Biopathologic Characterization and Grade Assessment of Breast Cancer With 3-D Multiparametric Ultrasound Combining Shear Wave Elastography and Backscatter Tensor Imaging.

OBJECTIVE: Despite recent improvements in medical imaging, the final diagnosis and biopathologic characterization of breast cancers currently still requires biopsies. Ultrasound is commonly used for clinical examination of breast masses. B-Mode and shear wave elastography (SWE) are already widely used to detect suspicious masses and differentiate benign lesions from cancers. But additional ultrasound modalities such as backscatter tensor imaging (BTI) could provide relevant biomarkers related to tissue organization. Here we describe a 3-D multiparametric ultrasound approach applied to breast carcinomas in the aims of (i) validating the ability of BTI to reveal the underlying organization of collagen fibers and (ii) assessing the complementarity of SWE and BTI to reveal biopathologic features of diagnostic interest. METHODS: Three-dimensional SWE and BTI were performed ex vivo on 64 human breast carcinoma samples using a linear ultrasound probe moved by a set of motors. Here we describe a 3-D multiparametric representation of the breast masses and quantitative measurements combining B-mode, SWE and BTI. RESULTS: Our results reveal for the first time that BTI can capture the orientation of the collagen fibers around tumors. BTI was found to be a relevant marker for assessing cancer stages, revealing a more tangent tissue orientation for in situ carcinomas than for invasive cancers. In invasive cases, the combination of BTI and SWE parameters allowed for classification of invasive tumors with respect to their grade with an accuracy of 95.7%. CONCLUSION: Our results highlight the potential of 3-D multiparametric ultrasound imaging for biopathologic characterization of breast tumors.

Assessment of coronary microcirculation alterations in a porcine model of no-reflow using ultrasound localization microscopy: a proof of concept study.

BACKGROUND: Coronary microvascular obstruction also known as no-reflow phenomenon is a major issue during myocardial infarction that bears important prognostic implications. Alterations of the microvascular network remains however challenging to assess as there is no imaging modality in the clinics that can image directly the coronary microvascular vessels. Ultrasound Localization Microscopy (ULM) imaging was recently introduced to map microvascular flows at high spatial resolution (∼10 µm). In this study, we developed an approach to image alterations of the microvascular coronary flow in ex vivo perfused swine hearts. METHODS: A porcine model of myocardial ischemia-reperfusion was used to obtain microvascular coronary alterations and no-reflow. Four female hearts with myocardial infarction in addition to 6 controls were explanted and placed immediately in a dedicated preservation and perfusion box manufactured for ultrasound imaging. Microbubbles (MB) were injected into the vasculature to perform Ultrasound Localization Microscopy (ULM) imaging and a linear ultrasound probe mounted on a motorized device was used to scan the heart on multiple slices. The coronary microvascular anatomy and flow velocity was reconstructed using dedicated ULM algorithms and analyzed quantitatively. FINDINGS: We were able to image the coronary microcirculation of ex vivo swine hearts at a resolution of tens of microns and measure flow velocities ranging from 10 mm/s in arterioles up to more than 200 mm/s in epicardial arteries. Under different aortic perfusion pressures, we measured in large arteries of a subset of control hearts an increase of flow velocity from 31 ± 11 mm/s at 87 mmHg to 47 ± 17 mm/s at 132 mmHg (N = 3 hearts, P < 0.05). This increase was compared with a control measurement with a flowmeter in the aorta. We also compared 6 control hearts to 4 hearts in which no-reflow was induced by the occlusion and reperfusion of a coronary artery. Using average MB velocity and average density of MB per unit of surface as two ULM quantitative markers of perfusion, we were able to detect areas of coronary no-reflow in good agreement with a control anatomical pathology analysis of the cardiac tissue. In the no-reflow zone, we measured an average perfusion of 204 ± 305 MB/mm2 compared to 3182 ± 1302 MB/mm2 in the surrounding re-perfused area. INTERPRETATION: We demonstrated this approach can directly image and quantify coronary microvascular obstruction and no-reflow on large mammal perfused hearts. This is a first step for noninvasive, quantitative and affordable assessment of the coronary microcirculation function and particularly coronary microvascular anatomy in the infarcted heart. This approach has the potential to be extended to other clinical situations characterized by microvascular dysfunction. FUNDING: This study was supported by the French National Research Agency (ANR) under ANR-21-CE19-0002 grant agreement.

Assessment of Takayasu's arteritis activity by ultrasound localization microscopy.

BACKGROUND: Ultrasound localization microscopy (ULM) based on ultrafast ultrasound imaging of circulating microbubbles (MB) can image microvascular blood flows in vivo up to the micron scale. Takayasu arteritis (TA) has an increased vascularisation of the thickened arterial wall when active. We aimed to perform vasa vasorum ULM of the carotid wall and demonstrate that ULM can provide imaging markers to assess the TA activity. METHODS: Patients with TA were consecutively included with assessment of activity by the National Institute of Health criteria: 5 had active TA (median age 35.8 [24.5-46.0] years) and 11 had quiescent TA (37.2 [31.7-47.3] years). ULM was performed using a 6.4 MHz probe and a dedicated imaging sequence (plane waves with 8 angles, frame rate 500 Hz), coupled with the intravenous injection of MB. Individual MB were localised at a subwavelength scale then tracked, allowing the reconstruction of the vasa vasorum flow anatomy and velocity. FINDINGS: ULM allowed to show microvessels and to measure their flow velocity within the arterial wall. The number of MB detected per second in the wall was 121 [80-146] in active cases vs. 10 [6-15] in quiescent cases (p = 0.0005), with a mean velocity of 40.5 [39.0-42.9] mm.s-1 in active cases. INTERPRETATION: ULM allows visualisation of microvessels within the thickened carotid wall in TA, with significantly greater MB density in active cases. ULM provides a precise visualisation in vivo of the vasa vasorum and gives access to the arterial wall vascularisation quantification. FUNDING: French Society of Cardiology. ART (Technological Research Accelerator) biomedical ultrasound program of INSERM, France.

Quantitative stiffness assessment of cardiac grafts using ultrasound in a porcine model: A tissue biomarker for heart transplantation.

BACKGROUND: Heart transplantation is the definitive treatment for many cardiovascular diseases. However, no ideal approach is established to evaluate heart grafts and it mostly relies on qualitative interpretation of surgeon based on the organ aspect including anatomy, color and manual palpation. In this study we propose to assess quantitatively the Shear Wave Velocity (SWV) using ultrasound as a biomarker of cardiac viability on a porcine model. METHODS: The SWV was assessed quantitatively using a clinical ultrasound elastography device (Aixplorer, Supersonics Imagine, France) linked to a robotic motorized arm (UR3, Universal Robots, Denmark) and the elastic anisotropy was obtained using a custom ultrasound research system. SWV was evaluated as function of time in two porcine heart model during 20h at controlled temperature (4°C). One control group (N = 8) with the heart removed and arrested by cold cardioplegia and immerged in a preservation solution. One ischemic group (N = 6) with the organ harvested after 30 min of in situ warm ischemia, to mimic a donation after cardiac death. Hearts graft were revived at two preservation times, at 4 h (N = 11) and 20 h (N = 10) and the parameters of the cardiac function evaluated. FINDINGS: On control hearts, SWV remained unchanged during the 4h of preservation. SWV increased significantly between 4 and 20h. For the ischemic group, SWV was found higher after 4h (3.04 +/- 0.69 vs 1.69+/-0.19 m/s, p = 0.007) and 20h (4.77+/-1.22 m/s vs 3.40+/-0.75 m/s, p = 0.034) of preservation with significant differences. A good correlation between SWV and cardiac function index was found (r2=0.88) and manual palpation score (r2=0.81). INTERPRETATION: Myocardial stiffness increase was quantified as a function of preservation time and harvesting conditions. The correlation between SWV and cardiac function index suggests that SWV could be used as a marker of graft viability. This technique may be transposed to clinical transplantation for assessing the graft viability during transplantation process. FUNDING: FRM PME20170637799, Agence Biomédecine AOR Greffe 2017, ANR-18-CE18-0015.

Coronary Flow Assessment Using 3-Dimensional Ultrafast Ultrasound Localization Microscopy.

BACKGROUND: Direct assessment of the coronary microcirculation has long been hampered by the limited spatial and temporal resolutions of cardiac imaging modalities. OBJECTIVES: The purpose of this study was to demonstrate 3-dimensional (3D) coronary ultrasound localization microscopy (CorULM) of the whole heart beyond the acoustic diffraction limit (<20 µm resolution) at ultrafast frame rate (>1000 images/s). METHODS: CorULM was performed in isolated beating rat hearts (N = 6) with ultrasound contrast agents (Sonovue, Bracco), using an ultrasonic matrix transducer connected to a high channel-count ultrafast electronics. We assessed the 3D coronary microvascular anatomy, flow velocity, and flow rate of beating hearts under normal conditions, during vasodilator adenosine infusion, and during coronary occlusion. The coronary vasculature was compared with micro-computed tomography performed on the fixed heart. In vivo transthoracic CorULM was eventually assessed on anaesthetized rats (N = 3). RESULTS: CorULM enables the 3D visualization of the coronary vasculature in beating hearts at a scale down to microvascular structures (<20 µm resolution). Absolute flow velocity estimates range from 10 mm/s in tiny arterioles up to more than 300 mm/s in large arteries. Fitting to a power law, the flow rate-radius relationship provides an exponent of 2.61 (r2 = 0.96; P < 0.001), which is consistent with theoretical predictions and experimental validations of scaling laws in vascular trees. A 2-fold increase of the microvascular coronary flow rate is found in response to adenosine, which is in good agreement with the overall perfusion flow rate measured in the aorta (control measurement) that increased from 8.80 ± 1.03 mL/min to 16.54 ± 2.35 mL/min (P < 0.001). The feasibility of CorULM was demonstrated in vivo for N = 3 rats. CONCLUSIONS: CorULM provides unprecedented insights into the anatomy and function of coronary arteries at the microvasculature level in beating hearts. This new technology is highly translational and has the potential to become a major tool for the clinical investigation of the coronary microcirculation.

Proof of Concept of 3-D Backscatter Tensor Imaging Tomography for Non-invasive Assessment of Human Breast Cancer Collagen Organization.

Tumor growth, similarly to several other pathologies, tends to change the structural orientation of soft tissue fibers, which can become relevant markers for diagnosis. Current diagnosis protocols may require a biopsy for histological analysis, which is an invasive, painful and stressful procedure with a minimum turnaround time of 2 d. Otherwise, diagnosis may involve the use of complex methods with limited availability such as diffusion tensor imaging (magnetic resonance diffusion tensor imaging), which is not widely used in medical practice. Conversely, advanced methodologies in ultrasound imaging such as backscatter tensor imaging (BTI) might become a routine procedure in clinical practice at a limited cost. This method evaluates the local organization of soft tissues based on the spatial coherence of their backscattered ultrasonic echoes. Previous work has proven that BTI applied with matrix probes enables measurement of the orientation of soft tissue fibers, especially in the myocardium. The aims of the study described here were (i) to present for the first time a methodology for performing BTI in a volume on ex vivo human breast tumors using a linear probe and (ii) to display a first proof of concept of the link between BTI measurements and the orientation of collagen fibers.

Arterial Stiffness Assessment by Shear Wave Elastography and Ultrafast Pulse Wave Imaging: Comparison with Reference Techniques in Normotensives and Hypertensives.

Shear wave elastography and ultrafast imaging of the carotid artery pulse wave were performed in 27 normotensive participants and 29 age- and sex-matched patients with essential hypertension, and compared with reference techniques: carotid-femoral pulse wave velocity (cfPWV) determined via arterial tonometry and carotid stiffness (carPWV) determined via echotracking. Shear wave speed in the carotid anterior (a-SWS) and posterior (p-SWS) walls were assessed throughout the cardiac cycle. Ultrafast PWV was measured in early systole (ufPWV-FW) and in end-systole (dicrotic notch, ufPWV-DN). Shear wave speed in the carotid anterior appeared to be the best candidate to evaluate arterial stiffness from ultrafast imaging. In univariate analysis, a-SWS was associated with carPWV (r = 0.56, p = 0.003) and carotid-to-femoral PWV (r = 0.66, p < 0.001). In multivariate analysis, a-SWS was independently associated with age (R²â€¯= 0.14, p = 0.02) and blood pressure (R²â€¯= 0.21, p = 0.004). Moreover, a-SWS increased with blood pressure throughout the cardiac cycle and did not differ between normotensive participants and patients with essential hypertension when compared at similar blood pressures.

Robust sound speed estimation for ultrasound-based hepatic steatosis assessment.

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.

Feasibility and Diagnostic Accuracy of Supersonic Shear-Wave Elastography for the Assessment of Liver Stiffness and Liver Fibrosis in Children: A Pilot Study of 96 Patients.

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.

Assessment of the Cervix in Pregnant Women Using Shear Wave Elastography: A Feasibility Study.

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.

Viscoelasticity in Achilles tendonopathy: quantitative assessment by using real-time shear-wave elastography.

PURPOSE: To investigate the differences in viscoelastic properties between normal and pathologic Achilles tendons (ATs) by using real-time shear-wave elastography (SWE). MATERIALS AND METHODS: The institutional review board approved this study, and written informed consent was obtained from 25 symptomatic patients and 80 volunteers. One hundred eighty ultrasonographic (US) and SWE studies of ATs without tendonopathy and 30 studies of the middle portion of the AT in patients with tendonopathy were assessed prospectively. Each study included data sets acquired at B-mode US (tendon morphology and cross-sectional area) and SWE (axial and sagittal mean velocity and relative anisotropic coefficient) for two passively mobilized ankle positions. The presence of AT tears at B-mode US and signal-void areas at SWE were noted. RESULTS: Significantly lower mean velocity was shown in tendons with tendonopathy than in normal tendons in the relaxed position at axial SWE (P < .001) and in the stretched position at sagittal (P < .001) and axial (P = .0026) SWE. Tendon softening was a sign of tendonopathy in relaxed ATs when the mean velocity was less than or equal to 4.06 m · sec(-1) at axial SWE (sensitivity, 54.2%; 95% confidence interval [CI]: 32.8, 74.4; specificity, 91.5%; 95% CI: 86.3, 95.1) and less than or equal to 5.70 m · sec(-1) at sagittal SWE (sensitivity, 41.7%; 95% CI: 22.1, 63.3; specificity, 81.8%; 95% CI: 75.3, 87.2) and in stretched ATs, when the mean velocity was less than or equal to 4.86 m · sec(-1) at axial SWE (sensitivity, 66.7%; 95% CI: 44.7, 84.3; specificity, 75.6%; 95% CI: 68.5, 81.7) and less than or equal to 14.58 m · sec(-1) at sagittal SWE (sensitivity, 58.3%; 95% CI: 36.7, 77.9; specificity, 83.5%; 95% CI: 77.2, 88.7). Anisotropic results were not significantly different between normal and pathologic ATs. Six of six (100%) partial-thickness tears appeared as signal-void areas at SWE. CONCLUSION: Whether the AT was relaxed or stretched, SWE helped to confirm and quantify pathologic tendon softening in patients with tendonopathy in the midportion of the AT and did not reveal modifications of viscoelastic anisotropy in the tendon. Tendon softening assessed by using SWE appeared to be highly specific, but sensitivity was relatively low.

Evaluation of Nonradiative Clinical Imaging Techniques for the Longitudinal Assessment of Tumour Growth in Murine CT26 Colon Carcinoma.

Background and Objectives. To determine the most appropriate technique for tumour followup in experimental therapeutics, we compared ultrasound (US) and magnetic resonance imaging (MRI) to characterize ectopic and orthotopic colon carcinoma models. Methods. CT26 tumours were implanted subcutaneously (s.c.) in Balb/c mice for the ectopic model or into the caecum for the orthotopic model. Tumours were evaluated by histology, spectrofluorescence, MRI, and US. Results. Histology of CT26 tumour showed homogeneously dispersed cancer cells and blood vessels. The visualization of the vascular network using labelled albumin showed that CT26 tumours were highly vascularized and disorganized. MRI allowed high-resolution and accurate 3D tumour measurements and provided additional anatomical and functional information. Noninvasive US imaging allowed good delineation of tumours despite an hypoechogenic signal. Monitoring of tumour growth with US could be accomplished as early as 5 days after implantation with a shorter acquisition time (<5 min) compared to MRI. Conclusion. MRI and US afforded excellent noninvasive imaging techniques to accurately follow tumour growth of ectopic and orthotopic CT26 tumours. These two techniques can be appropriately used for tumour treatment followup, with a preference for US imaging, due to its short acquisition time and simplicity of use.

Application of 1-D transient elastography for the shear modulus assessment of thin-layered soft tissue: comparison with supersonic shear imaging technique.

Elasticity estimation of thin-layered soft tissues has gained increasing interest propelled by medical applications like skin, corneal, or arterial wall shear modulus assessment. In this work, the authors propose one-dimensional transient elastography (1DTE) for the shear modulus assessment of thin-layered soft tissue. Experiments on three phantoms with different elasticities and plate thicknesses were performed. First, using 1DTE, the shear wave speed dispersion curve inside the plate was obtained and validated with finite difference simulation. No dispersive effects were observed and the shear wave speed was directly retrieved from time-of-flight measurements. Second, the supersonic shear imaging (SSI) technique (considered to be a gold standard) was performed. For the SSI technique, the propagating wave inside the plate is guided as a Lamb wave. Experimental SSI dispersion curves were compared with finite difference simulation and fitted using a generalized Lamb model to retrieve the plate bulk shear wave speed. Although they are based on totally different mechanical sources and induce completely different diffraction patterns for the shear wave propagation, the 1DTE and SSI techniques resulted in similar shear wave speed estimations. The main advantage of the 1DTE technique is that bulk shear wave speed can be directly retrieved without requiring a dispersion model.

Assessment of viscous and elastic properties of sub-wavelength layered soft tissues using shear wave spectroscopy: theoretical framework and in vitro experimental validation.

In elastography, quantitative imaging of soft tissue elastic properties is provided by local shear wave speed estimation. Shear wave imaging in a homogeneous medium thicker than the shear wavelength is eased by a simple relationship between shear wave speed and local shear modulus. In thin layered organs, the shear wave is guided and thus undergoes dispersive effects. This case is encountered in medical applications such as elastography of skin layers, corneas, or arterial walls. In this work, we proposed and validated shear wave spectroscopy as a method for elastic modulus quantification in such layered tissues. Shear wave dispersion curves in thin layers were obtained by finite-difference simulations and numerical solving of the boundary conditions. In addition, an analytical approximation of the dispersion equation was derived from the leaky Lamb wave theory. In vitro dispersion curves obtained from phantoms were consistent with numerical studies (deviation <1.4%). The least-mean-squares fitting of the dispersion curves enables a quantitative and accurate (error < 5% of the transverse speed) assessment of the elasticity. Dispersion curves were also found to be poorly influenced by shear viscosity. This phenomenon allows independent recovery of the shear modulus and the viscosity, using, respectively, the dispersion curve and the attenuation estimation along the propagation axis.

Real-time assessment of myocardial contractility using shear wave imaging.

OBJECTIVES: The goal of this study was to assess whether myocardial stiffness could be measured by shear wave imaging (SWI) and whether myocardial stiffness accurately quantified myocardial function. BACKGROUND: SWI is a novel ultrasound-based technique for quantitative, local, and noninvasive mapping of soft tissue elastic properties. METHODS: SWI was performed in Langendorff perfused isolated rat hearts (n = 6). Shear wave was generated and imaged in the left ventricular myocardium using a conventional ultrasonic probe connected to an ultrafast scanner (12,000 frames/s). The local myocardial stiffness was derived from shear wave velocity every 7.5 ms during 1 single cardiac cycle. RESULTS: The average myocardial stiffness was 8.6 ± 0.7 kPa in systole and 1.7 ± 0.8 kPa in diastole. Myocardial stiffness was compared with isovolumic systolic pressure at rest and during administration of isoproterenol (10(-9), 10(-8), and 10(-7) mol/l, 5 min each). Systolic myocardial stiffness increased strongly up to 23.4 ± 3.4 kPa. Myocardial stiffness correlated strongly with isovolumic systolic pressure (r(2) = [0.94; 0.98], p < 0.0001). CONCLUSIONS: Myocardial stiffness can be measured in real time over the cardiac cycle using SWI, which allows quantification of stiffness variation between systole and diastole. Systolic myocardial stiffness provides a noninvasive index of myocardial contractility.

Quantitative assessment of arterial wall biomechanical properties using shear wave imaging.

A new ultrasound-based technique is proposed to assess the arterial stiffness: the radiation force of an ultrasonic beam focused on the arterial wall induces a transient shear wave (∼10 ms) whose propagation is tracked by ultrafast imaging. The large and high-frequency content (100 to 1500 Hz) of the induced wave enables studying the wave dispersion, which is shown experimentally in vitro and numerically to be linked to arterial wall stiffness and geometry. The proposed method is applied in vivo. By repeating the acquisition up to 10 times per second (theoretical maximal frame rate is ∼100 Hz), it is possible to assess in vivo the arterial wall elasticity dynamics: shear modulus of a healthy volunteer carotid wall is shown to vary strongly during the cardiac cycle and measured to be 130 ± 15 kPa in systole and 80 ± 10 kPa in diastole.

Assessment of the mechanical properties of the musculoskeletal system using 2-D and 3-D very high frame rate ultrasound.

One of the great challenges for understanding muscular diseases is to assess noninvasively the active and passive mechanical properties of the musculoskeletal system. In this paper we report the use of ultrafast ultrasound imaging to explore with a submillimeter resolution the behavior of the contracting tissues in vivo (biceps brachii). To image the contraction, which is a very brief phenomenon (100 ms), a recently designed ultrasound scanner prototype able to take up to 6000 frames/s was used. A very high frame rate from 1000 to 2500 frames/s was used to image the cross section plane of the muscle (transverse to fibers) enabling us to catch in real time the muscle contraction during a transient electrostimulation. Tissue velocities were obtained from radiofrequency based speckle tracking techniques and their profiles are discussed with respect to electrostimulation intensities and pulse repetition frequencies for different volunteers. Three-dimensional (3-D) very high frame rate movies were also acquired by repeating the experiment for different acquisition planes while triggering the imaging system with the electrostimulation device. The reconstructed 3-D velocity field allows the full localization of the contracting fibers bundle. This ultrasound technique, referred to as echo mechanomyography, offers new perspectives for in vivo and in situ noninvasive muscle diagnosis of an active contractile tissue.

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.