Reports about 8 selected benchmark cases of model hierarchies : Deliverable number: D5.1 - Version 0.1

Based on the multitude of industrial applications, benchmarks for model hierarchies will be created that will form a basis for the interdisciplinary research and for the training programme. These will be equipped with publically available data and will be used for training in modelling, model testing, reduced order modelling, error estimation, efficiency optimization in algorithmic approaches, and testing of the generated MSO/MOR software. The present document includes the description about the selection of (at least) eight benchmark cases of model hierarchies.EC/H2020/765374/EU/Reduced Order Modelling, Simulation and Optimization of Coupled Systems/ROMSO

Improving flow-induced hemolysis prediction models.

Partial or complete failure of red blood cell membrane, also known as hemolysis, is a persistent issue with almost all blood contacting devices. Many experimental and theoretical contributions over the last few decades have increased insight into the mechanisms of mechanical hemolysis in both laminar and turbulent flow regimes, with the ultimate goal of developing a comprehensive, mechanistic and universal hemolysis prediction model. My research is broadly divided into two sections: theoretical/analytical/Computational Fluid Dynamics (CFD) analyses and experimental tests. The first part of my research revolved entirely around analyzing the simplest and most popular hemolysis model, commonly called as the power-law model. This model was developed only for laminar pure shear flow within a limited range of exposure time. Subsequently, modified versions of this model have been developed to be used for more complex flows. Many of these modified models assume that hemolysis scales with a resultant, scalar stress representing all components of the fluid stress tensor. The most common representative stress used in the power-law model is a von-Mises-like stress. However, using membrane tension models for pure shear and pure extension in both laminar and turbulent flows, for some simple example cases, we have shown that scalar stress alone is inadequate for scaling hemolysis. Alternatively, the rate of viscous energy dissipation rate has also been proposed as the parameter to scale hemolysis with. Applying the same order-of-magnitude estimate as vi mentioned above, we have found that dissipation rate even behaves worse than the resultant scalar stress for hemolysis prediction. It is therefore concluded that energy dissipation rate alone is also not sufficient to universally scale blood damage across complex flows. These show that a realistic model of hemolysis must take into account different responses of the viscoelastic cell membrane to different stress type. Various discretized version of the power-law model has also been introduced for post-processing of the CFD results. The power law can be either discretized in space, Eulerian treatment, or in time, Lagrangian treatment. Our study on the Eulerian approach revealed that the current equations used in the literature has a missing term, and thus incorrect. We also examined the mathematical stability of the discretized power-law model, and found that it may introduce significant error in red cell damage prediction for certain pathlines with specific stress history. Experimental results on deformation of red cell in pure shear flow is present for a relatively wide range of shear rates. However, red cell deformation/elongation in pure laminar extensional flow is scarce, with only one publication reporting their results on red cell deformation for only up to stress level of 10 Pa. For the experimental part of my research, we conducted experiments to observe the difference in deformation of red cell in pure shear and pure extensional flows, for stresses beyond what has already been reported in the literature. This dissertation is composed of three chapters. Chapter I is the literature survey and introductory materials. Chapter II contains the discussion and results for the theoretical/analytical/CFD part of the research. Finally, discussion and results for the experimental tests are presented in Chapter III

Doctor of Philosophy

dissertationAtrial fibrillation (AF) is the leading cause of ischemic stroke and is the most commonly observed arrhythmia in clinical cardiology. Catheter ablation of AF, in which specific regions of cardiac anatomy associated with AF are intenionally injured to create scar tissue, has been honed over the last 15 years to become a relatively common and safe treatment option. However, the success of these anatomically driven ablation strategies, particularly in hearts that have been exposed to AF for extended periods, remains poor. AF induces changes in the electrical and structural properties of the cardiac tissue that further promotes the permanence of AF. In a process known as electroanatomical (EAM) mapping, clinicians record time signals known as electrograms (EGMs) from the heart and the locations of the recording sites to create geometric representations, or maps, of the electrophysiological properties of the heart. Analysis of the maps and the individual EGM morphologies can indicate regions of abnormal tissue, or substrates that facilitate arrhythmogenesis and AF perpetuation. Despite this progress, limitations in the control of devices currently used for EAM acquisition and reliance on suboptimal metrics of tissue viability appear to be hindering the potential of treatment guided by substrate mapping. In this research, we used computational models of cardiac excitation to evaluate param- eters of EAM that affect the performance of substrate mapping. These models, which have been validated with experimental and clinical studies, have yielded new insights into the limitations of current mapping systems, but more importantly, they guided us to develop new systems and metrics for robust substrate mapping. We report here on the progress in these simulation studies and on novel measurement approaches that have the potential to improve the robustness and precision of EAM in patients with arrhythmias. Appropriate detection of proarrhythmic substrates promises to improve ablation of AF beyond rudimentary destruction of anatomical targets to directed targeting of complicit tissues. Targeted treatment of AF sustaining tissues, based on the substrate mapping approaches described in this dissertation, has the potential to improve upon the efficacy of current AF treatment options

Development and applications of in-vitro and in-silico models of the cardiovascular system to study the effects of mechanical circulatory support.

Cardiovascular diseases (CVDs) are the leading cause of mortality globally. With ongoing interest in CVDs treatment, preclinical models for drug/therapeutic development that allow for fast iterative research are needed. Owing to the inherent complexity of the cardiovascular system, current in-vitro models of the cardiovascular system fail to replicate many of the physiological aspects of the cardiovascular system. In this dissertation, the main concern is with heart failure (HF). In advanced HF, patients may receive Left Ventricular Assist Devices (LVADs) as a bridge to transplant or destination therapy. However, LVADs have many limitations, including inability to adapt to varying tissue demand conditions, risk of ventricular suction, and diminished arterial pulsatility. To address these issues, this dissertation aims to use and develop computer, cellular, and tissue models of the cardiovascular system. 1) Use an in-silico model of the cardiovascular system to develop a novel control algorithm for LVADs. The control system was rigorously tested and showed adequate perfusion during rest and exercise, protect against ventricular suction under reduced heart preload, and augment arterial pulsatility through pulse modulation without requiring sensor implantation or model-based estimations. 2) While pulsatility augmentation was feasible through the developed control algorithm, the pulse waveform that could normalize the vascular phenotype is unknown. To address this, an endothelial cell-smooth muscle cell microfluidic coculture model was developed to recreate the physiological mechanical stimulants in the vascular wall. The results demonstrated different effects of pulsatile shear stress and stretch on endothelial cells and may indicate that a pulse pressure of at least 30 mmHg is needed to maintain normal endothelial morphology. 3) In order to study the effects of mechanical unloading on the native ventricle, a novel cardiac tissue culture model (CTCM) was developed. CTCM provided physiological electromechanical and humoral stimulation with 25% preload stretch and thyroid and glucocorticoid treatment maintained the cardiac phenotype for 12 days. The device was thoroughly characterized and tested. Results demonstrated improved viability, energy utilization, fibrotic remodeling, and structural integrity compared to available culture systems. The system was also used to reproduce ventricular volume-overload and the results demonstrated hypertrophic and fibrotic remodeling, typical of volume-overload pathology

Experimental study of the mechanics of the intra-aortic balloon

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis deals with the mechanics of the Intra-Aortic Balloon Pump (IABP), the most widely used temporary cardiac assist device, whose beneficial action is based on the principle of counterpulsation. The investigation is carried out in vitro in increasingly more realistic setups, including a mock circulatory system with physiological distribution of peripheral resistance and compliance in which IABP counterpulsation was simulated. Pressure and flow measurements show the effect of variables such as intra-luminal pressure, angle and aortic compliance on balloon hemodynamics. These data are complemented by results on the duration of balloon inflation and deflation obtained by means of high-speed camera visualisation. Furthermore, wave intensity analysis is carried out and it is identified as a possible alternative method for the assessment of IABP performance. This work includes two prototypes of intra-aortic balloons of novel shape with the balloon chamber tapering both from and toward the balloon tip. In clinical terms, with reference to the semi-recumbent position in which patients assisted with the IABP are nursed in the intensive care unit, the results presented in this thesis indicate that operating the balloon at an angle compromises the benefit of counterpulsation when assessed in vitro

Abbott Cardiac Electrophysiology Wet Lab Project

Cardiac mapping systems provide electrophysiologists with pertinent information about ablation treatment plans for patients who suffer from cardiac arrhythmias. This thesis describes the process of designing a functional wet lab that integrates with Abbott’s EnSite Precision 3D Mapping System, with the purpose of providing Cal Poly students and faculty with an opportunity to have a hands-on learning experience with cardiac mapping. This project encompassed a thorough literature review of cardiology, electrophysiology, and in vitro lab systems, followed by the design, manufacturing, and evaluation of a functional and anatomically representative wet lab. This is a continuation of previous master’s projects that had similar goals. Improvements included more accurate geometry collection, anatomical landmarks and physiologically accurate conditions, and usability improvements. The outcome of this project was a functional wet lab, fully integrated with the Abbott EnSite System with accurate geometry collection within 6% error. Anatomically accurate vasculature and a left atrium were incorporated to further enhance the capabilities and authenticity of the lab. We hope that the Cal Poly community will continue to expand upon and make use of the wet lab

NASA technology applications team: Applications of aerospace technology

Two critical aspects of the Applications Engineering Program were especially successful: commercializing products of Application Projects; and leveraging NASA funds for projects by developing cofunding from industry and other agencies. Results are presented in the following areas: the excimer laser was commercialized for clearing plaque in the arteries of patients with coronary artery disease; the ultrasound burn depth analysis technology is to be licensed and commercialized; a phased commercialization plan was submitted to NASA for the intracranial pressure monitor; the Flexible Agricultural Robotics Manipulator System (FARMS) is making progress in the development of sensors and a customized end effector for a roboticized greenhouse operation; a dual robot are controller was improved; a multisensor urodynamic pressure catherer was successful in clinical tests; commercial applications were examined for diamond like carbon coatings; further work was done on the multichannel flow cytometer; progress on the liquid airpack for fire fighters; a wind energy conversion device was tested in a low speed wind tunnel; and the Space Shuttle Thermal Protection System was reviewed