Aggregation-induced emission nanoprobe assisted ultra-deep through-skull three-photon mouse brain imaging
Aggregation-induced emission nanoprobe assisted ultra-deep through-skull three-photon mouse brain imaging
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聚集诱导发射纳米探针辅助超深穿颅骨三光子小鼠脑成像
DOI：
10.1016/j.nantod.2022.101536
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发表时间：
2022-08
期刊：
影响因子：
17.4
通讯作者：
Jun Qian
中科院分区：
文献类型：
--
作者：
Mubin He;Dongyu Li;Zheng Zheng;Hequn Zhang;Tianxiang Wu;Weihang Geng;Zhengwu Hu;Zhe Feng;Shiyi Peng;Liang Zhu;Wang Xi;Dan Zhu;Ben Zhong Tang;Jun Qian
光学显微镜能够以高空间分辨率对大脑结构和功能进行体内监测。然而，浑浊的脑组织和颅骨中的强光学散射阻碍了对较深部位微血管和神经元结构的观察。在此，我们提出了一种策略，通过结合颅骨光学透明（SOC）技术和三光子荧光显微镜（3PM）来克服颅骨和脑组织的高散射效应所带来的影响。我们所应用的可见 - 近红外II区兼容的颅骨光学透明剂（VNSOCA）分别通过折射率匹配和用D₂O替代H₂O，降低了颅骨在长波长下的散射和水吸收。在1300纳米窗口激发的3PM，借助我们开发的一种具有大三光子吸收截面的明亮聚集诱导发光（AIE）纳米探针，在颅窗中实现了1.5毫米的脑血管成像深度。将这两项先进技术相结合，我们目前通过完整的小鼠颅骨实现了最大1.0毫米的脑血管成像深度和大于700微米的神经元成像深度。还成功实现了脑血管和神经元的双通道透颅骨成像，为在单细胞水平同时无创监测深部脑结构和功能提供了机会。
• 结合颅骨光学透明和三光子显微镜以减少散射干扰。
• 具有极大三光子吸收截面的聚集诱导发光纳米探针对深度成像有益。
• 透颅骨三光子小鼠脑血管成像实现了最大1.0毫米的成像深度。
Optical microscopy has enabled in vivo monitoring of brain structures and functions with high spatial resolution. However, the strong optical scattering in turbid brain tissue and skull impedes the observation of microvasculature and neuronal structures at a large depth. Herein, we proposed a strategy to overcome the influence induced by the high scattering effect of both skull and brain tissue via the combination of skull optical clearing (SOC) technique and three-photon fluorescence microscopy (3PM). The visible-NIR-II compatible skull optical clearing agents (VNSOCA) we applied reduced the skull scattering and water absorption in long wavelength by refractive index matching and H 2 O replacement to D 2 O respectively. 3PM with the excitation in the 1300-nm window reached 1.5 mm cerebrovascular imaging depth in cranial window assisted by a kind of bright aggregation-induced emission (AIE) nanoprobe we developed with a large three-photon absorption cross section. Combining the two advanced technologies together, we achieved so far the largest cerebrovascular imaging depth of 1.0 mm and neuronal imaging depth of> 700 µm through intact mouse skull. Dual-channel through-skull imaging of both brain vessels and neurons was also successfully realized, giving an opportunity of non-invasively monitoring the deep brain structures and functions at single-cell level simultaneously. • Skull optical clearing and three-photon microscopy were combined to reduce scattering interference. • Aggregation-induced emission nanoprobes with extremely large three-photon absorption section benefit deep imaging. • Through-skull three-photon mouse cerebrovascular imaging achieved the largest 1.0 mm imaging depth.
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影响因子：
14.8
作者：
Holtmaat, Anthony;Bonhoeffer, Tobias;Chow, David K.;Chuckowree, Jyoti;De Paola, Vincenzo;Hofer, Sonja B.;Huebener, Mark;Keck, Tara;Knott, Graham;Lee, Wei-Chung A.;Mostany, Ricardo;Mrsic-Flogel, Tom D.;Nedivi, Elly;Portera-Cailliau, Carlos;Svoboda, Karel;Trachtenberg, Joshua T.;Wilbrecht, Linda
通讯作者：
Wilbrecht, Linda
量子点实现的体内深部脑结构和血流动力学多光子显微镜
影响因子：
10.8
作者：
Liu, Hongji;Deng, Xiangquan;Wang, Ke
通讯作者：
Wang, Ke
影响因子：
34.7
作者：
Alexander-Bloch, Aaron;Giedd, Jay N.;Bullmore, Edward T.
通讯作者：
Bullmore, Edward T.
影响因子：
4.6
作者：
Li, Kai;Qin, Wei;Ding, Dan;Tomczak, Nikodem;Geng, Junlong;Liu, Rongrong;Liu, Jianzhao;Zhang, Xinhai;Liu, Hongwei;Liu, Bin;Tang, Ben Zhong
通讯作者：
Tang, Ben Zhong
影响因子：
12.4
作者：
Zhang C;Feng W;Zhao Y;Yu T;Li P;Xu T;Luo Q;Zhu D
通讯作者：
Zhu D