NOVEL STRATEGIES FOR THE MORPHOLOGICAL AND BIOMECHANICAL ANALYSIS OF THE CARDIAC VALVES BASED ON VOLUMETRIC CLINICAL IMAGES

This work was focused on the morphological and biomechanical analysis of the heart valves exploiting the volumetric data. Novel methods were implemented to perform cardiac valve structure and sub-structure segmentation by defining long axis planes evenly rotated around the long axis of the valve. These methods were exploited to successfully reconstruct the 3D geometry of the mitral, tricuspid and aortic valve structures. Firstly, the reconstructed models were used for the morphological analysis providing a detailed description of the geometry of the valve structures, also computing novel indexes that could improve the description of the valvular apparatus and help their clinical assessment. Additionally, the models obtained for the mitral valve complex were adopted for the development of a novel biomechanical approach to simulate the systolic closure of the valve, relying on highly-efficient mass-spring models thus obtaining a good trade-off between the accuracy and the computational cost of the numerical simulations. In specific: \u2022 First, an innovative and semi-automated method was implemented to generate the 3D model of the aortic valve and of its calcifications, to quantitively describe its 3D morphology and to compute the anatomical aortic valve area (AVA) based on multi-detector computed tomography images. The comparison of the obtained results vs. effective AVA measurements showed a good correlation. Additionally, these methods accounted for asymmetries or anatomical derangements, which would be difficult to correctly capture through either effective AVA or planimetric AVA. \u2022 Second, a tool to quantitively assess the geometry of the tricuspid valve during the cardiac cycle using multidetector CT was developed, in particular focusing on the 3D spatial relationship between the tricuspid annulus and the right coronary artery. The morphological analysis of the annulus and leaflets confirmed data reported in literature. The qualitative and quantitative analysis of the spatial relationship could standardize the analysis protocol and be pivotal in the procedure planning of the percutaneous device implantation that interact with the tricuspid annulus. \u2022 Third, we simulated the systolic closure of three patient specific mitral valve models, derived from CMR datasets, by means of the mass spring model approach. The comparison of the obtained results vs. finite element analyses (considered as the gold-standard) was performed tuning the parameters of the mass spring model, so to obtain the best trade-off between computational expense and accuracy of the results. A configuration mismatch between the two models lower than two times the in-plane resolution of starting imaging data was yielded using a mass spring model set-up that requires, on average, only ten minutes to simulate the valve closure. \u2022 Finally, in the last chapter, we performed a comprehensive analysis which aimed at exploring the morphological and mechanical changes induced by the myxomatous pathologies in the mitral valve tissue. The analysis of mitral valve thickness confirmed the data and patterns reported in literature, while the mechanical test accurately described the behavior of the pathological tissue. A preliminary implementation of this data into finite element simulations suggested that the use of more reliable patient-specific and pathology-specific characterization of the model could improve the realism and the accuracy of the biomechanical simulations

Treatment of Tricuspid Regurgitation at Subvalvular Level: Hemodynamic and Morphological Assessment in Ex-Vivo Beating Heart Model

ABSTRACTBackground: Functional tricuspid regurgitation (FTR) treatment is challenging and most therapies targeting tricuspid valve (TV) annulus have shown limited durability with high rate of resid..

A microscale biomimetic platform for generation and electro-mechanical stimulation of 3D cardiac microtissues

Organs-on-chip technology has recently emerged as a promising tool to generate advanced cardiac tissue in vitro models, by recapitulating key physiological cues of the native myocardium. Biochemical, mechanical, and electrical stimuli have been investigated and demonstrated to enhance the maturation of cardiac constructs. However, the combined application of such stimulations on 3D organized constructs within a microfluidic platform was not yet achieved. For this purpose, we developed an innovative microbioreactor designed to provide a uniform electric field and cyclic uniaxial strains to 3D cardiac microtissues, recapitulating the complex electro-mechanical environment of the heart. The platform encompasses a compartment to confine and culture cell-laden hydrogels, a pressure-actuated chamber to apply a cyclic uniaxial stretch to microtissues, and stainless-steel electrodes to accurately regulate the electric field. The platform was exploited to investigate the effect of two different electrical stimulation patterns on cardiac microtissues from neonatal rat cardiomyocytes: a controlled electric field [5 V/cm, or low voltage (LV)] and a controlled current density [74.4 mA/cm2, or high voltage (HV)]. Our results demonstrated that LV stimulation enhanced the beating properties of the microtissues. By fully exploiting the platform, we combined the LV electrical stimulation with a physiologic mechanical stretch (10% strain) to recapitulate the key cues of the native cardiac microenvironment. The proposed microbioreactor represents an innovative tool to culture improved miniaturized cardiac tissue models for basic research studies on heart physiopathology and for drug screening

Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial

IMPORTANCE: No effective pharmaceutical agents have yet been identified to treat acute kidney injury after cardiac surgery. OBJECTIVE: To determine whether fenoldopam reduces the need for renal replacement therapy in critically ill cardiac surgery patients with acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, double-blind, placebo-controlled, parallel-group study from March 2008 to April 2013 in 19 cardiovascular intensive care units in Italy. We randomly assigned 667 patients admitted to intensive care units after cardiac surgery with early acute kidney injury ( 6550% increase of serum creatinine level from baseline or oliguria for 656 hours) to receive fenoldopam (338 patients) or placebo (329 patients). We used a computer-generated permuted block randomization sequence for treatment allocation. All patients completed their follow-up 30 days after surgery, and data were analyzed according to the intention-to-treat principle. INTERVENTIONS: Continuous infusion of fenoldopam or placebo for up to 4 days with a starting dose of 0.1 \u3bcg/kg/min (range, 0.025-0.3 \ub5g/kg/min). MAIN OUTCOMES AND MEASURES: The primary end point was the rate of renal replacement therapy. Secondary end points included mortality (intensive care unit and 30-day mortality) and the rate of hypotension during study drug infusion. RESULTS: The study was stopped for futility as recommended by the safety committee after a planned interim analysis. Sixty-nine of 338 patients (20%) allocated to the fenoldopam group and 60 of 329 patients (18%) allocated to the placebo group received renal replacement therapy (P\u2009=\u2009.47). Mortality at 30 days was 78 of 338 (23%) in the fenoldopam group and 74 of 329 (22%) in the placebo group (P\u2009=\u2009.86). Hypotension occurred in 85 (26%) patients in the fenoldopam group and in 49 (15%) patients in the placebo group (P\u2009=\u2009.001). CONCLUSIONS AND RELEVANCE: Among patients with acute kidney injury after cardiac surgery, fenoldopam infusion, compared with placebo, did not reduce the need for renal replacement therapy or risk of 30-day mortality but was associated with an increased rate of hypotension

Performance of the ALICE Electromagnetic Calorimeter

International audienceThe performance of the electromagnetic calorimeter of theALICE experiment during operation in 2010–2018 at the Large HadronCollider is presented. After a short introduction into the design,readout, and trigger capabilities of the detector, the proceduresfor data taking, reconstruction, and validation are explained. Themethods used for the calibration and various derived corrections arepresented in detail. Subsequently, the capabilities of thecalorimeter to reconstruct and measure photons, light mesons,electrons and jets are discussed. The performance of thecalorimeter is illustrated mainly with data obtained with test beamsat the Proton Synchrotron and Super Proton Synchrotron or inproton-proton collisions at √s = 13 TeV, and compared tosimulations

π0\pi ^{0} and η\eta meson production in proton-proton collisions at s=8\sqrt{s}=8 TeV

An invariant differential cross section measurement of inclusive $\pi ^{0}$ and $\eta$ meson production at mid-rapidity in pp collisions at $\sqrt{s}=8$  TeV was carried out by the ALICE experiment at the LHC. The spectra of $\pi ^{0}$ and $\eta$ mesons were measured in transverse momentum ranges of $0.33.5$   $\text{ GeV/c }$ . However, a deviation from this empirical scaling rule is observed for transverse momenta below $p_{ \text{ T }} <3.5$   $\text{ GeV/c }$ in the $\eta /\pi ^0$ ratio with a significance of $6.2\sigma$

Systematic studies of correlations between different order flow harmonics in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The correlations between event-by-event fluctuations of anisotropic flow harmonic amplitudes have been measured in Pb-Pb collisions at sNN=2.76 TeV with the ALICE detector at the Large Hadron Collider. The results are reported in terms of multiparticle correlation observables dubbed symmetric cumulants. These observables are robust against biases originating from nonflow effects. The centrality dependence of correlations between the higher order harmonics (the quadrangular v4 and pentagonal v5 flow) and the lower order harmonics (the elliptic v2 and triangular v3 flow) is presented. The transverse momentum dependences of correlations between v3 and v2 and between v4 and v2 are also reported. The results are compared to calculations from viscous hydrodynamics and a multiphase transport (AMPT) model calculations. The comparisons to viscous hydrodynamic models demonstrate that the different order harmonic correlations respond differently to the initial conditions and the temperature dependence of the ratio of shear viscosity to entropy density (η/s). A small average value of η/s is favored independent of the specific choice of initial conditions in the models. The calculations with the AMPT initial conditions yield results closest to the measurements. Correlations among the magnitudes of v2, v3, and v4 show moderate pT dependence in midcentral collisions. This might be an indication of possible viscous corrections to the equilibrium distribution at hadronic freeze-out, which might help to understand the possible contribution of bulk viscosity in the hadronic phase of the system. Together with existing measurements of individual flow harmonics, the presented results provide further constraints on the initial conditions and the transport properties of the system produced in heavy-ion collisions

Measuring KS0^0_{\rm S}K±^{\rm \pm} interactions using Pb-Pb collisions at sNN=2.76{\sqrt{s_{\rm NN}}=2.76} TeV

We present the first ever measurements of femtoscopic correlations between the KS0 and K ± particles. The analysis was performed on the data from Pb–Pb collisions at sNN=2.76 TeV measured by the ALICE experiment. The observed femtoscopic correlations are consistent with final-state interactions proceeding via the a0(980) resonance. The extracted kaon source radius and correlation strength parameters for KS0K− are found to be equal within the experimental uncertainties to those for KS0K+ . Comparing the results of the present study with those from published identical-kaon femtoscopic studies by ALICE, mass and coupling parameters for the a0 resonance are tested. Our results are also compatible with the interpretation of the a0 having a tetraquark structure instead of that of a diquark

Measurement of D-meson production at mid-rapidity in pp collisions at s=7{\sqrt{s}=7} TeV

The production cross sections for prompt charmed mesons $\mathrm{D^0}$ , $\mathrm{D^+}$ , $\mathrm{D^{*+}}$ and $\mathrm{D_s^+}$ were measured at mid-rapidity in proton–proton collisions at a centre-of-mass energy $\sqrt{s}=7~{\mathrm {TeV}}$ with the ALICE detector at the Large Hadron Collider (LHC). D mesons were reconstructed from their decays $\mathrm{D}^0 \rightarrow \mathrm{K}^-\pi ^+$ , $\mathrm{D}^+\rightarrow \mathrm{K}^-\pi ^+\pi ^+$ , $\mathrm{D}^{*+} \rightarrow \mathrm{D}^0 \pi ^+$ , $\mathrm{D_s^{+}\rightarrow \phi \pi ^+\rightarrow K^-K^+\pi ^+}$ , and their charge conjugates.With respect to previous measurements in the same rapidity region, the coverage in transverse momentum ( $p_\mathrm{T}$ ) is extended and the uncertainties are reduced by a factor of about two. The accuracy on the estimated total $\mathrm{c}{\overline{\mathrm{c}}}$ production cross section is likewise improved. The measured $p_\mathrm{T}$ -differential cross sections are compared with the results of three perturbative QCD calculations