Voltage-sensitive dye based photoacoustic imaging visualization of whole brain electrodynamics

Brain voltage imaging plays a critical role in understanding brain function and diagnosing neurological conditions. In recent years, optical imaging of brain voltage has garnered encouraging progress, however, current techniques are limited by penetration depth, FOV, and the photostability of the voltage indicators. Photoacoustic imaging shows strong potential for whole-brain global imaging and real-time monitoring, especially for deep brain regions. Therefore, we developed a full-field photoacoustic brain detection (WF-PABD) platform adapted with a photostable voltage-sensitive dye (PA-VSD), enabling direct assessment of voltage dynamics across the entire mouse brain with epilepsy. The results illustrate that PA-VSD can resolve the microvasculature of the entire mouse brain at high resolution and present cranial structures with high contrast, even under conditions of low blood background. The monitoring indicates that PA-VSD can visualize seizures over extended periods and precisely locate active epileptic foci. Furthermore, through rapid temporal distribution and brain regions correlation analysis, we identified both the electrical conduction pathway and its directionality, which hold significant value for the long-term monitoring and diagnosis of electroencephalographic-related disorders.