Physiological Boundary Conditions Research Articles

Impact of juxta-anastomotic stent implantation on the haemodynamics within a single representative patient AVF

An arteriovenous fistula (AVF), a vascular structure surgically created to enable haemodialysis, is commonly affected by stenosis in the juxta-anastomotic region. A new treatment involving the implantation of a flexible stent has shown good potential for retaining healthy AVFs. Since vascular disease in the AVF is known to be related to the haemodynamic environment within the vasculature, this study aims to understand the impact of the stent implantation on the flow dynamics within a single patient-specific AVF. A virtual stented geometry of the AVF was obtained with micro-CT images of a benchtop AVF model implanted with a Supera stent. Reynolds averaged Navier–Stokes simulations were conducted with physiological boundary conditions (Reynolds numbers varying from 345 to 730) applied on the AVF model with and without the presence of the stent. Velocity contour slices within the vein showed the concentration of high velocity in the stent encapsulated region. Moreover, the ratios of flow rate across the stent-lumen cross-sections over the flow rate across the vessel-lumen cross-sections suggested that the flow was being funnelled through the stent encapsulated regions of a malapposed section, despite the porous structure of the stent. A larger low velocity recirculation region translated to a larger vessel wall area of high Oscillatory Shear Index (OSI) and low Time-Averaged Wall Shear Stress (TAWSS) in the AVF model with the stent absent, compared to the stented model. This suggested that the adverse haemodynamic behaviour was being funnelled away from the vessel wall, possibly leading to a protective environment in the malapposed region of the vein.

Abstract 9587: Combined Aortic Regurgitation and Stenosis of the Bicuspid Aortic Valve Increases Ascending Aortic Wall Shear Stress and Left Ventricle Energy Burden

Introduction: The bicuspid aortic valve (BAV) opening pattern and the degree of aortic stenosis (AS) are reportedly associated with the aneurysmal formation in the ascending aorta. Although AS is often accompanied by aortic regurgitation (AR), the combined effect of AR and AS on the wall of the ascending aorta and energy loss of the blood flow are not well understood. Hypothesis: We hypothesize that AR along with AS can increase the wall shear stress (WSS) to develop the aneurysm in the ascending aorta and increase the load on the left ventricle (LV). Methods: The effects of AR along with AS BAV on the hemodynamic features were assessed using an image-based subject-specific LV-aorta integrated computational model. The computational model was constructed based on an MRI dataset of a 72-year-old healthy volunteer. Four different types of stenosed (52% stenosis) BAV models were created: Type 0, RL fused, RN fused, and LN fused. Then, physiological boundary conditions were given based on a parameter-adjusted 0-1D cardiovascular model of the AS BAV with no AR, mild AR (17% regurgitant fraction (RF)), and severe AR (48% RF) to assess hemodynamic indices such as time-average of WSS in the ascending aorta and pulsatile energy loss index (PELI), an index to estimate energy loss in the aorta. Results: Averaged WSS was highest in the severe AR with AS BAV in 4.1±0.2 Pa, followed by the mild AR with AS BAV in 3.1±0.21 Pa, and no AR with AS BAV in 2.7±0.3 Pa. The intra-ventricular flow (LV) showed more disturbed flow in mid-diastole in severe AR with AS BAV. PELI was augmented in mild AR with AS BAV in 0.34±0.05 and severe AR with AS BAV in 0.25±0.06, compared to no AR with AS BAV in 0.19±0.16. Conclusions: AR along with AS in BAV has a great impact on increasing the WSS in the ascending aorta and increasing the energy loss of the flow in the aorta. These features imply that advanced AR along with AS in BAV may raise the risk of the development of aortic aneurysm as well as heart failure due to the increased workload on the LV.

Thin patient-specific clavicle fracture fixation plates can mechanically outperform commercial plates: An in silico approach.

Current fixation plates used to operatively stabilize clavicular fractures are suboptimal, leading to reoperation rates up to 53%. Plate irritation, which can be caused by a poor geometric fit and plate thickness, has been found to be an important factor for reoperation. Moreover, muscle attachment sites (MAS) have to be detached occasionally. To improve current surgical clavicle fracture treatment with plate osteosynthesis, a change in plate design is required. The goal of this study was to design a patient-specific clavicle fracture fixation plate that includes geometrical optimization and stiffness determination. Its biomechanical performance has been compared with a commercial plate by examining the geometric fit, anatomical outline, stresses and interfragmentary motion using a finite element analysis with physiological loading and boundary conditions. Evaluation showed a better geometrical fit of the patient-specific plate as well as an improved fracture reduction. Displacements between fracture fragments were lower in case of the patient-specific plate, both when a fracture gap and no fracture gap were present. Results indicate a superior mechanical performance in terms of all investigated outcomes of the patient-specific plate compared to the commercial plate, while better aligning with the patient-specific geometry and without the need for MAS release. Due to the patient-specific geometry and reduced thickness, these fixation plates are expected to decrease the operation time, as intraoperative contouring will become irrelevant, and to decrease reoperation rates as implant irritation will be minimized.

Computational analysis of the effects of interprosthetic distance on normal and reduced cortical thickness femur models.

Distal femoral fractures associated with the femoral stem in a well-fixed hip arthroplasty pose a risk of an interprosthetic fracture, the treatment of which is known as difficult. To effectively prevent and treat IP fractures, biomechanical effects must be demonstrated. We defined eight variations of the interprosthetic distance ranging from 48 mm overlap to 128 mm gap. Femoral geometries with normal and reduced cortical thickness were modeled to evaluate the effects of cortical thickness. In addition to the intact model, a total of 16 finite element models were analyzed under physiological boundary conditions. Maximum and minimum principal strains on the lateral and medial cortex surfaces were always found to be greater in models with reduced cortical thickness than in normal femurs. The model with 48 mm overlapping interprosthetic distance produced the least peak strain and the model with 16 mm interprosthetic gap produced the greatest strain with both normal and reduced cortical thickness. The screw holes produced local strain concentrations and increased the peak strains on the cortex surfaces, especially close to the stem tip. Statistically, a significant correlation (R2 = 0.9483) was found between strain shielding and interprosthetic distance. Axial stiffness, interfragmentary shear motion, and maximum von-Mises stress on the distal plate showed a high correlation with the interprosthetic distance. It was concluded that the overlapping structures are superior to other fixations we analyzed in that they offer better mechanical stability and eliminates the local strain concentrations.

One way to get there

People have mused that fusion as a source of energy is ‘30 years away and always will be’. Similarly, the application of computational fluid dynamics (CFD) to solve problems in...

Correlation of Computational Instantaneous Wave-Free Ratio With Fractional Flow Reserve for Intermediate Multivessel Coronary Disease.

This study computationally assesses the accuracy of an instantaneous wave-free ratio (iFR) threshold range compared to standard modalities such as fractional flow reserve (FFR) and coronary flow reserve (CFR) for multiple intermediate lesions near the left main (LM) coronary bifurcation. iFR is an adenosine-independent index encouraged for assessment of coronary artery disease (CAD), but different thresholds are debated. This becomes particularly challenging in cases of multivessel disease when sensitivity to downstream lesions is unclear. Idealized LM coronary arteries with 34 different intermediate stenoses were created and categorized (Medina) as single and multiple lesion groups. Computational fluid dynamics modeling was performed with physiologic boundary conditions using an open-source software (simvascular1) to solve the time-dependent Navier-Stokes equations. A strong linear relationship between iFR and FFR was observed among studied models, indicating computational iFR values of 0.92 and 0.93 are statistically equivalent to an FFR of 0.80 in single and multiple lesion groups, respectively. At the clinical FFR value (i.e., 0.8), a triple-lesion group had smaller CFR compared to the single and double lesion groups (e.g., triple = 3.077 versus single = 3.133 and double = 3.132). In general, the effect of additional intermediate downstream lesions (minimum lumen area > 3 mm2) was not statistically significant for iFR and CFR. A computational iFR of 0.92 best predicts an FFR of 0.80 and may be recommended as threshold criteria for computational assessment of LM stenosis following additional validation using patient-specific models.

Computational fluid dynamics of the right atrium: Assessment of modelling criteria for the evaluation of dialysis catheters.

Central venous catheters are widely used in haemodialysis therapy, having to respect design requirements for appropriate performance. These are placed within the right atrium (RA); however, there is no prior computational study assessing different catheter designs while mimicking their native environment. Here, a computational fluid dynamics model of the RA, based on realistic geometry and transient physiological boundary conditions, was developed and validated. Symmetric, split and step catheter designs were virtually placed in the RA and their performance was evaluated by: assessing their interaction with the RA haemodynamic environment through prediction of flow vorticity and wall shear stress (WSS) magnitudes (1); and quantifying recirculation and tip shear stress (2). Haemodynamic predictions from our RA model showed good agreement with the literature. Catheter placement in the RA increased average vorticity, which could indicate alterations of normal blood flow, and altered WSS magnitudes and distribution, which could indicate changes in tissue mechanical properties. All designs had recirculation and elevated shear stress values, which can induce platelet activation and subsequently thrombosis. The symmetric design, however, had the lowest associated values (best performance), while step design catheters working in reverse mode were associated with worsened performance. Different tip placements also impacted on catheter performance. Our findings suggest that using a realistically anatomical RA model to study catheter performance and interaction with the haemodynamic environment is crucial, and that care needs to be given to correct tip placement within the RA for improved recirculation percentages and diminished shear stress values.

Effect of Material and Population on the Delivery of Nanoparticles to an Atherosclerotic Plaque: A Patient-specific In Silico Study.

Coronary artery disease (CAD) is the prevalent reason of mortality all around the world. Targeting CAD, specifically atherosclerosis, with controlled delivery of micro and nanoparticles, as drug carriers, is a very proficient approach. In this work, a patient-specific and realistic model of an atherosclerotic plaque in the left anterior descending (LAD) artery was created by image-processing of CT-scan images and implementing a finite-element mesh. Next, a fluid-solid interaction simulation considering the physiological boundary conditions was conducted. By considering the simulated force fields and particle-particle interactions, the correlation between injected particles at each cardiac cycle and the surface density of adhered particles over the atherosclerotic plaque (SDP) were examined. For large particles (800 and 1000 nm) the amount of SDP on the plaque increased significantly when the number of the injected particles became higher. However, by increasing the number of the injected particles, for the larger particles (800 and 1000 nm) the increase in SDP was about 50% greater than that of the smaller ones (400 and 600 nm). Furthermore, for constant number of particles, depending on their size, different trends in SDP were observed. Subsequently, the distribution and adhesion of metal-based nanoparticles including SiO2, Fe3O4, NiO2, silver and gold with different properties were simulated. The injection of metal particles with medium density among the considered particles resulted in the highest SDP. Remarkably, the affinity, the geometrical features, and the biophysical factors involved in the adhesion outweighed the effect of difference in the density of particles on the SDP. Finally, the consideration of the lift force in the simulations significantly reduced the SDP and consistently decreased the particle residence time in the studied domain.

Numerical modeling in arterial hemodynamics incorporating fluid-structure interaction and microcirculation

BackgroundThe effects of arterial wall compliance on blood flow have been revealed using fluid-structure interaction in last decades. However, microcirculation is not considered in previous researches. In fact, microcirculation plays a key role in regulating blood flow. Therefore, it is very necessary to involve microcirculation in arterial hemodynamics.ObjectiveThe main purpose of the present study is to investigate how wall compliance affects the flow characteristics and to establish the comparisons of these flow variables with rigid wall when microcirculation is considered.MethodsWe present numerical modeling in arterial hemodynamics incorporating fluid-structure interaction and microcirculation. A novel outlet boundary condition is employed to prescribe microcirculation in an idealised model.ResultsThe novel finding in this work is that wall compliance under the consideration of microcirculation leads to the increase of wall shear stress in contrast to rigid wall, contrary to the traditional result that wall compliance makes wall shear stress decrease when a constant or time dependent pressure is specified at an outlet.ConclusionsThis work provides the valuable study of hemodynamics under physiological and realistic boundary conditions and proves that wall compliance may have a positive impact on wall shear stress based on this model. This methodology in this paper could be used in real model simulations.

Cross-Bridges and Sarcomeric Non-cross-bridge Structures Contribute to Increased Work in Stretch-Shortening Cycles.

Stretch-shortening cycles (SSCs) refer to the muscle action when an active muscle stretch is immediately followed by active muscle shortening. This combination of eccentric and concentric contractions is the most important type of daily muscle action and plays a significant role in natural locomotion such as walking, running or jumping. SSCs are used in human and animal movements especially when a high movement speed or economy is required. A key feature of SSCs is the increase in muscular force and work during the concentric phase of a SSC by more than 50% compared with concentric muscle actions without prior stretch (SSC-effect). This improved muscle capability is related to various mechanisms, including pre-activation, stretch-reflex responses and elastic recoil from serial elastic tissues. Moreover, it is assumed that a significant contribution to enhanced muscle capability lies in the sarcomeres itself. Thus, we investigated the force output and work produced by single skinned fibers of rat soleus muscles during and after ramp contractions at a constant velocity. Shortening, lengthening, and SSCs were performed under physiological boundary conditions with 85% of the maximum shortening velocity and stretch-shortening magnitudes of 18% of the optimum muscle length. The different contributions of cross-bridge (XB) and non-cross-bridge (non-XB) structures to the total muscle force were identified by using Blebbistatin. The experiments revealed three main results: (i) partial detachment of XBs during the eccentric phase of a SSC, (ii) significantly enhanced forces and mechanical work during the concentric phase of SSCs compared with shortening contractions with and without XB-inhibition, and (iii) no residual force depression after SSCs. The results obtained by administering Blebbistatin propose a titin-actin interaction that depends on XB-binding or active XB-based force production. The findings of this study further suggest that enhanced forces generated during the active lengthening phase of SSCs persist during the subsequent shortening phase, thereby contributing to enhanced work. Accordingly, our data support the hypothesis that sarcomeric mechanisms related to residual force enhancement also contribute to the SSC-effect. The preload of the titin molecule, acting as molecular spring, might be part of that mechanism by increasing the mechanical efficiency of work during physiological SSCs.

The Hemodynamic Effect of Enhanced External Counterpulsation Treatment on Atherosclerotic Plaque in the Carotid Artery: A Framework of Patient-Specific Computational Fluid Dynamics Analysis.

Long-term enhanced external counterpulsation (EECP) therapy has been recommended for antiatherogenesis in recent clinical observations and trials. However, the precise mechanism underlying the benefits has not been fully clarified. To quantify the effect of EECP intervention on arterial hemodynamic environment, a framework of numerical assessment was introduced using a parallel computing algorithm. A 3D endothelial surface of the carotid artery with mild atherosclerotic plaque was constructed from images of magnetic resonance angiography (MRA). Physiologic boundary conditions were derived from images of the ultrasound flow velocity spectrum measured at the common carotid artery and before and during EECP intervention. Hemodynamic factors relating to wall shear stress (WSS) and its spatial and temporal fluctuations were calculated and analyzed, which included AWSS, OSI, and AWSSG. Measuring and computational results showed that diastole blood pressure, perfusion, and WSS level in carotid bifurcation were significantly increased during EECP intervention. Mean AWSS level throughout the model increased by 16.9%, while OSI level did not show a significant change during EECP. We thus suggested that long-term EECP treatment might inhibit the initiation and development of atherosclerotic plaque via improving the hemodynamic environment in the carotid artery. Meanwhile, EECP performance induced a 19.6% increase in AWSSG level, and whether it would influence the endothelial functions may need a further study. Moreover, the numerical method proposed in this study was expected to be useful for the instant assessment of clinical application of EECP .

On the importance of spiral-flow inflow boundary conditions when using idealized artery geometries in the analysis of liver radioembolization: A parametric study.

In the last decades, the numerical studies on hemodynamics have become a valuable explorative scientific tool. The very first studies were done over idealized geometries, but as numerical methods and the power of computers have become more affordable, the studies tend to be patient specific. We apply the study to the numerical analysis of tumor-targeting during liver radioembolization (RE). RE is a treatment for liver cancer, and is performed by injecting radiolabeled microspheres via a catheter placed in the hepatic artery. The objective of the procedure is to maximize the release of radiolabeled microspheres into the tumor and avoid a healthy tissue damage. Idealized virtual arteries can serve as a generalist approach that permits to separately analyze the effect of a variable in the microsphere distribution with respect to others. However, it is important to use proper physiological boundary conditions (BCs). It is not obvious, the need to account for the effect of tortuosity when using an idealized virtual artery. We study the use of idealized geometry of a hepatic artery as a valid research tool, exploring the importance of using realistic spiral-flow inflow BC. By using a literature-based cancer scenario, we vary two parameters to analyze the microsphere distribution through the outlets of the geometry. The parameters varied are the type of microspheres injected and the microsphere injection velocity. The results with realistic inlet velocity profile showed that the particle distribution in the liver segments is not affected by the analyzed injection velocity values neither by the particle density. NOVELTY STATEMENT: In this article, we assessed the use of idealized geometries as a valid research tool and applied the use of an idealized geometry to the case of an idealized hepatic artery to study the particle-hemodynamics during radioembolization (RE). We studied three different inflow boundary conditions (BCs) to assess the usefulness of the geometry, two types of particle injection velocities and two types of commercially available microspheres for RE treatment. In recent years, the advent in computational resources allowed for more detailed patient-specific geometry generation and discretization and hemodynamics simulations. However, general studies based on idealized geometries can be performed in order to provide medical doctors with some basic and general guidelines when using a given catheter for a given cancer scenario. Moreover, using an idealized geometry can be a reasonable approach which allows us to isolate a given parameter and control other parameters, so that parameters can be independently assessed. Even though an idealized geometry does not match any patient's geometry, the use of an idealized geometry can be valid when drawing general conclusions that may be useful in patient-specific cases. However, we believe that even if an idealized hepatic artery geometry is used for the study, it is necessary to account for the upstream and downstream tortuosity of vessels through the BCs. In this work, we highlighted the need of modeling the tortuosity of upstream and downstream vasculatures through the BCs.

Bicuspid aortic valve aortopathies: An hemodynamics characterization in dilated aortas

Bicuspid aortic valve (BAV) aortopathy remains of difficult clinical management due to its heterogeneity and further assessment of related aortic hemodynamics is necessary. The aim of this study was to assess systolic hemodynamic indexes and wall stresses in patients with diverse BAV phenotypes and dilated ascending aortas. The aortic geometry was reconstructed from patient-specific images while the aortic valve was generated based on patient-specific measurements. Physiologic material properties and boundary conditions were applied and fully coupled fluid-structure interaction (FSI) analysis were conducted. Our dilated aortic models were characterized by the presence of abnormal hemodynamics with elevated degrees of flow skewness and eccentricity, regardless of BAV morphotype. Retrograde flow was also present. Both features, predicted by flow angle and flow reversal ratios, were consistently higher than those reported for non-dilated aortas. Right-handed helical flow was present, as well as elevated wall shear stress (WSS) on the outer ascending aortic wall. Our results suggest that the abnormal flow associated with BAV may play a role in aortic enlargement and progress it further on already dilated aortas.

Network Modeling of Liver Metabolism to Predict Plasma Metabolite Changes During Short-Term Fasting in the Laboratory Rat.

The liver—a central metabolic organ that integrates whole-body metabolism to maintain glucose and fatty-acid regulation, and detoxify ammonia—is susceptible to injuries induced by drugs and toxic substances. Although plasma metabolite profiles are increasingly investigated for their potential to detect liver injury earlier than current clinical markers, their utility may be compromised because such profiles are affected by the nutritional state and the physiological state of the animal, and by contributions from extrahepatic sources. To tease apart the contributions of liver and non-liver sources to alterations in plasma metabolite profiles, here we sought to computationally isolate the plasma metabolite changes originating in the liver during short-term fasting. We used a constraint-based metabolic modeling approach to integrate central carbon fluxes measured in our study, and physiological flux boundary conditions gathered from the literature, into a genome-scale model of rat liver metabolism. We then measured plasma metabolite profiles in rats fasted for 5–7 or 10–13 h to test our model predictions. Our computational model accounted for two-thirds of the observed directions of change (an increase or decrease) in plasma metabolites, indicating their origin in the liver. Specifically, our work suggests that changes in plasma lipid metabolites, which are reliably predicted by our liver metabolism model, are key features of short-term fasting. Our approach provides a mechanistic model for identifying plasma metabolite changes originating in the liver.

Performance of preconditioned iterative linear solvers for cardiovascular simulations in rigid and deformable vessels.

Computing the solution of linear systems of equations is invariably the most time consuming task in the numerical solutions of PDEs in many fields of computational science. In this study, we focus on the numerical simulation of cardiovascular hemodynamics with rigid and deformable walls, discretized in space and time through the variational multiscale finite element method. We focus on three approaches: the problem agnostic generalized minimum residual (GMRES) and stabilized bi-conjugate gradient (BICGS) methods, and a recently proposed, problem specific, bi-partitioned (BIPN) method. We also perform a comparative analysis of several preconditioners, including diagonal, block-diagonal, incomplete factorization, multigrid, and resistance based methods. Solver performance and matrix characteristics (diagonal dominance, symmetry, sparsity, bandwidth and spectral properties) are first examined for an idealized cylindrical geometry with physiologic boundary conditions and then successively tested on several patient-specific anatomies representative of realistic cardiovascular simulation problems. Incomplete factorization preconditioners provide the best performance and results in terms of both strong and weak scalability. The BIPN method was found to outperform other methods in patient-specific models with rigid walls. In models with deformable walls, BIPN was outperformed by BICG with diagonal and Incomplete LU preconditioners.

Numerical assessment of pulsatile flow through diverging tees with a sharp- and round-edge junction

Unsteady flow through diverging tees is of interest in many industrial systems and physiological applications. In this study, the characteristics of the transient flow behaviors at the junctions of diverging tees with sharp- and round-edge junctions were investigated numerically based on physiological boundary conditions. The flow conditions were characterized based on a Newtonian fluid analogous to blood with a Womersley number of 23.13 and a mean inlet Reynolds number of 652. The results from this study demonstrate the onset conditions of flow separation at the upstream end of both branches and the relationship between the axial and secondary flow fields. For both junctions, the onset condition of separation and the strength of recirculation correspond closely to the momentum of the secondary boundary layer adjacent to the inner-wall of the branch. The nature of the boundary layer is strongly dependent on the structures of the vortical cells. The round-edge junction attenuates the strength of recirculation by triggering flow separation at a much lower flow rate ratio. The strength of the recirculation was found to be inversely proportional to the strength of the secondary flow. The reduction of the strength of recirculation leads to an increase in wall shear stress level and a decrease in oscillation effects.

In silico study of patient-specific magnetic drug targeting for a coronary LAD atherosclerotic plaque

Coronary artery disease is the first cause of death across the world. Targeted delivery of therapeutics through controlled release of micro- and nano-particles remains a very capable approach to develop new strategies in treating restenosis and atherosclerotic plaques. In this research, to produce the arterial geometry, an image-processing was done using CT-scan images of a LAD coronary artery. After implementing the finite element mesh, the Fluid-Structure Interaction (FSI) simulation based on physiological boundary conditions was performed. Next, a Lagrangian description of particles dynamics in a non-Newtonian blood flow considering momentum equation of motion for each particle and the imposed external magnetic field was provided. Under the influence of the magnetic field, the optimal particle size scope for which the surface density of particles (SDP) adhered on the plaque lumen reaches its maximum was specified. Also, our results signify that applying a magnetic field can adversely affect the delivery of particles to the targeted site for near micron-size particles. Along with the evaluation of the Brownian and the gravitational forces on nanoparticles, the uniformity of the distribution of particles in the left coronary network with and without the presence of the magnetic field has been studied. In conclusion, the external magnetic field has increased the SDP adhered on the targeted surface by 49.4% and 59.7% for 400 and 600 nm particles, respectively.

Subject-Specific Finite Element Modeling of the Human Shoulder Complex Part 2: Quantitative Evaluation of the Effect of Rotator Cuff Tear Propagation on Glenohumeral Joint Stability

The objective of this paper is to quantitatively evaluate the effects of rotator cuff tear propagation on glenohumeral joint stability in a previously constructed and validated finite element shoulder model. Rotator cuff tears with a sequence of increasing sizes were created from the anterior portion of the supraspinatus osseous insertion site and propagated posteriorly through the infraspinatus tendon until a complete tear extended through the entire teres minor tendon. Finite element simulations were performed in the same physiological loading and boundary conditions as in the original model. A novel integrative stability index was proposed and used for quantitative analysis of the simulated results. By defining the healthy condition as the baseline (100%), the stability index decreased slightly with small tear sizes but declined suddenly after half tear of the infraspinatus accompanied by a complete tear of the supraspinatus tendon until the full tear condition, when the index reached 0.41%. These results confirm the clinical and cadaveric findings that glenohumeral joint stability generally decreases as the size of the rotator cuff tear increases and that the critical tear size which leads to the loss of normal shoulder biomechanics was half tear of the infraspinatus accompanied by a complete tear of the supraspinatus tendon. It is concluded that the finite element shoulder model and the proposed novel stability ratio can accurately predict shoulder biomechanics in the investigated rotator cuff condition. Both the model and ratio may have the potential to be used to improve diagnostic and therapeutic strategies for clinicians.

Metabolic network-based predictions of toxicant-induced metabolite changes in the laboratory rat

In order to provide timely treatment for organ damage initiated by therapeutic drugs or exposure to environmental toxicants, we first need to identify markers that provide an early diagnosis of potential adverse effects before permanent damage occurs. Specifically, the liver, as a primary organ prone to toxicants-induced injuries, lacks diagnostic markers that are specific and sensitive to the early onset of injury. Here, to identify plasma metabolites as markers of early toxicant-induced injury, we used a constraint-based modeling approach with a genome-scale network reconstruction of rat liver metabolism to incorporate perturbations of gene expression induced by acetaminophen, a known hepatotoxicant. A comparison of the model results against the global metabolic profiling data revealed that our approach satisfactorily predicted altered plasma metabolite levels as early as 5 h after exposure to 2 g/kg of acetaminophen, and that 10 h after treatment the predictions significantly improved when we integrated measured central carbon fluxes. Our approach is solely driven by gene expression and physiological boundary conditions, and does not rely on any toxicant-specific model component. As such, it provides a mechanistic model that serves as a first step in identifying a list of putative plasma metabolites that could change due to toxicant-induced perturbations.

In silico dynamic characterization of the femur: Physiological versus mechanical boundary conditions

It is established that bone tissue adapts and responds to mechanical loading. Several studies have suggested an existence of positive influence of vibration on the bone mass maintenance. Thus, some bone regeneration therapies are based on vibration of bone tissue under circumstances of disease to stimulate its formation. Frequency of loading should be properly selected and therefore a correct characterization of the dynamic properties of this tissue may be critical for the success of such orthopedic techniques. On the other hand, many studies implement vibration techniques with in silico models. Numerical results are exclusively dependent on properties of bone tissue, i.e. geometry, density distribution and stiffness, as well as boundary conditions. In the present study, the influence of boundary conditions and material properties on the dynamic characteristics of bone tissue was explored in a human femur. Bone shape and density were directly reconstructed from computer tomographies, whereas natural frequencies and modes of vibration were obtained for different boundary conditions including physiological and mechanical ones. Results of this study show the moderate effect of material properties compared to the much substantial effect of boundary conditions. A factor of 2 in the natural frequency was obtained depending on imposed boundary conditions, highlighting the importance in the selection of appropriate conditions in the analysis of the bone organ.