Advancing multiscale structural mapping of the brain through fluorescence imaging and analysis across length scales

Hogstrom, L. J.; Guo, Syuan-Ming; Murugadoss, K.; Bathe, Mark

doi:10.1098/rsfs.2015.0081

Cited by 8 publications

(7 citation statements)

References 85 publications

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“…Micro‐ and nanomorphology of the neuronal network is tightly linked with the brain's functionality. This has sparked significant interest and efforts aimed at uncovering hierarchically organized neuronal structures . Currently available imaging methodologies, however, are limited in their 3D representation of large specimens in a time‐efficient manner with sufficient nanoscale isotropic resolution while preserving the biological context.…”

Section: Introductionmentioning

confidence: 99%

Hard X‐Ray Nanoholotomography: Large‐Scale, Label‐Free, 3D Neuroimaging beyond Optical Limit

et al. 2018

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There have been great efforts on the nanoscale 3D probing of brain tissues to image subcellular morphologies. However, limitations in terms of tissue coverage, anisotropic resolution, stain dependence, and complex sample preparation all hinder achieving a better understanding of the human brain functioning in the subcellular context. Herein, X‐ray nanoholotomography is introduced as an emerging synchrotron radiation‐based technology for large‐scale, label‐free, direct imaging with isotropic voxel sizes down to 25 nm, exhibiting a spatial resolution down to 88 nm. The procedure is nondestructive as it does not require physical slicing. Hence, it allows subsequent imaging by complementary techniques, including histology. The feasibility of this 3D imaging approach is demonstrated on human cerebellum and neocortex specimens derived from paraffin‐embedded tissue blocks. The obtained results are compared to hematoxylin and eosin stained histological sections and showcase the ability for rapid hierarchical neuroimaging and automatic rebuilding of the neuronal architecture at the level of a single cell nucleolus. The findings indicate that nanoholotomography can complement microscopy not only by large isotropic volumetric data but also by morphological details on the sub‐100 nm level, addressing many of the present challenges in brain tissue characterization and probably becoming an important tool in nanoanatomy.

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Section: Introductionmentioning

confidence: 99%

Hard X‐Ray Nanoholotomography: Large‐Scale, Label‐Free, 3D Neuroimaging beyond Optical Limit

et al. 2018

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“…Although electron microscopy and magnetic resonance imaging have been dominant to date, a series of advanced fluorescence-based tools are becoming available that enable the rapid and accurate mapping of a specific animal's synaptic connections. As described by Hogstrom et al [29], these tools, concert with mathematical tools to integrate electron and fluorescence microscopy datasets, promise unprecedented cross-validation of mappings and a foundation for multiscale, structure-based modelling of brain function.…”

Section: Human Systemsmentioning

confidence: 99%

“…Current models of brain injury fail to capture the ways that repeated insult to the head relates to the likelihood of traumatic brain injury. Detailed computer models, eventuality to be based upon data like that described by Hogstrom et al [29], can be used to make estimates of mechanical fields such as stress and strain within the brain, but these models are too slow to run on an entire football season's worth of accelerometer data from a single player. Zhao & Ji [30] describe the validation of brain atlas techniques to estimate pressure histories within the heads of individual athletes over very large datasets, and discuss challenges and opportunities ahead for such approaches as the field steps towards more biophysically based injury criteria.…”

Section: Human Systemsmentioning

confidence: 99%

Integrated multiscale biomaterials experiment and modelling: a perspective

Buehler

Genin

2016

Interface Focus.

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Advances in multiscale models and computational power have enabled a broad toolset to predict how molecules, cells, tissues and organs behave and develop. A key theme in biological systems is the emergence of macroscale behaviour from collective behaviours across a range of length and timescales, and a key element of these models is therefore hierarchical simulation. However, this predictive capacity has far outstripped our ability to validate predictions experimentally, particularly when multiple hierarchical levels are involved. The state of the art represents careful integration of multiscale experiment and modelling, and yields not only validation, but also insights into deformation and relaxation mechanisms across scales. We present here a sampling of key results that highlight both challenges and opportunities for integrated multiscale experiment and modelling in biological systems.

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“…Neurons, as the main functional units of the spinal cord, are responsible for receiving and transmitting signals (Lovinger 2008). Hence, exploring the morphology of neuronal networks is important to understand the normal function of the spinal cord and the pathogenesis of related disorders (Hogstrom et al 2016;Xu et al 1993).…”

Section: Introductionmentioning

confidence: 99%

A combinatorial method to visualize the neuronal network in the mouse spinal cord: combination of a modified Golgi-Cox method and synchrotron radiation micro-computed tomography

Jiang

Cao

Yin

et al. 2021

Histochem Cell Biol

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Exploring the three-dimensional (3D) morphology of neurons is essential to understanding spinal cord function and associated diseases comprehensively. However, 3D imaging of the neuronal network in the broad region of the spinal cord at cellular resolution remains a challenge in the field of neuroscience. In this study, to obtain high-resolution 3D imaging of a detailed neuronal network in the mass of the spinal cord, the combination of synchrotron radiation micro-computed tomography (SRμCT) and the Golgi-cox staining were used. We optimized the Golgi-Cox method (GCM) and developed a modified GCM (M-GCM), which improved background staining, reduced the number of artefacts, and diminished the impact of incomplete vasculature compared to the current GCM. Moreover, we achieved high-resolution 3D imaging of the detailed neuronal network in the spinal cord through the combination of SRμCT and M-GCM. Our results showed that the M-GCM increased the contrast between the neuronal structure and its surrounding extracellular matrix. Compared to the GCM, the M-GCM also diminished the impact of the artefacts and incomplete vasculature on the 3D image. Additionally, the 3D neuronal architecture was successfully quantified using a combination of SRμCT and M-GCM. The SRμCT was shown to be a valuable non-destructive tool for 3D visualization of the neuronal network in the broad 3D region of the spinal cord. Such a combinatorial method will, therefore, transform the presentation of Golgi staining from 2 to 3D, providing significant improvements in the 3D rendering of the neuronal network.

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Advancing multiscale structural mapping of the brain through fluorescence imaging and analysis across length scales

Cited by 8 publications

References 85 publications

Hard X‐Ray Nanoholotomography: Large‐Scale, Label‐Free, 3D Neuroimaging beyond Optical Limit

Hard X‐Ray Nanoholotomography: Large‐Scale, Label‐Free, 3D Neuroimaging beyond Optical Limit

Integrated multiscale biomaterials experiment and modelling: a perspective

A combinatorial method to visualize the neuronal network in the mouse spinal cord: combination of a modified Golgi-Cox method and synchrotron radiation micro-computed tomography

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