Label-free nanoscale optical metrology on myelinated axons in vivo

Kwon, Junhwan; Kim, Moonseok; Park, Hyejin; Kang, Bok-Man; Jo, Yongjae; Kim, Jaehwan; James, Oliver; Yun, Seok Hyun; Kim, Seong‐Gi; Suh, Minah; Choi, Myunghwan

doi:10.1038/s41467-017-01979-2

Cited by 34 publications

(36 citation statements)

References 51 publications

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“…There is a need for live-imaging modalities to accurately measure sheath thickness along axons, as currently this requires cross-sectional measurement via electron microscopy, which limits analysis to a single time-point. Some label-free imaging techniques, such as third harmonic generation microscopy and spectral reflectometry, show promise for performing such measurements ( Lim et al, 2014 ; Kwon et al, 2017 ). Coupling these techniques with longitudinal studies of the rodent cortex could determine whether established myelin sheaths can adjust their thickness, or if neuronal activity simply pushes de novo myelination to produce thicker sheaths.…”

Section: Myelin Remodellingmentioning

confidence: 99%

Myelin Dynamics Throughout Life: An Ever-Changing Landscape?

Williamson

Lyons

2018

Front. Cell. Neurosci.

145

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Myelin sheaths speed up impulse propagation along the axons of neurons without the need for increasing axon diameter. Subsequently, myelin (which is made by oligodendrocytes in the central nervous system) allows for highly complex yet compact circuitry. Cognitive processes such as learning require central nervous system plasticity throughout life, and much research has focused on the role of neuronal, in particular synaptic, plasticity as a means of altering circuit function. An increasing body of evidence suggests that myelin may also play a role in circuit plasticity and that myelin may be an adaptable structure which could be altered to regulate experience and learning. However, the precise dynamics of myelination throughout life remain unclear – does the production of new myelin require the differentiation of new oligodendrocytes, and/or can existing myelin be remodelled dynamically over time? Here we review recent evidence for both de novo myelination and myelin remodelling from pioneering longitudinal studies of myelin dynamics in vivo, and discuss what remains to be done in order to fully understand how dynamic regulation of myelin affects lifelong circuit function.

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Section: Myelin Remodellingmentioning

confidence: 99%

Myelin Dynamics Throughout Life: An Ever-Changing Landscape?

Williamson

Lyons

2018

Front. Cell. Neurosci.

145

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“…To test the feasibility of reflectophores, we set up a spectral reflectometry (SpeRe) system by coupling a supercontinuum laser to a confocal microscope and directing the reflected light to an array spectrometer 27 , 28 (Supplementary Fig. 5 ).…”

Section: Resultsmentioning

confidence: 99%

Microsphere-based interferometric optical probe

Kwon

Kim

et al. 2018

Nat Commun

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Fluorescent optical probes have rapidly transformed our understanding of complex biological systems by providing specific information on biological targets in the natural living state. However, their utility is often limited by insufficient brightness, photostability, and multiplexing capacity. Here, we report a conceptually new optical probe, termed ‘reflectophore’, which is based on the spectral interference from a dielectric microsphere. Reflectophores are orders-of-magnitudes brighter than conventional fluorophores and are free from photobleaching, enabling practically unlimited readout at high fidelity. They also offer high-degree multiplexing, encoded in their optical size, which can be readily decoded through interferometric detection with nanoscale accuracy, even in turbid biological media. Furthermore, we showcase their biological applications in cellular barcoding and microenvironmental sensing of a target protein and local electric field.

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“…Polarization microscopy is emerging as a label-free method for analyzing mesoscale connectivity and the architecture of brain tissue (10-15, 32, 54) due to the following reasons: 1) High intrinsic anisotropy of the myelin sheath enables sensitive detection of distribution and orientation of axon fibers (55,56), 2) Light microscopy can achieve sub-micron, single-axon resolution across large brains. Quantitative phase microscopy has also enabled imaging of brain architecture ex-vivo (57), in-vivo (58), and during disease (59).…”

Section: C: Multi-scale Imaging Of Mouse Brain Tissue With Uptimentioning

confidence: 99%

uPTI: uniaxial permittivity tensor imaging of intrinsic density and anisotropy

Yeh

Ivanov

Guo

et al. 2020

Preprint

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Architecture of biological systems is important for their homeostatic functions and is predictive of pathology. Volumetric imaging of intrinsic density, anisotropy, and 3D orientation of cell and tissue components is informative, but still challenging. These physical properties can be described succinctly by the volumetric distribution of the specimen’s permittivity tensor (PT). We report uniaxial permittivity tensor imaging (uPTI), a novel approach for label-free volumetric imaging with diffraction-limited resolution. uPTI combines the oblique illumination and the polarization imaging with high numerical apertures to encode the specimen’s permittivity tensor into intensity modulations, which are decoded with a novel vector diffraction model and a multi-channel convex optimization. The uPTI volumes of polystyrene beads and laser-fabricated anisotropic glass targets show that 3D uPT measurements are quantitative, with diffraction-limited spatial resolution of 0.23 × 0.23 × 0.8 μm3. Automated 2D and 3D imaging of a mouse brain section reveals anatomy at multiple scales (cm – 250 nm) and demonstrates that uPTI enables analysis of the density, anisotropy, and orientation of axon bundles and single axons. We multiplex uPTI with fluorescence de-convolution microscopy to enable correlative analysis of physical and molecular architecture of iPSC-derived cardiomyocytes. uPTI can be added to an existing widefield microscope as a low cost module. We share our implementation of the forward model and optimization algorithms via open source repository. Collectively, the reported advances in optical design, image formation, reconstruction algorithms, and biological interpretation open multiple avenues to study architecture of organelles, cells and tissue sections, including human cells and tissues that are challenging to label.

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Label-free nanoscale optical metrology on myelinated axons in vivo

Cited by 34 publications

References 51 publications

Myelin Dynamics Throughout Life: An Ever-Changing Landscape?

Myelin Dynamics Throughout Life: An Ever-Changing Landscape?

Microsphere-based interferometric optical probe

uPTI: uniaxial permittivity tensor imaging of intrinsic density and anisotropy

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