  Spreading depolarization (SD) is a self-propagating wave of near-complete
neuronal depolarization that is abundant in a wide range of neurological
conditions, including stroke. SD was only recently documented in humans and is
now considered a therapeutic target for brain injury, but the mechanisms
related to SD in complex brains are not well understood. While there are
numerous approaches to interventional imaging of SD on the exposed brain
surface, measuring SD deep in brain is so far only possible with low
spatiotemporal resolution and poor contrast. Here, we show that photoacoustic
imaging enables the study of SD and its hemodynamics deep in the gyrencephalic
brain with high spatiotemporal resolution. As rapid neuronal depolarization
causes tissue hypoxia, we achieve this by continuously estimating blood
oxygenation with an intraoperative hybrid photoacoustic and ultrasonic (PAUS)
imaging system. Due to its high resolution, promising imaging depth and high
contrast, this novel approach to SD imaging can yield new insights into SD and
thereby lead to advances in stroke, and brain injury research.
