Abstract

NIR-II fluorescence imaging is a promising method for visualizing biological structures in deep tissue, owing to the advantages of significantly suppressed optical scattering and diminished autofluorescence in biological tissues. However, few NIR-II fluorescence imaging approaches can simultaneously achieve a large field of view, high resolution and superior penetration depth, while exhibiting optical sectioning capability. In this paper, we present a novel NIR-II fluorescence mesoscopy system based on the f-θ scanning scheme and confocal detection to overcome these limitations. When used with NIR-II fluorescent dyes, our setup performs NIR-II fluorescence imaging on samples as large as 7.5×7.5 mm2 with a lateral resolution of 6.3 µm. In addition, our system provides a depth-resolved imaging ability and zooming function. We successfully demonstrate in vivo cerebrovascular imaging of a mouse with local ischemia. Thus, our system provides new opportunities to explore the mechanism of cerebrovascular disease.

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

Full Article  |  PDF Article
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References

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    [Crossref]
  17. L. Zhang, X. Yan, C. Jiang, S. Zhang, Y. Chen, J. Chen, L. Kang, and P. Wu, “SNSPDs on a Magnesium Fluoride Substrate for High System Efficiency and Ultra-Wide Band,” IEEE Photonics Technol. Lett. 28(22), 2522–2525 (2016).
    [Crossref]
  18. Z. Feng, X. Yu, M. Jiang, L. Zhu, Y. Zhang, W. Yang, W. Xi, G. Li, and J. Qian, “Excretable IR-820 for in vivo NIR-II fluorescence cerebrovascular imaging and photothermal therapy of subcutaneous tumor,” Theranostics 9(19), 5706–5719 (2019).
    [Crossref]
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    [Crossref]
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    [Crossref]
  21. X. Li, H. Li, X. He, T. Chen, X. Xia, C. Yang, and W. Zheng, “Spectrum- and time-resolved endogenous multiphoton signals reveal quantitative differentiation of premalignant and malignant gastric mucosa,” Biomed. Opt. Express 9(2), 453–471 (2018).
    [Crossref]

2020 (1)

M. S. Ozturk, V. K. Lee, H. Zou, R. H. Friedel, X. Intes, and G. Dai, “High-resolution tomographic analysis of in vitro 3D glioblastoma tumor model under long-term drug treatment,” Sci. Adv. 6(10), eaay7513 (2020).
[Crossref]

2019 (3)

F. Wang, H. Wan, Z. Ma, Y. Zhong, Q. Sun, Y. Tian, L. Qu, H. Du, M. Zhang, L. Li, H. Ma, J. Luo, Y. Liang, W. J. Li, G. Hong, L. Liu, and H. Dai, “Light-sheet microscopy in the near-infrared II window,” Nat. Methods 16(6), 545–552 (2019).
[Crossref]

Z. Feng, X. Yu, M. Jiang, L. Zhu, Y. Zhang, W. Yang, W. Xi, G. Li, and J. Qian, “Excretable IR-820 for in vivo NIR-II fluorescence cerebrovascular imaging and photothermal therapy of subcutaneous tumor,” Theranostics 9(19), 5706–5719 (2019).
[Crossref]

W. Yu, B. Guo, H. Zhang, J. Zhou, X. Yu, L. Zhu, D. Xue, W. Liu, X. Sun, and J. Qian, “NIR-II fluorescence in vivo confocal microscopy with aggregation-induced emission dots,” Sci. Bull. 64(6), 410–416 (2019).
[Crossref]

2018 (5)

F. Ding, Y. Zhan, X. Lu, and Y. Sun, “Recent advances in near-infrared II fluorophores for multifunctional biomedical imaging,” Chem. Sci. 9(19), 4370–4380 (2018).
[Crossref]

H. Wan, J. Yue, S. Zhu, T. Uno, X. Zhang, Q. Yang, K. Yu, G. Hong, J. Wang, L. Li, Z. Ma, H. Gao, Y. Zhong, J. Su, A. L. Antaris, Y. Xia, J. Luo, Y. Liang, and H. Dai, “A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues,” Nat. Commun. 9(1), 1171 (2018).
[Crossref]

M. Zhang, J. Yue, R. Cui, Z. Ma, H. Wan, F. Wang, S. Zhu, Y. Zhou, Y. Kuang, Y. Zhong, D.-W. Pang, and H. Dai, “Bright quantum dots emitting at ∼1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging,” Proc. Natl. Acad. Sci. 115(26), 6590–6595 (2018).
[Crossref]

V. I. Shcheslavskiy, M. V. Shirmanova, V. V. Dudenkova, K. A. Lukyanov, A. I. Gavrina, A. V. Shumilova, E. Zagaynova, and W. Becker, “Fluorescence time-resolved macroimaging,” Opt. Lett. 43(13), 3152–3155 (2018).
[Crossref]

X. Li, H. Li, X. He, T. Chen, X. Xia, C. Yang, and W. Zheng, “Spectrum- and time-resolved endogenous multiphoton signals reveal quantitative differentiation of premalignant and malignant gastric mucosa,” Biomed. Opt. Express 9(2), 453–471 (2018).
[Crossref]

2017 (1)

Y. Zhong, Z. Ma, S. Zhu, J. Yue, M. Zhang, A. L. Antaris, J. Yuan, R. Cui, H. Wan, Y. Zhou, W. Wang, N. F. Huang, J. Luo, Z. Hu, and H. Dai, “Boosting the down-shifting luminescence of rare-earth nanocrystals for biological imaging beyond 1500 nm,” Nat. Commun. 8(1), 737 (2017).
[Crossref]

2016 (3)

N. J. Sofroniew, D. Flickinger, J. King, and K. Svoboda, “A large field of view two-photon mesoscope with subcellular resolution for in vivo imaging,” eLife 5, e14472 (2016).
[Crossref]

G. McConnell, J. Trägårdh, R. Amor, J. Dempster, E. Reid, and W. B. Amos, “A novel optical microscope for imaging large embryos and tissue volumes with sub-cellular resolution throughout,” eLife 5, e18659 (2016).
[Crossref]

L. Zhang, X. Yan, C. Jiang, S. Zhang, Y. Chen, J. Chen, L. Kang, and P. Wu, “SNSPDs on a Magnesium Fluoride Substrate for High System Efficiency and Ultra-Wide Band,” IEEE Photonics Technol. Lett. 28(22), 2522–2525 (2016).
[Crossref]

2015 (1)

B. K. Menon, B. C. V. Campbell, C. Levi, and M. Goyal, “Role of Imaging in Current Acute Ischemic Stroke Workflow for Endovascular Therapy,” Stroke 46(6), 1453–1461 (2015).
[Crossref]

2014 (2)

G. Hong, S. Diao, J. Chang, A. L. Antaris, C. Chen, B. Zhang, S. Zhao, D. N. Atochin, P. L. Huang, K. I. Andreasson, C. J. Kuo, and H. Dai, “Through-skull fluorescence imaging of the brain in a new near-infrared window,” Nat. Photonics 8(9), 723–730 (2014).
[Crossref]

G. Hong, Y. Zou, A. L. Antaris, S. Diao, D. Wu, K. Cheng, X. Zhang, C. Chen, B. Liu, Y. He, J. Z. Wu, J. Yuan, B. Zhang, Z. Tao, C. Fukunaga, and H. Dai, “Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window,” Nat. Commun. 5(1), 4206 (2014).
[Crossref]

2013 (1)

V. Labat-gest and S. Tomasi, “Photothrombotic ischemia: a minimally invasive and reproducible photochemical cortical lesion model for mouse stroke studies,” J. Visualized Exp. 76, 50370 (2013).
[Crossref]

2012 (1)

G. Hong, J. C. Lee, J. T. Robinson, U. Raaz, L. Xie, N. F. Huang, J. P. Cooke, and H. Dai, “Multifunctional in vivo vascular imaging using near-infrared II fluorescence,” Nat. Med. 18(12), 1841–1846 (2012).
[Crossref]

2011 (1)

J.-H. Lee, I. J. Gomez, V. B. Sitterle, and J. C. Meredith, “Dye-labeled polystyrene latex microspheres prepared via a combined swelling-diffusion technique,” J. Colloid Interface Sci. 363(1), 137–144 (2011).
[Crossref]

2000 (1)

K. König, “Multiphoton microscopy in life sciences,” J. Microsc. 200(2), 83–104 (2000).
[Crossref]

1995 (1)

A. E. Dixon, S. Damaskinos, A. Ribes, and K. M. Beesley, “A new confocal scanning beam laser MACROscope using a telecentric, f-theta laser scan lens,” J. Microsc. 178(3), 261–266 (1995).
[Crossref]

Amor, R.

G. McConnell, J. Trägårdh, R. Amor, J. Dempster, E. Reid, and W. B. Amos, “A novel optical microscope for imaging large embryos and tissue volumes with sub-cellular resolution throughout,” eLife 5, e18659 (2016).
[Crossref]

Amos, W. B.

G. McConnell, J. Trägårdh, R. Amor, J. Dempster, E. Reid, and W. B. Amos, “A novel optical microscope for imaging large embryos and tissue volumes with sub-cellular resolution throughout,” eLife 5, e18659 (2016).
[Crossref]

Andreasson, K. I.

G. Hong, S. Diao, J. Chang, A. L. Antaris, C. Chen, B. Zhang, S. Zhao, D. N. Atochin, P. L. Huang, K. I. Andreasson, C. J. Kuo, and H. Dai, “Through-skull fluorescence imaging of the brain in a new near-infrared window,” Nat. Photonics 8(9), 723–730 (2014).
[Crossref]

Antaris, A. L.

H. Wan, J. Yue, S. Zhu, T. Uno, X. Zhang, Q. Yang, K. Yu, G. Hong, J. Wang, L. Li, Z. Ma, H. Gao, Y. Zhong, J. Su, A. L. Antaris, Y. Xia, J. Luo, Y. Liang, and H. Dai, “A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues,” Nat. Commun. 9(1), 1171 (2018).
[Crossref]

Y. Zhong, Z. Ma, S. Zhu, J. Yue, M. Zhang, A. L. Antaris, J. Yuan, R. Cui, H. Wan, Y. Zhou, W. Wang, N. F. Huang, J. Luo, Z. Hu, and H. Dai, “Boosting the down-shifting luminescence of rare-earth nanocrystals for biological imaging beyond 1500 nm,” Nat. Commun. 8(1), 737 (2017).
[Crossref]

G. Hong, Y. Zou, A. L. Antaris, S. Diao, D. Wu, K. Cheng, X. Zhang, C. Chen, B. Liu, Y. He, J. Z. Wu, J. Yuan, B. Zhang, Z. Tao, C. Fukunaga, and H. Dai, “Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window,” Nat. Commun. 5(1), 4206 (2014).
[Crossref]

G. Hong, S. Diao, J. Chang, A. L. Antaris, C. Chen, B. Zhang, S. Zhao, D. N. Atochin, P. L. Huang, K. I. Andreasson, C. J. Kuo, and H. Dai, “Through-skull fluorescence imaging of the brain in a new near-infrared window,” Nat. Photonics 8(9), 723–730 (2014).
[Crossref]

Atochin, D. N.

G. Hong, S. Diao, J. Chang, A. L. Antaris, C. Chen, B. Zhang, S. Zhao, D. N. Atochin, P. L. Huang, K. I. Andreasson, C. J. Kuo, and H. Dai, “Through-skull fluorescence imaging of the brain in a new near-infrared window,” Nat. Photonics 8(9), 723–730 (2014).
[Crossref]

Becker, W.

Beesley, K. M.

A. E. Dixon, S. Damaskinos, A. Ribes, and K. M. Beesley, “A new confocal scanning beam laser MACROscope using a telecentric, f-theta laser scan lens,” J. Microsc. 178(3), 261–266 (1995).
[Crossref]

Campbell, B. C. V.

B. K. Menon, B. C. V. Campbell, C. Levi, and M. Goyal, “Role of Imaging in Current Acute Ischemic Stroke Workflow for Endovascular Therapy,” Stroke 46(6), 1453–1461 (2015).
[Crossref]

Chang, J.

G. Hong, S. Diao, J. Chang, A. L. Antaris, C. Chen, B. Zhang, S. Zhao, D. N. Atochin, P. L. Huang, K. I. Andreasson, C. J. Kuo, and H. Dai, “Through-skull fluorescence imaging of the brain in a new near-infrared window,” Nat. Photonics 8(9), 723–730 (2014).
[Crossref]

Chen, C.

G. Hong, Y. Zou, A. L. Antaris, S. Diao, D. Wu, K. Cheng, X. Zhang, C. Chen, B. Liu, Y. He, J. Z. Wu, J. Yuan, B. Zhang, Z. Tao, C. Fukunaga, and H. Dai, “Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window,” Nat. Commun. 5(1), 4206 (2014).
[Crossref]

G. Hong, S. Diao, J. Chang, A. L. Antaris, C. Chen, B. Zhang, S. Zhao, D. N. Atochin, P. L. Huang, K. I. Andreasson, C. J. Kuo, and H. Dai, “Through-skull fluorescence imaging of the brain in a new near-infrared window,” Nat. Photonics 8(9), 723–730 (2014).
[Crossref]

Chen, J.

L. Zhang, X. Yan, C. Jiang, S. Zhang, Y. Chen, J. Chen, L. Kang, and P. Wu, “SNSPDs on a Magnesium Fluoride Substrate for High System Efficiency and Ultra-Wide Band,” IEEE Photonics Technol. Lett. 28(22), 2522–2525 (2016).
[Crossref]

Chen, T.

Chen, Y.

L. Zhang, X. Yan, C. Jiang, S. Zhang, Y. Chen, J. Chen, L. Kang, and P. Wu, “SNSPDs on a Magnesium Fluoride Substrate for High System Efficiency and Ultra-Wide Band,” IEEE Photonics Technol. Lett. 28(22), 2522–2525 (2016).
[Crossref]

Cheng, K.

G. Hong, Y. Zou, A. L. Antaris, S. Diao, D. Wu, K. Cheng, X. Zhang, C. Chen, B. Liu, Y. He, J. Z. Wu, J. Yuan, B. Zhang, Z. Tao, C. Fukunaga, and H. Dai, “Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window,” Nat. Commun. 5(1), 4206 (2014).
[Crossref]

Cooke, J. P.

G. Hong, J. C. Lee, J. T. Robinson, U. Raaz, L. Xie, N. F. Huang, J. P. Cooke, and H. Dai, “Multifunctional in vivo vascular imaging using near-infrared II fluorescence,” Nat. Med. 18(12), 1841–1846 (2012).
[Crossref]

Cui, R.

M. Zhang, J. Yue, R. Cui, Z. Ma, H. Wan, F. Wang, S. Zhu, Y. Zhou, Y. Kuang, Y. Zhong, D.-W. Pang, and H. Dai, “Bright quantum dots emitting at ∼1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging,” Proc. Natl. Acad. Sci. 115(26), 6590–6595 (2018).
[Crossref]

Y. Zhong, Z. Ma, S. Zhu, J. Yue, M. Zhang, A. L. Antaris, J. Yuan, R. Cui, H. Wan, Y. Zhou, W. Wang, N. F. Huang, J. Luo, Z. Hu, and H. Dai, “Boosting the down-shifting luminescence of rare-earth nanocrystals for biological imaging beyond 1500 nm,” Nat. Commun. 8(1), 737 (2017).
[Crossref]

Dai, G.

M. S. Ozturk, V. K. Lee, H. Zou, R. H. Friedel, X. Intes, and G. Dai, “High-resolution tomographic analysis of in vitro 3D glioblastoma tumor model under long-term drug treatment,” Sci. Adv. 6(10), eaay7513 (2020).
[Crossref]

Dai, H.

F. Wang, H. Wan, Z. Ma, Y. Zhong, Q. Sun, Y. Tian, L. Qu, H. Du, M. Zhang, L. Li, H. Ma, J. Luo, Y. Liang, W. J. Li, G. Hong, L. Liu, and H. Dai, “Light-sheet microscopy in the near-infrared II window,” Nat. Methods 16(6), 545–552 (2019).
[Crossref]

H. Wan, J. Yue, S. Zhu, T. Uno, X. Zhang, Q. Yang, K. Yu, G. Hong, J. Wang, L. Li, Z. Ma, H. Gao, Y. Zhong, J. Su, A. L. Antaris, Y. Xia, J. Luo, Y. Liang, and H. Dai, “A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues,” Nat. Commun. 9(1), 1171 (2018).
[Crossref]

M. Zhang, J. Yue, R. Cui, Z. Ma, H. Wan, F. Wang, S. Zhu, Y. Zhou, Y. Kuang, Y. Zhong, D.-W. Pang, and H. Dai, “Bright quantum dots emitting at ∼1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging,” Proc. Natl. Acad. Sci. 115(26), 6590–6595 (2018).
[Crossref]

Y. Zhong, Z. Ma, S. Zhu, J. Yue, M. Zhang, A. L. Antaris, J. Yuan, R. Cui, H. Wan, Y. Zhou, W. Wang, N. F. Huang, J. Luo, Z. Hu, and H. Dai, “Boosting the down-shifting luminescence of rare-earth nanocrystals for biological imaging beyond 1500 nm,” Nat. Commun. 8(1), 737 (2017).
[Crossref]

G. Hong, Y. Zou, A. L. Antaris, S. Diao, D. Wu, K. Cheng, X. Zhang, C. Chen, B. Liu, Y. He, J. Z. Wu, J. Yuan, B. Zhang, Z. Tao, C. Fukunaga, and H. Dai, “Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window,” Nat. Commun. 5(1), 4206 (2014).
[Crossref]

G. Hong, S. Diao, J. Chang, A. L. Antaris, C. Chen, B. Zhang, S. Zhao, D. N. Atochin, P. L. Huang, K. I. Andreasson, C. J. Kuo, and H. Dai, “Through-skull fluorescence imaging of the brain in a new near-infrared window,” Nat. Photonics 8(9), 723–730 (2014).
[Crossref]

G. Hong, J. C. Lee, J. T. Robinson, U. Raaz, L. Xie, N. F. Huang, J. P. Cooke, and H. Dai, “Multifunctional in vivo vascular imaging using near-infrared II fluorescence,” Nat. Med. 18(12), 1841–1846 (2012).
[Crossref]

Damaskinos, S.

A. E. Dixon, S. Damaskinos, A. Ribes, and K. M. Beesley, “A new confocal scanning beam laser MACROscope using a telecentric, f-theta laser scan lens,” J. Microsc. 178(3), 261–266 (1995).
[Crossref]

Dempster, J.

G. McConnell, J. Trägårdh, R. Amor, J. Dempster, E. Reid, and W. B. Amos, “A novel optical microscope for imaging large embryos and tissue volumes with sub-cellular resolution throughout,” eLife 5, e18659 (2016).
[Crossref]

Diao, S.

G. Hong, Y. Zou, A. L. Antaris, S. Diao, D. Wu, K. Cheng, X. Zhang, C. Chen, B. Liu, Y. He, J. Z. Wu, J. Yuan, B. Zhang, Z. Tao, C. Fukunaga, and H. Dai, “Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window,” Nat. Commun. 5(1), 4206 (2014).
[Crossref]

G. Hong, S. Diao, J. Chang, A. L. Antaris, C. Chen, B. Zhang, S. Zhao, D. N. Atochin, P. L. Huang, K. I. Andreasson, C. J. Kuo, and H. Dai, “Through-skull fluorescence imaging of the brain in a new near-infrared window,” Nat. Photonics 8(9), 723–730 (2014).
[Crossref]

Ding, F.

F. Ding, Y. Zhan, X. Lu, and Y. Sun, “Recent advances in near-infrared II fluorophores for multifunctional biomedical imaging,” Chem. Sci. 9(19), 4370–4380 (2018).
[Crossref]

Dixon, A. E.

A. E. Dixon, S. Damaskinos, A. Ribes, and K. M. Beesley, “A new confocal scanning beam laser MACROscope using a telecentric, f-theta laser scan lens,” J. Microsc. 178(3), 261–266 (1995).
[Crossref]

Du, H.

F. Wang, H. Wan, Z. Ma, Y. Zhong, Q. Sun, Y. Tian, L. Qu, H. Du, M. Zhang, L. Li, H. Ma, J. Luo, Y. Liang, W. J. Li, G. Hong, L. Liu, and H. Dai, “Light-sheet microscopy in the near-infrared II window,” Nat. Methods 16(6), 545–552 (2019).
[Crossref]

Dudenkova, V. V.

Feng, Z.

Z. Feng, X. Yu, M. Jiang, L. Zhu, Y. Zhang, W. Yang, W. Xi, G. Li, and J. Qian, “Excretable IR-820 for in vivo NIR-II fluorescence cerebrovascular imaging and photothermal therapy of subcutaneous tumor,” Theranostics 9(19), 5706–5719 (2019).
[Crossref]

Flickinger, D.

N. J. Sofroniew, D. Flickinger, J. King, and K. Svoboda, “A large field of view two-photon mesoscope with subcellular resolution for in vivo imaging,” eLife 5, e14472 (2016).
[Crossref]

Friedel, R. H.

M. S. Ozturk, V. K. Lee, H. Zou, R. H. Friedel, X. Intes, and G. Dai, “High-resolution tomographic analysis of in vitro 3D glioblastoma tumor model under long-term drug treatment,” Sci. Adv. 6(10), eaay7513 (2020).
[Crossref]

Fukunaga, C.

G. Hong, Y. Zou, A. L. Antaris, S. Diao, D. Wu, K. Cheng, X. Zhang, C. Chen, B. Liu, Y. He, J. Z. Wu, J. Yuan, B. Zhang, Z. Tao, C. Fukunaga, and H. Dai, “Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window,” Nat. Commun. 5(1), 4206 (2014).
[Crossref]

Gao, H.

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G. Hong, Y. Zou, A. L. Antaris, S. Diao, D. Wu, K. Cheng, X. Zhang, C. Chen, B. Liu, Y. He, J. Z. Wu, J. Yuan, B. Zhang, Z. Tao, C. Fukunaga, and H. Dai, “Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window,” Nat. Commun. 5(1), 4206 (2014).
[Crossref]

Wu, P.

L. Zhang, X. Yan, C. Jiang, S. Zhang, Y. Chen, J. Chen, L. Kang, and P. Wu, “SNSPDs on a Magnesium Fluoride Substrate for High System Efficiency and Ultra-Wide Band,” IEEE Photonics Technol. Lett. 28(22), 2522–2525 (2016).
[Crossref]

Xi, W.

Z. Feng, X. Yu, M. Jiang, L. Zhu, Y. Zhang, W. Yang, W. Xi, G. Li, and J. Qian, “Excretable IR-820 for in vivo NIR-II fluorescence cerebrovascular imaging and photothermal therapy of subcutaneous tumor,” Theranostics 9(19), 5706–5719 (2019).
[Crossref]

Xia, X.

Xia, Y.

H. Wan, J. Yue, S. Zhu, T. Uno, X. Zhang, Q. Yang, K. Yu, G. Hong, J. Wang, L. Li, Z. Ma, H. Gao, Y. Zhong, J. Su, A. L. Antaris, Y. Xia, J. Luo, Y. Liang, and H. Dai, “A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues,” Nat. Commun. 9(1), 1171 (2018).
[Crossref]

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G. Hong, J. C. Lee, J. T. Robinson, U. Raaz, L. Xie, N. F. Huang, J. P. Cooke, and H. Dai, “Multifunctional in vivo vascular imaging using near-infrared II fluorescence,” Nat. Med. 18(12), 1841–1846 (2012).
[Crossref]

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[Crossref]

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L. Zhang, X. Yan, C. Jiang, S. Zhang, Y. Chen, J. Chen, L. Kang, and P. Wu, “SNSPDs on a Magnesium Fluoride Substrate for High System Efficiency and Ultra-Wide Band,” IEEE Photonics Technol. Lett. 28(22), 2522–2525 (2016).
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[Crossref]

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Z. Feng, X. Yu, M. Jiang, L. Zhu, Y. Zhang, W. Yang, W. Xi, G. Li, and J. Qian, “Excretable IR-820 for in vivo NIR-II fluorescence cerebrovascular imaging and photothermal therapy of subcutaneous tumor,” Theranostics 9(19), 5706–5719 (2019).
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H. Wan, J. Yue, S. Zhu, T. Uno, X. Zhang, Q. Yang, K. Yu, G. Hong, J. Wang, L. Li, Z. Ma, H. Gao, Y. Zhong, J. Su, A. L. Antaris, Y. Xia, J. Luo, Y. Liang, and H. Dai, “A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues,” Nat. Commun. 9(1), 1171 (2018).
[Crossref]

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W. Yu, B. Guo, H. Zhang, J. Zhou, X. Yu, L. Zhu, D. Xue, W. Liu, X. Sun, and J. Qian, “NIR-II fluorescence in vivo confocal microscopy with aggregation-induced emission dots,” Sci. Bull. 64(6), 410–416 (2019).
[Crossref]

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W. Yu, B. Guo, H. Zhang, J. Zhou, X. Yu, L. Zhu, D. Xue, W. Liu, X. Sun, and J. Qian, “NIR-II fluorescence in vivo confocal microscopy with aggregation-induced emission dots,” Sci. Bull. 64(6), 410–416 (2019).
[Crossref]

Z. Feng, X. Yu, M. Jiang, L. Zhu, Y. Zhang, W. Yang, W. Xi, G. Li, and J. Qian, “Excretable IR-820 for in vivo NIR-II fluorescence cerebrovascular imaging and photothermal therapy of subcutaneous tumor,” Theranostics 9(19), 5706–5719 (2019).
[Crossref]

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[Crossref]

G. Hong, Y. Zou, A. L. Antaris, S. Diao, D. Wu, K. Cheng, X. Zhang, C. Chen, B. Liu, Y. He, J. Z. Wu, J. Yuan, B. Zhang, Z. Tao, C. Fukunaga, and H. Dai, “Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window,” Nat. Commun. 5(1), 4206 (2014).
[Crossref]

Yue, J.

H. Wan, J. Yue, S. Zhu, T. Uno, X. Zhang, Q. Yang, K. Yu, G. Hong, J. Wang, L. Li, Z. Ma, H. Gao, Y. Zhong, J. Su, A. L. Antaris, Y. Xia, J. Luo, Y. Liang, and H. Dai, “A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues,” Nat. Commun. 9(1), 1171 (2018).
[Crossref]

M. Zhang, J. Yue, R. Cui, Z. Ma, H. Wan, F. Wang, S. Zhu, Y. Zhou, Y. Kuang, Y. Zhong, D.-W. Pang, and H. Dai, “Bright quantum dots emitting at ∼1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging,” Proc. Natl. Acad. Sci. 115(26), 6590–6595 (2018).
[Crossref]

Y. Zhong, Z. Ma, S. Zhu, J. Yue, M. Zhang, A. L. Antaris, J. Yuan, R. Cui, H. Wan, Y. Zhou, W. Wang, N. F. Huang, J. Luo, Z. Hu, and H. Dai, “Boosting the down-shifting luminescence of rare-earth nanocrystals for biological imaging beyond 1500 nm,” Nat. Commun. 8(1), 737 (2017).
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Zagaynova, E.

Zhan, Y.

F. Ding, Y. Zhan, X. Lu, and Y. Sun, “Recent advances in near-infrared II fluorophores for multifunctional biomedical imaging,” Chem. Sci. 9(19), 4370–4380 (2018).
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[Crossref]

G. Hong, S. Diao, J. Chang, A. L. Antaris, C. Chen, B. Zhang, S. Zhao, D. N. Atochin, P. L. Huang, K. I. Andreasson, C. J. Kuo, and H. Dai, “Through-skull fluorescence imaging of the brain in a new near-infrared window,” Nat. Photonics 8(9), 723–730 (2014).
[Crossref]

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W. Yu, B. Guo, H. Zhang, J. Zhou, X. Yu, L. Zhu, D. Xue, W. Liu, X. Sun, and J. Qian, “NIR-II fluorescence in vivo confocal microscopy with aggregation-induced emission dots,” Sci. Bull. 64(6), 410–416 (2019).
[Crossref]

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L. Zhang, X. Yan, C. Jiang, S. Zhang, Y. Chen, J. Chen, L. Kang, and P. Wu, “SNSPDs on a Magnesium Fluoride Substrate for High System Efficiency and Ultra-Wide Band,” IEEE Photonics Technol. Lett. 28(22), 2522–2525 (2016).
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M. Zhang, J. Yue, R. Cui, Z. Ma, H. Wan, F. Wang, S. Zhu, Y. Zhou, Y. Kuang, Y. Zhong, D.-W. Pang, and H. Dai, “Bright quantum dots emitting at ∼1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging,” Proc. Natl. Acad. Sci. 115(26), 6590–6595 (2018).
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Y. Zhong, Z. Ma, S. Zhu, J. Yue, M. Zhang, A. L. Antaris, J. Yuan, R. Cui, H. Wan, Y. Zhou, W. Wang, N. F. Huang, J. Luo, Z. Hu, and H. Dai, “Boosting the down-shifting luminescence of rare-earth nanocrystals for biological imaging beyond 1500 nm,” Nat. Commun. 8(1), 737 (2017).
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L. Zhang, X. Yan, C. Jiang, S. Zhang, Y. Chen, J. Chen, L. Kang, and P. Wu, “SNSPDs on a Magnesium Fluoride Substrate for High System Efficiency and Ultra-Wide Band,” IEEE Photonics Technol. Lett. 28(22), 2522–2525 (2016).
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[Crossref]

G. Hong, Y. Zou, A. L. Antaris, S. Diao, D. Wu, K. Cheng, X. Zhang, C. Chen, B. Liu, Y. He, J. Z. Wu, J. Yuan, B. Zhang, Z. Tao, C. Fukunaga, and H. Dai, “Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window,” Nat. Commun. 5(1), 4206 (2014).
[Crossref]

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Z. Feng, X. Yu, M. Jiang, L. Zhu, Y. Zhang, W. Yang, W. Xi, G. Li, and J. Qian, “Excretable IR-820 for in vivo NIR-II fluorescence cerebrovascular imaging and photothermal therapy of subcutaneous tumor,” Theranostics 9(19), 5706–5719 (2019).
[Crossref]

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G. Hong, S. Diao, J. Chang, A. L. Antaris, C. Chen, B. Zhang, S. Zhao, D. N. Atochin, P. L. Huang, K. I. Andreasson, C. J. Kuo, and H. Dai, “Through-skull fluorescence imaging of the brain in a new near-infrared window,” Nat. Photonics 8(9), 723–730 (2014).
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M. Zhang, J. Yue, R. Cui, Z. Ma, H. Wan, F. Wang, S. Zhu, Y. Zhou, Y. Kuang, Y. Zhong, D.-W. Pang, and H. Dai, “Bright quantum dots emitting at ∼1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging,” Proc. Natl. Acad. Sci. 115(26), 6590–6595 (2018).
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H. Wan, J. Yue, S. Zhu, T. Uno, X. Zhang, Q. Yang, K. Yu, G. Hong, J. Wang, L. Li, Z. Ma, H. Gao, Y. Zhong, J. Su, A. L. Antaris, Y. Xia, J. Luo, Y. Liang, and H. Dai, “A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues,” Nat. Commun. 9(1), 1171 (2018).
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Y. Zhong, Z. Ma, S. Zhu, J. Yue, M. Zhang, A. L. Antaris, J. Yuan, R. Cui, H. Wan, Y. Zhou, W. Wang, N. F. Huang, J. Luo, Z. Hu, and H. Dai, “Boosting the down-shifting luminescence of rare-earth nanocrystals for biological imaging beyond 1500 nm,” Nat. Commun. 8(1), 737 (2017).
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W. Yu, B. Guo, H. Zhang, J. Zhou, X. Yu, L. Zhu, D. Xue, W. Liu, X. Sun, and J. Qian, “NIR-II fluorescence in vivo confocal microscopy with aggregation-induced emission dots,” Sci. Bull. 64(6), 410–416 (2019).
[Crossref]

Zhou, Y.

M. Zhang, J. Yue, R. Cui, Z. Ma, H. Wan, F. Wang, S. Zhu, Y. Zhou, Y. Kuang, Y. Zhong, D.-W. Pang, and H. Dai, “Bright quantum dots emitting at ∼1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging,” Proc. Natl. Acad. Sci. 115(26), 6590–6595 (2018).
[Crossref]

Y. Zhong, Z. Ma, S. Zhu, J. Yue, M. Zhang, A. L. Antaris, J. Yuan, R. Cui, H. Wan, Y. Zhou, W. Wang, N. F. Huang, J. Luo, Z. Hu, and H. Dai, “Boosting the down-shifting luminescence of rare-earth nanocrystals for biological imaging beyond 1500 nm,” Nat. Commun. 8(1), 737 (2017).
[Crossref]

Zhu, L.

W. Yu, B. Guo, H. Zhang, J. Zhou, X. Yu, L. Zhu, D. Xue, W. Liu, X. Sun, and J. Qian, “NIR-II fluorescence in vivo confocal microscopy with aggregation-induced emission dots,” Sci. Bull. 64(6), 410–416 (2019).
[Crossref]

Z. Feng, X. Yu, M. Jiang, L. Zhu, Y. Zhang, W. Yang, W. Xi, G. Li, and J. Qian, “Excretable IR-820 for in vivo NIR-II fluorescence cerebrovascular imaging and photothermal therapy of subcutaneous tumor,” Theranostics 9(19), 5706–5719 (2019).
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M. Zhang, J. Yue, R. Cui, Z. Ma, H. Wan, F. Wang, S. Zhu, Y. Zhou, Y. Kuang, Y. Zhong, D.-W. Pang, and H. Dai, “Bright quantum dots emitting at ∼1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging,” Proc. Natl. Acad. Sci. 115(26), 6590–6595 (2018).
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H. Wan, J. Yue, S. Zhu, T. Uno, X. Zhang, Q. Yang, K. Yu, G. Hong, J. Wang, L. Li, Z. Ma, H. Gao, Y. Zhong, J. Su, A. L. Antaris, Y. Xia, J. Luo, Y. Liang, and H. Dai, “A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues,” Nat. Commun. 9(1), 1171 (2018).
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Y. Zhong, Z. Ma, S. Zhu, J. Yue, M. Zhang, A. L. Antaris, J. Yuan, R. Cui, H. Wan, Y. Zhou, W. Wang, N. F. Huang, J. Luo, Z. Hu, and H. Dai, “Boosting the down-shifting luminescence of rare-earth nanocrystals for biological imaging beyond 1500 nm,” Nat. Commun. 8(1), 737 (2017).
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Biomed. Opt. Express (1)

Chem. Sci. (1)

F. Ding, Y. Zhan, X. Lu, and Y. Sun, “Recent advances in near-infrared II fluorophores for multifunctional biomedical imaging,” Chem. Sci. 9(19), 4370–4380 (2018).
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M. S. Ozturk, V. K. Lee, H. Zou, R. H. Friedel, X. Intes, and G. Dai, “High-resolution tomographic analysis of in vitro 3D glioblastoma tumor model under long-term drug treatment,” Sci. Adv. 6(10), eaay7513 (2020).
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Z. Feng, X. Yu, M. Jiang, L. Zhu, Y. Zhang, W. Yang, W. Xi, G. Li, and J. Qian, “Excretable IR-820 for in vivo NIR-II fluorescence cerebrovascular imaging and photothermal therapy of subcutaneous tumor,” Theranostics 9(19), 5706–5719 (2019).
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Figures (4)

Fig. 1.
Fig. 1. (a) Schematic of NIR-II fluorescence mesoscopy system. DM: dichroic mirror; GM, galvanometric mirrors; LP, longpass filter; SNSPD, superconducting nanowire single-photon detector. (b) Lateral intensity profile of a fluorescent bead (diameter 1 µm) with Gaussian fit. Top left inset: x-y image of a fluorescent bead, scale bar is 25 µm. (c) Axial response plot generated by translating a fluorescent bead through focus. Top left inset: x-z image of a fluorescent bead, scale bar is 200 µm. (d) Reflection image of a steel rule after removing the longpass filter.
Fig. 2.
Fig. 2. In vivo through skull NIR-II fluorescence imaging of mouse cerebral vasculature. (a) The cerebral vasculature images of mouse at various depths. (b) Magnification graph of the solid rectangle in (a). (c) The cross-sectional intensity profiles along the capillary vessels indicated by the red line in (b). (d) 3D reconstruction of vasculatures in brain. (e) Magnification graph of the solid rectangle in (d).
Fig. 3.
Fig. 3. Images of IR-820 labeled C6 cells at different scanning range. (a) The largest scanning image of cells. (b) Zoomed image of the dashed rectangle area of (a). (c) Zoomed image of the solid rectangle area of (b). All images were acquired by only altering the scanning angles of the galvanometer, without changing any optical components.
Fig. 4.
Fig. 4. In vivo through skull cerebral vasculature imaging of a local cerebral ischemia mouse with photochemically induced thrombosis. (a) In vivo time-lapse cerebrovascular imaging of the cerebral ischemia mouse with the intravenous injection by 200 µL IR-820. All images in Fig. 4(a) consist of 256×256 pixels with 1.28 s/frame. (b) The max intensity project image of the cerebral vasculature from 0 mm to 2.5 mm deep. The z step size is 0.25 mm and total acquisition time is about 1 min. All images in Fig. 4(b) consist of 512×512 pixels and acquired at 5.12 s/frame.

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