Nonlinear multiscale analysis of coronary atherosclerotic vulnerable plaque artery: fluid-structural modeling with micromechanics.

A unique three-dimensional (3D) computational multiscale modeling approach is proposed to investigate the influence of presence of microcalcification particles on the stress field distribution in the thin cap layer of a coronary atherosclerotic vulnerable plaque system. A nested 3D modeling analysis framework spanning the multiscale nature of a coronary atherosclerotic vulnerable plaque is presented. At the microscale level, a micromechanical modeling approach, which is based on computational finite-element (FE) representative unit cell, is applied to obtain the homogenized nonlinear response of the calcified tissue.

A predictive multiscale model for simulating flow-induced platelet activation: Correlating in silico results with in vitro results.

Flow-induced platelet activation prompts complex filopodial formation. Continuum methods fail to capture such molecular-scale mechanisms. A multiscale numerical model was developed to simulate this activation process, where a Dissipative Particle Dynamics (DPD) model of viscous blood flow is interfaced with a Coarse Grained Molecular Dynamics (CGMD) platelet model.

New Insights into Valve Hemodynamics.

Heart valve diseases are common disorders with five million annual diagnoses being made in the United States alone. All heart valve disorders alter cardiac hemodynamic performance; therefore, treatments aim to restore normal flow. This paper reviews the state-of-the-art clinical and engineering advancements in heart valve treatments with a focus on hemodynamics.

Improving the Mechanical Rigidity of Hyaluronic Acid by Integration of a Supramolecular Peptide Matrix.

Hyaluronic acid (HA), a major component of the extracellular matrix, is an attractive material for various medical applications. Yet, its low mechanical rigidity and fast in vivo degradation hinder its utilization. Here, we demonstrate the reinforcement of HA by its integration with a low-molecular-weight peptide hydrogelator to produce a composite hydrogel.

Mechanical Compression Effects on the Secretion of vWF and IL-8 by Cultured Human Vein Endothelium.

Short peripheral catheters are ubiquitous in today's healthcare environment enabling effective delivery of fluids and medications directly into a patient's vasculature. However, complications related to their use, such as short peripheral catheter thrombophlebitis (SPCT), affect up to 80% of hospitalized patients. While indwelling within the vein, the catheters exert prolonged constant pressure upon the endothelium which can trigger inflammation processes.

Ventricular Assist Device Implantation Configurations Impact Overall Mechanical Circulatory Support System Thrombogenic Potential.

Ventricular assist devices (VADs) became in recent years the standard of care therapy for advanced heart failure with hemodynamic compromise. With the steadily growing population of device recipients, various postimplant complications have been reported, mostly associated with the hypershear generated by VADs that enhance their thrombogenicity by activating platelets. Although VAD design optimization can significantly improve its thromboresistance, the implanted VAD need to be evaluated as part of a system.

Pressure drop and arterial compliance - Two arterial parameters in one measurement.

Coronary artery pressure-drop and distensibility (compliance) are two major, seemingly unrelated, parameters in the cardiovascular clinical setting, which are indicative of coronary arteries patency and atherosclerosis severity. While pressure drop is related to flow, and therefore serves as a functional indicator of a stenosis severity, the arterial distensibility is indicative of the arterial stiffness, and hence the arterial wall composition. In the present study, we hypothesized that local pressure drops are dependent on the arterial distensibility, and hence can provide information on both indices.

Quantitative T2 mapping for detection and quantification of thrombophlebitis in a rabbit model.

Short peripheral catheter thrombophlebitis (SPCT), a sterile inflammation of the vein wall, is the most common complication associated with short peripheral catheters (SPCs) and affects up to 80% of hospitalized patients receiving IV therapy. Extensive research efforts have been devoted for improvement and optimization of the catheter material, but means for examination of any novel design are limited, inaccurate and require costly comprehensive pre-clinical and clinical trials. Therefore, there is a conclusive need for a reliable quantitative method for evaluation of SPCT, in particular for research purposes examining the thrombophlebitis-related symptoms of any novel catheter design.

The effect of pathologic venous valve on neighboring valves: fluid-structure interactions modeling.

Understanding the hemodynamics surrounding the venous valve environment is of a great importance for prosthetic valves design. The present study aims to evaluate the effect of leaflets' stiffening process on the venous valve hemodynamics, valve's failure on the next proximal valve hemodynamics and valve's failure in a secondary daughter vein on the healthy valve hemodynamics in the main vein when both of these valves are distal to a venous junction. Fully coupled, two-way fluid-structure interaction computational models were developed and employed.

Single additive mechanism predicts lateral interactions effects-computational model.

The mechanism underlying the lateral interactions (LI) phenomenon is still an enigma. Over the years, several groups have tried to explain the phenomenon and suggested models to predict its psychophysical results. Most of these models comprise both inhibitory and facilitatory mechanisms for describing the LI phenomenon.

High accuracy differential pressure measurements using fluid-filled catheters - A feasibility study in compliant tubes.

High accuracy differential pressure measurements are required in various biomedical and medical applications, such as in fluid-dynamic test systems, or in the cath-lab. Differential pressure measurements using fluid-filled catheters are relatively inexpensive, yet may be subjected to common mode pressure errors (CMP), which can significantly reduce the measurement accuracy. Recently, a novel correction method for high accuracy differential pressure measurements was presented, and was shown to effectively remove CMP distortions from measurements acquired in rigid tubes.

Modelling catheter-vein biomechanical interactions during an intravenous procedure.

A reliable intravenous (IV) access into the upper extremity veins requires the insertion of a temporary short peripheral catheter (SPC). This so common procedure is, however, associated with a risk of developing short peripheral catheter thrombophlebitis (SPCT) which causes distress and potentially prolongs patient hospitalization. We have developed and studied a biomechanical SPC-vein computational model during an IV procedure, and explored the biomechanical effects of repeated IV episodes on onset and reoccurrences of SPCT.

Progression of abdominal aortic aneurysm towards rupture: refining clinical risk assessment using a fully coupled fluid-structure interaction method.

Rupture of abdominal aortic aneurysm (AAA) is associated with high mortality rates. Risk of rupture is multi-factorial involving AAA geometric configuration, vessel tortuosity, and the presence of intraluminal pathology. Fluid structure interaction (FSI) simulations were conducted in patient based computed tomography scans reconstructed geometries in order to monitor aneurysmal disease progression from normal aortas to non-ruptured and contained ruptured AAA (rAAA), and the AAA risk of rupture was assessed.

Numerical models of net-structure stents inserted into arteries.

Introduction: Restenosis is strongly attributed to stresses caused by stent-artery interactions generated in the artery after balloon angioplasty. Numerical methods are often used to examine the stent-artery mechanical interactions. To overcome the extensive computational requirements demanded by these simulations, simplifications are needed.

Method for high accuracy differential pressure measurements using fluid-filled catheters.

The advantage of measuring differential pressure using fluid-filled catheters is that the system is relatively inexpensive, but the readings are not accurate and affected by the common mode pressure (CMP) distortion. High accuracy differential pressure measurements are required in various biomedical applications, such as in fluid-dynamic test rigs, or in the cath-lab, from cardiac valves efficacy to functional assessment of arterial stenoses. We have designed and built a unique system in which the pressure difference was measured along the fluid flow inside a rigid circular tube using a fluid-filled double-lumen catheter.

Wall shear stress effects on endothelial-endothelial and endothelial-smooth muscle cell interactions in tissue engineered models of the vascular wall.

Vascular functions are affected by wall shear stresses (WSS) applied on the endothelial cells (EC), as well as by the interactions of the EC with the adjacent smooth muscle cells (SMC). The present study was designed to investigate the effects of WSS on the endothelial interactions with its surroundings. For this purpose we developed and constructed two co-culture models of EC and SMC, and compared their response to that of a single monolayer of cultured EC.

Thromboresistance comparison of the HeartMate II ventricular assist device with the device thrombogenicity emulation- optimized HeartAssist 5 VAD.

Approximately 7.5 × 106 patients in the US currently suffer from end-stage heart failure. The FDA has recently approved the designations of the Thoratec HeartMate II ventricular assist device (VAD) for both bridge-to-transplant and destination therapy (DT) due to its mechanical durability and improved hemodynamics.

Biomechanical factors in coronary vulnerable plaque risk of rupture: intravascular ultrasound-based patient-specific fluid-structure interaction studies.

Objectives: The aim of this study was to elucidate the mechanisms and underlying biomechanical factors that may play a role in the risk of rupture of vulnerable plaques (VPs) by studying patient-based geometries of coronary arteries reconstructed from intravascular ultrasound (IVUS) imaging utilizing fluid-structure interaction (FSI) numerical simulations.

Background: According to recent estimates, coronary artery disease is responsible for one in six deaths in the USA, and causes about one million heart attacks each year. Among these, the rupture of coronary VPs followed by luminal blockage is widely recognized as a major cause of sudden heart attacks; most importantly, the patients may appear as asymptomatic under routine screening before the occurrence of the index event.

The Syncardia(™) total artificial heart: in vivo, in vitro, and computational modeling studies.

The SynCardia(™) total artificial heart (TAH) is the only FDA-approved TAH in the world. The SynCardia(™) TAH is a pneumatically driven, pulsatile system capable of flows of >9L/min. The TAH is indicated for use as a bridge to transplantation (BTT) in patients at imminent risk of death from non-reversible bi-ventricular failure.

Device thrombogenicity emulation: a novel methodology for optimizing the thromboresistance of cardiovascular devices.

Thrombotic complications with mechanical circulatory support (MCS) devices remain a critical limitation to their long-term use. Device-induced shear forces may enhance the thrombotic potential of MCS devices through chronic activation of platelets, with a known dose-time response of the platelets to the accumulated stress experienced while flowing through the device-mandating complex, lifelong anticoagulation therapy. To enhance the thromboresistance of these devices for facilitating their long-term use, a universal predictive methodology entitled device thrombogenicity emulation (DTE) was developed.

Intracoronary monocyte chemoattractant protein 1 and vascular endothelial growth factor levels are associated with necrotic core, calcium and fibrous tissue atherosclerotic plaque components: an intracoronary ultrasound radiofrequency study.

Aims: To investigate the relationship between various serum biomarkers and coronary atherosclerotic plaque composition obtained by intravascular ultrasound virtual histology (IVUS-VH).

Methods: Using ELISA, we measured the serum levels of CD40 ligand, C-reactive protein, monocyte chemoattractant protein 1 (MCP-1), metalloproteinase 9, P-selectin and vascular endothelial growth factor (VEGF) in 40 patients with manifested coronary artery disease.

Results: Correlation analysis between biomarkers levels, IVUS grayscale parameters and VH-defined necrotic core (NC), calcium, fibrous and fibrofatty components was performed.

Device thrombogenicity emulation: a novel method for optimizing mechanical circulatory support device thromboresistance.

Mechanical circulatory support (MCS) devices provide both short and long term hemodynamic support for advanced heart failure patients. Unfortunately these devices remain plagued by thromboembolic complications associated with chronic platelet activation--mandating complex, lifelong anticoagulation therapy. To address the unmet need for enhancing the thromboresistance of these devices to extend their long term use, we developed a universal predictive methodology entitled Device Thrombogenicity Emulation (DTE) that facilitates optimizing the thrombogenic performance of any MCS device--ideally to a level that may obviate the need for mandatory anticoagulation.

Necrotic core and thin cap fibrous atheroma distribution in native coronary artery lesion-containing segments: a virtual histology intravascular ultrasound study.

Objectives: The aim of this study was to assess the longitudinal topographical relationships between minimal luminal area (MLA) sites and plaques with the most vulnerable characteristics using radiofrequency-based virtual histology intravascular ultrasound analysis.

Methods: We analyzed 69 native coronary artery segments with de-novo lesions (>50% stenosis) obtained from 50 patients with ischemic coronary artery disease. Maximal necrotic core (maxNC) was defined as a virtual histology intravascular ultrasound frame with the maxNC area and virtual histology-characterized thin cap fibrous atheroma was defined as a cross-section, which contained a plaque burden of more than 40%, relative necrotic core area of 10% or more, and a narrow band encircling the lumen containing relative necrotic core area of more than 10%, in three consecutive frames.

Patient based abdominal aortic aneurysm rupture risk prediction combining clinical visualizing modalities with fluid structure interaction numerical simulations.

Fluid structure interaction (FSI) simulations of patient-specific fusiform non-ruptured and contained ruptured Abdominal Aortic Aneurysm (AAA) geometries were conducted. The goals were: (1) to test the ability of our FSI methodology to predict the location of rupture, by correlating the high wall stress regions with the rupture location, (2) estimate the state of the pathological condition by calculating the ruptured potential index (RPI) of the AAA and (3) predict the disease progression by comparing healthy and pathological aortas.