194 / 2024-07-08 19:56:42

Voltage-sensitive dye based photoacoustic visualization of whole brain electrodynamics

Photoacoustic imaging, whole brain electrodynamics, voltage-sensitive dye (VSD), high-spatiotemporal-resolution, epilepsy

Voltage dynamics in brain are essential responses indicating disease processes, such as epilepsy, that are highly associated with the abnormal electroactivity of neuronal population. Gene-encoded calcium indicators (GECIs) combined with all-optical voltage imaging are prevalent in neuroscience to study voltage activities. However, current implementations encounter restrictions in field of view (FOV), penetrating depth, and photostability, which have prevented them from seeing wider applications to monitor and predict the in-vivo electroactivities of the entire brain. To address these challenges, a robust voltage-sensitive dye (VSD)-based whole-field photoacoustic imaging platform is proposed, enabling direct evaluation of voltage dynamics across the whole brain, forming as PA-VSD. The platform is equipped with a 360-degree-scanning 512-element ring-array ultrasound detector, providing a large FOV of approximately 5 cm, high spatial resolution of around 110 µm, and rapid imaging acquisition. Moreover, the proposed VSD demonstrates a photostability of over 75% after 30 minutes of laser irradiation, surpassing that of most calcium indicators. The optical voltage response mechanism was successfully validated, and the effectiveness of PA-VSD screening epileptic seizures was further confirmed. It has been revealed that the PA-VSD enables precise localization of active epileptic foci, identification of electrical conduction pathways, and determination of their directionality through high-spatiotemporal-resolution visualization and analysis of connectivity between different brain regions. In conclusion, this study not only addresses the need for non-invasive, high-resolution, direct monitoring of brain voltages but also opens up exciting prospects for the application of photoacoustic imaging in neuroscience research.