In plane quantification ofin vivomuscle elastic anisotropy factor by steered ultrasound pushing beams.

Objective.Skeletal muscles are organized into distinct layers and exhibit anisotropic characteristics across various scales. Assessing the arrangement of skeletal muscles may provide valuable biomarkers for diagnosing muscle-related pathologies and evaluating the efficacy of clinical interventions.Approach. In this study, we propose a novel ultrafast ultrasound sequence constituted of steered pushing beams was proposed for ultrasound elastography applications in transverse isotropic muscle. Based on the propagation of the shear wave vertical mode, it is possible to fit the experimental results to retrieve in the same imaging plane, the shear modulus parallel to fibers as well as the elastic anisotropy factor (ratio of Young's moduli times the shear modulus perpendicular to fibers).Main results. The technique was demonstratedin vitroin phantoms andex vivoin fusiform beef muscles. At last, the technique was appliedin vivoon fusiform muscles (biceps brachii) and mono-pennate muscles (gastrocnemius medialis) during stretching and contraction.Significance. This novel sequence provides access to new structural and mechanical biomarkers of muscle tissue, including the elastic anisotropy factor, within the same imaging plane. Additionally, it enables the investigation of multiples parameters during muscle active and passive length changes.

In Vivo Ultrafast Doppler Imaging Combined with Confocal Microscopy and Behavioral Approaches to Gain Insight into the Central Expression of Peripheral Neuropathy in Trembler-J Mice.

The main human hereditary peripheral neuropathy (Charcot-Marie-Tooth, CMT), manifests in progressive sensory and motor deficits. Mutations in the compact myelin protein gene pmp22 cause more than 50% of all CMTs. CMT1E is a subtype of CMT1 myelinopathy carrying micro-mutations in pmp22. The Trembler-J mice have a spontaneous mutation in pmp22 identical to that present in CMT1E human patients. PMP22 is mainly (but not exclusively) expressed in Schwann cells. Some studies have found the presence of pmp22 together with some anomalies in the CNS of CMT patients. Recently, we identified the presence of higher hippocampal pmp22 expression and elevated levels of anxious behavior in TrJ/+ compared to those observed in wt. In the present paper, we delve deeper into the central expression of the neuropathy modeled in Trembler-J analyzing in vivo the cerebrovascular component by Ultrafast Doppler, exploring the vascular structure by scanning laser confocal microscopy, and analyzing the behavioral profile by anxiety and motor difficulty tests. We have found that TrJ/+ hippocampi have increased blood flow and a higher vessel volume compared with the wild type. Together with this, we found an anxiety-like profile in TrJ/+ and the motor difficulties described earlier. We demonstrate that there are specific cerebrovascular hemodynamics associated with a vascular structure and anxious behavior associated with the TrJ/+ clinical phenotype, a model of the human CMT1E disease.

Anisotropy in ultrasound shear wave elastography: An add-on to muscles characterization.

Ultrasound shear wave elastography was developed the past decade, bringing new stiffness biomarker in clinical practice. This biomarker reveals to be of primarily importance for the diagnosis of breast cancer or liver fibrosis. In muscle this biomarker become much more complex due to the nature of the muscle itself: an anisotropic medium. In this manuscript we depict the underlying theory of propagating waves in such anisotropic medium. Then we present the available methods that can consider and quantify this parameter. Advantages and drawbacks are discussed to open the way to imagine new methods that can free this biomarker in a daily clinical practice.

Intensity distribution segmentation in ultrafast Doppler combined with scanning laser confocal microscopy for assessing vascular changes associated with ageing in murine hippocampi.

The hippocampus plays an important role in learning and memory, requiring high-neuronal oxygenation. Understanding the relationship between blood flow and vascular structure-and how it changes with ageing-is physiologically and anatomically relevant. Ultrafast Doppler ([Formula: see text]Doppler) and scanning laser confocal microscopy (SLCM) are powerful imaging modalities that can measure in vivo cerebral blood volume (CBV) and post mortem vascular structure, respectively. Here, we apply both imaging modalities to a cross-sectional and longitudinal study of hippocampi vasculature in wild-type mice brains. We introduce a segmentation of CBV distribution obtained from [Formula: see text]Doppler and show that this mice-independent and mesoscopic measurement is correlated with vessel volume fraction (VVF) distribution obtained from SLCM-e.g., high CBV relates to specific vessel locations with large VVF. Moreover, we find significant changes in CBV distribution and vasculature due to ageing (5 vs. 21 month-old mice), highlighting the sensitivity of our approach. Overall, we are able to associate CBV with vascular structure-and track its longitudinal changes-at the artery-vein, venules, arteriole, and capillary levels. We believe that this combined approach can be a powerful tool for studying other acute (e.g., brain injuries), progressive (e.g., neurodegeneration) or induced pathological changes.

Vortex dynamics and transport phenomena in stenotic aortic models using Echo-PIV.

Atherosclerosis is the most fatal cardiovascular disease. As disease progresses, stenoses grow inside the arteries blocking their lumen and altering blood flow. Analysing flow dynamics can provide a deeper insight on the stenosis evolution. In this work we combined Eulerian and Lagrangian descriptors to analyze blood flow dynamics and fluid transport in stenotic aortic models with morphology, mechanical and optical properties close to those of real arteries. To this end, vorticity, particle residence time (PRT), particle's final position (FP) and finite time Lyapunov's exponents (FTLE) were computed from the experimental fluid velocity fields acquired using ultrasonic particle imaging velocimetry (Echo-PIV). For the experiments, CT-images were used to create morphological realistic models of the descending aorta with 0%, 35% and 50% occlusion degree with same mechanical properties as real arteries. Each model was connected to a circuit with a pulsatile programmable pump which mimics physiological flow and pressure conditions. The pulsatile frequency was set to ≈0.9 Hz (55 bpm) and the upstream peak Reynolds number (Re) was changed from 1100 to 2000. Flow in the post-stenotic region was composed of two main structures: a high velocity jet over the stenosis throat and a recirculation region behind the stenosis where vortex form and shed. We characterized vortex kinematics showing that vortex propagation velocity increases withRe. Moreover, from the FTLE field we identified Lagrangian coherent structures (i.e. material barriers) that dictate transport behind the stenosis. The size and strength of those barriers increased withReand the occlusion degree. Finally, from the PRT and FP maps, we showed that independently ofRe, the same amount of fluid remains on the stenosis over more than a pulsatile period.

Development and evaluation of anisotropic and nonlinear aortic models made from clinical images for in vitro experimentation.

In this work we developed a methodology to manufacture a new type of arterial model that could be used in experimental setting instead of excised arteries while developing new imaging modalities. CT-images of the descending aorta were used to create molds with patient specific morphology. A polyvinyl alcohol (PVA) solution with a reinforcing cotton mesh was used to generate the models. The mesh is circumferentially elastic while non-compliant longitudinally and is responsible for the non-linear anisotropic mechanical behavior of the models. Two models were fabricated following the same manufacturing procedure. Their circumferential and longitudinal mechanical properties were evaluated and compared to those of excised healthy pig aortas via tensile testing. A very good agreement was found for the circumferential direction, while the longitudinal direction showed to have a more marked anisotropic behavior compared to the excise arteries. An increase from 113 kPa at 2.5% strain, to 914 kPa at 40% strain was obtained for the models, while the arteries showed an increase from 172 kPa at 2.5% strain to 922 kPa at 38% strain. Furthermore, by plugging the models into a cardiovascular simulator their mechanical response in a more realistic setting was evaluated under static and dynamic pressure conditions by using shear wave elastography (SWE). Static and dynamic experiments showed an increase in the shear modulus as a function of pressure from 61 kPa to 263 kPa, between 20 mmHg and 150 mmHg for Model 1 (similar values within 10% were obtained for Model 2). These values are in good agreement with those reported in the literature for healthy human arteries. To our knowledge the models presented in this study are the first morphologically realistic phantoms that have demonstrated nonlinear and anisotropic elastic behaviors close to those of healthy arteries.

Drastic slowdown of the Rayleigh-like wave in unjammed granular suspensions.

We present an experimental investigation of Rayleigh-like wave propagation along the surface of a dense granular suspension. Using an ultrafast ultrasound scanner, we monitor the softening of the shear modulus via the Rayleigh-like wave velocity slowdown in the optically opaque medium as the driving amplitude increases. For such nonlinear behavior two regimes are found when increasingthe driving amplitude progressively: First, we observe a significant shear modulus weakening due to the microslip on the contact level without macroscopic rearrangements of grains. Second, there is a clear macroscopic plastic rearrangement accompanied by a modulus decrease up to 88%. A friction model is proposed to describe the interplay between nonlinear elasticity and plasticity, which highlights the crucial effect of contact slipping before contact breaking or loss. Investigation of this nonlinear Rayleigh-like wave may bridge the gap between two disjoint approaches for describing the dynamics near unjamming: linear elastic soft modes and nonlinear collisional shock.

Analysis of the transient surface wave propagation in soft-solid elastic plates.

In dynamic elastography, the goal is to estimate the Young's modulus from audio-frequency wave propagation in soft-tissues. Within this frequency range, the shear wavelength is centimeter-sized while the compressional wavelength is meter-sized. Thus, the experimental data are usually collected in the near-field of the source. Near-field effects have been widely studied for bulk wave propagation. However, the near- and transient-fields of surface and guided waves have received less attention. In this work, the transient surface displacement field in soft-solid elastic plates in vacuum is analyzed. Due to the high Poisson's ratio, mode conversion has special characteristics in soft-solids. They are analyzed through this work where it is shown that the transient-field over the surface can be interpreted by tracing a few reflections. The authors show the existence of a critical distance needed for the formation of Rayleigh-Lamb modes. Below this distance, only direct surface waves propagate without contribution from reflected waves. Thus, the dispersion curve differs from that predicted by Rayleigh-Lamb modes. Instead, the authors propose a model based on the interference of surface waves, which agree with the experimental data. In addition, the conditions needed in order to retrieve the shear wave phase velocity from the surface field are given.

A diffraction correction for storage and loss moduli imaging using radiation force based elastography.

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

Shear Wave Measurements for Evaluation of Tendon Diseases.

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

Quantitative shear elasticity imaging from a complex elastic wavefield in soft solids with application to passive elastography.

In passive elastography, the complex physiological noise present in the human body is used to conduct an elastography experiment. In the present work, quantitative shear elasticity imaging from a complex elastic wavefield is demonstrated in soft solids. By correlating the elastic field at different positions, which can be interpreted as a time-reversal experiment, shear waves are virtually focused on any point of the imaging plane. According to the Rayleigh criterion, the focus size is directly related to the shear wave speed and thus to the shear elasticity. To locally retrieve a shear wave speed estimation, analytical and empirical expressions that relate the focus size with the shear wave speed and the frequency band used in the correlation computation are derived. The validity of such expressions is demonstrated numerically and experimentally on a tissue-mimicking phantom consisting of two different elastic layers. The obtained results were in complete agreement with a prior shear wave speed estimation demonstrating the potential of the technique to quantitative shear elasticity assessment using a complex elastic wavefield. Finally, an ultraslow experiment at an imaging rate of 10 Hz shows the technique to be compatible with slow imaging devices such as standard echographs or MRI scanners.

A new high-resolution spectral approach to noninvasively evaluate wall deformations in arteries.

By locally measuring changes on arterial wall thickness as a function of pressure, the related Young modulus can be evaluated. This physical magnitude has shown to be an important predictive factor for cardiovascular diseases. For evaluating those changes, imaging segmentation or time correlations of ultrasonic echoes, coming from wall interfaces, are usually employed. In this paper, an alternative low-cost technique is proposed to locally evaluate variations on arterial walls, which are dynamically measured with an improved high-resolution calculation of power spectral densities in echo-traces of the wall interfaces, by using a parametric autoregressive processing. Certain wall deformations are finely detected by evaluating the echoes overtones peaks with power spectral estimations that implement Burg and Yule Walker algorithms. Results of this spectral approach are compared with a classical cross-correlation operator, in a tube phantom and "in vitro" carotid tissue. A circulating loop, mimicking heart periods and blood pressure changes, is employed to dynamically inspect each sample with a broadband ultrasonic probe, acquiring multiple A-Scans which are windowed to isolate echo-traces packets coming from distinct walls. Then the new technique and cross-correlation operator are applied to evaluate changing parietal deformations from the detection of displacements registered on the wall faces under periodic regime.

Estimation of PSD shifts for high-resolution metrology of thickness micro-changes with possible applications in vessel walls and biological membrane characterization.

Achieving accurate measurements of inflammation levels in tissues or thickness changes in biological membranes (e.g., amniotic sac, parietal pleura) and thin biological walls (e.g., blood vessels) from outside the human body, is a promising research line in the medical area. It would provide a technical basis to study the options for early diagnosis of some serious diseases such as hypertension, atherosclerosis or tuberculosis. Nevertheless, achieving the aim of non-invasive measurement of those scarcely-accessible parameters on patient internal tissues, currently presents many difficulties. The use of high-frequency ultrasonic transducer systems appears to offer a possible solution. Previous studies using conventional ultrasonic imaging have shown this, but the spatial resolution was not sufficient so as to permit a thickness evaluation with clinical significance, which requires an accuracy of a few microns. In this paper a broadband ultrasonic technique, that was recently developed by the authors to address other non-invasive medical detection problems (by integrating a piezoelectric transducer into a spectral measuring system), is extended to our new objective; the aim is its application to the thickness measurement of sub-millimeter membranes or layers made of materials similar to some biological tissues (phantoms). The modeling and design rules of such a transducer system are described, and various methods of estimating overtones location in the power spectral density (PSD) are quantitatively assessed with transducer signals acquired using piezoelectric systems and also generated from a multi-echo model. Their effects on the potential resolution of the proposed thickness measuring tool, and their capability to provide accuracies around the micron are studied in detail. Comparisons are made with typical tools for extracting spatial parameters in laminar samples from echo-waveforms acquired with ultrasonic transducers. Results of this advanced measurement spectral tool are found to improve the performance of typical cross-correlation methods and provide reliable and high-resolution estimations.

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.

Integrated Evaluation of Age-Related Changes in Structural and Functional Vascular Parameters Used to Assess Arterial Aging, Subclinical Atherosclerosis, and Cardiovascular Risk in Uruguayan Adults: CUiiDARTE Project.

This work was carried out in a Uruguayan (South American) population to characterize aging-associated physiological arterial changes. Parameters markers of subclinical atherosclerosis and that associate age-related changes were evaluated in healthy people. A conservative approach was used and people with nonphysiological and pathological conditions were excluded. Then, we excluded subjects with (a) cardiovascular (CV) symptoms, (b) CV disease, (c) diabetes mellitus or renal failure, and (d) traditional CV risk factors (other than age and gender). Subjects (n = 388) were submitted to non-invasive vascular studies (gold-standard techniques), to evaluate (1) common (CCA), internal, and external carotid plaque prevalence, (2) CCA intima-media thickness and diameter, (3) CCA stiffness (percentual pulsatility, compliance, distensibility, and stiffness index), (4) aortic stiffness (carotid-femoral pulse wave velocity), and (5) peripheral and central pressure wave-derived parameters. Age groups: ≤20, 21-30, 31-40, 41-50, 51-60, 61-70, and 71-80 years old. Age-related structural and functional vascular parameters profiles were obtained and analyzed considering data from other populations. The work has the strength of being the first, in Latin America, that uses an integrative approach to characterize vascular aging-related changes. Data could be used to define vascular aging and abnormal or disease-related changes.

Passive elastography: shear-wave tomography from physiological-noise correlation in soft tissues.

Inspired by seismic-noise correlation and time reversal, a shear-wave tomography of soft tissues using an ultrafast ultrasonic scanner is presented here. Free from the need for controlled shear-wave sources, this passive elastography is based on Green's function retrieval and takes advantage of the permanent physiological noise of the human body.

Arterial diameter measurement using high resolution ultrasonography: in vitro validation.

Simultaneous measurement of pressure and diameter in blood vessels or vascular prosthesis is of great importance in cardiovascular research. Knowledge of diameter changes as response to intravascular pressure is the basis to estimate the biomechanical properties of blood vessel. In this work a new method to quantify arterial diameter based in high resolution ultrasonography is proposed. Measurements on an arterial phantom placed on a cardiovascular simulator were performed. The results were compared to sonomicrometry measurements considered as gold standard technique. The obtained results indicate that the new method ensure an optimal diameter quantification. This method presents two main advantages respect to sonomicrometry: is noninvasive and the vessel wall strain can be measured directly.

1-D elasticity assessment in soft solids from shear wave correlation: the time-reversal approach.

One-channel time-reversal (TR) experiments allow focalization of waves in reverberant cavities. According to the Rayleigh criterion, the focal spot width is directly related to the wavelength and therefore depends on the mechanical properties of the medium. Thus, the general idea of this work is to extract quantitative estimations of these mechanical properties using a time-reversal approach based on cross-correlations of the wave field. An external source creates mechanical waves in the audible frequency range. One component of the vectorial field is measured along a line as function of time with signal processing developed in the field of 1-D elastography. The shear wavelength information is deduced from these mechanical waves using spatiotemporal correlations and interpreted in the frame of the time-reversal symmetry. The impact of wave attenuation in soft solids is reduced using a spatial average of the correlation field. The result is shown to be suitable for global elasticity estimation. The advantage is that the technique is almost independent of the source kind, shape, and time excitation function. This robustness as regard to shear wave source allows translation of this technique to applications in the medical field, including deep or moving organs.