Epi-fluorescence imaging of the human brain through a multimode fiber

Abstract

Visualization of the subcellular structures deep into the living brain is a major challenge in life science. Miniaturized microendoscopes allow for imaging of deep brain structures in vivo. Conventional approaches use gradient index (GRIN) microlenses, which unfortunately suffer from greater aberrations and restricted fields of view if they become smaller and less invasive. Multimode fiber based endoscopes offer minimal invasive access to deep tissue, and when combined with advanced wavefront engineering techniques, they provide high-resolution imaging. Here, we report auto-fluorescence human brain imaging through a single 50 μm-core multimode fiber probe with a numerical aperture of 0.22 via two approaches: raster-scan imaging by active wavefront shaping and speckle-based compressive imaging enabled by computational image recovery. The compressive imaging approach significantly decreases the acquisition time for an up to three times bigger area of interest while maintaining a high spatial resolution. Accumulation of age-related pigment lipofuscin in Alzheimer’s disease human brain has been visualized with sub-Nyquist–Shannon speed with an improvement of up to 18 times. The proposed technique offers fast, sensitive, and high-resolution endoscopic imaging through a single hair-thin fiber, which would be of broader interest in the fields of neuroimaging and (pre-)clinical research.