Abstract

The in vivo flow cytometry (IVFC) has shown a great potential for detecting circulating tumor cells quantitatively in the bloodstream. However, the detection depth suffers from the strong light scattering of tissue. In this study, an innovative ear skin optical clearing agent (ESOCA) is employed to improve the signal quality of the IVFC. Our results show that compared with commonly used glycerol, topical application of ESOCA can enhance the transmittance of rat ear significantly in vivo. The labeled red blood cells can be detected by the IVFC with higher signal quality and greater detection depth. This study is very helpful for potential tumor metastasis studies by the IVFC in deep tissues.

© 2013 Optical Society of America

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  1. G. S. Terentyuk, G. N. Maslyakova, L. V. Suleymanova, N. G. Khlebtsov, B. N. Khlebtsov, G. G. Akchurin, I. L. Maksimova, and V. V. Tuchin, “Laser-induced tissue hyperthermia mediated by gold nanoparticles: toward cancer phototherapy,” J. Biomed. Opt. 14(2), 021016 (2009).
    [Crossref] [PubMed]
  2. W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
    [Crossref] [PubMed]
  3. A. Herrmann, M. Kortylewski, M. Kujawski, C. Zhang, K. Reckamp, B. Armstrong, L. Wang, C. Kowolik, J. Deng, R. Figlin, and H. Yu, “Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells,” Cancer Res. 70(19), 7455–7464 (2010).
    [Crossref] [PubMed]
  4. I. J. Fidler, “The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited,” Nat. Rev. Cancer 3(6), 453–458 (2003).
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  5. I. Georgakoudi, N. Solban, J. Novak, W. L. Rice, X. Wei, T. Hasan, and C. P. Lin, “In vivo flow cytometry: a new method for enumerating circulating cancer cells,” Cancer Res. 64(15), 5044–5047 (2004).
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  6. J. Novak, “Development of in vivo flow cytometry,” Ph.D. dissertation, Dept. Mech. Eng., Harvard Univ. Cambridge, MA, 2004.
  7. Z. C. Fan, J. Yan, G. D. Liu, X. Y. Tan, X. F. Weng, W. Z. Wu, J. Zhou, and X. B. Wei, “Real-time monitoring of rare circulating hepatocellular carcinoma cells in an orthotopic model by in vivo flow cytometry Assesses Resection On Metastasis,” Cancer Res. 72(10), 2683–2691 (2012).
    [Crossref] [PubMed]
  8. J. Novak, I. Georgakoudi, X. Wei, A. Prossin, and C. P. Lin, “In vivo flow cytometer for real-time detection and quantification of circulating cells,” Opt. Lett. 29(1), 77–79 (2004).
    [Crossref] [PubMed]
  9. J. Guo, Z. Fan, Z. Gu, and X. Wei, “Studying the role of macrophages in circulating prostate cancer cells by in vivo flow cytometry,” J. Innov. Opt. Health Sci. 5(4), 1250027 (2012).
    [Crossref]
  10. Y. Li, J. Guo, C. Wang, Z. Fan, G. Liu, C. Wang, Z. Gu, D. Damm, A. Mosig, and X. Wei, “Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry,” Cytometry A 79(10), 848–854 (2011).
    [Crossref] [PubMed]
  11. A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).
    [Crossref]
  12. V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlyutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2(4), 401–417 (1997).
    [Crossref] [PubMed]
  13. V. V. Tuchin, Optical Clearing of Tissues and Blood, (SPIE Press, Bellingham, 2005), Vol. 154.
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    [Crossref]
  15. V. V. Tuchin, “Optical immersion as a new tool to control optical properties of tissues and blood,” Laser Phys. 15(8), 1109–1136 (2005).
  16. D. Zhu, K. V. Larin, Q. Luo, and V. V. Tuchin, “Recent progress in tissue optical clearing,” Laser Photonics Rev. 7(5), 732–757 (2013).
    [Crossref]
  17. X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, “In vivo skin optical clearing by glycerol solutions: mechanism,” J. Biophotonics 3(1-2), 44–52 (2010).
    [Crossref] [PubMed]
  18. D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, “Imaging dermal blood flow through the intact rat skin with an optical clearing method,” J. Biomed. Opt. 15(2), 026008 (2010).
    [Crossref] [PubMed]
  19. J. Wang, R. Shi, and D. Zhu, “Optical clearing method induced switchable skin window for dermal blood flow imaging,” J. Biomed. Opt. 18(6), 061209 (2013).
    [Crossref] [PubMed]
  20. X. Wen, S. L. Jacques, V. V. Tuchin, and D. Zhu, “Enhanced optical clearing of skin in vivo and optical coherence tomography in-depth imaging,” J. Biomed. Opt. 17(6), 066022 (2012).
    [Crossref] [PubMed]
  21. 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(2), 83–85 (2004).
    [Crossref] [PubMed]
  22. J. Wang, Y. Liang, S. Zhang, Y. Zhou, H. Ni, and Y. Li, “Evaluation of optical clearing with the combined liquid paraffin and glycerol mixture,” Biomed. Opt. Express 2(8), 2329–2338 (2011).
    [Crossref] [PubMed]
  23. Z. Zhi, Z. Han, Q. Luo, and D. Zhu, “Improve optical clearing of skin in vitro with propylene glycol as a penetration enhancer,” J. Innov. Opt. Health Sci. 2(3), 269–278 (2009).
    [Crossref]
  24. J. Wang, R. Shi, Y. Zhang, and D. Zhu, “Ear skin optical clearing for improving blood flow imaging,” Photon. Lasers Med. 2(1), 37–44 (2013).
  25. S. Boutrus, C. Greiner, D. Hwu, M. Chan, C. Kuperwasser, C. P. Lin, and I. Georgakoudi, “Portable two-color in vivo flow cytometer for real-time detection of fluorescently-labeled circulating cells,” J. Biomed. Opt. 12(2), 020507 (2007).
    [Crossref] [PubMed]
  26. Y. Li, Z. Fan, J. Guo, G. Liu, X. Tan, C. Wang, and et al.., “Circulation times of hepatocellular carcinoma cells by in vivo flow cytometry,” Chin. Opt. Lett. 10, 953–956 (2010).
  27. D. Donoho, “De-noising by soft-thresholding,” IEEE Trans. Inf. Theory 41(3), 613–627 (1995).
    [Crossref]
  28. E. A. Genina, A. N. Bashkatov, and V. V. Tuchin, “Tissue optical immersion clearing,” Expert Rev. Med. Devices 7(6), 825–842 (2010).
    [Crossref] [PubMed]
  29. G. Vargas, A. Readinger, S. S. Dozier, and A. J. Welch, “Morphological changes in blood vessels produced by hyperosmotic agents and measured by optical coherence tomography,” Photochem. Photobiol. 77(5), 541–549 (2003).
    [Crossref] [PubMed]
  30. H. Cheng, Q. Luo, S. Zeng, S. Chen, W. Luo, and H. Gong, “Hyperosmotic chemical agent’s effect on in vivo cerebral blood flow revealed by laser speckle,” Appl. Opt. 43(31), 5772–5777 (2004).
    [Crossref] [PubMed]
  31. D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, “Short-term and long-term effects of optical clearing agents on blood vessels in chick chorioallantoic membrane,” J. Biomed. Opt. 13(2), 021106 (2008).
    [Crossref] [PubMed]
  32. C. Liu, Z. Zhi, V. V. Tuchin, Q. Luo, and D. Zhu, “Enhancement of skin optical clearing efficacy using photo-irradiation,” Lasers Surg. Med. 42(2), 132–140 (2010).
    [Crossref] [PubMed]

2013 (3)

D. Zhu, K. V. Larin, Q. Luo, and V. V. Tuchin, “Recent progress in tissue optical clearing,” Laser Photonics Rev. 7(5), 732–757 (2013).
[Crossref]

J. Wang, R. Shi, and D. Zhu, “Optical clearing method induced switchable skin window for dermal blood flow imaging,” J. Biomed. Opt. 18(6), 061209 (2013).
[Crossref] [PubMed]

J. Wang, R. Shi, Y. Zhang, and D. Zhu, “Ear skin optical clearing for improving blood flow imaging,” Photon. Lasers Med. 2(1), 37–44 (2013).

2012 (3)

X. Wen, S. L. Jacques, V. V. Tuchin, and D. Zhu, “Enhanced optical clearing of skin in vivo and optical coherence tomography in-depth imaging,” J. Biomed. Opt. 17(6), 066022 (2012).
[Crossref] [PubMed]

Z. C. Fan, J. Yan, G. D. Liu, X. Y. Tan, X. F. Weng, W. Z. Wu, J. Zhou, and X. B. Wei, “Real-time monitoring of rare circulating hepatocellular carcinoma cells in an orthotopic model by in vivo flow cytometry Assesses Resection On Metastasis,” Cancer Res. 72(10), 2683–2691 (2012).
[Crossref] [PubMed]

J. Guo, Z. Fan, Z. Gu, and X. Wei, “Studying the role of macrophages in circulating prostate cancer cells by in vivo flow cytometry,” J. Innov. Opt. Health Sci. 5(4), 1250027 (2012).
[Crossref]

2011 (3)

Y. Li, J. Guo, C. Wang, Z. Fan, G. Liu, C. Wang, Z. Gu, D. Damm, A. Mosig, and X. Wei, “Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry,” Cytometry A 79(10), 848–854 (2011).
[Crossref] [PubMed]

A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).
[Crossref]

J. Wang, Y. Liang, S. Zhang, Y. Zhou, H. Ni, and Y. Li, “Evaluation of optical clearing with the combined liquid paraffin and glycerol mixture,” Biomed. Opt. Express 2(8), 2329–2338 (2011).
[Crossref] [PubMed]

2010 (7)

Y. Li, Z. Fan, J. Guo, G. Liu, X. Tan, C. Wang, and et al.., “Circulation times of hepatocellular carcinoma cells by in vivo flow cytometry,” Chin. Opt. Lett. 10, 953–956 (2010).

E. A. Genina, A. N. Bashkatov, and V. V. Tuchin, “Tissue optical immersion clearing,” Expert Rev. Med. Devices 7(6), 825–842 (2010).
[Crossref] [PubMed]

C. Liu, Z. Zhi, V. V. Tuchin, Q. Luo, and D. Zhu, “Enhancement of skin optical clearing efficacy using photo-irradiation,” Lasers Surg. Med. 42(2), 132–140 (2010).
[Crossref] [PubMed]

W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
[Crossref] [PubMed]

A. Herrmann, M. Kortylewski, M. Kujawski, C. Zhang, K. Reckamp, B. Armstrong, L. Wang, C. Kowolik, J. Deng, R. Figlin, and H. Yu, “Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells,” Cancer Res. 70(19), 7455–7464 (2010).
[Crossref] [PubMed]

X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, “In vivo skin optical clearing by glycerol solutions: mechanism,” J. Biophotonics 3(1-2), 44–52 (2010).
[Crossref] [PubMed]

D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, “Imaging dermal blood flow through the intact rat skin with an optical clearing method,” J. Biomed. Opt. 15(2), 026008 (2010).
[Crossref] [PubMed]

2009 (2)

G. S. Terentyuk, G. N. Maslyakova, L. V. Suleymanova, N. G. Khlebtsov, B. N. Khlebtsov, G. G. Akchurin, I. L. Maksimova, and V. V. Tuchin, “Laser-induced tissue hyperthermia mediated by gold nanoparticles: toward cancer phototherapy,” J. Biomed. Opt. 14(2), 021016 (2009).
[Crossref] [PubMed]

Z. Zhi, Z. Han, Q. Luo, and D. Zhu, “Improve optical clearing of skin in vitro with propylene glycol as a penetration enhancer,” J. Innov. Opt. Health Sci. 2(3), 269–278 (2009).
[Crossref]

2008 (1)

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, “Short-term and long-term effects of optical clearing agents on blood vessels in chick chorioallantoic membrane,” J. Biomed. Opt. 13(2), 021106 (2008).
[Crossref] [PubMed]

2007 (1)

S. Boutrus, C. Greiner, D. Hwu, M. Chan, C. Kuperwasser, C. P. Lin, and I. Georgakoudi, “Portable two-color in vivo flow cytometer for real-time detection of fluorescently-labeled circulating cells,” J. Biomed. Opt. 12(2), 020507 (2007).
[Crossref] [PubMed]

2005 (2)

V. V. Tuchin, “Optical clearing of tissue and blood using immersion method,” J. Phys. D Appl. Phys. 38(15), 2497–2518 (2005).
[Crossref]

V. V. Tuchin, “Optical immersion as a new tool to control optical properties of tissues and blood,” Laser Phys. 15(8), 1109–1136 (2005).

2004 (4)

J. Novak, I. Georgakoudi, X. Wei, A. Prossin, and C. P. Lin, “In vivo flow cytometer for real-time detection and quantification of circulating cells,” Opt. Lett. 29(1), 77–79 (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(2), 83–85 (2004).
[Crossref] [PubMed]

I. Georgakoudi, N. Solban, J. Novak, W. L. Rice, X. Wei, T. Hasan, and C. P. Lin, “In vivo flow cytometry: a new method for enumerating circulating cancer cells,” Cancer Res. 64(15), 5044–5047 (2004).
[Crossref] [PubMed]

H. Cheng, Q. Luo, S. Zeng, S. Chen, W. Luo, and H. Gong, “Hyperosmotic chemical agent’s effect on in vivo cerebral blood flow revealed by laser speckle,” Appl. Opt. 43(31), 5772–5777 (2004).
[Crossref] [PubMed]

2003 (2)

G. Vargas, A. Readinger, S. S. Dozier, and A. J. Welch, “Morphological changes in blood vessels produced by hyperosmotic agents and measured by optical coherence tomography,” Photochem. Photobiol. 77(5), 541–549 (2003).
[Crossref] [PubMed]

I. J. Fidler, “The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited,” Nat. Rev. Cancer 3(6), 453–458 (2003).
[Crossref] [PubMed]

1997 (1)

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlyutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2(4), 401–417 (1997).
[Crossref] [PubMed]

1995 (1)

D. Donoho, “De-noising by soft-thresholding,” IEEE Trans. Inf. Theory 41(3), 613–627 (1995).
[Crossref]

Akchurin, G. G.

G. S. Terentyuk, G. N. Maslyakova, L. V. Suleymanova, N. G. Khlebtsov, B. N. Khlebtsov, G. G. Akchurin, I. L. Maksimova, and V. V. Tuchin, “Laser-induced tissue hyperthermia mediated by gold nanoparticles: toward cancer phototherapy,” J. Biomed. Opt. 14(2), 021016 (2009).
[Crossref] [PubMed]

Armstrong, B.

A. Herrmann, M. Kortylewski, M. Kujawski, C. Zhang, K. Reckamp, B. Armstrong, L. Wang, C. Kowolik, J. Deng, R. Figlin, and H. Yu, “Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells,” Cancer Res. 70(19), 7455–7464 (2010).
[Crossref] [PubMed]

Bashkatov, A. N.

A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).
[Crossref]

E. A. Genina, A. N. Bashkatov, and V. V. Tuchin, “Tissue optical immersion clearing,” Expert Rev. Med. Devices 7(6), 825–842 (2010).
[Crossref] [PubMed]

Boutrus, S.

S. Boutrus, C. Greiner, D. Hwu, M. Chan, C. Kuperwasser, C. P. Lin, and I. Georgakoudi, “Portable two-color in vivo flow cytometer for real-time detection of fluorescently-labeled circulating cells,” J. Biomed. Opt. 12(2), 020507 (2007).
[Crossref] [PubMed]

Brecht, P.

W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
[Crossref] [PubMed]

Chan, M.

S. Boutrus, C. Greiner, D. Hwu, M. Chan, C. Kuperwasser, C. P. Lin, and I. Georgakoudi, “Portable two-color in vivo flow cytometer for real-time detection of fluorescently-labeled circulating cells,” J. Biomed. Opt. 12(2), 020507 (2007).
[Crossref] [PubMed]

Chen, S.

Cheng, H.

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(2), 83–85 (2004).
[Crossref] [PubMed]

Choi, B.

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(2), 83–85 (2004).
[Crossref] [PubMed]

Cui, H.

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, “Short-term and long-term effects of optical clearing agents on blood vessels in chick chorioallantoic membrane,” J. Biomed. Opt. 13(2), 021106 (2008).
[Crossref] [PubMed]

Damm, D.

Y. Li, J. Guo, C. Wang, Z. Fan, G. Liu, C. Wang, Z. Gu, D. Damm, A. Mosig, and X. Wei, “Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry,” Cytometry A 79(10), 848–854 (2011).
[Crossref] [PubMed]

Deng, J.

A. Herrmann, M. Kortylewski, M. Kujawski, C. Zhang, K. Reckamp, B. Armstrong, L. Wang, C. Kowolik, J. Deng, R. Figlin, and H. Yu, “Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells,” Cancer Res. 70(19), 7455–7464 (2010).
[Crossref] [PubMed]

Donoho, D.

D. Donoho, “De-noising by soft-thresholding,” IEEE Trans. Inf. Theory 41(3), 613–627 (1995).
[Crossref]

Dozier, S. S.

G. Vargas, A. Readinger, S. S. Dozier, and A. J. Welch, “Morphological changes in blood vessels produced by hyperosmotic agents and measured by optical coherence tomography,” Photochem. Photobiol. 77(5), 541–549 (2003).
[Crossref] [PubMed]

Fan, Z.

J. Guo, Z. Fan, Z. Gu, and X. Wei, “Studying the role of macrophages in circulating prostate cancer cells by in vivo flow cytometry,” J. Innov. Opt. Health Sci. 5(4), 1250027 (2012).
[Crossref]

Y. Li, J. Guo, C. Wang, Z. Fan, G. Liu, C. Wang, Z. Gu, D. Damm, A. Mosig, and X. Wei, “Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry,” Cytometry A 79(10), 848–854 (2011).
[Crossref] [PubMed]

Y. Li, Z. Fan, J. Guo, G. Liu, X. Tan, C. Wang, and et al.., “Circulation times of hepatocellular carcinoma cells by in vivo flow cytometry,” Chin. Opt. Lett. 10, 953–956 (2010).

Fan, Z. C.

Z. C. Fan, J. Yan, G. D. Liu, X. Y. Tan, X. F. Weng, W. Z. Wu, J. Zhou, and X. B. Wei, “Real-time monitoring of rare circulating hepatocellular carcinoma cells in an orthotopic model by in vivo flow cytometry Assesses Resection On Metastasis,” Cancer Res. 72(10), 2683–2691 (2012).
[Crossref] [PubMed]

Fidler, I. J.

I. J. Fidler, “The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited,” Nat. Rev. Cancer 3(6), 453–458 (2003).
[Crossref] [PubMed]

Figlin, R.

A. Herrmann, M. Kortylewski, M. Kujawski, C. Zhang, K. Reckamp, B. Armstrong, L. Wang, C. Kowolik, J. Deng, R. Figlin, and H. Yu, “Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells,” Cancer Res. 70(19), 7455–7464 (2010).
[Crossref] [PubMed]

Genina, E. A.

A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).
[Crossref]

E. A. Genina, A. N. Bashkatov, and V. V. Tuchin, “Tissue optical immersion clearing,” Expert Rev. Med. Devices 7(6), 825–842 (2010).
[Crossref] [PubMed]

Georgakoudi, I.

S. Boutrus, C. Greiner, D. Hwu, M. Chan, C. Kuperwasser, C. P. Lin, and I. Georgakoudi, “Portable two-color in vivo flow cytometer for real-time detection of fluorescently-labeled circulating cells,” J. Biomed. Opt. 12(2), 020507 (2007).
[Crossref] [PubMed]

J. Novak, I. Georgakoudi, X. Wei, A. Prossin, and C. P. Lin, “In vivo flow cytometer for real-time detection and quantification of circulating cells,” Opt. Lett. 29(1), 77–79 (2004).
[Crossref] [PubMed]

I. Georgakoudi, N. Solban, J. Novak, W. L. Rice, X. Wei, T. Hasan, and C. P. Lin, “In vivo flow cytometry: a new method for enumerating circulating cancer cells,” Cancer Res. 64(15), 5044–5047 (2004).
[Crossref] [PubMed]

Gong, H.

Greiner, C.

S. Boutrus, C. Greiner, D. Hwu, M. Chan, C. Kuperwasser, C. P. Lin, and I. Georgakoudi, “Portable two-color in vivo flow cytometer for real-time detection of fluorescently-labeled circulating cells,” J. Biomed. Opt. 12(2), 020507 (2007).
[Crossref] [PubMed]

Gu, Z.

J. Guo, Z. Fan, Z. Gu, and X. Wei, “Studying the role of macrophages in circulating prostate cancer cells by in vivo flow cytometry,” J. Innov. Opt. Health Sci. 5(4), 1250027 (2012).
[Crossref]

Y. Li, J. Guo, C. Wang, Z. Fan, G. Liu, C. Wang, Z. Gu, D. Damm, A. Mosig, and X. Wei, “Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry,” Cytometry A 79(10), 848–854 (2011).
[Crossref] [PubMed]

Guo, J.

J. Guo, Z. Fan, Z. Gu, and X. Wei, “Studying the role of macrophages in circulating prostate cancer cells by in vivo flow cytometry,” J. Innov. Opt. Health Sci. 5(4), 1250027 (2012).
[Crossref]

Y. Li, J. Guo, C. Wang, Z. Fan, G. Liu, C. Wang, Z. Gu, D. Damm, A. Mosig, and X. Wei, “Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry,” Cytometry A 79(10), 848–854 (2011).
[Crossref] [PubMed]

Y. Li, Z. Fan, J. Guo, G. Liu, X. Tan, C. Wang, and et al.., “Circulation times of hepatocellular carcinoma cells by in vivo flow cytometry,” Chin. Opt. Lett. 10, 953–956 (2010).

Guzatov, D.

W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
[Crossref] [PubMed]

Han, Z.

X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, “In vivo skin optical clearing by glycerol solutions: mechanism,” J. Biophotonics 3(1-2), 44–52 (2010).
[Crossref] [PubMed]

Z. Zhi, Z. Han, Q. Luo, and D. Zhu, “Improve optical clearing of skin in vitro with propylene glycol as a penetration enhancer,” J. Innov. Opt. Health Sci. 2(3), 269–278 (2009).
[Crossref]

Hasan, T.

I. Georgakoudi, N. Solban, J. Novak, W. L. Rice, X. Wei, T. Hasan, and C. P. Lin, “In vivo flow cytometry: a new method for enumerating circulating cancer cells,” Cancer Res. 64(15), 5044–5047 (2004).
[Crossref] [PubMed]

Herrmann, A.

A. Herrmann, M. Kortylewski, M. Kujawski, C. Zhang, K. Reckamp, B. Armstrong, L. Wang, C. Kowolik, J. Deng, R. Figlin, and H. Yu, “Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells,” Cancer Res. 70(19), 7455–7464 (2010).
[Crossref] [PubMed]

Huang, Q.

W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
[Crossref] [PubMed]

Hwu, D.

S. Boutrus, C. Greiner, D. Hwu, M. Chan, C. Kuperwasser, C. P. Lin, and I. Georgakoudi, “Portable two-color in vivo flow cytometer for real-time detection of fluorescently-labeled circulating cells,” J. Biomed. Opt. 12(2), 020507 (2007).
[Crossref] [PubMed]

Jacques, S. L.

X. Wen, S. L. Jacques, V. V. Tuchin, and D. Zhu, “Enhanced optical clearing of skin in vivo and optical coherence tomography in-depth imaging,” J. Biomed. Opt. 17(6), 066022 (2012).
[Crossref] [PubMed]

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(2), 83–85 (2004).
[Crossref] [PubMed]

Khlebtsov, B. N.

G. S. Terentyuk, G. N. Maslyakova, L. V. Suleymanova, N. G. Khlebtsov, B. N. Khlebtsov, G. G. Akchurin, I. L. Maksimova, and V. V. Tuchin, “Laser-induced tissue hyperthermia mediated by gold nanoparticles: toward cancer phototherapy,” J. Biomed. Opt. 14(2), 021016 (2009).
[Crossref] [PubMed]

Khlebtsov, N. G.

G. S. Terentyuk, G. N. Maslyakova, L. V. Suleymanova, N. G. Khlebtsov, B. N. Khlebtsov, G. G. Akchurin, I. L. Maksimova, and V. V. Tuchin, “Laser-induced tissue hyperthermia mediated by gold nanoparticles: toward cancer phototherapy,” J. Biomed. Opt. 14(2), 021016 (2009).
[Crossref] [PubMed]

Kon, I. L.

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlyutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2(4), 401–417 (1997).
[Crossref] [PubMed]

Kortylewski, M.

A. Herrmann, M. Kortylewski, M. Kujawski, C. Zhang, K. Reckamp, B. Armstrong, L. Wang, C. Kowolik, J. Deng, R. Figlin, and H. Yu, “Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells,” Cancer Res. 70(19), 7455–7464 (2010).
[Crossref] [PubMed]

Kowolik, C.

A. Herrmann, M. Kortylewski, M. Kujawski, C. Zhang, K. Reckamp, B. Armstrong, L. Wang, C. Kowolik, J. Deng, R. Figlin, and H. Yu, “Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells,” Cancer Res. 70(19), 7455–7464 (2010).
[Crossref] [PubMed]

Ku, G.

W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
[Crossref] [PubMed]

Kujawski, M.

A. Herrmann, M. Kortylewski, M. Kujawski, C. Zhang, K. Reckamp, B. Armstrong, L. Wang, C. Kowolik, J. Deng, R. Figlin, and H. Yu, “Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells,” Cancer Res. 70(19), 7455–7464 (2010).
[Crossref] [PubMed]

Kuperwasser, C.

S. Boutrus, C. Greiner, D. Hwu, M. Chan, C. Kuperwasser, C. P. Lin, and I. Georgakoudi, “Portable two-color in vivo flow cytometer for real-time detection of fluorescently-labeled circulating cells,” J. Biomed. Opt. 12(2), 020507 (2007).
[Crossref] [PubMed]

Larin, K. V.

D. Zhu, K. V. Larin, Q. Luo, and V. V. Tuchin, “Recent progress in tissue optical clearing,” Laser Photonics Rev. 7(5), 732–757 (2013).
[Crossref]

Li, C.

W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
[Crossref] [PubMed]

Li, P.

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, “Short-term and long-term effects of optical clearing agents on blood vessels in chick chorioallantoic membrane,” J. Biomed. Opt. 13(2), 021106 (2008).
[Crossref] [PubMed]

Li, Y.

Y. Li, J. Guo, C. Wang, Z. Fan, G. Liu, C. Wang, Z. Gu, D. Damm, A. Mosig, and X. Wei, “Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry,” Cytometry A 79(10), 848–854 (2011).
[Crossref] [PubMed]

J. Wang, Y. Liang, S. Zhang, Y. Zhou, H. Ni, and Y. Li, “Evaluation of optical clearing with the combined liquid paraffin and glycerol mixture,” Biomed. Opt. Express 2(8), 2329–2338 (2011).
[Crossref] [PubMed]

Y. Li, Z. Fan, J. Guo, G. Liu, X. Tan, C. Wang, and et al.., “Circulation times of hepatocellular carcinoma cells by in vivo flow cytometry,” Chin. Opt. Lett. 10, 953–956 (2010).

Liang, Y.

Lin, C. P.

S. Boutrus, C. Greiner, D. Hwu, M. Chan, C. Kuperwasser, C. P. Lin, and I. Georgakoudi, “Portable two-color in vivo flow cytometer for real-time detection of fluorescently-labeled circulating cells,” J. Biomed. Opt. 12(2), 020507 (2007).
[Crossref] [PubMed]

J. Novak, I. Georgakoudi, X. Wei, A. Prossin, and C. P. Lin, “In vivo flow cytometer for real-time detection and quantification of circulating cells,” Opt. Lett. 29(1), 77–79 (2004).
[Crossref] [PubMed]

I. Georgakoudi, N. Solban, J. Novak, W. L. Rice, X. Wei, T. Hasan, and C. P. Lin, “In vivo flow cytometry: a new method for enumerating circulating cancer cells,” Cancer Res. 64(15), 5044–5047 (2004).
[Crossref] [PubMed]

Liu, C.

C. Liu, Z. Zhi, V. V. Tuchin, Q. Luo, and D. Zhu, “Enhancement of skin optical clearing efficacy using photo-irradiation,” Lasers Surg. Med. 42(2), 132–140 (2010).
[Crossref] [PubMed]

Liu, G.

Y. Li, J. Guo, C. Wang, Z. Fan, G. Liu, C. Wang, Z. Gu, D. Damm, A. Mosig, and X. Wei, “Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry,” Cytometry A 79(10), 848–854 (2011).
[Crossref] [PubMed]

Y. Li, Z. Fan, J. Guo, G. Liu, X. Tan, C. Wang, and et al.., “Circulation times of hepatocellular carcinoma cells by in vivo flow cytometry,” Chin. Opt. Lett. 10, 953–956 (2010).

Liu, G. D.

Z. C. Fan, J. Yan, G. D. Liu, X. Y. Tan, X. F. Weng, W. Z. Wu, J. Zhou, and X. B. Wei, “Real-time monitoring of rare circulating hepatocellular carcinoma cells in an orthotopic model by in vivo flow cytometry Assesses Resection On Metastasis,” Cancer Res. 72(10), 2683–2691 (2012).
[Crossref] [PubMed]

Lu, W.

W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
[Crossref] [PubMed]

Luo, Q.

D. Zhu, K. V. Larin, Q. Luo, and V. V. Tuchin, “Recent progress in tissue optical clearing,” Laser Photonics Rev. 7(5), 732–757 (2013).
[Crossref]

C. Liu, Z. Zhi, V. V. Tuchin, Q. Luo, and D. Zhu, “Enhancement of skin optical clearing efficacy using photo-irradiation,” Lasers Surg. Med. 42(2), 132–140 (2010).
[Crossref] [PubMed]

D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, “Imaging dermal blood flow through the intact rat skin with an optical clearing method,” J. Biomed. Opt. 15(2), 026008 (2010).
[Crossref] [PubMed]

Z. Zhi, Z. Han, Q. Luo, and D. Zhu, “Improve optical clearing of skin in vitro with propylene glycol as a penetration enhancer,” J. Innov. Opt. Health Sci. 2(3), 269–278 (2009).
[Crossref]

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, “Short-term and long-term effects of optical clearing agents on blood vessels in chick chorioallantoic membrane,” J. Biomed. Opt. 13(2), 021106 (2008).
[Crossref] [PubMed]

H. Cheng, Q. Luo, S. Zeng, S. Chen, W. Luo, and H. Gong, “Hyperosmotic chemical agent’s effect on in vivo cerebral blood flow revealed by laser speckle,” Appl. Opt. 43(31), 5772–5777 (2004).
[Crossref] [PubMed]

Luo, W.

M Kelly, K.

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(2), 83–85 (2004).
[Crossref] [PubMed]

Maksimova, I. L.

G. S. Terentyuk, G. N. Maslyakova, L. V. Suleymanova, N. G. Khlebtsov, B. N. Khlebtsov, G. G. Akchurin, I. L. Maksimova, and V. V. Tuchin, “Laser-induced tissue hyperthermia mediated by gold nanoparticles: toward cancer phototherapy,” J. Biomed. Opt. 14(2), 021016 (2009).
[Crossref] [PubMed]

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlyutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2(4), 401–417 (1997).
[Crossref] [PubMed]

Mao, Z.

X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, “In vivo skin optical clearing by glycerol solutions: mechanism,” J. Biophotonics 3(1-2), 44–52 (2010).
[Crossref] [PubMed]

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, “Short-term and long-term effects of optical clearing agents on blood vessels in chick chorioallantoic membrane,” J. Biomed. Opt. 13(2), 021106 (2008).
[Crossref] [PubMed]

Maslyakova, G. N.

G. S. Terentyuk, G. N. Maslyakova, L. V. Suleymanova, N. G. Khlebtsov, B. N. Khlebtsov, G. G. Akchurin, I. L. Maksimova, and V. V. Tuchin, “Laser-induced tissue hyperthermia mediated by gold nanoparticles: toward cancer phototherapy,” J. Biomed. Opt. 14(2), 021016 (2009).
[Crossref] [PubMed]

Mavlyutov, A. H.

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlyutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2(4), 401–417 (1997).
[Crossref] [PubMed]

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(2), 83–85 (2004).
[Crossref] [PubMed]

Mishin, A. A.

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlyutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2(4), 401–417 (1997).
[Crossref] [PubMed]

Mosig, A.

Y. Li, J. Guo, C. Wang, Z. Fan, G. Liu, C. Wang, Z. Gu, D. Damm, A. Mosig, and X. Wei, “Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry,” Cytometry A 79(10), 848–854 (2011).
[Crossref] [PubMed]

Nelson, J. 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(2), 83–85 (2004).
[Crossref] [PubMed]

Ni, H.

Novak, J.

J. Novak, I. Georgakoudi, X. Wei, A. Prossin, and C. P. Lin, “In vivo flow cytometer for real-time detection and quantification of circulating cells,” Opt. Lett. 29(1), 77–79 (2004).
[Crossref] [PubMed]

I. Georgakoudi, N. Solban, J. Novak, W. L. Rice, X. Wei, T. Hasan, and C. P. Lin, “In vivo flow cytometry: a new method for enumerating circulating cancer cells,” Cancer Res. 64(15), 5044–5047 (2004).
[Crossref] [PubMed]

Oraevsky, A.

W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
[Crossref] [PubMed]

Prossin, A.

Readinger, A.

G. Vargas, A. Readinger, S. S. Dozier, and A. J. Welch, “Morphological changes in blood vessels produced by hyperosmotic agents and measured by optical coherence tomography,” Photochem. Photobiol. 77(5), 541–549 (2003).
[Crossref] [PubMed]

Reckamp, K.

A. Herrmann, M. Kortylewski, M. Kujawski, C. Zhang, K. Reckamp, B. Armstrong, L. Wang, C. Kowolik, J. Deng, R. Figlin, and H. Yu, “Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells,” Cancer Res. 70(19), 7455–7464 (2010).
[Crossref] [PubMed]

Rice, W. L.

I. Georgakoudi, N. Solban, J. Novak, W. L. Rice, X. Wei, T. Hasan, and C. P. Lin, “In vivo flow cytometry: a new method for enumerating circulating cancer cells,” Cancer Res. 64(15), 5044–5047 (2004).
[Crossref] [PubMed]

Shi, R.

J. Wang, R. Shi, Y. Zhang, and D. Zhu, “Ear skin optical clearing for improving blood flow imaging,” Photon. Lasers Med. 2(1), 37–44 (2013).

J. Wang, R. Shi, and D. Zhu, “Optical clearing method induced switchable skin window for dermal blood flow imaging,” J. Biomed. Opt. 18(6), 061209 (2013).
[Crossref] [PubMed]

Solban, N.

I. Georgakoudi, N. Solban, J. Novak, W. L. Rice, X. Wei, T. Hasan, and C. P. Lin, “In vivo flow cytometry: a new method for enumerating circulating cancer cells,” Cancer Res. 64(15), 5044–5047 (2004).
[Crossref] [PubMed]

Su, R.

W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
[Crossref] [PubMed]

Suleymanova, L. V.

G. S. Terentyuk, G. N. Maslyakova, L. V. Suleymanova, N. G. Khlebtsov, B. N. Khlebtsov, G. G. Akchurin, I. L. Maksimova, and V. V. Tuchin, “Laser-induced tissue hyperthermia mediated by gold nanoparticles: toward cancer phototherapy,” J. Biomed. Opt. 14(2), 021016 (2009).
[Crossref] [PubMed]

Tan, X.

Y. Li, Z. Fan, J. Guo, G. Liu, X. Tan, C. Wang, and et al.., “Circulation times of hepatocellular carcinoma cells by in vivo flow cytometry,” Chin. Opt. Lett. 10, 953–956 (2010).

Tan, X. Y.

Z. C. Fan, J. Yan, G. D. Liu, X. Y. Tan, X. F. Weng, W. Z. Wu, J. Zhou, and X. B. Wei, “Real-time monitoring of rare circulating hepatocellular carcinoma cells in an orthotopic model by in vivo flow cytometry Assesses Resection On Metastasis,” Cancer Res. 72(10), 2683–2691 (2012).
[Crossref] [PubMed]

Terentyuk, G. S.

G. S. Terentyuk, G. N. Maslyakova, L. V. Suleymanova, N. G. Khlebtsov, B. N. Khlebtsov, G. G. Akchurin, I. L. Maksimova, and V. V. Tuchin, “Laser-induced tissue hyperthermia mediated by gold nanoparticles: toward cancer phototherapy,” J. Biomed. Opt. 14(2), 021016 (2009).
[Crossref] [PubMed]

Tuchin, V. V.

D. Zhu, K. V. Larin, Q. Luo, and V. V. Tuchin, “Recent progress in tissue optical clearing,” Laser Photonics Rev. 7(5), 732–757 (2013).
[Crossref]

X. Wen, S. L. Jacques, V. V. Tuchin, and D. Zhu, “Enhanced optical clearing of skin in vivo and optical coherence tomography in-depth imaging,” J. Biomed. Opt. 17(6), 066022 (2012).
[Crossref] [PubMed]

A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).
[Crossref]

X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, “In vivo skin optical clearing by glycerol solutions: mechanism,” J. Biophotonics 3(1-2), 44–52 (2010).
[Crossref] [PubMed]

E. A. Genina, A. N. Bashkatov, and V. V. Tuchin, “Tissue optical immersion clearing,” Expert Rev. Med. Devices 7(6), 825–842 (2010).
[Crossref] [PubMed]

C. Liu, Z. Zhi, V. V. Tuchin, Q. Luo, and D. Zhu, “Enhancement of skin optical clearing efficacy using photo-irradiation,” Lasers Surg. Med. 42(2), 132–140 (2010).
[Crossref] [PubMed]

G. S. Terentyuk, G. N. Maslyakova, L. V. Suleymanova, N. G. Khlebtsov, B. N. Khlebtsov, G. G. Akchurin, I. L. Maksimova, and V. V. Tuchin, “Laser-induced tissue hyperthermia mediated by gold nanoparticles: toward cancer phototherapy,” J. Biomed. Opt. 14(2), 021016 (2009).
[Crossref] [PubMed]

V. V. Tuchin, “Optical clearing of tissue and blood using immersion method,” J. Phys. D Appl. Phys. 38(15), 2497–2518 (2005).
[Crossref]

V. V. Tuchin, “Optical immersion as a new tool to control optical properties of tissues and blood,” Laser Phys. 15(8), 1109–1136 (2005).

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlyutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2(4), 401–417 (1997).
[Crossref] [PubMed]

Vargas, G.

G. Vargas, A. Readinger, S. S. Dozier, and A. J. Welch, “Morphological changes in blood vessels produced by hyperosmotic agents and measured by optical coherence tomography,” Photochem. Photobiol. 77(5), 541–549 (2003).
[Crossref] [PubMed]

Wang, C.

Y. Li, J. Guo, C. Wang, Z. Fan, G. Liu, C. Wang, Z. Gu, D. Damm, A. Mosig, and X. Wei, “Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry,” Cytometry A 79(10), 848–854 (2011).
[Crossref] [PubMed]

Y. Li, J. Guo, C. Wang, Z. Fan, G. Liu, C. Wang, Z. Gu, D. Damm, A. Mosig, and X. Wei, “Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry,” Cytometry A 79(10), 848–854 (2011).
[Crossref] [PubMed]

Y. Li, Z. Fan, J. Guo, G. Liu, X. Tan, C. Wang, and et al.., “Circulation times of hepatocellular carcinoma cells by in vivo flow cytometry,” Chin. Opt. Lett. 10, 953–956 (2010).

Wang, J.

J. Wang, R. Shi, and D. Zhu, “Optical clearing method induced switchable skin window for dermal blood flow imaging,” J. Biomed. Opt. 18(6), 061209 (2013).
[Crossref] [PubMed]

J. Wang, R. Shi, Y. Zhang, and D. Zhu, “Ear skin optical clearing for improving blood flow imaging,” Photon. Lasers Med. 2(1), 37–44 (2013).

J. Wang, Y. Liang, S. Zhang, Y. Zhou, H. Ni, and Y. Li, “Evaluation of optical clearing with the combined liquid paraffin and glycerol mixture,” Biomed. Opt. Express 2(8), 2329–2338 (2011).
[Crossref] [PubMed]

D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, “Imaging dermal blood flow through the intact rat skin with an optical clearing method,” J. Biomed. Opt. 15(2), 026008 (2010).
[Crossref] [PubMed]

Wang, L.

A. Herrmann, M. Kortylewski, M. Kujawski, C. Zhang, K. Reckamp, B. Armstrong, L. Wang, C. Kowolik, J. Deng, R. Figlin, and H. Yu, “Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells,” Cancer Res. 70(19), 7455–7464 (2010).
[Crossref] [PubMed]

Wang, L. V.

W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
[Crossref] [PubMed]

Wei, X.

J. Guo, Z. Fan, Z. Gu, and X. Wei, “Studying the role of macrophages in circulating prostate cancer cells by in vivo flow cytometry,” J. Innov. Opt. Health Sci. 5(4), 1250027 (2012).
[Crossref]

Y. Li, J. Guo, C. Wang, Z. Fan, G. Liu, C. Wang, Z. Gu, D. Damm, A. Mosig, and X. Wei, “Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry,” Cytometry A 79(10), 848–854 (2011).
[Crossref] [PubMed]

I. Georgakoudi, N. Solban, J. Novak, W. L. Rice, X. Wei, T. Hasan, and C. P. Lin, “In vivo flow cytometry: a new method for enumerating circulating cancer cells,” Cancer Res. 64(15), 5044–5047 (2004).
[Crossref] [PubMed]

J. Novak, I. Georgakoudi, X. Wei, A. Prossin, and C. P. Lin, “In vivo flow cytometer for real-time detection and quantification of circulating cells,” Opt. Lett. 29(1), 77–79 (2004).
[Crossref] [PubMed]

Wei, X. B.

Z. C. Fan, J. Yan, G. D. Liu, X. Y. Tan, X. F. Weng, W. Z. Wu, J. Zhou, and X. B. Wei, “Real-time monitoring of rare circulating hepatocellular carcinoma cells in an orthotopic model by in vivo flow cytometry Assesses Resection On Metastasis,” Cancer Res. 72(10), 2683–2691 (2012).
[Crossref] [PubMed]

Welch, A. J.

G. Vargas, A. Readinger, S. S. Dozier, and A. J. Welch, “Morphological changes in blood vessels produced by hyperosmotic agents and measured by optical coherence tomography,” Photochem. Photobiol. 77(5), 541–549 (2003).
[Crossref] [PubMed]

Wen, X.

X. Wen, S. L. Jacques, V. V. Tuchin, and D. Zhu, “Enhanced optical clearing of skin in vivo and optical coherence tomography in-depth imaging,” J. Biomed. Opt. 17(6), 066022 (2012).
[Crossref] [PubMed]

D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, “Imaging dermal blood flow through the intact rat skin with an optical clearing method,” J. Biomed. Opt. 15(2), 026008 (2010).
[Crossref] [PubMed]

X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, “In vivo skin optical clearing by glycerol solutions: mechanism,” J. Biophotonics 3(1-2), 44–52 (2010).
[Crossref] [PubMed]

W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
[Crossref] [PubMed]

Weng, X. F.

Z. C. Fan, J. Yan, G. D. Liu, X. Y. Tan, X. F. Weng, W. Z. Wu, J. Zhou, and X. B. Wei, “Real-time monitoring of rare circulating hepatocellular carcinoma cells in an orthotopic model by in vivo flow cytometry Assesses Resection On Metastasis,” Cancer Res. 72(10), 2683–2691 (2012).
[Crossref] [PubMed]

Wu, W. Z.

Z. C. Fan, J. Yan, G. D. Liu, X. Y. Tan, X. F. Weng, W. Z. Wu, J. Zhou, and X. B. Wei, “Real-time monitoring of rare circulating hepatocellular carcinoma cells in an orthotopic model by in vivo flow cytometry Assesses Resection On Metastasis,” Cancer Res. 72(10), 2683–2691 (2012).
[Crossref] [PubMed]

Yan, J.

Z. C. Fan, J. Yan, G. D. Liu, X. Y. Tan, X. F. Weng, W. Z. Wu, J. Zhou, and X. B. Wei, “Real-time monitoring of rare circulating hepatocellular carcinoma cells in an orthotopic model by in vivo flow cytometry Assesses Resection On Metastasis,” Cancer Res. 72(10), 2683–2691 (2012).
[Crossref] [PubMed]

Yu, H.

A. Herrmann, M. Kortylewski, M. Kujawski, C. Zhang, K. Reckamp, B. Armstrong, L. Wang, C. Kowolik, J. Deng, R. Figlin, and H. Yu, “Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells,” Cancer Res. 70(19), 7455–7464 (2010).
[Crossref] [PubMed]

Zeng, S.

Zhang, C.

A. Herrmann, M. Kortylewski, M. Kujawski, C. Zhang, K. Reckamp, B. Armstrong, L. Wang, C. Kowolik, J. Deng, R. Figlin, and H. Yu, “Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells,” Cancer Res. 70(19), 7455–7464 (2010).
[Crossref] [PubMed]

Zhang, J.

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, “Short-term and long-term effects of optical clearing agents on blood vessels in chick chorioallantoic membrane,” J. Biomed. Opt. 13(2), 021106 (2008).
[Crossref] [PubMed]

Zhang, S.

Zhang, Y.

J. Wang, R. Shi, Y. Zhang, and D. Zhu, “Ear skin optical clearing for improving blood flow imaging,” Photon. Lasers Med. 2(1), 37–44 (2013).

Zhi, Z.

D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, “Imaging dermal blood flow through the intact rat skin with an optical clearing method,” J. Biomed. Opt. 15(2), 026008 (2010).
[Crossref] [PubMed]

C. Liu, Z. Zhi, V. V. Tuchin, Q. Luo, and D. Zhu, “Enhancement of skin optical clearing efficacy using photo-irradiation,” Lasers Surg. Med. 42(2), 132–140 (2010).
[Crossref] [PubMed]

Z. Zhi, Z. Han, Q. Luo, and D. Zhu, “Improve optical clearing of skin in vitro with propylene glycol as a penetration enhancer,” J. Innov. Opt. Health Sci. 2(3), 269–278 (2009).
[Crossref]

Zhou, J.

Z. C. Fan, J. Yan, G. D. Liu, X. Y. Tan, X. F. Weng, W. Z. Wu, J. Zhou, and X. B. Wei, “Real-time monitoring of rare circulating hepatocellular carcinoma cells in an orthotopic model by in vivo flow cytometry Assesses Resection On Metastasis,” Cancer Res. 72(10), 2683–2691 (2012).
[Crossref] [PubMed]

Zhou, M.

W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
[Crossref] [PubMed]

Zhou, Y.

Zhu, D.

D. Zhu, K. V. Larin, Q. Luo, and V. V. Tuchin, “Recent progress in tissue optical clearing,” Laser Photonics Rev. 7(5), 732–757 (2013).
[Crossref]

J. Wang, R. Shi, Y. Zhang, and D. Zhu, “Ear skin optical clearing for improving blood flow imaging,” Photon. Lasers Med. 2(1), 37–44 (2013).

J. Wang, R. Shi, and D. Zhu, “Optical clearing method induced switchable skin window for dermal blood flow imaging,” J. Biomed. Opt. 18(6), 061209 (2013).
[Crossref] [PubMed]

X. Wen, S. L. Jacques, V. V. Tuchin, and D. Zhu, “Enhanced optical clearing of skin in vivo and optical coherence tomography in-depth imaging,” J. Biomed. Opt. 17(6), 066022 (2012).
[Crossref] [PubMed]

X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, “In vivo skin optical clearing by glycerol solutions: mechanism,” J. Biophotonics 3(1-2), 44–52 (2010).
[Crossref] [PubMed]

D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, “Imaging dermal blood flow through the intact rat skin with an optical clearing method,” J. Biomed. Opt. 15(2), 026008 (2010).
[Crossref] [PubMed]

C. Liu, Z. Zhi, V. V. Tuchin, Q. Luo, and D. Zhu, “Enhancement of skin optical clearing efficacy using photo-irradiation,” Lasers Surg. Med. 42(2), 132–140 (2010).
[Crossref] [PubMed]

Z. Zhi, Z. Han, Q. Luo, and D. Zhu, “Improve optical clearing of skin in vitro with propylene glycol as a penetration enhancer,” J. Innov. Opt. Health Sci. 2(3), 269–278 (2009).
[Crossref]

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, “Short-term and long-term effects of optical clearing agents on blood vessels in chick chorioallantoic membrane,” J. Biomed. Opt. 13(2), 021106 (2008).
[Crossref] [PubMed]

Zimnyakov, D. A.

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlyutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2(4), 401–417 (1997).
[Crossref] [PubMed]

Appl. Opt. (1)

Biomaterials (1)

W. Lu, Q. Huang, G. Ku, X. Wen, M. Zhou, D. Guzatov, P. Brecht, R. Su, A. Oraevsky, L. V. Wang, and C. Li, “Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres,” Biomaterials 31(9), 2617–2626 (2010).
[Crossref] [PubMed]

Biomed. Opt. Express (1)

Cancer Res. (3)

A. Herrmann, M. Kortylewski, M. Kujawski, C. Zhang, K. Reckamp, B. Armstrong, L. Wang, C. Kowolik, J. Deng, R. Figlin, and H. Yu, “Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells,” Cancer Res. 70(19), 7455–7464 (2010).
[Crossref] [PubMed]

I. Georgakoudi, N. Solban, J. Novak, W. L. Rice, X. Wei, T. Hasan, and C. P. Lin, “In vivo flow cytometry: a new method for enumerating circulating cancer cells,” Cancer Res. 64(15), 5044–5047 (2004).
[Crossref] [PubMed]

Z. C. Fan, J. Yan, G. D. Liu, X. Y. Tan, X. F. Weng, W. Z. Wu, J. Zhou, and X. B. Wei, “Real-time monitoring of rare circulating hepatocellular carcinoma cells in an orthotopic model by in vivo flow cytometry Assesses Resection On Metastasis,” Cancer Res. 72(10), 2683–2691 (2012).
[Crossref] [PubMed]

Chin. Opt. Lett. (1)

Y. Li, Z. Fan, J. Guo, G. Liu, X. Tan, C. Wang, and et al.., “Circulation times of hepatocellular carcinoma cells by in vivo flow cytometry,” Chin. Opt. Lett. 10, 953–956 (2010).

Cytometry A (1)

Y. Li, J. Guo, C. Wang, Z. Fan, G. Liu, C. Wang, Z. Gu, D. Damm, A. Mosig, and X. Wei, “Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry,” Cytometry A 79(10), 848–854 (2011).
[Crossref] [PubMed]

Expert Rev. Med. Devices (1)

E. A. Genina, A. N. Bashkatov, and V. V. Tuchin, “Tissue optical immersion clearing,” Expert Rev. Med. Devices 7(6), 825–842 (2010).
[Crossref] [PubMed]

IEEE Trans. Inf. Theory (1)

D. Donoho, “De-noising by soft-thresholding,” IEEE Trans. Inf. Theory 41(3), 613–627 (1995).
[Crossref]

J. Biomed. Opt. (7)

D. Zhu, J. Wang, Z. Zhi, X. Wen, and Q. Luo, “Imaging dermal blood flow through the intact rat skin with an optical clearing method,” J. Biomed. Opt. 15(2), 026008 (2010).
[Crossref] [PubMed]

J. Wang, R. Shi, and D. Zhu, “Optical clearing method induced switchable skin window for dermal blood flow imaging,” J. Biomed. Opt. 18(6), 061209 (2013).
[Crossref] [PubMed]

X. Wen, S. L. Jacques, V. V. Tuchin, and D. Zhu, “Enhanced optical clearing of skin in vivo and optical coherence tomography in-depth imaging,” J. Biomed. Opt. 17(6), 066022 (2012).
[Crossref] [PubMed]

D. Zhu, J. Zhang, H. Cui, Z. Mao, P. Li, and Q. Luo, “Short-term and long-term effects of optical clearing agents on blood vessels in chick chorioallantoic membrane,” J. Biomed. Opt. 13(2), 021106 (2008).
[Crossref] [PubMed]

S. Boutrus, C. Greiner, D. Hwu, M. Chan, C. Kuperwasser, C. P. Lin, and I. Georgakoudi, “Portable two-color in vivo flow cytometer for real-time detection of fluorescently-labeled circulating cells,” J. Biomed. Opt. 12(2), 020507 (2007).
[Crossref] [PubMed]

V. V. Tuchin, I. L. Maksimova, D. A. Zimnyakov, I. L. Kon, A. H. Mavlyutov, and A. A. Mishin, “Light propagation in tissues with controlled optical properties,” J. Biomed. Opt. 2(4), 401–417 (1997).
[Crossref] [PubMed]

G. S. Terentyuk, G. N. Maslyakova, L. V. Suleymanova, N. G. Khlebtsov, B. N. Khlebtsov, G. G. Akchurin, I. L. Maksimova, and V. V. Tuchin, “Laser-induced tissue hyperthermia mediated by gold nanoparticles: toward cancer phototherapy,” J. Biomed. Opt. 14(2), 021016 (2009).
[Crossref] [PubMed]

J. Biophotonics (1)

X. Wen, Z. Mao, Z. Han, V. V. Tuchin, and D. Zhu, “In vivo skin optical clearing by glycerol solutions: mechanism,” J. Biophotonics 3(1-2), 44–52 (2010).
[Crossref] [PubMed]

J. Innov. Opt. Health Sci. (3)

A. N. Bashkatov, E. A. Genina, and V. V. Tuchin, “Optical properties of skin, subcutaneous, and muscle tissues: a review,” J. Innov. Opt. Health Sci. 4(1), 9–38 (2011).
[Crossref]

J. Guo, Z. Fan, Z. Gu, and X. Wei, “Studying the role of macrophages in circulating prostate cancer cells by in vivo flow cytometry,” J. Innov. Opt. Health Sci. 5(4), 1250027 (2012).
[Crossref]

Z. Zhi, Z. Han, Q. Luo, and D. Zhu, “Improve optical clearing of skin in vitro with propylene glycol as a penetration enhancer,” J. Innov. Opt. Health Sci. 2(3), 269–278 (2009).
[Crossref]

J. Phys. D Appl. Phys. (1)

V. V. Tuchin, “Optical clearing of tissue and blood using immersion method,” J. Phys. D Appl. Phys. 38(15), 2497–2518 (2005).
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Laser Photonics Rev. (1)

D. Zhu, K. V. Larin, Q. Luo, and V. V. Tuchin, “Recent progress in tissue optical clearing,” Laser Photonics Rev. 7(5), 732–757 (2013).
[Crossref]

Laser Phys. (1)

V. V. Tuchin, “Optical immersion as a new tool to control optical properties of tissues and blood,” Laser Phys. 15(8), 1109–1136 (2005).

Lasers Surg. Med. (2)

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(2), 83–85 (2004).
[Crossref] [PubMed]

C. Liu, Z. Zhi, V. V. Tuchin, Q. Luo, and D. Zhu, “Enhancement of skin optical clearing efficacy using photo-irradiation,” Lasers Surg. Med. 42(2), 132–140 (2010).
[Crossref] [PubMed]

Nat. Rev. Cancer (1)

I. J. Fidler, “The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited,” Nat. Rev. Cancer 3(6), 453–458 (2003).
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Opt. Lett. (1)

Photochem. Photobiol. (1)

G. Vargas, A. Readinger, S. S. Dozier, and A. J. Welch, “Morphological changes in blood vessels produced by hyperosmotic agents and measured by optical coherence tomography,” Photochem. Photobiol. 77(5), 541–549 (2003).
[Crossref] [PubMed]

Photon. Lasers Med. (1)

J. Wang, R. Shi, Y. Zhang, and D. Zhu, “Ear skin optical clearing for improving blood flow imaging,” Photon. Lasers Med. 2(1), 37–44 (2013).

Other (2)

J. Novak, “Development of in vivo flow cytometry,” Ph.D. dissertation, Dept. Mech. Eng., Harvard Univ. Cambridge, MA, 2004.

V. V. Tuchin, Optical Clearing of Tissues and Blood, (SPIE Press, Bellingham, 2005), Vol. 154.

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Figures (6)

Fig. 1
Fig. 1

Schematic of the in vivo flow cytometer experimental setup: CL, cylindrical lens; MS: mechanical slit; AL1-AL3: achromatic lens; M: mirrors; BS1-BS2: dichroic beam splitters; objective lens (40 × , NA = 0.6); F1-F2: band pass filters; PMT: photo-multiplier tube; DAQ: data acquisition.

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Fig. 2
Fig. 2

(a) Representative transmittance spectra of rat ear before and after the treatment with glycerol, saline solution and ESOCA, respectively. (b) Relative transmittance spectra after the treatment of different agents.

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Fig. 3
Fig. 3

IVFC signals of DiD-labeled red blood cells (left: treated by glycerol; right: treated by ESOCA). The signals were recorded at the depth of 80 μm (a), and 180 μm (b) for 6 minutes. Each peak represented a DiD-labeled cell traversing the excitation slit.

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Fig. 4
Fig. 4

Comparison of signal peak properties after the treatment with glycerol or ESOCA, respectively (a.u.: arbitrary unit, p<0.05 *).

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Fig. 5
Fig. 5

Changes in peak intensity of IVFC as a function of scanning depth. A depth of “0 μm” represented the upper surface of rat ear. The IVFC signals at various depths were recorded until no signals could be detected beyond a depth limit. The peak intensities of signals for 6 min with the same axial depth in this region were averaged.

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Fig. 6
Fig. 6

Full duration distribution at half maximum of IVFC signals after the treatment of OCAs for one hour. The FDHM indicates the speed of fluorescently labeled cells travelling through the laser slit. Thus a left shift to lower FDHM values indicates faster blood flow.

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Tables (1)

Tables Icon

Table 1 Transmittance of rat ear at different wavelengths before or after the treatment of agents (p<0.01**).

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Equations (3)

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Δ T = T t r e a t e d − T i n i t i a l T i n i t i a l
T h r e s h o l d = M e d i a n + M u l t i p l i e r * M A D / 0.6745
S N R = A s / A n

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