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Cardiovascular medical devices undergo a large number of pre- and post-market tests before their approval for clinical practice use. Sophisticated cardiovascular simulators can significantly expedite the evaluation process by providing a safe and controlled environment and representing clinically relevant case scenarios. The complex nature of the cardiovascular system affected by severe pathologies and the inherently intricate patient–device interaction creates a need for high-fidelity test benches able to reproduce intra- and inter-patient variability of disease states. Therefore, we propose an innovative cardiovascular simulator that combines in silico and in vitro modeling techniques with a soft robotic left ventricle. The simulator leverages patient-specific and echogenic soft robotic phantoms used to recreate the intracardiac pressure and volume waveforms, combined with an in silico lumped parameter model of the remaining cardiovascular system. Three different patient-specific profiles were recreated, to assess the capability of the simulator to represent a variety of working conditions and mechanical properties of the left ventricle. The simulator is shown to provide a realistic physiological and anatomical representation thanks to the use of soft robotics combined with in silico modeling. This tool proves valuable for optimizing and validating medical devices and delineating specific indications and boundary conditions. [ABSTRACT FROM AUTHOR]

Introduction: Mock circulatory loops (MCLs) are mechanical representations of the cardiovascular system largely used to test the hemodynamic performance of cardiovascular medical devices (MD). Thanks to 3 dimensional (3D) printing technologies, MCLs can nowadays also incorporate anatomical models so to offer enhanced testing capabilities. The aim of this review is to provide an overview on MCLs and to discuss the recent developments of 3D anatomical models for cardiovascular MD testing. Methods: The review first analyses the different techniques to develop 3D anatomical models, in both rigid and compliant materials. In the second section, the state of the art of MCLs with 3D models is discussed, along with the testing of different MDs: implantable blood pumps, heart valves, and imaging techniques. For each class of MD, the MCL is analyzed in terms of: the cardiovascular model embedded, the 3D model implemented (the anatomy represented, the material used, and the activation method), and the testing applications. Discussions and Conclusions: MCLs serve the purpose of testing cardiovascular MDs in different (patho‐)physiological scenarios. The addition of 3D anatomical models enables more realistic connections of the MD with the implantation site and enhances the testing capabilities of the MCL. Current attempts focus on the development of personalized MCLs to test MDs in patient‐specific hemodynamic and anatomical scenarios. The main limitation of MCLs is the impossibility to assess the impact of a MD in the long‐term and at a biological level, for which animal experiments are still needed. [ABSTRACT FROM AUTHOR]

Reports by P. H. Malatesta (1986) and B. McDonald (1987) suggest that joint generalized least squares (JGLS) methods of testing in regulatory event studies is unnecessary. They maintain ordinary least squares (OLS) estimates adequate for testing for abnormal returns following regulatory investment changes. However, research has tested JGLS and OLS methods in cases demonstrating cross-sectional dependence. JGLS methods are essential to compensate for cross-sectional correlation in residuals to prevent miscalculation.

Purpose: Despite the physical benefits of protons over conventional photon radiation in cancer treatment, range uncertainties impede the ability to harness the full potential of proton therapy. While monitoring the proton range in vivo could reduce the currently adopted safety margins, a routinely applicable range verification technique is still lacking. Recently, phase‐change nanodroplets were proposed for proton range verification, demonstrating a reproducible relationship between the proton range and generated ultrasound contrast after radiation‐induced vaporization at 25°C. In this study, previous findings are extended with proton irradiations at different temperatures, including the physiological temperature of 37°C, for a novel nanodroplet formulation. Moreover, the potential to modulate the linear energy transfer (LET) threshold for vaporization by varying the degree of superheat is investigated, where the aim is to demonstrate vaporization of nanodroplets directly by primary protons. Methods: Perfluorobutane nanodroplets with a shell made of polyvinyl alcohol (PVA‐PFB) or 10,12‐pentacosadyinoic acid (PCDA‐PFB) were dispersed in polyacrylamide hydrogels and irradiated with 62 MeV passively scattered protons at temperatures of 37°C and 50°C. Nanodroplet transition into echogenic microbubbles was assessed using ultrasound imaging (gray value and attenuation analysis) and optical images. The proton range was measured independently and compared to the generated contrast. Results: Nanodroplet design proved crucial to ensure thermal stability, as PVA‐shelled nanodroplets dramatically outperformed their PCDA‐shelled counterpart. At body temperature, a uniform radiation response proximal to the Bragg peak is attributed to nuclear reaction products interacting with PVA‐PFB nanodroplets, with the 50% drop in ultrasound contrast being 0.17 mm ± 0.20 mm (mean ± standard deviation) in front of the proton range. Also at 50°C, highly reproducible ultrasound contrast profiles were obtained with shifts of −0.74 mm ± 0.09 mm (gray value analysis), −0.86 mm ± 0.04 mm (attenuation analysis) and −0.64 mm ± 0.29 mm (optical analysis). Moreover, a strong contrast enhancement was observed near the Bragg peak, suggesting that nanodroplets were sensitive to primary protons. Conclusions: By varying the degree of superheat of the nanodroplets' core, one can modulate the intensity of the generated ultrasound contrast. Moreover, a submillimeter reproducible relationship between the ultrasound contrast and the proton range was obtained, either indirectly via the visualization of secondary reaction products or directly through the detection of primary protons, depending on the degree of superheat. The potential of PVA‐PFB nanodroplets for in vivo proton range verification was confirmed by observing a reproducible radiation response at physiological temperature, and further studies aim to assess the nanodroplets' performance in a physiological environment. Ultimately, cost‐effective online or offline ultrasound imaging of radiation‐induced nanodroplet vaporization could facilitate the reduction of safety margins in treatment planning and enable adaptive proton therapy. [ABSTRACT FROM AUTHOR]

In this article, ultrasonic phased arrays are deployed as an imaging tool for industrial process analysis. Such arrays are typically used for sonar, medical diagnosis, and nondestructive testing; however, they have not yet been applied to industrial process analysis. The precise positioning of array elements and high frequencies possible with this technology mean that highly focused images can be generated, which cannot currently be achieved using ultrasound tomography. This article aims to highlight the potential of this technology for the measurement of bubble size distribution (BSD) and to demonstrate its application to both intrusive and noninvasive process measurements. Ultrasound images of bubble reflectors are generated using the total focusing method deployed using a 32-element, 5-MHz linear phased array, and an image processing algorithm for BSD determination is presented and evaluated under stationary and dynamic acquisition conditions. It is found that the sizing accuracy is within 10% for stationary reflectors larger than $4\lambda $ in diameter and that the algorithm is stable across the expected spatial variation of reflectors. The phased array is coupled to a six-axis robotic arm to scan a solid sample containing bubble reflectors at velocities up to 500 mms−1. The sizing accuracy is within 45% for bubbles larger than $4\lambda $ in diameter and at velocities up to 300 mms−1. However, above this velocity, the algorithm breaks down for reflectors smaller than $9\lambda $ in diameter. The ultrasound system is applied to a stream of air bubbles rising through water, which is verified via photographic analysis. Images were generated both intrusive and noninvasive, via a 10-mm Perspex barrier, to the process stream. The high bubble density in the process stream introduced scattering, limiting the measurement repeatability and the sample size in the measured distribution. Notwithstanding, this result demonstrates the potential of this technology to size bubbles for intrusive and noninvasive process analyses. [ABSTRACT FROM AUTHOR]

Technologies enabling in vivo range verification during proton therapy are actively sought as a means to reduce the clinical safety margins currently adopted to avoid tumor underdosage. In this contribution, we applied the semi-empirical theory of radiation-induced vaporization of superheated liquids to coated nanodroplets. Nanodroplets are injectable phase-change contrast agents that can vaporize into highly echogenic microbubbles to provide contrast in ultrasound images. We exposed nanodroplet dispersions in aqueous phantoms to monoenergetic proton beams of varying energies and doses. Ultrasound imaging of the phantoms revealed that radiation-induced droplet vaporization occurred in regions proximal to the proton Bragg peak. A statistically significant increase in contrast was observed in irradiated regions for doses as low as 2 Gy and found to be proportional to the proton fluence. The absence of enhanced response in the vicinity of the Bragg peak, combined with theoretical considerations, suggest that droplet vaporization is induced by high linear energy transfer (LET) recoil ions produced by nuclear reactions with incoming protons. Vaporization profiles were compared to non-elastic cross sections and LET characteristics of oxygen recoils. Shifts between the ultrasound image contrast drop and the expected proton range showed a sub-millimeter reproducibility. These early findings confirm the potential of superheated nanodroplets as a novel tool for proton range verification. [ABSTRACT FROM AUTHOR]