Non-invasive estimation of the parameters of a three-element windkessel model of aortic arch arteries in patients undergoing thoracic endovascular aortic repair.

Image-based computational hemodynamic modeling and simulations are important for personalized diagnosis and treatment of cardiovascular diseases. However, the required patient-specific boundary conditions are often not available and need to be estimated. We propose a pipeline for estimating the parameters of the popular three-element Windkessel (WK3) models (a proximal resistor in series with a parallel combination of a distal resistor and a capacitor) of the aortic arch arteries in patients receiving thoracic endovascular aortic repair of aneurysms.

Distinct Temporal Pattern of the Prediction of Lumen Remodeling of Lower Extremity Vein Bypass Grafts by Initial Local Hemodynamics.

We predicted human lower extremity vein bypass graft remodeling by hemodynamics. Computed tomography and duplex ultrasound scans of 55 patients were performed at 1 week and 1, 6, and 12 months post-implantation to obtain wall shear stress (WSS) and oscillatory shear index (OSI) at 1-mm intervals via computational fluid dynamics simulations. Graft remodeling was quantified by computed tomography-measured lumen diameter changes in the early (1 week-1 month), intermediate (1-6 months), and late (6-12 months) periods.

Haemodynamics of Different Configurations of a Left Subclavian Artery Stent Graft for Thoracic Endovascular Aortic Repair.

Objective: Branched stent grafts represent a viable option for left subclavian artery (LSA) revascularisation in patients treated by thoracic endovascular aortic repair (TEVAR) for Zone 2 lesions. This study investigated the haemodynamic performance of different LSA branched stent graft configurations as potential determinants of thrombotic and stroke risks.

Methods: A three dimensional aortic arch geometry extracted from post-operative computed tomography images of a TEVAR patient using a single LSA branched aortic endograft was modified in silico to obtain ten potential LSA branched stent graft configurations: five down facing (0-5 - 10 mm aortic protrusion with 10-12 mm internal diameter), four curved (30-60° with antegrade/retrograde orientation), and one LSA orifice misalignment.

Heterogeneous and dynamic lumen remodeling of the entire infrainguinal vein bypass grafts in patients.

Objective: To examine the regional variation and temporal change in lumen size along the entire autogenous vein bypass graft used for treating arterial occlusive disease in lower extremity and to explore the factors associated with graft expansive or constrictive remodeling.

Methods: Patients were prospectively scanned using contrast-enhanced computed tomography at 1 week and 1, 6, and 12 months postoperatively to obtain lumen cross-sectional areas at 1-mm intervals along the entire grafts. Graft lumen remodeling characteristics and the associated demographic and clinical factors were examined.

Anatomic and hemodynamic investigation of an occluded common carotid chimney stent graft for hybrid thoracic aortic aneurysm repair.

We examined the possible reasons for common carotid artery chimney stent graft occlusion through computational fluid dynamics analyses of follow-up imaging of a patient-specific aortic configuration reconstructed from computed tomography aortography. Anatomic and hemodynamic parameters were extracted for the bilateral common carotid and subclavian arteries before and after endograft placement. Results suggested that postoperative reduction in lumen diameter within the chimney stent graft combined with an increased flow rate led to complex hemodynamics with high wall shear stress, probably resulting in high-shear thrombogenesis and chimney stent graft occlusion 2.

Hemodynamic and Anatomic Predictors of Renovisceral Stent-Graft Occlusion Following Chimney Endovascular Repair of Juxtarenal Aortic Aneurysms.

Purpose: To identify anatomic and hemodynamic changes associated with impending visceral chimney stent-graft occlusion after endovascular aneurysm repair (EVAR) with the chimney technique (chEVAR).

Methods: A retrospective evaluation was performed of computed tomography scans from 41 patients who underwent juxtarenal chEVAR from 2008 to 2012 to identify stent-grafts demonstrating conformational changes following initial placement. Six subjects (mean age 74 years; 3 men) were selected for detailed reconstruction and computational hemodynamic analysis; 4 had at least 1 occluded chimney stent-graft.

Hemodynamic Influence on Smooth Muscle Cell Kinetics and Phenotype During Early Vein Graft Adaptation.

Pathologic vascular adaptation following local injury is the primary driver for accelerated intimal hyperplasia and an occlusive phenotype. Smooth muscle cell (SMC) proliferation within the wall, and migration into the developing intima, is a major component of this remodeling response. The primary objective in the current study was to investigate the effect of the local biomechanical forces on early vein graft adaptation, specifically focusing on the spatial and temporal response of SMC proliferation and conversion from a contractile to synthetic architecture.

Multi-scale Modeling of the Cardiovascular System: Disease Development, Progression, and Clinical Intervention.

Cardiovascular diseases (CVDs) are the leading cause of death in the western world. With the current development of clinical diagnostics to more accurately measure the extent and specifics of CVDs, a laudable goal is a better understanding of the structure-function relation in the cardiovascular system. Much of this fundamental understanding comes from the development and study of models that integrate biology, medicine, imaging, and biomechanics.

Rule-based model of vein graft remodeling.

When vein segments are implanted into the arterial system for use in arterial bypass grafting, adaptation to the higher pressure and flow of the arterial system is accomplished thorough wall thickening and expansion. These early remodeling events have been found to be closely coupled to the local hemodynamic forces, such as shear stress and wall tension, and are believed to be the foundation for later vein graft failure. To further our mechanistic understanding of the cellular and extracellular interactions that lead to global changes in tissue architecture, a rule-based modeling method is developed through the application of basic rules of behaviors for these molecular and cellular activities.

Reconstructing regulatory networks from the dynamic plasticity of gene expression by mutual information.

The capacity of an organism to respond to its environment is facilitated by the environmentally induced alteration of gene and protein expression, i.e. expression plasticity.

The dynamics of vein graft remodeling induced by hemodynamic forces: a mathematical model.

Although vein bypass grafting is one of the primary options for the treatment of arterial occlusive disease and provides satisfactory results at an early stage of the treatment, the patency is limited to a few months in many patients. When the vein is implanted in the arterial system, it adapts to the high flow rate and high pressure of the arterial environment by changing the sizes of its layers, and this remodeling is believed to be a precursor of future graft failure. Hemodynamic forces, such as wall shear stress (WSS) and wall tension, have been recognized as major factors impacting vein graft remodeling.

Development of a calcium alginate tympanostomy tube.

Objectives/hypothesis: Tympanostomy tubes (TTs) are prone to complications resulting in part from the unpredictable duration that the TT remains in the tympanic membrane. General anesthesia may be necessary to remove TTs that fail to extrude. The purpose of this study was to develop a TT that could be dissolved on demand but remain functional with exposure to common otologic exposures.

The extracellular matrix microtopography drives critical changes in cellular motility and Rho A activity in colon cancer cells.

We have shown that the microtopography (mT) underlying colon cancer changes as a tumor de-differentiates. We distinguish the well-differentiated mT based on the increasing number of "pits" and poorly differentiated mT on the basis of increasing number of "posts." We investigated Rho A as a mechanosensing protein using mT features derived from those observed in the ECM of colon cancer.

In vitro testing of tympanostomy tube occlusion.

Objective: Tympanostomy tubes (TTs) are commonly rendered nonfunctional by mucus plug formation. The purpose of this study was to determine whether an in vitro model could be developed to assess TT plug formation with results consistent with human trials.

Study Design: An ear chamber was designed to mimic middle ear air and mucus flow conditions in post-TT otorrhea.

Rule-Based Simulation of Multi-Cellular Biological Systems-A Review of Modeling Techniques.

Emergent behaviors of multi-cellular biological systems (MCBS) result from the behaviors of each individual cells and their interactions with other cells and with the environment. Modeling MCBS requires incorporating these complex interactions among the individual cells and the environment. Modeling approaches for MCBS can be grouped into two categories: continuum models and cell-based models.

Hemodynamically driven vein graft remodeling: a systems biology approach.

Despite intense investigation over several decades to understand the mechanisms of vein graft failure, few therapeutic modalities have emerged. Emphasis using standard reductionist approaches has been focused on cataloging the components involved in the early events following vein graft implantation, but limited insight has been gained in understanding the dynamic interaction of these components. We propose that the application of systems theory offers the opportunity for significant advances in this area.

An experiment-based model of vein graft remodeling induced by shear stress.

Vein graft intimal hyperplasia induced by shear stress is considered to be one of the major causes of vein graft failure. We have developed a mathematical model of vein graft intimal hyperplasia induced by shear stress based on experimental data. Intimal thickness and the rate of intimal thickness change are expressed as functions of shear stress and time.

Marrow cell therapies for cardiovascular diseases.

The nascent field of regenerative medicine has taken root in cardiovascular disease. Preclinical data demonstrating hemangioblast potential of marrow cells and cardioprotective effects of growth factors served as the basis for numerous early phase clinical trials. With the first wave of safety and efficacy trials complete, much is still unknown regarding optimal cell dose and type, timing of injection, route of administration, mechanisms of action, and achievable response measures.

A novel method for low load friction testing on living cells.

A low load tribology technique for studying the effects of friction on living cells was developed. Results show a direct relationship between the coefficient of friction (COF) and the extent of cell damage. The COF, mu, for a glass pin on an intact layer of human corneal epithelial cells is determined to be on the order of mu = 0.

A model of vein graft intimal hyperplasia.

When vein graft is implanted in the arterial system, the vein graft wall becomes thicker as an adaptive process. We have developed a model of early adaptive vein graft intimal thickening induced by shear stress. Intimal thickness and the rate of intimal thickening are expressed as functions of shear stress and time based on experimental data.

Effects of EGF and bFGF on irradiated parotid glands.

Radiotherapy is common treatment for head-and-neck cancer, during which the salivary glands are often included within the radiation field. The most common side effect of this treatment is the development of oral dryness (xerostomia). This study considers the administration of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF or FGF2) at physiological concentrations before and after irradiation in order to repair radiation-induced damage in salivary gland cells.

Transient upregulation of GRP and its receptor critically regulate colon cancer cell motility during remodeling.

Gastrin-releasing peptide (GRP) is typically viewed as a growth factor in cancer. However, we have suggested that in colon cancer, GRP acts primarily as a morphogen when it and its receptor (GRP-R) are aberrantly upregulated. As such, GRP/GRP-R act(s) primarily to modulate processes contributing to the assumption or maintenance of tumor differentiation.

Strength measurement of the Sertoli-spermatid junctional complex.

The Sertoli cell ectoplasmic specialization (ES) is a specialized domain of the calcium-dependent Sertoli cell-spermatid junctional complex. Not only is it associated with the mechanical adhesion of the cells, but it also plays a role in the morphogenesis and differentiation of the developing germ cells. Abnormal or absent Sertoli ESs have been associated with step-8 spermatid sloughing and subsequent oligospermia.