Achieving intravital optical imaging with diffraction-limited spatial resolution of deep-brain structures represents an important step toward the goal of understanding the mammalian central nervous system1-4. Advances in wavefront-shaping methods and computational power have recently allowed for a novel approach to high-resolution imaging, utilizing deterministic light propagation through optically complex media and, of particular importance for this work, multimode optical fibers (MMFs)5-7. We report a compact and highly optimized approach for minimally invasive in vivo brain imaging applications. The volume of tissue lesion was reduced by more than 100-fold, while preserving diffraction-limited imaging performance utilizing wavefront control of light propagation through a single 50-μm-core MMF. Here, we demonstrated high-resolution fluorescence imaging of subcellular neuronal structures, dendrites and synaptic specializations, in deep-brain regions of living mice, as well as monitored stimulus-driven functional Ca2+ responses. These results represent a major breakthrough in the compromise between high-resolution imaging and tissue damage, heralding new possibilities for deep-brain imaging in vivo.

Department of Engineering Science University of Oxford Parks Road Oxford OX1 3PJ UK

Department of Pharmacology University of Oxford Mansfield Road Oxford OX1 3QT UK

Institute of Scientific Instruments of the CAS Královopolská 147 612 64 Brno Czech Republic

School of Engineering Physics and Mathematics College of Art Science and Engineering University of Dundee Nethergate Dundee DD1 4HN Scotland UK

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Advancing the path to in-vivo imaging in freely moving mice via multimode-multicore fiber based holographic endoscopy

"There's plenty of room at the bottom": deep brain imaging with holographic endo-microscopy

110 μm thin endo-microscope for deep-brain in vivo observations of neuronal connectivity, activity and blood flow dynamics

Suppression of the non-linear background in a multimode fibre CARS endoscope

Neurophotonic tools for microscopic measurements and manipulation: status report