J.-L. Gennisson

Measurement of viscoelastic properties of homogeneous soft solid using transient elastography: An inverse problem approach

Two main questions are at the center of this paper. The first one concerns the choice of a rheological model in the frequency range of transient elastography, sonoelasticity or NMR elastography for soft solids (20-1000 Hz). Transient elastography experiments based on plane shear waves that propagate in an Agar-gelatin phantom or in bovine muscles enable one to quantify their viscoelastic properties. The comparison of these experimental results to the prediction of the two simplest rheological models indicate clearly that Voigts model is the better. The second question studied in the paper deals with the feasibility of quantitative viscosity mapping using inverse problem algorithm. In the ideal situation where plane shear waves propagate in a sample, a simple inverse problem based on the Helmholtz equation correctly retrieves both elasticity and viscosity. In a more realistic situation with nonplane shear waves, this simple approach fails. Nevertheless, it is shown that quantitative viscosity mapping is still possible if one uses an appropriate inverse problem that fully takes into account diffraction in solids.

Measurement of elastic nonlinearity of soft solid with transient elastography

Transient elastography is a powerful tool to measure the speed of low-frequency shear waves in soft tissues and thus to determine the second-order elastic modulus mu (or the Youngs modulus E). In this paper, it is shown how transient elastography can also achieve the measurement of the nonlinear third-order elastic moduli of an Agar-gelatin-based phantom. This method requires speed measurements of polarized elastic waves measured in a statically stressed isotropic medium. A static uniaxial stress induces a hexagonal anisotropy (transverse isotropy) in solids. In the special case of uniaxially stressed isotropic media, the anisotropy is not caused by linear elastic coefficients but by the third-order nonlinear elastic constants, and the medium recovers its isotropic properties as soon as the uniaxial stress disappears. It has already been shown how transient elastography can measure the elastic (second-order) moduli in a media with transverse isotropy such as muscles. Consequently this method, based on the measurement of the speed variations of a low-frequency (50-Hz) polarized shear strain waves as a function of the applied stress, allows one to measure the Landau moduli A, B, C that completely describe the third-order nonlinearity. The several orders of magnitude found among these three constants can be justified from the theoretical expression of the internal energy.

Ultra high speed imaging of elasticity

Ultrafast ultrasonic imaging seems to have a strong potential for medical imaging applications. During the past five years, it has been applied successfully to quantitative assessment of soft tissues elasticity. An ultrafast ultrasonic scanner was built in our lab for quantitatively mapping the shear elasticity of soft tissues. The ultrafast Scanner provides images of the echogenecity of tissues similar to a standard echographic device but with a 200 times higher a frame rate. It allows to detect fast tissue motion induced by low frequency shear waves inside the body. From these displacements, a shear elasticity map is constructed using inverse problem algorithms. Preliminary in vivo results in breast demonstrate that this technique, known as transient elastography, is very sensitive to the presence of hard tumors. The same technique can also be combined with remote palpation induced par ultrasonic radiation pressure to replace the usual external vibrating system The same probe allows both to generate and detect shear waves propagation by using an unusual emission-reception sequence.

In vivo quantification of the shear modulus of the human Achilles tendon during passive loading using shear wave dispersion analysis.

The shear wave velocity dispersion was analyzed in the Achilles tendon (AT) during passive dorsiflexion using a phase velocity method in order to obtain the tendon shear modulus (C 55). Based on this analysis, the aims of the present study were (i) to assess the reproducibility of the shear modulus for different ankle angles, (ii) to assess the effect of the probe locations, and (iii) to compare results with elasticity values obtained with the supersonic shear imaging (SSI) technique. The AT shear modulus (C 55) consistently increased with the ankle dorsiflexion (N = 10, p < 0.05). Furthermore, the technique showed a very good reproducibility (all standard error of the mean values <10.7 kPa and all coefficient of variation (CV) values ⩽ 0.05%). In addition, independently from the ankle dorsiflexion, the shear modulus was significantly higher in the proximal location compared to the more distal one. The shear modulus provided by SSI was always lower than C55 and the difference increased with the ankle dorsiflexion. However, shear modulus values provided by both methods were highly correlated (R = 0.84), indicating that the conventional shear wave elastography technique (SSI technique) can be used to compare tendon mechanical properties across populations. Future studies should determine the clinical relevance of the shear wave dispersion analysis, for instance in the case of tendinopathy or tendon tear.

Nonlinearity studies in soft tissues with the supersonic shear imaging system

The ultrafast scanner has been shown to be a powerful tool to detect shear wave propagation within soft tissues in transient elastography experiments. More recently it was also used to generate shear waves thanks to the acoustic radiation pressure. This technique, the supersonic shear imaging, can easily be implemented in an acoustoelasticity experiment. Thus the association of static elastography with dynamic elastography can reveal the nonlinear properties of soft materials. Moreover, using a new theoretical approach of the strain energy in soft solid (Hamilton et al. (2003)), it is shown that the acoustoelasticity experiment can be greatly simplified. Instead of measuring shear wave speed for three different polarizations in order to completely determine the nonlinearity of standard solids, one is sufficient in soft solids to characterize the nonlinear shear elasticity.

Functional ultrasound imaging of the human brain activity: An intraoperative pilot study for cortical functional mapping

A wide spectrum of methods is used to image brain activation in vivo, such as functional MRI (fMRI) or positron emission tomography. Both techniques have excellent depth penetration but do not provide good spatial nor temporal resolution. By contrast, ultrasound imaging achieves good spatiotemporal resolution in depth, but until now its poor sensitivity has limited its use to the imaging of major vessels. Functional ultrasound (fUS) derived from the key concept of ultrafast imaging (up to 20 000 frames/s) overcomes this limitation. fUS enables high spatiotemporal resolution imaging of microvasculature dynamics in response to brain activation and was previously validated in rodents. We aim to demonstrate that fUS could find activation maps accurately during brain surgery in humans without requiring electrocortical stimulation mapping (ESM). A clinical study including 10 patients with brain lesion is undertaken, with both fMRI and ESM as gold standard. Patients underwent fMRI before surgery, data were intraoperatively used for ultrasound probe positioning on a targeted functional area using a neuronavigation system (Brainlab AG, Feldkirchen, Germany) and probe location was also confirmed by ESM. A sterilized linear probe driven by an ultrafast ultrasound scanner (Aixplorer, Supersonic Imagine, France) was placed directly on the brain after skull opening. Patients, awake during this part of their surgery, were asked to perform a specific task (motor, sensory or language). fUS imaging with a 6000 Hz frame rate determines regions of brain activity based on the cerebral blood volume (CBV) increase due to neurovascular coupling. This first pilot study demonstrates the ability of fUS imaging to map with a high signal-to-noise ratio (SNR) the stimulus-based neuronal activation in depth in real time during brain surgery. Such technique could be extremely useful for neurosurgeons to improve their surgery and therefore patient quality of life.

Intraoperative quantitative measurement of brain tumor stiffness and intracranial pressure assessment using ultrasound shear wave elastography

Ultrasonography is proving to be an invaluable tool in brain surgery. Recently, new ultrasonic modalities called shear wave elastography (SWE) enabled living tissue assessment of stiffness. SWE is routinely used for breast or liver diseases, but brain data are missing. We aim to characterize elasticity of normal brain and brain tumors by using SWE and to study if there is a relationship between SWE and intracranial pressure (ICP). Improving quality of brain tumor resection and predict brain swelling are major concerns for neurosurgeons. A clinical study was undertaken, including normal brain and tumors data collected from intraoperative SWE. The aim is to improve shear wave imaging for brain tissue investigation by correlating in vivo stiffness data and histology. At the same time ICP was studied, first ex vivo and then during in vivo surgery, to observe brain swelling by using SWE. Shear waves were generated by using ultrasonic acoustic radiation force and imaged in real-time by an ultrafast ultrasound scanner up to 20 000 frames/s. This study demonstrates that there are significant differences in elasticity among the most common types of brain tumors. We show that SWE could help for diagnosis during tumor resection by distinguishing benign tumors from malignant tumors (AUROC: 0.77, p<;10-4). Regarding pressure measurements, stiffness was found increasing with the pressure both ex vivo and in vivo. This study present great perspective for SWE to ensure grade differentiation and full tumor removal.

Assessment of the cervical stiffness in pregnant women using Shear Wave Elastography: A feasibility study

The quantitative and objective assessment of cervical stiffness has great potential for the estimation of pre-term delivery risk, as well as for the prediction of the success of labor induction. Various methods can be used in vivo for cervical assessment such as vaginal digital examination or static elastography but to our knowledge, none of them can provide a quantitative, absolute and independent evaluation of cervical stiffness in vivo. In this study, such values were obtained in pregnant patients in vivo by using Supersonic shear Imaging technique (SSI). The stiffness of the lower anterior part of the cervix was quantified over a Φ 8 mm region of interest, during vaginal ultrasound examination in 163 pregnant women. We were able i) to assess the range of normal elasticity values throughout the pregnancy, ii) to demonstrate the intra and inter-operator reproducibility of the measurement and iii) to evaluate the potential of SSI for the discrimination of pre-term labour. The elastic modulus of the cervix was found to decrease significantly throughout the pregnancy. This study provides for the first time a database for absolute elastic modulus values of the cervix throughout the pregnancy. Stiffness was observed to decrease with gestional age, which is consistent with results previously obtained using a cervicotonometer. Cervical stiffness is reduced in patients diagnosed with pre-term labour.