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Ultrasound in medicine & biology  2014;40(8):1785-1795.
Our aims were (i) to compare in vivo measurements of myocardial elasticity by shear wave dispersion ultrasound vibrometry (SDUV) with those by the conventional pressure-segment length method, and (ii) to quantify changes in myocardial viscoelasticity during systole and diastole after reperfused acute myocardial infarction. The shear elastic modulus (μ1) and viscous coefficient (μ2) of left ventricular myocardium were measured by SDUV in 10 pigs. Young’s elastic modulus was independently measured by the pressure-segment length method. Measurements made with the SDUV and pressure-segment length methods were strongly correlated. At reperfusion, μ1 and μ2 in end-diastole were increased. Less consistent changes were found during systole. In all animals, μ1 increased linearly with left ventricular pressure developed during systole. Preliminary results suggest that m1 is preload dependent. This is the first study to validate in vivo measurements of myocardial elasticity by a shear wave method. In this animal model, the alterations in myocardial viscoelasticity after a myocardial infarction were most consistently detected during diastole.
PMCID: PMC4118646  PMID: 24814645
Echocardiography; Elasticity; Elastography; Myocardial stiffness; Myocardial infarction; Shear elasticity; Shear wave; Ultrasound; Viscoelasticity
2.  Fast Shear Compounding Using Robust Two-dimensional Shear Wave Speed Calculation and Multi-directional Filtering 
Ultrasound in medicine & biology  2014;40(6):1343-1355.
A fast shear compounding method was developed in this study using only one shear wave push-detect cycle, such that the shear wave imaging frame rate is preserved and motion artifacts are minimized. The proposed method is composed of the following steps: 1. applying a comb-push to produce multiple differently angled shear waves at different spatial locations simultaneously; 2. decomposing the complex shear wave field into individual shear wave fields with differently oriented shear waves using a multi-directional filter; 3. using a robust two-dimensional (2D) shear wave speed calculation to reconstruct 2D shear elasticity maps from each filter direction; 4. compounding these 2D maps from different directions into a final map. An inclusion phantom study showed that the fast shear compounding method could achieve comparable performance to conventional shear compounding without sacrificing the imaging frame rate. A multi-inclusion phantom experiment showed that the fast shear compounding method could provide a full field-of-view (FOV), 2D, and compounded shear elasticity map with three types of inclusions clearly resolved and stiffness measurements showing excellent agreement to the nominal values.
PMCID: PMC4011964  PMID: 24613636
shear compounding; shear wave elastography; 2D shear wave speed; directional filter; comb-push; acoustic radiation force
3.  Improved Shear Wave Motion Detection Using Pulse-Inversion Harmonic Imaging with a Phased Array Transducer 
IEEE transactions on medical imaging  2013;10.1109/TMI.2013.2280903.
Ultrasound tissue harmonic imaging is widely used to improve ultrasound B-mode imaging quality thanks to its effectiveness in suppressing imaging artifacts associated with ultrasound reverberation, phase aberration, and clutter noise. In ultrasound shear wave elastography (SWE), because the shear wave motion signal is extracted from the ultrasound signal, these noise sources can significantly deteriorate the shear wave motion tracking process and consequently result in noisy and biased shear wave motion detection. This situation is exacerbated in in vivo SWE applications such as heart, liver, and kidney. This paper, therefore, investigated the possibility of implementing harmonic imaging, specifically pulse-inversion harmonic imaging, in shear wave tracking, with the hypothesis that harmonic imaging can improve shear wave motion detection based on the same principles that apply to general harmonic B-mode imaging. We first designed an experiment with a gelatin phantom covered by an excised piece of pork belly and show that harmonic imaging can significantly improve shear wave motion detection by producing less underestimated shear wave motion and more consistent shear wave speed measurements than fundamental imaging. Then, a transthoracic heart experiment on a freshly sacrificed pig showed that harmonic imaging could robustly track the shear wave motion and give consistent shear wave speed measurements while fundamental imaging could not. Finally, an in vivo transthoracic study of seven healthy volunteers showed that the proposed harmonic imaging tracking sequence could provide consistent estimates of the left ventricular myocardium stiffness in end-diastole with a general success rate of 80% and a success rate of 93.3% when excluding the subject with Body Mass Index (BMI) higher than 25. These promising results indicate that pulse-inversion harmonic imaging can significantly improve shear wave motion tracking and thus potentially facilitate more robust assessment of tissue elasticity by SWE.
PMCID: PMC3947393  PMID: 24021638
Harmonic imaging; shear wave elastography; acoustic radiation force; pulse inversion; in vivo human heart; transthoracic scanning; diastolic left ventricle stiffness
4.  Optimized shear wave generation using hybrid beamforming methods 
Ultrasound in medicine & biology  2013;40(1):10.1016/j.ultrasmedbio.2013.08.016.
Elasticity imaging is a medical imaging modality that measures tissue elasticity to aid in diagnosis of certain diseases. Shear wave-based methods have been developed to perform elasticity measurements in soft tissue. These methods often utilize the radiation force mechanism of focused ultrasound to induce shear waves in soft tissue such as liver, kidney, breast, thyroid, and skeletal muscle. The efficiency of the ultrasound beam for producing broadband extended shear waves in soft tissue is very important for widespread use of this modality. Hybrid beamforming combines two types of focusing, conventional spherical and axicon focusing, to produce a beam for generating a shear wave that has increased depth-of–field (DOF) so that measurements can be made with a shear wave with a consistent wave front. Spherical focusing is used in many applications to achieve high lateral resolution, but has low DOF. Axicon focusing, with a cone- shaped transducer can provide good lateral resolution with large DOF. We present our linear aperture design and beam optimization performed using angular spectrum simulations. A large parametric simulation study was performed which included varying the focal depth for the spherical focusing portion of the aperture, the number of elements devoted to spherical and axicon focusing portions of the aperture, and the opening angle used for axicon focusing. The hybrid beamforming method was experimentally tested in two phantoms and the shear wave speed measurement accuracy as well as the DOF for each hybrid beam was evaluated. We compared our results with shear waves generated using only spherical focusing. The results of this study show that hybrid beamforming is capable of producing a beam with increased DOF over which accurate shear wave speed measurements can be made for different size apertures and at different focal depths.
PMCID: PMC3849318  PMID: 24139918
shear wave; hybrid beamforming; axicon; shear wave speed; depth-of-field
5.  Comb-push Ultrasound Shear Elastography (CUSE) for Evaluation of Thyroid Nodules: Preliminary In vivo Results 
In clinical practice, an overwhelming majority of biopsied thyroid nodules are benign. Therefore, there is a need for a complementary and noninvasive imaging tool to provide clinically relevant diagnostic information about thyroid nodules to reduce the rate of unnecessary biopsies. The goal of this study was to evaluate the feasibility of utilizing Comb-push Ultrasound Shear Elastography (CUSE) to measure the mechanical properties (i.e., stiffness) of thyroid nodules and use this information to help classify nodules as benign or malignant. CUSE is a fast and robust 2D shear elastography technique in which multiple laterally distributed acoustic radiation force beams are utilized simultaneously to produce shear waves. Unlike other shear elasticity imaging modalities, CUSE does not suffer from limited field of view (FOV) due to shear wave attenuation and can provide a large FOV at high frame rates. To evaluate the utility of CUSE in thyroid imaging, a preliminary study was performed on a group of 5 healthy volunteers and 10 patients with ultrasound (US)-detected thyroid nodules prior to fine needle aspiration biopsy (FNAB). The measured shear wave speeds in normal thyroid tissue and thyroid nodules were converted to Young's modulus (E), indicating a measure of tissue stiffness. Our results indicate an increase in E for thyroid nodules compared to normal thyroid tissue. This increase was significantly higher in malignant nodules compared to benign. The Young's modulus in normal thyroid tissue, benign and malignant nodules were found to be 23.2±8.29 kPa, 91.2±34.8 kPa, and 173.0±17.1 kPa, respectively. Results of this study suggest the utility of CUSE in differentiating between benign and malignant thyroid nodules.
PMCID: PMC4280299  PMID: 25122532
Cancer; Elasticity; In vivo; Shear Wave Elastography; Thyroid; Ultrasound
6.  Validation of Shear Wave Elastography in Skeletal Muscle 
Journal of biomechanics  2013;46(14):10.1016/j.jbiomech.2013.07.033.
Skeletal muscle is a very dynamic tissue, thus accurate quantification of skeletal muscle stiffness throughout its functional range is crucial to improve the physical functioning and independence following pathology. Shear wave elastography (SWE) is an ultrasound-based technique that characterizes tissue mechanical properties based on the propagation of remotely induced shear waves. The objective of this study is to validate SWE throughout the functional range of motion of skeletal muscle for three ultrasound transducer orientations. We hypothesized that combining traditional materials testing (MTS) techniques with SWE measurements will show increased stiffness measures with increasing tensile load, and will correlate well with each other for trials in which the transducer is parallel to underlying muscle fibers. To evaluate this hypothesis, we monitored the deformation throughout tensile loading of four porcine brachialis whole-muscle tissue specimens, while simultaneously making SWE measurements of the same specimen. We used regression to examine the correlation between Young's modulus from MTS and shear modulus from SWE for each of the transducer orientations. We applied a generalized linear model to account for repeated testing. Model parameters were estimated via generalized estimating equations. The regression coefficient was 0.1944, with a 95% confidence interval of (0.1463 – 0.2425) for parallel transducer trials. Shear waves did not propagate well for both the 45° and perpendicular transducer orientations. Both parallel SWE and MTS showed increased stiffness with increasing tensile load. This study provides the necessary first step for additional studies that can evaluate the distribution of stiffness throughout muscle.
PMCID: PMC3818126  PMID: 23953670
Ultrasonography; passive stiffness; materials testing; elastic moduli; shear wave elastography
7.  Comb-push Ultrasound Shear Elastography (CUSE) with Various Ultrasound Push Beams 
IEEE transactions on medical imaging  2013;32(8):1435-1447.
Comb-push Ultrasound Shear Elastography (CUSE) has recently been shown to be a fast and accurate two-dimensional (2D) elasticity imaging technique that can provide a full field-of- view (FOV) shear wave speed map with only one rapid data acquisition. The initial version of CUSE was termed U-CUSE because unfocused ultrasound push beams were used. In this paper, we present two new versions of CUSE – Focused CUSE (F-CUSE) and Marching CUSE (M-CUSE), which use focused ultrasound push beams to improve acoustic radiation force penetration and produce stronger shear waves in deep tissues (e.g. kidney and liver). F-CUSE divides transducer elements into several subgroups which transmit multiple focused ultrasound beams simultaneously. M-CUSE uses more elements for each focused push beam and laterally marches the push beams. Both F-CUSE and M-CUSE can generate comb-shaped shear wave fields that have shear wave motion at each imaging pixel location so that a full FOV 2D shear wave speed map can be reconstructed with only one data acquisition. Homogeneous phantom experiments showed that U-CUSE, F-CUSE and M-CUSE can all produce smooth shear wave speed maps with accurate shear wave speed estimates. An inclusion phantom experiment showed that all CUSE methods could provide good contrast between the inclusion and background with sharp boundaries while F-CUSE and M-CUSE require shorter push durations to achieve shear wave speed maps with comparable SNR to U-CUSE. A more challenging inclusion phantom experiment with a very stiff and deep inclusion shows that better shear wave penetration could be gained by using F-CUSE and M-CUSE. Finally, a shallow inclusion experiment showed that good preservations of inclusion shapes could be achieved by both U-CUSE and F-CUSE in the near field. Safety measurements showed that all safety parameters are below FDA regulatory limits for all CUSE methods. These promising results suggest that, using various push beams, CUSE is capable of reconstructing a 2D full FOV shear elasticity map using only one push-detection data acquisition in a wide range of depths for soft tissue elasticity imaging.
PMCID: PMC3760382  PMID: 23591479
CUSE; comb-push; ultrasound elastography; shear wave; acoustic radiation force; unfocused ultrasound beam; focused ultrasound beam
8.  Acoustic Waves in Medical Imaging and Diagnostics 
Ultrasound in medicine & biology  2013;39(7):1133-1146.
Up until about two decades ago acoustic imaging and ultrasound imaging were synonymous. The term “ultrasonography,” or its abbreviated version “sonography” meant an imaging modality based on the use of ultrasonic compressional bulk waves. Since the 1990s numerous acoustic imaging modalities started to emerge based on the use of a different mode of acoustic wave: shear waves. It was demonstrated that imaging with these waves can provide very useful and very different information about the biological tissue being examined. We will discuss physical basis for the differences between these two basic modes of acoustic waves used in medical imaging and analyze the advantages associated with shear acoustic imaging. A comprehensive analysis of the range of acoustic wavelengths, velocities, and frequencies that have been used in different imaging applications will be presented. We will discuss the potential for future shear wave imaging applications.
PMCID: PMC3682421  PMID: 23643056
compressional wave; shear wave; elasticity; viscoelasticity; acoustic imaging; dispersion; anisotropy
10.  In vivo swine kidney viscoelasticity during acute gradual decrease in renal blood flow: pilot study 
Elasticity imaging methods have been used to study kidney mechanical properties and have demonstrated that the kidney elastic modulus increases with disease state. However, studies in swine suggests that kidney elastic modulus is also affected by hemodynamic variables. A newly emerging method called Shearwave Dispersion Ultrasound Vibrometry (SDUV) offers a tool to determine renal elasticity and viscosity in vivo. The purpose of this study is directed toward evaluating the feasibility of SDUV for in vivo measurements of healthy swine kidney during acute gradual decease of renal blood flow. In this study in vivo SDUV measurements were made on a group of 5 normal swine kidneys at baseline renal blood flow (RBF) and 25, 50, 75 and 100% decrease in RBF. The shear elastic modulus at full baseline was 7.04 ± 0.92 kPa and 3.48 ± 0.20 kPa at 100% decrease in RBF. The viscosity did not change between baseline (2.23 ± 0.33 Pa·s) and 100% decrease in RBF (2.03 ± 0.32 Pa·s). The data from this study indicates that other variables such as local blood flow, pressure and volume as well as method accuracy need to be measured to illustrate the relationship between shear elasticity and viscosity associated with acute kidney processes.
PMCID: PMC3922126  PMID: 24533039
Renal cortex; elasticity; viscosity
11.  Measurement of viscoelastic properties of in vivo swine myocardium using Lamb Wave Dispersion Ultrasound Vibrometry (LDUV) 
Viscoelastic properties of the myocardium are important for normal cardiac function and may be altered by disease. Thus, quantification of these properties may aid with evaluation of the health of the heart. Lamb Wave Dispersion Ultrasound Vibrometry (LDUV) is a shear wave-based method that uses wave velocity dispersion to measure the underlying viscoelastic material properties of soft tissue with plate-like geometries. We tested this method in eight pigs in an open-chest preparation. A mechanical actuator was used to create harmonic, propagating mechanical waves in the myocardial wall. The motion was tracked using a high frame rate acquisition sequence, typically 2500 Hz. The velocities of wave propagation were measured over the 50–400 Hz frequency range in 50 Hz increments. Data were acquired over several cardiac cycles. Dispersion curves were fit with a viscoelastic, anti-symmetric Lamb wave model to obtain estimates of the shear elasticity, μ1, and viscosity, μ2 as defined by the Kelvin-Voigt rheological model. The sensitivity of the Lamb wave model was also studied using simulated data. We demonstrated that wave velocity measurements and Lamb wave theory allow one to estimate the variation of viscoelastic moduli of the myocardial walls in vivo throughout the course of the cardiac cycle.
PMCID: PMC3562367  PMID: 23060325
12.  Shear Wave Speed Measurement Using an Unfocused Ultrasound Beam 
Ultrasound in medicine & biology  2012;38(9):1646-1655.
Tissue elasticity is related to pathology and therefore has important medical applications. Radiation force from a focused ultrasound beam has been used to produce shear waves in tissues for shear wave speed and tissue elasticity measurements. The feasibility of shear wave speed measurement using radiation force for an unfocused ultrasound beam is demonstrated in this study with a linear and a curved array transducer. Consistent measurement of shear wave speed was achieved over a relatively long axial extent (z = 10-40 mm for the linear array, and z = 15-60 mm for the curved array) in 3 calibrated phantoms with different shear moduli. In vivo measurements on the biceps of a healthy volunteer show consistent increase of shear wave speed for the biceps under 0, 1, 2, and 3 kg loading. Advantages and limitations of unfocused push are discussed.
PMCID: PMC3413738  PMID: 22766123
Elasticity; Shear wave; Ultrasound radiation force; Unfocused
13.  Comb-push Ultrasound Shear Elastography (CUSE): A Novel Method for Two-dimensional Shear Elasticity Imaging of Soft Tissues 
IEEE transactions on medical imaging  2012;31(9):1821-1832.
Fast and accurate tissue elasticity imaging is essential in studying dynamic tissue mechanical properties. Various ultrasound shear elasticity imaging techniques have been developed in the last two decades. However, to reconstruct a full field-of-view 2D shear elasticity map, multiple data acquisitions are typically required. In this paper, a novel shear elasticity imaging technique, comb-push ultrasound shear elastography (CUSE), is introduced in which only one rapid data acquisition (less than 35 ms) is needed to reconstruct a full field-of-view 2D shear wave speed map (40 mm × 38 mm). Multiple unfocused ultrasound beams arranged in a comb pattern (comb-push) are used to generate shear waves. A directional filter is then applied upon the shear wave field to extract the left-to-right (LR) and right-to-left (RL) propagating shear waves. Local shear wave speed is recovered using a time-of-flight method based on both LR and RL waves. Finally a 2D shear wave speed map is reconstructed by combining the LR and RL speed maps. Smooth and accurate shear wave speed maps are reconstructed using the proposed CUSE method in two calibrated homogeneous phantoms with different moduli. Inclusion phantom experiments demonstrate that CUSE is capable of providing good contrast (contrast-to-noise-ratio ≥ 25 dB) between the inclusion and background without artifacts and is insensitive to inclusion positions. Safety measurements demonstrate that all regulated parameters of the ultrasound output level used in CUSE sequence are well below the FDA limits for diagnostic ultrasound.
PMCID: PMC3475422  PMID: 22736690
comb-push; unfocused ultrasound beam; ultrasound elastography; acoustic radiation force; inclusion
14.  In vivo thyroid vibro-acoustography: a pilot study 
BMC Medical Imaging  2013;13:12.
The purpose of this study was to evaluate the utility of a noninvasive ultrasound-based method, vibro-acoustography (VA), for thyroid imaging and determine the feasibility and challenges of VA in detecting nodules in thyroid.
Our study included two parts. First, in an in vitro study, experiments were conducted on a number of excised thyroid specimens randomly taken from autopsy. Three types of images were acquired from most of the specimens: X-ray, B-mode ultrasound, and vibro-acoustography. The second and main part of the study includes results from performing VA and B-mode ultrasound imaging on 24 human subjects with thyroid nodules. The results were evaluated and compared qualitatively.
In vitro vibro-acoustography images displayed soft tissue structures, microcalcifications, cysts and nodules with high contrast and no speckle. In this group, all of US proven nodules and all of X-ray proven calcifications of thyroid tissues were detected by VA. In vivo results showed 100% of US proven calcifications and 91% of the US detected nodules were identified by VA, however, some artifacts were present in some cases.
In vitro and in vivo VA images show promising results for delineating the detailed structure of the thyroid, finding nodules and in particular calcifications with greater clarity compare to US. Our findings suggest that, with further development, VA may be a suitable imaging modality for clinical thyroid imaging.
PMCID: PMC3618245  PMID: 23530993
Elasticity imaging techniques; Vibro-acoustography; Thyroid neoplasm; Thyroid nodule; Ultrasound; Imaging
15.  Loss tangent and complex modulus estimated by acoustic radiation force creep and shear wave dispersion 
Physics in Medicine and Biology  2012;57(5):1263-1282.
Elasticity imaging methods have been used to study tissue mechanical properties and have demonstrated that tissue elasticity changes with disease state. In current shear wave elasticity imaging methods typically only shear wave speed is measured and rheological models, e.g., Kelvin-Voigt, Maxwell and Standard Linear Solid, are used to solve for tissue mechanical properties such as the shear viscoelastic complex modulus. This paper presents a method to quantify viscoelastic material properties in a model-independent way by estimating the complex shear elastic modulus over a wide frequency range using time-dependent creep response induced by acoustic radiation force. This radiation force induced creep (RFIC) method uses a conversion formula that is the analytic solution of a constitutive equation. The proposed method in combination with Shearwave Dispersion Ultrasound Vibrometry (SDUV) is used to measure the complex modulus so that knowledge of the applied radiation force magnitude is not necessary. The conversion formula is shown to be sensitive to sampling frequency and the first reliable measure in time according to numerical simulations using the Kelvin-Voigt model creep strain and compliance. Representative model-free shear complex moduli from homogeneous tissue mimicking phantoms and one excised swine kidney were obtained. This work proposes a novel model-free ultrasound-based elasticity method that does not require a rheological model with associated fitting requirements.
PMCID: PMC3376913  PMID: 22345425
16.  Shearwave Dispersion Ultrasound Vibrometry (SDUV) on swine kidney 
Shearwave Dispersion Ultrasound Vibrometry (SDUV) is used to quantify both tissue shear elasticity and shear viscosity by evaluating dispersion of shear wave propagation speed over a certain bandwidth (50–500 Hz). The motivation for developing elasticity imaging techniques is based on the possibility of diagnosing disease process. However, it is important to study the mechanical properties of healthy tissues; such data can enhance clinical knowledge and improve understanding of the mechanical properties of tissue. The purpose of this study is to evaluate the feasibility of SDUV for in vitro measurements of renal cortex shear elasticity and shear viscosity on healthy swine kidney. A total of eight excised kidneys from female pigs were used in these in vitro experiments, and a battery of different tests were performed to gain insight on the material properties of the renal cortex. From these eight kidneys, the overall renal cortex elasticity and viscosity was 1.81 ± 0.17 kPa and 1.48 ± 0.49 Pa·s, respectively. In an analysis of the material properties over time after excision, there was not a statistically significant difference in shear elasticity over a 24 hour period, but a statistically significant difference in shear viscosity was found. Homogeneity of the renal cortex was examined and it was found that shear elasticity and shear viscosity were statistically different within a kidney, suggesting global tissue inhomogeneity. More than 30% increases in shear elasticity and shear viscosity were observed after immersion in 10% formaldehyde. Lastly, it was found that the renal cortex is rather anisotropic. Two values for shear elasticity and shear viscosity were measured depending on shear wave propagation direction. These various tests elucidated different aspects of the material properties and the structure of the ex vivo renal cortex.
PMCID: PMC3588601  PMID: 23443697
17.  Bias Observed in Time-of-flight Shear Wave Speed Measurements Using Radiation Force of a Focused Ultrasound Beam 
Ultrasound in medicine & biology  2011;37(11):1884-1892.
Measurement of shear wave propagation speed has important clinical applications because it is related to tissue stiffness and health state. Shear waves can be generated in tissues by the radiation force of a focused ultrasound beam (push beam). Shear wave speed can be measured by tracking its propagation laterally from the push beam focus using the time-of-flight principle. This study shows that shear wave speed measurements with such methods can be transducer, depth, and lateral tracking range dependent. Three homogeneous phantoms with different stiffness were studied using curvilinear and linear array transducer. Shear wave speed measurements were made at different depths, using different aperture sizes for push, and at different lateral distance ranges from the push beam. The curvilinear transducer shows a relatively large measurement bias that is depth dependent. The possible causes of the bias and options for correction are discussed. These bias errors must be taken into account to provide accurate and precise time-of-flight shear wave speed measurements for clinical use.
PMCID: PMC3199321  PMID: 21924817
Shear wave speed; Liver fibrosis; Bias; ARFI
18.  A Review of Vibro-acoustography and its Applications in Medicine 
Current medical imaging reviews  2011;7(4):350-359.
In recent years, several new techniques based on the radiation force of ultrasound have been developed. Vibro-acoustography is a speckle-free ultrasound based imaging modality that can visualize normal and abnormal soft tissue through mapping the acoustic response of the object to a harmonic radiation force induced by ultrasound. In vibro-acoustography, the ultrasound energy is converted from high ultrasound frequencies to a low acoustic frequency (acoustic emission) that is often two orders of magnitude smaller than the ultrasound frequency. The acoustic emission is normally detected by a hydrophone. In medical imaging, vibroacoustography has been tested on breast, prostate, arteries, liver, and thyroid. These studies have shown that vibro-acoustic data can be used for quantitative evaluation of elastic properties. This paper presents an overview of vibro-acoustography and its applications in the areas of biomedicine.
PMCID: PMC3298414  PMID: 22423235
Ultrasound; Radiation force; Vibro-acoustography; Imaging
19.  On Lamb and Rayleigh Wave Convergence in Viscoelastic Tissues 
Physics in Medicine and Biology  2011;56(20):6723-6738.
Characterization of the viscoelastic material properties of soft tissue has become an important area of research over the last two decades. Our group has been investigating the feasibility of using Shearwave Dispersion Ultrasound Vibrometry (SDUV) method to excite Lamb waves in organs with plate-like geometry to estimate the viscoelasticity of the medium of interest. The use of Lamb wave Dispersion Ultrasound Vibrometry (LDUV) to quantify mechanical properties of viscoelastic solids has previously been reported. Two organs, the heart wall and the spleen, can be readily modeled using plate-like geometries. The elasticity of these two organs is important because they change in pathological conditions. Diastolic dysfunction is the inability of the left ventricle (LV) of the heart to supply sufficient stroke volumes into the systemic circulation and is accompanied by the loss of compliance and stiffening of the LV myocardium. It has been shown that there is a correlation between high splenic stiffness in patients with chronic liver disease and strong correlation between spleen and liver stiffness. Here, we investigate the use of the SDUV method to quantify viscoelasticity of the LV free-wall myocardium and spleen by exciting Rayleigh waves on the organ’s surface and measuring the wave dispersion (change of wave velocity as a function of frequency) in the frequency range 40–500 Hz. An equation for Rayleigh wave dispersion due to cylindrical excitation was derived by modeling the excised myocardium and spleen with a homogenous Voigt material plate immersed in a nonviscous fluid. Boundary conditions and wave potential functions were solved for the surface wave velocity. Analytical and experimental convergence between the Lamb and Rayleigh waves is reported in a finite element model of a plate in a fluid of similar density, gelatin plate and excised porcine spleen and left-ventricular free-wall myocardium.
PMCID: PMC3391711  PMID: 21970846
20.  Breast vibro-acoustography: initial results show promise 
Breast Cancer Research : BCR  2012;14(5):R128.
Vibro-acoustography (VA) is a recently developed imaging modality that is sensitive to the dynamic characteristics of tissue. It detects low-frequency harmonic vibrations in tissue that are induced by the radiation force of ultrasound. Here, we have investigated applications of VA for in vivo breast imaging.
A recently developed combined mammography-VA system for in vivo breast imaging was tested on female volunteers, aged 25 years or older, with suspected breast lesions on their clinical examination. After mammography, a set of VA scans was acquired by the experimental device. In a masked assessment, VA images were evaluated independently by 3 reviewers who identified mass lesions and calcifications. The diagnostic accuracy of this imaging method was determined by comparing the reviewers' responses with clinical data.
We collected images from 57 participants: 7 were used for training and 48 for evaluation of diagnostic accuracy (images from 2 participants were excluded because of unexpected imaging artifacts). In total, 16 malignant and 32 benign lesions were examined. Specificity for diagnostic accuracy was 94% or higher for all 3 reviewers, but sensitivity varied (69% to 100%). All reviewers were able to detect 97% of masses, but sensitivity for detection of calcification was lower (≤ 72% for all reviewers).
VA can be used to detect various breast abnormalities, including calcifications and benign and malignant masses, with relatively high specificity. VA technology may lead to a new clinical tool for breast imaging applications.
PMCID: PMC4053105  PMID: 23021305
acoustic imaging; breast lesions; radiation force breast imaging; ultrasound; vibro-acoustography
21.  Measurement of biaxial mechanical properties of soft tubes and arteries using piezoelectric elements and sonometry 
Physics in medicine and biology  2011;56(11):3371-3386.
Arterial elasticity has gained importance in the past decades because it has been shown to be an independent predictor of cardiovascular diseases. Several in vivo and ex vivo techniques have been developed to characterize the elastic properties of vessels. In vivo techniques tend to ignore the anisotropy of the mechanical properties in the vessel wall, and therefore, fail to characterize elasticity in different directions. Ex vivo techniques, have focused their efforts in studying the mechanical properties in different axes. In this paper, we present a technique that uses piezoelectric elements to measure the elasticity of soft tubes and excised arteries in two directions while maintaining the natural structure of these vessels. This technique uses sonometry data from piezoelectric elements to measure the strain in the longitudinal and circumferential directions while the tubes/arteries are being pressurized. We conducted experiments on urethane tubes to evaluate the technique and compared the experimental results with mechanical testing done on the materials used for making the tubes. We then performed sonometry experiments on excised pig carotid arteries assuming that they are transversely isotropic materials. To evaluate the sensitivity of this technique to changes in the material properties, we changed the temperature of the saline bath in which the arteries were immersed. The calculated Young’s modulus from sonometry experiments for the urethane tubes and the mechanical testing values showed good agreement, deviating no more than 13.1%. The elasticity values from the excised arteries and the behavior with the temperature changed agreed with previous work done in similar arteries. Therefore, we propose this technique for nondestructive testing of the biaxial properties of soft materials tubes and excised arteries in their natural physiological shape.
PMCID: PMC3129600  PMID: 21558593
Arterial elasticity; elastic moduli; piezoelectric elements; sonometry
22.  Shear elastic modulus estimation from indentation and SDUV on gelatin phantoms 
Tissue mechanical properties such as elasticity are linked to tissue pathology state. Several groups have proposed shear wave propagation speed to quantify tissue mechanical properties. It is well known that biological tissues are viscoelastic materials; therefore velocity dispersion resulting from material viscoelasticity is expected. A method called Shearwave Dispersion Ultrasound Vibrometry (SDUV) can be used to quantify tissue viscoelasticity by measuring dispersion of shear wave propagation speed. However, there is not a gold standard method for validation. In this study we present an independent validation method of shear elastic modulus estimation by SDUV in 3 gelatin phantoms of differing stiffness. In addition, the indentation measurements are compared to estimates of elasticity derived from shear wave group velocities. The shear elastic moduli from indentation were 1.16, 3.40 and 5.6 kPa for a 7, 10 and 15% gelatin phantom respectively. SDUV measurements were 1.61, 3.57 and 5.37 kPa for the gelatin phantoms respectively. Shear elastic moduli derived from shear wave group velocities were 1.78, 5.2 and 7.18 kPa for the gelatin phantoms respectively. The shear elastic modulus estimated from the SDUV, matched the elastic modulus measured by indentation. On the other hand, shear elastic modulus estimated by group velocity did not agree with indentation test estimations. These results suggest that shear elastic modulus estimation by group velocity will be bias when the medium being investigated is dispersive. Therefore a rheological model should be used in order to estimate mechanical properties of viscoelastic materials.
PMCID: PMC3134144  PMID: 21317078
Indentation; SDUV; elasticity
23.  Implementation of Vibro-acoustography on a Clinical Ultrasound System 
Vibro-acoustography is an ultrasound-based imaging modality that uses two ultrasound beams of slightly different frequencies to produce images based on the acoustic response due to harmonic ultrasound radiation force excitation at the difference frequency between the two ultrasound frequencies. Vibro-acoustography has demonstrated feasibility and usefulness in imaging of breast and prostate tissue. However, previous studies have been performed either in controlled water tank settings or a prototype breast scanner equipped with a water tank. In order to make vibro-acoustography more accessible and relevant to clinical use, we report here on the implementation of vibro-acoustography on a General Electric Vivid 7 ultrasound scanner. In this paper, we will describe software and hardware modifications that were performed to make vibro-acoustography functional on this system. We will discuss aperture definition for the two ultrasound beams and beamforming using a linear array transducer. Experimental results from beam measurements and phantom imaging studies will be shown. The implementation of vibro-acoustography provides a step towards clinical translation of this imaging modality for applications in various organs including breast, prostate, thyroid, kidney, and liver.
PMCID: PMC3138131  PMID: 21693399
24.  Lamb Wave Dispersion Ultrasound Vibrometry (LDUV) Method for Quantifying Mechanical Properties of Viscoelastic Solids 
Physics in medicine and biology  2011;56(7):2245-2264.
Diastolic dysfunction is the inability of the left ventricle to supply sufficient stroke volumes under normal physiological conditions and is often accompanied by stiffening of the left-ventricular myocardium. A noninvasive technique capable of quantifying viscoelasticity of the myocardium would be beneficial in clinical settings.
Our group has been investigating the use of Shearwave Dispersion Ultrasound Vibrometry (SDUV), a noninvasive ultrasound based method for quantifying viscoelasticity of soft tissues. The primary motive of this study is the design and testing of viscoelastic materials suitable for validation of the Lamb wave Dispersion Ultrasound Vibrometry (LDUV), an SDUV-based technique for measuring viscoelasticity of tissues with plate-like geometry. We report the results of quantifying viscoelasticity of urethane rubber and gelatin samples using LDUV and an embedded sphere method. The LDUV method was used to excite antisymmetric Lamb waves and measure the dispersion in urethane rubber and gelatin plates. An antisymmetric Lamb wave model was fitted to the wave speed dispersion data to estimate elasticity and viscosity of the materials. A finite element model of a viscoelastic plate submerged in water was used to study the appropriateness of the Lamb wave dispersion equations. An embedded sphere method was used as an independent measurement of the viscoelasticity of the urethane rubber and gelatin. The FEM dispersion data were in excellent agreement with the theoretical predictions. Viscoelasticity of the urethane rubber and gelatin obtained using the LDUV and embedded sphere methods agreed within one standard deviation. LDUV studies on excised porcine myocardium sample were performed to investigate the feasibility of the approach in preparation for open-chest in vivo studies. The results suggest that the LDUV technique can be used to quantify mechanical properties of soft tissues with a plate-like geometry.
PMCID: PMC3086697  PMID: 21403186
Ultrasound in medicine & biology  2010;36(2):343-349.
Vibro-acoustography (VA) is an imaging method that forms a two-dimensional (2-D) image by moving two cofocused ultrasound beams with slightly different frequencies over the object in a C-scan format and recording acoustic emission from the focal region at the difference frequency. This article studies tissue heating due to a VA scan using a concentric confocal transducer. The three-dimensional (3-D) ultrasound intensity field calculated by Field II is used with the bio-heat equation to estimate tissue heating due to ultrasound absorption. Results calculated with thermal conduction and with blood perfusion, with conduction and without perfusion and without conduction and without perfusion are compared. Maximum heating due to ultrasound absorption occurs in the transducer’s near-field and maximum temperature rise in soft tissue during a single VA scan is below 0.05°C for all three attenuation coefficients evaluated: 0.3, 0.5 and 0.7 dB/cm/MHz. Transducer self-heating during a single VA scan measured by a thermocouple is less than 0.27°C.
PMCID: PMC2835550  PMID: 20113864
Vibro-acoustography; Tissue heating; Bio-heat equation

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