Raoul Hopf

Simulation of transcatheter aortic valve implantation under consideration of leaflet calcification

Transcatheter aortic valve implantation (TAVI) is a minimally invasive off-pump procedure to replace diseased aortic heart valves. Known complications include paravalvular leaks, atrioventricular blocks, coronary obstruction and annular rupture. Careful procedure planning including appropriate stent selection and sizing are crucial. Few patient-specific geometric parameters, like annular diameters, annular perimeter and measurement of the distance to the coronary ostia, are currently used within this process. Biomechanical simulation allows the consideration of extracted anatomy and material parameters for the intervention, which may improve planning and execution phases. We present a simulation workflow using a fully segmented aortic root anatomy, which was extracted from pre-operative CT-scan data and apply individual material models and parameters to predict the procedure outcome. Our results indicate the high relevance of calcification location and size for intervention planning, which are not sufficiently considered at this time. Our analysis can further provide guidance for accurate, patient-specific device positioning and future adaptations to stent design.

Experimental and theoretical analyses of the age-dependent large-strain behavior of Sylgard 184 (10:1) silicone elastomer.

The commercial polydimethysiloxane elastomer Sylgard(®) 184 with mixing ratio 10:1 is in wide use for biomedical research or fundamental studies of mechanobiology. In this paper, a comprehensive study of the large strain mechanical behavior of this material under multiaxial monotonic and cyclic loads, and its change during the first 26 days after preparation is reported. The equibiaxial stress response studied in inflation experiments reveals a much stiffer and more nonlinear response compared to the uniaxial and pure shear characteristics. The polymer revealed remarkably elastic behavior, in particular, very little dependence on strain rates between 0.3%/s and 11%/s, and on the strain history in cyclic experiments. On the other hand, both the small-strain and large strain nonlinear mechanical characteristics of the elastomer are changing with sample age and the results suggest that this process has not ceased after 26 days. A recent re-interpretation of the well-known Ogden model for incompressible rubber-like materials was applied to rationalize the results and accurate agreement was obtained with the experimental data over all testing configurations and testing times. The change of a single parameter in this model is shown to govern the evolution of the nonlinear material characteristics with sample age, attributed to a continuation of the cross-linking process. Based on a kinetic relation to account for this process over time, the model provided successful predictions of the material behavior even after more than one year.

Image-Based Mechanical Analysis of Stent Deformation: Concept and Exemplary Implementation for Aortic Valve Stents

An approach for extracting the radial force load on an implanted stent from medical images is proposed. To exemplify the approach, a system is presented which computes a radial force estimation from computer tomography images acquired from patients who underwent transcatheter aortic valve implantation (TAVI). The deformed shape of the implanted valve prosthesis Nitinol frame is extracted from the images. A set of displacement vectors is computed that parameterizes the observed deformation. An iterative relaxation algorithm is employed to adapt the information extracted from the images to a finite-element model of the stent, and the radial components of the interaction forces between the stent and the tissue are extracted. For the evaluation of the method, tests were run using the clinical data from 21 patients. Stent modeling and extraction of the radial forces were successful in 18 cases. Synthetic test cases were generated, in addition, for assessing the sensitivity to the measurement errors. In a sensitivity analysis, the geometric error of the stent reconstruction was below 0.3 mm, which is below the image resolution. The distribution of the radial forces was qualitatively and quantitatively reasonable. An uncertainty remains in the quantitative evaluation of the radial forces due to the uncertainty in defining a radial direction on the deformed stent. With our approach, the mechanical situation of TAVI stents after the implantation can be studied in vivo, which may help to understand the mechanisms that lead to the complications and improve stent design.

A discrete network model to represent the deformation behavior of human amnion.

A discrete network model (DNM) to represent the mechanical behavior of the human amnion is proposed. The amnion is modeled as randomly distributed points interconnected with connector elements representing collagen crosslinks and fiber segments, respectively. This DNM is computationally efficient and allows simulations with large domains. A representative set of parameters has been selected to reproduce the uniaxial tension-stretch and kinematic responses of the amnion. Good agreement is found between the predicted and measured equibiaxial tension-stretch curves. Although the model represents the amnion phenomenologically, model parameters are physically motivated and their effect on the tension-stretch and in-plane kinematic responses is discussed. The model is used to investigate the local response in the near field of a circular hole, revealing that the kinematic response at the circular free boundaries leads to compaction and strong alignment of the network at the border of the defect.

Stent Maps — Comparative Visualization for the Prediction of Adverse Events of Transcatheter Aortic Valve Implantations

Transcatheter aortic valve implantation (TAVI) is a minimally-invasive method for the treatment of aortic valve stenosis in patients with high surgical risk. Despite the success of TAVI, side effects such as paravalvular leakages can occur postoperatively. The goal of this project is to quantitatively analyze the co-occurrence of this complication and several potential risk factors such as stent shape after implantation, implantation height, amount and distribution of calcifications, and contact forces between stent and surrounding structure. In this paper, we present a two-dimensional visualization (stent maps), which allows (1) to comprehensively display all these aspects from CT data and mechanical simulation results and (2) to compare different datasets to identify patterns that are typical for adverse effects. The area of a stent map represents the surface area of the implanted stent - virtually straightened and uncoiled. Several properties of interest, like radial forces or stent compression, are displayed in this stent map in a heatmap-like fashion. Important anatomical landmarks and calcifications are plotted to show their spatial relation to the stent and possible correlations with the color-coded parameters. To provide comparability, the maps of different patient datasets are spatially adjusted according to a corresponding anatomical landmark. Also, stent maps summarizing the characteristics of different populations (e.g. with or without side effects) can be generated. Up to this point several interesting patterns have been observed with our technique, which remained hidden when examining the raw CT data or 3D visualizations of the same data. One example are obvious radial force maxima between the right and non-coronary valve leaflet occurring mainly in cases without leakages. These observations confirm the usefulness of our approach and give starting points for new hypotheses and further analyses. Because of its reduced dimensionality, the stent map data is an appropriate input for statistical group evaluation and machine learning methods.

Buckled Thin-Film Transistors and Circuits on Soft Elastomers for Stretchable Electronics

Although recent progress in the field of flexible electronics has allowed the realization of biocompatible and conformable electronics, systematic approaches which combine high bendability (<3 mm bending radius), high stretchability (>3-4%), and low complexity in the fabrication process are still missing. Here, we show a technique to induce randomly oriented and customized wrinkles on the surface of a biocompatible elastomeric substrate, where Thin-Film Transistors (TFTs) and circuits (inverter and logic NAND gates) based on amorphous-IGZO are fabricated. By tuning the wavelength and the amplitude of the wrinkles, the devices are fully operational while bent to 13 μm bending radii as well as while stretched up to 5%, keeping unchanged electrical properties. Moreover, a flexible rectifier is also realized, showing no degradation in the performances while flat or wrapped on an artificial human wrist. As proof of concept, transparent TFTs are also fabricated, presenting comparable electrical performances to the nontransparent ones. The extension of the buckling approach from our TFTs to circuits demonstrates the scalability of the process, prospecting applications in wireless stretchable electronics to be worn or implanted.

Postoperative analysis of the mechanical interaction between stent and host tissue in patients after transcatheter aortic valve implantation

The analysis is based on a finite element procedure to extract the contact forces between an implanted Nitinol stent and the surrounding host tissue using postoperative CT images. The methodology was applied for patients (N=46) which have undergone a TAVI procedure with the Medtronic CoreValve Revalving System (MCRS) to obtain corresponding deformation and force maps. The postoperative CT data were recorded for each patient in both systolic and diastolic phase of the heart cycle. Scalar parameters were defined, which map deformed geometry and contact force field to mechanically relevant quantities: radial dilatation, radial shape distortion, non-convex points, mean force, a force deviation measure and a pressure equivalent. The latter demonstrates that in the area of the aortic root, the added circumferential loading is of the same order as the baseline average blood pressure, thus leading to a doubling of the local mechanical load. Generally the force distribution along the stent is non-homogeneous. A comparison of systolic and diastolic data revealed slightly higher contact forces during the diastole, indicating that the stent has to carry more load in this phase. The geometrical and mechanical parameters were compared for two types of clinical complication: para-valvular leakage (PVL) and permanent pacemaker requirement (PPM). It was found that an increase in mean force can be associated with both complications; significantly for PVL and as a trend for PPM.

The mechanical fingerprint of murine excisional wounds

A multiscale mechanics approach to the characterization of murine excisional wounds subjected to uniaxial tensile loading is presented. Local strain analysis at a physiological level of tension uncovers the presence of two distinct regions within the wound: i) a very compliant peripheral cushion and ii) a core area undergoing modest deformation. Microstructural visualizations of stretched wound specimens show negligible engagement of the collagen located in the center of a 7-day old wound; fibers remain coiled despite the applied tension, confirming the existence of a mechanically isolated wound core. The compliant cushion located at the wound periphery appears to protect the newly-formed tissue from excessive deformation during the phase of new tissue formation. The early remodeling phase (day 14) is characterized by a restored mechanical connection between far field and wound center. The latter remains less deformable, a characteristic possibly required for cell activities during tissue remodeling. The distribution of fibrillary collagens at these two time points corresponds well to the identified heterogeneity of mechanical properties of the wound region. This novel approach provides new insight into the mechanical properties of wounded skin and will be applicable to the analysis of compound-treated wounds or wounds in genetically modified tissue.nnnSTATEMENT OF SIGNIFICANCEnBiophysical characterization of healing wounds is crucial to assess the recovery of the skin barrier function and the associated mechanobiological processes. For the first time, we performed highly resolved local deformation analysis to identify mechanical characteristics of the wound and its periphery. Our results reveal the presence of a compliant cushion surrounding a stiffer wound core; we refer to this heterogeneous mechanical behavior as mechanical fingerprint of the wound. The mechanical response is shown to progress towards that of the intact skin as healing takes place. Histology and multiphoton microscopy suggest that wounded skin recovers its mechanical function via progressive reconnection of the newly-deposited collagen fibers with the surrounding intact matrix.

A novel ultra-light suction device for mechanical characterization of skin

Suction experiments have been extensively applied for skin characterization. In these tests the deformation behavior of superficial tissue layers determines the elevation of the skin surface observed when a predefined negative (suction) pressure history is applied. The ability of such measurements to differentiate between skin conditions is limited by the variability of the elevation response observed in repeated experiments. The scatter was shown to be associated with the force exerted by the observer when holding the instrument against the skin. We have developed a novel suction device and a measurement procedure aiming at a tighter control of mechanical boundary conditions during the experiments. The new device weighs only 3.5 g and thus allows to minimize the force applied on the skin during the test. In this way, it is possible to reliably characterize the mechanical response of skin, also in case of low values of suction pressure and deformation. The influence of the contact force is analyzed through experiments on skin and synthetic materials, and rationalized based on corresponding finite element calculations. A comparative study, involving measurements on four body locations in two subjects by three observers, showed the good performance of the new procedure, specific advantages, and limitations with respect to the Cutometer®, i.e. the suction device most widely applied for skin characterization. As a byproduct of the present investigation, a correction procedure is proposed for the Cutometer measurements, which allows to partially compensate for the influence of the contact force. The characteristics of the new suction method are discussed in view of future applications for diagnostic purposes.

Computational Stent Placement in Transcatheter Aortic Valve Implantation

Transcatheter aortic valve implantation (TAVI) is a minimally invasive procedure to treat severe aortic stenosis in patients with a high risk for conventional surgery. In-silico experiments of stent deployment within patient-specific models of the aortic root have created an opportunity to predict stent behavior during the intervention. Current limitations in procedure planning are a primary motivator for these simulations. The virtual stent placement preceding the deployment phase of such experiments has major influence on the outcome of the simulation, but only received little attention in literature up to now. This work presents a methodical approach to patient-specific planning of placement of self-expanding stent models by analyzing experimental outcomes of different sets of boundary conditions constraining the stent. As a results, different paradigms for automated or expert guided stent placement are evaluated, which demonstrate the benefits of virtual stent deployment for intervention planning. To build a predictive planning pipeline for TAVI we use an automatic segmentation of the aorta, aortic root and left ventricle, which is converted to a finite element mesh. The virtual stent is then placed along a guide wire model and deployed at multiple locations around the aortic root. The simulation has been evaluated using pre- and post-interventional CT scans with an average relative circumferential error of 4.0% (±2.5%), which is less than half of the average difference in circumference between individual stent sizes (8.6%). Our methods are therefore enabling patient-specific planning and provide better guidance during the intervention.