Reconnectable fiberscopes for chronic in vivo deep‐brain imaging

Abstract

Reconnectable bundles consisting of thousands of optical fibers are shown to enable high-quality image transmission, offering a platform for the creation of implantable fiberscopes for minimally invasive in vivo brain imaging. Experiments on various lines of transgenic mice verify the performance of this fiberscope as a powerful tool for chronic in vivo neuroimaging using genetically encoded calcium indicators, neuronal activity markers as well as axon growth regulators and brain-specific protein drivers in deep regions of live brain.

Fabrication and characterization of large numerical aperture, high-resolution optical fiber bundles based on high-contrast pairs of soft glasses for fluorescence imaging

“…Minimum core diameter and core-tocore distance values of 1.6 µm and 2.3 μm were sufficient for eliminating the optical crosstalk between individual cores even in the presence of bending for both sets of glass compositions. FBs 2, 4-7 have pixel sizes similar to the ones previously reported by other groups (NA = 0.4; core diameter = 2.2 µm; core-to-core distance<4 µm in Ref [31], NA = 0.27; core diameter = 1.8 µm; core-to-core distance~3.5 µm in Ref [41]), but offer much larger NA. As a result, they can collect higher fluorescent signal and achieve higher contrast values especially in fluorescence imaging.…”

“…As a result, for low NA FBs, it is not possible to collect all the emitted light into respective pixels. Some fluorescence emitted with relatively larger divergence angles leaks into neighboring fibers creating a bright background in the image, hence reducing the image quality [41]. In order to demonstrate the micro-endoscopic imaging capability of the studied FBs, exvivo imaging of cirrhotic mice liver stained with FITC was performed.…”

“…Several recent microscopic imaging demonstrations using FBs include: deep-brain imaging of a living animal [31], in vivo subcellular resolution imaging of cancerous tissues such as oral, cervical and ovarian [32][33][34][35], ex-vivo human stomach, animal colon, liver and belly tissue imaging [36], and thermal infrared imaging [37][38][39][40]. Currently best FBs dedicated for fluorescent imaging have pixel sizes larger than 3 μm and NA values smaller than 0.40 [31,41].…”

Multisite cell‐ and neural‐dynamics‐resolving deep brain imaging in freely moving mice with implanted reconnectable fiber bundles

“…Radiation energy at the output of the fiber bundle is seen to be split very unevenly between these fibers, varying from ≈ 1.5% to 8.0% of the total beam energy. This result is, in fact, expected, as it indicates that the efficiency of radiation energy transfer induced by a fiber‐to‐fiber cross‐talk is drastically different even for the nearest‐neighbor fibers, clearly showing that the variance of the parameters of individual fibers in the bundle and frustrated periodicity of fiber arrangement in the bundle help suppress coherent effects, reducing the fiber‐to‐fiber cross‐talk, as well as speckle‐ and Moiré‐pattern artifacts [31] in brain images collected through the BFB probe.…”

“…Within the past decade, fiber bundles have proven to be instrumental for a variety of brain imaging modalities, including the imaging of neuronal circuits in animal models [4,28], as well as multiplex, multifrequency fluorescence [29] and Raman [30] imaging in live brain. As a step toward adapting fiber-bundle probes to the needs of long-term deep-brain imaging, reconnectable bundles consisting of thousands of optical fibers have been demonstrated [31], enabling a high-quality image transmission in chronic brain studies of deep areas in awake brain.…”