7,859 research outputs found
Impact of Tissue Damage and Hemodynamics on Restenosis Following Percutaneous Transluminal Angioplasty: A Patient-Specific Multiscale Model.
No full textMultiscale agent-based modeling frameworks have recently emerged as promising mechanobiological models to capture the interplay between biomechanical forces, cellular behavior, and molecular pathways underlying restenosis following percutaneous transluminal angioplasty (PTA). However, their applications are mainly limited to idealized scenarios. Herein, a multiscale agent-based modeling framework for investigating restenosis following PTA in a patient-specific superficial femoral artery (SFA) is proposed. The framework replicates the 2-month arterial wall remodeling in response to the PTA-induced injury and altered hemodynamics, by combining three modules: (i) the PTA module, consisting in a finite element structural mechanics simulation of PTA, featuring anisotropic hyperelastic material models coupled with a damage formulation for fibrous soft tissue and the element deletion strategy, providing the arterial wall damage and post-intervention configuration, (ii) the hemodynamics module, quantifying the post-intervention hemodynamics through computational fluid dynamics simulations, and (iii) the tissue remodeling module, based on an agent-based model of cellular dynamics. Two scenarios were explored, considering balloon expansion diameters of 5.2 and 6.2 mm. The framework captured PTA-induced arterial tissue lacerations and the post-PTA arterial wall remodeling. This remodeling process involved rapid cellular migration to the PTA-damaged regions, exacerbated cell proliferation and extracellular matrix production, resulting in lumen area reduction up to 1-month follow-up. After this initial reduction, the growth stabilized, due to the resolution of the inflammatory state and changes in hemodynamics. The similarity of the obtained results to clinical observations in treated SFAs suggests the potential of the framework for capturing patient-specific mechanobiological events occurring after PTA intervention
Microstructural model for cyclic hardening in F-actin networks crosslinked by α-actinin
No full textThe rheology of F-actin networks has attracted a great attention during the last years. In order to gain a complete understanding of the rheological properties of these novel materials, it is necessary the study in a large deformations regime to alter their internal structure. In this sense, Schmoller et al. (2010) showed that the reconstituted networks of F-actin crosslinked with α-actinin unexpectedly harden when they are subjected to a cyclical shear. This observation contradicts the expected Mullins effect observed in most soft materials, such as rubber and living tissues, where a pronounced softening is observed when they are cyclically deformed. We think that the key to understand this stunning effect is the gelation process. To define it, the most relevant constituents are the chemical crosslinks - α-actinin -, the physical crosslinks - introduced by the entanglement of the semiflexible network - and the interaction between them. As a consequence of this interaction, a pre-stressed network emerges and introduces a feedback effect, where the pre-stress also regulates the adhesion energy of the α-actinin, setting the structure in a metastable reference configuration. Therefore, the external loads and the evolvement of the trapped stress drive the microstructural changes during the cyclic loading protocol. In this work, we propose a micromechanical model into the framework of nonlinear continuum mechanics. The mechanics of the F-actin filaments is modelled using the wormlike chain model for semiflexible filaments and the gelation process is modelled as mesoscale dynamics for the α-actinin and physical crosslink. The model has been validated with reported experimental results
Limitations in electrophysiological model development and validation caused by differences between simulations and experimental protocols
No full textModels of ion channel dynamics are usually built by fitting isolated cell experimental values of individual parameters while neglecting the interaction between them. Another shortcoming regards the estimation of ionic current conductances, which is often based on quantification of Action Potential (AP)-derived markers. Although this procedure reduces the uncertainty in the calculation of conductances, many studies evaluate electrophysiological AP-derived markers from single cell simulations, whereas experimental measurements are obtained from tissue preparations. In this work, we explore the limitations of these approaches to estimate ion channel dynamics and maximum current conductances and how they could be overcome by using multiscale simulations of experimental protocols. Four human ventricular cell models, namely ten Tusscher and Panfilov (2006), Grandi et al. (2010), O'Hara et al. (2011), and Carro et al. (2011), were used. Two problems involving scales from ion channels to tissue were investigated: 1) characterization of L-type calcium voltage-dependent inactivation ICa,L; 2) identification of major ionic conductance contributors to steady-state AP markers, including APD90, APD75, APD50, APD25, Triangulation and maximal and minimal values of V and dV/dt during the AP (Vmax, Vmin, dV/dtmax, dV/dtmin). Our results show that: 1) ICa,Linactivation characteristics differed significantly when calculated from model equations and from simulations reproducing the experimental protocols. 2) Large differences were found in the ionic currents contributors to APD25, Triangulation, Vmax, dV/dtmaxand dV/dtminbetween single cells and 1D-tissue. When proposing any new model formulation, or evaluating an existing model, consistency between simulated and experimental data should be verified considering all involved effects and scales
Electrotonic Coupling Effect on Pharmacological Cardiotoxicity Assessment in Atrial Tissue
No full textMarriage record of Rodriguez, Jose and Alvarez, Rosa
No full textMarriage license for Jose Rodriguez and Rosa Alvarez. F. Milian was the Notary Public
Marriage record of Rodriguez, Jose and Figuerado, Antonina C.
No full textMarriage license for Jose Rodriguez and Antonina C. Fuguerado. F. Milian was the Notary Public
Marriage record of Lopez, Jose Rodriguez and Radillo, Julia
No full textMarriage license for Jose Rodriguez Lopez and Julia Radillo. F. Milian was the Notary Public
Convergence of Trust Region Augmented Lagrangian Methods Using Variable Fidelity Approximation Data
No full textTo date the primary focus of most constrained approximate optimization strategies is that application of the method should lead to improved designs. Few researchers have focused on the development of constrained approximate optimization strategies that are assured of converging to a Karush-Kuhn-Tucker (KKT) point for the problem. Recent work by the authors based on a trust region model management strategy has shown promise in managing the convergence of constrained approximate optimization in application to a suite of single level optimization test problems. Using a trust-region model management strategy, coupled with an augmented Lagrangian approach for constrained approximate optimization, the authors have shown in application studies that the approximate optimization process converges to a KKT point for the problem. The approximate optimization strategy sequentially builds a cumulative response surface approximation of the augmented Lagrangian which is then optimized subject to a trust region constraint. In this research the authors develop a formal proof of convergence for the response surface approximation based optimization algorithm. Previous application studies were conducted on single level optimization problems for which response surface approximations were developed using conventional statistical response sampling techniques such as central composite design to query a high fidelity model over the design space. In this research the authors extend the scope of application studies to include the class of multidisciplinary design optimization (MDO) test problems. More importantly the authors show that response surface approximations constructed from variable fidelity data generated during concurrent subspace optimizations (CSSOs) can be effectively managed by the trust region model management strategy. Results for two multidisciplinary test problems are presented in which convergence to a KKT point is observed. The formal proof of convergence and the successfull MDO application of the algorithm using variable fidelity data generated by CSSO are original contributions to the growing body of research in MDO
The effect of material model formulation in the stress analysis of abdominal aortic aneurysms
No full textA reliable estimation of wall stress in Abdominal Aortic Aneurysms (AAAs), requires performing an accurate three-dimensional reconstruction of the medical image-based native geometry and modeling an appropriate constitutive law for the aneurysmal tissue material characterization. A recent study on the biaxial mechanical behavior of human AAA tissue specimens demonstrates that aneurysmal tissue behaves mechanically anisotropic. Results shown in this communication show that the peak wall stress is highly sensitive to the anisotropic model used for the stress analysis. In addition, the present investigation indicates that structural parameters (e.g., collagen fiber orientation) should be determined independently and not by means of non-linear fitting to stress-strain test data. Fiber orientation identified in this manner could lead to overestimated peak wall stresses.</p
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