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Light Sci Appl. 2018 Dec 19;7:110. doi: 10.1038/s41377-018-0111-0. eCollection 2018.

Subcellular spatial resolution achieved for deep-brain imaging in vivo using a minimally invasive multimode fiber.

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1Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT UK.
2Department of Engineering Science, University of Oxford, Parks Road, Oxford, OX1 3PJ UK.
3School of Engineering, Physics and Mathematics, College of Art, Science & Engineering, University of Dundee, Nethergate, Dundee, DD1 4HN Scotland UK.
4Institute of Scientific Instruments of the CAS, Královopolská 147, 612 64 Brno, Czech Republic.
Contributed equally


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.

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