Calculation of the 3-D dose distribution surrounding a 103Pd stent

Purpose: This study was designed to assess the suitability of a ¹⁰³Pd-implanted stent for use in intravascular brachytherapy. Materials and methods: A stent was modeled as a superposition of 201 identical struts and the EGS4/DOSRZ Monte Carlo code was used to calculate the dose distribution for each strut. To verify the simulation parameters, doses along the transverse axis of a Model 200 ¹⁰³Pd interstitial seed were calculated and compared to those calculated by the TG43 method. Results: Dose profiles within 1 mm of the stent's outer surface were heterogeneous and reflected the stent's structure. For a 2-mm outer-diameter ¹⁰³Pd-implanted stent, ∼2.68×10⁷ Bq were required to deliver 31.5 Gy in 28 days at a distance of 0.5 mm along the perpendicular bisector from the stent's outer surface. The Monte Carlo simulation of the ¹⁰³Pd seed showed relative doses within 7% of the values calculated by the TG43 method. Conclusion: The dosimetry about a ¹⁰³Pd-implanted stent suggests that the stent is suitable for use in intravascular brachytherapy.     

Radiofrequency tissue ablation inside of metal stent – A thermographic study

Biliary stents are used to treat obstructions that occur in the bile ducts. The stents can be blocked by new tissue in a few months after their implanting. This complication can be solved by using radiofrequency ablation. The present article deals with monitoring of the process of monopolar thermoablation of a metal stent by using an infrared camera ex vivo. The metallic EGIS Biliary stents 10 mm × 80 mm were used in experiments; radiofrequency ablation due by catheter EndoHPB 8F at 460 kHz was used. The Flir B200 thermocamera was used for monitoring. The results show an increase in temperature of the stent's material during thermoablation process. It is believed that the metal stent becomes an active electrode. The results show an increase in temperature of the stent and the surrounding tissue during the treatment. Temperature distribution measured on stent was affected by power applied and obviously non-homogeneous. The maximum temperature values were observed at the ends of the stent. The temperature value of the stent during termoablation depended also on the position of the second (inactive) surface electrode. Results of this study have shown that there are many factors able to affect the final temperature or process of tissue ablation inside of the stent and around the stent. Infrared camera seems to be an appropriate instrument for observing the distribution and changes in temperature during ex vivo radiofrequency ablation.     

A multi-scale mechanobiological model of in-stent restenosis: deciphering the role of matrix metalloproteinase and extracellular matrix changes

Since their first introduction, stents have revolutionised the treatment of atherosclerosis; however, the development of in-stent restenosis still remains the Achilles' heel of stent deployment procedures. Computational modelling can be used as a means to model the biological response of arteries to different stent designs using mechanobiological models, whereby the mechanical environment may be used to dictate the growth and remodelling of vascular cells. Changes occurring within the arterial wall due to stent-induced mechanical injury, specifically changes within the extracellular matrix, have been postulated to be a major cause of activation of vascular smooth muscle cells and the subsequent development of in-stent restenosis. In this study, a mechanistic multi-scale mechanobiological model of in-stent restenosis using finite element models and agent-based modelling is presented, which allows quantitative evaluation of the collagen matrix turnover following stent-induced arterial injury and the subsequent development of in-stent restenosis. The model is specifically used to study the influence of stent deployment diameter and stent strut thickness on the level of in-stent restenosis. The model demonstrates that there exists a direct correlation between the stent deployment diameter and the level of in-stent restenosis. In addition, investigating the influence of stent strut thickness using the mechanobiological model reveals that thicker strut stents induce a higher level of in-stent restenosis due to a higher extent of arterial injury. The presented mechanobiological modelling framework provides a robust platform for testing hypotheses on the mechanisms underlying the development of in-stent restenosis and lends itself for use as a tool for optimisation of the mechanical parameters involved in stent design.     

Numerical analysis of pulsatile blood flow and vessel wall mechanics in different degrees of stenoses

Hemodynamics factors and biomechanical forces play key roles in atherogenesis, plaque development and final rupture. In this paper, we investigated the flow field and stress field for different degrees of stenoses under physiological conditions. Disease is modelled as axisymmetric cosine shape stenoses with varying diameter reductions of 30%, 50% and 70%, respectively. A simulation model which incorporates fluid-structure interaction, a turbulence model and realistic boundary conditions has been developed. The results show that wall motion is constrained at the throat by 60% for the 30% stenosis and 85% for the 50% stenosis; while for the 70% stenosis, wall motion at the throat is negligible through the whole cycle. Peak velocity at the throat varies from 1.47 m/s in the 30% stenosis to 3.2m/s in the 70% stenosis against a value of 0.78 m/s in healthy arteries. Peak wall shear stress values greater than 100 Pa were found for > or =50% stenoses, which in vivo could lead to endothelial stripping. Maximum circumferential stress was found at the shoulders of plaques. The results from this investigation suggest that severe stenoses inhibit wall motion, resulting in higher blood velocities and higher peak wall shear stress, and localization of hoop stress. These factors may contribute to further development and rupture of plaques.     

An intergral method for the analysis of flow in arterial stenoses

An approximate solution is presented to the problem of incompressible flow through an axisymmetric constriction. The geometry is intended to simulate an arterial stenosis, and the solution is applicable to both mild and severe stenoses for Reynolds numbers below transition. Theoretical results obtained for specific geometries are given for the velocity distribution, pressure drop, wall shearing stress, and separation phenomena. These results reveal the significant alterations in flow caused by a stenosis. Experiments using model stenoses are described and compared with the theoretical results. Theoretical predictions of pressure drop and separation characteristics are in reasonably good agreement with the experimental observations.     

Patient specific finite element analysis results in more accurate prediction of stent fractures: Application to percutaneous pulmonary valve implantation

Stent fracture is a recognised complication following device implantation. Magnetic resonance data from a patient who underwent percutaneous pulmonary valve implantation (PPVI) and had subsequent stent fractures was used to create a finite element (FE) model of the patient's implantation site. Simulated expansion of the PPVI stent into this right ventricular outflow tract (RVOT) geometry was compared with free expansions of the PPVI stent up to a uniformly deployed configuration (conventional method employed in bench testing protocols), using FE analysis. PPVI biplane fluoroscopy images from the same patient were used to reconstruct the 3D shape and deformation of the stent in-situ and verify the FE geometrical results. Asymmetries were measured in all 3 orthogonal directions, in early systole and diastole.Although a simplified FE modelling of stent/implantation site interaction was adopted, this analysis gave useful information about the influence of the RVOT on the final geometry and mechanical performance of the stent. When deployed into the RVOT, the FE stent showed a non-uniform shape, similar to the geometry seen in the “real” fluoroscopy reconstructed stent, where the most expanded cells corresponded to the fracture locations. This asymmetrical geometry, when compared to the free-expanded stent, resulted in higher stresses in the portion of the stent where fractures occurred. Furthermore, fatigue fractures that were not predicted in the free-deployed stents, developed in the asymmetrically expanded device.In conclusion, the interaction between the PPVI device and the patient's RVOT is likely to be the crucial factor involved with this undesired event.     

Simulation of a balloon expandable stent in a realistic coronary artery—Determination of the optimum modelling strategy

Computational models of stent deployment in arteries have been widely used to shed light on various aspects of stent design and optimisation. In this context, modelling of balloon expandable stents has proved challenging due to the complex mechanics of balloon–stent interaction and the difficulties involved in creating folded balloon geometries. In this study, a method to create a folded balloon model is presented and utilised to numerically model the accurate deployment of a stent in a realistic geometry of an atherosclerotic human coronary artery. Stent deployment is, however, commonly modelled by applying an increasing pressure to the stent, thereby neglecting the balloon. This method is compared to the realistic balloon expansion simulation to fully elucidate the limitations of this procedure. The results illustrate that inclusion of a realistic balloon model is essential for accurate modelling of stent deformation and stent stresses. An alternative balloon simulation procedure is presented however, which overcomes many of the limitations of the applied pressure approach by using elements which restrain the stent as the desired diameter is achieved. This study shows that direct application of pressure to the stent inner surface may be used as an optimal modelling strategy to estimate the stresses in the vessel wall using these restraining elements and hence offer a very efficient alternative approach to numerically modelling stent deployment within complex arterial geometries. The method is limited however, in that it can only predict final stresses in the stented vessel and not those occurring during stent expansion, in which case the balloon expansion model is required.     

In silico prediction of the mechanobiological response of arterial tissue: application to angioplasty and stenting

One way to restore physiological blood flow to occluded arteries involves the deformation of plaque using an intravascular balloon and preventing elastic recoil using a stent. Angioplasty and stent implantation cause unphysiological loading of the arterial tissue, which may lead to tissue in-growth and reblockage; termed "restenosis." In this paper, a computational methodology for predicting the time-course of restenosis is presented. Stress-induced damage, computed using a remaining life approach, stimulates inflammation (production of matrix degrading factors and growth stimuli). This, in turn, induces a change in smooth muscle cell phenotype from contractile (as exists in the quiescent tissue) to synthetic (as exists in the growing tissue). In this paper, smooth muscle cell activity (migration, proliferation, and differentiation) is simulated in a lattice using a stochastic approach to model individual cell activity. The inflammation equations are examined under simplified loading cases. The mechanobiological parameters of the model were estimated by calibrating the model response to the results of a balloon angioplasty study in humans. The simulation method was then used to simulate restenosis in a two dimensional model of a stented artery. Cell activity predictions were similar to those observed during neointimal hyperplasia, culminating in the growth of restenosis. Similar to experiment, the amount of neointima produced increased with the degree of expansion of the stent, and this relationship was found to be highly dependant on the prescribed inflammatory response. It was found that the duration of inflammation affected the amount of restenosis produced, and that this effect was most pronounced with large stent expansions. In conclusion, the paper shows that the arterial tissue response to mechanical stimulation can be predicted using a stochastic cell modeling approach, and that the simulation captures features of restenosis development observed with real stents. The modeling approach is proposed for application in three dimensional models of cardiovascular stenting procedures.     

Intravascular-ultrasound-guided percutaneous transluminal coronary angioplasty/provisional stent implantation strategy: impact on long-term clinical follow-up

Two hundred and eighty-four consecutive patients with 438 native coronary artery stenoses were enrolled prospectively in a study of intravascular ultrasound (IVUS)-guided percutaneous transluminal coronary angioplasty (PTCA) with provisional stenting: (1) aggressive lesion-site media-to-media balloon-sizing; (2) IVUS-assessment of residual lumen dimensions to identify optimal PTCA results (minimum lumen area = 65% of the average of the proximal and distal reference lumen areas or = 6.0 mm(2) and no major dissection); and (3) liberal stent crossover. Overall, 206 stenoses in 134 patients (47%) were treated with PTCA alone. Reasons for crossover were flow-limiting or lumen-compromising dissections in 28% of patients and suboptimal IVUS minimum lumen area in 72% of patients. At one year, 8% of stenoses in the PTCA group and 16% in the stent crossover group required revascularization. In approximately half of the patients treated using an IVUS-guided aggressive PTCA strategy, stent implantation could be avoided without sacrificing an increase in acute complications or worse clinical outcome.     

Self-expanding stent modelling and radial force accuracy

Computational simulations using finite element analysis are a tool commonly used to analyse stent designs, deployment geometries and interactions between stent struts and arterial tissue. Such studies require large computational models and efforts are often made to simplify models in order to reduce computational time while maintaining reasonable accuracy. The objective of the study is focused on computational modelling and specifically aims to investigate how different methods of modelling stent–artery interactions can affect the results, computational time taken and computational size of the model. Various different models, each with increasing levels of complexity, are used to simulate this analysis, representing the many assumptions and simplifications used in other similar studies in order to determine what level of simplification will still allow for an accurate representation of stent radial force and resulting stress concentrations on the inner lining of the vessel during self-expanding stent deployment. The main conclusions of the study are that methods used in stent crimping impact on the resulting predicted radial force of the stent; that accurate representation of stent–artery interactions can only be made when modelling the full length of the stent due to the incorporation of end effects; and that modelling self-contact of the stent struts greatly impacts on the resulting stress concentrations within the stent, but that the effect of this on the unloading behaviour and resulting radial force of the stent is negligible.     

An Agent-Based Model of the Response to Angioplasty and Bare-Metal Stent Deployment in an Atherosclerotic Blood Vessel

Purpose

While animal models are widely used to investigate the development of restenosis in blood vessels following an intervention, computational models offer another means for investigating this phenomenon. A computational model of the response of a treated vessel would allow investigators to assess the effects of altering certain vessel- and stent-related variables. The authors aimed to develop a novel computational model of restenosis development following an angioplasty and bare-metal stent implantation in an atherosclerotic vessel using agent-based modeling techniques. The presented model is intended to demonstrate the body’s response to the intervention and to explore how different vessel geometries or stent arrangements may affect restenosis development.

Methods

The model was created on a two-dimensional grid space. It utilizes the post-procedural vessel lumen diameter and stent information as its input parameters. The simulation starting point of the model is an atherosclerotic vessel after an angioplasty and stent implantation procedure. The model subsequently generates the final lumen diameter, percent change in lumen cross-sectional area, time to lumen diameter stabilization, and local concentrations of inflammatory cytokines upon simulation completion. Simulation results were directly compared with the results from serial imaging studies and cytokine levels studies in atherosclerotic patients from the relevant literature.

Results

The final lumen diameter results were all within one standard deviation of the mean lumen diameters reported in the comparison studies. The overlapping-stent simulations yielded results that matched published trends. The cytokine levels remained within the range of physiological levels throughout the simulations.

Conclusion

We developed a novel computational model that successfully simulated the development of restenosis in a blood vessel following an angioplasty and bare-metal stent deployment based on the characteristics of the vessel cross-section and stent. A further development of this model could ultimately be used as a predictive tool to depict patient outcomes and inform treatment options.     

Degradation Model of Bioabsorbable Cardiovascular Stents

This study established a numerical model to investigate the degradation mechanism and behavior of bioabsorbable cardiovascular stents. In order to generate the constitutive degradation material model, the degradation characteristics were characterized with user-defined field variables. The radial strength bench test and analysis were used to verify the material model. In order to validate the numerical degradation model, in vitro bench test and in vivo implantation studies were conducted under physiological and normal conditions. The results showed that six months of degradation had not influenced the thermodynamic properties and mechanical integrity of the stent while the molecular weight of the stents implanted in the in vivo and in vitro models had decreased to 61.8% and 68.5% respectively after six month''s implantation. It was also found that the degradation rate, critical locations and changes in diameter of the stents in the numerical model were in good consistency in both in vivo and in vitro studies. It implies that the numerical degradation model could provide useful physical insights and prediction of the stent degradation behavior and evaluate, to some extent, the in-vivo performance of the stent. This model could eventually be used for design and optimization of bioabsorbable stent.     

Intravascular ultrasound assessment of culotte stent deployment for the treatment of stenoses at major coronary bifurcations

BACKGROUND: The mechanism for the disappointing late outcome following stenting of bifurcation lesions is unclear. This prospective observational study aims to evaluate culotte stent deployment and dimensions with intravascular ultrasound (IVUS). PATIENTS AND METHODS: Patients with bifurcation stenoses were treated using two stents in a culotte configuration. After optimizing the angiographic appearance of both stents, IVUS was used to evaluate both limbs of the culotte. The main outcome measures were cross-sectional area (CSA) and minimal lumen diameter (MLD) assessed by IVUS. RESULTS: Within the culotte stent, the final mean CSA in the main limb was 6.1 mm(2) (97% of reference) and in the side-limb was 5.9 mm(2) (97% of reference). However, in each case, the minimum CSA and IVUS MLD of both limbs was at the bifurcation point. For all patients, the final mean CSA at the bifurcation point of the main limb was 4.3 mm(2) (70% of main stent) and of the side-limb was 4.4 mm(2) (75% of side stent). The IVUS MLD at the bifurcation point of the main limb was 2.1 mm (78% of main stent) and of the side-limb was 2.1 mm (84% of the side stent). Importantly, this significant residual stenosis was not detectable with quantitative coronary angiography. CONCLUSIONS: IVUS evaluation of culotte stents is feasible. The minimum IVUS CSA and MLD of both limbs of the culotte stent is at the bifurcation point. Despite an optimal angiographic appearance a significant residual stenosis was noted with IVUS at each bifurcation point.     

Quantitative morphology of the intramural coronary arteries of the trabecula septomarginalis of pigmy goats and swine

There are musculo-elastic intimal thickenings in the intramural coronary arteries of the Trabecula septomarginalis, which results in a stenosing grade of 69% in average in 6 month old pigs, of 43% in 1-6 months old pygmy goats and of 35% in average in 4-7 years old pygmy goats. The degree of intimal thickenings is related to the arterial diameter (r = -0.60); the strongest of which are found in small vessels of 100-200 microns. With increasing arterial diameter during ageing the stenoses decrease. The role of the intramural coronaries of the Trabecula septomarginalis is discussed.     

Immediate and long-term results of coronary stent implantation without predilatation (direct stenting) in patients with coronary heart disease

The paper assesses the immediate and long-term results of direct stenting (without the stage of predilation) and compares with the outcomes of conventional stent implantation. A prospective study included 183 patients. All the patients were divided into two groups according to the procedure of stent implantation. In 85 (46.7%) patients, the stent was implanted without preliminary predilation of stenosis (direct stenting). These patients formed Group 1. Group 2 comprised 97 (53.3%) patients in whom the stent was placed by using the routine procedure. All the patients enrolled into the study had types A, B1, and B2 stenoses according to the ACC/AHA classification and received the conventional antiaggregatory and anticoagulant therapy. The technical success of direct stenting was 97.7%. There were no cases of stent dislocation and loss during direct stenting or expansion of a balloon and stent. Analyzing the immediate results in all the patients of the both groups showed a positive angiographic success. Thus, a primary angiographic and clinical success of direct stenting was achieved in all (100%) patients. Recurrent angina pectoris with restenosis was observed in 8 (9.4%) patients in Group 1 and in 21 (21.6%) in Group 2 (p < 0.05). Direct stenting significantly differs from the routine stent implantation in all procedure parameters. Thus, direct stenting in patients with uncomplicated stenoses is a safe and feasible procedure.     

Low Reynolds number turbulence modeling of blood flow in arterial stenoses.

Moderate and severe arterial stenoses can produce highly disturbed flow regions with transitional and or turbulent flow characteristics. Neither laminar flow modeling nor standard two-equation models such as the kappa-epsilon turbulence ones are suitable for this kind of blood flow. In order to analyze the transitional or turbulent flow distal to an arterial stenosis, authors of this study have used the Wilcox low-Re turbulence model. Flow simulations were carried out on stenoses with 50, 75 and 86% reductions in cross-sectional area over a range of physiologically relevant Reynolds numbers. The results obtained with this low-Re turbulence model were compared with experimental measurements and with the results obtained by the standard kappa-epsilon model in terms of velocity profile, vortex length, wall shear stress, wall static pressure, and turbulence intensity. The comparisons show that results predicted by the low-Re model are in good agreement with the experimental measurements. This model accurately predicts the critical Reynolds number at which blood flow becomes transitional or turbulent distal an arterial stenosis. Most interestingly, over the Re range of laminar flow, the vortex length calculated with the low-Re model also closely matches the vortex length predicted by laminar flow modeling. In conclusion, the study strongly suggests that the proposed model is suitable for blood flow studies in certain areas of the arterial tree where both laminar and transitional/turbulent flows coexist.     

Modelling drug elution from stents: effects of reversible binding in the vascular wall and degradable polymeric matrix

Today the most popular approach for the prevention of the restenosis consists in the use of the drug eluting stents. The stent acts as a source of drug, from a coating or from a reservoir, which is transported into and through the artery wall. In this study, the behaviour of a model of a hydrophilic drug (heparin) released from a coronary stent into the arterial wall is investigated. The presence of the specific binding site action is modelled using a reversible chemical reaction that explains the prolonged presence of drug in the vascular tissue. An axi-symmetric model of a single stent strut is considered. First an advection-diffusion problem is solved using the finite element method. Then a simplified model with diffusion only in the arterial wall is compared with: (i) a model including the presence of reversible binding sites in the vascular wall and (ii) a model featuring a drug reservoir made of a degradable polymeric matrix. The results show that the inclusion of a reversible binding for the drug leads to delayed release curves and that the polymer erosion affects the drug release showing a quicker elution of the drug from the stent.     

Effects of gradual expansign on arterial stenosis

The blood flow through an arterial stenosis can theoretically be increased by gradual expansion of the stenosis. This hypothesis was tested by comparing the flow through abruptly expanding and gradually expanding stenosed plastic conduits. The conduits were tested in non-pulsatile flow with water and bank blood and in pulsatile flow in dog's descending aorta. It was found that:

1. (a)
   The pressure drop in arterial stenoses is larger than that predicted by non-pulsatile theory.     
   
   

Modelling drug elution from stents: effects of reversible binding in the vascular wall and degradable polymeric matrix

Today the most popular approach for the prevention of the restenosis consists in the use of the drug eluting stents. The stent acts as a source of drug, from a coating or from a reservoir, which is transported into and through the artery wall. In this study, the behaviour of a model of a hydrophilic drug (heparin) released from a coronary stent into the arterial wall is investigated. The presence of the specific binding site action is modelled using a reversible chemical reaction that explains the prolonged presence of drug in the vascular tissue. An axi-symmetric model of a single stent strut is considered. First an advection–diffusion problem is solved using the finite element method. Then a simplified model with diffusion only in the arterial wall is compared with: (i) a model including the presence of reversible binding sites in the vascular wall and (ii) a model featuring a drug reservoir made of a degradable polymeric matrix. The results show that the inclusion of a reversible binding for the drug leads to delayed release curves and that the polymer erosion affects the drug release showing a quicker elution of the drug from the stent.     

Computer simulation of arterial flow with applications to arterial and aortic stenoses

A computer model for simulating pressure and flow propagation in the human arterial system is developed. The model is based on the one-dimensional flow equations and includes nonlinearities arising from geometry and material properties. Fifty-five arterial segments, representing the various major arteries, are combined to form the model of the arterial system. Particular attention is paid to the development of peripheral pressure and flow pulses under normal flow conditions and under conditions of arterial and aortic stenoses. Results show that the presence of severe arterial stenoses significantly affects the nature of the distal pressure and flow pulses. Aortic stenoses also have a profound effect on central and peripheral pressure pulse formation. Comparison with the published experimental data suggests that the model is capable of simulating arterial flow under normal flow conditions as well as conditions of stenotic obstructions in a satisfactory manner.