Single-Sided Ultrasound Imaging of the Bone Cortex: Anatomy, Tissue Characterization and Blood Flow.

In this chapter, we first review the reasons why conventional ultrasonography fails to image the interior of bones. Next we show our recent work on imaging a cortical bone layer with ultrasound. Revealing the shape of the cortex of a bone, in particular its thickness, is of interest for evaluating bone strength. In addition we describe how the process of reconstructing a truthful image of the bone cortex includes the estimation of ultrasound wave-speed in cortical bone tissue. Cortical bone exhibits elastic anisotropy, which causes anisotropy of ultrasound wave-speed as well. Therefore a faithful and high-quality picture of the bone cortex is obtained if wave-speed anisotropy is taken into account during image reconstruction. Capitalizing on prior knowledge on the elastic anisotropy of cortical bone, a procedure for estimating wave-speed and its anisotropy is described. It is based on the measurement of a head-wave velocity and an autofocus approach. The latter relies on the fact that the reconstructed ultrasound image shows optimal quality if the wave-speed model is correct. In order to achieve real-time imaging of a bone cortex, image reconstruction is performed with a delay-and-sum algorithm. Finally, we report recent advances in the measurement of blood flow in cortical bone.

Time-resolved absolute radius estimation of vibrating contrast microbubbles using an acoustical camera.

Ultrasound (US) contrast agents consist of microbubbles ranging from 1 to 10 µm in size. The acoustical response of individual microbubbles can be studied with high-frame-rate optics or an "acoustical camera" (AC). The AC measures the relative microbubble oscillation while the optical camera measures the absolute oscillation. In this article, the capabilities of the AC are extended to measure the absolute oscillations. In the AC setup, microbubbles are insonified with a high- (25 MHz) and low-frequency US wave (1-2.5 MHz). Other than the amplitude modulation (AM) from the relative size change of the microbubble (employed in Renaud, Bosch, van der Steen, and de Jong (2012a). "An 'acoustical camera' for in vitro characterization of contrast agent microbubble vibrations," Appl. Phys. Lett. 100(10), 101911, the high-frequency response from individual vibrating microbubbles contains a phase modulation (PM) from the microbubble wall displacement, which is the extension described here. The ratio of PM and AM is used to determine the absolute radius, R0. To test this sizing, the size distributions of two monodisperse microbubble populations ( R = 2.1 and 3.5 µm) acquired with the AC were matched to the distribution acquired with a Coulter counter. As a result of measuring the absolute size of the microbubbles, this "extended AC" can capture the full radial dynamics of single freely floating microbubbles with a throughput of hundreds of microbubbles per hour.

Dynamic acousto-elastic testing applied to a highly dispersive medium and evidence of shell buckling of lipid-coated gas microbubbles.

Dynamic acousto-elastic testing is applied to a mixture of lipid-coated microbubbles in water. A dynamic change of ambient pressure is produced by a 16 kHz pressure wave having a peak pressure amplitude of 28 kPa. The induced changes of phase velocity and attenuation are captured by a sequence of short ultrasound pulses with a center frequency of 4 MHz. As a consequence of the dispersion brought about by the resonance of microbubbles at a frequency close to 2 MHz, time-domain approaches like the cross-correlation method are shown to be unsuited to determine the variation in ultrasound wavespeed. A frequency-domain analysis shows that the acousto-elastic effect (first order pressure derivative of ultrasound phase velocity) depends on the ultrasound frequency. The acousto-elastic effect tends to that measured in water for an ultrasound frequency above the resonance frequency of microbubbles, while it is two orders of magnitude larger for an ultrasound frequency close to or below the resonance frequency of microbubbles. Besides the large magnitude of the acousto-elastic effect observed for an ultrasound frequency below the resonance frequency of microbubbles, the first order pressure derivative of ultrasound phase velocity is negative. This supports the occurrence of shell buckling of lipid-coated microbubbles induced by the 16 kHz pressure wave.

Opportunities and challenges in upcycling agri-food byproducts to generate insect manure (frass): A literature review.

A range of issues related to sustainability in the agrifood industry have spurred interest in mass production of insects as human food and animal feed alternatives. This rapidly evolving sector addresses several challenges, including the management of food waste or agrifood by-products and the production of alternative animal proteins demonstrating low environmental impacts that improve sector circularity. The mass production of insects on agrifood processing wastes or by-products represents an opportunity to address these challenges. While the production of insects offers prospects for sustainable protein production, a major side stream is the production of frass or larval excrement including uneaten feed and chitin-rich exuviae (derived from multiple larval moults). The production of each tonne of edible insects generates 2 to 4 tonnes of frass with an interesting potential in agriculture versus traditional organic amendments (compost, manure, biochar). This review aims to demonstrate the characteristics of frass, its common harvest and conditioning methods, its optimal application rates for planting crops, the mechanisms by which it can protect plants against biotic and abiotic stresses and demystify the risks and potential associated with its application in agriculture. The characteristics of frass are compared with those of conventional fertilizers or other. This report also compiles the Canadian, US and European regulatory frameworks as a novel plant fertilizer and aims to pave the way for future research necessary for its valorization in plant production.

Hormone replacement therapy improves contractile function and myonuclear organization of single muscle fibres from postmenopausal monozygotic female twin pairs.

Ageing is associated with a decline in muscle mass and strength leading to increased physical dependency in old age. Postmenopausal women experience a greater decline than men of similar age in parallel with the decrease in female sex steroid hormone production. We recruited six monozygous female twin pairs (55-59 years old) where only one twin pair was on hormone replacement therapy (HRT use = 7.8 ± 4.3 years) to investigate the association of HRT with the cytoplasmic volume supported by individual myonuclei (myonuclear domain (MND) size,) together with specific force at the single fibre level. HRT use was associated with a significantly smaller (∼27%; P < 0.05) mean MND size in muscle fibres expressing the type I but not the IIa myosin heavy chain (MyHC) isoform. In comparison to non-users, higher specific force was recorded in HRT users both in muscle fibres expressing type I (∼27%; P < 0.05) and type IIa (∼23%; P < 0.05) MyHC isoforms. These differences were fibre-type dependent, i.e. the higher specific force in fast-twitch muscle fibres was primarily caused by higher force per cross-bridge while slow-twitch fibres relied on both a higher number and force per cross-bridge. HRT use had no effect on fibre cross-sectional area (CSA), velocity of unloaded shortening (V0) and relative proportion of MyHC isoforms. In conclusion, HRT appears to have significant positive effects on both regulation of muscle contraction and myonuclei organization in postmenopausal women.

Sparing of muscle mass and function by passive loading in an experimental intensive care unit model.

The response to mechanical stimuli, i.e., tensegrity, plays an important role in regulating cell physiological and pathophysiological function, and the mechanical silencing observed in intensive care unit (ICU) patients leads to a severe and specific muscle wasting condition. This study aims to unravel the underlying mechanisms and the effects of passive mechanical loading on skeletal muscle mass and function at the gene, protein and cellular levels. A unique experimental rat ICU model has been used allowing long-term (weeks) time-resolved analyses of the effects of standardized unilateral passive mechanical loading on skeletal muscle size and function and underlying mechanisms. Results show that passive mechanical loading alleviated the muscle wasting and the loss of force-generation associated with the ICU intervention, resulting in a doubling of the functional capacity of the loaded versus the unloaded muscles after a 2-week ICU intervention. We demonstrate that the improved maintenance of muscle mass and function is probably a consequence of a reduced oxidative stress revealed by lower levels of carbonylated proteins, and a reduced loss of the molecular motor protein myosin. A complex temporal gene expression pattern, delineated by microarray analysis, was observed with loading-induced changes in transcript levels of sarcomeric proteins, muscle developmental processes, stress response, extracellular matrix/cell adhesion proteins and metabolism. Thus, the results from this study show that passive mechanical loading alleviates the severe negative consequences on muscle size and function associated with the mechanical silencing in ICU patients, strongly supporting early and intense physical therapy in immobilized ICU patients.

Is functional hypertrophy and specific force coupled with the addition of myonuclei at the single muscle fiber level?

Muscle force is typically proportional to muscle size, resulting in constant force normalized to muscle fiber cross-sectional area (specific force). Mice overexpressing insulin-like growth factor-1 (IGF-1) exhibit a proportional gain in muscle force and size, but not the myostatin-deficient mice. In an attempt to explore the role of the cytoplasmic volume supported by individual myonuclei [myonuclear domain (MND) size] on functional capacity of skeletal muscle, we have investigated specific force in relation to MND and the content of the molecular motor protein, myosin, at the single muscle fiber level from myostatin-knockout (Mstn(-/-)) and IGF-1-overexpressing (mIgf1(+/+)) mice. We hypothesize that the addition of extra myonuclei is a prerequisite for maintenance of specific force during muscle hypertrophy. A novel algorithm was used to measure individual MNDs in 3 dimensions along the length of single muscle fibers from the fast-twitch extensor digitorum longus and the slow-twitch soleus muscle. A significant effect of the size of individual MNDs in hypertrophic muscle fibers on both specific force and myosin content was observed. This effect was muscle cell type specific and suggested there is a critical volume individual myonuclei can support efficiently. The large MNDs found in fast muscles of Mstn(-/-) mice were correlated with the decrement in specific force and myosin content in Mstn(-/-) muscles. Thus, myostatin inhibition may not be able to maintain the appropriate MND for optimal function.

The influence of intra-cortical microstructure on the contrast in ultrasound images of the cortex of long bones: A 2D simulation study.

Decreased thickness of the bone cortex due to bone loss in the course of ageing and osteoporosis is associated with reduced bone strength. Cortical thickness measurement from ultrasound images was recently demonstrated in young adults. This requires the identification of both the outer (periosteum) and inner (endosteum) surfaces of the bone cortex. However, with bone loss, the cortical porosity and the size of the vascular pores increase resulting in enhanced ultrasound scattering which may prevent the detection of the endosteum. The aim of this work was to study the influence of cortical bone microstructure variables, such as porosity and pore size, on the contrast of the endosteum in ultrasound images. We wanted to estimate the range of these variables for which ultrasound imaging of the endosteum is feasible. We generated synthetic data using a two-dimensional time-domain code to simulate the propagation of elastodynamic waves. A synthetic aperture imaging sequence with an array transducer operating at a center frequency of 2.5 MHz was used. The numerical simulations were conducted for 105 cortical microstructures obtained from high resolution X-ray computed tomography images of ex vivo bone samples with a porosity ranging from 2% to 24 %. Images were reconstructed using a delay-and-sum (DAS) algorithm with optimized f-number, correction of refraction at the periosteum, and sample-specific wave-speed. We observed a range variation of 18 dB of endosteum contrast in our data set depending on the bone microstructure. We found that as porosity increases, speckle intensity inside the bone cortex increases whereas the intensity of the signal from the endosteum decreases. Also, a microstructure with large pores (diameter >250 µm) was associated with poor endosteum visibility, compared with a microstructure with equal porosity but a more narrow distribution of pore sizes. These findings suggest that ultrasound imaging of the bone cortex with a probe operating at a central frequency of 2.5 MHz using refraction-corrected DAS is capable of detecting the endosteum of a cortex with moderate porosity (less than about 10%) if the largest pores remain smaller than about 200 µm.

Prevention and management of health products shortages by the French national agency (ANSM), 10 years of experience.

Shortages of drugs and medical devices have tended to increase in France and worldwide, with consequences for patients and healthcare professionals. Preventing shortages of health products has become a priority for regulatory authorities, including the French National Agency for Medicines and Health Products Safety (ANSM). To highlight perspectives for a better prevention, we described and analyzed the management of shortages in the availability of health products in France over the last 10 years. The supply chain was mapped to identify the main causes of shortages and stakeholders involved in managing shortages throughout the supply chain. National and European initiatives and regulatory measures were reviewed. A retrospective nationwide data analysis from the French reporting system of health product shortage reports was conducted over 10 years for drugs (2013-2022) and over an 18-month period for medical devices, from 1st March 2022 to 31st August 2023. An increase in drug shortage reports was observed, rising from 404 in 2013 to 3,761 in 2022 for drugs, with a relatively constant distribution of affected therapeutic classes. In 2022, the main reported causes of drug shortage risk were insufficient production capacity (27.1%), increased sales volume (21.5%), or lack of supply (13.6%). Over half of the reports on medical devices (55.4%) were objectified as indispensable, and their causes were mainly due to a lack of supply (48.2%), discontinuation of marketing (14.9%), increased sales volume (13.2%), and regulatory reasons (9.6%). ANSM and French authorities have engaged a public health policy for prevention and management of health product shortages including financial penalties, minimum safety stocks for Major Therapeutic Interest drugs, and a shortage management plan. Based on 10 years of experience, four priority measures have been identified to anticipate the risk of heath products shortages based: the importance of a national coordination from raw materials to local market, the implementation of new prevention and management actions in the supply chain, strengthening European cooperation and regulation including the establishment of a list of critical drugs, and promoting transparency and information.

SUMS: synchronous undulator-monochromator scans at Synchrotron Soleil.

A strategy for performing synchronous undulator-monochromator scans (SUMS) compatible with the control system of Synchrotron Soleil has been developed. The implementation of the acquisition scheme has required the development of an electronic interface between the undulator and the beamline. The characterization of delays and jitters in the synchronous movement of various motor axes has motivated the development of a new electronic synchronization scheme among various axes, including the case when one of the axes is electronically accessible in `read-only' mode. A software prototype has been developed to allow the existing hard continuous software to work in user units. The complete strategy has been implemented and successfully tested at the TEMPO beamline.

Loss of muscle strength during sepsis is in part regulated by glucocorticoids and is associated with reduced muscle fiber stiffness.

Sepsis is associated with impaired muscle function but the role of glucocorticoids in sepsis-induced muscle weakness is not known. We tested the role of glucocorticoids in sepsis-induced muscle weakness by treating septic rats with the glucocorticoid receptor antagonist RU38486. In addition, normal rats were treated with dexamethasone to further examine the role of glucocorticoids in the regulation of muscle strength. Sepsis was induced in rats by cecal ligation and puncture, and muscle force generation (peak twitch and tetanic tension) was determined in lower extremity muscles. In other experiments, absolute and specific force as well as stiffness (reflecting the function of actomyosin cross bridges) were determined in isolated skinned muscle fibers from control and septic rats. Sepsis and treatment with dexamethasone resulted in reduced maximal twitch and tetanic force in intact isolated extensor digitorum longus muscles. The absolute and specific maximal force in isolated muscle fibers was reduced during sepsis together with decreased fiber stiffness. These effects of sepsis were blunted (but not abolished) by RU38486. The results suggest that muscle weakness during sepsis is at least in part regulated by glucocorticoids and reflects loss of contractility at the cellular (individual muscle fiber) level. In addition, the results suggest that reduced function of the cross bridges between actin and myosin (documented as reduced muscle fiber stiffness) may be involved in sepsis-induced muscle weakness. An increased understanding of mechanisms involved in loss of muscle strength will be important for the development of new treatment strategies in patients with this debilitating consequence of sepsis.

Mechanisms underlying ICU muscle wasting and effects of passive mechanical loading.

INTRODUCTION: Critically ill ICU patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decreased quality of life for survivors. Critical illness myopathy (CIM) is a frequently observed neuromuscular disorder in ICU patients. Sepsis, systemic corticosteroid hormone treatment and post-synaptic neuromuscular blockade have been forwarded as the dominating triggering factors. Recent experimental results from our group using a unique experimental rat ICU model show that the mechanical silencing associated with CIM is the primary triggering factor. This study aims to unravel the mechanisms underlying CIM, and to evaluate the effects of a specific intervention aiming at reducing mechanical silencing in sedated and mechanically ventilated ICU patients. METHODS: Muscle gene/protein expression, post-translational modifications (PTMs), muscle membrane excitability, muscle mass measurements, and contractile properties at the single muscle fiber level were explored in seven deeply sedated and mechanically ventilated ICU patients (not exposed to systemic corticosteroid hormone treatment, post-synaptic neuromuscular blockade or sepsis) subjected to unilateral passive mechanical loading for 10 hours per day (2.5 hours, four times) for 9 ± 1 days. RESULTS: These patients developed a phenotype considered pathognomonic of CIM; that is, severe muscle wasting and a preferential myosin loss (P < 0.001). In addition, myosin PTMs specific to the ICU condition were observed in parallel with an increased sarcolemmal expression and cytoplasmic translocation of neuronal nitric oxide synthase. Passive mechanical loading for 9 ± 1 days resulted in a 35% higher specific force (P < 0.001) compared with the unloaded leg, although it was not sufficient to prevent the loss of muscle mass. CONCLUSION: Mechanical silencing is suggested to be a primary mechanism underlying CIM; that is, triggering the myosin loss, muscle wasting and myosin PTMs. The higher neuronal nitric oxide synthase expression found in the ICU patients and its cytoplasmic translocation are forwarded as a probable mechanism underlying these modifications. The positive effect of passive loading on muscle fiber function strongly supports the importance of early physical therapy and mobilization in deeply sedated and mechanically ventilated ICU patients.

Accelerated 2-D Real-Time Refraction-Corrected Transcranial Ultrasound Imaging.

In a recent study, we proposed a technique to correct aberration caused by the skull and reconstruct a transcranial B-mode image with a refraction-corrected synthetic aperture imaging (SAI) scheme. Given a sound speed map, the arrival times were calculated using a fast marching technique (FMT), which solves the Eikonal equation and, therefore, is computationally expensive for real-time imaging. In this article, we introduce a two-point ray tracing method, based on Fermat's principle, for fast calculation of the travel times in the presence of a layered aberrator in front of the ultrasound probe. The ray tracing method along with the reconstruction technique is implemented on a graphical processing unite (GPU). The point spread function (PSF) in a wire phantom image reconstructed with the FMT and the GPU implementation was studied with numerical synthetic data and experiments with a bone-mimicking plate and a sagittally cut human skull. The numerical analysis showed that the error on travel times is less than 10% of the ultrasound temporal period at 2.5 MHz. As a result, the lateral resolution was not significantly degraded compared with images reconstructed with FMT-calculated travel times. The results using the synthetic, bone-mimicking plate, and skull dataset showed that the GPU implementation causes a lateral/axial localization error of 0.10/0.20, 0.15/0.13, and 0.26/0.32 mm compared with a reference measurement (no aberrator in front of the ultrasound probe), respectively. For an imaging depth of 70 mm, the proposed GPU implementation allows reconstructing 19 frames/s with full synthetic aperture (96 transmission events) and 32 frames/s with multiangle plane wave imaging schemes (with 11 steering angles) for a pixel size of [Formula: see text]. Finally, refraction-corrected power Doppler imaging is demonstrated with a string phantom and a bone-mimicking plate placed between the probe and the moving string. The proposed approach achieves a suitable frame rate for clinical scanning while maintaining the image quality.

Refraction-Corrected Transcranial Ultrasound Imaging Through the Human Temporal Window Using a Single Probe.

Transcranial ultrasound imaging (TUI) is a diagnostic modality with numerous applications, but unfortunately, it is hindered by phase aberration caused by the skull. In this article, we propose to reconstruct a transcranial B-mode image with a refraction-corrected synthetic aperture imaging (SAI) scheme. First, the compressional sound velocity of the aberrator (i.e., the skull) is estimated using the bidirectional headwave technique. The medium is described with four layers (i.e., lens, water, skull, and water), and a fast marching method calculates the travel times between individual array elements and image pixels. Finally, a delay-and-sum algorithm is used for image reconstruction with coherent compounding. The point spread function (PSF) in a wire phantom image and reconstructed with the conventional technique (using a constant sound speed throughout the medium), and the proposed method was quantified with numerical synthetic data and experiments with a bone-mimicking plate and a human skull, compared with the PSF achieved in a ground truth image of the medium without the aberrator (i.e., the bone plate or skull). A phased-array transducer (P4-1, ATL/Philips, 2.5 MHz, 96 elements, pitch = 0.295 mm) was used for the experiments. The results with the synthetic signals, the bone-mimicking plate, and the skull indicated that the proposed method reconstructs the scatterers with an average lateral/axial localization error of 0.06/0.14 mm, 0.11/0.13 mm, and 1.0/0.32 mm, respectively. With the human skull, an average contrast ratio (CR) and full-width-half-maximum (FWHM) of 37.1 dB and 1.75 mm were obtained with the proposed approach, respectively. This corresponds to an improvement of CR and FWHM by 7.1 dB and 36% compared with the conventional method, respectively. These numbers were 12.7 dB and 41% with the bone-mimicking plate.

Preferential skeletal muscle myosin loss in response to mechanical silencing in a novel rat intensive care unit model: underlying mechanisms.

The muscle wasting and impaired muscle function in critically ill intensive care unit (ICU) patients delay recovery from the primary disease, and have debilitating consequences that can persist for years after hospital discharge. It is likely that, in addition to pernicious effects of the primary disease, the basic life support procedures of long-term ICU treatment contribute directly to the progressive impairment of muscle function. This study aims at improving our understanding of the mechanisms underlying muscle wasting in ICU patients by using a unique experimental rat ICU model where animals are mechanically ventilated, sedated and pharmacologically paralysed for duration varying between 6 h and 14 days. Results show that the ICU intervention induces a phenotype resembling the severe muscle wasting and paralysis associated with the acute quadriplegic myopathy (AQM) observed in ICU patients, i.e. a preferential loss of myosin, transcriptional down-regulation of myosin synthesis, muscle atrophy and a dramatic decrease in muscle fibre force generation capacity. Detailed analyses of protein degradation pathways show that the ubiquitin proteasome pathway is highly involved in this process. A sequential change in localisation of muscle-specific RING finger proteins 1/2 (MuRF1/2) observed during the experimental period is suggested to play an instrumental role in both transcriptional regulation and protein degradation. We propose that, for those critically ill patients who develop AQM, complete mechanical silencing, due to pharmacological paralysis or sedation, is a critical factor underlying the preferential loss of the molecular motor protein myosin that leads to impaired muscle function or persisting paralysis.

High-accuracy acoustic detection of nonclassical component of material nonlinearity.

The aim is to assess the nonclassical component of material nonlinearity in several classes of materials with weak, intermediate, and high nonlinear properties. In this contribution, an optimized nonlinear resonant ultrasound spectroscopy (NRUS) measuring and data processing protocol applied to small samples is described. The protocol is used to overcome the effects of environmental condition changes that take place during an experiment, and that may mask the intrinsic nonlinearity. External temperature fluctuation is identified as a primary source of measurement contamination. For instance, a variation of 0.1 °C produced a frequency variation of 0.01%, which is similar to the expected nonlinear frequency shift for weakly nonlinear materials. In order to overcome environmental effects, the reference frequency measurements are repeated before each excitation level and then used to compute nonlinear parameters. Using this approach, relative resonant frequency shifts of 10(-5) can be measured, which is below the limit of 10(-4) often considered as the limit of NRUS sensitivity under common experimental conditions. Due to enhanced sensitivity resulting from the correction procedure applied in this work, nonclassical nonlinearity in materials that before have been assumed to only be classically nonlinear in past work (steel, brass, and aluminum) is reported.

Revealing Intraosseous Blood Flow in the Human Tibia With Ultrasound.

Intraosseous blood circulation is thought to have a critical role in bone growth and remodeling, fracture healing, and bone disorders. However, it is rarely considered in clinical practice because of the absence of a suitable noninvasive in vivo measurement technique. In this work, we assessed blood perfusion in tibial cortical bone simultaneously with blood flow in the superficial femoral artery with ultrasound imaging in five healthy volunteers. After suppression of stationary signal with singular-value-decomposition, pulsatile blood flow in cortical bone tissue is revealed, following the heart rate measured in the femoral artery. Using a method combining transverse oscillations and phase-based motion estimation, 2D vector flow was obtained in the cortex of the tibia. After spatial averaging over the cortex, the peak blood velocity along the long axis of the tibia was measured at four times larger than the peak blood velocity across the bone cortex. This suggests that blood flow in central (Haversian) canals is larger than in perforating (Volkmann's) canals, as expected from the intracortical vascular organization in humans. The peak blood velocity indicates a flow from the endosteum to the periosteum and from the heart to the foot for all subjects. Because aging and the development of bone disorders are thought to modify the direction and velocity of intracortical blood flow, their quantification is crucial. This work reports for the first time an in vivo quantification of the direction and velocity of blood flow in human cortical bone. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Dynamic acoustoelastic testing of weakly pre-loaded unconsolidated water-saturated glass beads.

Dynamic acoustoelastic testing is applied to weakly pre-loaded unconsolidated water-saturated glass beads. The gravitational acceleration produces, on the probed beads, a static stress of order 130 Pa, thus the granular medium is close to the jamming transition. A low-frequency (LF) acoustic wave gently disturbs the medium, inducing successively slight expansion and compaction of the granular packing expected to modulate the number of contacts between beads. Ultrasound (US) pulses are emitted simultaneously to dynamically detect the induced modification of the granular skeleton. US propagation velocity and attenuation both increase when the LF pressure increases. The quadratic nonlinear elastic parameter ß, related to the pressure dependence of US propagation velocity, was measured in the range 60-530 if water-saturated glass beads are considered as an effective medium. A dynamic modification of US scattering induced by beads is proposed to modulate US attenuation. Complex hysteretic behaviors and tension-compression asymmetry are also observed and analyzed by time-domain and spectral analyses. Furthermore acoustic nonlinearities are measured in cases of quasi-static and dynamic variations of the LF wave amplitude, providing quantitatively similar acoustic nonlinearities but qualitatively different.

Measuring anisotropy of elastic wave velocity with ultrasound imaging and an autofocus method: application to cortical bone.

This work investigates the feasibility of estimating the parameters of an exact transverse isotropy model in cortical bone. The model describes the anisotropy of the velocity of compressional and shear bulk elastic waves. We propose to achieve this with ultrasound imaging relying on the transmission of unfocused beams and with an autofocus method. The latter is based on the principle that the reconstructed ultrasound image shows optimal quality if the velocity model is correct. The autofocus approach is applied to a composite image of the interface between cortical bone and marrow. It is obtained by incoherent summation of four types of images exploiting four different ray paths in the cortical bone layer, three of them involving mode-converted shear waves. If the parameters of the model are correct, spatial co-localization of the interface appears in the four images. As a result, intensity and sharpness in the composite image are maximal. The five parameters of the model of transverse isotropy are successfully estimated in a tube made of a bone-mimicking material. The estimates are in good agreement with resonant ultrasound spectroscopy (RUS) measurements. The tube thickness is recovered with an error smaller than 0.3%. In vivo results at the forearm of a volunteer are promising, four parameters could be estimated and are in good agreement with ex vivo RUS measurements. Moreover x-ray peripheral computed tomography corroborates the thickness of the cortical bone layer in the ultrasound image. Weak-anisotropy and exact transverse isotropy models provide very close measurements of the thickness of the tube and the radius bone. Thus, we recommend using the model of weak transverse isotropy for real-time anatomical imaging because more computationally efficient. For material characterization however, the model of exact transverse isotropy is preferred because the elastic anisotropy of cortical bone is moderate, rather than weak.

Erratum: Lamb Waves and Adaptive Beamforming for Aberration Correction in Medical Ultrasound Imaging.

In our paper titled "Lamb Waves and Adaptive Beamforming for Aberration Correction in Medical Ultrasound Imaging" [1], we mentioned that the superposition of the different symmetric (S) modes in the frequency-wavenumber (f-k) domain results in a high intensity region where its slope corresponds to the longitudinal wave speed in the slab. However, we have recently understood that this high intensity region belongs to the propagation of a wave called lateral wave or head wave [2-5]. It is generated if the longitudinal sound speed of the aberrator (i.e. the PVC slab) is larger than that of water and if the incident wavefront is curved. When the incidence angle at the interface between water and PVC is near the critical angle, the refracted wave in PVC re-radiates a small part of its energy into the fluid (i.e. the head wave). As discussed in [4], if the thickness of the waveguide is larger than the wavelength, the first arriving signal is the head wave. This is also the case in our study [1] where the ultrasound wavelength of a compressional wave in PVC was close to 1 mm, and a PVC slab with a thickness of 8 mm was used.