Periodic Reporting for period 4 - OPTOACOUSTOGENETICS (Hybrid Volumetric Optoacoustic-Ultrasound Tomography for Noninvasive Large-Scale Recording of Brain Activity with High Spatiotemporal Resolution)
Reporting period: 2020-07-01 to 2021-09-30
Brain is the most complex and least studied organ in the body. Answers to questions spanning from the inner workings of consciousness to how to contain the upcoming rise of mental and neurodegenerative diseases critically depend on our ability to gather diverse anatomical, functional, metabolic and molecular information from the brain at multiple spatial and temporal scales. Efforts to scale neuroimaging towards the direct visualization of mammalian brain-wide neuronal activity have so far faced major challenges. Although high-resolution optical imaging of the whole brain in small animals has been achieved ex vivo, the realtime and direct monitoring of large-scale neuronal activity remains difficult, owing to the performance gap between localized, largely invasive, optical microscopy of rapid, cellular-resolved neuronal activity and whole-brain macroscopy of slow hemodynamics and metabolism. The OPTOACOUSTOGENETICS project was aimed at developing a new generation functional imaging technology that can perform rapid non-invasive volumetric imaging of neural activity across the entire rodent brain.
Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far
In particular, functional optoacoustic neuro-tomography (FONT) scanner has been devised based on a high-frequency spherical array transducer in order to enable noninvasive volumetric imaging of brains in mice and zebrafish at high spatio-temporal resolution. Due to the excessive data throughput requirements involved with optoacoustic image acquisition with high spatio-temporal resolution, sparse data acquisition approaches in combination with efficient compressed sensing reconstruction algorithms have been implemented in order to achieve high frame-rate imaging without sacrificing image quality and resolution. We subsequently performed large-scale recordings of brain activity with FONT in zebrafish and mice under localized and distributed stimuli. We were able to achieve rapid optoacoustic visualization of calcium dynamics in living adult zebrafish as well as freely behaving larvae labeled with genetically encoded calcium indicators (GECIs). For mouse brain imaging, algorithms have been developed for efficient separation (unmixing) of hemodynamic responses and general background blood absorption from signal alterations due to GECI activity. In this way, we were able to demonstrate the simultaneous optoacoustic tracking of both fast calcium transients and hemodynamic changes noninvasively in a living mouse brain.
Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)
Rapid volumetric neuroimaging has important applications in biomedicine, the central one being in dynamic functional imaging of large, distributed brain networks. The newly developed FONT technology is tailored for entirely non-invasive deep brain observations, attaining, for the first time, brain-wide imaging of neural activity at a rapid volumetric frame rates and a resolution approaching cellular scale. This pioneering work thus opened new vistas for studying neural activity, coding and neurovascular coupling in health and disease.