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Hepatic steatosis is a common condition, the prevalence of which is increasing along with non-alcoholic fatty liver disease (NAFLD). Currently, the most accurate noninvasive imaging method for diagnosing and quantifying hepatic steatosis is MRI, which estimates the proton-density fat fraction (PDFF) as a measure of fractional fat content. However, MRI suffers several limitations including cost, contra-indications and poor availability. Although conventional ultrasound is widely used by radiologists for hepatic steatosis assessment, it remains qualitative and operator dependent. Interestingly, the speed of sound within soft tissues is known to vary slightly from muscle (1.575 mm · µs -1 ) to fat (1.450 mm · µs -1 ). Building upon this fact, steatosis could affect liver sound speed when the fat content increases. The main objectives of this study are to propose a robust method for sound speed estimation (SSE) locally in the liver and to assess its accuracy for steatosis detection and staging. This technique was first validated on two phantoms and SSE was assessed with a precision of 0.006 and 0.003 mm · µs -1 respectively for the two phantoms. Then a preliminary clinical trial (N  =  17 patients) was performed. SSE results was found to be highly correlated with MRI proton density fat fraction (R 2   =  0.69) and biopsy (AUROC  =  0.952) results. This new method based on the assessment of spatio-temporal properties of the local speckle noise for SSE provides an efficient way to diagnose and stage hepatic steatosis.

The assessment of myocardial fiber disarray is of major interest for the study of the progression of myocardial disease. However, time-resolved imaging of the myocardial structure remains unavailable in clinical practice. In this study, we introduce 3D Backscatter Tensor Imaging (3D-BTI), an entirely novel ultrasound-based imaging technique that can map the myocardial fibers orientation and its dynamics with a temporal resolution of 10 ms during a single cardiac cycle, non-invasively and in vivo in entire volumes. 3D-BTI is based on ultrafast volumetric ultrasound acquisitions, which are used to quantify the spatial coherence of backscattered echoes at each point of the volume. The capability of 3D-BTI to map the fibers orientation was evaluated in vitro in 5 myocardial samples. The helicoidal transmural variation of fiber angles was in good agreement with the one obtained by histological analysis. 3D-BTI was then performed to map the fiber orientation dynamics in vivo in the beating heart of an open-chest sheep at a volume rate of 90 volumes/s. Finally, the clinical feasibility of 3D-BTI was shown on a healthy volunteer. These initial results indicate that 3D-BTI could become a fully non-invasive technique to assess myocardial disarray at the bedside of patients.

3D functional imaging of the whole brain activity during visual task is a challenging task in rodents due to the complex tri-dimensional shape of involved brain regions and the fine spatial and temporal resolutions required to reveal the visual tract. By coupling functional ultrasound (fUS) imaging with a translational motorized stage and an episodic visual stimulation device, we managed to accurately map and to recover the activity of the visual cortices, the Superior Colliculus (SC) and the Lateral Geniculate Nuclei (LGN) in 3D. Cerebral Blood Volume (CBV) responses during visual stimuli were found to be highly correlated with the visual stimulus time profile in visual cortices (r=0.6), SC (r=0.7) and LGN (r=0.7). These responses were found dependent on flickering frequency and contrast, and optimal stimulus parameters for largest CBV increases were obtained. In particular, increasing the flickering frequency higher than 7Hz revealed a decrease of visual cortices response while the SC response was preserved. Finally, cross-correlation between CBV signals exhibited significant delays (d=0.35s +/-0.1s) between blood volume response in SC and visual cortices in response to our visual stimulus. These results emphasize the interest of fUS imaging as a whole brain neuroimaging modality for brain vision studies in rodent models., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Our aim in the study described here was to prospectively establish the feasibility of using and reproducibility of testicular shear-wave elastography in the assessment of testicular stiffness in 62 normal patients and 539 infertile men with obstructive azoospermia (OA), non-Klinefelter syndrome non-obstructive azoospermia (non-KS NOA), Klinefelter syndrome NOA (KS NOA), oligoasthenoteratozoospermia (OAT) or a left varicocele. The feasibility rate was 96.9%, with an intra-class correlation coefficient of 0.85 (95% confidence interval: 0.83-0.88). Median stiffness (interquartile range) values were 2.4 kPa (2.0, 2.9), 2.1 kPa (1.8, 2.5), 2.4 kPa (2.0, 2.7), 2.0 kPa (1.7, 2.4), 2.6 kPa (2, 3.2) and 2.2 kPa (1.8, 2.6) for men with a normal testis (n = 108), OAT (n = 689), OA (n = 119), non-KS NOA (n = 183), KS NOA (n = 70) and varicocele (n = 132), respectively. Testicular shear wave elastography is a feasible and reproducible technique. A significant positive association was found between stiffness and testis volume (p = 0.001). Testicular stiffness was higher in OA than in non-KS NOA populations (p = 1.e-10) and in KS NOA than in NOA populations (p = 2.0e-8), but the substantial number of overlapping values limited the clinical impact., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Noninvasive evaluation of the rheological behavior of soft tissues may provide an important diagnosis tool. Nowadays, available commercial ultrasound systems only provide shear elasticity estimation by shear wave speed assessment under the hypothesis of a purely elastic model. However, to fully characterize the rheological behavior of tissues, given by its storage (G') and loss (G″) moduli, it is necessary to estimate both: shear wave speed and shear wave attenuation. Most elastography techniques use the acoustic radiation force to generate shear waves. For this type of source the shear waves are not plane and a diffraction correction is needed to properly estimate the shear wave attenuation. The use of a cylindrical wave approximation to evaluate diffraction has been proposed by other authors before. Here the validity of such approximation is numerically and experimentally revisited. Then, it is used to generate images of G' and G″ in heterogeneous viscoelastic mediums. A simulation algorithm based on the anisotropic and viscoelastic Green's function was used to establish the validity of the cylindrical approximation. Moreover, two experiments were carried out: a transient elastography experiment where plane shear waves were generated using a vibrating plate and a SSI experiment that uses the acoustic radiation force to generate shear waves. For both experiments the shear wave propagation was followed with an ultrafast ultrasound scanner. Then, the shear wave velocity and shear wave attenuation were recovered from the phase and amplitude decay versus distance respectively. In the SSI experiment the cylindrical approximation was applied to correct attenuation due to diffraction effects. The numerical and experimental results validate the use of a cylindrical correction to assess shear wave attenuation. Finally, by applying the cylindrical correction G' and G″ images were generated in heterogeneous phantoms and a preliminary in vivo feasibility study was carried out in the human liver.

Tumor stiffening, stemming from aberrant production and organization of extracellular matrix (ECM), has been considered a predictive marker of tumor malignancy, non-invasively assessed by ultrasound shear wave elastography (SWE). Being more than a passive marker, tumor stiffening restricts the delivery of diagnostic and therapeutic agents to the tumor and per se could modulate cellular mechano-signaling, tissue inflammation and tumor progression. Current strategies to modify the tumor extracellular matrix are based on ECM-targeting chemical agents but also showed deleterious systemic effects. On-demand excitable nanomaterials have shown their ability to perturb the tumor microenvironment in a spatiotemporal-controlled manner and synergistically with chemotherapy. Here, we investigated the evolution of tumor stiffness as well as tumor integrity and progression, under the effect of mild hyperthermia and thermal ablation generated by light-exposed multi-walled carbon nanotubes (MWCNTs) in an epidermoid carcinoma mouse xenograft. SWE was used for real-time mapping of the tumor stiffness, both during the two near infrared irradiation sessions and over the days after the treatment. We observed a transient and reversible stiffening of the tumor tissue during laser irradiation, which was lowered at the second session of mild hyperthermia or photoablation. In contrast, over the days following photothermal treatment, the treated tumors exhibited a significant softening together with volume reduction, whereas non-treated growing tumors showed an increase of tumor rigidity. The organization of the collagen matrix and the distribution of CNTs revealed a spatio-temporal correlation between the presence of nanoheaters and the damages on collagen and cells. This study highlights nanohyperthermia as a promising adjuvant strategy to reverse tumor stiffening and normalize the mechanical tumor environment., Competing Interests: The authors have declared that no competing interest exists.

Purpose  Firstly to evaluate the feasibility and diagnostic performance of three-dimensional (3 D) shear wave elastography (SWE) volume measurements in patients with breast lesions compared to breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) lesion volumes and 3D-US B-mode volumes. Secondly to assess the treatment monitoring performance of 3D-SWE in patients under neoadjuvant chemotherapy for breast cancer by comparing it to 3D-US lesion volume. Materials and Methods  This prospective study was approved by the institutional review board. Informed consent was provided. 33 patients with 33 lesions were included. The feasibility of 3D-SWE was evaluated in 23 patients. In the 10 remaining patients receiving neoadjuvant chemotherapy, 3D-SWE was evaluated before and during treatment. Tumor volume and qualitative and quantitative elasticity analysis measurements were performed and compared to the tumor volume as estimated by 3D-US and DCE-MRI. Statistical analysis was performed using the Pearson correlation coefficient. Results  3D-SWE was feasible in patients with breast lesions. Tumor volume calculated with 3D-US and 3D-SWE showed very good and moderate concordances with DCE-MRI volume, respectively (Pearson correlation coefficients equal to ρ = r = 0.88, p < 0.00 002 and ρ = r = 0.5, p = 0.32, respectively). Modification of tumor elasticity and heterogeneity was correlated with response to treatment. In good responders, elasticity and elasticity heterogeneity diminished. Conclusion  Tumor 3D-US volume measurements showed very good concordance with DCE-MRI volume. 3D-SWE can provide valuable information: reduction of tissue stiffness during treatment could be a potential indicator of response. These preliminary results should be confirmed on a larger number of patients., (© Georg Thieme Verlag KG Stuttgart · New York.)

In recent years, several novel ultrasound (US)-based techniques have emerged for kidney diagnostic imaging, including tissue stiffness assessment with elastography, Ultrasensitive Doppler techniques, and contrast-enhanced ultrasonography to assess renal microvascularization. Renal elastography has become available with the development of noninvasive quantitative techniques, following the rapidly growing field of liver fibrosis diagnosis. With the increased incidence of chronic kidney disease, noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application of US elastography from one organ to the other due to anatomic and technical issues. Today, renal elastography appears to be a promising application that, however, still requires optimization and validation. New ultrasensitive Doppler techniques improve the detection of slow blood flow and can be used alone or after administration of US contrast agents. These microbubble-based agents are extremely well tolerated and can be administered even in cases of impaired renal function. Despite the lack of approval, they improve the characterization of atypical renal masses, complex cystic renal masses, and peripheral vascular disorders. Dynamic contrast-enhanced US is based on quantification of the signal intensity from region of interest and mathematical fits of the time-intensity curves. Perfusion-related parameters can be extracted for the monitoring of vascular changes in the renal parenchyma and in tumors in order to evaluate drug response. This estimation of renal perfusion depends on many parameters that should be kept constant for follow-up studies, and, when possible, an internal reference should be used to normalize the measurements., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Purpose: Objective Shear wave elastography (SWE) enabled living tissue assessment of stiffness. This is routinely used for breast, thyroid and liver diseases, but there is currently no data for the brain. We aim to characterize elasticity of normal brain parenchyma and brain tumors using SWE. Materials and Methods: Patients with scheduled brain tumor removal were included in this study. In addition to standard ultrasonography, intraoperative SWE using an ultrafast ultrasonic device was used to measure the elasticity of each tumor and its surrounding normal brain. Data were collected by an investigator blinded to the diagnosis. Descriptive statistics, box plot analysis as well as intraoperator and interoperator reproducibility analysis were also performed. Results: 63 patients were included and classified into four main types of tumor: meningiomas, low-grade gliomas, high-grade gliomas and metastasis. Young's Modulus measured by SWE has given new insight to differentiate brain tumors: 33.1 ± 5.9 kPa, 23.7 ± 4.9 kPa, 11.4 ± 3.6 kPa and 16.7 ± 2.5 kPa, respectively, for the four subgroups. Normal brain tissue has been characterized by a reproducible mean stiffness of 7.3 ± 2.1 kPa. Moreover, low-grade glioma stiffness is different from high-grade glioma stiffness (p = 0.01) and normal brain stiffness is very different from low-grade gliomas stiffness (p < 0.01). Conclusion: This study demonstrates that there are significant differences in elasticity among the most common types of brain tumors. With intraoperative SWE, neurosurgeons may have innovative information to predict diagnosis and guide their resection., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: Due to limitations of classic imaging approaches, the internal response of abdominal organs is difficult to observe during an impact. Within the context of impact biomechanics for the protection of the occupant of transports, this could be an issue for human model validation and injury prediction., Methods: In the current study, a previously developed technique (ultrafast ultrasound imaging) was used as the basis to develop a protocol to observe the internal response of abdominal organs in situ at high imaging rates. The protocol was applied to 3 postmortem human surrogates to observe the liver and the colon during impacts delivered to the abdomen., Results: The results show the sensitivity of the liver motion to the impact location. Compression of the colon was also quantified and compared to the abdominal compression., Conclusions: These results illustrate the feasibility of the approach. Further tests and comparisons with simulations are under preparation.

This paper investigated the feasibility of using supersonic shear wave measurements to quantitatively differentiate normal and damaged tendons based on their mechanical properties. Five freshly harvested porcine tendons excised from pig legs were used. Tendon damage was induced by incubating the tendons with a 1% w/v collagenase solution. Values of shear modulus were derived both by a time-of-flight (TOF) approach and a transverse isotropic plate model (TI-model). The results show that as the preload applied to the tendon increased from 0 to 3 N, the mean shear modulus derived based on the TOF approach, the TI-model, and Young's modulus estimated from mechanical testing increased from 14.6 to 89.9 kPa, 53.9 to 348 kPa, and from 1.45 to 10.36 MPa, respectively, in untreated tendons, and from 8.4 to 67 kPa, 28 to 258 kPa, and from 0.93 to 7.2 MPa in collagenase-treated tendons. Both the TOF approach and the TI-model correlated well with the changes in Young's modulus. Although there is bias on the estimation of shear modulus using the TOF approach, it still provides statistical significance to differentiate normal and damaged tendons. Our data indicate that supersonic shear wave imaging is a valuable imaging technique to assess tendon stiffness dynamics and characterize normal and collagenase-damaged tendons.

The evaluation of muscle and joint forces in vivo is still a challenge. Musculo-Skeletal (musculo-skeletal) models are used to compute forces based on movement analysis. Most of them are built from a scaled-generic model based on cadaver measurements, which provides a low level of personalization, or from Magnetic Resonance Images, which provide a personalized model in lying position. This study proposed an original two steps method to access a subject-specific musculo-skeletal model in 30 min, which is based solely on biplanar X-Rays. First, the subject-specific 3D geometry of bones and skin envelopes were reconstructed from biplanar X-Rays radiography. Then, 2200 corresponding control points were identified between a reference model and the subject-specific X-Rays model. Finally, the shape of 21 lower limb muscles was estimated using a non-linear transformation between the control points in order to fit the muscle shape of the reference model to the X-Rays model. Twelfth musculo-skeletal models were reconstructed and compared to their reference. The muscle volume was not accurately estimated with a standard deviation (SD) ranging from 10 to 68%. However, this method provided an accurate estimation the muscle line of action with a SD of the length difference lower than 2% and a positioning error lower than 20 mm. The moment arm was also well estimated with SD lower than 15% for most muscle, which was significantly better than scaled-generic model for most muscle. This method open the way to a quick modeling method for gait analysis based on biplanar radiography.

Renal elastography has become available with the development of noninvasive quantitative techniques (including shear-wave elastography), following the rapidly growing field of diagnosis and quantification of liver fibrosis, which has a demonstrated major clinical impact. Ultrasound or even magnetic resonance techniques are leaving the pure research area to reach the routine clinical use. With the increased incidence of chronic kidney disease and its specific morbidity and mortality, the noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application from one organ to the other due to a large number of anatomical and technical issues. Indeed, the kidney exhibits various features that make stiffness assessment more complex, such as the presence of various tissue types (cortex, medulla), high spatial orientation (anisotropy), local blood flow, fatty sinus with variable volume and echotexture, perirenal space with variable fatty content, and the variable depth of the organ. Furthermore, the stiffness changes of the renal parenchyma are not exclusively related to fibrosis, as renal perfusion or hydronephrosis will impact the local elasticity. Renal elastography might be able to diagnose acute or chronic obstruction, or to renal tumor or pseudotumor characterization. Today, renal elastography appears as a promising application that still requires optimization and validation, which is the contrary for liver stiffness assessment., (Copyright © 2016 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

Objectives: Intervertebral disc (IVD) is key to spine biomechanics, and it is often involved in the cascade leading to spinal deformities such as idiopathic scoliosis, especially during the growth spurt. Recent progress in elastography techniques allows access to non-invasive measurement of cervical IVD in adults; the aim of this study was to determine the feasibility and reliability of shear wave elastography in healthy children lumbar IVD., Methods: Elastography measurements were performed in 31 healthy children (6-17 years old), in the annulus fibrosus and in the transverse plane of L5-S1 or L4-L5 IVD. Reliability was determined by three experienced operators repeating measurements., Results: Average shear wave speed in IVD was 2.9 ± 0.5 m/s; no significant correlations were observed with sex, age or body morphology. Intra-operator repeatability was 5.0 % while inter-operator reproducibility was 6.2 %. Intraclass correlation coefficient was higher than 0.9 for each operator., Conclusions: Feasibility and reliability of IVD shear wave elastography were demonstrated. The measurement protocol is compatible with clinical routine and the results show the method's potential to give an insight into spine deformity progression and early detection., Key Points: • Intervertebral disc mechanical properties are key to spine biomechanics • Feasibility of shear wave elastography in children lumbar disc was assessed • Measurement was fast and reliable • Elastography could represent a novel biomarker for spine pathologies.

Our objective was to determine if supersonic shear wave elastography (SSWE) can detect changes in stiffness of a breast cancer model under therapy. A human invasive carcinoma was implanted in 22 mice. Eleven were treated with an anti-angiogenic therapy and 11 with glucose for 24 d. Tumor volume and stiffness were assessed during 2 wk before treatment and 0, 7, 12, 20 and 24 d after the start of therapy using SSWE. Pathology was assessed after 12 and 24 d of treatment. We found that response to therapy was associated with early softening of treated tumors only, resulting in a significant difference from non-treated tumors after 12 d of treatment (p = 0.03). On pathology, large areas of necrosis were observed at 12 d in treated tumors. Although treatment was still effective, treated tumors subsequently stiffened during a second phase of the treatment (days 12-24), with a small amount of necrosis observed on pathology on day 24. In conclusion, SSWE was able to measure changes in the stiffness of tumors in response to anti-cancer treatment. However, stiffness changes associated with good response to treatment may change over time, and increased stiffness may also reflect therapy efficacy., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

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.

Due to multiple light scattering inside biological tissues, deep non-invasive optical medical imaging is very challenging. Acousto-optic imaging is a technique coupling ultrasound and light that allows recovering optical contrast at depths of few centimeters with a millimeter resolution. Recent advances in acousto-optic imaging are using short focused ultrasound pulses often averaged over several hundred or thousand pulses. As the pulsing rate of commercial probes is limited to about few ultrasound cycles every 100 μs, acquiring an acousto-optic image usually takes several tens of seconds due to the high number of acoustic pulses excitation. We propose here a new acousto-optic imaging technique based on the use of ultrasound plane waves instead of focused ones that allows increasing drastically the imaging rate.

4D ultrasound microvascular imaging was demonstrated by applying ultrafast Doppler tomography (UFD-T) to the imaging of brain hemodynamics in rodents. In vivo real-time imaging of the rat brain was performed using ultrasonic plane wave transmissions at very high frame rates (18,000 frames per second). Such ultrafast frame rates allow for highly sensitive and wide-field-of-view 2D Doppler imaging of blood vessels far beyond conventional ultrasonography. Voxel anisotropy (100 μm × 100 μm × 500 μm) was corrected for by using a tomographic approach, which consisted of ultrafast acquisitions repeated for different imaging plane orientations over multiple cardiac cycles. UFT-D allows for 4D dynamic microvascular imaging of deep-seated vasculature (up to 20 mm) with a very high 4D resolution (respectively 100 μm × 100 μm × 100 μm and 10 ms) and high sensitivity to flow in small vessels (>1 mm/s) for a whole-brain imaging technique without requiring any contrast agent. 4D ultrasound microvascular imaging in vivo could become a valuable tool for the study of brain hemodynamics, such as cerebral flow autoregulation or vascular remodeling after ischemic stroke recovery, and, more generally, tumor vasculature response to therapeutic treatment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the feasibility of using supersonic shear-wave elastography (SSWE) in children and normal values of liver stiffness with the use of control patients of different ages (from neonates to teenagers) and the diagnostic accuracy of supersonic shear wave elastography for assessing liver fibrosis by using the histologic scoring system as the reference method in patients with liver disease, with a special concern for early stages of fibrosis., Materials and Methods: The institutional review board approved this prospective study. Informed consent was obtained from parents and children older than 7 years. First, 51 healthy children (from neonate to 15 years) were analyzed as the control group, and univariate and multivariate comparisons were performed to study the effect of age, transducer, breathing condition, probe, and position on elasticity values. Next, 45 children (from 1 month to 17.2 years old) who underwent liver biopsy were analyzed. SSWE measurements were obtained in the same region of the liver as the biopsy specimens. Biopsy specimens were reviewed in a blinded manner by a pathologist with the use of METAVIR criteria. The areas under the receiver operating characteristics curve (AUCs) were calculated for patients with fibrosis stage F0 versus those with stage F1-F2, F2 or higher, F3 or higher, and F4 or higher., Results: A successful rate of SSWE measurement was 100% in 96 patients, including neonates. Liver stiffness values were significantly higher when an SC6-1 probe (Aixplorer; SuperSonic Imagine SA, Aix-enProvence, France) was used than when an SL15-4 probe (Aixplorer) was used (mean ± standard deviation, 6.94 kPa ± 1.42 vs 5.96 kPa ± 1.31; P = .006). There was no influence of sex, the location of measurement, or respiratory status on liver elasticity values (P = .41-.93), although the power to detect such a difference was low. According to the degree of liver fibrosis at liver biopsy, 88.5%-96.8% of patients were correctly classified, with AUCs of 0.90-0.98 (95% confidence interval [CI]: 0.8, 1.0). The AUC for patients with stage F0 versus stage F1-F2 was 0.93 (95% CI: 0.87, 0.99)., Conclusion: SSWE allows accurate assessment of liver fibrosis, even in children with early stage (F1-F2) disease, and the choice of transducer influences liver stiffness values., (© RSNA, 2015.)

Breast cancer detection in the early stages is of great importance since the prognosis, and the treatment depends more on this. Multiple techniques relying on the mechanical properties of soft tissues have been developed to help in early detection. In this study, we implemented a technique that measures the nonlinear shear modulus (NLSM) (μ(NL)) in vivo and showed its utility to detect breast lesions from healthy tissue. The technique relies on the acoustoelasticity theory in quasi-incompressible media. In order to recover μ(NL), static elastography and supersonic shear imaging are combined to subsequently register strain maps and shear modulus maps while the medium is compressed. Then, μ(NL) can be recovered from the relationship between the stress, deduced from strain maps, and the shear modulus. For this study, a series of five nonlinear phantoms were built using biological tissue (pork liver) inclusions immersed in an agar-gelatin gel. Furthermore, 11 in vivo acquisitions were performed to characterize the NLSM of breast tissue. The phantom results showed a very good differentiation of the liver inclusions when measuring μ(NL) with a mean value of -114.1 kPa compared to -34.7 kPa for the gelatin. Meanwhile, values for the shear modulus for the liver and the gelatin were very similar, 3.7 and 3.4 kPa, respectively. In vivo NLSM mean value for the healthy breast tissue was of -95 kPa, while mean values of the benign and the malignant lesions were -619 and -806 kPa with a strong v ariability, respectively. This study shows the potential of the acoustoelasticity theory in quasi-incompressible medium to bring a new parameter for breast cancer diagnosis.

The quantitative assessment of the cervix is crucial for the estimation of pre-term delivery risk and the prediction of the success of labor induction. We conducted a cross-sectional study using shear wave elastography based on the supersonic shear imaging technique. The shear wave speed (SWS) of the lower anterior part of the cervix was quantified over an 8-mm region of interest in 157 pregnant women. Cervical SWS is slightly but significantly reduced in patients diagnosed with pre-term labor and in patients who actually delivered pre-term., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

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.

Objective: To compare placental elasticity in normal versus intrauterine growth restriction (IUGR) murine pregnancies using shear wave elastography (SWE)., Methods: Intrauterine growth restriction was created by ligation of the left uterine artery of Sprague-Dawley rats on E17. Ultrasonography (US) and elastography were performed 2 days later on exteriorized horns after laparotomy. Biparietal diameter (BPD) and abdominal diameter (AD) were measured and compared in each horn. Placental elasticity of each placenta was compared in the right and left horns, respectively, using the Young's modulus, which increases with increasing stiffness of the tissue., Results: Two hundred seventeen feto-placental units from 18 rats were included. Fetuses in the left ligated horn had smaller biometric measurements than those in the right horn (6.7 vs 7.2 mm, p < 0.001, and 9.2 vs 11.2 mm, p < 0.001 for BPD and AD, respectively). Mean fetal weight was lower in the pups from the left than the right horn (1.65 vs 2.11 g; p < 0.001). Mean (SD) Young's modulus was higher for placentas from the left than the right horn (11.7 ± 1.5 kPa vs 8.01 ± 3.8 kPa, respectively; p < 0.001), indicating increased stiffness in placentas from the left than the right horn. There was an inverse relationship between fetal weight and placental elasticity (r = 0.42; p < 0.001)., Conclusion: Shear wave elastography may be used to provide quantitative elasticity measurements of the placenta. In our model, placentas from IUGR fetuses demonstrated greater stiffness, which correlated with the degree of fetal growth restriction., (© 2015 John Wiley & Sons, Ltd.)

Development of shear wave elastography gave access to non-invasive muscle stiffness assessment in vivo. The aim of the present study was to define a measurement protocol to be used in clinical routine for quantifying the shear modulus of lower limb muscles. Four positions were defined to evaluate shear modulus in 10 healthy subjects: parallel to the fibers, in the anterior and posterior aspects of the lower limb, at rest and during passive stretching. Reliability was first evaluated on two muscles by three operators; these measurements were repeated six times. Then, measurement reliability was compared in 11 muscles by two operators; these measurements were repeated three times. Reproducibility of shear modulus was 0.48 kPa and repeatability was 0.41 kPa, with all muscles pooled. Position did not significantly influence reliability. Shear wave elastography appeared to be an appropriate and reliable tool to evaluate the shear modulus of lower limb muscles with the proposed protocol., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

We developed an integrated experimental framework that extends the brain exploration capabilities of functional ultrasound imaging to awake and mobile rats. In addition to acquiring hemodynamic data, this method further allows parallel access to electroencephalography (EEG) recordings of neuronal activity. We illustrate this approach with two proofs of concept: a behavioral study on theta rhythm activation in a maze running task and a disease-related study on spontaneous epileptic seizures.

Ultrafast Doppler imaging was introduced as a technique to quantify blood flow in an entire 2-D field of view, expanding the field of application of ultrasound imaging to the highly sensitive anatomical and functional mapping of blood vessels. We have recently developed 3-D ultrafast ultrasound imaging, a technique that can produce thousands of ultrasound volumes per second, based on a 3-D plane and diverging wave emissions, and demonstrated its clinical feasibility in human subjects in vivo. In this study, we show that noninvasive 3-D ultrafast power Doppler, pulsed Doppler, and color Doppler imaging can be used to perform imaging of blood vessels in humans when using coherent compounding of 3-D tilted plane waves. A customized, programmable, 1024-channel ultrasound system was designed to perform 3-D ultrafast imaging. Using a 32 × 32, 3-MHz matrix phased array (Vermon, Tours, France), volumes were beamformed by coherently compounding successive tilted plane wave emissions. Doppler processing was then applied in a voxel-wise fashion. The proof of principle of 3-D ultrafast power Doppler imaging was first performed by imaging Tygon tubes of various diameters, and in vivo feasibility was demonstrated by imaging small vessels in the human thyroid. Simultaneous 3-D color and pulsed Doppler imaging using compounded emissions were also applied in the carotid artery and the jugular vein in one healthy volunteer.

A protocol based on ultrafast ultrasonography was developed to study the internal response of isolated perfused human (n=3) and porcine (n=11) kidneys subjected to loading at 0.003 m/s and 0.3m/s respectively. Regional uniaxial strains were calculated based on natural target tracking. The effect of loading speed and regional differences could be statistically detected on the porcine specimens. However, despite the inhomogeneity of their anatomical structures, strains' responses appeared relatively homogeneous at 0.3m/s in both porcine and human kidneys. Failure, identified as a sudden change on the ultrasonography movie, also appeared at similar compression levels for both species (38.3% of applied strain in average for human and 35.8% of applied strain in average for porcine)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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. 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(+)Apc(+/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 in vivo, 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.

Estimation of individual muscle force remains one of the main challenges in biomechanics. This review presents a series of experiments that used ultrasound shear wave elastography to support the hypothesis that muscle stiffness is linearly related to both active and passive muscle forces. Examples of studies that used measurement of muscle stiffness to estimate changes in muscle force are presented.

Over the last ten years, shear wave elastography (SWE) has seen considerable development and is now routinely used in clinics to provide mechanical characterization of tissues to improve diagnosis. The most advanced technique relies on the use of an ultrafast scanner to generate and image shear waves in real time in a 2-D plane at several thousands of frames per second. We have recently introduced 3-D ultrafast ultrasound imaging to acquire with matrix probes the 3-D propagation of shear waves generated by a dedicated radiation pressure transducer in a single acquisition. In this study, we demonstrate 3-D SWE based on ultrafast volumetric imaging in a clinically applicable configuration. A 32 × 32 matrix phased array driven by a customized, programmable, 1024-channel ultrasound system was designed to perform 4-D shear-wave imaging. A matrix phased array was used to generate and control in 3-D the shear waves inside the medium using the acoustic radiation force. The same matrix array was used with 3-D coherent plane wave compounding to perform high-quality ultrafast imaging of the shear wave propagation. Volumetric ultrafast acquisitions were then beamformed in 3-D using a delay-and-sum algorithm. 3-D volumetric maps of the shear modulus were reconstructed using a time-of-flight algorithm based on local multiscale cross-correlation of shear wave profiles in the three main directions using directional filters. Results are first presented in an isotropic homogeneous and elastic breast phantom. Then, a full 3-D stiffness reconstruction of the breast was performed in vivo on healthy volunteers. This new full 3-D ultrafast ultrasound system paves the way toward real-time 3-D SWE.

The generation of shear waves from an ultrasound focused beam has been developed as a major concept for remote palpation using shear wave elastography (SWE). For muscular diagnostic applications, characteristics of the shear wave profile will strongly depend on characteristics of the transducer as well as the orientation of muscular fibers and the tissue viscoelastic properties. The numerical simulation of shear waves generated from a specific probe in an anisotropic viscoelastic medium is a key issue for further developments of SWE in fibrous soft tissues. In this study we propose a complete numerical tool allowing 3D simulation of a shear wave front in anisotropic viscoelastic media. From the description of an ultrasonic transducer, the shear wave source is simulated by using Field's II software and shear wave propagation described by using the Green's formalism. Finally, the comparison between simulations and experiments are successively performed for both shear wave velocity and dispersion profile in a transverse isotropic hydrogel phantom, in vivo forearm muscle and in vivo biceps brachii.

Biological tissues are very strong light-scattering media. As a consequence, current medical imaging devices do not allow deep optical imaging unless invasive techniques are used. Acousto-optic imaging is a light-ultrasound coupling technique that takes advantage of the ballistic propagation of ultrasound in biological tissues to access optical contrast with a millimeter resolution. We have developed a photorefractive-crystal-based system that performs self-adaptive wavefront holography and works within the optical therapeutic window. As it works at an appropriate wavelength range for biological tissues imaging, it was tested on ex vivo liver samples containing tumors as a pre-clinical study. Optical contrast was obtained even if acoustical one was not significant. Ultrasound image (left) and acousto-optic image (right) of a liver biopsy with tumors. Acousto-optic imaging exhibits tumors that are not detected through ultrasound., (© 2014 The Authors. Journal of Biophotonics published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background & Aims: Quantitative shear wave elastography was shown to be an effective tool for the non-invasive diagnosis and staging of chronic liver diseases. The liver shear modulus, estimated from the propagation velocity of shear waves, is correlated to the degree of fibrosis and can therefore be used for the non-invasive staging of fibrosis., Methods: We performed a clinical prospective study in a total of 120 patients with various chronic liver diseases to compare the accuracy of supersonic shear imaging (SSI), a technique based on acoustic radiation and ultrafast ultrasound imaging, to 1D transient elastography (FibroScan) for the staging and grading of fibrosis as assessed by liver biopsy. Since shear wave propagation spectroscopy can also provide additional mechanical information on soft tissues, such as viscosity, we also investigated those new mechanical parameters as possible predictors of fibrosis, steatosis, and disease activity., Results: SSI was successfully performed in 98.3% of patients and it was shown to be as accurate as FibroScan for the staging of fibrosis both for the whole population (N=120) and for the subgroup with viral hepatitis (n=70) (AUC=0.85 [0.77-0.96] and 0.89 [0.81-0.97] for significant fibrosis, AUC=0.90 [0.83-0.97] and 0.87 [0.75-0.98] for cirrhosis, with respect to SSI [n=68/70] and FibroScan [n=66/68]). Viscosity could also be used to stage the degree of fibrosis (AUC=0.76 [0.64-0.87] for significant fibrosis and AUC=0.87 [0.74-0.99] for cirrhosis), for the subgroup of patients with viral hepatitis (n=67/70) but was a poor predictor of disease activity and steatosis levels., Conclusions: Supersonic shear imaging is a robust technique for the staging of liver fibrosis. Liver viscosity was found to be correlated with fibrosis but not to steatosis or disease activity., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Very little is known about the myometrium's physiology in terms of its elasticity but shear wave elastography could be an efficient tool to better understand it. This could considerably help the prevention of difficult births, the consequences of which are tremendous for neonate morbidity and pathologies. The purpose of this paper is to show the feasibility of the in vivo monitoring of myometrial stiffness changes in contraction and relaxation during pregnancy. In this study, Supersonic Shear Wave Imaging, a real-time and quantitative imaging technique that has been proven efficient for the investigation of tissue elasticity, was used to quantify the uterus shear-wave speed and stiffness in 6 patients, through the abdomen, using an 8-MHz linear ultrasound probe. Changes in shear wave speed were tracked in real time during the uterine contraction and were well correlated with the uterine pressure, which is currently considered to be a gold standard. These results open a new way to better understand the myometrium contraction during labour., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Eleven fresh ex vivo porcine kidneys were perfused in the artery, vein and ureter with degassed Dulbecco׳s Modified Eagle Medium (DMEM). The effect of perfusion pressure was evaluated using ten different pressures combinations. The shear modulus of the tissues was estimated during perfusion using shear wave elastography. The organ weight change was measured by a digital scale and cameras were used to follow the changes of the dimensions after each pressure combination. The effect of perfusion on the weight and the thickness was non-reversible, whereas the effect on the shear modulus was reversible. Pressure was found to increase the average shear modulus in the cortex by as much as 73%. A pressure of 80 mmHg was needed to observe tissues shear modulus in the same range as in vivo tests (Gcortex=9.1 kPa, Gmedulla=8.5 kPa ex vivo versus Gcortex=9.1 kPa, Gmedulla=8.7 kPa in vivo in Gennisson et al., 2012)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: Although magnetic resonance is widely spread to assess qualitatively disc morphology, a simple method to determine reliably intervertebral disc status is still lacking. Shear wave elastography is a novel technique that allows quantitative evaluation of soft-tissues' mechanical properties. The aim of this study was to assess preliminary the feasibility and reliability of mechanical characterization of cervical intervertebral discs by elastography and to provide first reference values for asymptomatic subjects., Methods: Elastographic measurements were performed to determine shear wave speed (SWS) in C6-C7 or C7-T1 disc of 47 subjects; repeatability and inter-operator reproducibility were assessed., Results: Global average shear wave speed (SWS) was 3.0 ± 0.4 m/s; measurement repeatability and inter-user reproducibility were 7 and 10%, respectively. SWS was correlated with both subject's age (p = 1.3 × 10(-5)) and body mass index (p = 0.008)., Conclusions: Shear wave elastography in intervertebral discs proved reliable and allowed stratification of subjects according to age and BMI. Applications could be relevant, for instance, in early detection of disc degeneration or in follow-up after trauma; these results open the way to larger cohort studies to define the place of this technique in routine intervertebral disc assessment., Key Points: A simple method to obtain objectively intervertebral disc status is still lacking. Shear wave elastography was applied in vivo to assess intervertebral discs. Elastography showed promising results in biomechanical disc evaluation. Elastography could be relevant in clinical routine for intervertebral disc assessment.

Shear wave elastography imaging techniques provide quantitative measurement of soft tissues elastic properties. Tendons, muscles and cerebral tissues are composed of fibers, which induce a strong anisotropic effect on the mechanical behavior. Currently, these tissues cannot be accurately represented by existing elastography phantoms. Recently, a novel approach for orthotropic hydrogel mimicking soft tissues has been developed (Millon et al 2006 J. Biomed. Mater. Res. B 305-11). The mechanical anisotropy is induced in a polyvinyl alcohol (PVA) cryogel by stretching the physical crosslinks of the polymeric chains while undergoing freeze/thaw cycles. In the present study we propose an original multimodality imaging characterization of this new transverse isotropic (TI) PVA hydrogel. Multiple properties were investigated using a large variety of techniques at different scales compared with an isotropic PVA hydrogel undergoing similar imaging and rheology protocols. The anisotropic mechanical (dynamic and static) properties were studied using supersonic shear wave imaging technique, full-field optical coherence tomography (FFOCT) strain imaging and classical linear rheometry using dynamic mechanical analysis. The anisotropic optical and ultrasonic spatial coherence properties were measured by FFOCT volumetric imaging and backscatter tensor imaging, respectively. Correlation of mechanical and optical properties demonstrates the complementarity of these techniques for the study of anisotropy on a multi-scale range as well as the potential of this TI phantom as fibrous tissue-mimicking phantom for shear wave elastographic applications.

Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in 3D based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32  ×  32 matrix-array probe. Its ability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3D Shear-Wave Imaging, 3D Ultrafast Doppler Imaging, and, finally, 3D Ultrafast combined Tissue and Flow Doppler Imaging. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3D Ultrafast Doppler was used to obtain 3D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, at thousands of volumes per second, the complex 3D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, as well as the 3D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3D Ultrafast Ultrasound Imaging for the 3D mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra--and inter-observer variability.

Shear shock waves in soft solids, such as in tissue, have different regions of complex motion that can change rapidly across a single wave profile, especially at the shock front. Conventional tracking algorithms are not well adapted to the task of simultaneously tracking the discontinuous shock front and smooth regions away from the shock. An adaptive algorithm based on the normalized cross-correlation and a correlation-weighted median filter is presented. The proposed adaptive algorithm combines two features: first, it adapts the window size to optimize the correlation value based on the deformation, and second, it rejects inaccurate estimates with a median-weighted filter. For simulated ultrasound data, where the displacements are known, it is shown that the estimated velocity error for the adaptive algorithm is less than 1/3 of the error for non-adaptive normalized cross-correlation. The addition of the weighted median filter to the adaptive algorithm significantly improves the shock tracking performance. The shock position and rise-time error is almost an order of magnitude better with the median-weighted filter. This algorithm is then used to track shock wave propagation with data acquired by a high-frame-rate ultrasound scanner in a tissue-mimicking agar and gelatin phantom. The shock front is not resolved with conventional algorithms but it is clearly visible with the proposed adaptive median-weighted algorithm.

Patient-specific numerical simulation of the spine is a useful tool both in clinic and research. While geometrical personalization of the spine is no more an issue, thanks to recent technological advances, non-invasive personalization of soft tissue's mechanical properties remains a challenge. Ultrasound elastography is a relatively recent measurement technique allowing the evaluation of soft tissue's elastic modulus through the measurement of shear wave speed. The aim of this study was to determine the feasibility of elastographic measurements in intervertebral disc. An in vitro approach was chosen to test the hypothesis that shear wave speed can be used to evaluate intervertebral disc mechanical properties and to assess measurement repeatability. In total, 11 oxtail intervertebral discs were tested in compression to determine their stiffness and apparent elastic modulus at rest and at 400 N. Elastographic measurements were performed in these two conditions and compared to these mechanical parameters. The protocol was repeated six times to determine elastographic measurement repeatability. Average shear wave speed over all samples was 5.3 ± 1.0 m/s, with a repeatability of 7% at rest and 4.6% at 400 N; stiffness and apparent elastic modulus were 266.3 ± 70.5 N/mm and 5.4 ± 1.1 MPa at rest, respectively, while at 400 N they were 781.0 ± 153.8 N/mm and 13.2 ± 2.4 MPa, respectively. Correlations were found between elastographic measurements and intervertebral disc mechanical properties; these preliminary results are promising for further in vivo application., (© IMechE 2014.)

Shear wave elastography helps physicians to characterize pathologies by assessing biomechanical properties of soft tissues. Compared with classical rheology, these techniques allow the quantification of the mechanical properties of tissues in the frequency range of hundreds of hertz. In this paper, ultrasound elastographic measurements and classical rheology are compared over a frequency range spanning five orders of magnitude [0.01 to 1200 Hz] to characterize model gels at multiple scales. Hybrid hydrogels were specially synthesized to get a fine tuning of the material dissipative response. Strain-controlled rheology (SCR) experiments were performed to get the elastic moduli G" and loss moduli G" from 0.01 Hz to 10 Hz and were confirmed by tensile tests. Transient elastography (TE from 50 to 400 Hz) and supersonic shear imaging (SSI from 200 to 1200 Hz) were used to characterize polymers at high frequency. Two different hydrogels were tested in the ultrasound setup with different concentration of scatterers. From low-frequency measurements, elastic moduli were extrapolated at high frequency and a very good correlation was obtained between SCR and TE and between SCR and SSI (r = 0.92 and r = 0.95, respectively). This paper demonstrates the capability of shear wave elastography to accurately image rheological properties of soft tissues, to differentiate soft elastic domains from viscous ones. It also gives new insights into soft material science because it provides a rheological tool in a high-frequency domain complementary to conventional rheometry.

Purpose: To assess corneal stiffening with supersonic shear wave imaging (SSI) technology in an experimental model of iontophoresis-assisted transepithelial corneal collagen cross-linking (I-CXL)., Methods: Six rabbits underwent full, central I-CXL in one eye. The contralateral eye served as control. In vivo iontophoresis was used for 10 minutes to perform transepithelial delivery of riboflavin prior to UV-A irradiation. Accelerated UV-A protocol was applied for 9 minutes with a 10-mW/cm(2) irradiance. Animals were killed and both treated and control corneas were then immediately mounted on a corneal artificial anterior chamber and internal pressure was varied from 15 to 50 mm Hg in 5-mm Hg increments. Swelling was evaluated via central corneal thickness measurements. Ex vivo inflation tests were monitored using SSI technology that provides real-time mapping of the corneal elasticity., Results: Corneal yellowing of the central 9-mm diameter area was clearly visible in the iontophoresis area of all treated eyes. Elasticity versus internal pressure revealed significant differences of the change in elasticity coefficient with pressure between I-CXL-treated and control corneas with a mean slope that was 27.1 and 16.9 kPa/mm Hg, respectively (P = 0.029). Differences in elasticity at individual pressure levels between groups were statistically significant above 40 mm Hg (P < 0.05)., Conclusions: Intraocular pressure variations were the most important limitations for in vivo stiffness monitoring with SSI because stiffness is a function of internal pressure. Supersonic shear wave imaging succeeded in comparing corneas that underwent I-CXL by performing ex vivo inflation tests where pressure was controlled. Iontophoresis-assisted transepithelial corneal collagen cross-linking corneas exhibited increased resistance to pressure rise, indicating stiffening. In vivo I-CXL and ex vivo SSI is an interesting model to evaluate the sole effect of photopolymerization occurring in the CXL process close to physiological conditions.

Non-invasive evaluation of the Achilles tendon elastic properties may enhance diagnosis of tendon injury and the assessment of recovery treatments. Shear wave elastography has shown to be a powerful tool to estimate tissue mechanical properties. However, its applicability to quantitatively evaluate tendon stiffness is limited by the understanding of the physics on the shear wave propagation in such a complex medium. First, tendon tissue is transverse isotropic. Second, tendons are characterized by a marked stiffness in the 400 to 1300 kPa range (i.e. fast shear waves). Hence, the shear wavelengths are greater than the tendon thickness leading to guided wave propagation. Thus, to better understand shear wave propagation in tendons and consequently to properly estimate its mechanical properties, a dispersion analysis is required. In this study, shear wave velocity dispersion was measured in vivo in ten Achilles tendons parallel and perpendicular to the tendon fibre orientation. By modelling the tendon as a transverse isotropic viscoelastic plate immersed in fluid it was possible to fully describe the experimental data (deviation<1.4%). We show that parallel to fibres the shear wave velocity dispersion is not influenced by viscosity, while it is perpendicularly to fibres. Elasticity (found to be in the range from 473 to 1537 kPa) and viscosity (found to be in the range from 1.7 to 4 Pa.s) values were retrieved from the model in good agreement with reported results.

The objective of this study was to evaluate the effects of different conservation techniques on the mechanical properties of the ex vivo porcine kidney in order to select an appropriate conservation protocol to use prior to mechanical testing. Five groups of eight kidneys each were subjected to different methods of conservation: storage at 4°C, -18°C, -34°C and -71°C, for 7 days, or storage at 20°C for 2 days only (as the tissues degraded quickly). Their shear modulus as a function of depth in the organ was evaluated before (fresh) and after conservation using shear wave elastography. Results obtained on fresh kidneys were collected within 6h of death. Freezing lead to a significant decrease (p<0.05) of the shear modulus in the most superficial zone (renal cortex), irrespectively of the freezing temperature (-18°C, -34°C, -71°C). There were no significant change (p>0.05) in the properties of the renal cortex when stored at 4°C or 20°C. The average moduli in the central region of the kidney (medulla) were much higher than in the cortex and exhibited also exhibited larger specimen to specimen variations. The effects of the conservation method on the central region were not significant. Overall, the results suggest that kidney tissues should not be frozen prior to biomechanical characterization and that inhomogeneity may be important to consider for in biomechanical models., (© 2013 Elsevier Ltd. All rights reserved.)

The assessment of coagulating blood elasticity has gained importance as a result of several studies that have correlated it to cardiovascular pathologic conditions. In this study we use supersonic shear wave imaging (SSI) to measure viscoelastic properties of blood clots. At the same time, classical rheometry experiments were carried out on the same blood samples taken within the first few seconds of coagulation. Using SSI, phase velocities of the shear wave indicated increasing dispersion with time. In all cases, the frequency bandwidth of propagating shear waves changed from 20-50 Hz at the first few min of coagulation to around 300 Hz toward the end of experiments. Using the values of G' and G″ from the rheometry studies, the theoretical shear wave velocities were calculated and correlated with SSI measurements. Results of the two techniques were in very good agreement, confirming that SSI provides accurate measurements of viscoelastic properties as corroborated by conventional rheometric measurements., (Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objective: To assess stiffness in a human breast cancer implanted in mice using shear wave elastography (SWE) during tumour growth and to correlate the results with pathology., Methods: Local ethics committee for animal research approval was obtained. A human invasive ductal carcinoma was implanted subcutaneously in 24 athymic nude female mice. Ultrasound was longitudinally performed in 22 tumours, every 1-2 weeks. Maximum diameter and mean stiffness were collected. Seven tumours were measured both in vivo and ex vivo. Tumours of different sizes were removed for pathological analysis on which the percentages of viable cellular tissue, fibrosis and necrosis were measured., Results: A total of 63 SWE measurements were performed. Stiffness increased during tumour growth with an excellent correlation with size (r = 0.94, P < 0.0001). No differences were found between the values of stiffness in vivo and ex vivo (P = 0.81). There was a significant correlation between elasticity and fibrosis (r = 0.83, P < 0.0001), a negative correlation with necrosis (r = -0.76, p = 0.0004) but no significant correlation with cellular tissue (r = 0.40, p = 0.1)., Conclusion: Fibrosis plays an important role in stiffness as measured by SWE, whereas necrosis is correlated with softness., Key Points: • In a breast cancer model, ultrasound tumour stiffness is correlated with size. • Stiffness changes with tumour growth are correlated with pathological changes. • Stiffness is very well correlated with proportion of tumour fibrosis. • Stiffness is inversely correlated with proportion of tumour necrosis. • Tumour stiffness measurements are similar in vivo and ex vivo.

Ultrasonography has been widely used for diagnosis since it was first introduced in clinical practice in the 1970's. Since then, new ultrasound modalities have been developed, such as Doppler imaging, which provides new information for diagnosis. Elastography was developed in the 1990's 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., (Copyright © 2013 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Chronic kidney disease (CKD) incidence and prevalence are increasing in Western countries, due particularly to diabetes mellitus and hypertension-related nephropathies. CKD may lead to end-stage renal failure, with extensive morbidity, mortality and increasing health costs. Primary and secondary prevention requires a better knowledge of mechanisms underlying renal scarring, the development of specific therapies to slow down the progression of the disease and the development of non-invasive diagnostic tools to characterize the process. Ultrasound elastography is a new imaging technique under development that provides information about renal stiffness. Kidney elasticity measurements with ultrasound should be performed with a quantitative technique, such as Shearwave techniques. However kidney stiffness is not only related to fibrosis, as it also sensitive to mechanical and functional parameters such as anisotropy, vascularization, hydronephrosis and external pressure. This paper reviews the existing ultrasound elastography techniques. Elastography is a new tool under development for renal tissue characterization and needs further validation in clinical practice., (Copyright © 2013. Published by Elsevier Masson SAS.)