Mapping physiological and pathological functions of cortical vasculature through aggregation-induced emission nanoprobes assisted quantitative, in vivo NIR-II imaging.

Abstract

Cerebrovascular disease includes all disorders that affect cerebrovascular and cerebral circulation. Unfortunately, there is currently a lack of a systematic method to image blood vessels directly and achieve accurate quantification. Herein, we build a non-invasive, quantitative imaging and characterization system applicable to mapping physiological and pathological functions of cortical vasculature. Assisted by aggregation-induced emission (AIE) luminogens with either excitation or emission at near-infrared-II (NIR-II) region, large-depth and/or high signal-to-background ratio images of cerebral blood vessels from mice and marmosets are captured, based on which we develop an optical metric of vessel thickness in an automated, pixel-wise manner and both two-dimensional (2D) and three-dimensional (3D) contexts. By monitoring time-dependent cerebrovascular images in marmosets, periodic changes in the diameter of vibrating cerebral blood vessels are found to be regulated mainly by heartbeat. In mice photothrombosis model, vessel alterations throughout the whole process of thrombotic stroke are found to be stage-dependent. From a large field of view, the distance-dependent vessel thickness variation before and right after stroke is obtained away from the thrombus site. Importantly, a buffer zone exists right surrounding the lesion, indicating the inhomogeneity of vascular morphological changes. Biologically excretable AIE nanoparticles are used for assessing physiological and pathological functions, offering great potential for clinical translation.