Roy C. P. Kerckhoffs

Bio: Roy C. P. Kerckhoffs is an academic researcher from University of California, San Diego. The author has contributed to research in topics: Cardiac resynchronization therapy & Heart failure. The author has an hindex of 20, co-authored 41 publications receiving 1638 citations. Previous affiliations of Roy C. P. Kerckhoffs include University of California, Berkeley & Eindhoven University of Technology.

Coupling of a 3D Finite Element Model of Cardiac Ventricular Mechanics to Lumped Systems Models of the Systemic and Pulmonic Circulation

Abstract: In this study we present a novel, robust method to couple finite element (FE) models of cardiac mechanics to systems models of the circulation (CIRC), independent of cardiac phase. For each time step through a cardiac cycle, left and right ventricular pressures were calculated using ventricular compliances from the FE and CIRC models. These pressures served as boundary conditions in the FE and CIRC models. In succeeding steps, pressures were updated to minimize cavity volume error (FE minus CIRC volume) using Newton iterations. Coupling was achieved when a predefined criterion for the volume error was satisfied. Initial conditions for the multi-scale model were obtained by replacing the FE model with a varying elastance model, which takes into account direct ventricular interactions. Applying the coupling, a novel multi-scale model of the canine cardiovascular system was developed. Global hemodynamics and regional mechanics were calculated for multiple beats in two separate simulations with a left ventricular ischemic region and pulmonary artery constriction, respectively. After the interventions, global hemodynamics changed due to direct and indirect ventricular interactions, in agreement with previously published experimental results. The coupling method allows for simulations of multiple cardiac cycles for normal and pathophysiology, encompassing levels from cell to system.

Homogeneity of cardiac contraction despite physiological asynchrony of depolarization: a model study.

Abstract: The use of mathematical models combining wave propagation and wall mechanics may provide new insights in the interpretation of cardiac deformation toward various forms of cardiac pathology. In the present study we investigated whether combining accepted mechanisms on propagation of the depolarization wave, time variant mechanical properties of car- diac tissue after depolarization, and hemodynamic load of the left ventricle ~LV! by the aortic impedance in a three- dimensional finite element model results in a physiological pattern of cardiac contraction. We assumed that the delay be- tween depolarization for all myocytes and the onset of cross- bridge formation was constant. Two simulations were per- formed, one in which contraction was initiated according to the regular depolarization pattern ~NORM simulation!, and another in which contraction was initiated after synchronous depolar- ization ~SYNC simulation!. In the NORM simulation propaga- tion of depolarization was physiological, but wall strain was unphysiologically inhomogeneous. When simulating LV me- chanics with unphysiological synchronous depolarization ~SYNC! myofiber strain was more homogeneous and more physiologic. Apparently, the assumption of a constant delay between depolarization and onset of crossbridge formation re- sults in an unrealistic contraction pattern. The present finding may indicate that electromechanical delay times are heteroge- neously distributed, such that a contraction in a normal heart is more synchronous than depolarization. © 2003 Biomedical Engineering Society. @DOI: 10.1114/1.1566447#

Current progress in patient-specific modeling

Abstract: We present a survey of recent advancements in the emerging field of patient-specific modeling (PSM). Researchers in this field are currently simulating a wide variety of tissue and organ dynamics to address challenges in various clinical domains. The majority of this research employs three-dimensional, image-based modeling techniques. Recent PSM publications mostly represent feasibility or preliminary validation studies on modeling technologies, and these systems will require further clinical validation and usability testing before they can become a standard of care. We anticipate that with further testing and research, PSM-derived technologies will eventually become valuable, versatile clinical tools.

Patient-specific modeling of dyssynchronous heart failure: a case study.

Abstract: The development and clinical use of patient-specific models of the heart is now a feasible goal. Models have the potential to aid in diagnosis and support decision-making in clinical cardiology. Several groups are now working on developing multi-scale models of the heart for understanding therapeutic mechanisms and better predicting clinical outcomes of interventions such as cardiac resynchronization therapy. Here we describe the methodology for generating a patient-specific model of the failing heart with a myocardial infarct and left ventricular bundle branch block. We discuss some of the remaining challenges in developing reliable patient-specific models of cardiac electromechanical activity, and identify some of the main areas for focusing future research efforts. Key challenges include: efficiently generating accurate patient-specific geometric meshes and mapping regional myofiber architecture to them; modeling electrical activation patterns based on cellular alterations in human heart failure, and estimating regional tissue conductivities based on clinically available electrocardiographic recordings; estimating unloaded ventricular reference geometry and material properties for biomechanical simulations; and parameterizing systemic models of circulatory dynamics from available hemodynamic measurements.

A synchronized quorum of genetic clocks

Abstract: The engineering of genetic circuits with predictive functionality in living cells represents a defining focus of the expanding field of synthetic biology. This focus was elegantly set in motion a decade ago with the design and construction of a genetic toggle switch and an oscillator, with subsequent highlights that have included circuits capable of pattern generation, noise shaping, edge detection and event counting. Here we describe an engineered gene network with global intercellular coupling that is capable of generating synchronized oscillations in a growing population of cells. Using microfluidic devices tailored for cellular populations at differing length scales, we investigate the collective synchronization properties along with spatiotemporal waves occurring at millimetre scales. We use computational modelling to describe quantitatively the observed dependence of the period and amplitude of the bulk oscillations on the flow rate. The synchronized genetic clock sets the stage for the use of microbes in the creation of a macroscopic biosensor with an oscillatory output. Furthermore, it provides a specific model system for the generation of a mechanistic description of emergent coordinated behaviour at the colony level.

A survey of MRI-based medical image analysis for brain tumor studies

Abstract: MRI-based medical image analysis for brain tumor studies is gaining attention in recent times due to an increased need for efficient and objective evaluation of large amounts of data. While the pioneering approaches applying automated methods for the analysis of brain tumor images date back almost two decades, the current methods are becoming more mature and coming closer to routine clinical application. This review aims to provide a comprehensive overview by giving a brief introduction to brain tumors and imaging of brain tumors first. Then, we review the state of the art in segmentation, registration and modeling related to tumor-bearing brain images with a focus on gliomas. The objective in the segmentation is outlining the tumor including its sub-compartments and surrounding tissues, while the main challenge in registration and modeling is the handling of morphological changes caused by the tumor. The qualities of different approaches are discussed with a focus on methods that can be applied on standard clinical imaging protocols. Finally, a critical assessment of the current state is performed and future developments and trends are addressed, giving special attention to recent developments in radiological tumor assessment guidelines.

Constitutive modelling of passive myocardium: A structurally-based framework for material characterization

Abstract: In this paper, we first of all review the morphology and structure of the myocardium and discuss the main features of the mechanical response of passive myocardium tissue, which is an orthotropic material. Locally within the architecture of the myocardium three mutually orthogonal directions can be identified, forming planes with distinct material responses. We treat the left ventricular myocardium as a non-homogeneous, thick-walled, nonlinearly elastic and incompressible material and develop a general theoretical framework based on invariants associated with the three directions. Within this framework we review existing constitutive models and then develop a structurally based model that accounts for the muscle fibre direction and the myocyte sheet structure. The model is applied to simple shear and biaxial deformations and a specific form fitted to the existing (and somewhat limited) experimental data, emphasizing the orthotropy and the limitations of biaxial tests. The need for additional data is highlighted. A brief discussion of issues of convexity of the model and related matters concludes the paper.

Sudden Cardiac Death Prediction and Prevention: Report From a National Heart, Lung, and Blood Institute and Heart Rhythm Society Workshop

Abstract: Despite the significant decline in coronary artery disease (CAD) mortality in the second half of the 20th century,1 sudden cardiac death (SCD) continues to claim 250 000 to 300 000 US lives annually.2 In North America and Europe the annual incidence of SCD ranges between 50 to 100 per 100 000 in the general population.3,–,6 Because of the absence of emergency medical response systems in most world regions, worldwide estimates are currently not available.7 However, even in the presence of advanced first responder systems for resuscitation of out-of-hospital cardiac arrest, the overall survival rate in a recent North American analysis was 4.6%.8 SCD can manifest as ventricular tachycardia (VT), ventricular fibrillation (VF), pulseless electric activity (PEA), or asystole. In a significant proportion of patients, SCD can present without warning or a recognized triggering mechanism. The mean age of those affected is in the mid 60s, and at least 40% of patients will suffer SCD before the age of 65.4 Consequently, enhancement of methodologies for prediction and prevention of SCD acquires a unique and critical importance for management of this significant public health issue. Prediction and prevention of SCD is an area of active investigation, but considerable challenges persist that limit the efficacy and cost-effectiveness of available methodologies.7,9,10 It was recognized early on that optimization of SCD risk stratification will require integration of multi-disciplinary efforts at the bench and bedside, with studies in the general population.11,–,13 This integration has yet to be effectively accomplished. There is also increasing awareness that more investigation needs to be directed toward identification of early predictors of SCD.14 Significant advancements have occurred for risk prediction in the inherited channelopathies15,–,17 and …