Trends in biomedical engineering: focus on Patient Specific Modeling and Life Support Systems.

Over the last twenty years major advancements have taken place in the design of medical devices and personalized therapies. They have paralleled the impressive evolution of three-dimensional, non invasive, medical imaging techniques and have been continuously fuelled by increasing computing power and the emergence of novel and sophisticated software tools. This paper aims to showcase a number of major contributions to the advancements of modeling of surgical and interventional procedures and to the design of life support systems. The selected examples will span from pediatric cardiac surgery procedures to valve and ventricle repair techniques, from stent design and endovascular procedures to life support systems and innovative ventilation techniques.

Mitral valve finite element modeling: implications of tissues' nonlinear response and annular motion.

Finite element modeling represents an established method for the comprehension of the mitral function and for the simulation of interesting clinical scenarios. However, current models still do not include all the key aspects of the real system. We implemented a new structural finite element model that considers (i) an accurate morphological description of the valve, (ii) a description of the tissues' mechanical properties that accounts for anisotropy and nonlinearity, and (iii) dynamic boundary conditions that mimic annulus and papillary muscles' contraction. The influence of such contraction on valve biomechanics was assessed by comparing the computed results with the ones obtained through an auxiliary model with fixed annulus and papillary muscles. At the systolic peak, the leaflets' maximum principal stress contour showed peak values in the anterior leaflet at the strut chordae insertion zone (300 kPa) and near the annulus (200-250 kPa), while much lower values were detected in the posterior leaflet. Both leaflets underwent larger tensile strains in the longitudinal direction, while in the circumferential one the anterior leaflet experienced nominal tensile strains up to 18% and the posterior one experienced compressive strains up to 23% associated with the folding of commissures and paracommissures, consistently with tissue redundancy. The force exerted by papillary muscles at the systolic peak was equal to 4.11 N, mainly borne by marginal chordae (76% of the force). Local reaction forces up to 45 mN were calculated on the annulus, leading to tensions of 89 N/m and 54 N/m for its anterior and posterior tracts, respectively. The comparison with the results of the auxiliary model showed that annular contraction mainly affects the leaflets' circumferential strains. When it was suppressed, no more compressive strains could be observed and peak strain values were located in the belly of the anterior leaflet. Computational results agree to a great extent with experimental data from literature. They provided insight into some of the features characterizing normal mitral function, such as annular contraction and leaflets' tissue anisotropy and nonlinearity. Some of the computed results may be useful in the design of surgical devices and techniques. In particular, forces applied on the annulus by the surrounding tissues could be considered as an indication for annular prostheses design.

Computational evaluation of the thrombogenic potential of a hollow-fiber oxygenator with integrated heat exchanger during extracorporeal circulation.

The onset of thromboembolic phenomena in blood oxygenators, even in the presence of adequate anticoagulant strategies, is a relevant concern during extracorporeal circulation (ECC). For this reason, the evaluation of the thrombogenic potential associated with extracorporeal membrane oxygenators should play a critical role into the preclinical design process of these devices. This study extends the use of computational fluid dynamics simulations to guide the hemodynamic design optimization of oxygenators and evaluate their thrombogenic potential during ECC. The computational analysis accounted for both macro- (i.e., vortex formation) and micro-scale (i.e., flow-induced platelet activation) phenomena affecting the performances of a hollow-fiber membrane oxygenator with integrated heat exchanger. A multiscale Lagrangian approach was adopted to infer the trajectory and loading history experienced by platelet-like particles in the entire device and in a repetitive subunit of the fiber bundles. The loading history was incorporated into a damage accumulation model in order to estimate the platelet activation state (PAS) associated with repeated passes of the blood within the device. Our results highlighted the presence of blood stagnation areas in the inlet section that significantly increased the platelet activation levels in particles remaining trapped in this region. The order of magnitude of PAS in the device was the same as the one calculated for the components of the ECC tubing system, chosen as a term of comparison for their extensive diffusion. Interpolating the mean PAS values with respect to the number of passes, we obtained a straightforward prediction of the thrombogenic potential as a function of the duration of ECC.

Is it possible to assess the best mitral valve repair in the individual patient? Preliminary results of a finite element study from magnetic resonance imaging data.

OBJECTIVES: Finite element modeling was adopted to quantitatively compare, for the first time and on a patient-specific basis, the biomechanical effects of a broad spectrum of different neochordal implantation techniques for the repair of isolated posterior mitral leaflet prolapse. METHODS: Cardiac magnetic resonance images were acquired from 4 patients undergoing surgery. A patient-specific 3-dimensional model of the mitral apparatus and the motion of the annulus and papillary muscles were reconstructed. The location and extent of the prolapsing region were confirmed by intraoperative findings, and the mechanical properties of the mitral leaflets, chordae tendineae and expanded polytetrafluoroethylene neochordae were included. Mitral systolic biomechanics was simulated under preoperative conditions and after 5 different neochordal procedures: single neochorda, double neochorda, standard neochordal loop with 3 neochordae of the same length and 2 premeasured loops with 1 common neochordal loop and 3 different branched neochordae arising from it, alternatively one third and two thirds of the entire length. RESULTS: The best repair in terms of biomechanics was achieved with a specific neochordal technique in the single patient, according to the location of the prolapsing region. However, all techniques achieved a slight reduction in papillary muscle forces and tension relief in intact native chordae proximal to the prolapsing region. Multiple neochordae implantation improved the repositioning of the prolapsing region below the annular plane and better redistributed mechanical stresses on the leaflet. CONCLUSIONS: Although applied on a small cohort of patients, systematic biomechanical differences were noticed between neochordal techniques, potentially affecting their short- to long-term clinical outcomes. This study opens the way to patient-specific optimization of neochordal techniques.

In vitro study of a standardized approach to aortic cusp extension.

PURPOSE: Cusp extension technique (CET) is a reparative surgical procedure for restoring aortic valve function by suturing patches to the compromised native leaflets. Its outcomes are strongly dependent on the ability of the surgeon. We proposed and tested a novel approach on an in vitro model, aimed at standardizing and simplifying the surgical procedure. METHODS: A set of standard pre-cut bovine pericardium patches, available in different sizes, was developed. The surgeon can choose the leaflet-specific patches to be implanted according to the patient anatomy, using a geometrical model of the aortic valve whose inputs are the measured intercommissural distances. The hemodynamic performance of this approach was evaluated on porcine aortic roots in a pulsatile mock loop. Hydrodynamic and kinematic evaluation of the samples was provided. RESULTS: After CET, mean and maximum pressure drops were 3.1±1.3 mmHg and 25.4±5.0 mmHg respectively, and EOA was 3.8±0.8 cm. CONCLUSIONS: Our approach to cusp extension proved to be reliable and effective in restoring valve functioning, without significantly altering the physiological kinematics. The use of pre-cut patches considerably simplified the surgery, increasing standardization and repeatability.

Impact of modeling fluid-structure interaction in the computational analysis of aortic root biomechanics.

Numerical modeling can provide detailed and quantitative information on aortic root (AR) biomechanics, improving the understanding of AR complex pathophysiology and supporting the development of more effective clinical treatments. From this standpoint, fluid-structure interaction (FSI) models are currently the most exhaustive and potentially realistic computational tools. However, AR FSI modeling is extremely challenging and computationally expensive, due to the explicit simulation of coupled AR fluid dynamics and structural response, while accounting for complex morphological and mechanical features. We developed a novel FSI model of the physiological AR simulating its function throughout the entire cardiac cycle. The model includes an asymmetric MRI-based geometry, the description of aortic valve (AV) non-linear and anisotropic mechanical properties, and time-dependent blood pressures. By comparison to an equivalent finite element structural model, we quantified the balance between the extra information and the extra computational cost associated with the FSI approach. Tissue strains and stresses computed through the two approaches did not differ significantly. The FSI approach better captured the fast AV opening and closure, and its interplay with blood fluid dynamics within the Valsalva sinuses. It also reproduced the main features of in vivo AR fluid dynamics. However, the FSI simulation was ten times more computationally demanding than its structural counterpart. Hence, the FSI approach may be worth the extra computational cost when the tackled scenarios are strongly dependent on AV transient dynamics, Valsalva sinuses fluid dynamics in relation to coronary perfusion (e.g. sparing techniques), or AR fluid dynamic alterations (e.g. bicuspid AV).

Toward patient-specific simulations of cardiac valves: state-of-the-art and future directions.

Recent computational methods enabling patient-specific simulations of native and prosthetic heart valves are reviewed. Emphasis is placed on two critical components of such methods: (1) anatomically realistic finite element models for simulating the structural dynamics of heart valves; and (2) fluid structure interaction methods for simulating the performance of heart valves in a patient-specific beating left ventricle. It is shown that the significant progress achieved in both fronts paves the way toward clinically relevant computational models that can simulate the performance of a range of heart valves, native and prosthetic, in a patient-specific left heart environment. The significant algorithmic and model validation challenges that need to be tackled in the future to realize this goal are also discussed.

Mitral leaflet modeling: Importance of in vivo shape and material properties.

The anterior mitral leaflet (AML) is a thin membrane that withstands high left ventricular (LV) pressure pulses 100,000 times per day. The presence of contractile cells determines AML in vivo stiffness and complex geometry. Until recently, mitral valve finite element (FE) models have neglected both of these aspects. In this study we assess their effect on AML strains and stresses, hypothesizing that these will differ significantly from those reported in literature. Radiopaque markers were sewn on the LV, the mitral annulus, and AML in sheep hearts, and their four-dimensional coordinates obtained with biplane video fluoroscopy. Employing in vivo data from three representative hearts, AML FE models were created from the marker coordinates at the end of isovolumic relaxation assumed as the unloaded reference state. AML function was simulated backward through systole, applying the measured trans-mitral pressure on AML LV surface and marker displacements on AML boundaries. Simulated AML displacements and curvatures were consistent with in vivo measurements, confirming model accuracy. AML circumferential strains were mostly tensile (1-3%), despite being compressive (-1%) near the commissures. Radial strains were compressive in the belly (-1 to -0.2%), and tensile (2-8%) near the free edge. These results differ significantly from those of previous FE models. They reflect the synergy of high tissue stiffness, which limits tensile circumferential strains, and initial compound curvature, which forces LV pressure to compress AML radially. The obtained AML shape may play a role not only in preventing mitral regurgitation, but also in optimizing LV outflow fluid dynamics.

Finite element modelling of the tricuspid valve: A preliminary study.

The incomplete efficacy of current surgical repair procedures of the tricuspid valve (TV) demands a deeper comprehension of the physiological TV biomechanics. To this purpose, computational models can provide quantitative insight into TV biomechanical response and allow analysing the role of each TV substructure. We present here a three-dimensional finite element model of the tricuspid valve that takes into account most of its peculiar features. Experimental measurements were performed on human and porcine valves to obtain a more detailed TV anatomical framework. To overcome the complete lack of information on leaflets mechanical properties, we performed a sensitivity analysis on the parameters of the adopted non-linear hyperelastic constitutive model, hypothesizing three different parameter sets for three significant collagen fibre distributions. Results showed that leaflets' motion and maximum principal stress distribution were almost insensitive to the different material parameters considered. Highest stresses (about 100kPa) were located near the annulus of the anterior and septal leaflets, while the posterior leaflet experienced lower stresses (about 55kPa); stresses at the commissures were nearly zero. Conversely, changes in constitutive parameters deeply affected leaflets' strains magnitude, but not their overall pattern. Strains computed assuming that TV leaflets tissue are reinforced by a sparse and loosely arranged network of collagen fibres fitted best experimental data, thus suggesting that this may be the actual microstructure of TV leaflets. In a long-term perspective, this preliminary study aims at providing a starting point for the development of a predictive tool to quantitatively evaluate TV diseases and surgical repair procedures.