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Quantification of plaque stiffness byBrillouin microscopy in experimentalthin cap fibroatheroma

TLDR
This is the first study, to the best of the knowledge, to apply Brillouin spectroscopy to quantify atherosclerotic plaque stiffness, which motivates combining this technology with intravascular imaging to improve detection of vulnerable plaques in patients.
Abstract
Plaques vulnerable to rupture are characterized by a thin and stiff fibrous cap overlaying a soft lipid-rich necrotic core. The ability to measure local plaque stiffness directly to quantify plaque stress and predict rupture potential would be very attractive, but no current technology does so. This study seeks to validate the use of Brillouin microscopy to measure the Brillouin frequency shift, which is related to stiffness, within vulnerable plaques. The left carotid artery of an ApoE−/−mouse was instrumented with a cuff that induced vulnerable plaque development in nine weeks. Adjacent histological sections from the instrumented and control arteries were stained for either lipids or collagen content, or imaged with confocal Brillouin microscopy. Mean Brillouin frequency shift was 15.79 ± 0.09 GHz in the plaque compared with 16.24 ± 0.15 (p < 0.002) and 17.16 ± 0.56 GHz (p < 0.002) in the media of the diseased and control vessel sections, respectively. In addition, frequency shift exhibited a strong inverse correlation with lipid area of −0.67 ± 0.06 (p < 0.01) and strong direct correlation with collagen area of 0.71 ± 0.15 (p < 0.05). This is the first study, to the best of our knowledge, to apply Brillouin spectroscopy to quantify atherosclerotic plaque stiffness, which motivates combining this technology with intravascular imaging to improve detection of vulnerable plaques in patients.

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Citations
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Journal ArticleDOI

Brillouin microscopy: an emerging tool for mechanobiology

TL;DR: This Review discusses the principles, advantages and limitations of Brillouin microscopy, a non-invasive tool for measuring mechanical properties of biological samples in three dimensions, as well as its potential for gaining insights in biology.
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The emergence of optical elastography in biomedicine

TL;DR: Optical elastography, the use of optics to characterize and map the mechanical properties of biological tissue, involves measuring the deformation of tissue in response to a load.
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Mapping the subcellular mechanical properties of live cells in tissues with fluorescence emission–Brillouin imaging

TL;DR: Fluorescence emission–Brillouin scattering imaging (FBi) is introduced, a method for the parallel and all-optical measurements of mechanical properties and fluorescence at the submicrometer scale in living organisms and it is shown that changes in cellular hydrostatic pressure and cytoplasm viscoelasticity modulate the mechanical signatures of plant ECMs.
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Mechanical Mapping of Spinal Cord Growth and Repair in Living Zebrafish Larvae by Brillouin Imaging

TL;DR: The presented work constitutes the first step toward an in vivo assessment of spinal cord tissue mechanics during regeneration, provides a methodical basis to identify key determinants of mechanical tissue properties, and allows us to test their relative importance in combination with biochemical and genetic factors during developmental and regenerative processes.
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Biomechanics of subcellular structures by non-invasive Brillouin microscopy.

TL;DR: Three-dimensional biomechanical images of single cells obtained with non-invasive, non-destructive Brillouin microscopy with an unprecedented spatial resolution are shown and the longitudinal elastic modulus of subcellular structures are quantified, finding the nucleoli to be stiffer than both the nuclear envelope and the surrounding cytoplasm.
References
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Atherosclerotic Lesion Size and Vulnerability Are Determined by Patterns of Fluid Shear Stress

TL;DR: A perivascular shear stress modifier is developed that induces regions of lowered, increased, and lowered/oscillatory (ie, with vortices) shear stresses in mouse carotid arteries and studied plaque formation and composition, finding lowered shear stressed lesions induce larger lesions with a vulnerable plaque phenotype.
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Coronary Artery Wall Shear Stress Is Associated With Progression and Transformation of Atherosclerotic Plaque and Arterial Remodeling in Patients With Coronary Artery Disease

TL;DR: Low-WSS segments in patients with coronary artery disease develop greater plaque and necrotic core progression and constrictive remodeling, and high-W SS segments develop greater nec rotic core and calcium progression, regression of fibrous and fibrofatty tissue, and excessive expansive remodelling, suggestive of transformation to a more vulnerable phenotype.
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Confocal Brillouin microscopy for three-dimensional mechanical imaging

TL;DR: A confocal Brillouin microscope based on a fully parallel spectrometer-a virtually imaged phased array-that improves the detection efficiency by nearly 100-fold over previous approaches is demonstrated and the first cross-sectional BrillouIn imaging based on elastic properties as the contrast mechanism is shown.
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Anisotropic mechanical properties of tissue components in human atherosclerotic plaques.

TL;DR: Experimental data of individual samples indicated anisotropic and highly nonlinear tissue properties as well as considerable interspecimen differences in the atherosclerotic lesions.
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Pathology of the thin-cap fibroatheroma: a type of vulnerable plaque.

TL;DR: Targeted therapy for the purpose of stabilizing coronary lesions that are prone to rupture is a major future goal of the interventionist.
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