M. Malvè

On the necessity of modelling fluid-structure interaction for stented coronary arteries.

Although stenting is the most commonly performed procedure for the treatment of coronary atherosclerotic lesions, in-stent restenosis (ISR) remains one of the most serious clinical complications. An important stimulus to ISR is the altered hemodynamics with abnormal shear stresses on endothelial cells generated by the stent presence. Computational fluid dynamics is a valid tool for studying the local hemodynamics of stented vessels, allowing the calculation of the wall shear stress (WSS), which is otherwise not directly possible to be measured in vivo. However, in these numerical simulations the arterial wall and the stent are considered rigid and fixed, an assumption that may influence the WSS and flow patterns. Therefore, the aim of this work is to perform fluid-structure interaction (FSI) analyses of a stented coronary artery in order to understand the effects of the wall compliance on the hemodynamic quantities. Two different materials are considered for the stent: cobalt-chromium (CoCr) and poly-l-lactide (PLLA). The results of the FSI and the corresponding rigid-wall models are compared, focusing in particular on the analysis of the WSS distribution. Results showed similar trends in terms of instantaneous and time-averaged WSS between compliant and rigid-wall cases. In particular, the difference of percentage area exposed to TAWSS lower than 0.4Pa between the CoCr FSI and the rigid-wall cases was about 1.5% while between the PLLA cases 1.0%. The results indicate that, for idealized models of a stented coronary artery, the rigid-wall assumption for fluid dynamic simulations appears adequate when the aim of the study is the analysis of near-wall quantities like WSS.

Is arterial wall-strain stiffening an additional process responsible for atherosclerosis in coronary bifurcations?: an in vivo study based on dynamic CT and MRI

Coronary bifurcations represent specific regions of the arterial tree that are susceptible to atherosclerotic lesions. While the effects of vessel compliance, curvature, pulsatile blood flow, and cardiac motion on coronary endothelial shear stress have been widely explored, the effects of myocardial contraction on arterial wall stress/strain (WS/S) and vessel stiffness distributions remain unclear. Local increase of vessel stiffness resulting from wall-strain stiffening phenomenon (a local process due to the nonlinear mechanical properties of the arterial wall) may be critical in the development of atherosclerotic lesions. Therefore, the aim of this study was to quantify WS/S and stiffness in coronary bifurcations and to investigate correlations with plaque sites. Anatomic coronary geometry and cardiac motion were generated based on both computed tomography and MRI examinations of eight patients with minimal coronary disease. Computational structural analyses using the finite element method were subsequently performed, and spatial luminal arterial wall stretch (LW(Stretch)) and stiffness (LW(Stiff)) distributions in the left main coronary bifurcations were calculated. Our results show that all plaque sites were concomitantly subject to high LW(Stretch) and high LW(Stiff), with mean amplitudes of 34.7 ± 1.6% and 442.4 ± 113.0 kPa, respectively. The mean LW(Stiff) amplitude was found slightly greater at the plaque sites on the left main coronary artery (mean value: 482.2 ± 88.1 kPa) compared with those computed on the left anterior descending and left circumflex coronary arteries (416.3 ± 61.5 and 428.7 ± 181.8 kPa, respectively). These findings suggest that local wall stiffness plays a role in the initiation of atherosclerotic lesions.

Influence of breathing movements and Valsalva maneuver on vena caval dynamics

AIM To study changes produced within the inferior vena cava (IVC) during respiratory movements and identify their possible clinical implications. METHODS This study included 100 patients (46 women; 54 men) over 18 years of age who required an abdominal computed tomography (CT) and central venous access. IVC cross-sectional areas were measured on CT scans at three levels, suprarenal (SR), juxtarenal (JR) and infrarenal (IR), during neutral breathing and again during the Valsalva maneuver. All patients were instructed on how to perform a correct Valsalva maneuver. In order to reduce the total radiation dose in our patients, low-dose CT protocols were used in all patients. The venous blood pressure (systolic, diastolic and mean) was invasively measured at the same three levels with neutral breathing and the Valsalva maneuver during venous port implantation. From CT scans, three-dimensional models of the IVC were constructed and a collapsibility index was calculated for each patient. These data were then correlated with venous pressures and cross-sectional areas. RESULTS The mean patient age was 51.64 ± 12.01 years. The areas of the ellipse in neutral breathing were 394.49 ± 85.83 (SR), 380.10 ± 74.55 (JR), and 342.72 ± 49.77 mm(2) (IR), and 87.46 ± 18.35 (SR), 92.64 ± 15.36 (JR) and 70.05 ± 9.64 mm(2) (IR) during the Valsalva (Ps < 0.001). There was a correlation between areas in neutral breathing and in the Valsalva maneuver (P < 0.05 in all areas). Large areas decreased more than smaller areas. The collapsibility indices were 0.49 ± 0.06 (SR), 0.50 ± 0.04 (JR) and 0.50 ± 0.04 (IR), with no significant differences in any region. Reconstructed three-dimensional models showed a flattening of the IVC during Valsalva, adopting an ellipsoid cross-sectional shape. The mean pressures with neutral breathing were 9.44 ± 1.78 (SR), 9.40 ± 1.44 (JR) and 8.84 ± 1.03 mmHg (IR), and 81.08 ± 21.82 (SR), 79.88 ± 19.01 (JR) and 74.04 ± 16.56 mmHg (IR) during Valsalva (Ps < 0.001). There was a negative correlation between cross-sectional caval area and venous blood pressure, but this was not statistically significant in any of the cases. There was a significant correlation between diastolic and mean pressures measured during neutral breathing and in Valsalva. CONCLUSION Respiratory movements have a major influence on IVC dynamics. The increase in intracaval pressure during Valsalva results in a significant decrease in the IVC cross-sectional area.

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.

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-β 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.

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.

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.