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Dual GRIN lens two-photon endoscopy for high-speed volumetric and deep brain imaging

Yu-Feng Chien, Jyun-Yi Lin, Po-Ting Yeh, Kuo-Jen Hsu, Yu-Hsuan Tsai, Shih-Kuo Chen, Shi-Wei Chu
doi: https://doi.org/10.1101/2020.09.19.304675
Yu-Feng Chien
1Department of Physics, National Taiwan University, Taipei 10617, Taiwan
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Jyun-Yi Lin
1Department of Physics, National Taiwan University, Taipei 10617, Taiwan
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Po-Ting Yeh
2Department of Life Science, National Taiwan University, Taipei 10617, Taiwan
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Kuo-Jen Hsu
1Department of Physics, National Taiwan University, Taipei 10617, Taiwan
3Brain Research Center, National Tsing Hua University, Hsinchu 30013, Taiwan
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Yu-Hsuan Tsai
1Department of Physics, National Taiwan University, Taipei 10617, Taiwan
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Shih-Kuo Chen
2Department of Life Science, National Taiwan University, Taipei 10617, Taiwan
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Shi-Wei Chu
1Department of Physics, National Taiwan University, Taipei 10617, Taiwan
3Brain Research Center, National Tsing Hua University, Hsinchu 30013, Taiwan
4Molecular Imaging Center, National Taiwan University, Taipei 10617, Taiwan
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  • For correspondence: swchu@phys.ntu.edu.tw
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Abstract

Studying neural connections and activities in vivo is fundamental to understanding brain functions. Given the cm-size brain and three-dimensional neural circuit dynamics, deep-tissue, high-speed volumetric imaging is highly desirable for brain study. With sub-micrometer spatial resolution, intrinsic optical sectioning, and deep-tissue penetration capability, two-photon microscopy (2PM) has found a niche in neuroscience. However, current 2PM typically relies on slow axial scan for volumetric imaging, and the maximal penetration depth is only about 1 mm. Here, we demonstrate that by integrating two gradient-index (GRIN) lenses into 2PM, both penetration depth and volume-imaging rate can be significantly improved. Specifically, an 8-mm long GRIN lens allows imaging relay through a whole mouse brain, while a tunable acoustic gradient-index (TAG) lens provides sub-second volume rate via 100 kHz ∼ 1 MHz axial scan. This technique enables the study of calcium dynamics in cm-deep brain regions with sub-cellular and sub-second spatiotemporal resolution, paving the way for interrogating deep-brain functional connectome.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 20, 2020.
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Dual GRIN lens two-photon endoscopy for high-speed volumetric and deep brain imaging
Yu-Feng Chien, Jyun-Yi Lin, Po-Ting Yeh, Kuo-Jen Hsu, Yu-Hsuan Tsai, Shih-Kuo Chen, Shi-Wei Chu
bioRxiv 2020.09.19.304675; doi: https://doi.org/10.1101/2020.09.19.304675
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Dual GRIN lens two-photon endoscopy for high-speed volumetric and deep brain imaging
Yu-Feng Chien, Jyun-Yi Lin, Po-Ting Yeh, Kuo-Jen Hsu, Yu-Hsuan Tsai, Shih-Kuo Chen, Shi-Wei Chu
bioRxiv 2020.09.19.304675; doi: https://doi.org/10.1101/2020.09.19.304675

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