Abstract

Ultrasound-switchable fluorescence (USF) is a novel imaging technique that provides high spatial resolution fluorescence images in centimeter-deep biological tissue. Recently, we successfully demonstrated the feasibility of in vivo USF imaging using a frequency-domain photomultiplier tube-based system. In this work, for the first time we carried out in vivo USF imaging via a camera-based USF imaging system. The system acquires a USF signal on a two-dimensional (2D) plane, which facilitates the image acquisition because the USF scanning area can be planned based on the 2D image and provides high USF photon collection efficiency. We demonstrated in vivo USF imaging in the mouse’s glioblastoma tumor with multiple targets via local injection. In addition, we designed the USF contrast agents with different particle sizes (70 nm and 330 nm) so that they could bio-distribute to various organs (spleen, liver, and kidney) via intravenous (IV) injections. The results showed that the contrast agents retained stable USF properties in tumors and some organs (spleen and liver). We successfully achieved in vivo USF imaging of the mouse’s spleen and liver via IV injections. The USF imaging results were compared with the images acquired from a commercial X-ray micro computed tomography (micro-CT) system.

© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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References

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    [Crossref]

2019 (3)

T. Yao, S. Yu, Y. Liu, and B. Yuan, “Ultrasound-Switchable Fluorescence Imaging via an EMCCD Camera and a Z-Scan Method,” IEEE J. Sel. Top. Quantum Electron. 25(2), 1–8 (2019).
[Crossref]

T. Yao, S. Yu, Y. Liu, and B. Yuan, “In vivo ultrasound-switchable fluorescence imaging,” Sci. Rep. 9(1), 9855 (2019).
[Crossref]

S. Yu, T. Yao, and B. Yuan, “An ICCD camera-based time-domain ultrasound-switchable fluorescence imaging system,” Sci. Rep. 9(1), 10552 (2019).
[Crossref]

2017 (4)

B. Cheng, V. Bandi, S. Yu, F. D’Souza, K. Nguyen, Y. Hong, L. Tang, and B. Yuan, “The mechanisms and biomedical applications of an NIR BODIPY-based switchable fluorescent probe,” Int. J. Mol. Sci. 18(2), 384 (2017).
[Crossref]

J. Kandukuri, S. Yu, T. Yao, and B. Yuan, “Modulation of ultrasound-switchable fluorescence for improving signal-to-noise ratio,” J. Biomed. Opt. 22(7), 076021 (2017).
[Crossref]

J. Kandukuri, S. Yu, B. Cheng, V. Bandi, F. D’Souza, K. Nguyen, Y. Hong, and B. Yuan, “A dual-modality system for both multi-color ultrasound-switchable fluorescence and ultrasound imaging,” Int. J. Mol. Sci. 18(2), 323 (2017).
[Crossref]

X. Deán-Ben, S. Gottschalk, B. Mc Larney, S. Shoham, and D. Razansky, “Advanced optoacoustic methods for multiscale imaging of in vivo dynamics,” Chem. Soc. Rev. 46(8), 2158–2198 (2017).
[Crossref]

2016 (3)

S. Yu, B. Cheng, T. Yao, C. Xu, K. T. Nguyen, Y. Hong, and B. Yuan, “New generation ICG-based contrast agents for ultrasound-switchable fluorescence imaging,” Sci. Rep. 6(1), 35942 (2016).
[Crossref]

B. Cheng, V. Bandi, M.-Y. Wei, Y. Pei, F. D’Souza, K. T. Nguyen, Y. Hong, and B. Yuan, “High-resolution ultrasound-switchable fluorescence imaging in centimeter-deep tissue phantoms with high signal-to-noise ratio and high sensitivity via novel contrast agents,” PLoS One 11(11), e0165963 (2016).
[Crossref]

L. V. Wang and J. Yao, “A practical guide to photoacoustic tomography in the life sciences,” Nat. Methods 13(8), 627–638 (2016).
[Crossref]

2015 (2)

Y. Pei, M.-Y. Wei, B. Cheng, Y. Liu, Z. Xie, K. Nguyen, and B. Yuan, “High resolution imaging beyond the acoustic diffraction limit in deep tissue via ultrasound-switchable NIR fluorescence,” Sci. Rep. 4(1), 4690 (2015).
[Crossref]

Y. Liu, P. Lai, C. Ma, X. Xu, A. A. Grabar, and L. V. Wang, “Optical focusing deep inside dynamic scattering media with near-infrared time-reversed ultrasonically encoded (TRUE) light,” Nat. Commun. 6(1), 5904 (2015).
[Crossref]

2014 (1)

B. Cheng, M.-Y. Wei, Y. Liu, H. Pitta, Z. Xie, Y. Hong, K. T. Nguyen, and B. Yuan, “Development of ultrasound-switchable fluorescence imaging contrast agents based on thermosensitive polymers and nanoparticles,” IEEE J. Sel. Top. Quantum Electron. 20(3), 67–80 (2014).
[Crossref]

2013 (2)

B. Yuan, Y. Pei, and J. Kandukuri, “Breaking the acoustic diffraction limit via nonlinear effect and thermal confinement for potential deep-tissue high-resolution imaging,” Appl. Phys. Lett. 102(6), 063703 (2013).
[Crossref]

B. Judkewitz, Y. M. Wang, R. Horstmeyer, A. Mathy, and C. Yang, “Speckle-scale focusing in the diffusive regime with time reversal of variance-encoded light (TROVE),” Nat. Photonics 7(4), 300–305 (2013).
[Crossref]

2012 (3)

K. Si, R. Fiolka, and M. Cui, “Fluorescence imaging beyond the ballistic regime by ultrasound-pulse-guided digital phase conjugation,” Nat. Photonics 6(10), 657–661 (2012).
[Crossref]

B. Yuan, S. Uchiyama, Y. Liu, K. T. Nguyen, and G. Alexandrakis, “High-resolution imaging in a deep turbid medium based on an ultrasound-switchable fluorescence technique,” Appl. Phys. Lett. 101(3), 033703 (2012).
[Crossref]

L. V. Wang and S. Hu, “Photoacoustic tomography: in vivo imaging from organelles to organs,” Science 335(6075), 1458–1462 (2012).
[Crossref]

2011 (3)

X. Xu, H. Liu, and L. V. Wang, “Time-reversed ultrasonically encoded optical focusing into scattering media,” Nat. Photonics 5(3), 154–157 (2011).
[Crossref]

N. Yamamoto, H. Tsuchiya, and R. M. Hoffman, “Tumor imaging with multicolor fluorescent protein expression,” Int. J. Clin. Oncol. 16(2), 84–91 (2011).
[Crossref]

A. G. T. van Scheltinga, G. M. van Dam, W. B. Nagengast, V. Ntziachristos, H. Hollema, J. L. Herek, C. P. Schröder, J. G. Kosterink, M. N. Lub-de Hoog, and E. G. de Vries, “Intraoperative near-infrared fluorescence tumor imaging with vascular endothelial growth factor and human epidermal growth factor receptor 2 targeting antibodies,” J. Nucl. Med. 52(11), 1778–1785 (2011).
[Crossref]

2010 (1)

S. A. Hilderbrand and R. Weissleder, “Near-infrared fluorescence: application to in vivo molecular imaging,” Curr. Opin. Chem. Biol. 14(1), 71–79 (2010).
[Crossref]

2009 (1)

L. V. Wang, “Multiscale photoacoustic microscopy and computed tomography,” Nat. Photonics 3(9), 503–509 (2009).
[Crossref]

2008 (1)

W. H. De Jong, W. I. Hagens, P. Krystek, M. C. Burger, A. J. Sips, and R. E. Geertsma, “Particle size-dependent organ distribution of gold nanoparticles after intravenous administration,” Biomaterials 29(12), 1912–1919 (2008).
[Crossref]

2007 (1)

M. V. Backer, Z. Levashova, V. Patel, B. T. Jehning, K. Claffey, F. G. Blankenberg, and J. M. Backer, “Molecular imaging of VEGF receptors in angiogenic vasculature with single-chain VEGF-based probes,” Nat. Med. 13(4), 504–509 (2007).
[Crossref]

2003 (2)

J. V. Frangioni, “In vivo near-infrared fluorescence imaging,” Curr. Opin. Chem. Biol. 7(5), 626–634 (2003).
[Crossref]

C.-D. Hu and T. K. Kerppola, “Simultaneous visualization of multiple protein interactions in living cells using multicolor fluorescence complementation analysis,” Nat. Biotechnol. 21(5), 539–545 (2003).
[Crossref]

2001 (1)

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, and C. Grötzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19(4), 327–331 (2001).
[Crossref]

1999 (1)

R. Weissleder, C.-H. Tung, U. Mahmood, and A. Bogdanov Jr, “In vivo imaging of tumors with protease-activated near-infrared fluorescent probes,” Nat. Biotechnol. 17(4), 375–378 (1999).
[Crossref]

1993 (1)

L. J. L. Wenqing, “The Automatic thresholding of gray-level pictures via two-dimensional otsu method [J],” Acta Automatica Sinica 1, 325–327 (1993).
[Crossref]

Alexandrakis, G.

B. Yuan, S. Uchiyama, Y. Liu, K. T. Nguyen, and G. Alexandrakis, “High-resolution imaging in a deep turbid medium based on an ultrasound-switchable fluorescence technique,” Appl. Phys. Lett. 101(3), 033703 (2012).
[Crossref]

Backer, J. M.

M. V. Backer, Z. Levashova, V. Patel, B. T. Jehning, K. Claffey, F. G. Blankenberg, and J. M. Backer, “Molecular imaging of VEGF receptors in angiogenic vasculature with single-chain VEGF-based probes,” Nat. Med. 13(4), 504–509 (2007).
[Crossref]

Backer, M. V.

M. V. Backer, Z. Levashova, V. Patel, B. T. Jehning, K. Claffey, F. G. Blankenberg, and J. M. Backer, “Molecular imaging of VEGF receptors in angiogenic vasculature with single-chain VEGF-based probes,” Nat. Med. 13(4), 504–509 (2007).
[Crossref]

Bandi, V.

B. Cheng, V. Bandi, S. Yu, F. D’Souza, K. Nguyen, Y. Hong, L. Tang, and B. Yuan, “The mechanisms and biomedical applications of an NIR BODIPY-based switchable fluorescent probe,” Int. J. Mol. Sci. 18(2), 384 (2017).
[Crossref]

J. Kandukuri, S. Yu, B. Cheng, V. Bandi, F. D’Souza, K. Nguyen, Y. Hong, and B. Yuan, “A dual-modality system for both multi-color ultrasound-switchable fluorescence and ultrasound imaging,” Int. J. Mol. Sci. 18(2), 323 (2017).
[Crossref]

B. Cheng, V. Bandi, M.-Y. Wei, Y. Pei, F. D’Souza, K. T. Nguyen, Y. Hong, and B. Yuan, “High-resolution ultrasound-switchable fluorescence imaging in centimeter-deep tissue phantoms with high signal-to-noise ratio and high sensitivity via novel contrast agents,” PLoS One 11(11), e0165963 (2016).
[Crossref]

Becker, A.

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, and C. Grötzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19(4), 327–331 (2001).
[Crossref]

Blankenberg, F. G.

M. V. Backer, Z. Levashova, V. Patel, B. T. Jehning, K. Claffey, F. G. Blankenberg, and J. M. Backer, “Molecular imaging of VEGF receptors in angiogenic vasculature with single-chain VEGF-based probes,” Nat. Med. 13(4), 504–509 (2007).
[Crossref]

Bogdanov Jr, A.

R. Weissleder, C.-H. Tung, U. Mahmood, and A. Bogdanov Jr, “In vivo imaging of tumors with protease-activated near-infrared fluorescent probes,” Nat. Biotechnol. 17(4), 375–378 (1999).
[Crossref]

Burger, M. C.

W. H. De Jong, W. I. Hagens, P. Krystek, M. C. Burger, A. J. Sips, and R. E. Geertsma, “Particle size-dependent organ distribution of gold nanoparticles after intravenous administration,” Biomaterials 29(12), 1912–1919 (2008).
[Crossref]

Cheng, B.

B. Cheng, V. Bandi, S. Yu, F. D’Souza, K. Nguyen, Y. Hong, L. Tang, and B. Yuan, “The mechanisms and biomedical applications of an NIR BODIPY-based switchable fluorescent probe,” Int. J. Mol. Sci. 18(2), 384 (2017).
[Crossref]

J. Kandukuri, S. Yu, B. Cheng, V. Bandi, F. D’Souza, K. Nguyen, Y. Hong, and B. Yuan, “A dual-modality system for both multi-color ultrasound-switchable fluorescence and ultrasound imaging,” Int. J. Mol. Sci. 18(2), 323 (2017).
[Crossref]

B. Cheng, V. Bandi, M.-Y. Wei, Y. Pei, F. D’Souza, K. T. Nguyen, Y. Hong, and B. Yuan, “High-resolution ultrasound-switchable fluorescence imaging in centimeter-deep tissue phantoms with high signal-to-noise ratio and high sensitivity via novel contrast agents,” PLoS One 11(11), e0165963 (2016).
[Crossref]

S. Yu, B. Cheng, T. Yao, C. Xu, K. T. Nguyen, Y. Hong, and B. Yuan, “New generation ICG-based contrast agents for ultrasound-switchable fluorescence imaging,” Sci. Rep. 6(1), 35942 (2016).
[Crossref]

Y. Pei, M.-Y. Wei, B. Cheng, Y. Liu, Z. Xie, K. Nguyen, and B. Yuan, “High resolution imaging beyond the acoustic diffraction limit in deep tissue via ultrasound-switchable NIR fluorescence,” Sci. Rep. 4(1), 4690 (2015).
[Crossref]

B. Cheng, M.-Y. Wei, Y. Liu, H. Pitta, Z. Xie, Y. Hong, K. T. Nguyen, and B. Yuan, “Development of ultrasound-switchable fluorescence imaging contrast agents based on thermosensitive polymers and nanoparticles,” IEEE J. Sel. Top. Quantum Electron. 20(3), 67–80 (2014).
[Crossref]

Claffey, K.

M. V. Backer, Z. Levashova, V. Patel, B. T. Jehning, K. Claffey, F. G. Blankenberg, and J. M. Backer, “Molecular imaging of VEGF receptors in angiogenic vasculature with single-chain VEGF-based probes,” Nat. Med. 13(4), 504–509 (2007).
[Crossref]

Cui, M.

K. Si, R. Fiolka, and M. Cui, “Fluorescence imaging beyond the ballistic regime by ultrasound-pulse-guided digital phase conjugation,” Nat. Photonics 6(10), 657–661 (2012).
[Crossref]

D’Souza, F.

B. Cheng, V. Bandi, S. Yu, F. D’Souza, K. Nguyen, Y. Hong, L. Tang, and B. Yuan, “The mechanisms and biomedical applications of an NIR BODIPY-based switchable fluorescent probe,” Int. J. Mol. Sci. 18(2), 384 (2017).
[Crossref]

J. Kandukuri, S. Yu, B. Cheng, V. Bandi, F. D’Souza, K. Nguyen, Y. Hong, and B. Yuan, “A dual-modality system for both multi-color ultrasound-switchable fluorescence and ultrasound imaging,” Int. J. Mol. Sci. 18(2), 323 (2017).
[Crossref]

B. Cheng, V. Bandi, M.-Y. Wei, Y. Pei, F. D’Souza, K. T. Nguyen, Y. Hong, and B. Yuan, “High-resolution ultrasound-switchable fluorescence imaging in centimeter-deep tissue phantoms with high signal-to-noise ratio and high sensitivity via novel contrast agents,” PLoS One 11(11), e0165963 (2016).
[Crossref]

De Jong, W. H.

W. H. De Jong, W. I. Hagens, P. Krystek, M. C. Burger, A. J. Sips, and R. E. Geertsma, “Particle size-dependent organ distribution of gold nanoparticles after intravenous administration,” Biomaterials 29(12), 1912–1919 (2008).
[Crossref]

de Vries, E. G.

A. G. T. van Scheltinga, G. M. van Dam, W. B. Nagengast, V. Ntziachristos, H. Hollema, J. L. Herek, C. P. Schröder, J. G. Kosterink, M. N. Lub-de Hoog, and E. G. de Vries, “Intraoperative near-infrared fluorescence tumor imaging with vascular endothelial growth factor and human epidermal growth factor receptor 2 targeting antibodies,” J. Nucl. Med. 52(11), 1778–1785 (2011).
[Crossref]

Deán-Ben, X.

X. Deán-Ben, S. Gottschalk, B. Mc Larney, S. Shoham, and D. Razansky, “Advanced optoacoustic methods for multiscale imaging of in vivo dynamics,” Chem. Soc. Rev. 46(8), 2158–2198 (2017).
[Crossref]

Ebert, B.

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, and C. Grötzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19(4), 327–331 (2001).
[Crossref]

Fiolka, R.

K. Si, R. Fiolka, and M. Cui, “Fluorescence imaging beyond the ballistic regime by ultrasound-pulse-guided digital phase conjugation,” Nat. Photonics 6(10), 657–661 (2012).
[Crossref]

Frangioni, J. V.

J. V. Frangioni, “In vivo near-infrared fluorescence imaging,” Curr. Opin. Chem. Biol. 7(5), 626–634 (2003).
[Crossref]

Geertsma, R. E.

W. H. De Jong, W. I. Hagens, P. Krystek, M. C. Burger, A. J. Sips, and R. E. Geertsma, “Particle size-dependent organ distribution of gold nanoparticles after intravenous administration,” Biomaterials 29(12), 1912–1919 (2008).
[Crossref]

Gottschalk, S.

X. Deán-Ben, S. Gottschalk, B. Mc Larney, S. Shoham, and D. Razansky, “Advanced optoacoustic methods for multiscale imaging of in vivo dynamics,” Chem. Soc. Rev. 46(8), 2158–2198 (2017).
[Crossref]

Grabar, A. A.

Y. Liu, P. Lai, C. Ma, X. Xu, A. A. Grabar, and L. V. Wang, “Optical focusing deep inside dynamic scattering media with near-infrared time-reversed ultrasonically encoded (TRUE) light,” Nat. Commun. 6(1), 5904 (2015).
[Crossref]

Grötzinger, C.

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, and C. Grötzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19(4), 327–331 (2001).
[Crossref]

Hagens, W. I.

W. H. De Jong, W. I. Hagens, P. Krystek, M. C. Burger, A. J. Sips, and R. E. Geertsma, “Particle size-dependent organ distribution of gold nanoparticles after intravenous administration,” Biomaterials 29(12), 1912–1919 (2008).
[Crossref]

Herek, J. L.

A. G. T. van Scheltinga, G. M. van Dam, W. B. Nagengast, V. Ntziachristos, H. Hollema, J. L. Herek, C. P. Schröder, J. G. Kosterink, M. N. Lub-de Hoog, and E. G. de Vries, “Intraoperative near-infrared fluorescence tumor imaging with vascular endothelial growth factor and human epidermal growth factor receptor 2 targeting antibodies,” J. Nucl. Med. 52(11), 1778–1785 (2011).
[Crossref]

Hessenius, C.

A. Becker, C. Hessenius, K. Licha, B. Ebert, U. Sukowski, W. Semmler, B. Wiedenmann, and C. Grötzinger, “Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands,” Nat. Biotechnol. 19(4), 327–331 (2001).
[Crossref]

Hilderbrand, S. A.

S. A. Hilderbrand and R. Weissleder, “Near-infrared fluorescence: application to in vivo molecular imaging,” Curr. Opin. Chem. Biol. 14(1), 71–79 (2010).
[Crossref]

Hoffman, R. M.

N. Yamamoto, H. Tsuchiya, and R. M. Hoffman, “Tumor imaging with multicolor fluorescent protein expression,” Int. J. Clin. Oncol. 16(2), 84–91 (2011).
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B. Cheng, V. Bandi, M.-Y. Wei, Y. Pei, F. D’Souza, K. T. Nguyen, Y. Hong, and B. Yuan, “High-resolution ultrasound-switchable fluorescence imaging in centimeter-deep tissue phantoms with high signal-to-noise ratio and high sensitivity via novel contrast agents,” PLoS One 11(11), e0165963 (2016).
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B. Cheng, M.-Y. Wei, Y. Liu, H. Pitta, Z. Xie, Y. Hong, K. T. Nguyen, and B. Yuan, “Development of ultrasound-switchable fluorescence imaging contrast agents based on thermosensitive polymers and nanoparticles,” IEEE J. Sel. Top. Quantum Electron. 20(3), 67–80 (2014).
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X. Deán-Ben, S. Gottschalk, B. Mc Larney, S. Shoham, and D. Razansky, “Advanced optoacoustic methods for multiscale imaging of in vivo dynamics,” Chem. Soc. Rev. 46(8), 2158–2198 (2017).
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X. Deán-Ben, S. Gottschalk, B. Mc Larney, S. Shoham, and D. Razansky, “Advanced optoacoustic methods for multiscale imaging of in vivo dynamics,” Chem. Soc. Rev. 46(8), 2158–2198 (2017).
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R. Weissleder, C.-H. Tung, U. Mahmood, and A. Bogdanov Jr, “In vivo imaging of tumors with protease-activated near-infrared fluorescent probes,” Nat. Biotechnol. 17(4), 375–378 (1999).
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B. Cheng, V. Bandi, M.-Y. Wei, Y. Pei, F. D’Souza, K. T. Nguyen, Y. Hong, and B. Yuan, “High-resolution ultrasound-switchable fluorescence imaging in centimeter-deep tissue phantoms with high signal-to-noise ratio and high sensitivity via novel contrast agents,” PLoS One 11(11), e0165963 (2016).
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Y. Pei, M.-Y. Wei, B. Cheng, Y. Liu, Z. Xie, K. Nguyen, and B. Yuan, “High resolution imaging beyond the acoustic diffraction limit in deep tissue via ultrasound-switchable NIR fluorescence,” Sci. Rep. 4(1), 4690 (2015).
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B. Cheng, M.-Y. Wei, Y. Liu, H. Pitta, Z. Xie, Y. Hong, K. T. Nguyen, and B. Yuan, “Development of ultrasound-switchable fluorescence imaging contrast agents based on thermosensitive polymers and nanoparticles,” IEEE J. Sel. Top. Quantum Electron. 20(3), 67–80 (2014).
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S. Yu, B. Cheng, T. Yao, C. Xu, K. T. Nguyen, Y. Hong, and B. Yuan, “New generation ICG-based contrast agents for ultrasound-switchable fluorescence imaging,” Sci. Rep. 6(1), 35942 (2016).
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Y. Liu, P. Lai, C. Ma, X. Xu, A. A. Grabar, and L. V. Wang, “Optical focusing deep inside dynamic scattering media with near-infrared time-reversed ultrasonically encoded (TRUE) light,” Nat. Commun. 6(1), 5904 (2015).
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X. Xu, H. Liu, and L. V. Wang, “Time-reversed ultrasonically encoded optical focusing into scattering media,” Nat. Photonics 5(3), 154–157 (2011).
[Crossref]

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N. Yamamoto, H. Tsuchiya, and R. M. Hoffman, “Tumor imaging with multicolor fluorescent protein expression,” Int. J. Clin. Oncol. 16(2), 84–91 (2011).
[Crossref]

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B. Judkewitz, Y. M. Wang, R. Horstmeyer, A. Mathy, and C. Yang, “Speckle-scale focusing in the diffusive regime with time reversal of variance-encoded light (TROVE),” Nat. Photonics 7(4), 300–305 (2013).
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L. V. Wang and J. Yao, “A practical guide to photoacoustic tomography in the life sciences,” Nat. Methods 13(8), 627–638 (2016).
[Crossref]

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T. Yao, S. Yu, Y. Liu, and B. Yuan, “In vivo ultrasound-switchable fluorescence imaging,” Sci. Rep. 9(1), 9855 (2019).
[Crossref]

S. Yu, T. Yao, and B. Yuan, “An ICCD camera-based time-domain ultrasound-switchable fluorescence imaging system,” Sci. Rep. 9(1), 10552 (2019).
[Crossref]

T. Yao, S. Yu, Y. Liu, and B. Yuan, “Ultrasound-Switchable Fluorescence Imaging via an EMCCD Camera and a Z-Scan Method,” IEEE J. Sel. Top. Quantum Electron. 25(2), 1–8 (2019).
[Crossref]

J. Kandukuri, S. Yu, T. Yao, and B. Yuan, “Modulation of ultrasound-switchable fluorescence for improving signal-to-noise ratio,” J. Biomed. Opt. 22(7), 076021 (2017).
[Crossref]

S. Yu, B. Cheng, T. Yao, C. Xu, K. T. Nguyen, Y. Hong, and B. Yuan, “New generation ICG-based contrast agents for ultrasound-switchable fluorescence imaging,” Sci. Rep. 6(1), 35942 (2016).
[Crossref]

Yu, S.

T. Yao, S. Yu, Y. Liu, and B. Yuan, “Ultrasound-Switchable Fluorescence Imaging via an EMCCD Camera and a Z-Scan Method,” IEEE J. Sel. Top. Quantum Electron. 25(2), 1–8 (2019).
[Crossref]

S. Yu, T. Yao, and B. Yuan, “An ICCD camera-based time-domain ultrasound-switchable fluorescence imaging system,” Sci. Rep. 9(1), 10552 (2019).
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T. Yao, S. Yu, Y. Liu, and B. Yuan, “In vivo ultrasound-switchable fluorescence imaging,” Sci. Rep. 9(1), 9855 (2019).
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J. Kandukuri, S. Yu, B. Cheng, V. Bandi, F. D’Souza, K. Nguyen, Y. Hong, and B. Yuan, “A dual-modality system for both multi-color ultrasound-switchable fluorescence and ultrasound imaging,” Int. J. Mol. Sci. 18(2), 323 (2017).
[Crossref]

J. Kandukuri, S. Yu, T. Yao, and B. Yuan, “Modulation of ultrasound-switchable fluorescence for improving signal-to-noise ratio,” J. Biomed. Opt. 22(7), 076021 (2017).
[Crossref]

B. Cheng, V. Bandi, S. Yu, F. D’Souza, K. Nguyen, Y. Hong, L. Tang, and B. Yuan, “The mechanisms and biomedical applications of an NIR BODIPY-based switchable fluorescent probe,” Int. J. Mol. Sci. 18(2), 384 (2017).
[Crossref]

S. Yu, B. Cheng, T. Yao, C. Xu, K. T. Nguyen, Y. Hong, and B. Yuan, “New generation ICG-based contrast agents for ultrasound-switchable fluorescence imaging,” Sci. Rep. 6(1), 35942 (2016).
[Crossref]

Yuan, B.

T. Yao, S. Yu, Y. Liu, and B. Yuan, “Ultrasound-Switchable Fluorescence Imaging via an EMCCD Camera and a Z-Scan Method,” IEEE J. Sel. Top. Quantum Electron. 25(2), 1–8 (2019).
[Crossref]

T. Yao, S. Yu, Y. Liu, and B. Yuan, “In vivo ultrasound-switchable fluorescence imaging,” Sci. Rep. 9(1), 9855 (2019).
[Crossref]

S. Yu, T. Yao, and B. Yuan, “An ICCD camera-based time-domain ultrasound-switchable fluorescence imaging system,” Sci. Rep. 9(1), 10552 (2019).
[Crossref]

J. Kandukuri, S. Yu, B. Cheng, V. Bandi, F. D’Souza, K. Nguyen, Y. Hong, and B. Yuan, “A dual-modality system for both multi-color ultrasound-switchable fluorescence and ultrasound imaging,” Int. J. Mol. Sci. 18(2), 323 (2017).
[Crossref]

B. Cheng, V. Bandi, S. Yu, F. D’Souza, K. Nguyen, Y. Hong, L. Tang, and B. Yuan, “The mechanisms and biomedical applications of an NIR BODIPY-based switchable fluorescent probe,” Int. J. Mol. Sci. 18(2), 384 (2017).
[Crossref]

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Figures (8)

Fig. 1.
Fig. 1. (a) Schematic diagram of the ICCD camera-based USF imaging system. (b) Time sequence diagram of acquiring a USF signal.
Fig. 2.
Fig. 2. (a) Normalized 2D planar fluorescence image of the porcine heart tissue in FOV 2. (b) Top view of the 3D CT image of the porcine heart tissue. (c) An example of acquired USF signals from the porcine heart tissue. (d) Acquired USF images on x-y plane at different z locations. The data was normalized and interpolated. (e) The USF image of the USF contrast volume from 3D view, left side view, top view, and front view. (f) The CT image of the CT contrast volume from 3D view, left side view, top view, and front view. (g) 3D co-registration results of the USF and CT image. The green volume represents the USF contrast only. The blue volume represents the CT contrast agents only. The red volume represents their overlapped area. (h) The co-registration results on x-y plane at different z locations.
Fig. 3.
Fig. 3. (a) Normalized 2D planar fluorescence image of the mouse in FOV 1. The yellow dash square highlights the fluorescence from the tumor. (b) Zoomed-in normalized 2D planar fluorescence image of the mouse’s tumor area in FOV 2, which corresponds to the yellow dash square in (a). (c) Top view of the 3D CT image of the mouse’s dorsal side. The red dash square highlights the distribution of the CT contrast agents in the tumor. (d) An example of acquired USF signals from the tumor. (e) Acquired USF images on x-y plane at different z locations. The data was normalized and interpolated. (f) The USF image of the USF contrast volume from 3D view, left side view, top view, and front view. (g) The CT image of the CT contrast volume from 3D view, left side view, top view, and front view. (h) 3D co-registration results of the USF and CT image. The green volume represents the USF contrast only. The blue volume represents the CT contrast agents only. The red volume represents their overlapped area. (i) The co-registration results on x-y plane at different z locations.
Fig. 4.
Fig. 4. (a) Normalized 2D planar fluorescence image of the mouse in FOV 1. (b) Zoomed-in normalized 2D planar fluorescence image of the mouse’s tumor area in FOV 2. (c) Top view of the 3D CT image of the mouse’s ventral side. (d) Examples of acquired USF signals from each tumor. (d1) represents the USF signal acquired from the first tumor at the upper location. (d2) represents the USF signal acquired from the second tumor at the lower location. (e) Acquired USF images on x-y plane at different z locations. (f) The USF image of the USF contrast volume from 3D view, left side view, top view, and front view. (g) The CT image of the CT contrast volume from 3D view, left side view, top view, and front view. (h) 3D co-registration results of the USF and CT image. (i) The co-registration results on x-y plane at different z locations.
Fig. 5.
Fig. 5. (a) Normalized fluorescence intensity variation on the left side of one mouse over 24 hours after it was intravenously injected 100 µL ICG-NPs with its Tth = ∼36 °C and particle size = ∼330 nm. (b) Normalized fluorescence intensity variation on the left side of a second mouse over 3 hours (the first three images) after it was intravenously injected the same ICG-NPs solution, as well as the normalized fluorescence from the mouse’s organs (the last image) after the mouse was sacrificed at 3 hours. (c) The first image is a white photo of the second mouse’s spleen sample. The next five images show its normalized fluorescence intensity change as a function of temperature.
Fig. 6.
Fig. 6. (a) 24 hours bio-distribution of one mouse after it was intravenously injected 150 µL ICG-NPs with its Tth = ∼39 °C and particle size = ∼70 nm. (a1) Normalized fluorescence intensity variation on the dorsal side of the mouse over 24 hours. (a2) Normalized fluorescence intensity variation on the ventral side of the mouse over 24 hours. (b) 3 hours bio-distribution of a second mouse after it was intravenously injected the same ICG-NPs solution. (b1) Normalized fluorescence intensity variation on the dorsal side of the mouse over 3 hours. (b2) Normalized fluorescence intensity variation on the ventral side of the mouse over 3 hours. (b3) Normalized fluorescence from the mouse’s organs after sacrifice at 3 hours. (c) The fluorescence intensity change from the second mouse’s liver and kidney as a function of temperature. (c1) The first image is a white photo of the liver sample. The next five images show its normalized fluorescence intensity change as a function of temperature. (c2) The first image is a white photo of the kidney sample. The next five images show its normalized fluorescence intensity change as a function of temperature.
Fig. 7.
Fig. 7. (a) Normalized 2D planar fluorescence image of the mouse on its left side in FOV 1. The fluorescence mainly accumulated in the mouse’s spleen. (b) Zoomed-in normalized 2D planar fluorescence image of the mouse’s spleen area in FOV 2. (c) Top view of the 3D CT image of the mouse’s left side. (d) An example of acquired USF signals from the spleen area of the mouse. (e) Acquired USF images on x-y plane at different z locations. (f) The USF image of the USF contrast volume from 3D view, left side view, top view, and front view. (g) The CT image of the CT contrast volume from 3D view, left side view, top view, and front view. (h) 3D co-registration results of the USF and CT image. (i) The co-registration results on x-y plane at different z locations.
Fig. 8.
Fig. 8. (a) Normalized 2D planar fluorescence image of the mouse on its ventral side in FOV 1. The fluorescence mainly accumulated in the mouse’s liver. (b) Zoomed-in normalized 2D planar fluorescence image of the mouse’s liver area in FOV 2. (c) Top view of the 3D CT image of the mouse’s ventral side. (d) An example of acquired USF signals from the liver area of the mouse. (e) Acquired USF images on x-y plane at different z locations. (f) The USF image of the USF contrast volume from 3D view, left side view, top view, and front view. (g) The CT image of the CT contrast volume from 3D view, left side view, top view, and front view. (h) 3D co-registration results of the USF and CT image. (i) The co-registration results on x-y plane at different z locations.

Tables (1)

Tables Icon

Table 1. Performance Comparison between PMT-based and ICCD Camera-based USF System

Metrics