Although biological fluorescence imaging in the second near-infrared window (NIR-Ⅱ, 1000-1700 nm) has embodied the advantages of deep tissue penetration, low background noise and high spatial resolution, shortage of high quantum yield (QY) organic fluorophores has become the bottleneck for further development to this field. Now, an ingenious strategy is proposed to address this: constitutional isomerization by utilizing the molecular design philosophy of aggregation-induced emission (AIE). By solely shifting alkyl chain from meta to ortho position, the resulting twisted structure drives the NIR-Ⅱ fluorophores from aggregation-caused quenching (ACQ) to AIE. In this way, the AIE luminogen (AIEgen), 2TT-oC6B, is provided with an emission peak at 1030 nm and a QY of 11% in nanoparticles, one of the highest reported so far. To endow the targeting ability to deeply located diseases, neutrophils (NEs), the most common immune cells, are used to penetrate the brain tissues. Herein, we show that NEs carrying 2TT-oC6B NPs can penetrate the brain and visualize the deeply located inflammation through intact scalp and skull (3 mm of depth). Notably, the bright 2TT-oC6B fluorophore contributes to a significantly enhanced signal-to-noise ratio of 30.6 in brain inflammation site, which is among the best ones to date. This modern molecule design philosophy could enable a powerful platform for high QY fluorophores and their potential biological applications.