Comparison of ultrasound elastography, magnetic resonance elastography and finite element model to quantify nonlinear shear modulus.

Objective. The aim of this study is to validate the estimation of the nonlinear shear modulus (A) from the acoustoelasticity theory with two experimental methods, ultrasound (US) elastography and magnetic resonance elastography (MRE), and a finite element method.Approach. Experiments were performed on agar (2%)-gelatin (8%) phantom considered as homogeneous, elastic and isotropic. Two specific setups were built to ensure a uniaxial stress step by step on the phantom, one for US and a nonmagnetic version for MRE. The stress was controlled identically in both imaging techniques, with a water tank placed on the top of the phantom and filled with increasing masses of water during the experiment. In US, the supersonic shear wave elastography was implemented on an ultrafast US device, driving a 6 MHz linear array to measure shear wave speed. In MRE, a gradient-echo sequence was used in which the three spatial directions of a 40 Hz continuous wave displacement generated with an external driver were encoded successively. Numerically, a finite element method was developed to simulate the propagation of the shear wave in a uniaxially stressed soft medium.Main results. Similar shear moduli were estimated at zero stress using experimental methods,µ0US= 12.3 ± 0.3 kPa andµ0MRE= 11.5 ± 0.7 kPa. Numerical simulations were set with a shear modulus of 12 kPa and the resulting nonlinear shear modulus was found to be -58.1 ± 0.7 kPa. A very good agreement between the finite element model and the experimental models (AUS= -58.9 ± 9.9 kPa andAMRE= -52.8 ± 6.5 kPa) was obtained.Significance. These results show the validity of such nonlinear shear modulus measurement quantification in shear wave elastography. This work paves the way to develop nonlinear elastography technique to get a new biomarker for medical diagnosis.

A photoswitchable inhibitor of TREK channels controls pain in wild-type intact freely moving animals.

By endowing light control of neuronal activity, optogenetics and photopharmacology are powerful methods notably used to probe the transmission of pain signals. However, costs, animal handling and ethical issues have reduced their dissemination and routine use. Here we report LAKI (Light Activated K+ channel Inhibitor), a specific photoswitchable inhibitor of the pain-related two-pore-domain potassium TREK and TRESK channels. In the dark or ambient light, LAKI is inactive. However, alternating transdermal illumination at 365 nm and 480 nm reversibly blocks and unblocks TREK/TRESK current in nociceptors, enabling rapid control of pain and nociception in intact and freely moving mice and nematode. These results demonstrate, in vivo, the subcellular localization of TREK/TRESK at the nociceptor free nerve endings in which their acute inhibition is sufficient to induce pain, showing LAKI potential as a valuable tool for TREK/TRESK channel studies. More importantly, LAKI gives the ability to reversibly remote-control pain in a non-invasive and physiological manner in naive animals, which has utility in basic and translational pain research but also in in vivo analgesic drug screening and validation, without the need of genetic manipulations or viral infection.

Flux coupling, not specificity, shapes the transport and phylogeny of SLC6 glycine transporters.

ATB[Formula: see text] (SLC6A14) is a member of the amino acid transporter branch of the SLC6 family along with GlyT1 (SLC6A9) and GlyT2 (SLC6A5), two glycine-specific transporters coupled to 2:1 and 3:1 Na[Formula: see text]:Cl[Formula: see text], respectively. In contrast, ATB[Formula: see text] exhibits broad substrate specificity for all neutral and cationic amino acids, and its ionic coupling remains unsettled. Using the reversal potential slope method, we demonstrate a 3:1:1 Na[Formula: see text]:Cl[Formula: see text]:Gly stoichiometry for ATB[Formula: see text] that is consistent with its 2.1 e/Gly charge coupling. Like GlyT2, ATB[Formula: see text] behaves as a unidirectional transporter with virtually no glycine efflux at negative potentials after uptake, except by heteroexchange as remarkably shown by leucine activation of NMDARs in Xenopus oocytes coexpressing both membrane proteins. Analysis and computational modeling of the charge movement of ATB[Formula: see text] reveal a higher affinity for sodium in the absence of substrate than GlyT2 and a gating mechanism that locks Na[Formula: see text] into the apo-transporter at depolarized potentials. A 3:1 Na[Formula: see text]:Cl[Formula: see text] stoichiometry justifies the concentrative transport properties of ATB[Formula: see text] and explains its trophic role in tumor growth, while rationalizing its phylogenetic proximity to GlyT2 despite their extreme divergence in specificity.

Quantitative structural imaging of keratoconic corneas using polarization-resolved SHG microscopy.

The human cornea is mainly composed of collagen fibrils aligned together within stacked lamellae. This lamellar structure can be affected in pathologies such as keratoconus, which is characterized by progressive corneal thinning and local steepening. In this study, we use polarization-resolved second harmonic generation (P-SHG) microscopy to characterize 8 control and 6 keratoconic human corneas. Automated processing of P-SHG images of transverse sections provides the collagen orientation in every pixel with sub-micrometer resolution. Series of P-SHG images recorded in the most anterior region of the stroma evidence sutural lamellae inclined at 22° ± 5° to the corneal surface, but show no significant difference between control and keratoconic corneas. In contrast, series of P-SHG images acquired along the full thickness of the stroma show a loss of order in the lamellar structure of keratoconic corneas, in agreement with their defective mechanical properties. This structural difference is analyzed quantitatively by computing the entropy and the orientation index of the collagen orientation distribution and significant differences are obtained along the full thickness of the stroma. This study shows that P-SHG is an effective tool for automatic quantitative analysis of structural defects of human corneas and should be applied to other collagen-rich tissues.

Acoustoelasticity in transversely isotropic soft tissues: Quantification of muscle nonlinear elasticity.

Recent developments in the field of elastography aim at developing the quantification of new mechanical properties of tissues, that are complementary to the shear modulus, which is characteristic of the linear elastic properties of a quasi-incompressible medium. In this context, measurement of the elastic nonlinearity of tissues was recently proposed based on acoustoelasticity. Up to now, most of the experimental applications of acoustoelasticity theory using Landau formalism in human tissues have assumed isotropy. However, this strong hypothesis does not hold in all human tissues, such as muscles that are generally considered as transversely isotropic (TI). In this work, after reviewing the constraints imposed by TI symmetry on the linear and nonlinear elastic properties of TI media, the acoustoelasticity theory in TI incompressible media is developed and implemented experimentally on a TI polyvinyl alcohol phantom and on ex vivo muscular tissues. Based on this theory and on the evolutions of the shear wave speed, with respect to uniaxial static stress, the nonlinear elastic parameter A is experimentally quantified. The estimations of A in ex vivo bovine and porcine muscles are on the order of hundreds of kPa. This work paves the way for more thorough muscle mechanical properties characterization as well as for the development of a potential new biomarker.