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Emerging pollutants, such as pharmaceuticals and microplastics have become a pressing concern due to their widespread presence and potential impacts on ecological systems. To assess the ecosystem-level effects of these pollutants within a multi-stressor context, we simulated real-world conditions by exposing a near-natural multi-trophic aquatic food web to a gradient of environmentally relevant concentrations of fluoxetine and microplastics in large mesocosms over a period of more than three months. We measured the biomass and abundance of different trophic groups, as well as ecological functions such as nutrient availability and decomposition rate. To explore the mechanisms underlying potential community and ecosystem-level effects, we also performed behavioral assays focusing on locomotion parameters as a response variable in three species: Daphnia magna (zooplankton prey), Chaoborus flavicans larvae (invertebrate pelagic predator of zooplankton) and Asellus aquaticus (benthic macroinvertebrate), using water from the mesocosms. Our mesocosm results demonstrate that presence of microplastics governs the response in phytoplankton biomass, with a weak non-monotonic dose-response relationship due to the interaction between microplastics and fluoxetine. However, exposure to fluoxetine evoked a strong non-monotonic dose-response in zooplankton abundance and microbial decomposition rate of plant material. In the behavioral assays, the locomotion of zooplankton prey D. magna showed a similar non-monotonic response primarily induced by fluoxetine. Its predator C. flavicans, however, showed a significant non-monotonic response governed by both microplastics and fluoxetine. The behavior of the decomposer A. aquaticus significantly decreased at higher fluoxetine concentrations, potentially leading to reduced decomposition rates near the sediment. Our study demonstrates that effects observed upon short-term exposure result in more pronounced ecosystem-level effects following c

Objective: Post-operative brain injury in neonates may result from disturbed cerebral perfusion, but accurate peri-operative monitoring is lacking. High-frame-rate (HFR) cerebral ultrasound could visualize and quantify flow in all detectable vessels using spectral Doppler; however, automated quantification in small vessels is challenging because of low signal amplitude. We have developed an automatic envelope detection algorithm for HFR pulsed wave spectral Doppler signals, enabling neonatal brain quantitative parameter maps during and after surgery. Methods: HFR ultrasound data from high-risk neonatal surgeries were recorded with a custom HFR mode (frame rate = 1000 Hz) on a Zonare ZS3 system. A pulsed wave Doppler spectrogram was calculated for each pixel containing blood flow in the image, and spectral peak velocity was tracked using a max-likelihood estimation algorithm of signal and noise regions in the spectrogram, where the most likely cross-over point marks the blood flow velocity. The resulting peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistivity index (RI) were compared with other detection schemes, manual tracking and RIs from regular pulsed wave Doppler measurements in 10 neonates. Results: Envelope detection was successful in both high- and low-quality arterial and venous flow spectrograms. Our technique had the lowest root mean square error for EDV, PSV and RI (0.46 cm/s, 0.53 cm/s and 0.15, respectively) when compared with manual tracking. There was good agreement between the clinical pulsed wave Doppler RI and HFR measurement with a mean difference of 0.07. Conclusion: The max-likelihood algorithm is a promising approach to accurate, automated cerebral blood flow monitoring with HFR imaging in neonates., ImPhys/Verweij group

The accurate determination of the transfer function of ultrasound transducers is important for their design and operational performance. However, conventional methods for quantifying the transfer function, such as hydrophone measurements, radiation force balance, and pulse-echo measurements, are costly and complex due to specialized equipment required. In this study, we introduce a novel approach to estimate the transfer function of ultrasound transducers by measuring the acoustic streaming velocity generated by the transducer. We utilize an experimental setup consisting of a water tank with a millimeter scale, an ink-filled syringe, and a camera for recording the streaming phenomenon. Through streaming velocity measurements in the frequency range from 2 to 8 MHz, we determined the transfer function of an unfocused circular transducer with a center frequency of 5 MHz and a radius of 5.6 mm. We compared the performance of our method with hydrophone and pulse-echo measurements. At the center frequency, we measured a transmit efficiency of 1.9 kPa/V using the streaming approach, while hydrophone and pulse-echo measurements yielded transmit efficiencies of 2.1 kPa/V and 1.8 kPa/V, respectively. These findings demonstrate that the proposed method for estimating the transfer function of ultrasound transducers achieves a sufficient level of accuracy comparable to pulse-echo and hydrophone measurements., ImPhys/Verweij group, ImPhys/Medical Imaging, ImPhys/De Jong group

Objective: Described here is the development of an ultrasound matrix transducer prototype for high-frame-rate 3-D intra-cardiac echocardiography. Methods: The matrix array consists of 16 × 18 lead zirconate titanate elements with a pitch of 160 µm × 160 µm built on top of an application-specific integrated circuit that generates transmission signals and digitizes the received signals. To reduce the number of cables in the catheter to a feasible number, we implement subarray beamforming and digitization in receive and use a combination of time-division multiplexing and pulse amplitude modulation data transmission, achieving an 18-fold reduction. The proposed imaging scheme employs seven fan-shaped diverging transmit beams operating at a pulse repetition frequency of 7.7 kHz to obtain a high frame rate. The performance of the prototype is characterized, and its functionality is fully verified. Results: The transducer exhibits a transmit efficiency of 28 Pa/V at 5 cm per element and a bandwidth of 60% in transmission. In receive, a dynamic range of 80 dB is measured with a minimum detectable pressure of 10 Pa per element. The element yield of the prototype is 98%, indicating the efficacy of the manufacturing process. The transducer is capable of imaging at a frame rate of up to 1000 volumes/s and is intended to cover a volume of 70° × 70° × 10 cm. Conclusion: These advanced imaging capabilities have the potential to support complex interventional procedures and enable full-volumetric flow, tissue, and electromechanical wave tracking in the heart., ImPhys/Verweij group, ImPhys/Medical Imaging, Electronic Instrumentation, ImPhys/De Jong group

Assessing the coronary circulation with contrast-enhanced echocardiography has high clinical relevance. However, it is not being routinely performed in clinical practice because the current clinical tools generally cannot provide adequate image quality. The contrast agent's visibility in the myocardium is generally poor, impaired by motion and nonlinear propagation artifacts. The established multipulse contrast schemes (MPCSs) and the more experimental singular value decomposition (SVD) filter also fall short to solve these issues. Here, we propose a scheme to process amplitude modulation/amplitude-modulated pulse inversion (AM/AMPI) echoes with higher order SVD (HOSVD) instead of conventionally summing the complementary pulses. The echoes from the complementary pulses form a separate dimension in the HOSVD algorithm. Then, removing the ranks in that dimension with dominant coherent signals coming from tissue scattering would provide the contrast detection. We performed both in vitro and in vivo experiments to assess the performance of our proposed method in comparison with the current standard methods. A flow phantom study shows that HOSVD on AM pulsing exceeds the contrast-to-background ratio (CBR) of conventional AM and an SVD filter by 10 and 14 dB, respectively. In vivo porcine heart results also demonstrate that, compared to AM, HOSVD improves CBR in open-chest acquisition (up to 19 dB) and contrast ratio (CR) in closed-chest acquisition (3 dB)., ImPhys/Medical Imaging, ImPhys/De Jong group, ImPhys/Verweij group

Ultrasound imaging is an attractive imaging modality due to its low-cost and real-time feedback, although it often falls short in image quality compared to MRI and CT imaging. Conventional ultrasound image reconstruction, such as Delay-and-Sum beamforming, is derived from maximum-likelihood estimation. As such, no prior information is exploited in the image formation process, which limits potential image quality. Maximum-a-posteriori (MAP) beamforming aims to overcome this issue, but often relies on rough approximations of the underlying signal statistics. Deep learning based reconstruction methods have demonstrated impressive results over the past years, but often lack interpretability and require vast amounts of data.In this work we present a neural MAP beamforming technique, which efficiently combines deep learning in the MAP beamforming framework. We show that this model-based deep learning approach can achieve high-quality imaging, improving over the state-of-the-art, without compromising the real-time abilities of ultrasound imaging., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., ImPhys/Verweij group, ImPhys/Medical Imaging, ImPhys/De Jong group

Ultrasound-based shear wave elastography is a promising technique to non-invasively assess the dynamic stiffness variations of the heart. The technique is based on tracking the propagation of acoustically induced shear waves in the myocardium of which the propagation speed is linked to tissue stiffness. This measurement is repeated multiple times across the cardiac cycle to assess the natural variations in wave propagation speed. The interpretation of these measurements remains however complex, as factors such as loading and contractility affect wave propagation. We therefore applied transthoracic shear wave elastography in 13 pigs to investigate the dependencies of wave speed on pressure–volume derived indices of loading, myocardial stiffness, and contractility, while altering loading and inducing myocardial ischemia/reperfusion injury. Our results show that diastolic wave speed correlates to a pressure–volume derived index of operational myocardial stiffness (R = 0.75, p < 0.001), suggesting that both loading and intrinsic properties can affect diastolic wave speed. Additionally, the wave speed ratio, i.e. the ratio of systolic and diastolic speed, correlates to a pressure–volume derived index of contractility, i.e. preload-recruitable stroke work (R = 0.67, p < 0.001). Measuring wave speed ratio might thus provide a non-invasive index of contractility during ischemia/reperfusion injury., ImPhys/De Jong group, ImPhys/Verweij group

Purpose: Intraventricular blood flow dynamics are associated with cardiac function. Accurate, noninvasive, and easy assessments of hemodynamic quantities (such as velocity, vortex, and pressure) could be an important addition to the clinical diagnosis and treatment of heart diseases. However, the complex time-varying flow brings many challenges to the existing noninvasive image-based hemodynamic assessments. The development of reliable techniques and analysis tools is essential for the application of hemodynamic biomarkers in clinical practice. Methods: In this study, a time-resolved particle tracking method, Shake-the-Box, was applied to reconstruct the flow in a realistic left ventricle (LV) silicone model with biological valves. Based on the obtained velocity, 4D pressure field was calculated using a Poisson equation-based pressure solver. Furthermore, flow analysis by proper orthogonal decomposition (POD) of the 4D velocity field has been performed. Results: As a result of the Shake-the-Box algorithm, we have extracted: (i) particle positions, (ii) particle tracks, and finally, (iii) 4D velocity fields. From the latter, the temporal evolution of the 3D pressure field during the full cardiac cycle was obtained. The obtained maximal pressure difference extracted along the base-to-apex was about 2.7 mmHg, which is in good agreement with those reported in vivo. The POD analysis results showed a clear picture of different scale of vortices in the pulsatile LV flow, together with their time-varying information and corresponding kinetic energy content. To reconstruct 95% of the kinetic energy of the LV flow, only the first six POD modes would be required, leading to significant data reduction. Conclusions: This work demonstrated Shake-the-Box is a promising technique to accurately reconstruct the left ventricle flow field in vitro. The good spatial and temporal resolutions of the velocity measurements enabled a 4D reconstruction of the pressure field in the left ven, ChemE/Transport Phenomena

Objective: The aim of this study was to assess the feasibility and imaging options of contrast-enhanced volumetric ultrasound kidney vasculature imaging in a porcine model using a prototype sparse spiral array. Methods: Transcutaneous freehand in vivo imaging of two healthy porcine kidneys was performed according to three protocols with different microbubble concentrations and transmission sequences. Combining high-frame-rate transmission sequences with our previously described spatial coherence beamformer, we determined the ability to produce detailed volumetric images of the vasculature. We also determined power, color and spectral Doppler, as well as super-resolved microvasculature in a volume. The results were compared against a clinical 2-D ultrasound machine. Results: Three-dimensional visualization of the kidney vasculature structure and blood flow was possible with our method. Good structural agreement was found between the visualized vasculature structure and the 2-D reference. Microvasculature patterns in the kidney cortex were visible with super-resolution processing. Blood flow velocity estimations were within a physiological range and pattern, also in agreement with the 2-D reference results. Conclusion: Volumetric imaging of the kidney vasculature was possible using a prototype sparse spiral array. Reliable structural and temporal information could be extracted from these imaging results., ImPhys/Verweij group, ImPhys/Medical Imaging, ImPhys/De Jong group

Acute kidney injury (AKI) is frequently seen in patients with hemorrhagic shock due to hypotension, tissue hypoxia, and inflammation despite adequate resuscitation. There is a lack of information concerning the alteration of renal microcirculation and perfusion during shock and resuscitation. The aim of this study was to investigate the possible role of renal microcirculatory alterations on development of renal dysfunction in a pig model of non-traumatic hemorrhagic shock (HS) induced AKI. Fully instrumented female pigs were divided into the two groups as Control (n = 6) and HS (n = 11). HS was achieved by withdrawing blood until mean arterial pressure (MAP) reached around 50 mmHg. After an hour cessation period, fluid resuscitation with balanced crystalloid was started for the duration of 1 h. The systemic and renal hemodynamics, renal microcirculatory perfusion (contrast-enhanced ultrasound (CEUS)) and the sublingual microcirculation were measured. CEUS peak enhancement was significantly increased in HS during shock, early-, and late resuscitation indicating perfusion defects in the renal cortex (p < 0.05 vs. baseline, BL) despite a stable renal blood flow (RBF) and urine output. Following normalization of systemic hemodynamics, we observed persistent hypoxia (high lactate) and high red blood cell (RBC) velocity just after initiation of resuscitation resulting in further endothelial and renal damage as shown by increased plasma sialic acid (p < 0.05 vs. BL) and NGAL levels. We also showed that total vessel density (TVD) and functional capillary density (FCD) were depleted during resuscitation (p < 0.05). In this study, we showed that the correction of systemic hemodynamic variables may not be accompanied with the improvement of renal cortical perfusion, intra-renal blood volume and renal damage following fluid resuscitation. We suggest that the measurement of renal injury biomarkers, systemic and renal microcirculation can be used for guiding to the op, ImPhys/De Jong group

There is an increased desire for miniature ultrasound probes with small apertures to provide volumetric images at high frame rates for in-body applications. Satisfying these increased requirements makes simultaneous achievement of a good lateral resolution a challenge. As micro-beamforming is often employed to reduce data rate and cable count to acceptable levels, receive processing methods that try to improve spatial resolution will have to compensate the introduced reduction in focusing. Existing beamformers do not realize sufficient improvement and/or have a computational cost that prohibits their use. Here we propose the use of adaptive beamforming by deep learning (ABLE) in combination with training targets generated by a large aperture array, which inherently has better lateral resolution. In addition, we modify ABLE to extend its receptive field across multiple voxels. We illustrate that this method improves lateral resolution both quantitatively and qualitatively, such that image quality is improved compared with that achieved by existing delay-and-sum, coherence factor, filtered-delay-multiplication-and-sum and Eigen-based minimum variance beamformers. We found that only in silica data are required to train the network, making the method easily implementable in practice., ImPhys/Imaging Physics, ImPhys/Medical Imaging, Technology, Policy and Management

Ultrasound contrast-mediated medical imaging and therapy both rely on the dynamics of micron- and nanometer-sized ultrasound cavitation nuclei, such as phospholipid-coated microbubbles and phase-change droplets. Ultrasound cavitation nuclei respond non-linearly to ultrasound on a nanosecond time scale that necessitates the use of ultra-high-speed imaging to fully visualize these dynamics in detail. In this study, we developed an ultra-high-speed optical imaging system that can record up to 20 million frames per second (Mfps) by coupling two small-sized, commercially available, 10-Mfps cameras. The timing and reliability of the interleaved cameras needed to achieve 20 Mfps was validated using two synchronized light-emitting diode strobe lights. Once verified, ultrasound-activated microbubble responses were recorded and analyzed. A unique characteristic of this coupled system is its ability to be reconfigured to provide orthogonal observations at 10 Mfps. Acoustic droplet vaporization was imaged from two orthogonal views, by which the 3-D dynamics of the phase transition could be visualized. This optical imaging system provides the temporal resolution and experimental flexibility needed to further elucidate the dynamics of ultrasound cavitation nuclei to potentiate the clinical translation of ultrasound-mediated imaging and therapy developments., ImPhys/Medical Imaging, Technology, Policy and Management

Volumetric echocardiography can potentially give a more complete picture of cardiac dynamics than its two-dimensional (2D) counterpart. Current clinical volumetric imaging probes have relatively low frame rates, and often require ECG gating to stitch together an entire volume. This makes measuring fast dynamics of the heart as well as imaging patients with irregular heartbeats difficult. We have previously designed and manufactured 2D sparse arrays with elements seeded in a density-tapered spiral pattern for cardiac imaging. Using these prototypes, we demonstrate in this paper the first high-frame-rate volumetric closed-chest porcine cardiac as well as open-chest myocardial blood flow results. These preliminary results suggest the potential of performing high-frame-rate volumetric cardiac imaging using the sparse spiral arrays., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., ImPhys/Verweij group, ImPhys/Medical Imaging, ImPhys/De Jong group

Intra-cardiac echography (ICE) probes (Fig. 32.2.1) are widely used in electrophysiology for their good procedure guidance and relatively safe application. ASICs are increasingly employed in these miniature probes to enhance signal quality and reduce the number of connections needed in mm-diameter catheters [1]-[5]. 3D visualization in real-time is additionally enabled by 2D transducer arrays with, for each transducer element, a high-voltage (HV) transmit (TX) part, to generate acoustic pulses of sufficient pressure, and a receive (RX) path, to process the resulting echoes. To achieve the required reduction in RX channels, micro-beamforming (BF), which merges the signals from a subarray using a delay-and-sum operation, has been shown to be an effective solution [3], [4]. However, due to the frame-rate reduction that is associated with BF, these designs cannot serve emerging high-frame-rate imaging modes (1000 volumes/s) like 3D blood-flow and elastography imaging. In-probe digitization has recently been investigated to provide further channel-count reduction, make data transmission more robust, and enable pre-processing in the probe [1]-[3]. However, these earlier designs have either no TX functionality [2], [3] or only low-voltage (LV) TX [1] integrated. Combining BF and digitization with area-hungry HV transmitters in a pitch-matched scalable fashion while supporting high-frame-rate imaging remains an unmet challenge. The work presented in this paper meets this target, enabled by a hybrid ADC, the small die size of which allows for co-integration with 65V element-level pulsers., Accepted author manuscript, Electronic Instrumentation, ImPhys/Medical Imaging

The integration of 2D ultrasonic transducer arrays and pitch-matched ASICs has enabled the realization of various 3D ultrasound imaging devices in recent years [1]-[3]. As applications such as 3D intravascular ultrasonography, intra-cardiac echocardiography, and trans-fontanelle ultrasonography call for miniaturization and improved spatial resolution, higher-frequency transducers (>5MHz) with a correspondingly smaller array pitch (<150m) are needed. Such devices generally employ a large number of transducer elements, calling for channel-count reduction in the ASIC while meeting stringent restrictions on per-element power consumption and die area. Micro-beamforming (BF) is an effective way of reducing channel count by performing a delay-and-sum operation on the echo signals received within a sub-array [1]. However, prior BF implementations employ per-element capacitive memory to realize the delay [1], [2], making it increasingly difficult to apply BF in smaller-pitch arrays., Accepted author manuscript, Electronic Instrumentation, ImPhys/Medical Imaging

An in vivo range verification technology for proton beam cancer therapy, preferably in real-time and with submillimeter resolution, is desired to reduce the present uncertainty in dose localization. Acoustical imaging technologies exploiting possible local interactions between protons and microbubbles or nanodroplets might be an interesting option. Unfortunately, a theoretical model capable of characterising the acoustical field generated by an individual proton on nanometer and micrometer scales is still missing. In this work, such a model is presented. The proton acoustic field is generated by the adiabatic expansion of a region that is locally heated by a passing proton. To model the proton heat deposition, secondary electron production due to protons has been quantified using a semi-empirical model based on Rutherford's scattering theory, which reproduces experimentally obtained electronic stopping power values for protons in water within 10% over the full energy range. The electrons transfer energy into heat via electron-phonon coupling to atoms along the proton track. The resulting temperature increase is calculated using an inelastic thermal spike model. Heat deposition can be regarded as instantaneous, thus, stress confinement is ensured and acoustical initial conditions are set. The resulting thermoacoustic field in the nanometer and micrometer range from the single proton track is computed by solving the thermoacoustic wave equation using k-space Green's functions, yielding the characteristic amplitudes and frequencies present in the acoustic signal generated by a single proton in an aqueous medium. Wavefield expansion and asymptotic approximations are used to extend the spatial and temporal ranges of the proton acoustic field., ImPhys/Medical Imaging

In recent years, several fitting techniques have been presented to reconstruct the parameters of a plate from its Lamb wave dispersion curves. Published studies show that these techniques can yield high accuracy results and have the potential of reconstructing several parameters at once. The precision with which parameters can be reconstructed by inverting Lamb wave dispersion curves, however, remains an open question of fundamental importance to many applications. In this work, we introduce a method of analyzing dispersion curves that yields quantitative information on the precision with which the parameters can be extracted. In our method, rather than employing error minimization algorithms, we compare a target dispersion curve to a database of theoretical ones that covers a given parameter space. By calculating a measure of dissimilarity (error) for every point in the parameter space, we reconstruct the distribution of the error in that space, beside the location of its minimum. We then introduce dimensionless quantities that describe the distribution of this error, thus yielding information about the spread of similar curves in the parameter space. We demonstrate our approach by considering both idealized and realistic scenarios, analyzing the dispersion curves obtained numerically for a plate and experimentally for a pipe. Our results show that the precision with which each parameter is reconstructed depends on the mode used, as well as the frequency range in which it is considered., Human-Robot Interaction, ImPhys/Medical Imaging, BUS/TNO STAFF

Bacteria encased in a biofilm poses significant challenges to successful treatment, since both the immune system and antibiotics are ineffective. Sonobactericide, which uses ultrasound and microbubbles, is a potential new strategy for increasing antimicrobial effectiveness or directly killing bacteria. Several studies suggest that sonobactericide can lead to bacterial dispersion or sonoporation (i.e., cell membrane permeabilization); however, real-time observations distinguishing individual bacteria during and directly after insonification are missing. Therefore, in this study, we investigated, in real-time and at high-resolution, the effects of ultrasound-induced microbubble oscillation on Staphylococcus aureus biofilms, without or with an antibiotic (oxacillin, 1 µg/mL). Biofilms were exposed to ultrasound (2 MHz, 100–400 kPa, 100–1000 cycles, every second for 30 s) during time-lapse confocal microscopy recordings of 10 min. Bacterial responses were quantified using post hoc image analysis with particle counting. Bacterial dispersion was observed as the dominant effect over sonoporation, resulting from oscillating microbubbles. Increasing pressure and cycles both led to significantly more dispersion, with the highest pressure leading to the most biofilm removal (up to 83.7%). Antibiotic presence led to more variable treatment responses, yet did not significantly impact the therapeutic efficacy of sonobactericide, suggesting synergism is not an immediate effect. These findings elucidate the direct effects induced by sonobactericide to best utilize its potential as a biofilm treatment strategy., ImPhys/Medical Imaging

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., Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., ImPhys/Medical Imaging, ImPhys/Computational Imaging

Clamp-on ultrasonic flow meters (UFMs) are installed on the outside of the pipe wall. Typically, they consist of two single-element transducers mounted on angled wedges, which are acoustically coupled to the pipe wall. Before flow metering, the transducers are placed at the correct axial position by manually moving one transducer along the pipe wall until the maximum amplitude of the relevant acoustic pulse is obtained. This process is time-consuming and operator-dependent. Next to this, at least five parameters of the pipe and the liquid need to be provided manually to compute the flow speed. In this work, a method is proposed to obtain the five parameters of the pipe and the liquid required to compute the flow speed. The method consists of obtaining the optimal angles for different wave travel paths by varying the steering angle of the emitted acoustic beam systematically. Based on these optimal angles, a system of equations is built and solved to extract the desired parameters. The proposed method was tested experimentally with a custom-made clamp-on UFM consisting of two linear arrays placed on a water-filled stainless steel pipe. The obtained parameters of the pipe and the liquid correspond very well with the expected (nominal) values. Furthermore, the performed experiment also demonstrates that a clamp-on UFM based on transducer arrays can achieve self-alignment without the need to manually move the transducers, ImPhys/Medical Imaging, Electronic Instrumentation

Superheated nanodroplet (ND) vaporization by proton radiation was recently demonstrated, opening the door to ultrasound-based in vivo proton range verification. However, at body temperature and physiological pressures, perfluorobutane nanodroplets (PFB-NDs), which offer a good compromise between stability and radiation sensitivity, are not directly sensitive to primary protons. Instead, they are vaporized by infrequent secondary particles, which limits the precision for range verification. The radiation-induced vaporization threshold (i.e., sensitization threshold) can be reduced by lowering the pressure in the droplet such that ND vaporization by primary protons can occur. Here, we propose to use an acoustic field to modulate the pressure, intermittently lowering the proton sensitization threshold of PFB-NDs during the rarefactional phase of the ultrasound wave. Simultaneous proton irradiation and sonication with a 1.1 MHz focused transducer, using increasing peak negative pressures (PNPs), were applied on a dilution of PFB-NDs flowing in a tube, while vaporization was acoustically monitored with a linear array. Sensitization to primary protons was achieved at temperatures between 29 °C and 40 °C using acoustic PNPs of relatively low amplitude (from 800 to 200 kPa, respectively), while sonication alone did not lead to ND vaporization at those PNPs. Sensitization was also measured at the clinically relevant body temperature (i.e., 37 °C) using a PNP of 400 kPa. These findings confirm that acoustic modulation lowers the sensitization threshold of superheated NDs, enabling a direct proton response at body temperature., ImPhys/Medical Imaging

Suppressing tissue clutter is an essential step in blood flow estimation and visualization, even when using ultrasound contrast agents. Blind source separation (BSS)-based clutter filter for high frame rate ultrasound imaging has been reported to perform better in tissue clutter suppression than the conventional frequency-based wall filter and nonlinear contrast pulsing schemes. The most notable BSS technique, singular value decomposition (SVD) has shown compelling results in cases of slow tissue motion. However, its performance degrades when the tissue motion is faster than the blood flow speed, conditions which are likely to occur when imaging the small vessels, such as in the myocardium. Independent component analysis (ICA) is another BSS technique that has been implemented as a clutter filter in the spatiotemporal domain. Instead, we propose to implement ICA in the spatial domain where motion should have less impact. In this work, we propose a clutter filter with the combination of SVD and ICA to improve the contrast-to-background ratio (CBR) in cases where tissue velocity is significantly faster than the flow speed. In an in vitro study, the range of fast tissue motion velocity was 5-25 mm/s and the range of flow speed was 1-12 mm/s. Our results show that the combination of ICA and SVD yields 7 – 10 dB higher CBR than SVD alone, especially in the tissue high-velocity range. The improvement is crucial for cardiac imaging where relatively fast myocardial motions are expected., ImPhys/Medical Imaging

The potential of proton therapy to improve the conformity of the delivered dose to the tumor volume is currently limited by range uncertainties. Injectable superheated nanodroplets have recently been proposed for ultrasound-based in vivo range verification, as these vaporize into echogenic microbubbles on proton irradiation. In previous studies, offline ultrasound images of phantoms with dispersed nanodroplets were acquired after irradiation, relating the induced vaporization profiles to the proton range. However, the aforementioned method did not enable the counting of individual vaporization events, and offline imaging cannot provide real-time feedback. In this study, we overcame these limitations using high-frame-rate ultrasound imaging with a linear array during proton irradiation of phantoms with dispersed perfluorobutane nanodroplets at 37°C and 50°C. Differential image analysis of subsequent frames allowed us to count individual vaporization events and to localize them with a resolution beyond the ultrasound diffraction limit, enabling spatial and temporal quantification of the interaction between ionizing radiation and nanodroplets. Vaporization maps were found to accurately correlate with the stopping distribution of protons (at 50°C) or secondary particles (at both temperatures). Furthermore, a linear relationship between the vaporization count and the number of incoming protons was observed. These results indicate the potential of real-time high-frame-rate contrast-enhanced ultrasound imaging for proton range verification and dosimetry. © 2021 The Authors

BACKGROUND: Patients affected by different types of autoimmune diseases, including common conditions such as multiple sclerosis (MS) and rheumatoid arthritis (RA), are often treated with immunosuppressants to suppress disease activity. It is not fully understood how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral and cellular immunity induced by infection and/or upon vaccination is affected by immunosuppressants. METHODS: The dynamics of cellular immune reactivation upon vaccination of SARS-CoV-2 experienced MS patients treated with the humanized anti-CD20 monoclonal antibody ocrelizumab (OCR) and RA patients treated with methotrexate (MTX) monotherapy were analyzed at great depth via high-dimensional flow cytometry of whole blood samples upon vaccination with the SARS-CoV-2 mRNA-1273 (Moderna) vaccine. Longitudinal B and T cell immune responses were compared to SARS-CoV-2 experienced healthy controls (HCs) before and 7 days after the first and second vaccination. RESULTS: OCR-treated MS patients exhibit a preserved recall response of CD8+ T central memory cells following first vaccination compared to HCs and a similar CD4+ circulating T follicular helper 1 and T helper 1 dynamics, whereas humoral and B cell responses were strongly impaired resulting in absence of SARS-CoV-2-specific humoral immunity. MTX treatment significantly delayed antibody levels and B reactivation following the first vaccination, including sustained inhibition of overall reactivation marker dynamics of the responding CD4+ and CD8+ T cells. CONCLUSIONS: Together, these findings indicate that SARS-CoV-2 experienced MS-OCR patients may still benefit from vaccination by inducing a broad CD8+ T cell response which has been associated with milder disease outcome. The delayed vaccine-induced IgG kinetics in RA-MTX patients indicate an increased risk after the first vaccination, which might require additional shielding or alternative strategies such as treatment inte

In recent years, transcranial photoacoustic (TPA) imaging has become a popular modality for diagnosis of brain disorders. However, due to the presence of skull, TPA images are strongly degraded. Acoustically, this degradation is mainly categorized into the phase aberration, mode-converted shear waves, and multiple scattering. Previous studies numerically investigated the effects of mode-converted shear waves and multiple scattering on TPA images while the phase aberration caused by the skull was ignored and a conventional delay-and-sum method was employed for reconstructing TPA images. In this paper, we investigate these effects while a refraction-corrected image reconstruction approach is used to form TPA images. This approach enables separating the effects of phase aberration, mode-converted shear wave and multiple scattering. A realistic human temporal bone based on a MicroCT was used in the numerical model. In average for all the absorbers, the power of the artifacts caused by the mode-converted shear wave and multiple scattering are -13.7 dB and -20.1 dB when the refraction is corrected during image formation, respectively. These values were -7.9 and -18.8 if the conventional reconstruction is used. Accounting for phase aberration enables accurate quantification of the effects of the mode-converted shear waves and multiple scattering, which is necessary for evaluating the methods developed for degrading these effects., Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., ImPhys/Medical Imaging

Two-dimensional (2-D) arrays offer volumetric imaging capabilities without the need for probe translation or rotation. A sparse array with elements seeded in a tapering spiral pattern enables one-to-one connection to an ultrasound machine, thus allowing flexible transmission and reception strategies. To test the concept of sparse spiral array imaging, we have designed, realized, and characterized two prototype probes designed at 2.5-MHz low-frequency (LF) and 5-MHz high-frequency (HF) center frequencies. Both probes share the same electronic design, based on piezoelectric ceramics and rapid prototyping with printed circuit board substrates to wire the elements to external connectors. Different center frequencies were achieved by adjusting the piezoelectric layer thickness. The LF and HF prototype probes had 88% and 95% of working elements, producing peak pressures of 21 and 96 kPa/V when focused at 5 and 3 cm, respectively. The one-way -3-dB bandwidths were 26% and 32%. These results, together with experimental tests on tissue-mimicking phantoms, show that the probes are viable for volumetric imaging., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., ImPhys/Medical Imaging