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

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.

Flexible lensless endoscope with a conformationally invariant multi-core fiber

“…This represents the ultimate limit in miniaturization, since the head-mounted device can be as small as an optical fiber itself. Cellular-level imaging in live mice by lensless endoscopes has recently been demonstrated [11,12], but imaging modality was restricted to one-photon fluorescence imaging and fiber length to few cm, and the animal subject was fixed.…”

Characterizing Optical Fiber Transmission Matrices Using Metasurface Reflector Stacks for Lensless Imaging without Distal Access

“…for minimally invasive optical imaging in inaccessible areas of the body, e.g. deep in the brain where the fibre may need to curve for safe access [8]. Placing a holographic plate on the distal facet of the fibre, which is illuminated via a physically separate single-mode fibre, can be used to create a 'virtual beacon' [9].…”

Overcoming the penetration depth limit in optical microscopy: Adaptive optics and wavefront shaping

“…By shaping the incident wavefront, di®raction limited foci can be generated at arbitrary positions beyond the single multimode¯ber, just like focusing through multiple scattering media. Using this approach, recent work has demonstrated high resolution°uorescence imaging of subcellular neural structures as well as functional brain activity in living mice 93 with reduced tissue lesion volume by more than 100-fold.…”