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Copper dysmetabolism is associated with various neurodegenerative disorders, making high‐spatiotemporal‐resolution imaging of Cu2+ in the brain essential for understanding the underlying pathophysiological processes. Nevertheless, the current probes encounter obstacles in crossing the blood–brain barrier (BBB) and providing high‐spatial‐resolution in deep tissues. Herein, we present a photoacoustic probe capable of imaging Cu2+ dynamics in the mouse brain with high‐spatiotemporal‐resolution. The probe demonstrates selective ratiometric and reversible responses to Cu2+, while also efficiently crossing the BBB. Using the probe as the imaging agent, we successfully visualized Cu2+ in the brain of Parkinson's disease (PD) model mouse with a remarkable micron‐level resolution. The imaging results revealed a significant increase in Cu2+ levels in the cerebral cortex as PD progresses, highlighting the close association between Cu2+ alternations in the region and the disease. We also demonstrated that the probe can be used to monitor changes in Cu2+ distribution in the PD model mouse brain during L‐dopa intervention. Mechanism studies suggest that the copper dyshomeostasis in the PD mouse brain was dominated by the expression levels of divalent metal transporter 1. The application of our probe in imaging Cu2+ dynamics in the mouse brain offers valuable insights into the copper‐related molecular mechanisms underlying neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Spatiotemporal assessment of the oxidative stress dynamics in the brain is crucial for understanding the molecular mechanism underlying neurodegenerative diseases. However, existing oxidative stress probes have poor blood‐brain barrier permeability or poor penetration depth, making them unsuitable for brain imaging. Herein, we developed a photoacoustic probe that enables real‐time imaging of oxidative stress dynamics in the mouse brain. The probe not only responds to oxidative stress in a reversible and ratiometric manner, but it can also cross the blood‐brain barrier of the mouse brain. Notably, the probe displayed excellent photoacoustic imaging of oxidative stress dynamics in the brains of Parkinson's disease mouse models. In addition, we investigated the antioxidant properties of natural polyphenols in the brain of a Parkinson's disease mouse model using the probe as an imaging agent and suggested the potential of the probe for screening anti‐oxidative stress agents. [ABSTRACT FROM AUTHOR]