Journal Home > Volume 13 , Issue 11

The in vivo spatio-temporal patterns of neovascularization are still poorly understood because it is limited to multi-scale techniques from the cellular level to living animal level. Owing to deep tissue-penetration and zero autofluorescence background, the second near-infrared (NIR-II, 1,000-1,700 nm) fluorescence imaging recently shows promise in breaking through this dilemma by dynamically tracking the pathophysiological process of neovascularization in vivo. Here, NIR-II fluorescence imaging was recruited for monitoring blood vessels in order to visualize the vascular injury and quantitively assess neovascularization in mouse models of acute skeleton muscle contusion and hindlimb ischemia. The temporal analysis of real-time NIR-II fluorescence intensity demonstrated that the blood flow perfusion of ischemia area was able to rapidly restore to 96% of pre-ischemic state within one week. Moreover, the spatial analysis revealed that the lower and outer quadrants of ischemia area in the mouse model of hindlimb ischemia always had relatively high blood flow perfusion compared with other quadrants during three weeks post-ischemia, and even exceeded pre-ischemic quantity at 21 days post-ischemia. In conclusion, this in vivo imaging technique has significant potential utility for studying the spatio-temporal patterns of neovascularization in vivo.


menu
Abstract
Full text
Outline
About this article

Tracking the in vivo spatio-temporal patterns of neovascularization via NIR-II fluorescence imaging

Show Author's information Mo Chen§Sijia Feng§Yimeng YangYunxia LiJian ZhangShiyi Chen( )Jun Chen( )
Institute of Sports Medicine of Fudan University, Department of Orthopaedic Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200041, China

§ Mo Chen and Sijia Feng contributed equally to this work.

Abstract

The in vivo spatio-temporal patterns of neovascularization are still poorly understood because it is limited to multi-scale techniques from the cellular level to living animal level. Owing to deep tissue-penetration and zero autofluorescence background, the second near-infrared (NIR-II, 1,000-1,700 nm) fluorescence imaging recently shows promise in breaking through this dilemma by dynamically tracking the pathophysiological process of neovascularization in vivo. Here, NIR-II fluorescence imaging was recruited for monitoring blood vessels in order to visualize the vascular injury and quantitively assess neovascularization in mouse models of acute skeleton muscle contusion and hindlimb ischemia. The temporal analysis of real-time NIR-II fluorescence intensity demonstrated that the blood flow perfusion of ischemia area was able to rapidly restore to 96% of pre-ischemic state within one week. Moreover, the spatial analysis revealed that the lower and outer quadrants of ischemia area in the mouse model of hindlimb ischemia always had relatively high blood flow perfusion compared with other quadrants during three weeks post-ischemia, and even exceeded pre-ischemic quantity at 21 days post-ischemia. In conclusion, this in vivo imaging technique has significant potential utility for studying the spatio-temporal patterns of neovascularization in vivo.

Keywords: bioimaging, nanoprobes, second near-infrared (NIR-II) fluorescence, spatio-temporal, neovascularization

References(25)

[1]
Limbourg, A.; Korff, T.; Napp, L. C.; Schaper, W.; Drexler, H.; Limbourg, F. P. Evaluation of postnatal arteriogenesis and angiogenesis in a mouse model of hind-limb ischemia. Nat. Protoc. 2009, 4, 1737-1746.
[2]
Ma, Z. R.; Zhang, M. X.; Yue, J. Y.; Alcazar, C.; Zhong, Y. T.; Doyle, T. C.; Dai, H. J.; Huang, N. F. Near-infrared IIb fluorescence imaging of vascular regeneration with dynamic tissue perfusion measurement and high spatial resolution. Adv. Funct. Mater. 2018, 28, 1803417.
[3]
Chen, L.; Zhang, L. S.; Fang, Z. R.; Li, C. X.; Yang, Y.; You, X. Y.; Song, M.; Coffie, J.; Zhang, L. Y.; Gao, X. M. et al. Naoxintong restores collateral blood flow in a murine model of hindlimb ischemia through PPARδ-dependent mechanism. J. Ethnopharmacol. 2018, 227, 121-130.
[4]
Weissleder, R.; Pittet, M. J. Imaging in the era of molecular oncology. Nature 2008, 452, 580-589.
[5]
Xue, Z. L.; Zeng, S. J.; Hao, J. H. Non-invasive through-skull brain vascular imaging and small tumor diagnosis based on NIR-II emissive lanthanide nanoprobes beyond 1,500 nm. Biomaterials 2018, 171, 153-163.
[6]
Grüneboom, A.; Kling, L.; Christiansen, S.; Mill, L.; Maier, A.; Engelke, K.; Quick, H. H.; Schett, G.; Gunzer, M. Next-generation imaging of the skeletal system and its blood supply. Nat. Rev. Rheumatol. 2019, 15, 533-549.
[7]
Lin, J. C.; Zeng, X. D.; Xiao, Y. L.; Tang, L.; Nong, J. X.; Liu, Y. F.; Zhou, H.; Ding, B. B.; Xu, F. C.; Tong, H. X. et al. Novel near- infrared II aggregation-induced emission dots for in vivo bioimaging. Chem. Sci. 2019, 10, 1219-1226.
[8]
Wan, H.; Yue, J. Y.; Zhu, S. J.; Uno, T.; Zhang, X. D.; Yang, Q. L.; Yu, K.; Hong, G. S.; Wang, J. Y.; Li, L. L. et al. A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues. Nat. Commun. 2018, 9, 1171.
[9]
Antaris, A. L.; Chen, H.; Diao, S.; Ma, Z. R.; Zhang, Z.; Zhu, S. J.; Wang, J.; Lozano, A. X.; Fan, Q. L.; Chew, L. et al. A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging. Nat. Commun. 2017, 8, 15269.
[10]
Hong, G. S.; Lee, J. C.; Jha, A.; Diao, S.; Nakayama, K. H.; Hou, L. Q.; Doyle, T. C.; Robinson, J. T.; Antaris, A. L.; Dai, H. J. et al. Near-infrared II fluorescence for imaging hindlimb vessel regeneration with dynamic tissue perfusion measurement. Circ. Cardiovasc. Imaging 2014, 7, 517-525.
[11]
Hu, Z. H.; Fang, C.; Li, B.; Zhang, Z. Y.; Cao, C. G.; Cai, M. S.; Su, S.; Sun, X. W.; Shi, X. J.; Li, C. et al. First-in-human liver-tumour surgery guided by multispectral fluorescence imaging in the visible and near-infrared-I/II windows. Nat. Biomed. Eng. 2020, 4, 259-271.
[12]
Koller, M.; Qiu, S. Q.; Linssen, M. D.; Jansen, L.; Kelder, W.; De Vries, J.; Kruithof, I.; Zhang, G. J.; Robinson, D. J.; Nagengast, W. B. et al. Implementation and benchmarking of a novel analytical framework to clinically evaluate tumor-specific fluorescent tracers. Nat. Commun. 2018, 9, 3739.
[13]
Kong, Y. F.; Chen, J.; Fang, H. W.; Heath, G.; Wo, Y.; Wang, W. L.; Li, Y. X.; Guo, Y.; Evans, S. D.; Chen, S. Y. et al. Highly fluorescent ribonuclease-A-encapsulated lead sulfide quantum dots for ultrasensitive fluorescence in vivo imaging in the second near-infrared window. Chem. Mater. 2016, 28, 3041-3050.
[14]
Feng, S. Q.; Chen, J.; Yan, W.; Li, Y. X.; Chen, S. Y.; Zhang, Y. X.; Zhang, W. J. Real-time and long-time in vivo imaging in the shortwave infrared window of perforator vessels for more precise evaluation of flap perfusion. Biomaterials 2016, 103, 256-264.
[15]
Du, Q. X.; Li, N.; Dang, L. H.; Dong, T. N.; Lu, H. L.; Shi, F. X.; Jin, Q. Q.; Jie, C.; Sun, J. H. Temporal expression of wound healing- related genes inform wound age estimation in rats after a skeletal muscle contusion: A multivariate statistical model analysis. Int. J. Legal Med. 2020, 134, 273-282.
[16]
Bresler, A.; Vogel, J.; Niederer, D.; Gray, D.; Schmitz-Rixen, T.; Troidl, K. Development of an exercise training protocol to investigate arteriogenesis in a murine model of peripheral artery disease. Int. J. Mol. Sci. 2019, 20, 3956.
[17]
Lee, E. W.; Michalkiewicz, M.; Kitlinska, J.; Kalezic, I.; Switalska, H.; Yoo, P.; Sangkharat, A.; Ji, H.; Li, L. J.; Michalkiewicz, T. et al. Neuropeptide Y induces ischemic angiogenesis and restores function of ischemic skeletal muscles. J. Clin. Invest. 2003, 111, 1853-1862.
[18]
Järvinen, T. A. H.; Järvinen, T. L. N.; Kääriäinen, M.; Kalimo, H.; Järvinen, M. Muscle injuries: Biology and treatment. Am. J. Sports Med. 2005, 33, 745-764.
[19]
Takeda, Y.; Costa, S.; Delamarre, E.; Roncal, C.; Leite De Oliveira, R.; Squadrito, M. L.; Finisguerra, V.; Deschoemaeker, S.; Bruyère, F.; Wenes, M. et al. Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis. Nature 2011, 479, 122-126.
[20]
Nowak-Sliwinska, P.; Alitalo, K.; Allen, E.; Anisimov, A.; Aplin, A. C.; Auerbach, R.; Augustin, H. G.; Bates, D. O.; Van Beijnum, J. R.; Bender, R. H. F. et al. Consensus guidelines for the use and interpretation of angiogenesis assays. Angiogenesis 2018, 21, 425-532.
[21]
Carmeliet, P.; Jain, R. K. Angiogenesis in cancer and other diseases. Nature 2000, 407, 249-257.
[22]
Kasemkijwattana, C.; Menetrey, J.; Somogyi, G.; Moreland, M. S.; Fu, F. H.; Buranapanitkit, B.; Watkins, S. C.; Huard, J. Development of approaches to improve the healing following muscle contusion. Cell Transplant. 1998, 7, 585-598.
[23]
Van Driel, P. B. A. A.; Van De Giessen, M.; Boonstra, M. C.; Snoeks, T. J. A.; Keereweer, S.; Oliveira, S.; Van De Velde, C. J. H.; Lelieveldt, B. P. F.; Vahrmeijer, A. L.; Löwik, C. W. G. M. et al. Characterization and evaluation of the artemis camera for fluorescence-guided cancer surgery. Mol. Imaging Biol. 2015, 17, 413-423.
[24]
He, Z. X.; Zhou, Y.; Wang, F. R.; Xu, Q.; Zhang, W.; Ni, X. J.; Ni, S. J. Clinical value of postoperative sentinel lymph node biopsy. Ann. Transl. Med. 2019, 7, 683.
[25]
Constantinescu, I. M.; Bolfa, P.; Constantinescu, D.; Mironiuc, A. I.; Gherman, C. D. Treatment with sildenafil and donepezil improves angiogenesis in experimentally induced critical limb ischemia. BioMed Res. Int. 2017, 2017, 9532381.
Publication history
Copyright
Acknowledgements

Publication history

Received: 08 May 2020
Revised: 09 July 2020
Accepted: 10 July 2020
Published: 10 August 2020
Issue date: November 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Acknowledgements

The authors thank Qiangbin Wang from the Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Lihua Wang, Yanhong Sun and Meiling Yan from Shanghai Institute of Applied Physics, Chinese Academy of Sciences for providing the NIR-II in vivo imaging instrument. The authors acknowledge fundings from the National Key R&D Program of China (No. 2016YFC1100300), the National Natural Science Foundation of China (Nos. 81572108, 81772339, 8181101445, 81811530750, 81811530389, and 81972129), the Key Clinical Medicine Center of Shanghai (No. 2017ZZ01006), Sanming Project of Medicine in Shenzhen (No. SZSM201612078), Shanghai Rising-Star Project (No. 18QB1400500) and the Introduction Project of Clinical Medicine Expert Team for Suzhou (No. SZYJTD201714), Development Project of Shanghai Peak Disciplines-Integrative Medicine (No. 20180101), and Shanghai Committee of Science and Technology (Nos. 19441901600 and 19441902000).

Return