A parametric model for studying the aorta hemodynamics by means of the computational fluid dynamics.

Perturbed aorta hemodynamics, as for the carotid and the coronary artery, has been identified as potential predicting factor for cardiovascular diseases. In this study, we propose a parametric study based on the computational fluid dynamics with the aim of providing information regarding aortic disease. In particular, the blood flow inside a parametrized aortic arch is computed as a function of morphological changes of baseline aorta geometry. Flow patterns, wall shear stress, time average wall shear stress and oscillatory shear index were calculated during the cardiac cycle. The influence of geometrical changes on the hemodynamics and on these variables was evaluated. The results suggest that the distance between inflow and aortic arch and the angle between aortic arch and descending trunk are the most influencing parameters regarding the WSS-related indices while the effect of the inlet diameter seems limited. In particular, an increase of the aforementioned distance produces a reduction of the spatial distribution of the higher values of the time average wall shear stress and of the oscillatory shear index independently on the other two parameters while an increase of the angle produce an opposite effect. Moreover, as expected, the analysis of the wall shear stress descriptors suggests that the inlet diameter influences only the flow intensity. As conclusion, the proposed parametric study can be used to evaluate the aorta hemodynamics and could be also applied in the future, for analyzing pathological cases and virtual situations, such as pre- and/or post-operative cardiovascular surgical states that present enhanced changes in the aorta morphology yet promoting important variations on the considered indexes.

Modelling Particle Transport and Deposition in the Human Healthy and Stented Tracheobronchial Airways.

The main goal of this study is the quantification of the particle transport and deposition within the human airways during light, normal and exercise breathing conditions using the computational fluid dynamics. In particular we presented a comparison between healthy and stented airways. The considered tracheobronchial model is based on the Weibel symmetric model in which we have inserted the Dumon prosthesis at different locations and on the CT-based geometries of a healthy and a stented airway. The results indicate an important redistribution of the particle deposition locations. Local overdoses can be found in the proximal regions of the prostheses, independently of the breathing conditions, of the particle size and of the considered geometry. The presented work is aimed to contribute to the understanding of the particle deposition in the human lung and to improve drug-aerosol therapies. For patients that underwent airways reconstructive surgery, it can give detailed information about the deposition efficiency and it may help targeting specific airways regions.

Use of computational fluid dynamics to compare upper airway pressures and airflow resistance in brachycephalic, mesocephalic, and dolichocephalic dogs.

Brachycephalic dog breeds are prone to breathing difficulties because of their upper airway anatomy. Several surgical techniques exist to correct anatomical pathologies and common surgical approaches aim to correct functional abnormalities in the nares and/or the soft palate. However, further research is needed to improve clinical outcomes. This study evaluated air pressure and airflow resistance in the upper airways and trachea in nine sedated, sternally recumbent dogs of different skull types (dolichocephalic, n=3; mesocephalic, n=3; brachycephalic, n=3). CT images were acquired from the nostrils to the caudal border of the lungs and geometrical reconstruction of the upper airway and trachea was performed. Analysis of computational fluid dynamics was performed using inspiratory flow adapted to bodyweight for each dog. Flow (L/min) and pressure (cmH2O) were computed for the entire upper airway and trachea. Resistance (cmH2O/L/min) was calculated using pressure differences between the nose, larynx, and trachea. In this pilot study, statistical comparisons were not performed. Pressure maps, airflow, and resistance were similar in dolichocephalic and mesocephalic breeds. Median pressure difference (3.76cmH2O) and resistance (0.154cmH2O/L/min) between the nose and larynx were numerically higher in brachycephalic dogs than in other breeds (0.45cmH2O and 0.016cmH2O/L/min, respectively). Median pressure difference (0.205cmH2O) and resistance (0.009cmH2O/L/min) between the larynx and trachea was numerically similar in all dogs, except for the English bulldog. The methodology used in this preliminary study to quantify airflow characteristics such as pressure and resistance could improve the understanding of brachycephalic obstruction airway syndrome.

On Studying the Interaction Between Different Stent Models and Rabbit Tracheal Tissue: Numerical, Endoscopic and Histological Comparison.

Stenting technique is employed worldwide for treating atherosclerotic vessel and tracheal stenosis. Both diseases can be treated by means of metallic stents which present advantages but are affected by the main problem of restenosis of the stented area. In this study we have built a rabbit trachea numerical model and we have analyzed it before and after insertion and opening of two types of commercial stent: a Zilver(®) Flex™ Stent and a WallStent™. In experimental parallel work, two types of stent were implanted in 30 New Zealand rabbits divided in two groups of 10 animals corresponding to each stent type and a third group made up of 10 animals without stent. The tracheal wall response was assessed by means of computerized tomography by endoscopy, macroscopic findings and histopathological study 90 days after stent deployment. Three idealized trachea models, one model for each group, were created in order to perform the computational study. The animal model was used to validate the numerical findings and to attempt to find qualitative correlations between numerical and experimental results. Experimental findings such as inflammation, granuloma and abnormal tissue growth, assessed from histomorphometric analyses were compared with derived numerical parameters such as wall shear stress (WSS) and maximum principal stress. The direct comparison of these parameters and the biological response supports the hypothesis that WSS and tensile stresses may lead to a greater tracheal epithelium response within the stented region, with the latter seeming to have the dominant role. This study may be helpful for improving stent design and demonstrates the feasibility offered by in-silico investigated tracheal structural and fluid dynamics.

Mathematical modeling of the fibrosis process in the implantation of inferior vena cava filters.

An inferior vena cava filter is a medical device that is implanted in the inferior vena cava and is in charge of capturing blood clots before they reach the lungs, preventing from pulmonary embolism. There are some clinical problems regarding the use of inferior vena cava filters. One of them is the difficulty when retrieving the device due to the remodeling of the vena cava. Huge effort has been made in creating computational models that reproduce tissue remodeling, but no attention has been paid to the fibrosis phenomenon occurring in the inferior vena cava. In this work, a continuum computational model that reproduces the fibrosis in the presence of an antithrombotic filter is presented. Diffusion-reaction equations are used for modeling the mass balance between species in the venous wall. The main species considered to play a key role in the process of fibrosis are smooth muscle cells, endothelial cells, matrix metalloproteinases, vascular growth factors and the extracellular matrix. The developed model has been implemented on an idealized axisymmetric geometric vena cava model. Moreover, a sensitivity analysis has been performed to study the parameters influence on the evolution of the model. Results show that the computational model is able to predict the behavior of the species considered and it captures the key characteristics of lesion growth and the healing process within a vein subjected to non-physiological mechanical forces. Our results suggests that the vessel wall response is mainly caused by the endothelium denudation area and the collagen turnover among other factors.

A theoretical model of the endothelial cell morphology due to different waveforms.

Endothelial cells are key units in the regulatory biological process of blood vessels. They represent an interface to transmit variations on the fluid dynamic changes. They are able to adapt its cytoskeleton, by means of microtubules reorientation and F-actin reorganization, due to new mechanical environments. Moreover, they are responsible for initiating a huge cascade of biological processes, such as the release of endothelins (ET-1), in charge of the constriction of the vessel and growth factors such as TGF-ß and PDGF. Although a huge efforts have been made in the experimental characterization and description of these two issues the computational modeling has not gained such an attention. In this work we study the 3D remodeling of endothelial cells based on the main features of blood flow. In particular we study how different oscillatory shear index and the time average wall shear stresses modify the endothelial cell shape. We found our model fitted the experimental works presented before in in vitro studies. We also include our model within a computational fluid dynamics simulation of a carotid artery to evaluate endothelial cell shape index which is a key predictor of atheroma plaque formation. Moreover, our approach can be coupled with models of collagen and smooth muscle cell growth, where remodeling and the associated release of chemical substance are involved.

In vitro comparison of Günther Tulip and Celect filters: testing filtering efficiency and pressure drop.

In this study, the trapping ability of the Günther Tulip and Celect inferior vena cava filters was evaluated. Thrombus capture rates of the filters were tested in vitro in horizontal position with thrombus diameters of 3 and 6mm and tube diameter of 19mm. The filters were tested in centered and tilted positions. Sets of 30 clots were injected into the model and the same process was repeated 20 times for each different condition simulated. Pressure drop experienced along the system was also measured and the percentage of clots captured was recorded. The Günther Tulip filter showed superiority in all cases, trapping almost 100% of 6mm clots both in an eccentric and tilted position and trapping 81.7% of the 3mm clots in a centered position and 69.3% in a maximum tilted position. The efficiency of all filters tested decreased as the size of the embolus decreased and as the filter was tilted. The injection of 6 clots raised the pressure drop to 4.1mmHg, which is a reasonable value that does not cause the obstruction of blood flow through the system.

Tortuosity of coronary bifurcation as a potential local risk factor for atherosclerosis: CFD steady state study based on in vivo dynamic CT measurements.

The purpose of the present study was to determine whether in vivo bifurcation geometric factors would permit prediction of the risk of atherosclerosis. It is worldwide accepted that low or oscillatory wall shear stress (WSS) is a robust hemodynamic factor in the development of atherosclerotic plaque and has a strong correlation with the local site of plaque deposition. However, it still remains unclear how coronary bifurcation geometries are correlated with such hemodynamic forces. Computational fluid dynamics simulations were performed on left main (LM) coronary bifurcation geometries derived from CT of eight patients without significant atherosclerosis. WSS amplitudes were accurately quantified at two high risk zones of atherosclerosis, namely at proximal left anterior descending artery (LAD) and at proximal left circumflex artery (LCx), and also at three high WSS concentration sites near the bifurcation. Statistical analysis was used to highlight relationships between WSS amplitudes calculated at these five zones of interest and various geometric factors. The tortuosity index of the LM-LAD segment appears to be an emergent geometric factor in determining the low WSS amplitude at proximal LAD. Strong correlations were found between the high WSS amplitudes calculated at the endothelial regions close to the flow divider. This study not only demonstrated that CT imaging studies of local risk factor for atherosclerosis could be clinically performed, but also showed that tortuosity of LM-LAD coronary branch could be used as a surrogate marker for the onset of atherosclerosis.

Simulation of swallowing dysfunction and mechanical ventilation after a Montgomery T-tube insertion.

The Montgomery T-tube is used as a combined tracheal stent and airway after laryngotracheoplasty, to keep the lumen open and prevent mucosal laceration from scarring. It is valuable in the management of upper and mid-tracheal lesions, while invaluable in long and multisegmental stenting lesions. Numerical simulations based on real-patient-tracheal geometry, experimental tissue characterization, and previous numerical estimation of the physiological swallowing force are performed to estimate the consequences of Montgomery T-tube implantation on swallowing and assisted ventilation: structural analysis of swallowing is performed to evaluate patient swallowing capacity, and computational fluid dynamics simulation is carried out to analyze related mechanical ventilation. With an inserted Montgomery T-tube, vertical displacement (Z-axis) reaches 8.01 mm, whereas in the Y-axis, it reaches 6.63 mm. The maximal principal stress obtained during swallowing was 1.6 MPa surrounding the hole and in the upper contact with the tracheal wall. Fluid flow simulation of the mechanical ventilation revealed positive pressure for both inhalation and exhalation, being higher for inspiration. The muscular deflections, considerable during normal breathing, are nonphysiological, and this aspect results in a constant overload of the tracheal muscle. During swallowing, the trachea ascends producing a nonhomogeneous elongation. This movement can be compromised when prosthesis is inserted, which explains the high incidence of glottis close inefficiency. Fluid simulations showed that nonphysiological pressure is established inside the trachea due to mechanical ventilation. This may lead to an overload of the tracheal muscle, explaining several related problems as muscle thinning or decrease in contractile function.

Estudio biomecánico de las modificaciones del flujo aéreo traqueal durante los movimientos respiratorios y la tos tras la colocación de una endoprótesis. Posible influencia en la retención de secreciones / Biomechanical study of changes in tracheal airflow during respiratory movements and coughing after placement of an endoprosthesis. Possible influence in secretion retention

Es frecuente que sea precisa la utilización de endoprótesis para el tratamiento de las estenosis traqueales. Aunque solucionan el problema de una forma rápida y segura, su colocación acarrea una serie de efectos secundarios. Los más frecuentes, la retención de secreciones. Utilizando un modelo informático que reproduce el comportamiento biomecánico de la tráquea, se pretende dar explicación a los fenómenos que ocurren tras la implantación de una endoprótesis. Se ha estudiado la variación del flujo aéreo producida tras la intervención durante la respiración normal y la tos. Los resultados obtenidos muestran una disminución de las velocidades de circulación del aire, junto con alteraciones en el patrón de flujo, originadas por la propia morfología de la prótesis, que pueden justificar la dificultad que presentan algunos pacientes para eliminar las secreciones respiratorias, permitiendo que estas se acumulen, sobre todo, en los alrededores de la zona de implantación

Frequently, the use of prosthesis is necessary to deal with a tracheal stenosis. They achieve a rapid and safe resolution of the stenosis, but in some instances, their insertion results in some secondary effects, more often, retained secretions. By using a computer-assisted model that mimics the biome chanical behaviour of the trachea, we aimed at clarifying those phenomena occurring following the prosthesis implantation by assessing the airflow changes during both normal breathing and cough. Our results revealed a decrease in airflow speed and changes in flow patterns secondary to the morphological features of the prosthesis, which might be involved in the inability of these patients to clear secretions, which are retained in the periprosthetic area

Impedance-based outflow boundary conditions for human carotid haemodynamics.

In this study, we develop structured tree outflow boundary conditions for modelling the human carotid haemodynamics. The model geometry was reconstructed through computerised tomography scan. Unsteady-state computational fluid dynamic analyses were performed under different conditions using a commercial software package ADINA R&D, Inc., (Watertown, MA, USA) in order to assess the impact of the boundary conditions on the flow variables. In particular, the results showed that the peripheral vessels massively impact the pressure while the flow is relatively unaffected. As an example of application of these outflow conditions, an unsteady fluid-structure interaction (FSI) simulation was carried out and the dependence of the wall shear stress (WSS) on the arterial wall compliance in the carotid bifurcation was studied. In particular, a comparison between FSI and rigid-wall models was conducted. Results showed that the WSS distributions were substantially affected by the diameter variation of the arterial wall. In particular, even similar WSS distributions were found for both cases, and differences in the computed WSS values were also found.

Computational methodology to determine fluid related parameters of non regular three-dimensional scaffolds.

The application of three-dimensional (3D) biomaterials to facilitate the adhesion, proliferation, and differentiation of cells has been widely studied for tissue engineering purposes. The fabrication methods used to improve the mechanical response of the scaffold produce complex and non regular structures. Apart from the mechanical aspect, the fluid behavior in the inner part of the scaffold should also be considered. Parameters such as permeability (k) or wall shear stress (WSS) are important aspects in the provision of nutrients, the removal of metabolic waste products or the mechanically-induced differentiation of cells attached in the trabecular network of the scaffolds. Experimental measurements of these parameters are not available in all labs. However, fluid parameters should be known prior to other types of experiments. The present work compares an experimental study with a computational fluid dynamics (CFD) methodology to determine the related fluid parameters (k and WSS) of complex non regular poly(L-lactic acid) scaffolds based only on the treatment of microphotographic images obtained with a microCT (µCT). The CFD analysis shows similar tendencies and results with low relative difference compared to those of the experimental study, for high flow rates. For low flow rates the accuracy of this prediction reduces. The correlation between the computational and experimental results validates the robustness of the proposed methodology.

Three-dimensional geometries representing the retinal nerve fiber layer in multiple sclerosis, optic neuritis, and healthy eyes.

BACKGROUND: To represent and interpret the three-dimensional (3D) geometry and the distribution of the axonal damage to the retinal nerve fiber layer (RNFL) in patients with multiple sclerosis (MS) compared with healthy subjects. To analyze alterations in RNFL morphology in eyes of MS patients with or without previous episodes of optic neuritis (ON). METHODS: MS patients (n = 122) and age-matched healthy subjects (n = 108) were enrolled. The Spectralis optical coherence tomography system was used to determine the circumpapillary RNFL thickness. The 768 RNFL thickness measurements were used to evaluate thickness measurements in patients with or without antecedent ON and to design a 3D reconstruction of the RNFL thickness representing the mechanobiologic tissue response to neurodegeneration caused by MS and ON episodes. RESULTS: RNFL thickness was decreased in MS patients, and was higher in the MS group with previous ON. Statistical analysis and 3D RNFL reconstruction revealed greater damage to the ganglionar cells in the superonasal RNFL area (101.77 µm in MS vs. 125.47 µm in healthy subjects) and in the inferotemporal RNFL (119.05 µm in MS eyes and 149.26 µm in healthy eyes). CONCLUSIONS: The 3D representation of RNFL thickness based on measurements allows physicians to better observe damage in the temporal areas, especially in patients with previous ON.

CFD analysis of the human airways under impedance-based boundary conditions: application to healthy, diseased and stented trachea.

A computational fluid dynamics model of a healthy, a stenotic and a post-operatory stented human trachea was developed to study the respiration under physiological boundary conditions. For this, outflow pressure waveforms were computed from patient-specific spirometries by means of a method that allows to compute the peripheral impedance of the truncated bronchial generation, modelling the lungs as fractal networks. Intratracheal flow pattern was analysed under different scenarios. First, results obtained using different outflow conditions were compared for the healthy trachea in order to assess the importance of using impedance-based conditions. The resulted intratracheal pressures were affected by the different boundary conditions, while the resulted velocity field was unaffected. Impedance conditions were finally applied to the diseased and the stented trachea. The proposed impedance method represents an attractive tool to compute physiological pressure conditions that are not possible to extract in vivo. This method can be applied to healthy, pre- and post-operatory tracheas showing the possibility of predicting, through numerical simulation, the flow and the pressure field before and after surgery.

Evaluation of migration forces of a retrievable filter: experimental setup and finite element study.

The aim of this paper is to provide a computational study of migration forces of a retrievable filter (Günther Tulip inferior vena cava filter). Using an experimental setup and finite element simulation, the migration forces and stress at the end of the anchored hooks in the struts were estimated. After that, the estimation value of migration stress (τ(rup)) was used to analyze the effect of different mechanical factors (strut thickness, vena cava diameter) in the migration of the IVC filter. Our results show that the migration stress is τ(rup)=4.37 N/mm(2). Using this value we obtain that the filter with higher strut diameter (ϕ(strut)=0.45 mm) shows the maximal migration forces in every cava diameter. On the other hand, the value of the migration force decreases when the cava diameter increases. In addition, the finite element simulations also show that there are contact between the struts of the filter and the vein in regions close to the anchors.

FSI analysis of a human trachea before and after prosthesis implantation.

In this work we analyzed the response of a stenotic trachea after a stent implantation. An endotracheal stent is the common treatment for tracheal diseases such as stenosis, chronic cough, or dispnoea episodes. Medical treatment and surgical techniques are still challenging due to the difficulties in overcoming potential complications after prosthesis implantation. A finite element model of a diseased and stented trachea was developed starting from a patient specific computerized tomography (CT) scan. The tracheal wall was modeled as a fiber reinforced hyperelastic material in which we modeled the anisotropy due to the orientation of the collagen fibers. Deformations of the tracheal cartilage rings and of the muscular membrane, as well as the maximum principal stresses, are analyzed using a fluid solid interaction (FSI) approach. For this reason, as boundary conditions, impedance-based pressure waveforms were computed modeling the nonreconstructed vessels as a binary fractal network. The results showed that the presence of the stent prevents tracheal muscle deflections and indicated a local recirculatory flow on the stent top surface which may play a role in the process of mucous accumulation. The present work gives new insight into clinical procedures, predicting their mechanical consequences. This tool could be used in the future as preoperative planning software to help the thoracic surgeons in deciding the optimal prosthesis type as well as its size and positioning.

FSI Analysis of a healthy and a stenotic human trachea under impedance-based boundary conditions.

In this work, a fluid-solid interaction (FSI) analysis of a healthy and a stenotic human trachea was studied to evaluate flow patterns, wall stresses, and deformations under physiological and pathological conditions. The two analyzed tracheal geometries, which include the first bifurcation after the carina, were obtained from computed tomography images of healthy and diseased patients, respectively. A finite element-based commercial software code was used to perform the simulations. The tracheal wall was modeled as a fiber reinforced hyperelastic solid material in which the anisotropy due to the orientation of the fibers was introduced. Impedance-based pressure waveforms were computed using a method developed for the cardiovascular system, where the resistance of the respiratory system was calculated taking into account the entire bronchial tree, modeled as binary fractal network. Intratracheal flow patterns and tracheal wall deformation were analyzed under different scenarios. The simulations show the possibility of predicting, with FSI computations, flow and wall behavior for healthy and pathological tracheas. The computational modeling procedure presented herein can be a useful tool capable of evaluating quantities that cannot be assessed in vivo, such as wall stresses, pressure drop, and flow patterns, and to derive parameters that could help clinical decisions and improve surgical outcomes.

FSI analysis of the coughing mechanism in a human trachea.

The main physiological function of coughing is to remove from the airways the mucus and foreign particles that enter the lungs with respirable air. However, in patients with endotracheal tubes, further surgery has to be performed to improve cough effectiveness. Thus, it is necessary to analyze how this process is carried out in healthy tracheas to suggest ways to improve its efficacy in operated patients. A finite element model of a human trachea is developed and used to analyze the deformability of the tracheal walls under coughing. The geometry of the trachea is obtained from CT of a 70-year-old male patient. A fluid structure interaction approach is used to analyze the deformation of the wall when the fluid (in this case, air) flows inside the trachea. A structured hexahedral-based grid for the tracheal walls and an unstructured tetrahedral-based mesh with coincident nodes for the fluid are used to perform the simulations with the finite element-based commercial software code (ADINA R&D Inc.). Tracheal wall is modeled as an anisotropic fiber reinforced hyperelastic solid material in which the different orientation of the fibers is introduced. The implantation of an endotracheal prosthesis is simulated. Boundary conditions for breathing and coughing are applied at the inlet and at the outlet surfaces of the fluid mesh. The collapsibility of a human trachea under breathing and coughing is shown in terms of flow patterns and wall stresses. The ability of the model to reproduce the normal breathing and coughing is proved by comparing the deformed shape of the trachea with experimental results. Moreover the implantation of an endotracheal prosthesis would be related with a decrease of coughing efficiency, as clinically seen.

Successive explosions in Mumbai the economic center of India.

Terrorist activities in India are increasing day by day with sophistication in modus operandi. Mumbai the economic center of India was attacked by a series of bomb blasts at twelve different places within a span of an hour on 12th March 1993. The main explosive used was RDX [Krishnamurthy R, Malve MK, Shinde BM. J Indian Acad Forensic Sci 1996;35(1& 2):46-61.]. After about 10 years, terrorist activity of late has again erupted taking a toll on innocent lives, with the use of explosives causing death and destruction. On 2.12.02 a public bus at Ghatkopar was blown up by an improvised explosive device (IED) with two casualties. On 27.1.03 the public vegetable market at Vileparle was targeted causing heavy damage and panic among common people. On 13.3.03 a fully packed local train compartment at Mulund railway station was blown up by an improved explosive device and the casualties ranged up to 10. In most of the explosions the explosives used were RDX, NC-NG, etc. The blasts that occurred at the Zaveri bazaar and the gateway of India on 25/8/03 showed the presence of big craters at the blast site and on analysis the presence of RDX and petroleum oil.