Regional variations in stiffness in live mouse brain tissue determined by depth-controlled indentation mapping

Antonovaité, Nelda; Beekmans, Steven V.; Hol, Elly M.; Wadman, Wytse J.; Iannuzzi, Davide

doi:10.1038/s41598-018-31035-y

Cited by 85 publications

(101 citation statements)

References 69 publications

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“…Other studies investigated the contribution of myelin in WM fibers as a mechanical support structure in the brain, suggesting a higher stiffness of WM than GM . In addition, recent dynamic indentation experiments in hippocampal tissues showed that stiffness appears to be lower in areas where cell nuclei density is high . These examples illustrate that regional values of brain stiffness, including WM‐GM ratios, provide rich structural information, which still remain to be disentangled.…”

Section: Discussionmentioning

confidence: 92%

“…43 In addition, recent dynamic indentation experiments in hippocampal tissues showed that stiffness appears to be lower in areas where cell nuclei density is high. 44 These examples illustrate that regional values of brain stiffness, including WM-GM ratios, provide rich structural information, which still remain to be disentangled. Different dynamic ranges of test methods, prestrains, geometric conditions, and in vivo versus ex vivo conditions including blood perfusion effects translate into different mechanical measures that are hard to compare among different modalities.…”

Section: F I G U R Ementioning

confidence: 99%

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Fast tomoelastography of the mouse brain by multifrequency single‐shot MR elastography

Bertalan

Guo

Tzschätzsch

et al. 2018

Magnetic Resonance in Med

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Purpose To introduce in vivo multifrequency single‐shot magnetic resonance elastography for full‐FOV stiffness mapping of the mouse brain and to compare in vivo stiffness of neural tissues with different white‐to‐gray matter ratios. Methods Viscous phantoms and 10 C57BL‐6 mice were investigated by 7T small‐animal MRI using a single‐shot spin‐echo planar imaging magnetic resonance elastography sequence with motion‐encoding gradients positioned before the refocusing pulse. Wave images were acquired over 10 minutes for 6 mechanical vibration frequencies between 900 and 1400 Hz. Stiffness maps of shear wave speed (SWS) were computed using tomoelastography data processing and compared with algebraic Helmholtz inversion (AHI) for signal‐to‐noise ratio (SNR) analysis. Different brain regions were analyzed including cerebral cortex, corpus callosum, hippocampus, and diencephalon. Results In phantoms, algebraic Helmholtz inversion–based SWS was systematically biased by noise and discretization, whereas tomoelastography‐derived SWS was consistent over the full SNR range analyzed. Mean in vivo SWS of the whole brain was 3.76 ± 0.33 m/s with significant regional variation (hippocampus = 4.91 ± 0.49 m/s, diencephalon = 4.78 ± 0.78 m/s, cerebral cortex = 3.53 ± 0.29 m/s, and corpus callosum = 2.89 ± 0.17 m/s). Conclusion Tomoelastography retrieves mouse brain stiffness within shorter scan times and with greater detail resolution than classical algebraic Helmholtz inversion–based magnetic resonance elastography. The range of SWS values obtained here indicates that mouse white matter is softer than gray matter at the frequencies investigated.

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Section: Discussionmentioning

confidence: 92%

Section: F I G U R Ementioning

confidence: 99%

Fast tomoelastography of the mouse brain by multifrequency single‐shot MR elastography

Bertalan

Guo

Tzschätzsch

et al. 2018

Magnetic Resonance in Med

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“…6A. Specifically, all regions stiffen with strain, revealing the non-linear viscoelastic properties of fixed chicken embryos, a result that highlights the importance of measuring the mechanical properties of embryonic tissues in depth-controlled mode (Antonovaite et al, 2018).…”

Section: Resultsmentioning

confidence: 87%

“…The indenter is based on ferrule-top technology (Chavan et al, 2010;Gruca et al, 2010), where the deflection of a micro-machined cantilever, equipped with a spherical tip, is used to determine the viscoelastic properties of the embryo via depth-controlled oscillatory ramp indentation ( Fig. 1A-D) (Antonovaite et al, 2018;van Hoorn et al, 2016). The OCT system images the embryonic structures during the indentation measurements and allows localizing the indentation point and evaluating the quality and the immobilization of the sample.…”

Section: Resultsmentioning

confidence: 99%

“…Those maps clearly show the inner morphological and mechanical heterogeneity of three main embryonic regions of interest, from young to old: the tail, the presomitic mesoderm, and the somitic mesoderm. To further validate the potential of the approach proposed, we demonstrate the non-linear behavior of chicken embryos by evaluating its mechanical properties as a function of indentation strain (Antonovaite et al, 2018;Lin et al, 2009a).…”

Section: Introductionmentioning

confidence: 99%

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Micro-indentation and optical coherence tomography for the mechanical characterization of embryos: Experimental setup and measurements on fixed chicken embryos

Marrese

Antonovaité

Nelemans

et al. 2019

Preprint

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statementWe introduce an experimental technique that combines micro-indentation and optical coherence tomography to map the viscoelastic properties of embryonic tissue and investigate correlations between local mechanical features and tissue morphology. AbstractThe investigation of the mechanical properties of embryos is expected to provide valuable information on the phenomenology of morphogenesis. It is thus believed that, by mapping the viscoelastic features of an embryo at different stages of growth, it may be possible to shed light on the role of mechanics in embryonic development. To contribute to this field, we present a new instrument that can determine spatiotemporal distributions of mechanical properties of embryos over a wide area and with unprecedented accuracy. The method relies on combining ferrule-top micro-indentation, which provides local measurements of viscoelasticity, with Optical Coherence Tomography, which can reveal changes in tissue morphology and help the user to localize the indentation locations. To prove the working principle, we have collected viscoelasticity maps of fixed HH11-HH12 chicken embryos. Our study highlights the nonlinear behavior of the tissue and qualitatively shows the correlation between local mechanical properties and tissue morphology for different regions of interest.

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Transparent, Compliant 3D Mesostructures for Precise Evaluation of Mechanical Characteristics of Organoids

et al. 2021

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Recently developed methods for transforming 2D patterns of thin‐film materials into 3D mesostructures create many interesting opportunities in microsystems design. A growing area of interest is in multifunctional thermal, electrical, chemical, and optical interfaces to biological tissues, particularly 3D multicellular, millimeter‐scale constructs, such as spheroids, assembloids, and organoids. Herein, examples of 3D mechanical interfaces are presented, in which thin ribbons of parylene‐C form the basis of transparent, highly compliant frameworks that can be reversibly opened and closed to capture, envelop, and mechanically restrain fragile 3D tissues in a gentle, nondestructive manner, for precise measurements of viscoelastic properties using techniques in nanoindentation. Finite element analysis serves as a design tool to guide selection of geometries and material parameters for shape‐matching 3D architectures tailored to organoids of interest. These computational approaches also quantitate all aspects of deformations during the processes of opening and closing the structures and of forces imparted by them onto the surfaces of enclosed soft tissues. Studies of cerebral organoids by nanoindentation show effective Young's moduli in the range from 1.5 to 2.5 kPa depending on the age of the organoid. This collection of results suggests broad utility of compliant 3D mesostructures in noninvasive mechanical measurements of millimeter‐scale, soft biological tissues.

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Regional variations in stiffness in live mouse brain tissue determined by depth-controlled indentation mapping

Cited by 85 publications

References 69 publications

Fast tomoelastography of the mouse brain by multifrequency single‐shot MR elastography

Fast tomoelastography of the mouse brain by multifrequency single‐shot MR elastography

Micro-indentation and optical coherence tomography for the mechanical characterization of embryos: Experimental setup and measurements on fixed chicken embryos

Transparent, Compliant 3D Mesostructures for Precise Evaluation of Mechanical Characteristics of Organoids

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