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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.

Author information

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

Abstract

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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