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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.

Objective. In proton therapy, range uncertainties prevent optimal benefit from the superior depth-dose characteristics of proton beams over conventional photon-based radiotherapy. To reduce these uncertainties we recently proposed the use of phase-change ultrasound contrast agents as an affordable and effective range verification tool. In particular, superheated nanodroplets can convert into echogenic microbubbles upon proton irradiation, whereby the resulting ultrasound contrast relates to the proton range with high reproducibility. Here, we provide a first in vivo proof-of-concept of this technology. Approach. First, the in vitro biocompatibility of radiation-sensitive poly(vinyl alcohol) perfluorobutane nanodroplets was investigated using several colorimetric assays. Then, in vivo ultrasound contrast was characterized using acoustic droplet vaporization (ADV) and later using proton beam irradiations at varying energies (49.7 MeV and 62 MeV) in healthy Sprague Dawley rats. A preliminary evaluation of the in vivo biocompatibility was performed using ADV and a combination of physiology monitoring and histology. Main results. Nanodroplets were non-toxic over a wide concentration range (<1 mM). In healthy rats, intravenously injected nanodroplets primarily accumulated in the organs of the reticuloendothelial system, where the lifetime of the generated ultrasound contrast (<30 min) was compatible with a typical radiotherapy fraction (<5 min). Spontaneous droplet vaporization did not result in significant background signals. Online ultrasound imaging of the liver of droplet-injected rats demonstrated an energy-dependent proton response, which can be tuned by varying the nanodroplet concentration. However, caution is warranted when deciding on the exact nanodroplet dose regimen as a mild physiological response (drop in cardiac rate, granuloma formation) was observed after ADV. Significance. These findings underline the potential of phase-change ultrasound contrast agents for in vivo proton range verification and provide the next step towards eventual clinical applications., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)