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Book of abstracts of the 15th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering and 3rd Conference on Imaging and Visualization, CMBBE2018

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Cells are quintessential examples of out-of-equilibrium systems, but they maintain a homeostatic state over a timescale of hours to days. As a consequence, the statistics of all observables is remarkably consistent. Here, we develop a statistical mechanics framework for living cells by including the homeostatic constraint that exists over the interphase period of the cell cycle. The consequence is the introduction of the concept of a homeostatic ensemble and an associated homeostatic temperature, along with a formalism for the (dynamic) homeostatic equilibrium that intervenes to allow living cells to evade thermodynamic decay. As a first application, the framework is shown to accurately predict the observed effect of the mechanical environment on the in vitro response of smooth muscle cells. This includes predictions that both the mean values and diversity/variability in the measured values of observables such as cell area, shape and tractions decrease with decreasing stiffness of the environment. Thus, we argue that the observed variabilities are inherent to the entropic nature of the homeostatic equilibrium of cells and not a result of in vitro experimental errors.
Conference Paper
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The purpose of this study was to determine the muscle activity patterns resulting from dynamic optimization of a novel continuous wheelchair propulsion movement having a circularity ratio of 0.89. For the study four major muscle groups were selected and a bang-bang control strategy was adopted to reduce the complexity and time for the optimization with a cost function to increase the net propulsion power. The successful completion of the optimization resulted in muscle excitation and activation curves for each actuator and a net power > 30 watts. The proposed propulsion mechanism can act as a substitute for the normal propulsion mechanisms used in daily life and sports activities.
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Multiple studies have demonstrated that the pathological geometries unique to each patient can affect the durability of mitral valve (MV) repairs. While computational modeling of the MV is a promising approach to improve the surgical outcomes, the complex MV geometry precludes use of simplified models. Moreover, the lack of complete in-vivo geometric information presents significant challenges in the development of patient-specific computational models. There is thus a need to determine the level of detail necessary for predictive MV models. To address this issue, we have developed a novel pipeline for building attribute-rich computational models of MV with varying fidelity directly from the in-vitro imaging data. The approach combines high-resolution geometric information from loaded and unloaded states to achieve a high level of anatomic detail, followed by mapping and parametric embedding of tissue attributes to build a high resolution, attribute-rich computational models. Subsequent lower resolution models were then developed, and evaluated by comparing the displacements and surface strains to those extracted from the imaging data. We then identified the critical levels of fidelity for building predictive MV models in the dilated and repaired states. We demonstrated that a model with a feature size of ~5 mm and mesh size of ~1 mm was sufficient to predict the overall MV shape, stress, and strain distributions with high accuracy. However, we also noted that more detailed models were found to be needed to simulate microstructural events. We conclude that the developed pipeline enables sufficiently complex models for biomechanical simulations of MV in normal, dilated, repaired states.
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Myocardial stiffness is a valuable clinical biomarker for the monitoring and stratification of heart failure (HF). Cardiac finite element models provide a biomechanical framework for the assessment of stiffness through the determination of the myocardial constitutive model parameters. The reported parameter intercorrelations in popular constitutive relations, however, obstruct the unique estimation of material parameters and limit the reliable translation of this stiffness metric to clinical practice. Focusing on the role of the cost function (CF) in parameter identifiability, we investigate the performance of a set of geometric indices (based on displacements, strains, cavity volume, wall thickness and apicobasal dimension of the ventricle) and a novel CF derived from energy conservation. Our results, with a commonly used transversely isotropic material model (proposed by Guccione et al.), demonstrate that a single geometry-based CF is unable to uniquely constrain the parameter space. The energy-based CF, conversely, isolates one of the parameters and in conjunction with one of the geometric metrics provides a unique estimation of the parameter set. This gives rise to a new methodology for estimating myocardial material parameters based on the combination of deformation and energetics analysis. The accuracy of the pipeline is demonstrated in silico, and its robustness in vivo, in a total of 8 clinical data sets (7 HF and one control). The mean identified parameters of the Guccione material law were [Formula: see text] and [Formula: see text] ([Formula: see text], [Formula: see text], [Formula: see text]) for the HF cases and [Formula: see text] and [Formula: see text] ([Formula: see text], [Formula: see text], [Formula: see text]) for the healthy case.
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Purpose: Access to the left atrium is required for several minimally invasive cardiac interventions in the left heart. For this purpose, transseptal puncture (TSP) technique is often performed, perforating the atrial septum under fluoroscopic or/and ultrasound imaging guidance. Although this approach has been used for many years, complications/failures are not uncommon mainly in patients with abnormal atrial anatomy and repeated TSP. Thus, this study presents an overview of methods and techniques that have been proposed to increase the safety and feasibility of the TSP. Methods: A systematic review of literature was conducted through the analysis of the articles published between 2008 and 2015. The search was performed in PubMed, Scopus and ISI Web of Knowledge using the expression “transseptal puncture”. Results: A total of 354 articles were retrieved from the databases, and 64 articles were selected for this review. Moreover, these 64 articles were divided into four categories, namely: 1) incidence studies; 2) intra-procedural guidance techniques; 3) pre-procedural planning methods and 4) surgical instruments. A total of 36 articles focused on incidence studies, 24 articles suggested novel intra-procedural guidance techniques, 5 works focused on pre-procedural planning strategies and 21 works proposed surgical instruments. Conclusions: The novel 3D guidance techniques, radio-frequency surgical instruments and pre-interventional planning approaches showed potential to overcome the main procedural limitations/complications, through the reduction of the intervention time, radiation, number of failures and complications.
Article
We present a least-squares based inverse analysis of visco-elastic biological tissues. The proposed method computes the set of contractile forces (dipoles) at the cell boundaries that induce the observed and quantified deformations. We show that the computation of these forces requires the regularisation of the problem functional for some load configurations that we study here. The functional measures the error of the dynamic problem being discretised in time with a second-order implicit time-stepping and in space with standard finite elements. We analyse the uniqueness of the inverse problem and estimate the regularisation parameter by means of an L-curved criterion. We apply the methodology to a simple toy problem and to an in vivo set of morphogenetic deformations of the Drosophila embryo.
Article
Understanding load-sharing in the spine during in-vivo conditions is critical for better spinal implant design and testing. Previous studies of load-sharing that considered actual spinal geometry applied compressive follower load, with or without moment, to simulate muscle forces. Other studies used musculoskeletal models, which include muscle forces, but model the discs by simple beams or spherical joints and ignore the articular facet joints. This study investigated load-sharing in neutral standing and flexed postures using a detailed Finite Element (FE) model of the ligamentous lumbosacral spine, where muscle forces, gravity loads and intra-abdominal pressure, as predicted by a musculoskeletal model of the upper body, are input into the FE model. Flexion was simulated by applying vertebral rotations following spine rhythm measured in a previous in-vivo study, to the musculoskeletal model. The FE model predicted intradiscal pressure (IDP), strains in the annular fibers, contact forces in the facet joints, and forces in the ligaments. The disc forces and moments were determined using equilibrium equations, which considered the applied loads, including muscle forces and IDP, as well as forces in the ligaments and facet joints predicted by the FE model. Load-sharing was calculated as the portion of the total spinal load carried along the spine by each individual spinal structure. The results revealed that spinal loads which increased substantially from the upright to the flexed posture were mainly supported by the discs in the upright posture, whereas the ligaments’ contribution in resisting shear, compression, and moment was more significant in the flexed posture.
Article
We present a hybrid vertex/cell-centred model for mechanically simulating planar cellular monolayers undergoing cell reorganisation. Cell centres are represented by a triangular nodal network, while the cell boundaries are formed by an associated vertex network. The two networks are coupled through a kinematic constraint which we allow to relax progressively. Special attention is paid to the change of cell-cell connectivity due to cell reorganisation or remodelling events. We handle these situations by using a variable resting length and applying an Equilibrium-Preserving Mapping (EPM) on the new connectivity, which computes a new set of resting lengths that preserve nodal and vertex equilibrium. We illustrate the properties of the model by simulating monolayers subjected to imposed extension and during a wound healing process. The evolution of forces and the EPM are analysed during the remodelling events. As a by-product, the proposed technique enables to recover fully vertex or fully cell-centred models in a seamlessly manner by modifying a numerical parameter of the model.
Article
A number of geometrically-detailed passive finite element (FE) models of the lumbar spine have been developed and validated under in vitro loading conditions. These models are devoid of muscles and thus cannot be directly used to simulate in vivo loading conditions acting on the lumbar joint structures or spinal implants. Gravity loads and muscle forces estimated by a trunk musculoskeletal (MS) model under twelve static activities were applied to a passive FE model of the L4-L5 segment to estimate load sharing among the joint structures (disc, ligaments, and facets) under simulated in vivo loading conditions. An equivalent follower (FL), that generates IDP equal to that generated by muscle forces, was computed in each task. Results indicated that under in vivo loading conditions, the passive FE model predicted intradiscal pressures (IDPs) that closely matched those measured under the simulated tasks (R² = 0.98 and root-mean-squared-error, RMSE = 0.18 MPa). The calculated equivalent FL compared well with the resultant force of all muscle forces and gravity loads acting on the L4-L5 segment (R² = 0.99 and RMSE = 58 N). Therefore, as an alternative approach to represent in vivo loading conditions in passive FE model studies, this FL can be estimated by available in-house or commercial MS models. In clinical applications and design of implants, commonly considered in vitro loading conditions on the passive FE models do not adequately represent the in vivo loading conditions under muscle exertions. Therefore, more realistic in vivo loading conditions should instead be used.
Article
Significance A physically realistic understanding of any morphogenetic process requires the knowledge of material properties of the tissue, almost all of which we currently lack. This paper introduces a technique that allows measuring physical properties of the interior constituents of a fruit fly embryo. To interpret our measurements, we developed a computational framework that allowed us to deduce underlying material properties of embryonic tissues from the measured data. Using our protocol we have determined a number of key physical properties of embryonic tissue (e.g., cytoplasmic viscosity and the timescale of elastic stress relaxation). Finally, we used pharmacological perturbations to examine which cellular structures are responsible for the observed elastic response.