Non-invasive Evaluation of Aortic Stiffness Dependence with Aortic Blood Pressure and Internal Radius by Shear Wave Elastography and Ultrafast Imaging

Elastic properties of arteries have long been recognized as playing a major role in the cardiovascular system. However, non-invasive in vivo assessment of local arterial stiffness remains challenging and imprecise as current techniques rely on indirect estimates such as wall deformation or pulse wave velocity. Recently, Shear Wave Elastography (SWE) has been proposed to non-invasively assess the intrinsic arterial stiffness. In this study, we applied SWE in the abdominal aortas of rats while increasing blood pressure (BP) to investigate the dependence of shear wave speed with invasive arterial pressure and non-invasive arterial diameter measurements. A 15MHz linear array connected to an ultrafast ultrasonic scanner, set non-invasively, on the abdominal aorta of anesthetized rats (N=5) was used. The SWE acquisition followed by an ultrafast (UF) acquisition was repeated at different moment of the cardiac cycle to assess shear wave speed and arterial diameter variations respectively. Invasive arterial BP catheter placed in the carotid, allowed the accurate measurement of pressure responses to increasing does of phenylephrine infused via a venous catheter. The SWE acquisition coupled to the UF acquisition was repeated for different range of pressure. For normal range of BP, the shear wave speed was found to follow the aortic BP variation during a cardiac cycle. A minimum of (5.06$\pm$0.82) m/s during diastole and a maximum of (5.97$\pm$0.90) m/s during systole was measured. After injection of phenylephrine, a strong increase of shear wave speed (13.85$\pm$5.51) m/s was observed for a peak systolic arterial pressure of (190$\pm$10) mmHg. A non-linear relationship between shear wave speed and arterial BP was found. A complete non-invasive method was proposed to characterize the artery with shear wave speed combined with arterial diameter variations. Finally, the results were validated against two parameters the incremental elastic modulus and the pressure elastic modulus derived from BP and arterial diameter variations

A versatile and robust microfluidic device for capillary-sized simple or multiple emulsions production

International audienceUltrasound-vaporizable microdroplets can be exploited for targeted drug delivery. However, it requires customized microfluidic techniques able to produce monodisperse, capillary-sized and biocompatible multiple emulsions. Recent development of microfluidic devices led to the optimization of microdroplet production with high yields, low polydispersity and well-defined diameters. So far, only few were shown to be efficient for simple droplets or multiple emulsions production below 5 microns in diameter, which is required to prevent microembolism after intravenous injection. Here, we present a versatile microchip for both simple and multiple emulsion production. This parallelized system based on microchannel emulsification was designed to produce perfluorocarbon in water or water within perfluorocarbon in water emulsions with capillary sizes (<5 μm) and polydispersity index down to 5 % for in vivo applications such as spatiotemporally-triggered drug delivery using Ultrasound. We show that droplet production at this scale is mainly controlled by interfacial tension forces, how capillary and viscosity ratios influence droplet characteristics and how different production regimes may take place. The better understanding of droplet formation and its relation to applied pressures is supported by observations with a high-speed camera. Compared to previous microchips, this device opens perspectives to produce injectable and biocompatible droplets with a reasonable yield in order to realize preclinical studies in mice

Shear Wave Imaging of Passive Diastolic Myocardial Stiffness: Stunned Versus Infarcted Myocardium

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Mapping Myocardial Fiber Orientation Using Echocardiography-Based Shear Wave Imaging

The assessment of disrupted myocardial fiber arrangement may help to understand and diagnose hypertrophic or ischemic cardiomyopathy. We hereby proposed and developed shear wave imaging (SWI), which is an echocardiography-based, noninvasive, real-time, and easy-to-use technique, to map myofiber orientation. Five in vitro porcine and three in vivo open-chest ovine hearts were studied. Known in physics, shear wave propagates faster along than across the fiber direction. SWI is a technique that can generate shear waves travelling in different directions with respect to each myocardial layer. SWI further analyzed the shear wave velocity across the entire left-ventricular (LV) myocardial thickness, ranging between 10 (diastole) and 25 mm (systole), with a resolution of 0.2 mm in the middle segment of the LV anterior wall region. The fiber angle at each myocardial layer was thus estimated by finding the maximum shear wave speed. In the in vitro porcine myocardium (n=5), the SWI-estimated fiber angles gradually changed from +80° ± 7° (endocardium) to +30° ± 13° (midwall) and-40° ± 10° (epicardium) with 0° aligning with the circumference of the heart. This transmural fiber orientation was well correlated with histology findings (r2=0.91± 0.02, p<0.0001). SWI further succeeded in mapping the transmural fiber orientation in three beating ovine hearts in vivo. At midsystole, the average fiber orientation exhibited 71° ± 13° (endocardium), 27° ± 8° (midwall), and-26° ± 30° (epicardium). We demonstrated the capability of SWI in mapping myocardial fiber orientation in vitro and in vivo. SWI may serve as a new tool for the noninvasive characterization of myocardial fiber structure. © 2012 IEEE.published_or_final_versio

A Universal Model of Global Civil Unrest

Civil unrest is a powerful form of collective human dynamics, which has led to major transitions of societies in modern history. The study of collective human dynamics, including collective aggression, has been the focus of much discussion in the context of modeling and identification of universal patterns of behavior. In contrast, the possibility that civil unrest activities, across countries and over long time periods, are governed by universal mechanisms has not been explored. Here, we analyze records of civil unrest of 170 countries during the period 1919-2008. We demonstrate that the distributions of the number of unrest events per year are robustly reproduced by a nonlinear, spatially extended dynamical model, which reflects the spread of civil disorder between geographic regions connected through social and communication networks. The results also expose the similarity between global social instability and the dynamics of natural hazards and epidemics.Comment: 8 pages, 3 figure

Understanding Design Patterns Density with Aspects: A Case Study in JHotDraw using AspectJ

International audienceDesign patterns offer solutions to common engineering prob- lems in programs [1]. In particular, they shape the evolution of program elements. However, their implementations tend to vanish in the code: thus it is hard to spot them and to understand their impact. The prob- lem becomes even more difficult with a "high density of pattern": then the program becomes easy to evolve in the direction allowed by patterns but hard to change [2]. Aspect languages offer new means to modular- ize elements. Implementations of object-oriented design patterns with AspectJ have been proposed [3]. We aim at testing the scalability of such solutions in the JHotDraw framework. We first explore the impact of density on pattern implementation. We show how AspectJ helps to reduce this impact. This unveils the principles of aspects and AspectJ to control pattern density

An Empirical Study of Goto in C Code from GitHub Repositories

ABSTRACT It is nearly 50 years since Dijkstra argued that goto obscures the flow of control in program execution and urged programmers to abandon the goto statement. While past research has shown that goto is still in use, little is known about whether goto is used in the unrestricted manner that Dijkstra feared, and if it is &apos;harmful&apos; enough to be a part of a post-release bug. We, therefore, conduct a two part empirical study -(1) qualitatively analyze a statistically representative sample of 384 files from a population of almost 250K C programming language files collected from over 11K GitHub repositories and find that developers use goto in C files for error handling (80.21±5%) and cleaning up resources at the end of a procedure (40.36 ± 5%); an

3D ultrafast ultrasound imaging in vivo

Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in 3D based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32 x 32 matrix-array probe. Its ability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3D Shear-Wave Imaging, 3D Ultrafast Doppler Imaging, and, finally, 3D Ultrafast combined Tissue and Flow Doppler Imaging. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3D Ultrafast Doppler was used to obtain 3D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, at thousands of volumes per second, the complex 3D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, as well as the 3D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3D Ultrafast Ultrasound Imaging for the 3D mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra--and inter-observer variability

In Vivo Evaluation of Cervical Stiffness Evolution during Induced Ripening Using Shear Wave Elastography, Histology and 2 Photon Excitation Microscopy: Insight from an Animal Model

Prematurity affects 11% of the births and is the main cause of infant mortality. On the opposite case, the failure of induction of parturition in the case of delayed spontaneous birth is associated with fetal suffering. Both conditions are associated with precocious and/or delayed cervical ripening. Quantitative and objective information about the temporal evolution of the cervical ripening may provide a complementary method to identify cases at risk of preterm delivery and to assess the likelihood of successful induction of labour. In this study, the cervical stiffness was measured in vivo in pregnant sheep by using Shear Wave Elastography (SWE). This technique assesses the stiffness of tissue through the measurement of shear waves speed (SWS). In the present study, 9 pregnant ewes were used. Cervical ripening was induced at 127 days of pregnancy (term: 145 days) by dexamethasone injection in 5 animals, while 4 animals were used as control. Elastographic images of the cervix were obtained by two independent operators every 4 hours during 24 hours after injection to monitor the cervical maturation induced by the dexamethasone. Based on the measurements of SWS during vaginal ultrasound examination, the stiffness in the second ring of the cervix was quantified over a circular region of interest of 5 mm diameter. SWS was found to decrease significantly in the first 4–8 hours after dexamethasone compared to controls, which was associated with cervical ripening induced by dexamethasone (from 1.779 m/s ± 0.548 m/s, p < 0.0005, to 1.291 m/s ± 0.516 m/s, p < 0.000). Consequently a drop in the cervical elasticity was quantified too (from 9.5 kPa ± 0.9 kPa, p < 0.0005, to 5.0 kPa ± 0.8 kPa, p < 0.000). Moreover, SWE measurements were highly reproducible between both operators at all times. Cervical ripening induced by dexamethasone was confirmed by the significant increase in maternal plasma Prostaglandin E2 (PGE2), as evidenced by the assay of its metabolite PGEM. Histological analyses and two-photon excitation microscopy, combining both Second Harmonic Generation (SHG) and Two-photon Fluorescence microscopy (2PF) contrasts, were used to investigate, at the microscopic scale, the structure of cervical tissue. Results show that both collagen and 2PF-active fibrillar structures could be closely related to the mechanical properties of cervical tissue that are perceptible in elastography. In conclusion, SWE may be a valuable method to objectively quantify the cervical stiffness and as a complementary diagnostic tool for preterm birth and for labour induction success