Regularization-Based 2D Strain Tensor Imaging in Quasi-Static Ultrasound Elastography SAGE Publications.

Accurately estimating all strain components in quasi-static ultrasound elastography is crucial for the full analysis of biological media. In this study, 2D strain tensor imaging was investigated, focusing on the use of a regularization method to improve strain images. This method enforces the tissue property of (quasi-) incompressibility, while penalizing strong field variations, to smooth the displacement fields and reduce the noise in the strain components. The performance of the method was assessed with numerical simulations, phantoms, and in vivo breast tissues. For all the media examined, the results showed a significant improvement in both lateral displacement and strain, while axial fields were only slightly modified by the regularization. The introduction of penalty terms allowed us to obtain shear strain and rotation elastograms where the patterns around the inclusions/lesions were clearly visible. In phantom cases, the findings were consistent with the results obtained from the modeling of the experiments. Finally, the easier detectability of the inclusions/lesions in the final lateral strain images was associated with higher elastographic contrast-to-noise ratios (CNRs), with values in the range of [0.54-9.57] versus [0.08-0.38] before regularization.

Generalization of Multipulse Transmission Techniques for Ultrasound Imaging.

To increase the contrast-to-tissue ratio (CTR) in contrast imaging or the signal-to-noise ratio (SNR) in tissue harmonic imaging, many multipulse transmission techniques have been suggested. This article first recalls the various imaging techniques proposed in the literature and then presents a mathematical background to synthesize and generalize most of the multipulse ultrasound imaging techniques. The formulation presented can be used to predict the relative amplitude of the nonlinear components in each frequency band and to design new transmission sequences to either increase or decrease specified nonlinear components in each harmonic band. Simulation results on several multipulse techniques agree with the results from previous studies.

Optimized Virtual Sources Distributions for 3-D Ultrafast Diverging Wave Compounding Imaging: A Simulation Study.

Ultrafast ultrasound imaging allows observing rapid phenomena; combined with 3-D imaging it has the potential to provide a more accurate analysis of organs which leads, in the end, to better diagnosis. Coherent compounding using diverging waves is commonly used to reconstruct high-quality images on large volumes while keeping the frame rate high enough to allow dynamic analysis. In practice, the virtual sources (VSs) that drive the diverging waves are often distributed in a deterministic way: following a regular grid, concentric rings, and spirals. Even though those deterministic distributions can offer various tradeoffs in terms of imaging performance, other distributions can be considered to improve imaging performance. It is herein suggested to look at alternative VSs distributions for optimizing the lateral resolution and the secondary lobes level (SLL) on several point spread functions (PSFs) by means of a multiobjective genetic algorithm. The optimization framework has led to seven pseudo-irregular distributions of VSs distributions that have not yet been found in the literature. An analysis of the imaging performance with a simulated phantom shows that these new distributions offer different tradeoffs between lateral resolution and contrast, respectively, measured on point-like reflectors and anechoic cysts. As an example, one of these optimized distributions improves the lateral resolution by 16% and gives equivalent contrast values on cysts and PSF isotropy properties, when compared to a concentric-rings-based distribution.

On the potential of ultrasound elastography for pressure ulcer early detection.

PURPOSE: Pressure ulcers are areas of soft tissue breakdown induced by a sustained mechanical stress that damages the skin and underlying tissues. They represent a considerable burden to the society in terms of health care and cost. Yet, techniques for prevention and detection of pressure ulcers still remain very limited. In this article, the authors investigated the potential of ultrasound elastography for pressure ulcer early detection. Elastography is an imaging technique providing local information on biological tissue mechanical properties. It is relevant for pressure ulcer detection as this pathology is associated with a gradual stiffening of damaged tissues, beginning in the deeper tissues and progressing toward the skin surface. METHODS: A 2D ultrasound elastography method was proposed and its ability in terms of pressure ulcer detection was validated through numerical simulations and physical acquisitions on pressure ulcer mimicking phantoms. In vivo experiments on a rat model are also reported. A maintained pressure was applied on the animal thigh, with a view to generate a pressure ulcer, and ultrasound data were acquired and processed before and after application of this pressure. RESULTS: Numerical simulations demonstrated that a pressure ulcer can theoretically be detected at a very early stage with ultrasound elastography. Even when the ulcer region was characterized by a low stiffening (ratio of 1.8 relative to normal tissues), the corresponding elastogram clearly underlined the pathological area. This observation was confirmed by the results obtained on a physical phantom mimicking a pressure ulcer at an early stage. Computed elastograms showed strain differences between areas mimicking healthy and pathological tissues. Results corresponding to in vivo experiments revealed a difference in the way tissues behaved before and after the pressure was applied on the animal thigh, which strongly suggests the presence of a pathological area. CONCLUSIONS: Experiments demonstrated that ultrasound elastography is a promising technique for pressure ulcer detection, especially at an early stage of the pathology, when the disease is still visually undetectable. In the absence of any gold standard method, this is also a first step toward the development of a quantitative technique.

A compensative model for the angle-dependence of motion estimates in noninvasive vascular elastography.

PURPOSE: Atherosclerosis of peripheral cerebral arteries can lead to stroke either by stenosis formation or plaque rupture. This pathology is initiated by the alteration of arterial wall mechanical properties shown to be assessable by ultrasound elastography. Recently, noninvasive vascular elastography (NIVE) was introduced for noninvasive imaging of the mechanical properties of superficial arteries as markers of vulnerable plaques. However, NIVE motion estimates are angle-dependent, with optimal scanning angle being represented by the alignment of tissue motion with ultrasound beam orientation. The objective of this study was to introduce a model that compensates for such angle-dependence in order to reduce the bias on strain estimates, namely, when investigating longitudinal vessel segments. METHODS: The model is based on the Lagrangian speckle model estimator (LSME) because the LSME assesses the 2D-deformation matrix required to compute the scanning angle. RESULTS: Experiments on vessel-mimicking phantoms indicated that such a model enables the estimation of scanning angle with less than 3-degrees error. The method was also validated in vivo in human carotid arteries where less than 4-degrees error was observed. In both cases, the compensative model estimated the inclination angles with low variability. CONCLUSION: Angle-dependence may be an important factor to consider in avoiding potentially distort clinical diagnoses. Results, reported in this article, suggest that the LSME-based compensative model might be considered as a very interesting and promising clinical tool for NIVE applications.

2D tissue strain tensor imaging in quasi-static ultrasound elastography.

Accurately estimating all strain components in quasi-static ultrasound elastography is crucial for the full analysis of biological media. In this paper, 2D strain tensor imaging is investigated, using a partial differential equation (PDE)-based regularization method. More specifically, this method employs the tissue property of incompressibility to smooth the displacement fields and reduce the noise in the strain components. The performance of the method is assessed with phantoms and in vivo breast tissues. For all the media examined, the results showed a significant improvement in both lateral displacement and strain but also, to a lesser extent, in the shear strain. Moreover, axial displacement and strain were only slightly modified by the regularization, as expected. Finally, the easier detectability of the inclusion/lesion in the final lateral strain images is associated with higher elastographic contrast-to-noise ratios (CNRs), with values in the range [0.68 - 9.40] vs [0.09 - 0.38] before regularization.

Quantitative assessment of media concentration using the Homodyned K distribution.

The Homodyned K distribution has been used successfully as a tool in the ultrasound characterization of sparse media, where the scatterer clustering parameter α accurately discriminates between media with different numbers of scatterers per resolution cell. However, as the number of scatterers increases and the corresponding amplitude statistics become Rician, the reliability of the α estimates decreases rapidly. In the present study, we assess the usefulness of α for the characterization of both sparse and concentrated media, using simulated independent and identically distributed (i.i.d.) samples from Homodyned K distributions, ultrasound images of media with up to 68 scatterers per resolution cell and ultrasound signals acquired from particle phantoms with up to 101 scatterers per resolution cell. All parameter estimates are obtained using the XU estimator (Destrempes et al., 2013). Results suggest that the parameter α can be used to distinguish between media with up to 40 scatterers per resolution cell at 22 MHz, provided that parameter estimation can be performed on very large sample sizes (i.e., >10,000 i.i.d. samples).

Spectral Doppler Measurements With 2-D Sparse Arrays.

The 2-D sparse arrays, in which a few hundreds of elements are distributed on the probe surface according to an optimization procedure, represent an alternative to full 2-D arrays, including thousands of elements usually organized in a grid. Sparse arrays have already been used in B-mode imaging tests, but their application to Doppler investigations has not been reported yet. Since the sparsity of the elements influences the acoustic field, a corresponding influence on the mean frequency (Fm), bandwidth (BW), and signal-to-noise ratio (SNR) of the Doppler spectra is expected. This article aims to assess, by simulations and experiments, to what extent the use of a sparse rather than a full gridded 2-D array has an impact on spectral Doppler measurements. Parabolic flows were investigated by a 3 MHz, 1024-element gridded array and by a sparse array; the latter was obtained by properly selecting a subgroup of 256 elements from the full array. Simulations show that the mean Doppler frequency does not change between the sparse and the full array while there are significant differences on the BW (average reduction of 17.2% for the sparse array, due to different apertures of the two probes) and on the signal power (Ps) (22 dB, due to the different number of active elements). These results are confirmed by flow phantom experiments, which also highlight that the most critical difference between sparse and full gridded array in Doppler measurements is in terms of SNR (-16.8 dB).

Quantitative Ultrasound in Ex Vivo Fibrotic Rabbit Livers.

Liver fibrosis is the common result of chronic liver disease. Diagnosis and grading liver fibrosis for patient management is mainly based on blood tests and hepatic puncture-biopsy, which is particularly invasive. Quantitative ultrasound (QUS) techniques provide insight into tissue microstructure and are based on the frequency-based analysis of the signals from biologic tissues. This study aims to quantify how spectral-based QUS parameters change with fibrosis grade. The changes in QUS parameters of healthy and fibrotic rabbit liver samples were investigated and were compared with the changes in liver stiffness, using shear wave elastography. Overall, the acoustic concentration was found to decrease with increasing fibrosis grade, and the effective scatterer size was found to be higher in fibrotic livers when compared with normal liver. The result of this study indicates that the combination of three QUS parameters (stiffness, effective scatterer size and acoustic concentration) provides the best classification performance, especially for classifying healthy and fibrotic livers.

3D dynamic model of healthy and pathologic arteries for ultrasound technique evaluation.

A 3D model reproducing the biomechanical behavior of human blood vessels is presented. The model, based on a multilayer geometry composed of right generalized cylinders, enables the representation of different vessel morphologies, including bifurcations, either healthy or affected by stenoses. Using a finite element approach, blood flow is simulated by considering a dynamic displacement of the scatterers (erythrocytes), while arterial pulsation due to the hydraulic pressure is taken into account through a fluid-structure interaction based on a wall model. Each region is acoustically characterized using FIELD II software, which produces the radio frequency echo signals corresponding to echographic scans. Three acoustic physiological phantoms of carotid arteries surrounded by elastic tissue are presented to illustrate the model's capability. The first corresponds to a healthy blood vessel, the second includes a 50% stenosis, and the third represents a carotid bifurcation. Examples of M mode, B mode and color Doppler images derived from these phantoms are shown. Two examples of M-mode image segmentation and the identification of the atherosclerotic plaque boundaries on Doppler color images are reported. The model could be used as a tool for the preliminary evaluation of ultrasound signal processing and visualization techniques.

2-D locally regularized tissue strain estimation from radio-frequency ultrasound images: theoretical developments and results on experimental data.

In this paper, a 2-D locally regularized strain estimation method for imaging deformation of soft biological tissues from radio-frequency (RF) ultrasound (US) data is introduced. Contrary to most 2-D techniques that model the compression-induced local displacement as a 2-D shift, our algorithm also considers a local scaling factor in the axial direction. This direction-dependent model of tissue motion and deformation is induced by the highly anisotropic resolution of RF US images. Optimal parameters are computed through the constrained maximization of a similarity criterion defined as the normalized correlation coefficient. Its value at the solution is then used as an indicator of estimation reliability, the probability of correct estimation increasing with the correlation value. In case of correlation loss, the estimation integrates an additional constraint, imposing local continuity within displacement and strain fields. Using local scaling factors and regularization increase the method's robustness with regard to decorrelation noise, resulting in a wider range of precise measurements. Results on simulated US data from a mechanically homogeneous medium subjected to successive uniaxial loadings demonstrate that our method is theoretically able to accurately estimate strains up to 17%. Experimental strain images of phantom and cut specimens of bovine liver clearly show the harder inclusions.

Experimental Implementation of a Pulse Compression Technique Using Coherent Plane-Wave Compounding.

The axial resolution of an ultrasound imaging system is inversely proportional to the bandwidth of the emitted signal. When conventional pulsing (CP) is used, the impulse response of the transducer and the excitation signal determine together the shape of the emitted pulse and its bandwidth. A way to increase the ultrasound image resolution is to increase the transducer's limited passband. The resolution enhancement compression (REC) is a coding technique that boosts the signal energy in the transition frequency bands, where the energy transduction of the ultrasound probe is less efficient. Consequently, image quality metrics including axial resolution, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) can be improved. In this paper, the objective is to combine REC with coherent plane-wave compounding (CPWC) in order to achieve better image quality at an ultrafast acquisition rate. Promising results are obtained from both wire and cyst phantoms using an excitation signal designed to provide a 54% increase in bandwidth over the one obtained with a broadband pulse excitation at -6 dB. The experimental bandwidth measured from the backscattered echoes was improved by 49% for the wire phantom, when using the CPWC-REC technique compared to CPWC-CP. Furthermore, the axial resolution as derived from the modulation transfer function of the envelope of the wire target was enhanced by 29%. The CNR and SNR were improved up to 9 and up to 4 dB, respectively, in the cyst phantom. These results reveal that CPWC-REC is able to achieve higher spatial resolution, compared to CPWC-CP, with better SNR and CNR. Moreover, experimental results show that an effective implementation on a research scanner of REC using plane-wave imaging is possible. Consistent in vivo acquisition results on rabbit are presented and discussed.

Bcl-2 overexpression prevents calcium overload and subsequent apoptosis in dystrophic myotubes.

Duchenne muscular dystrophy (DMD) is a lethal disease caused by the lack of the cytoskeletal protein dystrophin. Altered calcium homoeostasis and increased calcium concentrations in dystrophic fibres may be responsible for the degeneration of muscle occurring in DMD. In the present study, we used subsarcolemmal- and mitochondrial-targeted aequorin to study the effect of the antiapoptotic Bcl-2 protein overexpression on carbachol-induced near-plasma membrane and mitochondrial calcium responses in myotubes derived from control C57 and dystrophic (mdx) mice. We show that Bcl-2 overexpression decreases subsarcolemmal and mitochondrial calcium overload that occurs during activation of nicotinic acetylcholine receptors in dystrophic myotubes. Moreover, our results suggest that overexpressed Bcl-2 protein may prevent near-plasma membrane and mitochondrial calcium overload by inhibiting IP3Rs (inositol 1,4,5-trisphosphate receptors), which we have shown previously to be involved in abnormal calcium homoeostasis in dystrophic myotubes. Most likely as a consequence, the inhibition of IP3R function by Bcl-2 also inhibits calcium-dependent apoptosis in these cells.

Noninvasive Young's modulus evaluation of tissues surrounding pulsatile vessels using ultrasound Doppler measurement.

This paper presents an indirect approach to estimating the mechanical properties of tissues surrounding the arterial vessels using ultrasound (US) Doppler measurements combined with an inverse problem-solving method. The geometry of the structure and the dynamic behavior of the inner fluid are first evaluated using a novel dual-beam US system. A numerical phantom associated with a parametric finite element simulator that calculates the hydrodynamic pressure and the displacement on the walls' boundaries is then built. The simulation results are iteratively compared to the US measurement results to deduce the value of the unknown parameters, i.e., the Young's modulus and the pressure resulting from the downstream load. The feasibility of the proposed approach was experimentally tested in vitro using a phantom composed of a latex tube surrounded by a cryogel tissue-mimicking material.

Radiofrequency ultrasound data acquisition with a 640-element array transducer for strain imaging: Experimental results with phantoms and biological tissue samples.

This paper presents ultrasound elastography results obtained with a 640-element array transducer we have recently developed. This probe allows the acquisition of series of three adjacent imaging planes over time and therefore makes possible the computation of 2-D elastograms, with consideration of out-of-plane motion. In this study, elastography experiments were conducted on phantoms and bovine tissue samples, and compression was manually applied to the media via the hand-held ultrasound transducer. The results obtained with the proposed data acquisition and 3-D processing are presented and compared to those from a classical 2-D approach.

Fast Nonlinear Ultrasound Propagation Simulation Using a Slowly Varying Envelope Approximation.

Medical systems usually consider linear propagation of ultrasound, an approximation of reality. However, numerous studies have attempted to accurately simulate the nonlinear pressure wave distortion and to evaluate the contribution of harmonic frequencies. In such simulations, the computation time is very large, except for the method based on the angular spectrum scheme where the derivative order is reduced using the Fourier transform. However, the harmonic computation is usually limited to the second harmonic because of quasi-linear approximation. In this paper, a slowly varying envelope approximation (SVEA) is used in the Fourier domain to compute the entire nonlinear distortion induced, including high harmonics and nonlinear mixing frequencies. The simulation by SVEA is evaluated by comparison with other simulation tools. The obtained deviation and difference remain low enough to fully validate such an approximation. Moreover, the simulator is implemented on a GPU to obtain a very fast tool, where the full nonlinear distorted [Formula: see text] field is computed in less than 10 s.

Specific Ultrasound Data Acquisition for Tissue Motion and Strain Estimation: Initial Results.

Ultrasound applications such as elastography can benefit from 3-D data acquisition and processing. In this article, we describe a specific ultrasound probe, designed to acquire series of three adjacent imaging planes over time. This data acquisition makes it possible to consider the out-of-plane motion that can occur at the central plane during medium scanning, and is proposed with the aim of improving the results of strain imaging. In this first study, experiments were conducted on phantoms, and controlled axial and elevational displacements were applied to the probe using a motorized system. Radiofrequency ultrasound data were acquired at a 40-MHz sampling frequency with an Ultrasonix ultrasound scanner, and processed using a 3-D motion estimation method. For each of the 2-D regions of interest of the central plane in pre-compression data, a 3-D search was run to determine its corresponding version in post-compression data, with this search taking into account the region-of-interest deformation model chosen. The results obtained with the proposed ultrasound data acquisition and strain estimation were compared with results from a classic approach and illustrate the improvement produced by considering the medium's local displacements in elevation, with notably an increase in the mean correlation coefficients achieved.

Mitochondria buffer NCX-mediated Ca2+-entry and limit its diffusion into vascular smooth muscle cells.

The reverse-mode of the Na(+)/Ca(2+)-exchanger (NCX) mediates Ca(2+)-entry in agonist-stimulated vascular smooth muscle (VSM) and plays a central role in salt-sensitive hypertension. We investigated buffering of Ca(2+)-entry by peripheral mitochondria upon NCX reversal in rat aortic smooth muscle cells (RASMC). [Ca(2+)] was measured in mitochondria ([Ca(2+)](MT)) and the sub-plasmalemmal space ([Ca(2+)](subPM)) with targeted aequorins and in the bulk cytosol ([Ca(2+)](i)) with fura-2. Substitution of extracellular Na(+) by N-methyl-d-glucamine transiently increased [Ca(2+)](MT) ( approximately 2microM) and [Ca(2+)](subPM) ( approximately 1.3microM), which then decreased to sustained plateaus. In contrast, Na(+)-substitution caused a delayed and tonic increase in [Ca(2+)](i) (<100nM). Inhibition of Ca(2+)-uptake by the sarcoplasmic reticulum (SR) (30microM cyclopiazonic acid) or mitochondria (2microM FCCP or 2microM ruthenium red) enhanced the elevation of [Ca(2+)](subPM). These treatments also abolished the delay in the [Ca(2+)](i) response to 0Na(+) and increased its amplitude. Extracellular ATP (1mM) caused a peak and plateau in [Ca(2+)](i), and only the plateau was inhibited by KB-R7943 (10microM), a selective blocker of reverse-mode NCX. Evidence for ATP-mediated NCX-reversal was also found in changes in [Na(+)](i). Mitochondria normally exhibited a transient elevation of [Ca(2+)] in response to ATP, but inhibiting the mitochondrial NCX with CGP-37157 (10microM) unmasked an agonist-induced increase in mitochondrial Ca(2+)-flux. This flux was blocked by KB-R7943. In summary, mitochondria and the sarcoplasmic reticulum co-operate to buffer changes in [Ca(2+)](i) due to agonist-induced NCX reversal.

Evaluation of NADPH oxidases as drug targets in a mouse model of familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by progressive loss of motor neurons, gliosis, neuroinflammation and oxidative stress. The aim of this study was to evaluate the involvement of NADPH oxidases (NOX) in the oxidative damage and progression of ALS neuropathology. We examined the pattern of NOX expression in spinal cords of patients and mouse models of ALS and analyzed the impact of genetic deletion of the NOX1 and 2 isoforms as well as pharmacological NOX inhibition in the SOD1(G93A) ALS mouse model. A substantial (10-60 times) increase of NOX2 expression was detected in three etiologically different ALS mouse models while up-regulation of some other NOX isoforms was model-specific. In human spinal cord samples, high NOX2 expression was detected in microglia. In contrast to previous publications, survival of SOD1(G93A) mice was not modified upon breeding with constitutive NOX1 and NOX2 deficient mice. As genetic deficiency of a single NOX isoform is not necessarily predictive of a pharmacological intervention, we treated SOD1(G93A) mice with broad-spectrum NOX inhibitors perphenazine and thioridazine. Both compounds reached in vivo CNS concentrations compatible with NOX inhibition and thioridazine significantly decreased superoxide levels in the spinal cord of SOD1(G93A) mice in vivo. Yet, neither perphenazine nor thioridazine prolonged survival. Thioridazine, but not perphenazine, dampened the increase of microglia markers in SOD1(G93A) mice. Thioridazine induced an immediate and temporary enhancement of motor performance (rotarod) but its precise mode of action needs further investigation. Additional studies using specific NOX inhibitors will provide further evidence on the relevance of NOX as drug targets for ALS and other neurodegenerative disorders.

Thomson's multitaper approach combined with coherent plane-wave compounding to reduce speckle in ultrasound imaging.

In ultrasound imaging, the speckle pattern limits the image quality. Spatial and frequency compounding are commonly used to reduce speckle noise or improve the contrast. Although recent implementations can preserve a frame rate that is compatible with real-time imaging (e.g., synthetic aperture compounding), most classic compounding techniques are based on the coherent combination of several radiofrequency images from the same investigated area, which reduces the frame rate. Furthermore, Thomson's multitaper approach aims to smooth the speckle by incoherently combining the obtained B-mode images after applying different apodization windows on the same original data. With only one acquisition, the frame rate remains high, but the spatial resolution is decreased. To improve the resolution and contrast while reducing the speckle noise, this paper proposes combining the coherent plane-wave compounding technique (CPWC) with Thomson's multitaper method. The resulting multitaper coherent plane-wave compounding (MCPWC) takes advantage of coherent and incoherent approaches. Simulations and experimental results demonstrate that in terms of the signal-to-noise ratio, contrast, and resolution, the image quality is increased using plane wave emissions at approximately ten steering angles with three Thomson's tapers. Outside the focal area, the lateral resolution is improved by a factor of 2, and the contrast is increased by approximately 2dB compared with images obtained using a single focalization technique and Thomson's multitaper approach.