Institute for Biological and Medical Imaging, Helmholtz Center Munich, Neuherberg, Germany.
Faculty of Medicine, Technical University of Munich, Munich, Germany.
Nat Biomed Eng. 2019 May;3(5):392-401. doi: 10.1038/s41551-019-0372-9. Epub 2019 Mar 25.
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.
努力将神经影像学扩展到直接可视化哺乳动物全脑神经元活动，面临着重大挑战。尽管已经在小动物中实现了整个大脑的高分辨率光学成像，但由于局部、侵入性强的快速细胞分辨神经元活动的光学显微镜与慢血流动力学和代谢的全脑宏观测量之间的性能差距，仍然难以实时和直接监测大规模神经元活动。在这里，我们展示了在体和非侵入性的体内功能光声（OA）神经成像，用于表达基因编码钙指示剂 GCaMP6f 的小鼠。该方法使用单个 OA 激发，快速、高分辨率地获得全脑神经元活动图谱的三维快照，以及在强血红蛋白背景吸收存在下刺激诱发的慢血流动力学和快速钙活动。通过提供优于光学荧光成像的深度和时空分辨率的直接神经成像，功能 OA 神经成像在功能显微镜和全脑宏观测量之间架起了桥梁。
