Three-dimensional printed models as an effective tool for the management of complex congenital heart disease.

Introduction: Three-dimensional printed models are widely used in the medical field for surgical and interventional planning. In the context of complex cardiovascular defects such as pediatric congenital heart diseases (CHDs), the adoption of 3D printed models could be an effective tool to improve decision-making. In this paper, an investigation was conducted into the characteristics of 3D printed models and their added value in understanding and managing complex pediatric congenital heart disease, also considering the associated cost. Methods: Volumetric MRI and CT images of subjects with complex CHDs were retrospectively segmented, and the associated 3D models were reconstructed. Different 3D printing technologies and materials were evaluated to obtain the 3D printed models of cardiac structures. An evaluation of time and costs associated with the 3D printing procedure was also provided. A two-level 3D printed model assessment was carried out to investigate the most suitable 3D printing technology for the management of complex CHDs and the effectiveness of 3D printed models in the pre-surgical planning and surgical strategies' simulations. Results: Among the different techniques, selective laser sintering resulted to be the most suitable due to its reduced time and cost and for the positive clinical feedback (procedure simulation, surface finish, and reproduction of details). Conclusion: The adoption of 3D printed models contributes as an effective tool in the management of complex CHDs, enabling planning and simulations of surgical procedures in a safer way.

Numerical investigation on circular and elliptical bulge tests for inverse soft tissue characterization.

The acquisition of insights concerning the mechanobiology of aneurysmatic aortic tissues is an important field of investigation. The complete characterization of aneurysm mechanical behaviour can be carried out by biaxial experimental tests on ex vivo specimens. In literature, several works proposed bulge inflation tests as a valid method to analyse aneurysmatic tissue. Bulge test data processing requires the adoption of digital image correlation and inverse analysis approaches to estimate strain and stress distributions, respectively. In this context, however, the accuracy of inverse analysis method has not been evaluated yet. This aspect appears particularly interesting given the anisotropic behaviour of the soft tissue and the possibility to adopt different die geometries. The goal of this study is to provide an accuracy characterization of the inverse analysis applied to the bulge test technique using a numerical approach. In particular, different cases of bulge inflation were simulated in a finite element environment as a reference. To investigate the effect of tissue anisotropic degree and bulge die geometries (circular and elliptical), different input parameters were considered to obtain multiple test cases. The specimen deformed shapes, resulting from the reference finite element simulations, were then analysed through an inverse analysis approach to produce an estimation of stress distributions. The estimated stresses were, at last, compared with the values from the reference finite element simulations. The results demonstrated that the circular die geometry produces a satisfactory estimation accuracy only under certain conditions of material quasi-isotropy. On the other hand, the choice of an elliptical bulge die was proven to be more suitable for the analysis of anisotropic tissues.

3D Printed Model-Guided Neonatal Transcatheter Closure of Left Main Coronary Artery-to-Right Ventricle Fistula.

We report on a 2-week-old infant with huge left main coronary artery-to-right ventricular outflow tract fistula causing myocardial ischemia due to global coronary steal who was successfully submitted to percutaneous closure guided by a 3-dimensional-printed model using a duct-occluder vascular plug. (Level of Difficulty: Advanced.).

An image-based approach for the estimation of arterial local stiffness in vivo.

The analysis of mechanobiology of arterial tissues remains an important topic of research for cardiovascular pathologies evaluation. In the current state of the art, the gold standard to characterize the tissue mechanical behavior is represented by experimental tests, requiring the harvesting of ex-vivo specimens. In recent years though, image-based techniques for the in vivo estimation of arterial tissue stiffness were presented. The aim of this study is to define a new approach to provide local distribution of arterial stiffness, estimated as the linearized Young's Modulus, based on the knowledge of in vivo patient-specific imaging data. In particular, the strain and stress are estimated with sectional contour length ratios and a Laplace hypothesis/inverse engineering approach, respectively, and then used to calculate the Young's Modulus. After describing the method, this was validated by using a set of Finite Element simulations as input. In particular, idealized cylinder and elbow shapes plus a single patient-specific geometry were simulated. Different stiffness distributions were tested for the simulated patient-specific case. After the validation from Finite Element data, the method was then applied to patient-specific ECG-gated Computed Tomography data by also introducing a mesh morphing approach to map the aortic surface along the cardiac phases. The validation process revealed satisfactory results. In the simulated patient-specific case, root mean square percentage errors below 10% for the homogeneous distribution and below 20% for proximal/distal distribution of stiffness. The method was then successfully used on the three ECG-gated patient-specific cases. The resulting distributions of stiffness exhibited significant heterogeneity, nevertheless the resulting Young's moduli were always contained within the 1-3 MPa range, which is in line with literature.

HPC+ in the medical field: Overview and current examples.

BACKGROUND: To say data is revolutionising the medical sector would be a vast understatement. The amount of medical data available today is unprecedented and has the potential to enable to date unseen forms of healthcare. To process this huge amount of data, an equally huge amount of computing power is required, which cannot be provided by regular desktop computers. These areas can be (and already are) supported by High-Performance-Computing (HPC), High-Performance Data Analytics (HPDA), and AI (together "HPC+"). OBJECTIVE: This overview article aims to show state-of-the-art examples of studies supported by the National Competence Centres (NCCs) in HPC+ within the EuroCC project, employing HPC, HPDA and AI for medical applications. METHOD: The included studies on different applications of HPC in the medical sector were sourced from the National Competence Centres in HPC and compiled into an overview article. Methods include the application of HPC+ for medical image processing, high-performance medical and pharmaceutical data analytics, an application for pediatric dosimetry, and a cloud-based HPC platform to support systemic pulmonary shunting procedures. RESULTS: This article showcases state-of-the-art applications and large-scale data analytics in the medical sector employing HPC+ within surgery, medical image processing in diagnostics, nutritional support of patients in hospitals, treating congenital heart diseases in children, and within basic research. CONCLUSION: HPC+ support scientific fields from research to industrial applications in the medical area, enabling researchers to run faster and more complex calculations, simulations and data analyses for the direct benefit of patients, doctors, clinicians and as an accelerator for medical research.

A Hybrid Mock Circulatory Loop for Fluid Dynamic Characterization of 3D Anatomical Phantoms.

GOAL: This work presents the development of a Hybrid Mock Circulatory Loop (HMCL) to simulate hemodynamics at patient-specific level in terms of both 3D geometry and inlet/outlet boundary conditions. METHODS: Clinical data have been processed to define the morphological and functional patient-specific settings. A piston pump is used to impose a parametric flow rate profile at the inlet of the hemodynamic circuit. In order to guarantee the physiological pressure and flow conditions, a specific hybrid chamber system including a real-time control has been designed and implemented. The developed system was validated firstly in a single outlet branch model and, secondly, on a 3D printed patient-specific multi-branch phantom. Finally, for the 3D phantom, the outlet flow profiles were compared with the corresponding in-vivo flow data. RESULTS: Results showed that the root mean squared error between the prescribed setpoint and the measured pressures was always below 3 mmHg (about 2.5%) for all cases. The obtained flow profiles for the patient-specific model were in agreement with the related functional in-vivo data. SIGNIFICANCE: The capability to reproduce physiological hemodynamics condition, with high-fidelity, plays a significant role in the cardiovascular research. The developed platform can be used to assess the performances of cardiovascular devices, to validate numerical simulations, and to test imaging systems.

High-Versatility Left Ventricle Pump and Aortic Mock Circulatory Loop Development for Patient-Specific Hemodynamic In Vitro Analysis.

The importance of experimental setups able to reproduce cardiac functions was well established in the field of clinical innovations. The mock circulatory loops acquired rising relevance, and the possibility to have a complete reproduction of different and specific fluid dynamic conditions within the setup is pivotal. A system with enough versatility to reproduce the physiologic range of both flows and pressures is required. This study describes the design of a versatile setup composed by a custom pulsatile left ventricular pump system and a 3D-printed mock circulatory loop for the in vitro analysis of a patient-specific case of an aortic complex. The performances of the pump were validated first with a set of test flow profiles. It was demonstrated that the system was able to cover a wide range of aortic and mitral flows. Second, the pump system was inserted within the full mock circulatory loop. A patient-specific case was reproduced, both in terms of flow and pressure profiles. A successful validation of the flow and pressure waveforms was obtained by using patient-specific in vivo data from magnetic resonance analysis.

Fully-Coupled FSI Computational Analyses in the Ascending Thoracic Aorta Using Patient-Specific Conditions and Anisotropic Material Properties.

Computational hemodynamics has become increasingly important within the context of precision medicine, providing major insight in cardiovascular pathologies. However, finding appropriate compromise between speed and accuracy remains challenging in computational hemodynamics for an extensive use in decision making. For example, in the ascending thoracic aorta, interactions between the blood and the aortic wall must be taken into account for the sake of accuracy, but these fluid structure interactions (FSI) induce significant computational costs, especially when the tissue exhibits a hyperelastic and anisotropic response. The objective of the current study is to use the Small On Large (SOL) theory to linearize the anisotropic hyperelastic behavior in order to propose a reduced-order model for FSI simulations of the aorta. The SOL method is tested for fully-coupled FSI simulations in a patient-specific aortic geometry presenting an Ascending Thoracic Aortic Aneurysm (aTAA). The same model is also simulated with a fully-coupled FSI with non-linear material behavior, without SOL linearization. Eventually, the results and computational times with and without the SOL are compared. The SOL approach is demonstrated to provide a significant reduction of computational costs for FSI analysis in the aTAA, and the results in terms of stress state distribution are comparable. The method is implemented in ANSYS and will be further evaluated for clinical applications.

3D Printing in Modern Cardiology.

BACKGROUND: 3D printing represents an emerging technology in the field of cardiovascular medicine. 3D printing can help to perform a better analysis of complex anatomies to optimize intervention planning. METHODS: A systematic review was performed to illustrate the 3D printing technology and to describe the workflow to obtain 3D printed models from patient-specific images. Examples from our laboratory of the benefit of 3D printing in planning interventions were also reported. RESULTS: 3D printing technique is reliable when applied to high-quality 3D image data (CTA, CMR, 3D echography), but it still needs the involvement of expert operators for image segmentation and mesh refinement. 3D printed models could be useful in interventional planning, although prospective studies with comprehensive and clinically meaningful endpoints are required to demonstrate the clinical utility. CONCLUSION: 3D printing can be used to improve anatomy understanding and surgical planning.

On the Role and Effects of Uncertainties in Cardiovascular in silico Analyses.

The assessment of cardiovascular hemodynamics with computational techniques is establishing its fundamental contribution within the world of modern clinics. Great research interest was focused on the aortic vessel. The study of aortic flow, pressure, and stresses is at the basis of the understanding of complex pathologies such as aneurysms. Nevertheless, the computational approaches are still affected by sources of errors and uncertainties. These phenomena occur at different levels of the computational analysis, and they also strongly depend on the type of approach adopted. With the current study, the effect of error sources was characterized for an aortic case. In particular, the geometry of a patient-specific aorta structure was segmented at different phases of a cardiac cycle to be adopted in a computational analysis. Different levels of surface smoothing were imposed to define their influence on the numerical results. After this, three different simulation methods were imposed on the same geometry: a rigid wall computational fluid dynamics (CFD), a moving-wall CFD based on radial basis functions (RBF) CFD, and a fluid-structure interaction (FSI) simulation. The differences of the implemented methods were defined in terms of wall shear stress (WSS) analysis. In particular, for all the cases reported, the systolic WSS and the time-averaged WSS (TAWSS) were defined.

Correlation between micro and macrostructural biaxial behavior of ascending thoracic aneurysm: a novel experimental technique.

Mechanical properties and microstructural modifications of vessel tissues are strongly linked, as established in the state of the art of cardiovascular diseases. Techniques to obtain both mechanical and structural information are reported, but the possibility to obtain real-time microstructural and macrostructural data correlated is still lacking. An experimental approach to characterize the aortic tissue is presented. A setup integrating biaxial traction and Small Angle Light Scattering (SALS) analysis is described. The system was adopted to test ex-vivo aorta specimens from healthy and aneusymatic (aTAA) cases. A significant variation of the fiber dispersion with respect to the unloaded state was encountered during the material traction. The corresponding microstructural and mechanical data were successfully used to fit a given anisotropic constitutive model, with satisfactory R2 values (0.97±0.11 and 0.96±0.17, for aTAA and healthy population, respectively) and fiber dispersion parameters variations between the aTAA and healthy populations (0.39±0.23 and 0.15±0.10). The method integrating the biaxial/SALS technique was validated, allowing for real-time synchronization between mechanical and microstructural analysis of anisotropic biological tissues.

Design, simulation, and fabrication of a three-dimensional printed pump mimicking the left ventricle motion.

The development of accurate replicas of the circulatory and cardiac system is fundamental for a deeper understanding of cardiovascular diseases and the testing of new devices. Although numerous works concerning mock circulatory loops are present in the current state of the art, still some limitations are present. In particular, a pumping system able to reproduce the left ventricle motion and completely compatible with the magnetic resonance environment to permit the four-dimensional flow monitoring is still missing. The aim of this work was to evaluate the feasibility of an actuator suitable for cardiovascular mock circuits. Particular attention was given to the ability to mimic the left ventricle dynamics including both compression and twisting with the magnetic resonance compatibility. In our study, a left ventricle model to be actuated through vacuum was designed. The realization of the system was evaluated with finite element analysis of different design solutions. After the in silico evaluation phase, the most suitable design in terms of physiological values reproduction was fabricated through three-dimensional printing for in vitro validation. A pneumatic experimental setup was developed to evaluate the pump performances in terms of actuation, in particular ventricle radial and longitudinal displacement, twist rotation, and ejection fraction. The study demonstrated the feasibility of a custom pneumatic pump for mock circulatory loops able to reproduce the physiological ventricle movement and completely suitable for the magnetic resonance environment.

Computational Fluid Dynamic Study for aTAA Hemodynamics: An Integrated Image-Based and Radial Basis Functions Mesh Morphing Approach.

We present a novel framework for the fluid dynamics analysis of healthy subjects and patients affected by ascending thoracic aorta aneurysm (aTAA). Our aim is to obtain indications about the effect of a bulge on the hemodynamic environment at different enlargements. Three-dimensional (3D) surface models defined from healthy subjects and patients with aTAA, selected for surgical repair, were generated. A representative shape model for both healthy and pathological groups has been identified. A morphing technique based on radial basis functions (RBF) was applied to mold the shape relative to healthy patient into the representative shape of aTAA dataset to enable the parametric simulation of the aTAA formation. Computational fluid dynamics (CFD) simulations were performed by means of a finite volume solver using the mean boundary conditions obtained from three-dimensional (PC-MRI) acquisition. Blood flow helicity and flow descriptors were assessed for all the investigated models. The feasibility of the proposed integrated approach pertaining the coupling between an RBF morphing technique and CFD simulation for aTAA was demonstrated. Significant hemodynamic changes appear at the 60% of the bulge progression. An impingement of the flow toward the bulge was observed by analyzing the normalized flow eccentricity (NFE) index.