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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Fundamental wave amplitude difference imaging for detection and characterization of embedded cracks.

An ultrasonic technique for imaging nonlinear scatterers, such as partially-closed cracks, buried in a medium has been recently proposed. The method called fundamental wave amplitude difference (FAD) consists of a sequence of acquisitions with different subsets of elements for each line of the image. An image revealing nonlinear scatterers in the medium is reconstructed line by line by subtracting the responses measured with the subsets of elements from the response obtained with all elements transmitting. In order to get a better insight of the capabilities of FAD, two metallic samples having a fatigue or thermal crack are inspected by translating the probe with ultrasonic beam perpendicular (i.e. parallel) to the crack direction which is the most (i.e. less) favorable case. Each time, the responses of the linear scatterers (i.e. conventional image) and nonlinear scatterers (i.e. FAD image) are compared in term of intensity and spatial repartition. FAD exhibits higher detection specificity of the crack with a better contrast than conventional ultrasound imaging. Moreover, we observe that both methods give complementary results as nonlinear and linear scatterers are mostly not co-localized. In addition, we show experimentally that FAD resolution in elevation and lateral follows the same rule as the theoretical resolution of conventional ultrasonic technique. Finally, we report that FAD gives the possibility to perform parametric studies which let the opportunity to address the physical mechanisms causing the distortion of the signal. FAD is a promising and reliable tool which can be directly implemented on a conventional open scanner ultrasound device for real-time imaging. This might contribute to its fast and wide spread in the industry.

In vivo ultrasound imaging of the bone cortex.

Current clinical ultrasound scanners cannot be used to image the interior morphology of bones because these scanners fail to address the complicated physics involved for exact image reconstruction. Here, we show that if the physics is properly addressed, bone cortex can be imaged using a conventional transducer array and a programmable ultrasound scanner. We provide in vivo proof for this technique by scanning the radius and tibia of two healthy volunteers and comparing the thickness of the radius bone with high-resolution peripheral x-ray computed tomography. Our method assumes a medium that is composed of different homogeneous layers with unique elastic anisotropy and ultrasonic wave-speed values. The applicable values of these layers are found by optimizing image sharpness and intensity over a range of relevant values. In the algorithm of image reconstruction we take wave refraction between the layers into account using a ray-tracing technique. The estimated values of the ultrasonic wave-speed and anisotropy in cortical bone are in agreement with ex vivo studies reported in the literature. These parameters are of interest since they were proposed as biomarkers for cortical bone quality. In this paper we discuss the physics involved with ultrasound imaging of bone and provide an algorithm to successfully image the first segment of cortical bone.

Nonlinear X-wave ultrasound imaging of acoustic biomolecules.

The basic physics of sound waves enables ultrasound to visualize biological tissues with high spatial and temporal resolution. Recently, this capability was enhanced with the development of acoustic biomolecules - proteins with physical properties enabling them to scatter sound. The expression of these unique air-filled proteins, known as gas vesicles (GVs), in cells allows ultrasound to image cellular functions such as gene expression in vivo, providing ultrasound with its analog of optical fluorescent proteins. Acoustical methods for the in vivo detection of GVs are now required to maximize the impact of this technology in biology and medicine. We previously engineered GVs exhibiting a nonlinear scattering behavior in response to acoustic pressures above 300 kPa, and showed that amplitude-modulated (AM) ultrasound pulse sequences that both excite the linear and nonlinear GV scattering regimes were highly effective at distinguishing GVs from linear scatterers like soft biological tissues. Unfortunately, the in vivo specificity of AM ultrasound imaging is systematically compromised by the nonlinearity added by the GVs to propagating waves, resulting in strong image artifacts from linear scatterers downstream of GV inclusions. To address this issue, we present an imaging paradigm, cross-amplitude modulation (xAM), which relies on cross-propagating plane-wave transmissions of finite aperture X-waves to achieve quasi artifact-free in vivo imaging of GVs. The xAM method derives from counter-propagating wave interaction theory which predicts that, in media exhibiting quadratic elastic nonlinearity like biological tissue, the nonlinear interaction of counter-propagating acoustic waves is inefficient. By transmitting cross-propagating plane-waves, we minimize cumulative nonlinear interaction effects due to collinear wave propagation, while generating a transient wave-amplitude modulation at the two plane-waves' intersection. We show in both simulations and experiments that residual xAM nonlinearity due to wave propagation decreases as the plane-wave cross-propagation angle increases. We demonstrate in tissue-mimicking phantoms that imaging artifacts distal to GV inclusions decrease as the plane-wave cross-propagation angle opens, nearing complete extinction at angles above 16.5 degrees. Finally, we demonstrate that xAM enables highly specific in vivo imaging of GVs located in the gastrointestinal tract, a target of prime interest for future cellular imaging. These results advance the physical facet of the emerging field of biomolecular ultrasound, and are also relevant to synthetic ultrasound contrast agents.

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.

Increasing specificity of contrast-enhanced ultrasound imaging using the interaction of quasi counter-propagating wavefronts: a proof of concept.

Detection methods implemented in present clinical ultrasound scanners for contrast-enhanced ultrasound imaging show high sensitivity but a rather poor specificity due to pseudo-enhancement (false detection of contrast agent) produced by nonlinear wave propagation. They all require linear ultrasound propagation to detect nonlinear scattering of contrast agent microbubbles. Even at low transmit pressure, nonlinear wave propagation occurs in regions perfused with contrast agent because contrast agent microbubbles can dramatically enhance the nonlinear elastic behavior of the medium. This image artifact hinders further development of contrast-enhanced ultrasound imaging toward reliable quantitative measurement of local concentration of contrast agent and blood perfusion kinetics. We propose in this manuscript a new detection method, with specific beamforming and pulsing scheme, that produces contrast images with highly reduced pseudo-enhancement. It is based on the interaction of two diverging wavefronts broadcasted by two single elements of a conventional probe array. The contrast image is formed line by line; one single image line is the line segment bisector defined by the centers of the two transmitting elements. Each image line is formed by a three-step pulse sequence: (1) transmission with one element, (2) transmission with the other element, and (3) transmission with both elements. The proof of principle is shown with numerical simulations and in vitro experiments. The method is implemented in a programmable ultrasound system and tested in a tissue-mimicking phantom containing a vessel filled with diluted contrast agent. At a given depth, increasing the distance between the two transmitting elements increases the angle describing the propagation directions of the two wavefronts. As a result, the nonlinear interaction between the two broadcasted waves is reduced. We show experimentally that increasing the distance between the transmitting elements from 0.6 to 24 mm reduces the amplitude of the pseudoenhancement at the far wall of the vessel relative to true contrast signal amplitude in the vessel by 12 dB, therefore improving specificity in the contrast-enhanced image.

Non-linear response and viscoelastic properties of lipid-coated microbubbles: DSPC versus DPPC.

For successful in vivo contrast-enhanced ultrasound imaging (CEUS) and ultrasound molecular imaging, detailed knowledge of stability and acoustical properties of the microbubbles is essential. Here, we compare these aspects of lipid-coated microbubbles that have either 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) as their main lipid; the other components were identical. The microbubbles were investigated in vitro over the frequency range 1-4 MHz at pressures between 10 and 100 kPa, and their response to the applied ultrasound was recorded using ultrahigh-speed imaging (15 Mfps). Relative to DPPC-coated microbubbles, DSPC-coated microbubbles had (i) higher acoustical stability; (ii) higher shell elasticity as derived using the Marmottant model (DSPC: 0.26 ± 0.13 N/m, DPPC: 0.06 ± 0.06 N/m); (iii) pressure amplitudes twice as high at the second harmonic frequency; and (iv) a smaller amount of microbubbles that responded at the subharmonic frequency. Because of their higher acoustical stability and higher non-linear response, DSPC-coated microbubbles may be more suitable for contrast-enhanced ultrasound.

Assessment of carotid atherosclerosis, intraplaque neovascularization, and plaque ulceration using quantitative contrast-enhanced ultrasound in asymptomatic patients with diabetes mellitus.

AIMS: Patients with diabetes mellitus (DM) are at severely increased risk of developing atherosclerosis. Intraplaque neovascularization (IPN) and plaque ulceration are markers of the vulnerable plaque, which is at an increased risk of rupture and may lead to cardiovascular events. The aim of this study was to assess the prevalence of subclinical carotid atherosclerosis, intraplaque neovascularization (IPN), and plaque ulceration in asymptomatic patients with DM. METHODS AND RESULTS: A total of 51 asymptomatic patients with DM underwent standard carotid ultrasound in conjunction with contrast-enhanced ultrasound (CEUS) to assess the prevalence of subclinical atherosclerosis, IPN, and plaque ulceration. Subclinical atherosclerosis was defined as the presence of atherosclerotic plaque, according to the Mannheim consensus. Semi-automated quantification software was used to assess IPN in suitable plaques. Plaque ulceration was defined as a disruption of the plaque-lumen border of ≥ 1 × 1 mm. A total of 408 carotid segments in 102 carotid arteries were investigated. Forty-six (90%) patients had subclinical atherosclerotic plaques, with a median plaque thickness of 2.4 mm (inter-quartile range 1.9-3.0). CEUS revealed IPN in 88% of the patients. In 10 carotid segments (8%), the plaque had an ulcerated surface. The presence of IPN could not be predicted by the presence of clinical characteristics including complications of DM (P > 0.05). CONCLUSION: Patients with DM have a high prevalence (90%) of subclinical carotid atherosclerosis. Severe IPN and plaque ulceration, which are markers of the vulnerable plaque type, were detected in, respectively, 13 and 9% of these patients.

Low-amplitude non-linear volume vibrations of single microbubbles measured with an "acoustical camera".

Contrast-enhanced ultrasound imaging is based on the detection of non-linear vibrational responses of a contrast agent after its intravenous administration. Improving contrast-enhanced images requires an accurate understanding of the vibrational response to ultrasound of the lipid-coated gas microbubbles that constitute most ultrasound contrast agents. Variations in the volume of microbubbles provide the most efficient radiation of ultrasound and, therefore, are the most important bubble vibrations for medical diagnostic ultrasound imaging. We developed an "acoustical camera" that measures the dynamic volume change of individual microbubbles when excited by a pressure wave. In the work described here, the technique was applied to the characterization of low-amplitude non-linear behaviors of BR14 microbubbles (Bracco Research, Geneva, Switzerland). The amplitude dependence of the resonance frequency and the damping, the prevalence of efficient subharmonic and ultraharmonic vibrations and the amplitude dependence of the response at the fundamental frequency and at the second harmonic frequency were investigated. Because of the large number of measurements, we provide a statistical characterization of the low-amplitude non-linear properties of the contrast agent.