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

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 wavefrontshaping 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.