Efforts to scale neuroimaging towards the direct visualization of mammalian brain-wide neuronal activity have faced major challenges. Although high-resolution optical imaging of the whole brain in small animals has been achieved ex vivo, the real-time 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 haemodynamics and metabolism. Here, we demonstrate both ex vivo and non-invasive in vivo functional optoacoustic (OA) neuroimaging of mice expressing the genetically encoded calcium indicator GCaMP6f. The approach offers rapid, high-resolution three-dimensional snapshots of whole-brain neuronal activity maps using single OA excitations, and of stimulus-evoked slow haemodynamics and fast calcium activity in the presence of strong haemoglobin background absorption. By providing direct neuroimaging at depths and spatiotemporal resolutions superior to optical fluorescence imaging, functional OA neuroimaging bridges the gap between functional microscopy and whole-brain macroscopy.
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All custom code generated for this study can be obtained from the corresponding authors on reasonable request.
The authors declare that all data supporting the findings of this study are available within the paper and its Supplementary Information. All datasets generated during this study are available from the corresponding authors.
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The authors acknowledge grant support from the European Research Council (under grant agreement ERC-2015-CoG-682379) and the US National Institutes of Health (grants R21-EY026382 and UF1-NS107680). We also acknowledge the help of N. Tritsch and L. Mcley with reading and commenting on the manuscript.
The authors declare no competing interests.
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Supplementary figures and video captions.
OA calcium activity map in a single 2D slice located at an approximate depth of 1 mm in the mouse brain.
OA calcium activity in a single 2D slice located at an approximate depth of 0.5 mm in the mouse brain.
Haemodynamic responses across the entire mouse cortex in response to paw stimulation.
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Gottschalk, S., Degtyaruk, O., Mc Larney, B. et al. Rapid volumetric optoacoustic imaging of neural dynamics across the mouse brain. Nat Biomed Eng 3, 392–401 (2019). https://doi.org/10.1038/s41551-019-0372-9
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