Conventional biomedical imaging modalities, including endoscopy, X-rays, and magnetic resonance, are invasive and cannot provide sufficient spatial and temporal resolutions for regular imaging of gastrointestinal (GI) tract to guide prognosis and therapy of GI diseases. Here we report a non-invasive method for optical imaging of GI tract. It is based on a new type of lanthanide-doped nanocrystal with near-infrared (NIR) excitation at 980 nm and second NIR window (NIR-IIb) (1500~1700 nm) fluorescence emission at around 1530 nm. The rational design and controlled synthesis of nanocrystals with high brightness have led to an absolute quantum yield (QY) up to 48.6%. Further benefitting from the minimized scattering through the NIR-IIb window, we enhanced the spatial resolution by 3 times compared with the other NIR-IIa (1000~1500 nm) contract agents for GI tract imaging. The approach also led to a high temporal resolution of 8 frames per second, so that the moment of mice intestinal peristalsis happened in one minute can be captured. Furthermore, with a light-sheet imaging system, we demonstrated a three-dimensional (3D) imaging of the stereoscopic structure of the GI tract. Moreover, we successfully translate these advances to diagnose inflammatory bowel disease (IBD) in a pre-clinical model of mice colitis.
