Direct monitoring of whole-brain electrodynamics via high-spatiotemporal-resolution photoacoustics with voltage-sensitive dye

Abstract

Brain voltage plays a crucial role in indicating internal functions or diseases, and optical voltage imaging has gained intensive attention in recent years. Despite encouraging progress, current implementations encounter limitations pertaining to penetration depth, field of view (FOV), and photostability of indicators. To mitigate these challenges, a robust voltage-sensitive dye (VSD)-based whole-field photoacoustic brain detection (WF-PABD) platform is proposed, enabling direct evaluation of voltage dynamics across the whole brain, forming as PA-VSD. WF-PABD is equipped with a 512-element ring-array ultrasound detector capable of 360-degree scanning, providing a large FOV (≈5 cm), high spatial resolution (≈110 µm), and rapid imaging acquisition. The proposed VSD remained ≈75% photostability after 30 min laser exposure, much greater than most calcium sensors. The optical voltage-response mechanisms are validated and the capability of PA-VSD to directly screen seizures is established. It is demonstrated that investigating connectivity among different brain regions allows to identify the precise location of active epileptic foci as well as the electrical conduction pathways and their directionality through fast temporal visualization. In summary, this study not only addresses the need for non-invasive, high-resolution, long-term, and direct monitoring of brain voltage but also empowers exciting venues for PA applications in neuroscience.