In vivo fluorescence imaging in the second near-infrared window (NIR-II) has been considered as a promising technique for visualizing mammals. However, the definition of the NIR-II region and the mechanism accounting for the excellent performance still need to be perfected. Herein, we simulate the photon propagation in the NIR region (to 2340 nm), confirm the positive contribution of moderate light absorption by water in intravital imaging and perfect the NIR-II window as 900–1880 nm, where 1400–1500 and 1700–1880 nm are defined as NIR-IIx and NIR-IIc regions, respectively. Moreover, 2080–2340 nm is newly proposed as the third near-infrared (NIR-III) window, which is believed to provide the best imaging quality. The wide-field fluorescence microscopy in the brain is performed around the NIR-IIx region, with excellent optical sectioning strength and the largest imaging depth of intravital NIR-II fluorescence microscopy to date. We also propose 1400 nm long-pass detection in off-peak NIR-II imaging whose performance exceeds that of NIR-IIb imaging, using bright fluorophores with short emission wavelength.

Rationale: Cerebrovascular diseases, together with malignancies, still pose a huge threat to human health nowadays. With the advantages of its high spatial resolution and large penetration depth, fluorescence bioimaging in the second near-infrared spectral region (NIR-II, 900-1700 nm) and its related imaging-guided therapy based on biocompatible fluorescence dyes have become a promising theranostics method. Methods: The biocompatibility of IR-820 we used in NIR-II fluorescence bioimaging was verified by long-term observation. The model of the mouse with a cranial window, the mouse model of middle cerebral artery occlusion (MCAO) and a subcutaneous xenograft mouse model of bladder tumor were established. NIR-II fluorescence cerebrovascular functional imaging was carried out by IR-820 assisted NIR-II fluorescence microscopy. Bladder tumor was treated by NIR-II fluorescence imaging-guided photothermal therapy. Results: We have found that IR-820 has considerable NIR-II fluorescence intensity, and shows increased brightness in serum than in water. Herein, we achieved real time and in vivo cerebrovascular functional imaging of mice with high spatial resolution and large penetration depth, based on IR-820 assisted NIR-II fluorescence microscopy. In addition, IR-820 was successfully employed for NIR-II fluorescence imaging and photothermal therapy of tumor in vivo, and the subcutaneous tumors were inhibited obviously or eradicated completely. Conclusion: Due to the considerable fluorescence intensity in NIR-II spectral region and the good photothermal effect, biocompatible and excretable IR-820 holds great potentials for functional angiography and cancer theranostics in clinical practice.

The limited signal of long-wavelength near-infrared-II (NIR-II, 900–1880 nm) fluorophores and the strong background caused by the diffused photons make high-contrast fluorescence imaging in vivo with deep tissue disturbed still challenging. Here, we develop NIR-II fluorescent small molecules with aggregation-induced emission properties, high brightness, and maximal emission beyond 1200 nm by enhancing electron-donating ability and reducing the donor-acceptor (D-A) distance, to complement the scarce bright long-wavelength emissive organic dyes. The convincing single-crystal evidence of D-A-D molecular structure reveals the strong inhibition of the π-π stacking with ultralong molecular packing distance exceeding 8 Å. The delicately-designed nanofluorophores with bright fluorescent signals extending to 1900 nm match the background-suppressed imaging window, enabling the signal-to-background ratio of the tissue image to reach over 100 with the tissue thickness of ~4–6 mm. In addition, the intraluminal lesions with strong negatively stained can be identified with almost zero background. This method can provide new avenues for future long-wavelength NIR-II molecular design and biomedical imaging of deep and highly scattering tissues.

Aggregation‐induced emission (AIE) is a photophysical phenomenon that a certain group of luminescent materials that become highly luminous when aggregated in a bad solvent or solid state. This year is the 20th anniversary since the AIE concept firstly proposed in 2001. Many advanced applications were gradually being explored, covering optics, electronics, energy, and bioscience and so on. At present, bibliometrics can enlighten the researchers with comprehensive sights of the achievements and trends of a specific field, which is critical for academic investigations. Herein, we presented a general bibliometric overview of AIE covering 20 years of evolution. With the assistance of Web of Science Core Collection database and several bibliometric software tools, the annual publication and citation, most influential countries/regions, most contributing authors, journals and institutions, second near‐infrared (NIR‐II) related hotspots, as well as the forecast of frontiers were demonstrated and systematically analyzed. This study summarizes the current research status in AIE research field and provides a reference for future research directions.