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The peripheral nervous system (PNS) is essential for performing and maintaining various motor and sensory functions. Abnormalities can lead to a series of peripheral neurological conditions, such as paraesthesia, pain, or spasms, which are debilitating and lowering the quality of life. The current guidelines for diagnosis rely predominantly on clinical symptoms resulting from PNS dysfunction, which occur already at an advanced stage. There are currently no effective methods that visually reflect the extent of peripheral neuropathy. In our study, we present a novel in vivo and in situ real-time imaging of peripheral nerves based on the second near-infrared window (NIR-II) fluorescence. In NIR-II system, PbS Qds with NIR-II fluorescence specifically bound to motor neuron-specific protein agrin, acting as image contrast. In mice model, peripheral nerves were visible as soon as after 2 h post injection. We provide evidence for the efficacy of this approach, which allows to directly demonstrate peripheral nerves, their structure, and potential damage sites and degree. Furthermore, our products were of good biocompatibility, while the neural fluorescence signal was solid, bright and stable for 4 h in vivo. Thus, overall, our results suggest that NIR-II is an effective new method for direct imaging of peripheral nerves in vivo, opening new horizons on early, improved and more precise, targeted diagnosis. A resulting more rapid installation of personalized therapy facilitates a better prognosis of clinical peripheral neuropathy.


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In vivo and in situ real-time fluorescence imaging of peripheral nerves in the NIR-II window

Show Author's information Zhujun Feng1,§Yimeng Yang2,§Jian Zhang2,§Kan Wang3Yunxia Li2Heng Xu4Zhen Wang5Ewelina Biskup6Shixian Dong1Xing Yang7Yuefeng Hao7( )Jun Chen2( )Yan Wo1( )
Department of Anatomy and PhysiologySchool of MedicineShanghai Jiao Tong UniversityShanghai200025China
Sports Medicine Institute of Fudan UniversityDepartment of Orthopedic Sports MedicineHuashan Hospital, Fudan University, ShanghaiChina
Department of Instrument Science and EngineeringSchool of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai Engineering Research Center for Intelligent diagnosis and treatment instrumentKey Laboratory of Thin Film and Microfabrication (Ministry of Education)Shanghai200240China
Department of Plastic SurgeryNinth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai200025China
Department of physical educationFudan UniversityShanghai200040China
Department of Internal MedicineUniversity Hospital of BaselPetersgraben 44051Basel, Switzerland
Department of orthopedicsAffiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou215500China

§Zhujun Feng, Yimeng Yang, and Jian Zhang contributed equally to this work.

Abstract

The peripheral nervous system (PNS) is essential for performing and maintaining various motor and sensory functions. Abnormalities can lead to a series of peripheral neurological conditions, such as paraesthesia, pain, or spasms, which are debilitating and lowering the quality of life. The current guidelines for diagnosis rely predominantly on clinical symptoms resulting from PNS dysfunction, which occur already at an advanced stage. There are currently no effective methods that visually reflect the extent of peripheral neuropathy. In our study, we present a novel in vivo and in situ real-time imaging of peripheral nerves based on the second near-infrared window (NIR-II) fluorescence. In NIR-II system, PbS Qds with NIR-II fluorescence specifically bound to motor neuron-specific protein agrin, acting as image contrast. In mice model, peripheral nerves were visible as soon as after 2 h post injection. We provide evidence for the efficacy of this approach, which allows to directly demonstrate peripheral nerves, their structure, and potential damage sites and degree. Furthermore, our products were of good biocompatibility, while the neural fluorescence signal was solid, bright and stable for 4 h in vivo. Thus, overall, our results suggest that NIR-II is an effective new method for direct imaging of peripheral nerves in vivo, opening new horizons on early, improved and more precise, targeted diagnosis. A resulting more rapid installation of personalized therapy facilitates a better prognosis of clinical peripheral neuropathy.

Keywords: peripheral nerve, biocompatibility, the second near-infrared window (NIR-II), fluorescent imaging, Agrin@PbS Qds

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Publication history
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Acknowledgements

Publication history

Received: 18 August 2019
Revised: 21 October 2019
Accepted: 24 October 2019
Published: 20 November 2019
Issue date: December 2019

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Acknowledgements

Acknowledgements

This work was supported by National Natural Science Foundation of China (Nos. 81672247, 81772339, 8181101445, 81811530750, and 81811530389), Shanghai Rising-Star Project (No. 18QB1400500), The Key Clinical Medicine Center of Shanghai (No. 2017ZZ01006), Sanming Project of Medicine in Shenzhen (No. SZSM201612078), The Introduction Project of Clinical Medicine Expert Team for Suzhou (No. SZYJTD201714), and Development Project of Shanghai Peak Disciplines-Integrative Medicine (No. 20180101).

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