Aggregation-induced emission nanoprobe assisted ultra-deep through-skull three-photon mouse brain imaging

作者：He, Mubin; Li, Dongyu; Zheng, Zheng; Zhang, Hequn; Wu, Tianxiang; Geng, Weihang; Hu, Zhengwu; Feng, Zhe; Peng, Shiyi; Zhu, Liang; Xi, Wang; Zhu, Dan; Tang, Ben Zhong^*; Qian, Jun^*

来源：Nano Today, 2022, 45: 101536.

DOI：10.1016/j.nantod.2022.101536

• Aggregation-induced emission
• Brain imaging
• Through skull
• Optical clearing
• Three-photon microscopy

Optical microscopy has enabled in vivo monitoring of brain structures and functions with high spatial re-solution. 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 ab-sorption in long wavelength by refractive index matching and H2O replacement to D2O respectively. 3PM with the excitation in the 130 0-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 mu m 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.

• 单位
  浙江大学; 华中科技大学