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The tumour microenvironment may contribute to tumorigenesis owing to mechanical forces such as fibrotic stiffness or mechanical pressure caused by the expansion of hyper-proliferative cells (1,2). Here we explore the contribution of the mechanical pressure exerted by tumour growth onto non-tumorous adjacent epithelium. In the early stage of mouse colon tumour development in the [Notch.sup.+][Apc.sup.+/1638N] mouse model, we observed mechanistic pressure stress in the non-tumorous epithelial cells caused by hyper-proliferative adjacent crypts overexpressing active Notch, which is associated with increased Ret and β-catenin signalling. We thus developed a method that allows the delivery of a defined mechanical pressure invivo, by subcutaneously inserting a magnet close to the mouse colon. The implanted magnet generated a magnetic force on ultra-magnetic liposomes, stabilized in the mesenchymal cells of the connective tissue surrounding colonic crypts after intravenous injection. The magnetically induced pressure quantitatively mimicked the endogenous early tumour growth stress in the order of 1,200 Pa, without affecting tissue stiffness, as monitored by ultrasound strain imaging and shear wave elastography. The exertion of pressure mimicking that of tumour growth led to rapid Ret activation and downstream phosphorylation of β-catenin on Tyr654, imparing its interaction with the E-cadherin in adherens junctions, and which was followed by β-catenin nuclear translocation after 15 days. As a consequence, increased expression of β-catenin-target genes was observed at 1 month, together with crypt enlargement accompanying the formation of early tumorous aberrant crypt foci. Mechanical activation of the tumorigenic β-catenin pathway suggests unexplored modes of tumour propagation based on mechanical signalling pathways in healthy epithelial cells surrounding the tumour, which may contribute to tumour heterogeneity., To test the tumorous impact of early tumour growth pressure on non-tumorous epithelial tissues in vivo, apart from the mechanical stiffness characteristic of the microenvironment of late tumours (1-6) (see [...]

In vivo assessment of dispersion affecting the propagation of visco-elastic waves in soft tissues is key to understand the rheology of human tissues. In this paper, the ability of the supersonic shear imaging (SSI) technique to generate planar shear waves propagating in tissues is fully exploited. First, by strongly limiting shear wave diffraction in the imaging plane, this imaging technique enables to discriminate between the usually concomitant influences of both medium rheological properties and diffraction affecting the shear wave dispersion. Second, transient propagation of these plane shear waves in soft tissues can be measured using echographic images acquired at very high frame. In vitro and in vivo experiments demonstrate that dispersion curves, which characterize the rheological behavior of tissues by measuring the frequency dependence of shear wave speed and attenuation, can be recovered in the 75-600 Hz frequency range. Based on a phase difference algorithm, the dispersion curves are computed in 1 [cm.sup.2] regions of interest from the acquired propagation movie. In vivo measurements in Biceps Brachii muscle and liver of three healthy volunteers show important differences in the rheological behavior of these different tissues. Liver tissue appears to be much more dispersive with a phase velocity ranging from ~ 1.5 m/s at 75 Hz to ~ 3 m/s at 500 Hz whereas muscle tissue shows an important anisotropy, shear waves propagating longitudinally to the muscular fibers are almost nondispersive while those propagating transversally are very dispersive with a shear wave speed ranging from 0.5 to 2 m/s between 75 and 500 Hz. The estimation of dispersion curves is local and can be performed separately in different regions of the organ. This signal processing approach based on the SSI modality introduces the new concept of in vivo shear wave spectroscopy (SWS) that could become an additional tool for tissue characterization. This paper demonstrates the in vivo ability of this SWS to quantify both local shear elasticity and dispersion in real time. Index Terms--Dispersion, elastography, liver, muscle, rheology, shear wave spectroscopy (SWS), supersonic shear imaging (SSI).

The article presents a new approach called the echo mechanomypgraphy, where in the two-dimensional (2-D) and three-dimensional (3-D) very high frame rate ultrasound imaging is employed to study the mechanical properties of the musculoskeletal system. The approach is shown to be widely used for the noninvasive muscle diagnosis of an active contractile tissue.

A method is proposed to qualitatively evaluate the existence of higher-order viscoelastic parameters. The technique, in which, low-frequency, monochromatic elastic waves are emitted into the material through an external vibrator and resultant steady-state motion in real time are identified through an ultra fast ultrasound system using classical, one-dimensional ultrasound speckle correlation for motion estimation, demonstrates the feasibility to detect the areas of nonlinear viscoelastic properties in a tissue.

A different concept that allowed to obtain electronic three-dimensional (3-D) focusing with a small number of transducers was proposed. The mechanical impedance mismatch between the cavity and the imaged medium was responsible for the ability of time-reversal processing to focus waves in a 3-D volume with a very small number of transducers.

An iterative time-reversal method capable of taking into account all the heterogeneities of the medium, concerning density, speed of sound, and absorption variations is proposed. The iterative focusing process that converges toward a spatio-temporal inverse filter focusing, the first step of the process that is time-reversal focusing on the targeted point is shown.

An explicit formulation of the Green's function in a viscous and an elastic medium is derived. Based on this mathematical framework, a simulation tool is proposed and experimentally validated in tissue-mimicking phantoms.

The high-resolution device of measuring local Young's modulus in very thin layers, which is the principle assessment parameter, is described. Experimental results revealed that Young's modulus was found to be higher in the dermis than in the hypodermis and other soft tissues.

The feasibility of temperature estimation during high-intensity focused ultrasound data has been studied. It is seen that compound imaging significantly reduces the amount of artifacts in temperature estimates.

The new technique called supersonic shear imaging (SSI) depends on ultrasonic rays that create mechanical vibrations with low frequency that give a clear picture of soft tissue viscoelastic properties. This new technique permits tissue elasticity mapping in less than 20 ms.

A new method for 2-D motion vector estimation is proposed. It is shown experimentally that the method has potential with regard to transient elastography.

Propagation of low frequency (LF) shear waves can be used to determine tissue parameters such as elasticity. A new technique for measuring the shear velocity in soft tissues is proposed.

Propagation of transient low frequency (LF) shear waves is examined in tissue-equivalent phantoms by means of ultra-fast ultrasonics. A vibrating device is optimized to induce large displacements in the image area, and quantitative information is obtaines by means of a local inversion algorithm.