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

Optical microscopy has enabled in vivo monitoring of brain structures and functions with high spatial resolution. However, the strong optical scattering turbid tissue skull impedes observation microvasculature neuronal at a large depth. Herein, we proposed strategy to overcome influence induced by effect both via combination clearing (SOC) technique three-photon fluorescence (3PM). The visible-NIR-II compatible agents (VNSOCA) applied reduced water absorption long wavelength refractive index matching H2O replacement D2O respectively. 3PM excitation 1300-nm window reached 1.5 mm cerebrovascular imaging depth cranial assisted kind bright aggregation-induced emission (AIE) nanoprobe developed cross section. Combining two advanced technologies together, achieved so far largest 1.0 of> 700 µm through intact mouse skull. Dual-channel through-skull vessels neurons was also successfully realized, giving an opportunity non-invasively deep single-cell level simultaneously.