Thomas Deffieux

Quantitative Assessment of Breast Lesion Viscoelasticity: Initial Clinical Results Using Supersonic Shear Imaging

This paper presents an initial clinical evaluation of in vivo elastography for breast lesion imaging using the concept of supersonic shear imaging. This technique is based on the combination of a radiation force induced in tissue by an ultrasonic beam and an ultrafast imaging sequence capable of catching in real time the propagation of the resulting shear waves. The local shear wave velocity is recovered using a time-offlight technique and enables the 2-D mapping of shear elasticity. This imaging modality is implemented on a conventional linear probe driven by a dedicated ultrafast echographic device. Consequently, it can be performed during a standard echographic examination. The clinical investigation was performed on 15 patients, which corresponded to 15 lesions (4 cases BI-RADS 3, 7 cases BI-RADS 4 and 4 cases BI-RADS 5). The ability of the supersonic shear imaging technique to provide a quantitative and local estimation of the shear modulus of abnormalities with a millimetric resolution is illustrated on several malignant (invasive ductal and lobular carcinoma) and benign cases (fibrocystic changes and viscous cysts). In the investigated cases, malignant lesions were found to be significantly different from benign solid lesions with respect to their elasticity values. Cystic lesions have shown no shear wave propagate at all in the lesion (because shear waves do not propage in liquid). These preliminary clinical results directly demonstrate the clinical feasibility of this new elastography technique in providing quantitative assessment of relative stiffness of breast tissues. This technique of evaluating tissue elasticity gives valuable information that is complementary to the B-mode morphologic information. More extensive studies are necessary to validate the assumption that this new mode potentially helps the physician in both false-positive and false-negative rejection.

Breast lesions: quantitative elastography with supersonic shear imaging--preliminary results.

PURPOSE To determine the appearance of breast lesions at quantitative ultrasonographic (US) elastography by using supersonic shear imaging (SSI) and to assess the correlation between quantitative values of lesion stiffness and pathologic results, which were used as the reference standard. MATERIALS AND METHODS This study was approved by the French National Committee for the Protection of Patients Participating in Biomedical Research Programs. All patients provided written informed consent. Conventional US and SSI quantitative elastography were performed in 46 women (mean age, 57.6 years; age range, 38-71 years) with 48 breast lesions (28 benign, 20 malignant; mean size, 14.7 mm); pathologic results were available in all cases. Quantitative lesion elasticity was measured in terms of the Young modulus (in kilopascals). Sensitivity, specificity, and area under the curve were obtained by using a receiver operating characteristic curve analysis to assess diagnostic performance. RESULTS All breast lesions were detected at SSI. Malignant lesions exhibited a mean elasticity value of 146.6 kPa +/- 40.05 (standard deviation), whereas benign ones had an elasticity value of 45.3 kPa +/- 41.1 (P < .001). Complicated cysts were differentiated from solid lesions because they had elasticity values of 0 kPa (no signal was retrieved from liquid areas). CONCLUSION SSI provides quantitative elasticity measurements, thus adding complementary information that potentially could help in breast lesion characterization with B-mode US.

VISCOELASTIC AND ANISOTROPIC MECHANICAL PROPERTIES OF IN VIVO MUSCLE TISSUE ASSESSED BY SUPERSONIC SHEAR IMAGING

The in vivo assessment of the biomechanical properties of the skeletal muscle is a complex issue because the muscle is an anisotropic, viscoelastic and dynamic medium. In this article, these mechanical properties are characterized for the brachialis muscle in vivo using a noninvasive ultrasound-based technique. This supersonic shear imaging technique combines an ultra-fast ultrasonic system and the remote generation of transient mechanical forces into tissue via the radiation force of focused ultrasonic beams. Such an ultrasonic radiation force is induced deep within the muscle by a conventional ultrasonic probe and the resulting shear waves are then imaged with the same probe (5 MHz) at an ultra-fast framerate (up to 5000 frames/s). Local tissue velocity maps are obtained with a conventional speckle tracking technique and provide a full movie of the shear wave propagation through the entire muscle. Shear wave group velocities are then estimated using a time of flight algorithm. This approach provides a complete set of quantitative and in vivo parameters describing the muscles mechanical properties as a function of active voluntary contraction as well as passive extension of healthy volunteers. Anisotropic properties are also estimated by tilting the probe head with respects to the main muscular fibers direction. Finally, the dispersion of the shear waves is studied for these different configurations and shear modulus and shear viscosity are quantitatively assessed assuming the viscoelastic Voigts model.

Quantitative Viscoelasticity Mapping of Human Liver Using Supersonic Shear Imaging: Preliminary In Vivo Feasability Study

This paper demonstrates the feasibility of in vivo quantitative mapping of liver viscoelasticity using the concept of supersonic shear wave imaging. This technique is based on the combination of a radiation force induced in tissues by focused ultrasonic beams and a very high frame rate ultrasound imaging sequence capable of catching in real time the transient propagation of resulting shear waves. The local shear wave velocity is recovered using a dedicated time-of-flight estimation technique and enables the 2-D quantitative mapping of shear elasticity. This imaging modality is performed using a conventional ultrasound probe during a standard intercostal ultrasonographic examination. Three supersonic shear imaging (SSI) sequences are applied successively in the left, middle and right parts of the 2-D ultrasonographic image. Resulting shear elasticity images in the three regions are concatenated to provide the final image covering the entire region-of-interest. The ability of the SSI technique to provide a quantitative and local estimation of liver shear modulus with a millimetric resolution is proven in vivo on 15 healthy volunteers. Liver moduli extracted from in vivo data from healthy volunteers are consistent with those reported in the literature (Youngs modulus ranging from 4 to 7.5 kPa). Moreover, liver stiffness estimation using the SSI mode is shown to be fast (less than one second), repeatable (5.7% standard deviation) and reproducible (6.7% standard deviation). This technique, used as a complementary tool for B-mode ultrasound, could complement morphologic information both for fibrosis staging and hepatic lesions imaging.

Shear Wave Spectroscopy for In Vivo Quantification of Human Soft Tissues Visco-Elasticity

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 cm2 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.

Ultrasound elastography: Principles and techniques

Ultrasonography has been widely used for diagnosis since it was first introduced in clinical practice in the 1970s. Since then, new ultrasound modalities have been developed, such as Doppler imaging, which provides new information for diagnosis. Elastography was developed in the 1990s to map tissue stiffness, and reproduces/replaces the palpation performed by clinicians. In this paper, we introduce the principles of elastography and give a technical summary for the main elastography techniques: from quasi-static methods that require a static compression of the tissue to dynamic methods that uses the propagation of mechanical waves in the body. Several dynamic methods are discussed: vibro-acoustography, Acoustic Radiation Force Impulsion (ARFI), transient elastography, shear wave imaging, etc. This paper aims to help the reader at understanding the differences between the different methods of this promising imaging modality that may become a significant tool in medical imaging.

In vivo transcranial cavitation threshold detection during ultrasound-induced blood–brain barrier opening in mice

The in vivo cavitation response associated with blood-brain barrier (BBB) opening as induced by transcranial focused ultrasound (FUS) in conjunction with microbubbles was studied in order to better identify the underlying mechanism in its noninvasive application. A cylindrically focused hydrophone, confocal with the FUS transducer, was used as a passive cavitation detector (PCD) to identify the threshold of inertial cavitation (IC) in the presence of Definity® microbubbles (mean diameter range: 1.1-3.3 µm, Lantheus Medical Imaging, MA, USA). A vessel phantom was first used to determine the reliability of the PCD prior to in vivo use. A cerebral blood vessel was simulated by generating a cylindrical channel of 610 µm in diameter inside a polyacrylamide gel and by saturating its volume with microbubbles. The microbubbles were sonicated through an excised mouse skull. Second, the same PCD setup was employed for in vivo noninvasive (i.e. transdermal and transcranial) cavitation detection during BBB opening. After the intravenous administration of Definity® microbubbles, pulsed FUS was applied (frequency: 1.525 or 1.5 MHz, peak-rarefactional pressure: 0.15-0.60 MPa, duty cycle: 20%, PRF: 10 Hz, duration: 1 min with a 30 s interval) to the right hippocampus of twenty-six (n = 26) mice in vivo through intact scalp and skull. T1 and T2-weighted MR images were used to verify the BBB opening. A spectrogram was generated at each pressure in order to detect the IC onset and duration. The threshold of BBB opening was found to be at a 0.30 MPa peak-rarefactional pressure in vivo. Both the phantom and in vivo studies indicated that the IC pressure threshold had a peak-rarefactional amplitude of 0.45 MPa. This indicated that BBB opening may not require IC at or near the threshold. Histological analysis showed that BBB opening could be induced without any cellular damage at 0.30 and 0.45 MPa. In conclusion, the cavitation response could be detected without craniotomy in mice and IC may not be required for BBB opening at relatively low pressures.

Spatiotemporal Clutter Filtering of Ultrafast Ultrasound Data Highly Increases Doppler and fUltrasound Sensitivity

Ultrafast ultrasonic imaging is a rapidly developing field based on the unfocused transmission of plane or diverging ultrasound waves. This recent approach to ultrasound imaging leads to a large increase in raw ultrasound data available per acquisition. Bigger synchronous ultrasound imaging datasets can be exploited in order to strongly improve the discrimination between tissue and blood motion in the field of Doppler imaging. Here we propose a spatiotemporal singular value decomposition clutter rejection of ultrasonic data acquired at ultrafast frame rate. The singular value decomposition (SVD) takes benefits of the different features of tissue and blood motion in terms of spatiotemporal coherence and strongly outperforms conventional clutter rejection filters based on high pass temporal filtering. Whereas classical clutter filters operate on the temporal dimension only, SVD clutter filtering provides up to a four-dimensional approach (3D in space and 1D in time). We demonstrate the performance of SVD clutter filtering with a flow phantom study that showed an increased performance compared to other classical filters (better contrast to noise ratio with tissue motion between 1 and 10mm/s and axial blood flow as low as 2.6 mm/s). SVD clutter filtering revealed previously undetected blood flows such as microvascular networks or blood flows corrupted by significant tissue or probe motion artifacts. We report in vivo applications including small animal fUltrasound brain imaging (blood flow detection limit of 0.5 mm/s) and several clinical imaging cases, such as neonate brain imaging, liver or kidney Doppler imaging.

On the effects of reflected waves in transient shear wave elastography

In recent years, novel quantitative techniques have been developed to provide noninvasive and quantitative stiffness images based on shear wave propagation. Using radiation force and ultrafast ultrasound imaging, the supersonic shear imaging technique allows one to remotely generate and follow a transient plane shear wave propagating in vivo in real time. The tissue shear modulus, i.e., its stiffness, can then be estimated from the shear wave local velocity. However, because the local shear wave velocity is estimated using a time-of-flight approach, reflected shear waves can cause artifacts in the estimated shear velocity because the incident and reflected waves propagate in opposite directions. Such effects have been reported in the literature as a potential drawback of elastography techniques based on shear wave speed, particularly in the case of high stiffness contrasts, such as in atherosclerotic plaque or stiff lesions. In this letter, we present our implementation of a simple directional filter, previously used for magnetic resonance elastography, which separates the forward- and backward-propagating waves to solve this problem. Such a directional filter could be applied to many elastography techniques based on the local estimation of shear wave speed propagation, such as acoustic radiation force imaging (ARFI), shearwave dispersion ultrasound vibrometry (SDUV), needle-based elastography, harmonic motion imaging, or crawling waves when the local propagation direction is known and high-resolution spatial and temporal data are acquired.

Low-intensity focused ultrasound modulates monkey visuomotor behavior.

In vivo feasibility of using low-intensity focused ultrasound (FUS) to transiently modulate the function of regional brain tissue has been recently tested in anesthetized lagomorphs [1] and rodents [2-4]. Hypothetically, ultrasonic stimulation of the brain possesses several advantages [5]: it does not necessitate surgery or genetic alteration but could ultimately confer spatial resolutions superior to other noninvasive methods. Here, we gauged the ability of noninvasive FUS to causally modulate high-level cognitive behavior. Therefore, we examined how FUS might interfere with prefrontal activity in two awake macaque rhesus monkeys that had been trained to perform an antisaccade (AS) task. We show that ultrasound significantly modulated AS latencies. Such effects proved to be dependent on FUS hemifield of stimulation (relative latency increases most for ipsilateral AS). These results are interpreted in terms of a modulation of saccade inhibition to the contralateral visual field due to the disruption of processing across the frontal eye fields. Our study demonstrates for the first time the feasibility of using FUS stimulation to causally modulate behavior in the awake nonhuman primate brain. This result supports the use of this approach to study brain function. Neurostimulation with ultrasound could be used for exploratory and therapeutic purposes noninvasively, with potentially unprecedented spatial resolution.