Functional optoacoustic neuro-tomography (FONT) for whole-brain monitoring of calcium indicators

Non-invasive observation of spatiotemporal neural activity of large neural populations distributed over entire brains is a longstanding goal of neuroscience. We developed a real-time volumetric and multispectral optoacoustic tomography platform for imaging of neural activation deep in scattering brains. The system can record 100 volumetric frames per second across a 200mm field of view and spatial resolutions below 70μm. Experiments performed in immobilized and freely swimming larvae and in adult zebrafish brains demonstrate, for the first time, the fundamental ability to optoacoustically track neural calcium dynamics in animals labeled with genetically encoded calcium indicator GCaMP5G, while overcoming the longstanding penetration barrier of optical imaging in scattering brains. The newly developed platform offers unprecedented capabilities for functional whole-brain observations of fast calcium dynamics; in combination with optoacoustics' well-established capacity in resolving vascular hemodynamics, it could open new vistas in the study of neural activity and neurovascular coupling in health and disease.