An in silico trials platform for the evaluation of effect of the arterial anatomy configuration on stent implantation.

The introduction of Bioresorbable Vascular Scaffolds (BVS) has revolutionized the treatment of atherosclerosis. InSilc is an in silico clinical trial (ISCT) platform in a Cloud-based environment used for the design, development and evaluation of BVS. Advanced multi-disciplinary and multiscale models are integrated in the platform towards predicting the short/acute and medium/long term scaffold performance. In this study, InSilc platform is employed in a use case scenario and demonstrates how the whole in silico pipeline allows the interpretation of the effect of the arterial anatomy configuration on stent implantation.

A Computational Fluid Dynamics Study of the Extracorporeal Membrane Oxygenation-Failing Heart Circulation.

Extracorporeal membrane oxygenation (ECMO) is increasingly deployed to provide percutaneous mechanical circulatory support despite incomplete understanding of its complex interactions with the failing heart and its effects on hemodynamics and perfusion. Using an idealized geometry of the aorta and its major branches and a peripherally inserted return cannula terminating in the iliac artery, computational fluid dynamic simulations were performed to (1) quantify perfusion as function of relative ECMO flow and (2) describe the watershed region produced by the collision of antegrade flow from the heart and retrograde ECMO flow. To simulate varying degrees of cardiac failure, ECMO flow as a fraction of systemic perfusion was evaluated at 100%, 90%, 75%, and 50% of total flow with the remainder supplied by the heart calculated from a patient-derived flow waveform. Dynamic boundary conditions were generated with a three-element lumped parameter model to accurately simulate distal perfusion. In profound failure (ECMO providing 90% or more of flow), the watershed region was positioned in the aortic arch with minimal pulsatility observed in the flow to the visceral organs. Modest increases in cardiac flow advanced the watershed region into the thoracic aorta with arch perfusion entirely supplied by the heart.

Multimodal Loading Environment Predicts Bioresorbable Vascular Scaffolds' Durability.

Bioresorbable vascular scaffolds were considered the fourth generation of endovascular implants deemed to revolutionize cardiovascular interventions. Yet, unexpected high risk of scaffold thrombosis and post-procedural myocardial infractions quenched the early enthusiasm and highlighted the gap between benchtop predictions and clinical observations. To better understand scaffold behavior in the mechanical environment of vessels, animal, and benchtop tests with multimodal loading environment were conducted using industrial standard scaffolds. Finite element analysis was also performed to study the relationship among structural failure, scaffold design, and load types. We identified that applying the combination of bending, axial compression, and torsion better reflects incidence observed in-vivo, far more than tranditional single mode loads. Predication of fracture locations is also more accurate when at least bending and axial compression are applied during benchtop tests (>60% fractures at connected peak). These structural failures may be initiated by implantation-induced microstructural damages and worsened by cyclic loads from the beating heart. Ignoring the multi-modal loading environment in benchtop fatigue tests and computational platforms can lead to undetected potential design defects, calling for redefining consensus evaluation strategies for scaffold performance. With the robust evaluation strategy presented herein, which exploits the results of in-vivo, in-vitro and in-silico investigations, we may be able to compare alternative designs of prototypes at the early stages of device development and optimize the performance of endovascular implants according to patients-specific vessel dynamics and lesion configurations in the future.

Design and implementation of in silico clinical trial for Bioresorbable Vascular Scaffolds.

In the recent years, Bioresorbable Vascular Scaffolds (BVS) for the treatment of atherosclerosis have been introduced. InSilc is a cloud based in silico clinical trial (ISCT) platform for drug-eluting BVS. The platform integrates multidisciplinary and multiscale models predicting the BVS performance. In this study, we present a use case scenario and demonstrate the functioning of the individual modules and of the whole pipeline and the ability to predict BVS short, medium, long-term outcomes.

Hemodynamic consequences of a multilayer flow modulator in aortic dissection.

Aortic dissections are challenging for it remains perplexing to determine when surgical, endovascular, or medical therapies are optimal. We studied the effect of the multilayer flow modulator (MFM) device in patients with different forms of type-B aortic dissections. CT scans were performed pre-, immediately post-MFM implantation, and multiple times within a 24-month follow-up. Three-dimensional reconstructions were created from these scans and the multilayer or single-layer mesh device placed virtually into the true lumen. We observed that MFM device can sufficiently restore flow perfusion, reduce the false lumen, eliminate local flow recirculation, and reduce wall shear stress distribution globally. Single-layer devices can reduce false lumen dimensions; however, they generate local disturbance and recirculation zones in selected areas at specific time points. Moreover, in polar extremes of dissection, the MFM device restored flow to vital organs perfusing vessels independent of effects on luminal patency. Management of aortic dissections should focus on modulation of blood flow, suppression of local recirculation, and restoration of vital organ perfusion rather than primarily restoring vascular lumen morphology. While the latter restores the geometry of the true lumen, only the former restores homeostasis. Graphical abstract.

A Mechanical Approach for Smooth Surface Fitting to Delineate Vessel Walls in Optical Coherence Tomography Images.

Automated analysis of vascular imaging techniques is limited by the inability to precisely determine arterial borders. Intravascular optical coherence tomography (OCT) offers unprecedented detail of artery wall structure and composition, but does not provide consistent visibility of the outer border of the vessel due to the limited penetration depth. Existing interpolation and surface fitting methods prove insufficient to accurately fill the gaps between the irregularly spaced and sometimes unreliably identified visible segments of the vessel outer border. This paper describes an intuitive, efficient, and flexible new method of 3D surface fitting and smoothing suitable for this task. An anisotropic linear-elastic mesh is fit to irregularly spaced and uncertain data points corresponding to visible segments of vessel borders, enabling the fully automated delineation of the entire inner and outer borders of diseased vessels in OCT images for the first time. In a clinical dataset, the proposed smooth surface fitting approach had great agreement when compared with human annotations: areas differed by just 11 ± 11% (0.93 ± 0.84 mm2), with a coefficient of determination of 0.89. Overlapping and non-overlapping area ratios were 0.91 and 0.18, respectively, with a sensitivity of 90.8 and specificity of 99.0. This spring mesh method of contour fitting significantly outperformed all alternative surface fitting and interpolation approaches tested. The application of this promising proposed method is expected to enhance clinical intervention and translational research using OCT.

Position Paper Computational Cardiology.

Computational cardiology is the scientific field devoted to the development of methodologies that enhance our mechanistic understanding, diagnosis and treatment of cardiovascular disease. In this regard, the field embraces the extraordinary pace of discovery in imaging, computational modeling, and cardiovascular informatics at the intersection of atherogenesis and vascular biology. This paper highlights existing methods, practices, and computational models and proposes new strategies to support a multidisciplinary effort in this space. We focus on the means by that to leverage and coalesce these multiple disciplines to advance translational science and computational cardiology. Analyzing the scientific trends and understanding the current needs we present our perspective for the future of cardiovascular treatment.

Effect of working environment and procedural strategies on mechanical performance of bioresorbable vascular scaffolds.

Polymeric bioresorbable scaffolds (BRS), at their early stages of invention, were considered as a promising revolution in interventional cardiology. However, they failed dramatically compared to metal stents showing substantially higher incidence of device failure and clinical events, especially thrombosis. One problem is that use of paradigms inherited from metal stents ignores dependency of polymer material properties on working environment and manufacturing/deployment steps. Unlike metals, polymeric material characterization experiments cannot be considered identical under dry and submerged conditions at varying rates of operation. We demonstrated different material behaviors associated with variable testing environment and parameters. We, then, have employed extracted material models, which are verified by computational methods, to assess the performance of a full-scale BRS in different working condition and under varying procedural strategies. Our results confirm the accepted notion that slower rate of crimping and inflation can potentially reduce stress concentrations and thus reduce localized damages. However, we reveal that using a universal set of material properties derived from a benchtop experiment conducted regardless of working environment and procedural variability may lead to a significant error in estimation of stress-induced damages and overestimation of benefits procedural updates might offer. We conclude that, for polymeric devices, microstructural damages and localized loss of structural integrity should complement former macroscopic performance-assessment measures (fracture and recoil). Though, to precisely capture localized stress concentration and microstructural damages, context-related testing environment and clinically-relevant procedural scenarios should be devised in preliminary experiments of polymeric resorbable devices to enhance their efficacy and avoid unpredicted clinical events. STATEMENT OF SIGNIFICANCE: Bioresorbable scaffolds (BRS) with the hope to become the next cardiovascular interventional revolution failed in comparison to metal stents. When BRS were characterized using methods for metal stents, designers were misled to seek problem sources at erroneous timeframe and use inefficient indicators, and thus no signal of concern emerged. We demonstrated fundamental flaws associated with applying a universal set of material properties to study device performances in different phases of manufacturing/implantation, and these may be responsible for failure in predicting performance in first-generation BRS. We introduced new criterion for the assessment of structural integrity and device efficacy in next-generation BRS, and indeed all devices using polymeric materials which evolve with the environment they reside in.

Optimized Computer-Aided Segmentation and Three-Dimensional Reconstruction Using Intracoronary Optical Coherence Tomography.

We present a novel and time-efficient method for intracoronary lumen detection, which produces three-dimensional (3-D) coronary arteries using optical coherence tomographic (OCT) images. OCT images are acquired for multiple patients and longitudinal cross-section (LOCS) images are reconstructed using different acquisition angles. The lumen contours for each LOCS image are extracted and translated to 2-D cross-sectional images. Using two angiographic projections, the centerline of the coronary vessel is reconstructed in 3-D, and the detected 2-D contours are transformed to 3-D and placed perpendicular to the centerline. To validate the proposed method, 613 manual annotations from medical experts were used as gold standard. The 2-D detected contours were compared with the annotated contours, and the 3-D reconstructed models produced using the detected contours were compared to the models produced by the annotated contours. Wall shear stress (WSS), as dominant hemodynamics factor, was calculated using computational fluid dynamics and 844 consecutive 2-mm segments of the 3-D models were extracted and compared with each other. High Pearson's correlation coefficients were obtained for the lumen area (r = 0.98) and local WSS (r = 0.97) measurements, while no significant bias with good limits of agreement was shown in the Bland-Altman analysis. The overlapping and nonoverlapping areas ratio between experts' annotations and presented method was 0.92 and 0.14, respectively. The proposed computer-aided lumen extraction and 3-D vessel reconstruction method is fast, accurate, and likely to assist in a number of research and clinical applications.

Nitinol Stent Oversizing in Patients Undergoing Popliteal Artery Revascularization: A Finite Element Study.

Nitinol stent oversizing is frequently performed in peripheral arteries to ensure a desirable lumen gain. However, the clinical effect of mis-sizing remains controversial. The goal of this study was to provide a better understanding of the structural and hemodynamic effects of Nitinol stent oversizing. Five patient-specific numerical models of non-calcified popliteal arteries were developed to simulate the deployment of Nitinol stents with oversizing ratios ranging from 1.1 to 1.8. In addition to arterial biomechanics, computational fluid dynamics methods were adopted to simulate the physiological blood flow inside the stented arteries. Results showed that stent oversizing led to a limited increase in the acute lumen gain, albeit at the cost of a significant increase in arterial wall stresses. Furthermore, localized areas affected by low Wall Shear Stress increased with higher oversizing ratios. Stents were also negatively impacted by the procedure as their fatigue safety factors gradually decreased with oversizing. These adverse effects to both the artery walls and stents may create circumstances for restenosis. Although the ideal oversizing ratio is stent-specific, this study showed that Nitinol stent oversizing has a very small impact on the immediate lumen gain, which contradicts the clinical motivations of the procedure.