Sensitivity analysis of a strongly-coupled human-based electromechanical cardiac model: Effect of mechanical parameters on physiologically relevant biomarkers.

The human heart beats as a result of multiscale nonlinear dynamics coupling subcellular to whole organ processes, achieving electrophysiologically-driven mechanical contraction. Computational cardiac modelling and simulation have achieved a great degree of maturity, both in terms of mathematical models of underlying biophysical processes and the development of simulation software. In this study, we present the detailed description of a human-based physiologically-based, and fully-coupled ventricular electromechanical modelling and simulation framework, and a sensitivity analysis focused on its mechanical properties. The biophysical detail of the model, from ionic to whole-organ, is crucial to enable future simulations of disease and drug action. Key novelties include the coupling of state-of-the-art human-based electrophysiology membrane kinetics, excitation-contraction and active contraction models, and the incorporation of a pre-stress model to allow for pre-stressing and pre-loading the ventricles in a dynamical regime. Through high performance computing simulations, we demonstrate that 50% to 200% - 1000% variations in key parameters result in changes in clinically-relevant mechanical biomarkers ranging from diseased to healthy values in clinical studies. Furthermore mechanical biomarkers are primarily affected by only one or two parameters. Specifically, ejection fraction is dominated by the scaling parameter of the active tension model and its scaling parameter in the normal direction ( k ort 2 ); the end systolic pressure is dominated by the pressure at which the ejection phase is triggered ( P ej ) and the compliance of the Windkessel fluid model ( C ); and the longitudinal fractional shortening is dominated by the fibre angle ( ϕ ) and k ort 2 . The wall thickening does not seem to be clearly dominated by any of the considered input parameters. In summary, this study presents in detail the description and implementation of a human-based coupled electromechanical modelling and simulation framework, and a high performance computing study on the sensitivity of mechanical biomarkers to key model parameters. The tools and knowledge generated enable future investigations into disease and drug action on human ventricles.

Modeling and quantification of repolarization feature dependency on heart rate.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Studying Cardiovascular and Respiratory Systems". OBJECTIVES: This work aims at providing an efficient method to estimate the parameters of a non linear model including memory, previously proposed to characterize rate adaptation of repolarization indices. METHODS: The physiological restrictions on the model parameters have been included in the cost function in such a way that unconstrained optimization techniques such as descent optimization methods can be used for parameter estimation. The proposed method has been evaluated on electrocardiogram (ECG) recordings of healthy subjects performing a tilt test, where rate adaptation of QT and Tpeak-to-Tend (Tpe) intervals has been characterized. RESULTS: The proposed strategy results in an efficient methodology to characterize rate adaptation of repolarization features, improving the convergence time with respect to previous strategies. Moreover, Tpe interval adapts faster to changes in heart rate than the QT interval. CONCLUSIONS: In this work an efficient estimation of the parameters of a model aimed at characterizing rate adaptation of repolarization features has been proposed. The Tpe interval has been shown to be rate related and with a shorter memory lag than the QT interval.

Brain regions related to fear extinction in obsessive-compulsive disorder and its relation to exposure therapy outcome: a morphometric study.

BACKGROUND: The size of particular sub-regions within the ventromedial prefrontal cortex (vmPFC) has been associated with fear extinction in humans. Exposure therapy is a form of extinction learning widely used in the treatment of obsessive-compulsive disorder (OCD). Here we investigated the relationship between morphometric measurements of different sub-regions of the vmPFC and exposure therapy outcome in OCD. METHOD: A total of 74 OCD patients and 86 healthy controls underwent magnetic resonance imaging (MRI). Cortical thickness and volumetric measurements were obtained for the rostral anterior cingulate cortex (rACC), the medial orbital frontal cortex and the subcallosal cortex. After MRI acquisition, patients were enrolled in an exposure therapy protocol, and we assessed the relationship between MRI-derived measurements and treatment outcome. Baseline between-group differences for such measurements were also assessed. RESULTS: Compared with healthy controls, OCD patients showed a thinner left rACC (p = 0.008). Also, left rACC thickness was inversely associated with exposure therapy outcome (r - 0.32, p = 0.008), and this region was significantly thinner in OCD patients who responded to exposure therapy than in those who did not (p = 0.006). Analyses based on regional volumetry did not yield any significant results. CONCLUSIONS: OCD patients showed cortical thickness reductions in the left rACC, and these alterations were related to exposure therapy outcome. The precise characterization of neuroimaging predictors of treatment response derived from the study of the brain areas involved in fear extinction may optimize exposure therapy planning in OCD and other anxiety disorders.

Equipment for hydrogen absorption-desorption cycling characterization of hydride forming materials.

Hydrogen storage materials suffer different degradation processes when they are cycled, forming and decomposing their associated hydride phases. In order to study these processes, we have designed and built an automated apparatus specifically developed for cycling samples of hydride forming materials by changing the external hydrogen pressure. Instead of the standard open configuration involving a high-pressure, high-quality gas bottle and a vacuum pump, the equipment uses another hydride forming material (in our case LaNi5) as a source and sink of hydrogen. The resulting closed-loop configuration eliminates hydrogen waste and ensures that extremely high purity gas is used during the whole experiment, thanks to the purifying properties of the selected hydride as source/sink. Hydrogen pressure is set by changing the source/sink temperature. Cycles can be performed as fast as one cycle every 5 min, a period comparable with typical good hydride forming material kinetics. An example of application of the apparatus is given for 1000 absorption/ desorption cycles on a Mm0.8Ca0.2Ni5 sample.