Minimally invasive deep-brain imaging through a 50 μm-core multimode fibre

Achieving optical access to deep-brain structures represents an important step towards the goal of understanding the mammalian central nervous system. The complex refractive index distribution within brain tissue introduces severe aberrations to long-distance light propagation thereby prohibiting image reconstruction using currently available non-invasive techniques. In an attempt to overcome this challenge endoscopic approaches have been adopted, principally in the form of fibre bundles or GRIN-lens based endoscopes. Unfortunately, these approaches create substantial mechanical lesions of the tissue precipitating neuropathological responses that include inflammation and gliosis. Together, lesions and the associated neuropathology may compromise neural circuit performance. By replacing Fourier-based image relay with a holographic approach, we have been able to reduce the volume of tissue lesion by more than 100-fold, while preserving diffraction-limited imaging performance. Here we demonstrate high-resolution fluorescence imaging of neuronal structures, dendrites and synaptic specialisations, in deep-brain regions of living mice. 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 .