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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Myocardial Thermal Ablation with a Transesophageal High-Intensity Focused Ultrasound Probe: Experiments on Beating Heart Models.

Described here is a study of transesophageal thermal ablation of isolated and perfused beating hearts and non-human primates. An endoscope integrating a transesophageal echocardiography probe and a high-intensity focused ultrasound transducer was built and tested on five Langendorff-isolated hearts and three 30-kg baboons. B-Mode ultrasound, passive elastography and magnetic resonance imaging were performed to monitor thermal lesions. In isolated hearts, continuous and gated sonication parameters were evaluated with acoustic intensities of 9-12 W/cm2. Sonication parameters of gated exposures with 12 W/cm2 acoustic intensity for 5 min consistently produced visible lesions in the ventricles of isolated hearts. In animals, left atria and ventricles were exposed to repeated continuous sonications (4-15 times for 16 s) at an acoustic intensity at the surface of the transducer of 9 W/cm2. Clinical states of the baboons during and after the treatment were good. One suspected lesion in the left ventricle could be evidenced by elastography, but was not confirmed by magnetic resonance imaging. The transesophageal procedure therefore has the potential to create thermal lesions in beating hearts and its safety in clinical practice seems promising. However, further technical exploration of the energy deposition in the target would be necessary before the next pre-clinical experiments.

Lorentz Force Electrical-Impedance Tomography Using Linearly Frequency-Modulated Ultrasound Pulse.

Lorentz force electrical-impedance tomography (LFEIT) combines ultrasound stimulation and electromagnetic field detection with the goal of creating a high-contrast and high-resolution hybrid imaging modality. To reduce the peak stimulation power to the ultrasound transducer in LFEIT, linearly frequency-modulated (LFM) ultrasound pulse was investigated in this paper. First, the coherency between LFM ultrasound excitation and the resulting local current density was established theoretically. Then, experiments were done using different agar phantoms of conductivity ranging from 0.2 to 0.5 S/m. The results showed: 1) using electrical signal of peak instantaneous power of 39.54 dBm to the ultrasound transducer, which was 25.5 dB lower than the peak instantaneous power of the high-voltage narrow pulse adopted in traditional LFEIT (65.05 dBm), the LFM ultrasound pulse-based LFEIT can detect the electrical conductivity discontinuity positions precisely; 2) the reconstructed B-scan image of the electrical conductivity discontinuity distribution is comparable to that obtained through LFEIT with high-voltage narrow pulse; and 3) axial resolution of 1 mm was achieved with the experimental setup. The method of LFM ultrasound pulse stimulation and coherent detection initiates an alternative scheme toward the clinical application of LFEIT.

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.

Diffuse shear wave imaging: toward passive elastography using low-frame rate spectral-domain optical coherence tomography.

Optical coherence tomography (OCT) can map the stiffness of biological tissue by imaging mechanical perturbations (shear waves) propagating in the tissue. Most shear wave elastography (SWE) techniques rely on active shear sources to generate controlled displacements that are tracked at ultrafast imaging rates. Here, we propose a noise-correlation approach to retrieve stiffness information from the imaging of diffuse displacement fields using low-frame rate spectral-domain OCT. We demonstrated the method on tissue-mimicking phantoms and validated the results by comparison with classic ultrafast SWE. Then we investigated the in vivo feasibility on the eye of an anesthetized rat by applying noise correlation to naturally occurring displacements. The results suggest a great potential for passive elastography based on the detection of natural pulsatile motions using conventional spectral-domain OCT systems. This would facilitate the transfer of OCT-elastography to clinical practice, in particular, in ophthalmology or dermatology.

Contactless remote induction of shear waves in soft tissues using a transcranial magnetic stimulation device.

This study presents the first observation of shear waves induced remotely within soft tissues. It was performed through the combination of a transcranial magnetic stimulation device and a permanent magnet. A physical model based on Maxwell and Navier equations was developed. Experiments were performed on a cryogel phantom and a chicken breast sample. Using an ultrafast ultrasound scanner, shear waves of respective amplitudes of 5 and 0.5 µm were observed. Experimental and numerical results were in good agreement. This study constitutes the framework of an alternative shear wave elastography method.

Generation of Shear Waves by Laser in Soft Media in the Ablative and Thermoelastic Regimes.

This article describes the generation of elastic shear waves in a soft medium using a laser beam. Our experiments show two different regimes depending on laser energy. Physical modeling of the underlying phenomena reveals a thermoelastic regime caused by a local dilatation resulting from temperature increase, and an ablative regime caused by a partial vaporization of the medium by the laser. Computed theoretical displacements are close to experimental measurements. A numerical study based on the physical modeling gives propagation patterns comparable to those generated experimentally. These results provide a physical basis for the feasibility of a shear wave elastography technique (a technique which measures a soft solid stiffness from shear wave propagation) by using a laser beam.