A Multiscale Mathematical Model for the Fetal Blood Circulation of the Second Half of Pregnancy.

Doppler ultrasound is a commonly used method to assess hemodynamics of the fetal cardiovascular system and to monitor the well-being of the fetus. Indices based on the velocity profile are often used for diagnosis. However, precisely linking these indices to specific underlying physiology factors is challenging.

Impact of cardiac patch alignment on restoring post-infarct ventricular function.

Acute myocardial infarction (MI) leads to a loss of cardiac function which, following adverse ventricular remodeling (AVR), can ultimately result in heart failure. Tissue-engineered contractile patches placed over the infarct offer potential for restoring cardiac function and reducing AVR. In this computational study, we investigate how improvement of pump function depends on the orientation of the cardiac patch and the fibers therein relative to the left ventricle (LV).

Strain-controlled electrophysiological wave propagation alters scar-based substrate for ventricular tachycardia.

Assessing a patient's risk of scar-based ventricular tachycardia (VT) after myocardial infarction is a challenging task. It can take months to years after infarction for VT to occur. Also, if selected for ablation therapy, success rates are low.

Post-infarct evolution of ventricular and myocardial function.

Adverse ventricular remodeling following acute myocardial infarction (MI) may induce ventricular dilation, fibrosis, and loss of global contractile function, possibly resulting in heart failure (HF). Understanding the relation between the time-dependent changes in material properties of the myocardium and the contractile function of the heart may further our understanding of the development of HF post-MI and guide the development of novel therapies. A finite element model of cardiac mechanics was used to model MI in a thick-walled truncated ellipsoidal geometry.

The effect of apnea length on vital parameters in apnea of prematurity - Hybrid observations from clinical data and simulation in a mathematical model.

Apnea of prematurity (AOP) is a critical condition for preterm infants which can lead to several adverse outcomes. Despite its relevance, mechanisms underlying AOP are still unclear. In this work we aimed at improving the understanding of AOP and its physiologic responses by analyzing and comparing characteristics of real infant data and model-based simulations of AOP.

Stimulus-effect relations for left ventricular growth obtained with a simple multi-scale model: the influence of hemodynamic feedback.

Cardiac growth is an important mechanism for the human body to respond to changes in blood flow demand. Being able to predict the development of chronic growth is clinically relevant, but so far models to predict growth have not reached consensus on the stimulus-effect relation. In a previously published study, we modeled cardiac and hemodynamic function through a lumped parameter approach.

Evaluation of stimulus-effect relations in left ventricular growth using a simple multiscale model.

Cardiac growth is the natural capability of the heart to change size in response to changes in blood flow demand of the growing body. Cardiac diseases can trigger the same process leading to an abnormal type of growth. Prediction of cardiac growth would be clinically valuable, but so far published models on cardiac growth differ with respect to the stimulus-effect relation and constraints used for maximum growth.

A mathematical model to investigate the effects of intravenous fluid administration and fluid loss.

The optimal fluid administration protocol for critically ill perioperative patients is hard to estimate due to the lack of tools to directly measure the patient fluid status. This results in the suboptimal clinical outcome of interventions. Previously developed predictive mathematical models focus on describing the fluid exchange over time but they lack clinical applicability, since they do not allow prediction of clinically measurable indices.

Simulation of fetal heart rate variability with a mathematical model.

In the clinic, the cardiotocogram (CTG), the combined registration of fetal heart rate (FHR) and uterine contractions, is used to predict fetal well-being. Amongst others, fetal heart rate variability (FHRV) is an important indicator of fetal distress. In this study we add FHRV to our previously developed CTG simulation model, in order to improve its use as a research and educational tool.

New insights from a computational model on the relation between pacing site and CRT response.

Aims: Cardiac resynchronization therapy (CRT) produces clinical benefits in chronic heart failure patients with left bundle-branch block (LBBB). The position of the pacing site on the left ventricle (LV) is considered an important determinant of CRT response, but the mechanism how the LV pacing site determines CRT response is not completely understood. The objective of this study is to investigate the relation between LV pacing site during biventricular (BiV) pacing and cardiac function.

Determinants of biventricular cardiac function: a mathematical model study on geometry and myofiber orientation.

In patient-specific mathematical models of cardiac electromechanics, usually a patient-specific geometry and a generic myofiber orientation field are used as input, upon which myocardial tissue properties are tuned to clinical data. It remains unclear to what extent deviations in myofiber orientation and geometry between model and patient influence model predictions on cardiac function. Therefore, we evaluated the sensitivity of cardiac function for geometry and myofiber orientation in a biventricular (BiV) finite element model of cardiac mechanics.

A mathematical model to simulate the cardiotocogram during labor. Part A: Model setup and simulation of late decelerations.

The cardiotocogram (CTG) is commonly used to monitor fetal well-being during labor and delivery. It shows the input (uterine contractions) and output (fetal heart rate, FHR) of a complex chain of events including hemodynamics, oxygenation and regulation. Previously we developed a mathematical model to obtain better understanding of the relation between CTG signals and vital, but clinically unavailable signals such as fetal blood pressure and oxygenation.

A mathematical model to simulate the cardiotocogram during labor. Part B: Parameter estimation and simulation of variable decelerations.

During labor and delivery the cardiotocogram (CTG), the combined registration of fetal heart rate (FHR) and uterine contractions, is used to monitor fetal well-being. In part A of our study we introduced a new mathematical computer model for CTG simulation in order to gain insight into the complex relation between these signals. By reducing model complexity and by using physically more realistic descriptions, this model was improved with respect to our previous model.

Assessment and comparison of left ventricular shear in normal and situs inversus totalis hearts by means of magnetic resonance tagging.

Situs inversus totalis (SIT) is characterized by complete mirroring of gross cardiac anatomy and position combined with an incompletely mirrored myofiber arrangement, being normal at the apex but inverted at the base of the left ventricle (LV). This study relates myocardial structure to mechanical function by analyzing and comparing myocardial deformation patterns of normal and SIT subjects, focusing especially on circumferential-radial shear. In nine control and nine SIT normotensive human subjects, myocardial deformation was assessed from magnetic resonance tagging (MRT) image sequences of five LV short-axis slices.

Effects of activation pattern and active stress development on myocardial shear in a model with adaptive myofiber reorientation.

It has been hypothesized that myofiber orientation adapts to achieve a preferred mechanical loading state in the myocardial tissue. Earlier studies tested this hypothesis in a combined model of left ventricular (LV) mechanics and remodeling of myofiber orientation in response to fiber cross-fiber shear, assuming synchronous timing of activation and uniaxial active stress development. Differences between computed and measured patterns of circumferential-radial shear strain E(cr) were assumed to be caused by limitations in either the LV mechanics model or the myofiber reorientation model.

Layer-specific radiofrequency ultrasound-based strain analysis in a porcine model of ischemic cardiomyopathy validated by a geometric model.

Local layer-specific myocardial deformation after myocardial infarction (MI) has not been studied extensively although the sub-endocardium is more vulnerable to ischemia and interstitial fibrosis deposition. Radiofrequency (RF) ultrasound-based analysis could provide superior layer-specific radial strain estimation compared with clinically available deformation imaging techniques. In this study, we used RF-based myocardial deformation measurements to investigate layer-specific differences between healthy and damaged myocardium in a porcine model of chronic MI.

Simulation of changes in myocardial tissue properties during left ventricular assistance with a rotary blood pump.

We considered a mathematical model to investigate changes in geometric and hemodynamic indices of left ventricular function in response to changes in myofiber contractility and myocardial tissue stiffness during rotary blood pump support. Left ventricular assistance with a rotary blood pump was simulated based on a previously published biventricular model of the assisted heart and circulation. The ventricles in this model were based on the one-fiber model that relates ventricular function to myofiber contractility and myocardial tissue stiffness.

Insight into variable fetal heart rate decelerations from a mathematical model.

During labor and delivery, variable decelerations in the fetal heart rate (FHR) are commonly seen on the cardiotocogram (CTG) that is used to monitor fetal welfare. These decelerations are often induced by umbilical cord compression from uterine contractions. Via changes in oxygenation and blood pressure, umbilical cord compression activates the chemo- and baroreceptor reflex, and thus affects FHR.

Why SIT works: normal function despite typical myofiber pattern in Situs Inversus Totalis (SIT) hearts derived by shear-induced myofiber reorientation.

The left ventricle (LV) of mammals with Situs Solitus (SS, normal organ arrangement) displays hardly any interindividual variation in myofiber pattern and experimentally determined torsion. SS LV myofiber pattern has been suggested to result from adaptive myofiber reorientation, in turn leading to efficient pump and myofiber function. Limited data from the Situs Inversus Totalis (SIT, a complete mirror image of organ anatomy and position) LV demonstrated an essential different myofiber pattern, being normal at the apex but mirrored at the base.

Simulation of reflex late decelerations in labor with a mathematical model.

Fetal welfare during labor and delivery is commonly monitored through the cardiotocogram (CTG), the combined registration of uterus contractions and fetal heart rate (FHR). From the CTG, the fetal oxygen state is estimated as the main indicator of the fetal condition, but this estimate is difficult to make, due to the complex relation between CTG and oxygen state. Mathematical models can be used to assist in the interpretation of the CTG, since they enable quantitative modeling of the flow of events through which uterine contractions affect fetal oxygenation and FHR.

A method for the quantification of the pressure dependent 3D collagen configuration in the arterial adventitia.

Collagen plays an important role in the response of the arterial wall to mechanical loading and presumably has a load-bearing function preventing overdistension. Collagen configuration is important for understanding this role, in particular in mathematical models of arterial wall mechanics. In this study a new method is presented to image and quantify this configuration.

Modeling cardiac electromechanics and mechanoelectrical coupling in dyssynchronous and failing hearts: insight from adaptive computer models.

Computer models have become more and more a research tool to obtain mechanistic insight in the effects of dyssynchrony and heart failure. Increasing computational power in combination with increasing amounts of experimental and clinical data enables the development of mathematical models that describe electrical and mechanical behavior of the heart. By combining models based on data at the molecular and cellular level with models that describe organ function, so-called multi-scale models are created that describe heart function at different length and time scales.

Validation of a preterm infant cardiovascular system model under baroreflex control with heart rate and blood pressure data.

In this paper we present an autonomic cardiovascular model of a preterm infant of 28 weeks of gestation with a birth weight of 1000 g and a closed ductus arteriosus by the end of the first week, that is capable of describing the complex interactions between heart rate, blood pressure and respiration. The hemodynamic model consists of a pulsatile heart and several vascular compartments, and is regulated by a baroreflex control system. The model is relatively simple to allow for a mathematical analysis of the dynamics but sufficiently complex to provide a realistic representation of the underlying physiology.

Modeling of cardiac growth and remodeling of myofiber orientation.

The heart has the ability to respond to long-term changes in its environment through changes in mass (growth), shape (morphogenesis) and tissue properties (remodeling). For improved quantitative understanding of cardiac growth and remodeling (G&R) experimental studies need to be complemented by mathematical models. This paper reviews models for cardiac growth and remodeling of myofiber orientation, as induced by mechanical stimuli.

A mathematical model for simulation of early decelerations in the cardiotocogram during labor.

Fetal welfare during labor and delivery is commonly monitored through the cardiotocogram (CTG), the combined registration of uterus contractions and fetal heart rate (FHR). The CTG gives an indication of the main determinant of the acute fetal condition, namely its oxygen state. However, interpretation is complicated by the complex relationship between the two.