 (2006).
[CrossRef] [PubMed]

Ramanujam, N.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, "In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12, 024014 (2007).
[CrossRef] [PubMed]

Redford-Badwal, D.

O. Nadiarnykh, S. Plotnikov, W. A. Mohler, I. Kalajzic, D. Redford-Badwal, and P. J. Campagnola, "Second Harmonic Generation imaging microscopy studies of Osteogenesis Imperfecta," J. Biomed. Opt. 12, 051805 (2007).
[CrossRef] [PubMed]

Reiser, K. M.

P. Stoller, B.-M. Kim, A. M. Rubinchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J.Biomed. Opt. 7, 205-214 (2001).
[CrossRef]

Riching, K. M.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, "In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12, 024014 (2007).
[CrossRef] [PubMed]

Rubinchik, A. M.

P. Stoller, B.-M. Kim, A. M. Rubinchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J.Biomed. Opt. 7, 205-214 (2001).
[CrossRef]

Rylander, H. G.

G. Vargas, E. K. Chan, J. K. Barton, H. G. Rylander, 3rd, and A. J. Welch, "Use of an agent to reduce scattering in skin," Lasers Surg. Med. 24, 133-141 (1999).
[CrossRef] [PubMed]

Schulmerich, M. V.

M. V. Schulmerich, J. H. Cole, K. A. Dooley, M. D. Morris, J. M. Kreider, and S. A. Goldstein, "Optical clearing in transcutaneous Raman spectroscopy of murine cortical bone tissue," J. Biomed. Opt. 13, 021108 (2008).
[CrossRef] [PubMed]

Scranton, V. L.

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

Seed, B.

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (2003).
[CrossRef] [PubMed]

Sestini, S.

Sinichkin, Y. P.

E. A. Genina, A. N. Bashkatov, Y. P. Sinichkin, and V. V. Tuchin, "Optical clearing of the eye sclera in vivo caused by glucose," Quantum Electron. 36, 1119-1124 (2006).
[CrossRef]

A. N. Bashkatov, E. A. Genina, Y. P. Sinichkin, V. I. Kochubey, N. A. Lakodina, and V. V. Tuchin, "Glucose and mannitol diffusion in human dura mater," Biophys. J. 85, 3310-3318 (2003).
[CrossRef] [PubMed]

Skala, M. C.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, "In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12, 024014 (2007).
[CrossRef] [PubMed]

Son, T.

J. Yoon, T. Son, E. H. Choi, B. Choi, J. S. Nelson, and B. Jung, "Enhancement of optical skin clearing efficacy using a microneedle roller," J. Biomed. Opt. 13, 021103 (2008).
[CrossRef] [PubMed]

Stoller, P.

P. Stoller, B.-M. Kim, A. M. Rubinchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J.Biomed. Opt. 7, 205-214 (2001).
[CrossRef]

Sun, C.-K.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Sun, C.-W.

Terasaki, M.

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).
[CrossRef]

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]

Tsai, T. F.

Tsai, T.-H.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Tuchin, V. V.

M. G. Ghosn, E. F. Carbajal, N. A. Befrui, V. V. Tuchin, and K. V. Larin, "Differential permeability rate and percent clearing of glucose in different regions in rabbit sclera," J. Biomed. Opt. 13, 021110 (2008).
[CrossRef] [PubMed]

E. A. Genina, A. N. Bashkatov, Y. P. Sinichkin, and V. V. Tuchin, "Optical clearing of the eye sclera in vivo caused by glucose," Quantum Electron. 36, 1119-1124 (2006).
[CrossRef]

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

A. N. Bashkatov, E. A. Genina, Y. P. Sinichkin, V. I. Kochubey, N. A. Lakodina, and V. V. Tuchin, "Glucose and mannitol diffusion in human dura mater," Biophys. J. 85, 3310-3318 (2003).
[CrossRef] [PubMed]

V. V. Tuchin, X. Q. Xu, and R. K. Wang, "Dynamic optical coherence tomography in studies of optical clearing, sedimentation, and aggregation of immersed blood," Appl. Opt. 41, 258-271 (2002).
[CrossRef] [PubMed]

Turner, P.

J. Y. Jiang, M. Boese, P. Turner, and R. K. K. Wang, "Penetration kinetics of dimethyl sulphoxide and glycerol in dynamic optical clearing of porcine skin tissue in vitro studied by Fourier transform infrared spectroscopic imaging," J. Biomed. Opt. 13, 021105 (2008).
[CrossRef] [PubMed]

Vargas, G.

G. Vargas, E. K. Chan, J. K. Barton, H. G. Rylander, 3rd, and A. J. Welch, "Use of an agent to reduce scattering in skin," Lasers Surg. Med. 24, 133-141 (1999).
[CrossRef] [PubMed]

Walsh, S.

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

Wang, C.-Y.

Wang, L. V.

X. Wang and L. V. Wang, "Propagation of polarized light in birefringent turbid media: a Monte Carlo study," J. Biomed. Opt. 7, 279-290 (2002).
[CrossRef] [PubMed]

Wang, R. K.

X. Q. Xu, R. K. Wang, and J. B. Elder, "Optical clearing effect on gastric tissues immersed with biocompatible chemical agents investigated by near infrared reflectance spectroscopy," J. Phys. D 36, 1707-1713 (2003).
[CrossRef]

V. V. Tuchin, X. Q. Xu, and R. K. Wang, "Dynamic optical coherence tomography in studies of optical clearing, sedimentation, and aggregation of immersed blood," Appl. Opt. 41, 258-271 (2002).
[CrossRef] [PubMed]

Wang, R. K. K.

J. Y. Jiang, M. Boese, P. Turner, and R. K. K. Wang, "Penetration kinetics of dimethyl sulphoxide and glycerol in dynamic optical clearing of porcine skin tissue in vitro studied by Fourier transform infrared spectroscopic imaging," J. Biomed. Opt. 13, 021105 (2008).
[CrossRef] [PubMed]

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

Wang, X.

X. Wang and L. V. Wang, "Propagation of polarized light in birefringent turbid media: a Monte Carlo study," J. Biomed. Opt. 7, 279-290 (2002).
[CrossRef] [PubMed]

Welch, A. J.

G. Vargas, E. K. Chan, J. K. Barton, H. G. Rylander, 3rd, and A. J. Welch, "Use of an agent to reduce scattering in skin," Lasers Surg. Med. 24, 133-141 (1999).
[CrossRef] [PubMed]

White, J. G.

P. P. Provenzano, K. W. Eliceiri, J. M. Campbell, D. R. Inman, J. G. White, and P. J. Keely, "Collagen reorganization at the tumor-stromal interface facilitates local invasion," BMC Med. 4, 38 (2006).
[CrossRef] [PubMed]

Wu, R. J.

Xu, M.

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

Xu, X. Q.

X. Q. Xu, L. F. Yu, and Z. P. Chen, "Optical clearing of flowing blood using dextrans with spectral domain optical coherence tomography," J. Biomed. Opt. 13, 021107 (2008).
[CrossRef] [PubMed]

X. Q. Xu, R. K. Wang, and J. B. Elder, "Optical clearing effect on gastric tissues immersed with biocompatible chemical agents investigated by near infrared reflectance spectroscopy," J. Phys. D 36, 1707-1713 (2003).
[CrossRef]

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

V. V. Tuchin, X. Q. Xu, and R. K. Wang, "Dynamic optical coherence tomography in studies of optical clearing, sedimentation, and aggregation of immersed blood," Appl. Opt. 41, 258-271 (2002).
[CrossRef] [PubMed]

Yang, C. C.

Yeh, A. T.

A. T. Yeh and J. Hirshburg, "Molecular interactions of exogenous chemical agents with collagen--implications for tissue optical clearing," J Biomed. Opt. 11, 014003 (2006).
[CrossRef] [PubMed]

Yoon, J.

J. Yoon, T. Son, E. H. Choi, B. Choi, J. S. Nelson, and B. Jung, "Enhancement of optical skin clearing efficacy using a microneedle roller," J. Biomed. Opt. 13, 021103 (2008).
[CrossRef] [PubMed]

Yu, L. F.

X. Q. Xu, L. F. Yu, and Z. P. Chen, "Optical clearing of flowing blood using dextrans with spectral domain optical coherence tomography," J. Biomed. Opt. 13, 021107 (2008).
[CrossRef] [PubMed]

Zubrowski, B.

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

Appl. Opt. (1)

Biophys J (1)

R. Lacomb, O. Nadiarnykh, and P. J. Campagnola, "Quantitative SHG imaging of the diseased state Osteogenesis Imperfecta: Experiment and Simulation," Biophys J 94, 4104- (2008).
[CrossRef]

Biophys J. (2)

S. V. Plotnikov, A. C. Millard, P. J. Campagnola, and W. A. Mohler, "Characterization of the Myosin-based source for second-harmonic generation from muscle sarcomeres," Biophys J. 90, 693-703 (2006).
[CrossRef]

S. Plotnikov, V. Juneja, 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]

Biophys. J. (3)

A. N. Bashkatov, E. A. Genina, Y. P. Sinichkin, V. I. Kochubey, N. A. Lakodina, and V. V. Tuchin, "Glucose and mannitol diffusion in human dura mater," Biophys. J. 85, 3310-3318 (2003).
[CrossRef] [PubMed]

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "3-Dimesional High-Resolution Second Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J. 82, 493-508 (2002).
[CrossRef]

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of (2)/(3) Tensors in Submicron-Scaled Bio-Tissues by Polarization Harmonics Optical Microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

BMC Med. (1)

P. P. Provenzano, K. W. Eliceiri, J. M. Campbell, D. R. Inman, J. G. White, and P. J. Keely, "Collagen reorganization at the tumor-stromal interface facilitates local invasion," BMC Med. 4, 38 (2006).
[CrossRef] [PubMed]

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

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

J Biomed. Opt. (1)

A. T. Yeh and J. Hirshburg, "Molecular interactions of exogenous chemical agents with collagen--implications for tissue optical clearing," J Biomed. Opt. 11, 014003 (2006).
[CrossRef] [PubMed]

J. Biomed. Opt. (10)

X. Wang and L. V. Wang, "Propagation of polarized light in birefringent turbid media: a Monte Carlo study," J. Biomed. Opt. 7, 279-290 (2002).
[CrossRef] [PubMed]

J. Yoon, T. Son, E. H. Choi, B. Choi, J. S. Nelson, and B. Jung, "Enhancement of optical skin clearing efficacy using a microneedle roller," J. Biomed. Opt. 13, 021103 (2008).
[CrossRef] [PubMed]

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

X. Q. Xu, L. F. Yu, and Z. P. Chen, "Optical clearing of flowing blood using dextrans with spectral domain optical coherence tomography," J. Biomed. Opt. 13, 021107 (2008).
[CrossRef] [PubMed]

M. G. Ghosn, E. F. Carbajal, N. A. Befrui, V. V. Tuchin, and K. V. Larin, "Differential permeability rate and percent clearing of glucose in different regions in rabbit sclera," J. Biomed. Opt. 13, 021110 (2008).
[CrossRef] [PubMed]

M. V. Schulmerich, J. H. Cole, K. A. Dooley, M. D. Morris, J. M. Kreider, and S. A. Goldstein, "Optical clearing in transcutaneous Raman spectroscopy of murine cortical bone tissue," J. Biomed. Opt. 13, 021108 (2008).
[CrossRef] [PubMed]

S. V. Plotnikov, A. Kenny, S. Walsh, B. Zubrowski, C. Joseph, V. L. Scranton, G. A. Kuchel, D. Dauser, M. Xu, C. Pilbeam, D. Adams, R. Dougherty, P. J. Campagnola, and W. A. Mohler, "Measurement of muscle disease by quantitative second-harmonic generation imaging," J. Biomed. Opt. 13, 044018 (2008).
[CrossRef] [PubMed]

O. Nadiarnykh, S. Plotnikov, W. A. Mohler, I. Kalajzic, D. Redford-Badwal, and P. J. Campagnola, "Second Harmonic Generation imaging microscopy studies of Osteogenesis Imperfecta," J. Biomed. Opt. 12, 051805 (2007).
[CrossRef] [PubMed]

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, "In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia," J. Biomed. Opt. 12, 024014 (2007).
[CrossRef] [PubMed]

J. Y. Jiang, M. Boese, P. Turner, and R. K. K. Wang, "Penetration kinetics of dimethyl sulphoxide and glycerol in dynamic optical clearing of porcine skin tissue in vitro studied by Fourier transform infrared spectroscopic imaging," J. Biomed. Opt. 13, 021105 (2008).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A (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. Phys. D (1)

X. Q. Xu, R. K. Wang, and J. B. Elder, "Optical clearing effect on gastric tissues immersed with biocompatible chemical agents investigated by near infrared reflectance spectroscopy," J. Phys. D 36, 1707-1713 (2003).
[CrossRef]

J.Biomed. Opt. (1)

P. Stoller, B.-M. Kim, A. M. Rubinchik, K. M. Reiser, and L. B. Da Silva, "Polarization-dependent optical second-harmonic imaging of a rat-tail tendon," J.Biomed. Opt. 7, 205-214 (2001).
[CrossRef]

Lasers Surg. Med. (3)

M. H. Khan, B. Choi, S. Chess, K. M. Kelly, J. McCullough, and J. S. Nelson, "Optical clearing of in vivo human skin: Implications for light-based diagnostic imaging and therapeutics," Lasers Surg. Med. 34, 83-85 (2004).
[CrossRef] [PubMed]

M. Khan, B. Choi, S. Chess, J. McCullough, K. Kelly, and J. S. Nelson, "The use of topically applied chemical agents for optical clearing of skin to improve diagnostics and laser therapeutic applications," Lasers Surg. Med., 34, 407-13 (2004).

G. Vargas, E. K. Chan, J. K. Barton, H. G. Rylander, 3rd, and A. J. Welch, "Use of an agent to reduce scattering in skin," Lasers Surg. Med. 24, 133-141 (1999).
[CrossRef] [PubMed]

Nat. Med. (1)

E. Brown, T. McKee, E. diTomaso, A. Pluen, B. Seed, Y. Boucher, and R. K. Jain, "Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation," Nat. Med. 9, 796-800 (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 (2)

Opt. Lett. (2)

Quantum Electron. (1)

E. A. Genina, A. N. Bashkatov, Y. P. Sinichkin, and V. V. Tuchin, "Optical clearing of the eye sclera in vivo caused by glucose," Quantum Electron. 36, 1119-1124 (2006).
[CrossRef]

Other (1)

V. Tuchin, Optical Clearing of Tissues and Blood (SPIE Press, Bellingham, WA, 2006), Vol. PM 154.

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Figures (6)

Fig. 1.
Fig. 1.

Angular dependence of the forward SHG intensity from control tendon at depths of 5 and 45 microns. Representative optical sections at several polarization angles are shown in the top panels. Representative error bars (standard error) are given for one laser polarization for each depth.

Fig. 2.
Fig. 2.

Angular dependence of the forward SHG intensity from optically cleared tendon at 10 (black squares) and 100 (red circles) micron depths. Representative optical sections for 100 microns are shown in the top panel Representative error bars (standard error) are given for one laser polarization for each depth.

Fig. 3.
Fig. 3.

SHG anisotropy β measured for forward (red squares) and backward (blue circles) for control tendon.

Fig. 4.
Fig. 4.

(a) Forward SHG anisotropy β measured for forward SHG from control (red squares) and cleared (blue squares) tendon. (b) Forward (red squares) and backward (blue circles) anisotropy in cleared tendon.

Fig. 5.
Fig. 5.

Angular dependence of the forward SHG from control and optically cleared muscle at different depths up to 180 microns.

Fig. 6.
Fig. 6.

SHG anisotropy β calculated for forward SHG from control (red squares) and cleared (blue circles) muscle samples. The data is presented at two depths corresponding to the middle regions of two muscle cells at 50 and 180 microns.

Equations (1)

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β = I par I orth I par + 2 I orth

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