Quantification of plaque stiffness by Brillouin microscopy in experimental thin cap fibroatheroma

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 2/2 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 20.67 + 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.

Biomechanics of subcellular structures by non-invasive Brillouin microscopy

“…The high-frequency longitudinal elastic modulus (M′) of a viscoelastic material is obtained by measuring the frequency shift of the light scattered inelastically by local spontaneous acoustic waves (see Methods)1516. Up to now, Brillouin microscopy has been used to characterise the biomechanical properties of the lens cornea17; to quantify plaque stiffness in atherosclerosis18; to screen bacterial meningitis19; and to assess cytoskeleton stiffening20. Spectral broadening arising from the collection of photons by high numerical aperture (NA) lenses had limited the technique to a low spatial resolution1321.…”

Mechanical mapping of spinal cord development and repair in living zebrafish larvae using Brillouin microscopy

“…With the emergence of virtually imaged phased array (VIPA) based spectrometers in the last decade, this technique has become applicable for the point-wise measurement within living biological samples to build up a three-dimensional image with diffraction-limited resolution 51 . Brillouin microscopy has so far been applied to human cornea [52][53][54] , murine carotid arteries 55 , ruminant retina 56 , rabbit bone tissue 57 and zebrafish embryos [58][59][60] . Here, we exploit the optical transparency and high regenerative capacity of zebrafish larvae to systematically explore the in vivo mechanical properties of larval tissue during development and repair using a custom-built Brillouin microscopy setup.…”

SNR enhancement in brillouin microspectroscopy using spectrum reconstruction

“…Moreover, study of the linewidth of the Brillouin spectral peaks enables measurement of phonon lifetimes thereby also enabling viscous characteristics to be quantified [4,5]. More recently, Brillouin spectroscopy has seen a renaissance as it has developed from a point sampling technique into a more powerful hyper-spectral imaging modality in which mechanical information is mapped with micron level resolution [6][7][8][9][10]. This is particularly attractive for its applicability in, for example, in vivo diagnostics and cellular imaging (see e.g.…”