Flexural pulse wave velocity in blood vessels.

Arteriosclerosis is a major risk factor for cardiovascular disease and results in arterial vessel stiffening. Velocity estimation of the pulse wave sent by the heart and propagating into the arteries is a widely accepted biomarker. This symmetrical pulse wave propagates at a speed which is related to the Young's modulus through the Moens Korteweg (MK) equation. Recently, an antisymmetric flexural wave has been observed in vivo. Unlike the symmetrical wave, it is highly dispersive. This property offers promising applications for monitoring arterial stiffness and early detection of atheromatous plaque. However, as far as it is known, no equivalent of the MK equation exists for flexural pulse waves. To bridge this gap, a beam based theory was developed, and approximate analytical solutions were reached. An experiment in soft polymer artery phantoms was built to observe the dispersion of flexural waves. A good agreement was found between the analytical expression derived from beam theory and experiments. Moreover, numerical simulations validated wave speed dependence on the elastic and geometric parameters at low frequencies. Clinical applications, such as arterial age estimation and arterial pressure measurement, are foreseen.

High-frequency ultrasound point-of-care device to quantify myopia-induced microstructural changes in the anterior sclera.

PURPOSE: To develop a point-of-care (POC) device using high-frequency ultrasound (US) for evaluating microstructural changes in the anterior sclera associated with myopia. METHODS: The proposed POC device must satisfy four primary requirements for effective clinical use: the measurement component is handheld; the software must be simple and provide real-time feedback; patient safety and health data security requirements set forth by relevant governing bodies must be satisfied and the measurement data must have sufficient signal-to-noise ratio (SNR) and repeatability. Radiofrequency (RF) echo data acquired by the POC device will be processed using our quantitative US methods to characterise tissue microstructure and biomechanical properties. RESULTS: All stated requirements have been met in the developed POC device. The high-frequency transducer is housed in a custom, 3D-printed, pen-like holder that allows for easy measurements of the anterior sclera. Custom software provides a simple interface for data acquisition, real-time data display and secure data storage. Exposimetry measurements of the US pressure field indicate device compliance with United States Food and Drug Administration limits for ophthalmic US. In vivo measurements on a volunteer suggest the RF data SNR and acquisition consistency are suitable for quantitative analysis. CONCLUSIONS: A fully functioning POC device using high-frequency US has been created for evaluating the microstructure of the anterior sclera. Planned studies using the POC device to scan the eyes of myopia patients will help clarify how the anterior sclera microstructure may be affected by myopia. If effective, this portable, inexpensive and user-friendly system could be an important part of routine eye examinations.

Ultrafast imaging of cell elasticity with optical microelastography.

Elasticity is a fundamental cellular property that is related to the anatomy, functionality, and pathological state of cells and tissues. However, current techniques based on cell deformation, atomic force microscopy, or Brillouin scattering are rather slow and do not always accurately represent cell elasticity. Here, we have developed an alternative technique by applying shear wave elastography to the micrometer scale. Elastic waves were mechanically induced in live mammalian oocytes using a vibrating micropipette. These audible frequency waves were observed optically at 200,000 frames per second and tracked with an optical flow algorithm. Whole-cell elasticity was then mapped using an elastography method inspired by the seismology field. Using this approach we show that the elasticity of mouse oocytes is decreased when the oocyte cytoskeleton is disrupted with cytochalasin B. The technique is fast (less than 1 ms for data acquisition), precise (spatial resolution of a few micrometers), able to map internal cell structures, and robust and thus represents a tractable option for interrogating biomechanical properties of diverse cell types.

Full-field passive elastography using digital holography.

Off-axis digital holography is an imaging technique that allows direct measurement of phase and amplitude from one image. We utilize this technique to capture displacements induced by a diffuse shear wave field with high sensitivity. A noise-correlation-based algorithm is then used to measure mechanical properties of samples. This approach enables full-field quantitative passive elastography without the need of contact or a synchronized source of a mechanical wave. This passive elastography method is first validated on agarose test samples mimicking biological tissues, and first results on an ex vivo biological sample are presented.

Brain palpation from physiological vibrations using MRI.

We present a magnetic resonance elastography approach for tissue characterization that is inspired by seismic noise correlation and time reversal. The idea consists of extracting the elasticity from the natural shear waves in living tissues that are caused by cardiac motion, blood pulsatility, and any muscle activity. In contrast to other magnetic resonance elastography techniques, this noise-based approach is, thus, passive and broadband and does not need any synchronization with sources. The experimental demonstration is conducted in a calibrated phantom and in vivo in the brain of two healthy volunteers. Potential applications of this "brain palpation" approach for characterizing brain anomalies and diseases are foreseen.

Bone-conducted sound in a dolphin's mandible: Experimental investigation of elastic waves mediating information on sound source position.

Mammals use binaural or monaural (spectral) cues to localize acoustic sources. While the sensitivity of terrestrial mammals to changes in source elevation is relatively poor, the accuracy achieved by the odontocete cetaceans' biosonar is high, independently of where the source is. Binaural/spectral cues are unlikely to account for this remarkable skill. In this paper, bone-conducted sound in a dolphin's mandible is studied, investigating its possible contribution to sound localization. Experiments are conducted in a water tank by deploying, on the horizontal and median planes of the skull, ultrasound sources that emit synthetic clicks between 45 and 55 kHz. Elastic waves propagating through the mandible are measured at the pan bones and used to localize source positions via either binaural cues or a correlation-based full-waveform algorithm. Exploiting the full waveforms and, most importantly, reverberated coda, it is possible to enhance the accuracy of source localization in the vertical plane and achieve similar resolution of horizontal- vs vertical-plane sources. The results noted in this paper need to be substantiated by further experimental work, accounting for soft tissues and making sure that the data are correctly mediated to the internal ear. If confirmed, the results would favor the idea that dolphin's echolocation skills rely on the capability to analyze the coda of biosonar echoes.

Full-field noise-correlation elastography for in-plane mechanical anisotropy imaging.

Elastography contrast imaging has great potential for the detection and characterization of abnormalities in soft biological tissues to help physicians in diagnosis. Transient shear-waves elastography has notably shown promising results for a range of clinical applications. In biological soft tissues such as muscle, high mechanical anisotropy implies different stiffness estimations depending on the direction of the measurement. In this study, we propose the evolution of a noise-correlation elastography approach for in-plane anisotropy mapping. This method is shown to retrieve anisotropy from simulation images before being validated on agarose anisotropic tissue-mimicking phantoms, and the first results on in-vivo biological fibrous tissues are presented.

Passive Elastography for Clinical HIFU Lesion Detection.

High-intensity Focused Ultrasound (HIFU) is a promising treatment modality for a wide range of pathologies including prostate cancer. However, the lack of a reliable ultrasound-based monitoring technique limits its clinical use. Ultrasound currently provides real-time HIFU planning, but its use for monitoring is usually limited to detecting the backscatter increase resulting from chaotic bubble appearance. HIFU has been shown to generate stiffening in various tissues, so elastography is an interesting lead for ablation monitoring. However, the standard techniques usually require the generation of a controlled push which can be problematic in deeper organs. Passive elastography offers a potential alternative as it uses the physiological wave field to estimate the elasticity in tissues and not an external perturbation. This technique was adapted to process B-mode images acquired with a clinical system. It was first shown to faithfully assess elasticity in calibrated phantoms. The technique was then implemented on the Focal One® clinical system to evaluate its capacity to detect HIFU lesions in vitro (CNR = 9.2 dB) showing its independence regarding the bubbles resulting from HIFU and in vivo where the physiological wave field was successfully used to detect and delineate lesions of different sizes in porcine liver. Finally, the technique was performed for the very first time in four prostate cancer patients showing strong variation in elasticity before and after HIFU treatment (average variation of 33.0 ± 16.0 % ). Passive elastography has shown evidence of its potential to monitor HIFU treatment and thus help spread its use.

A mechanistic interpretation of relativistic rigid body rotation.

The starting point of this manuscript is classical rigid body rotation. As it is well known, it contradicts basis of relativity since infinite speed is reached at infinite distance from the rotation center O. In order to fix this problem, a phenomenological circle-based construction using Euclidian trigonometry is first described: the relativistic rigid body rotation. The physical Eulerian acceleration implied by this geometrical construction then sketches future links with Maxwell's equation and Lense-Thirring effect. More importantly, relativistic rigid body rotation is shown to be compatible with Lorentz transformation and brings new geometrical interpretations of time and space intervals.

Observation of natural flexural pulse waves in retinal and carotid arteries for wall elasticity estimation.

The risk of cardiovascular events is linked to arterial elasticity that can be estimated from the pulse wave velocity. This symmetric wave velocity is related to the wall elasticity through the Moens-Korteweg equation. However, ultrasound imaging techniques need improved accuracy, and optical measurements on retinal arteries produce inconsistent results. Here, we report the first observation of an antisymmetric pulse wave: the flexural pulse wave. An optical system performs in vivo wave velocity measurements on retinal arteries and veins. Velocity estimation ranges between 1 and 10 millimeter per second. The theory of guided waves confirms the existence of this wave mode and its low velocity. Natural flexural waves can also be detected at the bigger scale of a carotid artery using ultrafast ultrasound imaging. This second natural pulse wave has great potential of becoming a biomarker of blood vessel aging.

A passive inverse filter for Green's function retrieval.

Passive methods for the recovery of Green's functions from ambient noise require strong hypotheses, including isotropic distribution of the noise sources. Very often, this distribution is nonisotropic, which introduces bias in the Green's function reconstruction. To minimize this bias, a spatiotemporal inverse filter is proposed. The method is tested on a directive noise field computed from an experimental active seismic data set. The results indicate that the passive inverse filter allows the manipulation of the spatiotemporal degrees of freedom of a complex wave field, and it can efficiently compensate for the noise wavefield directivity.

Spectral Analysis of Tissue Displacement for Cardiac Activation Mapping: Ex Vivo Working Heart and In Vivo Study.

Characterizing myocardial activation is of major interest for understanding the underlying mechanism of cardiac arrhythmias. Electromechanical wave imaging (EWI) is an ultrafast ultrasound-based method used to map the propagation of the local contraction triggered by electrical activation of the heart. This study introduces a novel way to characterize cardiac activation based on the time evolution of the instantaneous frequency content of the cardiac tissue displacement curves. The first validation of this method was performed on an ex vivo dataset of 36 acquisitions acquired from two working heart models in paced rhythms. It was shown that the activation mapping described by spectral analysis of interframe displacement is similar to the standard EWI method based on zero-crossing of interframe strain. An average median error of 3.3 ms was found in the ex vivo dataset between the activation maps obtained with the two methods. The feasibility of mapping cardiac activation by EWI was then investigated on two open-chest pigs during sinus and paced rhythms in a pilot trial of cardiac mapping with an intracardiac probe. Seventy-five acquisitions were performed with reasonable stability and analyzed with the novel algorithm to map cardiac contraction propagation in the left ventricle (LV). Sixty-one qualitatively continuous isochrones were successfully computed based on this method. The region of contraction onset was coherently described while pacing in the imaging plane. These findings highlight the potential of implementing EWI acquisition on intracardiac probes and emphasize the benefit of performing short time-frequency analysis of displacement data to characterize cardiac activation in vivo.

Electromechanical delay in biceps brachii assessed by ultrafast ultrasonography.

Using ultrasound we tested the utility of determining the relative contribution of the main muscle structures/mechanisms to the electromechanical delay in the biceps brachii. Nine subjects underwent electrically evoked contractions with the echographic probe maintained over the muscle and the myotendinous junction. No difference was found between the onset of muscle fascicle motion (Dm, 5.57 ± 1.37 ms) and the onset of myotendinous junction motion (Dt, 5.47 ± 1.38 ms), whereas significant differences were found between Dm/Dt and electromechanical delay (approximately 10 ms). Electromechanical delay can be used as a model for studying the effects of neuromuscular disorders or various constraints that affect excitation-contraction coupling and/or muscle force transmission.

Coherent backscattering enhancement in cavities. Highlights of the role of symmetry.

Through experiments and simulations, the consequences of symmetry on coherent backscattering enhancement (CBE) are studied in cavities. Three main results are highlighted. First, the CBE outside the source is observed: (a) on a single symmetric point in a one-dimensional (1-D) cavity, in a disk and in a symmetric chaotic plate; (b) on three symmetric points in a two-dimensional (2-D) rectangle; and (c) on seven symmetric points in a three-dimensional (3-D) parallelepiped cavity. Second, the existence of enhanced intensity lines and planes in 2-D and 3-D simple-shape cavities is demonstrated. Third, it is shown how the anti-symmetry caused by the special boundary conditions is responsible for the existence of a coherent backscattering decrement with a dimensional dependence of R = (½)(d), with d = 1,2,3 as the dimensionality of the cavity.

Shear Wave Generation by Remotely Stimulating Aluminum Patches With a Transient Magnetic Field and Its Preliminary Application in Elastography.

OBJECTIVE: This article presents shear wave generation by remotely stimulating aluminum patches through a transient magnetic field, and its preliminary application in the cross-correlation approach based ultrasound elastography. METHODS: A transient magnetic field is employed to remotely vibrate the patch actuators through the Lorentz force. The origin, and the characteristics of the Lorentz force are confirmed using an interferometric laser probe. The shear wave displacement fields generated in the soft medium are studied through the ultrafast ultrasound imaging. The potential of the shear wave fields generated through the patch actuators for the cross-correlation approach based elastography is confirmed through experiments on an agar phantom sample. RESULTS: Under a transient magnetic field of changing rate of 10.44 kT/s, the patch actuator generates a shear wave source of amplitude of 100  µm in a polyvinyl alcohol (PVA) phantom sample. The shear wave fields created by experiments agree qualitatively well with those by theory. From the shear wave velocity map computed from 100 frames of shear wave fields, the boundaries of cylindrical regions of different stiffness can be clearly recognized, which are completely concealed in the ultrasound image. CONCLUSION: Shear wave fields in the level of 100  µm can be remotely generated in soft medium through stimulating aluminum patches with a transient magnetic field, and qualitative shear wave velocity maps can be reconstructed from the shear wave fields generated. SIGNIFICANCE: The proposed method allows potential application of the cross-correlation approach based elastography in intravascular-based or catheter-based cardiology.

Time-of-flight and noise-correlation-inspired algorithms for full-field shear-wave elastography using digital holography.

SIGNIFICANCE: Quantitative stiffness information can be a powerful aid for tumor or fibrosis diagnosis. Currently, very promising elastography approaches developed for non-contact biomedical imaging are based on transient shear-waves imaging. Transient elastography offers quantitative stiffness information by tracking the propagation of a wave front. The most common method used to compute stiffness from the acquired propagation movie is based on shear-wave time-of-flight calculations. AIM: We introduce an approach to transient shear-wave elastography with spatially coherent sources, able to yield full-field quantitative stiffness maps with reduced artifacts compared to typical artifacts observed in time-of-flight. APPROACH: A noise-correlation algorithm developed for passive elastography is adapted to spatially coherent narrow or any band sources. This noise-correlation-inspired (NCi) method is employed in parallel with a classic time-of-flight approach. Testing is done on simulation images, experimental validation is conducted with a digital holography setup on controlled homogeneous samples, and full-field quantitative stiffness maps are presented for heterogeneous samples and ex-vivo biological tissues. RESULTS: The NCi approach is first validated on simulations images. Stiffness images processed by the NCi approach on simulated inclusions display significantly less artifacts than with a time-of-flight reconstruction. The adaptability of the NCi algorithm to narrow or any band shear-wave sources was tested successfully. Experimental testing on homogeneous samples demonstrates similar values for both the time-of-flight and the NCi approach. Soft inclusions in agarose sample could be resolved using the NCi method and feasibility on ex-vivo biological tissues is presented. CONCLUSIONS: The presented NCi approach was successful in computing quantitative full-field stiffness maps with narrow and broadband source signals on simulation and experimental images from a digital holography setup. Results in heterogeneous media show that the NCi approach could provide stiffness maps with less artifacts than with time-of-flight, demonstrating that a NCi algorithm is a promising approach for shear-wave transient elastography with spatially coherent sources.

Imaging of Thermal Effects during High-Intensity Ultrasound Treatment in Liver by Passive Elastography: A Preliminary Feasibility in Vitro Study.

High-intensity focused ultrasound is a non-invasive modality for thermal ablation of tissues through locally increased temperature. Thermal lesions can be monitored by elastography, following the changes in the elastic properties of the tissue as reflected by the shear-wave velocity. Most studies on ultrasound elastography use shear waves created by acoustic radiation force. However, in the human body, the natural noise resulting from cardiac activity or arterial pulsatility can be used to characterize elasticity through noise-correlation techniques, in the method known as passive elastography. The objective of this study was to investigate the feasibility of monitoring high-intensity ultrasound treatments of liver tissue using passive elastography. Bovine livers were heated to 80°C using a high-intensity planar transducer and imaged with a high-frame-rate ultrasound imaging device. The dynamics of lesion formation are captured through tissue stiffening and lesion expansion.

Electromechanical delay revisited using very high frame rate ultrasound.

Electromechanical delay (EMD) represents the time lag between muscle activation and muscle force production and is used to assess muscle function in healthy and pathological subjects. There is no experimental methodology to quantify the actual contribution of each series elastic component structures that together contribute to the EMD. We designed the present study to determine, using very high frame rate ultrasound (4 kHz), the onset of muscle fascicles and tendon motion induced by electrical stimulation. Nine subjects underwent two bouts composed of five electrically evoked contractions with the echographic probe maintained over 1) the gastrocnemius medialis muscle belly (muscle trials) and 2) the myotendinous junction of the gastrocnemius medialis muscle (tendon trials). EMD was 11.63 +/- 1.51 and 11.67 +/- 1.27 ms for muscle trials and tendon trials, respectively. Significant difference (P < 0.001) was found between the onset of muscle fascicles motion (6.05 +/- 0.64 ms) and the onset of myotendinous junction motion (8.42 +/- 1.63 ms). The noninvasive methodology used in the present study enabled us to determine the relative contribution of the passive part of the series elastic component (47.5 +/- 6.0% of EMD) and each of the two main structures of this component (aponeurosis and tendon, representing 20.3 +/- 10.7% and 27.6 +/- 11.4% of EMD, respectively). The relative contributions of the synaptic transmission, the excitation-contraction coupling, and the active part of the series elastic component could not be directly quantified with our results. However, they suggest a minor role of the active part of the series elastic component that needs to be confirmed by further experiments.

Optical elastography: tracking surface waves with digital image correlation.

Elastography consists in evaluating the propagation speed of waves into a tissue to estimate its stiffness. Usually this method is based on Ultrasounds, magnetic resonance imaging or optical coherent tomography. This paper proposes a simple optic method using ultrafast cameras. Based on digital image correlation (DIC), the tracking of elastic surface wave from white light intensity pattern, allows estimating the propagation speed as an indicator of the tissue local stiffness. Two configurations are presented: (1) 2D imaging of a flat phantom surface with a single camera and (2) 3D imaging of a curved phantom surface with two cameras. As a feasibility study of the first configuration, surface wave speed was measured on isotropic and anisotropic phantoms. Comparisons with ultrasound methods fully validate this approach. Although more sophisticated, the second configuration account for propagation distortions caused by locally curved topology. Triangulation techniques used to retrieve local topology are named stereo-correlation in the field of biomechanics. Stereo-elastography is thus proposed to determine tissue local elasticity from any soft tissue surface wave.