Multi-Frequency 3D Shear Wave Absolute Vibro-Elastography (S-WAVE) System for the Prostate.

This article describes a novel system for quantitative and volumetric measurement of tissue elasticity in the prostate using simultaneous multi-frequency tissue excitation. Elasticity is computed by using a local frequency estimator to measure the three-dimensional local wavelengths of steady-state shear waves within the prostate gland. The shear wave is created using a mechanical voice coil shaker which transmits simultaneous multi-frequency vibrations transperineally. Radio frequency data is streamed directly from a BK Medical 8848 transrectal ultrasound transducer to an external computer where tissue displacement due to the excitation is measured using a speckle tracking algorithm. Bandpass sampling is used that eliminates the need for an ultra-fast frame rate to track the tissue motion and allows for accurate reconstruction at a sampling frequency that is below the Nyquist rate. A roll motor with computer control is used to rotate the transducer and obtain 3D data. Two commercially available phantoms were used to validate both the accuracy of the elasticity measurements as well as the functional feasibility of using the system for in vivo prostate imaging. The phantom measurements were compared with 3D Magnetic Resonance Elastography (MRE), where a high correlation of 96% was achieved. In addition, the system has been used in two separate clinical studies as a method for cancer identification. Qualitative and quantitative results of 11 patients from these clinical studies are presented here. Furthermore, an AUC of 0.87±0.12 was achieved for malignant vs. benign classification using a binary support vector machine classifier trained with data from the latest clinical study with leave one patient out cross-validation.

Ultrasound RF time series for classification of breast lesions.

This work reports the use of ultrasound radio frequency (RF) time series analysis as a method for ultrasound-based classification of malignant breast lesions. The RF time series method is versatile and requires only a few seconds of raw ultrasound data with no need for additional instrumentation. Using the RF time series features, and a machine learning framework, we have generated malignancy maps, from the estimated cancer likelihood, for decision support in biopsy recommendation. These maps depict the likelihood of malignancy for regions of size 1 mm(2) within the suspicious lesions. We report an area under receiver operating characteristics curve of 0.86 (95% confidence interval [CI]: 0.84%-0.90%) using support vector machines and 0.81 (95% CI: 0.78-0.85) using Random Forests classification algorithms, on 22 subjects with leave-one-subject-out cross-validation. Changing the classification method yielded consistent results which indicates the robustness of this tissue typing method. The findings of this report suggest that ultrasound RF time series, along with the developed machine learning framework, can help in differentiating malignant from benign breast lesions, subsequently reducing the number of unnecessary biopsies after mammography screening.

Multi-parametric 3D quantitative ultrasound vibro-elastography imaging for detecting palpable prostate tumors.

In this article, we describe a system for detecting dominant prostate tumors, based on a combination of features extracted from a novel multi-parametric quantitative ultrasound elastography technique. The performance of the system was validated on a data-set acquired from n = 10 patients undergoing radical prostatectomy. Multi-frequency steady-state mechanical excitations were applied to each patient's prostate through the perineum and prostate tissue displacements were captured by a transrectal ultrasound system. 3D volumetric data including absolute value of tissue elasticity, strain and frequency-response were computed for each patient. Based on the combination of all extracted features, a random forest classification algorithm was used to separate cancerous regions from normal tissue, and to compute a measure of cancer probability. Registered whole mount histopathology images of the excised prostate gland were used as a ground truth of cancer distribution for classifier training. An area under receiver operating characteristic curve of 0.82 +/- 0.01 was achieved in a leave-one-patient-out cross validation. Our results show the potential of multi-parametric quantitative elastography for prostate cancer detection for the first time in a clinical setting, and justify further studies to establish whether the approach can have clinical use.

Mesh adaptation for improving elasticity reconstruction using the FEM inverse problem.

The finite element method is commonly used to model tissue deformation in order to solve for unknown parameters in the inverse problem of viscoelasticity. Typically, a (regular-grid) structured mesh is used since the internal geometry of the domain to be identified is not known a priori. In this work, the generation of problem-specific meshes is studied and such meshes are shown to significantly improve inverse-problem elastic parameter reconstruction. Improved meshes are generated from axial strain images, which provide an approximation to the underlying structure, using an optimization-based mesh adaptation approach. Such strain-based adapted meshes fit the underlying geometry even at coarse mesh resolutions, therefore improving the effective resolution of the reconstruction at a given mesh size/complexity. Elasticity reconstructions are then performed iteratively using the reflective trust-region method for optimizing the fit between estimated and observed displacements. This approach is studied for Young's modulus reconstruction at various mesh resolutions through simulations, yielding 40%-72% decrease in root-mean-square reconstruction error and 4-52 times improvement in contrast-to-noise ratio in simulations of a numerical phantom with a circular inclusion. A noise study indicates that conventional structured meshes with no noise perform considerably worse than the proposed adapted meshes with noise levels up to 20% of the compression amplitude. A phantom study and preliminary in vivo results from a breast tumor case confirm the benefit of the proposed technique. Not only conventional axial strain images but also other elasticity approximations can be used to adapt meshes. This is demonstrated on images generated by combining axial strain and axial-shear strain, which enhances lateral image contrast in particular settings, consequently further improving mesh-adapted reconstructions.

Dilatation parameterization for two-dimensional modeling of nearly incompressible isotropic materials.

A new method to model the stress­strain relationship in two dimensions is proposed, which is particularly suited for analyzing nearly incompressible materials, such as soft tissue. In most cases of soft tissue modeling, plane strain is reported to approximate the deformation when an external compression is applied. However, it is subject to limitations when dealing with incompressible materials, e.g., when solving the inverse problem of elasticity. We propose a novel 2D model for the linear stress­strain relationship by describing the out-of-plane strain as a linear combination of the two in-plane strains. As such, the model can be represented in 2D while being able to explain the three-dimensional deformation. We show that in simple cases where the applied force is dominantly in one direction, one can approximate the sum of the three principal strain components in a plane by a scalar multiplied by the out-of-plane strain. 3D finite-element simulations have been performed. The proposed model has been tested under different boundary conditions and material properties. The results show that the model parametrization is affected mostly by the boundary conditions, while being relatively independent of the underlying distribution of Young's modulus. An application to the inverse problem of elasticity is presented where a more accurate estimate is obtained using the proposed dilatation model compared to the plane-stress and plane-strain models.

Real-time quantitative elasticity imaging of deep tissue using free-hand conventional ultrasound.

In this article an ultrasound elastography technology is reported which provides quantitative images of tissue elasticity from deep soft tissue. The technique is analogous to Magnetic Resonance Elastography in the use of external mechanical vibrations which can penetrate deep tissue. Multifrequency steady-state mechanical vibrations are applied to the tissue at the skin and tissue displacements are measured by a conventional ultrasound system. Absolute values of tissue elasticity are computed in real-time for each frequency and displayed to the physician. The quantitative elasticity images produced by the technology are validated with magnetic resonance elastography images as the gold standard on standard elasticity phantoms. Preliminary in-vivo data from healthy volunteers are presented which show the potential of the technology for clinical use. The system is currently being used in different clinical studies to image kidney fibrosis, liver fibrosis, and prostate cancer.

Bandpass sampling of high-frequency tissue motion.

The characterization of tissue viscoelastic properties requires the measurement of tissue motion over a region of interest at frequencies that significantly exceed the frame rates of conventional ultrasound systems. In this paper, we propose that the bandpass sampling technique be applied to tissue motion sampling. With this approach, high-frequency signals limited to a frequency band can be sampled and reconstructed without aliasing at a sampling frequency that is lower than the Nyquist rate. We first review this approach and discuss the selection of the tissue excitation frequency band and of the feasible sampling frequencies that allow signal reconstruction without aliasing. We then demonstrate the approach using simulations based on the finite element method and ultrasound simulations. Finally, we perform experiments on tissue-mimicking materials and demonstrate accurate motion estimation using a lower sampling rate than that required by the conventional sampling theorem. The estimated displacements were used to measure the elasticity and viscosity in a phantom in which an inclusion has been correctly delineated. Thus, with bandpass sampling, it is feasible to use conventional beamforming on diagnostic ultrasound systems to perform high-frequency dynamic elastography. The method is simple to implement because it does not require beam interleaving, additional hardware, or synchronization.

Measurement of viscoelastic properties of tissue-mimicking material using longitudinal wave excitation.

This paper presents an experimental framework for the measurement of the viscoelastic properties of tissue-mimicking material. The novelty of the presented framework is in the use of longitudinal wave excitation and the study of the longitudinal wave patterns in finite media for the measurement of the viscoelastic properties. Ultrasound is used to track the longitudinal motions inside a test block. The viscoelastic parameters of the block are then estimated by 2 methods: a wavelength measurement method and a model fitting method. Connections are also made with shear elastography. The viscoelastic parameters are estimated for several homogeneous phantom blocks. The results from the new methods are compared with the conventional rheometry results.

The influence of the boundary conditions on longitudinal wave propagation in a viscoelastic medium.

In this paper, the effect of the boundary conditions and excitation dimensions on the speed of longitudinal waves in a medium is investigated. It is shown that with appropriate boundary conditions, a low-speed longitudinal wave can be generated in the medium which can be tracked by standard pulse-echo ultrasound motion tracking techniques. Three different cases of boundary conditions are explored in which the longitudinal wave speed in an incompressible material can be as high as the acoustic wave speed or as low as the shear wave speed. It is shown that the displacement spectrum can be used to estimate the wave speed in a viscoelastic medium. Numerical simulations with 3D viscoelastic finite element models and experiments on tissue-mimicking phantoms are performed to validate the theory.

Viscoelastic characterization of soft tissue from dynamic finite element models.

An iterative solution to the inverse problem of elasticity and viscosity is proposed in this paper. A new dynamic finite element model that is consistent with known rheological models has been derived to account for the viscoelastic changes in soft tissue. The model assumes known lumped masses at the nodes, and comprises two vectors of elasticity and viscosity parameters that depend on the material elasticity and viscosity distribution, respectively. Using this deformation model and the observed dynamic data for harmonic excitation, the inverse problem is solved to reconstruct the viscosity and elasticity in the medium by using a Gauss-Newton-based approach. As in other inverse problems, previous knowledge of the parameters on the boundaries of the medium is necessary to assure uniqueness and convergence and to obtain an accurate map of the viscoelastic properties. The sensitivity of the solutions to noise, model and boundary conditions has been studied through numerical simulations. Experimental results are also presented. The viscosity and elasticity of a gelatin-based phantom with inclusion of known properties have been reconstructed and have been shown to be close to the values obtained using standard rheometry.

Characterization of the viscosity and elasticity in soft tissue using dynamic finite elements.

An iterative solution to the inverse problem of elasticity and viscosity is proposed in this paper. A finite elements model has been derived to account for the viscoelastic changes in soft tissue that is consistent with known rheological models. Using this deformation model and the observed dynamic data, the viscosity and elasticity have been reconstructed in the medium by using a Gauss-Newton based approach. Previous knowledge of the parameters on the boundaries of the medium are necessary to assure uniqueness and convergence and to obtain an accurate map of the viscoelastic properties. The methods have been studied in FEM simulations and also tested through experiments, where the viscosity and elasticity of a gelatin based phantom with an inclusion of known properties have been reconstructed successfully.

Tissue strain imaging using a wavelet transform-based peak search algorithm.

A new method is proposed to estimate the motion and relative local compression between two successive ultrasound RF signals under different compression states. The algorithm uses the continuous wavelet transform to locate the peaks in the RF signals. The estimated peaks in the pre- and post-compression signals are assigned to each other by a peak matching technique with the goal of minimizing the number of false matches. The method allows local shifts of the tissue to be estimated. The method has been tested in one-dimensional simulations and phantom experiments. The signal-to-noise ratio and the rms error are shown to be better than for the standard cross-correlation method (CC). The new estimator remains unbiased for up to 10% strain which is a larger range than that of CC. The maximum signal-to-noise ratio is 3 times as high as that of the CC method, showing higher sensitivity as well. The method is computationally efficient, achieving 0.7 msec/RF line on a standard personal computer.