Dynamic Pathophysiological Insight into the Brain by NIR‐II Imaging

Abstract Cerebral collateral circulation and blood‐brain barrier (BBB) are critically required to maintain the normal brain functions, a fact stressing the need for accurate and in vivo diagnostic tools that can afford valuable pathophysiological insight into the functioning of neurovascular unit in space and time. Currently, understanding of collateral perfusion and BBB evolution under both physiological and pathological conditions remains sparse, largely owing to limitations in methods for recording diminutive route of cerebral blood flow. Here, it is reported that highly crystalline semiconducting organic nanoprobes (named 4T‐BSA) composed of small‐molecule dye and bovine serum albumin showed vast potential for live‐brain vascular imaging in the second near‐infrared window (NIR‐II, 1000–1700 nm). The 4T‐BSA nanoprobes had superior imaging penetration depth in intact mouse brain with high signal‐to‐background ratio (SBR) of 6.0 and down to sub‐50‐µm spatial resolution of cerebral vasculature in three typical models of neurological pathophysiology. By visualizing the vascular collateral perfusion and albumin leakage, 4T‐BSA nanoprobes identified the pathological activities of brain associated with the arterial/venous collateral flow network and BBB disruption. It is anticipated that NIR‐II imaging of cerebral collateral circulation and BBB disruption will bring broad opportunities to address major medical challenges across timely, protective, and restorative interventions for neurological diseases.