Abstract

Optical imaging of brain activity has mostly employed genetically manipulated mice, which cannot be translated to clinical human usage. Observation of brain activity directly is challenging due to the difficulty in delivering dyes and other agents through the blood brain barrier (BBB). Using fluorescence imaging, we have demonstrated the feasibility of delivering the near-infrared voltage-sensitive dye (VSD) IR-780 perchlorate to the brain tissue through pharmacological techniques, via an adenosine agonist (regadenoson). Comparison of VSD fluorescence of mouse brains without and with regadenoson showed significantly increased residence time of the fluorescence signal in the latter case, indicative of VSD diffusion into the brain tissue. Dose and timing of regadenoson were varied to optimize BBB permeability for VSD delivery.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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  1. A. D. Mehta, J. C. Jung, B. A. Flusberg, and M. J. Schnitzer, “Fiber optic in vivo imaging in the mammalian nervous system,” Curr. Opin. Neurobiol. 14(5), 617–628 (2004).
    [Crossref] [PubMed]
  2. C. Grienberger and A. Konnerth, “Imaging calcium in neurons,” Neuron 73(5), 862–885 (2012).
    [Crossref] [PubMed]
  3. M. Paukert, A. Agarwal, J. Cha, V. A. Doze, J. U. Kang, and D. E. Bergles, “Norepinephrine controls astroglial responsiveness to local circuit activity,” Neuron 82(6), 1263–1270 (2014).
    [Crossref] [PubMed]
  4. S. Chemla and F. Chavane, “Voltage-sensitive dye imaging: Technique review and models,” J. Physiol. Paris 104(1-2), 40–50 (2010).
    [Crossref] [PubMed]
  5. E. W. Miller, J. Y. Lin, E. P. Frady, P. A. Steinbach, W. B. Kristan, and R. Y. Tsien, “Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires,” Proc. Natl. Acad. Sci. U.S.A. 109(6), 2114–2119 (2012).
    [Crossref] [PubMed]
  6. S. I. Rapoport, “Osmotic opening of the blood-brain barrier: principles, mechanism, and therapeutic applications,” Cell. Mol. Neurobiol. 20(2), 217–230 (2000).
    [Crossref] [PubMed]
  7. C. Saraiva, C. Praça, R. Ferreira, T. Santos, L. Ferreira, and L. Bernardino, “Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases,” J. Control. Release 235, 34–47 (2016).
    [Crossref] [PubMed]
  8. G.-H. Son, B.-J. Lee, and C.-W. Cho, “Mechanisms of drug release from advanced drug formulations such as polymeric-based drug-delivery systems and lipid nanoparticles,” J. Pharm. Investig. 47(4), 287–296 (2017).
    [Crossref]
  9. Q.-L. Zhou, Z.-Y. Chen, Y.-X. Wang, F. Yang, Y. Lin, and Y.-Y. Liao, “Ultrasound-mediated local drug and gene delivery using nanocarriers,” BioMed Res. Int. 2014, 963891 (2014).
    [Crossref] [PubMed]
  10. P.-C. Chu, H.-L. Liu, H.-Y. Lai, C.-Y. Lin, H.-C. Tsai, and Y.-C. Pei, “Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening,” Sci. Rep. 5(1), 15477–15489 (2015).
    [Crossref] [PubMed]
  11. J. J. Choi, K. Selert, F. Vlachos, A. Wong, and E. E. Konofagou, “Noninvasive and localized neuronal delivery using short ultrasonic pulses and microbubbles,” Proc. Natl. Acad. Sci. U.S.A. 108(40), 16539–16544 (2011).
    [Crossref] [PubMed]
  12. A. J. Carman, J. H. Mills, A. Krenz, D.-G. Kim, and M. S. Bynoe, “Adenosine receptor signaling modulates permeability of the blood-brain barrier,” J. Neurosci. 31(37), 13272–13280 (2011).
    [Crossref] [PubMed]
  13. D.-G. Kim and M. S. Bynoe, “A2A adenosine receptor modulates drug efflux transporter P-glycoprotein at the blood-brain barrier,” J. Clin. Invest. 126(5), 1717–1733 (2016).
    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  15. Y. Duan, B. Q. Yang, C. C. Chang, J. Zhou, H. Y. Li, Z. H. Xu, Z. W. Wang, and D. Y. Li, “[Preliminary study on assessment of lexiscan-induced blood-brain barrier opening and its level by CT perfusion imaging],” Zhonghua Yi Xue Za Zhi 96(35), 2825–2829 (2016).
    [PubMed]
  16. P. J. Sims, A. S. Waggoner, C.-H. Wang, and J. F. Hoffman, “Studies on the Mechanism by Which Cyanine Dyes Measure Membrane Potential in Red Blood Cells and Phosphatidylcholine Vesicles,” Biochemistry 13(16), 3315–3330 (1974).
    [Crossref] [PubMed]
  17. M. Reers, T. W. Smith, and L. B. Chen, “J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential,” Biochemistry 30(18), 4480–4486 (1991).
    [Crossref] [PubMed]
  18. A. S. Waggoner, “Dye Indicators of Membrane Potential,” Annu. Rev. Biophys. Bioeng. 8(1), 47–68 (1979).
    [Crossref] [PubMed]
  19. J. S. Treger, “Sensors and probes: A universal voltage indicator,” Nat. Methods 11(107), L09–L12 (2014).
  20. J. S. Treger, M. F. Priest, R. Iezzi, and F. Bezanilla, “Indocyanine Green is a Voltage-Sensitive Fluorescent Dye,” Biophys. J. 106(2), 793a (2014).
    [Crossref]
  21. H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
    [Crossref] [PubMed]

2017 (2)

G.-H. Son, B.-J. Lee, and C.-W. Cho, “Mechanisms of drug release from advanced drug formulations such as polymeric-based drug-delivery systems and lipid nanoparticles,” J. Pharm. Investig. 47(4), 287–296 (2017).
[Crossref]

H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
[Crossref] [PubMed]

2016 (3)

C. Saraiva, C. Praça, R. Ferreira, T. Santos, L. Ferreira, and L. Bernardino, “Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases,” J. Control. Release 235, 34–47 (2016).
[Crossref] [PubMed]

D.-G. Kim and M. S. Bynoe, “A2A adenosine receptor modulates drug efflux transporter P-glycoprotein at the blood-brain barrier,” J. Clin. Invest. 126(5), 1717–1733 (2016).
[Crossref] [PubMed]

Y. Duan, B. Q. Yang, C. C. Chang, J. Zhou, H. Y. Li, Z. H. Xu, Z. W. Wang, and D. Y. Li, “[Preliminary study on assessment of lexiscan-induced blood-brain barrier opening and its level by CT perfusion imaging],” Zhonghua Yi Xue Za Zhi 96(35), 2825–2829 (2016).
[PubMed]

2015 (2)

D.-G. Kim and M. S. Bynoe, “A2A Adenosine Receptor Regulates the Human Blood-Brain Barrier Permeability,” Mol. Neurobiol. 52(1), 664–678 (2015).
[Crossref] [PubMed]

P.-C. Chu, H.-L. Liu, H.-Y. Lai, C.-Y. Lin, H.-C. Tsai, and Y.-C. Pei, “Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening,” Sci. Rep. 5(1), 15477–15489 (2015).
[Crossref] [PubMed]

2014 (4)

Q.-L. Zhou, Z.-Y. Chen, Y.-X. Wang, F. Yang, Y. Lin, and Y.-Y. Liao, “Ultrasound-mediated local drug and gene delivery using nanocarriers,” BioMed Res. Int. 2014, 963891 (2014).
[Crossref] [PubMed]

M. Paukert, A. Agarwal, J. Cha, V. A. Doze, J. U. Kang, and D. E. Bergles, “Norepinephrine controls astroglial responsiveness to local circuit activity,” Neuron 82(6), 1263–1270 (2014).
[Crossref] [PubMed]

J. S. Treger, “Sensors and probes: A universal voltage indicator,” Nat. Methods 11(107), L09–L12 (2014).

J. S. Treger, M. F. Priest, R. Iezzi, and F. Bezanilla, “Indocyanine Green is a Voltage-Sensitive Fluorescent Dye,” Biophys. J. 106(2), 793a (2014).
[Crossref]

2012 (2)

C. Grienberger and A. Konnerth, “Imaging calcium in neurons,” Neuron 73(5), 862–885 (2012).
[Crossref] [PubMed]

E. W. Miller, J. Y. Lin, E. P. Frady, P. A. Steinbach, W. B. Kristan, and R. Y. Tsien, “Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires,” Proc. Natl. Acad. Sci. U.S.A. 109(6), 2114–2119 (2012).
[Crossref] [PubMed]

2011 (2)

J. J. Choi, K. Selert, F. Vlachos, A. Wong, and E. E. Konofagou, “Noninvasive and localized neuronal delivery using short ultrasonic pulses and microbubbles,” Proc. Natl. Acad. Sci. U.S.A. 108(40), 16539–16544 (2011).
[Crossref] [PubMed]

A. J. Carman, J. H. Mills, A. Krenz, D.-G. Kim, and M. S. Bynoe, “Adenosine receptor signaling modulates permeability of the blood-brain barrier,” J. Neurosci. 31(37), 13272–13280 (2011).
[Crossref] [PubMed]

2010 (1)

S. Chemla and F. Chavane, “Voltage-sensitive dye imaging: Technique review and models,” J. Physiol. Paris 104(1-2), 40–50 (2010).
[Crossref] [PubMed]

2004 (1)

A. D. Mehta, J. C. Jung, B. A. Flusberg, and M. J. Schnitzer, “Fiber optic in vivo imaging in the mammalian nervous system,” Curr. Opin. Neurobiol. 14(5), 617–628 (2004).
[Crossref] [PubMed]

2000 (1)

S. I. Rapoport, “Osmotic opening of the blood-brain barrier: principles, mechanism, and therapeutic applications,” Cell. Mol. Neurobiol. 20(2), 217–230 (2000).
[Crossref] [PubMed]

1991 (1)

M. Reers, T. W. Smith, and L. B. Chen, “J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential,” Biochemistry 30(18), 4480–4486 (1991).
[Crossref] [PubMed]

1979 (1)

A. S. Waggoner, “Dye Indicators of Membrane Potential,” Annu. Rev. Biophys. Bioeng. 8(1), 47–68 (1979).
[Crossref] [PubMed]

1974 (1)

P. J. Sims, A. S. Waggoner, C.-H. Wang, and J. F. Hoffman, “Studies on the Mechanism by Which Cyanine Dyes Measure Membrane Potential in Red Blood Cells and Phosphatidylcholine Vesicles,” Biochemistry 13(16), 3315–3330 (1974).
[Crossref] [PubMed]

Abou, D. S.

H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
[Crossref] [PubMed]

Agarwal, A.

M. Paukert, A. Agarwal, J. Cha, V. A. Doze, J. U. Kang, and D. E. Bergles, “Norepinephrine controls astroglial responsiveness to local circuit activity,” Neuron 82(6), 1263–1270 (2014).
[Crossref] [PubMed]

Bergles, D. E.

M. Paukert, A. Agarwal, J. Cha, V. A. Doze, J. U. Kang, and D. E. Bergles, “Norepinephrine controls astroglial responsiveness to local circuit activity,” Neuron 82(6), 1263–1270 (2014).
[Crossref] [PubMed]

Bernardino, L.

C. Saraiva, C. Praça, R. Ferreira, T. Santos, L. Ferreira, and L. Bernardino, “Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases,” J. Control. Release 235, 34–47 (2016).
[Crossref] [PubMed]

Bezanilla, F.

J. S. Treger, M. F. Priest, R. Iezzi, and F. Bezanilla, “Indocyanine Green is a Voltage-Sensitive Fluorescent Dye,” Biophys. J. 106(2), 793a (2014).
[Crossref]

Boctor, E. M.

H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
[Crossref] [PubMed]

Bynoe, M. S.

D.-G. Kim and M. S. Bynoe, “A2A adenosine receptor modulates drug efflux transporter P-glycoprotein at the blood-brain barrier,” J. Clin. Invest. 126(5), 1717–1733 (2016).
[Crossref] [PubMed]

D.-G. Kim and M. S. Bynoe, “A2A Adenosine Receptor Regulates the Human Blood-Brain Barrier Permeability,” Mol. Neurobiol. 52(1), 664–678 (2015).
[Crossref] [PubMed]

A. J. Carman, J. H. Mills, A. Krenz, D.-G. Kim, and M. S. Bynoe, “Adenosine receptor signaling modulates permeability of the blood-brain barrier,” J. Neurosci. 31(37), 13272–13280 (2011).
[Crossref] [PubMed]

Carman, A. J.

A. J. Carman, J. H. Mills, A. Krenz, D.-G. Kim, and M. S. Bynoe, “Adenosine receptor signaling modulates permeability of the blood-brain barrier,” J. Neurosci. 31(37), 13272–13280 (2011).
[Crossref] [PubMed]

Cha, J.

M. Paukert, A. Agarwal, J. Cha, V. A. Doze, J. U. Kang, and D. E. Bergles, “Norepinephrine controls astroglial responsiveness to local circuit activity,” Neuron 82(6), 1263–1270 (2014).
[Crossref] [PubMed]

Chang, C. C.

Y. Duan, B. Q. Yang, C. C. Chang, J. Zhou, H. Y. Li, Z. H. Xu, Z. W. Wang, and D. Y. Li, “[Preliminary study on assessment of lexiscan-induced blood-brain barrier opening and its level by CT perfusion imaging],” Zhonghua Yi Xue Za Zhi 96(35), 2825–2829 (2016).
[PubMed]

Chavane, F.

S. Chemla and F. Chavane, “Voltage-sensitive dye imaging: Technique review and models,” J. Physiol. Paris 104(1-2), 40–50 (2010).
[Crossref] [PubMed]

Chemla, S.

S. Chemla and F. Chavane, “Voltage-sensitive dye imaging: Technique review and models,” J. Physiol. Paris 104(1-2), 40–50 (2010).
[Crossref] [PubMed]

Chen, L. B.

M. Reers, T. W. Smith, and L. B. Chen, “J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential,” Biochemistry 30(18), 4480–4486 (1991).
[Crossref] [PubMed]

Chen, Z.-Y.

Q.-L. Zhou, Z.-Y. Chen, Y.-X. Wang, F. Yang, Y. Lin, and Y.-Y. Liao, “Ultrasound-mediated local drug and gene delivery using nanocarriers,” BioMed Res. Int. 2014, 963891 (2014).
[Crossref] [PubMed]

Cho, C.-W.

G.-H. Son, B.-J. Lee, and C.-W. Cho, “Mechanisms of drug release from advanced drug formulations such as polymeric-based drug-delivery systems and lipid nanoparticles,” J. Pharm. Investig. 47(4), 287–296 (2017).
[Crossref]

Choi, J. J.

J. J. Choi, K. Selert, F. Vlachos, A. Wong, and E. E. Konofagou, “Noninvasive and localized neuronal delivery using short ultrasonic pulses and microbubbles,” Proc. Natl. Acad. Sci. U.S.A. 108(40), 16539–16544 (2011).
[Crossref] [PubMed]

Chu, P.-C.

P.-C. Chu, H.-L. Liu, H.-Y. Lai, C.-Y. Lin, H.-C. Tsai, and Y.-C. Pei, “Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening,” Sci. Rep. 5(1), 15477–15489 (2015).
[Crossref] [PubMed]

Doze, V. A.

M. Paukert, A. Agarwal, J. Cha, V. A. Doze, J. U. Kang, and D. E. Bergles, “Norepinephrine controls astroglial responsiveness to local circuit activity,” Neuron 82(6), 1263–1270 (2014).
[Crossref] [PubMed]

Duan, Y.

Y. Duan, B. Q. Yang, C. C. Chang, J. Zhou, H. Y. Li, Z. H. Xu, Z. W. Wang, and D. Y. Li, “[Preliminary study on assessment of lexiscan-induced blood-brain barrier opening and its level by CT perfusion imaging],” Zhonghua Yi Xue Za Zhi 96(35), 2825–2829 (2016).
[PubMed]

Ferreira, L.

C. Saraiva, C. Praça, R. Ferreira, T. Santos, L. Ferreira, and L. Bernardino, “Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases,” J. Control. Release 235, 34–47 (2016).
[Crossref] [PubMed]

Ferreira, R.

C. Saraiva, C. Praça, R. Ferreira, T. Santos, L. Ferreira, and L. Bernardino, “Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases,” J. Control. Release 235, 34–47 (2016).
[Crossref] [PubMed]

Flusberg, B. A.

A. D. Mehta, J. C. Jung, B. A. Flusberg, and M. J. Schnitzer, “Fiber optic in vivo imaging in the mammalian nervous system,” Curr. Opin. Neurobiol. 14(5), 617–628 (2004).
[Crossref] [PubMed]

Frady, E. P.

E. W. Miller, J. Y. Lin, E. P. Frady, P. A. Steinbach, W. B. Kristan, and R. Y. Tsien, “Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires,” Proc. Natl. Acad. Sci. U.S.A. 109(6), 2114–2119 (2012).
[Crossref] [PubMed]

Grienberger, C.

C. Grienberger and A. Konnerth, “Imaging calcium in neurons,” Neuron 73(5), 862–885 (2012).
[Crossref] [PubMed]

Hoffman, J. F.

P. J. Sims, A. S. Waggoner, C.-H. Wang, and J. F. Hoffman, “Studies on the Mechanism by Which Cyanine Dyes Measure Membrane Potential in Red Blood Cells and Phosphatidylcholine Vesicles,” Biochemistry 13(16), 3315–3330 (1974).
[Crossref] [PubMed]

Iezzi, R.

J. S. Treger, M. F. Priest, R. Iezzi, and F. Bezanilla, “Indocyanine Green is a Voltage-Sensitive Fluorescent Dye,” Biophys. J. 106(2), 793a (2014).
[Crossref]

Jha, A. K.

H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
[Crossref] [PubMed]

Jung, J. C.

A. D. Mehta, J. C. Jung, B. A. Flusberg, and M. J. Schnitzer, “Fiber optic in vivo imaging in the mammalian nervous system,” Curr. Opin. Neurobiol. 14(5), 617–628 (2004).
[Crossref] [PubMed]

Kang, J.

H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
[Crossref] [PubMed]

Kang, J. U.

H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
[Crossref] [PubMed]

M. Paukert, A. Agarwal, J. Cha, V. A. Doze, J. U. Kang, and D. E. Bergles, “Norepinephrine controls astroglial responsiveness to local circuit activity,” Neuron 82(6), 1263–1270 (2014).
[Crossref] [PubMed]

Kim, D.-G.

D.-G. Kim and M. S. Bynoe, “A2A adenosine receptor modulates drug efflux transporter P-glycoprotein at the blood-brain barrier,” J. Clin. Invest. 126(5), 1717–1733 (2016).
[Crossref] [PubMed]

D.-G. Kim and M. S. Bynoe, “A2A Adenosine Receptor Regulates the Human Blood-Brain Barrier Permeability,” Mol. Neurobiol. 52(1), 664–678 (2015).
[Crossref] [PubMed]

A. J. Carman, J. H. Mills, A. Krenz, D.-G. Kim, and M. S. Bynoe, “Adenosine receptor signaling modulates permeability of the blood-brain barrier,” J. Neurosci. 31(37), 13272–13280 (2011).
[Crossref] [PubMed]

Konnerth, A.

C. Grienberger and A. Konnerth, “Imaging calcium in neurons,” Neuron 73(5), 862–885 (2012).
[Crossref] [PubMed]

Konofagou, E. E.

J. J. Choi, K. Selert, F. Vlachos, A. Wong, and E. E. Konofagou, “Noninvasive and localized neuronal delivery using short ultrasonic pulses and microbubbles,” Proc. Natl. Acad. Sci. U.S.A. 108(40), 16539–16544 (2011).
[Crossref] [PubMed]

Krenz, A.

A. J. Carman, J. H. Mills, A. Krenz, D.-G. Kim, and M. S. Bynoe, “Adenosine receptor signaling modulates permeability of the blood-brain barrier,” J. Neurosci. 31(37), 13272–13280 (2011).
[Crossref] [PubMed]

Kristan, W. B.

E. W. Miller, J. Y. Lin, E. P. Frady, P. A. Steinbach, W. B. Kristan, and R. Y. Tsien, “Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires,” Proc. Natl. Acad. Sci. U.S.A. 109(6), 2114–2119 (2012).
[Crossref] [PubMed]

Lai, H.-Y.

P.-C. Chu, H.-L. Liu, H.-Y. Lai, C.-Y. Lin, H.-C. Tsai, and Y.-C. Pei, “Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening,” Sci. Rep. 5(1), 15477–15489 (2015).
[Crossref] [PubMed]

Le, H. N. D.

H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
[Crossref] [PubMed]

Lee, B.-J.

G.-H. Son, B.-J. Lee, and C.-W. Cho, “Mechanisms of drug release from advanced drug formulations such as polymeric-based drug-delivery systems and lipid nanoparticles,” J. Pharm. Investig. 47(4), 287–296 (2017).
[Crossref]

Li, D. Y.

Y. Duan, B. Q. Yang, C. C. Chang, J. Zhou, H. Y. Li, Z. H. Xu, Z. W. Wang, and D. Y. Li, “[Preliminary study on assessment of lexiscan-induced blood-brain barrier opening and its level by CT perfusion imaging],” Zhonghua Yi Xue Za Zhi 96(35), 2825–2829 (2016).
[PubMed]

Li, H. Y.

Y. Duan, B. Q. Yang, C. C. Chang, J. Zhou, H. Y. Li, Z. H. Xu, Z. W. Wang, and D. Y. Li, “[Preliminary study on assessment of lexiscan-induced blood-brain barrier opening and its level by CT perfusion imaging],” Zhonghua Yi Xue Za Zhi 96(35), 2825–2829 (2016).
[PubMed]

Liao, Y.-Y.

Q.-L. Zhou, Z.-Y. Chen, Y.-X. Wang, F. Yang, Y. Lin, and Y.-Y. Liao, “Ultrasound-mediated local drug and gene delivery using nanocarriers,” BioMed Res. Int. 2014, 963891 (2014).
[Crossref] [PubMed]

Lin, C.-Y.

P.-C. Chu, H.-L. Liu, H.-Y. Lai, C.-Y. Lin, H.-C. Tsai, and Y.-C. Pei, “Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening,” Sci. Rep. 5(1), 15477–15489 (2015).
[Crossref] [PubMed]

Lin, J. Y.

E. W. Miller, J. Y. Lin, E. P. Frady, P. A. Steinbach, W. B. Kristan, and R. Y. Tsien, “Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires,” Proc. Natl. Acad. Sci. U.S.A. 109(6), 2114–2119 (2012).
[Crossref] [PubMed]

Lin, Y.

Q.-L. Zhou, Z.-Y. Chen, Y.-X. Wang, F. Yang, Y. Lin, and Y.-Y. Liao, “Ultrasound-mediated local drug and gene delivery using nanocarriers,” BioMed Res. Int. 2014, 963891 (2014).
[Crossref] [PubMed]

Liu, H.-L.

P.-C. Chu, H.-L. Liu, H.-Y. Lai, C.-Y. Lin, H.-C. Tsai, and Y.-C. Pei, “Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening,” Sci. Rep. 5(1), 15477–15489 (2015).
[Crossref] [PubMed]

Loew, L. M.

H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
[Crossref] [PubMed]

Mehta, A. D.

A. D. Mehta, J. C. Jung, B. A. Flusberg, and M. J. Schnitzer, “Fiber optic in vivo imaging in the mammalian nervous system,” Curr. Opin. Neurobiol. 14(5), 617–628 (2004).
[Crossref] [PubMed]

Miller, E. W.

E. W. Miller, J. Y. Lin, E. P. Frady, P. A. Steinbach, W. B. Kristan, and R. Y. Tsien, “Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires,” Proc. Natl. Acad. Sci. U.S.A. 109(6), 2114–2119 (2012).
[Crossref] [PubMed]

Mills, J. H.

A. J. Carman, J. H. Mills, A. Krenz, D.-G. Kim, and M. S. Bynoe, “Adenosine receptor signaling modulates permeability of the blood-brain barrier,” J. Neurosci. 31(37), 13272–13280 (2011).
[Crossref] [PubMed]

Paukert, M.

M. Paukert, A. Agarwal, J. Cha, V. A. Doze, J. U. Kang, and D. E. Bergles, “Norepinephrine controls astroglial responsiveness to local circuit activity,” Neuron 82(6), 1263–1270 (2014).
[Crossref] [PubMed]

Pei, Y.-C.

P.-C. Chu, H.-L. Liu, H.-Y. Lai, C.-Y. Lin, H.-C. Tsai, and Y.-C. Pei, “Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening,” Sci. Rep. 5(1), 15477–15489 (2015).
[Crossref] [PubMed]

Praça, C.

C. Saraiva, C. Praça, R. Ferreira, T. Santos, L. Ferreira, and L. Bernardino, “Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases,” J. Control. Release 235, 34–47 (2016).
[Crossref] [PubMed]

Priest, M. F.

J. S. Treger, M. F. Priest, R. Iezzi, and F. Bezanilla, “Indocyanine Green is a Voltage-Sensitive Fluorescent Dye,” Biophys. J. 106(2), 793a (2014).
[Crossref]

Rahmim, A.

H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
[Crossref] [PubMed]

Rapoport, S. I.

S. I. Rapoport, “Osmotic opening of the blood-brain barrier: principles, mechanism, and therapeutic applications,” Cell. Mol. Neurobiol. 20(2), 217–230 (2000).
[Crossref] [PubMed]

Reers, M.

M. Reers, T. W. Smith, and L. B. Chen, “J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential,” Biochemistry 30(18), 4480–4486 (1991).
[Crossref] [PubMed]

Santos, T.

C. Saraiva, C. Praça, R. Ferreira, T. Santos, L. Ferreira, and L. Bernardino, “Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases,” J. Control. Release 235, 34–47 (2016).
[Crossref] [PubMed]

Saraiva, C.

C. Saraiva, C. Praça, R. Ferreira, T. Santos, L. Ferreira, and L. Bernardino, “Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases,” J. Control. Release 235, 34–47 (2016).
[Crossref] [PubMed]

Schnitzer, M. J.

A. D. Mehta, J. C. Jung, B. A. Flusberg, and M. J. Schnitzer, “Fiber optic in vivo imaging in the mammalian nervous system,” Curr. Opin. Neurobiol. 14(5), 617–628 (2004).
[Crossref] [PubMed]

Selert, K.

J. J. Choi, K. Selert, F. Vlachos, A. Wong, and E. E. Konofagou, “Noninvasive and localized neuronal delivery using short ultrasonic pulses and microbubbles,” Proc. Natl. Acad. Sci. U.S.A. 108(40), 16539–16544 (2011).
[Crossref] [PubMed]

Sims, P. J.

P. J. Sims, A. S. Waggoner, C.-H. Wang, and J. F. Hoffman, “Studies on the Mechanism by Which Cyanine Dyes Measure Membrane Potential in Red Blood Cells and Phosphatidylcholine Vesicles,” Biochemistry 13(16), 3315–3330 (1974).
[Crossref] [PubMed]

Smith, T. W.

M. Reers, T. W. Smith, and L. B. Chen, “J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential,” Biochemistry 30(18), 4480–4486 (1991).
[Crossref] [PubMed]

Son, G.-H.

G.-H. Son, B.-J. Lee, and C.-W. Cho, “Mechanisms of drug release from advanced drug formulations such as polymeric-based drug-delivery systems and lipid nanoparticles,” J. Pharm. Investig. 47(4), 287–296 (2017).
[Crossref]

Steinbach, P. A.

E. W. Miller, J. Y. Lin, E. P. Frady, P. A. Steinbach, W. B. Kristan, and R. Y. Tsien, “Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires,” Proc. Natl. Acad. Sci. U.S.A. 109(6), 2114–2119 (2012).
[Crossref] [PubMed]

Thorek, D. L. J.

H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
[Crossref] [PubMed]

Treger, J. S.

J. S. Treger, “Sensors and probes: A universal voltage indicator,” Nat. Methods 11(107), L09–L12 (2014).

J. S. Treger, M. F. Priest, R. Iezzi, and F. Bezanilla, “Indocyanine Green is a Voltage-Sensitive Fluorescent Dye,” Biophys. J. 106(2), 793a (2014).
[Crossref]

Tsai, H.-C.

P.-C. Chu, H.-L. Liu, H.-Y. Lai, C.-Y. Lin, H.-C. Tsai, and Y.-C. Pei, “Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening,” Sci. Rep. 5(1), 15477–15489 (2015).
[Crossref] [PubMed]

Tsien, R. Y.

E. W. Miller, J. Y. Lin, E. P. Frady, P. A. Steinbach, W. B. Kristan, and R. Y. Tsien, “Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires,” Proc. Natl. Acad. Sci. U.S.A. 109(6), 2114–2119 (2012).
[Crossref] [PubMed]

Vlachos, F.

J. J. Choi, K. Selert, F. Vlachos, A. Wong, and E. E. Konofagou, “Noninvasive and localized neuronal delivery using short ultrasonic pulses and microbubbles,” Proc. Natl. Acad. Sci. U.S.A. 108(40), 16539–16544 (2011).
[Crossref] [PubMed]

Waggoner, A. S.

A. S. Waggoner, “Dye Indicators of Membrane Potential,” Annu. Rev. Biophys. Bioeng. 8(1), 47–68 (1979).
[Crossref] [PubMed]

P. J. Sims, A. S. Waggoner, C.-H. Wang, and J. F. Hoffman, “Studies on the Mechanism by Which Cyanine Dyes Measure Membrane Potential in Red Blood Cells and Phosphatidylcholine Vesicles,” Biochemistry 13(16), 3315–3330 (1974).
[Crossref] [PubMed]

Wang, C.-H.

P. J. Sims, A. S. Waggoner, C.-H. Wang, and J. F. Hoffman, “Studies on the Mechanism by Which Cyanine Dyes Measure Membrane Potential in Red Blood Cells and Phosphatidylcholine Vesicles,” Biochemistry 13(16), 3315–3330 (1974).
[Crossref] [PubMed]

Wang, Y.-X.

Q.-L. Zhou, Z.-Y. Chen, Y.-X. Wang, F. Yang, Y. Lin, and Y.-Y. Liao, “Ultrasound-mediated local drug and gene delivery using nanocarriers,” BioMed Res. Int. 2014, 963891 (2014).
[Crossref] [PubMed]

Wang, Z. W.

Y. Duan, B. Q. Yang, C. C. Chang, J. Zhou, H. Y. Li, Z. H. Xu, Z. W. Wang, and D. Y. Li, “[Preliminary study on assessment of lexiscan-induced blood-brain barrier opening and its level by CT perfusion imaging],” Zhonghua Yi Xue Za Zhi 96(35), 2825–2829 (2016).
[PubMed]

Wong, A.

J. J. Choi, K. Selert, F. Vlachos, A. Wong, and E. E. Konofagou, “Noninvasive and localized neuronal delivery using short ultrasonic pulses and microbubbles,” Proc. Natl. Acad. Sci. U.S.A. 108(40), 16539–16544 (2011).
[Crossref] [PubMed]

Wong, D. F.

H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
[Crossref] [PubMed]

Xu, Z. H.

Y. Duan, B. Q. Yang, C. C. Chang, J. Zhou, H. Y. Li, Z. H. Xu, Z. W. Wang, and D. Y. Li, “[Preliminary study on assessment of lexiscan-induced blood-brain barrier opening and its level by CT perfusion imaging],” Zhonghua Yi Xue Za Zhi 96(35), 2825–2829 (2016).
[PubMed]

Yan, P.

H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
[Crossref] [PubMed]

Yang, B. Q.

Y. Duan, B. Q. Yang, C. C. Chang, J. Zhou, H. Y. Li, Z. H. Xu, Z. W. Wang, and D. Y. Li, “[Preliminary study on assessment of lexiscan-induced blood-brain barrier opening and its level by CT perfusion imaging],” Zhonghua Yi Xue Za Zhi 96(35), 2825–2829 (2016).
[PubMed]

Yang, F.

Q.-L. Zhou, Z.-Y. Chen, Y.-X. Wang, F. Yang, Y. Lin, and Y.-Y. Liao, “Ultrasound-mediated local drug and gene delivery using nanocarriers,” BioMed Res. Int. 2014, 963891 (2014).
[Crossref] [PubMed]

Zhang, H. K.

H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
[Crossref] [PubMed]

Zhou, J.

Y. Duan, B. Q. Yang, C. C. Chang, J. Zhou, H. Y. Li, Z. H. Xu, Z. W. Wang, and D. Y. Li, “[Preliminary study on assessment of lexiscan-induced blood-brain barrier opening and its level by CT perfusion imaging],” Zhonghua Yi Xue Za Zhi 96(35), 2825–2829 (2016).
[PubMed]

Zhou, Q.-L.

Q.-L. Zhou, Z.-Y. Chen, Y.-X. Wang, F. Yang, Y. Lin, and Y.-Y. Liao, “Ultrasound-mediated local drug and gene delivery using nanocarriers,” BioMed Res. Int. 2014, 963891 (2014).
[Crossref] [PubMed]

Annu. Rev. Biophys. Bioeng. (1)

A. S. Waggoner, “Dye Indicators of Membrane Potential,” Annu. Rev. Biophys. Bioeng. 8(1), 47–68 (1979).
[Crossref] [PubMed]

Biochemistry (2)

P. J. Sims, A. S. Waggoner, C.-H. Wang, and J. F. Hoffman, “Studies on the Mechanism by Which Cyanine Dyes Measure Membrane Potential in Red Blood Cells and Phosphatidylcholine Vesicles,” Biochemistry 13(16), 3315–3330 (1974).
[Crossref] [PubMed]

M. Reers, T. W. Smith, and L. B. Chen, “J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential,” Biochemistry 30(18), 4480–4486 (1991).
[Crossref] [PubMed]

BioMed Res. Int. (1)

Q.-L. Zhou, Z.-Y. Chen, Y.-X. Wang, F. Yang, Y. Lin, and Y.-Y. Liao, “Ultrasound-mediated local drug and gene delivery using nanocarriers,” BioMed Res. Int. 2014, 963891 (2014).
[Crossref] [PubMed]

Biophys. J. (1)

J. S. Treger, M. F. Priest, R. Iezzi, and F. Bezanilla, “Indocyanine Green is a Voltage-Sensitive Fluorescent Dye,” Biophys. J. 106(2), 793a (2014).
[Crossref]

Cell. Mol. Neurobiol. (1)

S. I. Rapoport, “Osmotic opening of the blood-brain barrier: principles, mechanism, and therapeutic applications,” Cell. Mol. Neurobiol. 20(2), 217–230 (2000).
[Crossref] [PubMed]

Curr. Opin. Neurobiol. (1)

A. D. Mehta, J. C. Jung, B. A. Flusberg, and M. J. Schnitzer, “Fiber optic in vivo imaging in the mammalian nervous system,” Curr. Opin. Neurobiol. 14(5), 617–628 (2004).
[Crossref] [PubMed]

J. Biomed. Opt. (1)

H. K. Zhang, P. Yan, J. Kang, D. S. Abou, H. N. D. Le, A. K. Jha, D. L. J. Thorek, J. U. Kang, A. Rahmim, D. F. Wong, E. M. Boctor, and L. M. Loew, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” J. Biomed. Opt. 22(4), 045006 (2017).
[Crossref] [PubMed]

J. Clin. Invest. (1)

D.-G. Kim and M. S. Bynoe, “A2A adenosine receptor modulates drug efflux transporter P-glycoprotein at the blood-brain barrier,” J. Clin. Invest. 126(5), 1717–1733 (2016).
[Crossref] [PubMed]

J. Control. Release (1)

C. Saraiva, C. Praça, R. Ferreira, T. Santos, L. Ferreira, and L. Bernardino, “Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases,” J. Control. Release 235, 34–47 (2016).
[Crossref] [PubMed]

J. Neurosci. (1)

A. J. Carman, J. H. Mills, A. Krenz, D.-G. Kim, and M. S. Bynoe, “Adenosine receptor signaling modulates permeability of the blood-brain barrier,” J. Neurosci. 31(37), 13272–13280 (2011).
[Crossref] [PubMed]

J. Pharm. Investig. (1)

G.-H. Son, B.-J. Lee, and C.-W. Cho, “Mechanisms of drug release from advanced drug formulations such as polymeric-based drug-delivery systems and lipid nanoparticles,” J. Pharm. Investig. 47(4), 287–296 (2017).
[Crossref]

J. Physiol. Paris (1)

S. Chemla and F. Chavane, “Voltage-sensitive dye imaging: Technique review and models,” J. Physiol. Paris 104(1-2), 40–50 (2010).
[Crossref] [PubMed]

Mol. Neurobiol. (1)

D.-G. Kim and M. S. Bynoe, “A2A Adenosine Receptor Regulates the Human Blood-Brain Barrier Permeability,” Mol. Neurobiol. 52(1), 664–678 (2015).
[Crossref] [PubMed]

Nat. Methods (1)

J. S. Treger, “Sensors and probes: A universal voltage indicator,” Nat. Methods 11(107), L09–L12 (2014).

Neuron (2)

C. Grienberger and A. Konnerth, “Imaging calcium in neurons,” Neuron 73(5), 862–885 (2012).
[Crossref] [PubMed]

M. Paukert, A. Agarwal, J. Cha, V. A. Doze, J. U. Kang, and D. E. Bergles, “Norepinephrine controls astroglial responsiveness to local circuit activity,” Neuron 82(6), 1263–1270 (2014).
[Crossref] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (2)

E. W. Miller, J. Y. Lin, E. P. Frady, P. A. Steinbach, W. B. Kristan, and R. Y. Tsien, “Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires,” Proc. Natl. Acad. Sci. U.S.A. 109(6), 2114–2119 (2012).
[Crossref] [PubMed]

J. J. Choi, K. Selert, F. Vlachos, A. Wong, and E. E. Konofagou, “Noninvasive and localized neuronal delivery using short ultrasonic pulses and microbubbles,” Proc. Natl. Acad. Sci. U.S.A. 108(40), 16539–16544 (2011).
[Crossref] [PubMed]

Sci. Rep. (1)

P.-C. Chu, H.-L. Liu, H.-Y. Lai, C.-Y. Lin, H.-C. Tsai, and Y.-C. Pei, “Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening,” Sci. Rep. 5(1), 15477–15489 (2015).
[Crossref] [PubMed]

Zhonghua Yi Xue Za Zhi (1)

Y. Duan, B. Q. Yang, C. C. Chang, J. Zhou, H. Y. Li, Z. H. Xu, Z. W. Wang, and D. Y. Li, “[Preliminary study on assessment of lexiscan-induced blood-brain barrier opening and its level by CT perfusion imaging],” Zhonghua Yi Xue Za Zhi 96(35), 2825–2829 (2016).
[PubMed]

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Figures (6)

Fig. 1
Fig. 1 (a) In vivo experimental protocol, (b) NIR fluorescence system setup: AS = aspheric lens, SP = shortpass filter, M = mirror, DM = dichroic mirror, LP = longpass filter, ZL = zoom lens, and (c) VSD spectral characteristics.
Fig. 2
Fig. 2 Through-skull (a) decay curves and (b) image time sequence showing fluorescence signal without and with regadenoson.
Fig. 3
Fig. 3 Sample scaled injection curves (dashed) plotted with condition subtraction curves (solid) with increasing regadenoson doses towards the right with a 35-min wait time between injections.
Fig. 4
Fig. 4 Sample a) raw VSD fluorescence profiles with the selected range of condition subtraction curve indices for b) exponential fitting and analysis on the range of τ diff values for fits within a tolerance of 2×RMS E BestFit .
Fig. 5
Fig. 5 Diffusion time constant ( τ diff ) variation with a) wait time between injections and b) with regadenoson dose. Error bars represent the τ tolerance within 2×RMS E BestFit .
Fig. 6
Fig. 6 Brain slices with regadenoson only (left), regadenoson + VSD (middle), and VSD only (right).

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