Tailoring left ventricular assist device cannula implantation using coupled multi-scale multi-objective optimization.

BACKGROUND: The frequent occurrence of thromboembolic cerebral events continues to limit the widespread implementation of Ventricular Assist Devices (VAD) despite continued advancements in VAD design and anti-coagulation treatments. Recent studies point to the optimal positioning of the outflow graft (OG) as a potential mitigator of post implantation thromboembolism. OBJECTIVE: This study aims to examine the tailoring of the OG implantation orientation with the goal of minimizing the number of thrombi reaching the cerebral vessels by means of a formal shape optimization scheme incorporated into a multi-scale hemodynamics analysis. METHODS: A 3-D patient-specific computational fluid dynamics model is loosely coupled in a two-way manner to a 0-D lumped parameter model of the peripheral circulation. A Lagrangian particle-tracking scheme models and tracks thrombi as non-interacting solid spheres. The loose coupling between CFD and LPM is integrated into a geometric shape optimization scheme which aims to optimize an objective function that targets a drop in cerebral embolization, and an overall reduction in particle residence times. RESULTS: The results elucidate the importance of OG anastomosis orientation and placement particularly in the case that studied particle release from the OG, as a fivefold decrease in cerebral embolization was observed between the optimal and non-optimal implantations. Another case considered particle release from the ventricle and aortic root walls, in which optimal implantation was achieved with a shallow insertion angle. Particle release from all three origins was investigated in the third case, demonstrating that the optimal configurations were generally characterized by VAD flow directed along the central lumen of the aortic arch. Because optimal configurations depended on the anatomic origin of the thrombus, it is important to determine, in clinical studies, the most likely sites of thrombus formation in VAD patients.

Multiscale model for blood flow after a bileaflet artificial aortic valve implantation.

Cardiovascular diseases are the leading cause of mortality in the world, mainly due to atherosclerosis and its consequences. The article presents the numerical model of the blood flow through artificial aortic valve. The overset mesh approach was applied to simulate the valve leaflets motion and to realize the moving mesh, in the aortic arch and the main branches of cardiovascular system. To capture the cardiac system's response and the effect of vessel compliance on the outlet pressure, the lumped parameter model has been also included within the solution procedure. Three different turbulence modeling approaches were used and compared - the laminar, k-ϵ and k-ω model. The simulation results were also compared with the model excluding the moving valve geometry and the importance of the lumped parameter model for the outlet boundary condition was analyzed. Proposed numerical model and protocol was found as suitable for performing the virtual operations on the real patient vasculature geometry. The time-efficient turbulence model and overall solving procedure allows to support the clinicians in making decisions about the patient treatment and to predict the results of the future surgery.

In-Silico and In-Vitro Analysis of the Novel Hybrid Comprehensive Stage II Operation for Single Ventricle Circulation.

Single ventricle (SV) anomalies account for one-fourth of all congenital heart disease cases. The existing palliative treatment for this anomaly achieves a survival rate of only 50%. To reduce the trauma associated with surgical management, the hybrid comprehensive stage II (HCSII) operation was designed as an alternative for a select subset of SV patients with the adequate antegrade aortic flow. This study aims to provide better insight into the hemodynamics of HCSII patients utilizing a multiscale Computational Fluid Dynamics (CFD) model and a mock flow loop (MFL). Both 3D-0D loosely coupled CFD and MFL models have been tuned to match baseline hemodynamic parameters obtained from patient-specific catheterization data. The hemodynamic findings from clinical data closely match the in-vitro and in-silico measurements and show a strong correlation (r = 0.9). The geometrical modification applied to the models had little effect on the oxygen delivery. Similarly, the particle residence time study reveals that particles injected in the main pulmonary artery (MPA) have successfully ejected within one cardiac cycle, and no pathological flows were observed.

Phenotypic and transcriptional changes in Escherichia coli K12 in response to simulated microgravity on the EagleStat, a new 2D microgravity analog for bacterial studies.

Understanding the impacts of microgravity on bacteria is vital for successful long duration space missions. In this environment, bacteria have been shown to become more virulent, more resistant to antibiotics and to regulate biofilm formation. Since the study of these phenomena under true microgravity is cost- and time challenging, the use of ground-based analogs might allow researchers to test hypotheses before planning and executing experiments in the space environment. We designed and developed a 2D clinostat with capabilities robust enough for bacterial studies to allow for multiple simultaneous replicates of treatment and control conditions, thus permitting the generation of growth curves, in a single run. We used computational fluid dynamics (CFD), biofilm growth measurement and differential gene expression analysis on Escherichia coli cultures grown to late exponential phase (24 h) to validate the system's ability to simulate microgravity conditions. The CFD model with a rotational speed of 8 rpm projected cells growing homogeneously distributed along the tube, while the static condition showed the accumulation of the cells at the bottom of the container. These results were empirically validated with cultures on nutrient broth. Additionally, crystal violet assays showed that higher biofilm biomass grew on the internal walls of the gravity control tubes, compared to the simulated microgravity treatment. In contrast, when cells from both treatments were grown under standard conditions, those exposed to simulated microgravity formed significantly more biofilms than their gravity counterparts. Consistent with this result, transcriptome analysis showed the upregulation of several gene families related to biofilm formation and development such as cells adhesion, aggregation and regulation of cell motility, which provides a potential transcriptional explanation for the differential phenotype observed. Our results show that when operated under parameters for simulated microgravity, our 2D clinostat creates conditions that maintain a proportion of the cells in a constant free-falling state, consistent with the effect of microgravity. Also, the high-throughput nature of our instrument facilitates, significantly, bacterial experiments that require multiple sampling timepoints and small working volumes, making this new instrument extremely efficient.

Parametric investigation of an injection-jet self-powered Fontan circulation.

Approximately [Formula: see text] babies are born with only one functioning ventricle and the Fontan is the third and, ideally final staged palliative operation for these patients. This altered circulation is prone to failure with survival rates below [Formula: see text] into adulthood. Chronically elevated inferior vena cava (IVC) pressure is implicated as one cause of the mortality and morbidity in this population. An injection jet shunt (IJS) drawing blood-flow directly from the aortic arch to significantly lower IVC pressure is proposed. A computer-generated 3D model of a 2-4 year old patient with a fenestrated Fontan and a cardiac output of 2.3 L/min was generated. The detailed 3D pulsatile hemodynamics are resolved in a zero-dimensional lumped parameter network tightly-coupled to a 3D computational fluid dynamics model accounting for non-Newtonian blood rheology and resolving turbulence using large eddy simulation. IVC pressure and systemic oxygen saturation were tracked for various IJS-assisted Fontan configurations, altering design parameters such as shunt and fenestration diameters and locations. A baseline "failing" Fontan with a 4 mm fenestration was tuned to have an elevated IVC pressure (+ 17.8 mmHg). Enlargement of the fenestration to 8 mm resulted in a 3 mmHg IVC pressure drop but an unacceptable reduction in systemic oxygen saturation below 80%. Addition of an IJS with a 2 mm nozzle and minor volume load to the ventricle improved the IVC pressure drop to 3.2 mmHg while increasing systemic oxygen saturation above 80%. The salutary effects of the IJS to effectively lower IVC pressure while retaining acceptable levels of oxygen saturation are successfully demonstrated.

In-silico analysis of outflow graft implantation orientation and cerebral thromboembolism incidence for full LVAD support.

We investigate tailoring cannula implantation angles of left ventricle assist devices (LVAD) to reduce cerebral embolism risk for full LVAD support. We resolve pulsatile hemodynamics with a multi-scale computational fluid dynamics model coupled to a Lagrangian scheme tracking 2-5 mm particles for three cannula implantations. Blood is modeled as non-Newtonian. Cerebral flow distribution is altered depending on anastomosis angle and comparison of means embolization rates between steady and unsteady flow models show that unsteady modeling is more accurate even in the full LVAD support case. Intermediate angle implantation yields lowest cerebral embolization incidence of 11% vs 29% for normal and 36% for shallow implantation.

Computational Fluid Dynamics Study of Cerebral Thromboembolism Risk in Ventricular Assist Device Patients: Effects of Pulsatility and Thrombus Origin.

This study investigates the hypothesis that by surgically manipulating the outflow graft (OG) implantation during ventricle assist device placement, it may be possible to reduce the risk of cerebral embolism. We investigate this hypothesis using a computational approach on a patient-specific basis under fully pulsatile hemodynamics with a multiscale computational fluid dynamics model incorporating a coupled Eulerian-Lagrangian scheme that effectively tracks emboli in the fluid domain. Blood is modeled as a non-Newtonian fluid based on the hematocrit level. Preliminary flow analysis shows that depending on the anastomosis angle the left ventricular assist device (LVAD) can enhance the flow to the cerebral circulation by nearly 31%. Z-test results suggest that unsteady-flow modeling ought to be an integral part of any cardiovascular simulation with residual ventricular function. Assuming unsteady-flow conditions, a shallow LVAD outflow graft anastomosis angle is the most optimal if thrombi are released from the aortic-root reducing cerebral embolization incidence to 15.5% and from the ventricle to 17%, while a more pronounced anastomosis angle becomes advantageous when particles originate from the LVAD with an embolization rate of 16.9%. Overall, computations suggest that a pronounced LVAD anastomosis angle is the better implementation. Unsteady modeling is shown to be necessary for the presence of significant antegrade aortic-root flow which induces cyclical flow patterns due to residual pulsatility. On the other hand, depending on thrombus origin and ventricular assist devices (VAD) anastomosis angle there is a strong tradeoff in embolization rates.

Computational fluid dynamics investigation of the novel hybrid comprehensive stage II operation.

Background: The hybrid comprehensive stage 2 (HCS2) procedure is a novel palliative operation applicable to a select subset of single ventricle patients with adequate native antegrade aortic flow to the upper body. Flow to the descending aorta, through the pulmonary outlet and ductal arch, is influenced by a stented intrapulmonary baffle connecting the branch pulmonary arteries. We used computational fluid dynamics (CFD) to elucidate the hemodynamic characteristics of this reconstruction. Methods: We used multiscale CFD analysis of a synthetic, patient-derived HCS2 anatomic configuration with unsteady laminar flow conditions and a non-Newtonian blood model to quantify the resultant hemodynamics. The 3-dimensional CFD model was coupled to a 0-dimensional lumped parameter model of the peripheral circulation to determine the required boundary conditions. Results: For the specific anatomy studied, the intrapulmonary baffle did not obstruct flow from the pulmonary trunk to ductal arch as long as the distance between the anterior pulmonary artery wall and baffle wall exceeded ∼7 mm. Vortex shedding off of the baffle wall did not develop, because of the short distance to the ductal arch. The stented baffle experienced significantly uneven "inward" loading from the systemic side. Pulmonary outlet flow separation distal to the baffle produced a low-speed recirculation region. Conclusions: Hemodynamic patterns in this complex anatomy are generally favorable. Low flow recirculation could be mitigated by preoperative shape optimization. Calculated inward stresses on the pulmonary baffle can be used in the future to study baffle stent deformation, which is expected to be small.

Biomechanical evaluation of femoral anteversion in developmental dysplasia of the hip and potential implications for closed reduction.

BACKGROUND: Earlier clinical reports have identified femoral anteversion as a factor associated with developmental dysplasia of the hip. This study investigates the biomechanical influence of femoral anteversion on severe dislocations and its effect on hip reduction using the Pavlik harness. METHODS: A computational model of an infant lower-extremity, representing a ten-week old female was used to analyze the biomechanics of anteversion angles ranging from 30° to 70° when severe dislocation was being treated with the Pavlik harness. Specifically, the effects and relationships between muscle passive response and femoral anteversion angle were investigated over a range of hip abduction and external rotation. FINDINGS: Results of this study suggest that increased femoral anteversion may decrease the success rate for treatment of high-grade developmental dysplasia of the hip when using the Pavlik harness. However, hip external rotation and decreased abduction in the harness may facilitate initial reduction in these cases. INTERPRETATION: This biomechanical study may help explain why dissections of newborn specimen with developmental dysplasia of the hip have shown normal distribution of femoral anteversion in contrast to studies of patients requiring surgery where greater frequency of increased femoral anteversion has been reported. This study also suggests that adjusting the Pavlik harness to increase external hip rotation and decrease hip abduction may facilitate initial reduction for severe dislocations with increased femoral anteversion.

Patient-Specific Multi-Scale Model Analysis of Hemodynamics Following the Hybrid Norwood Procedure for Hypoplastic Left Heart Syndrome: Effects of Reverse Blalock-Taussig Shunt Diameter.

INTRODUCTION: The hybrid Norwood (HN) is a relatively new first stage palliative procedure for neonates with hypoplastic left heart syndrome, in which a sustainable uni-ventricular circulation is established in a less invasive manner than with the standard Norwood procedure. A computational multiscale model of the circulation following the HN procedure was used to obtain detailed hemodynamics. Implementation of a reverse-BT shunt (RBTS), a synthetic bypass from the main pulmonary to the innominate artery placed to counteract aortic arch stenosis, and its effects on local and global hemodynamics were studied. METHODS: A post-op patient-derived anatomy of the HN procedure was utilized with varying degrees of distal arch obstruction, or stenosis, (nominal and 90% lumenal area reduction) and varying RBTS diameters (3.0, 3.5, 4.0 mm). A closed lumped parameter model (LPM) for the proximal and peripheral circulations was coupled to a 3D computational fluid dynamics (CFD) model in order to obtain converged flow fields for analysis. RESULTS: CFD analyses of patient-derived anatomic configurations demonstrated consistent trends of vascular bed perfusion, vorticity, oscillatory shear index and wall shear stress levels. In the models with severe stenosis, implementation of the RBTS resulted in a restoration of arterial perfusion to near-nominal levels regardless of the shunt diameter. Shunt flow velocity, vorticity, and overall wall shear stress levels decreased with increasing shunt diameter, while shunt flow and systemic oxygen delivery increased with increased shunt diameter. In the absence of distal arch stenosis, large (4.0 mm) grafts may risk thrombosis due to low velocities and flow patterns. CONCLUSION: Among the three graft sizes, the best option seems to be the 3.5 mm RBTS which provides a more organized flow similar to that of the 3.0 mm configuration with lower levels of wall shear stress. As such, in the setting of this study and for comparable HN physiologies our results suggest that: (1) the 4.0 mm shunt is a generous shunt diameter choice that may be problematic particularly when implemented prophylactically in the absence of stenosis, and (2) the 3.5 mm shunt may be a more suitable alternative since it exhibits more favorable hemodynamics at lower levels of wall shear stress.

Patient-specific multiscale computational fluid dynamics assessment of embolization rates in the hybrid Norwood: effects of size and placement of the reverse Blalock-Taussig shunt.

The hybrid Norwood operation is performed to treat hypoplastic left heart syndrome. Distal arch obstruction may compromise flow to the brain. In a variant of this procedure, a synthetic graft (reverse Blalock-Taussig shunt) is placed between the pulmonary trunk and innominate artery to improve upper torso blood flow. Thrombi originating in the graft may embolize to the brain. In this study, we used computational fluid dynamics and particle tracking to investigate the patterns of particle embolization as a function of the anatomic position of the reverse Blalock-Taussig shunt. The degree of distal arch obstruction and position of particle origin influence embolization probabilities to the cerebral arteries. Cerebral embolization probabilities can be reduced by as much as 20% by optimizing graft position, for a given arch geometry, degree of distal arch obstruction, and particle origin. There is a tradeoff, however, between cerebral pulmonary and coronary embolization probabilities.

Computational Investigation of a Self-Powered Fontan Circulation.

Children born with anatomic or functional "single ventricle" must progress through two or more major operations to sustain life. This management sequence culminates in the total cavopulmonary connection, or "Fontan" operation. A consequence of the "Fontan circulation", however, is elevated central venous pressure and inadequate ventricular preload, which contribute to continued morbidity. We propose a solution to these problems by increasing pulmonary blood flow using an "injection jet" (IJS) in which the source of blood flow and energy is the ventricle itself. The IJS has the unique property of lowering venous pressure while enhancing pulmonary blood flow and ventricular preload. We report preliminary results of an analysis of this circulation using a tightly-coupled, multi-scale computational fluid dynamics model. Our calculations show that, constraining the excess volume load to the ventricle at 50% (pulmonary to systemic flow ratio of 1.5), an optimally configured IJS can lower venous pressure by 3 mmHg while increasing systemic oxygen delivery. Even this small decrease in venous pressure may have substantial clinical impact on the Fontan patient. These findings support the potential for a straightforward surgical modification to decrease venous pressure, and perhaps improve clinical outcome in selected patients.

Experimental Study of Anisotropic Stress/Strain Relationships of Aortic and Pulmonary Artery Homografts and Synthetic Vascular Grafts.

Homografts and synthetic grafts are used in surgery for congenital heart disease (CHD). Determining these materials' mechanical properties will aid in understanding tissue behavior when subjected to abnormal CHD hemodynamics. Homograft tissue samples from anterior/posterior aspects, of ascending/descending aorta (AA, DA), innominate artery (IA), left subclavian artery (LScA), left common carotid artery (LCCA), main/left/right pulmonary artery (MPA, LPA, RPA), and synthetic vascular grafts, were obtained in three orientations: circumferential, diagonal (45 deg relative to circumferential direction), and longitudinal. Samples were subjected to uniaxial tensile testing (UTT). True strain-Cauchy stress curves were individually fitted for each orientation to calibrate Fung model. Then, they were used to calibrate anisotropic Holzapfel-Gasser model (R2 > 0.95). Most samples demonstrated a nonlinear hyperelastic strain-stress response to UTT. Stiffness (measured by tangent modulus at different strains) in all orientations were compared and shown as contour plots. For each vessel segment at all strain levels, stiffness was not significantly different among aspects and orientations. For synthetic grafts, stiffness was significantly different among orientations (p < 0.042). Aorta is significantly stiffer than pulmonary artery at 10% strain, comparing all orientations, aspects, and regions (p = 0.0001). Synthetic grafts are significantly stiffer than aortic and pulmonary homografts at all strain levels (p < 0.046). Aortic, pulmonary artery, and synthetic grafts exhibit hyperelastic biomechanical behavior with anisotropic effect. Differences in mechanical properties among vascular grafts may affect native tissue behavior and ventricular/arterial mechanical coupling, and increase the risk of deformation due to abnormal CHD hemodynamics.

Developmental dysplasia of the hip: A computational biomechanical model of the path of least energy for closed reduction.

This study utilized a computational biomechanical model and applied the least energy path principle to investigate two pathways for closed reduction of high grade infantile hip dislocation. The principle of least energy when applied to moving the femoral head from an initial to a final position considers all possible paths that connect them and identifies the path of least resistance. Clinical reports of severe hip dysplasia have concluded that reduction of the femoral head into the acetabulum may occur by a direct pathway over the posterior rim of the acetabulum when using the Pavlik harness, or by an indirect pathway with reduction through the acetabular notch when using the modified Hoffman-Daimler method. This computational study also compared the energy requirements for both pathways. The anatomical and muscular aspects of the model were derived using a combination of MRI and OpenSim data. Results of this study indicate that the path of least energy closely approximates the indirect pathway of the modified Hoffman-Daimler method. The direct pathway over the posterior rim of the acetabulum required more energy for reduction. This biomechanical analysis confirms the clinical observations of the two pathways for closed reduction of severe hip dysplasia. The path of least energy closely approximated the modified Hoffman-Daimler method. Further study of the modified Hoffman-Daimler method for reduction of severe hip dysplasia may be warranted based on this computational biomechanical analysis. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1799-1805, 2017.

Computational analysis of pediatric ventricular assist device implantation to decrease cerebral particulate embolization.

Stroke is the most devastating complication after ventricular assist device (VAD) implantation with a 19% incidence and 65% mortality in the pediatric population. Current pediatric VAD technology and anticoagulation strategies alone are suboptimal. VAD implantation assisted by computational methods (CFD) may contribute reducing the risk of cerebral embolization. Representative three-dimensional aortic arch models of an infant and a child were generated. An 8 mm VAD outflow-graft (VAD-OG) anastomosed to the aorta was rendered and CFD was applied to study blood flow patterns. Particle tracks, originating in the VAD, were computed with a Lagrangian phase model and the percentage of particles entering the cerebral vessels was calculated. Eight implantation configurations (infant = 5 and child = 3) and 5 particle sizes (0.5, 1, 2, 3, and 4 mm) were considered. For the infant model, percentage of particles entering the cerebral vessels ranged from 15% for a VAD-OG anastomosed at 90° to the aorta, to 31% for 30° VAD-OG anastomosis (overall percentages: X(2) = 10,852, p < 0.0001). For the child model, cerebral embolization ranged from 9% for the 30° VAD-OG anastomosis to 15% for the 60° anastomosis (overall percentages: χ(2) = 10,323, p < 0.0001). Using detailed CFD calculations, we demonstrate that the risk of stroke depends significantly on the VAD implantation geometry. In turn, the risk probably depends on patient-specific anatomy. CFD can be used to optimize VAD implantation geometry to minimize stroke risk.

Comparison Between Bench-Top and Computational Modelling of Cerebral Thromboembolism in Ventricular Assist Device Circulation.

Despite improvements in ventricular assist devices (VAD) design, VAD-induced stroke rates remain remarkably high at 14-47%. We previously employed computational fluid dynamics (CFD) to propose adjustment of VAD outflow graft (VAD-OG) implantation to reduce stoke. Herein, we present an in-vitro model of cerebral vessel embolization in VAD-assisted circulation, and compare benchtop results to CFD predictions. The benchtop flow-loop consists of a 3D printed aortic bed using Accura 60 polymer driven by a continuous-flow pump. Three hundred spherical particles simulating thrombi of 2, 3.5, and 5 mm diameters were injected at the mock VAD-OG inlet. A water and glycerin mixture (3.8 cP viscosity) synthetically mimicked blood. The flowrate was adjusted to match the CFD Reynolds number. Catch cans were used to capture and count particles reaching cerebral vessels. VAD-OG geometries were evaluated using comparison of means Z-score range of -1.96 ≤ Z ≤ 1.96 to demonstrate overall agreement between computational and in-vitro techniques. Z-scores were: (i) Z = -1.05 for perpendicular (0°), (ii) Z = 0.32 for intermediate (30°), and (iii) Z = -0.52 for shallow (60°) anastomosis and confirmed agreement for all geometries. This study confirmed added benefits of using a left carotid artery bypass-graft with percent embolization reduction: 22.6% for perpendicular, 21.2% for intermediate, and 11.9% for shallow anastomoses. The shallow anastomosis demonstrated lower degrees of aortic arch flow recirculation, consistent with steady-flow computations. Quantitatively and qualitatively, contemporary steady-flow computational models for predicting VAD-induced cerebral embolization can be achieved in-vitro to validate the CFD equivalent.

A patient-specific model of the biomechanics of hip reduction for neonatal Developmental Dysplasia of the Hip: Investigation of strategies for low to severe grades of Developmental Dysplasia of the Hip.

A physics-based computational model of neonatal Developmental Dysplasia of the Hip (DDH) following treatment with the Pavlik Harness (PV) was developed to obtain muscle force contribution in order to elucidate biomechanical factors influencing the reduction of dislocated hips. Clinical observation suggests that reduction occurs in deep sleep involving passive muscle action. Consequently, a set of five (5) adductor muscles were identified as mediators of reduction using the PV. A Fung/Hill-type model was used to characterize muscle response. Four grades (1-4) of dislocation were considered, with one (1) being a low subluxation and four (4) a severe dislocation. A three-dimensional model of the pelvis-femur lower limb of a representative 10 week-old female was generated based on CT-scans with the aid of anthropomorphic scaling of anatomical landmarks. The model was calibrated to achieve equilibrium at 90° flexion and 80° abduction. The hip was computationally dislocated according to the grade under investigation, the femur was restrained to move in an envelope consistent with PV restraints, and the dynamic response under passive muscle action and the effect of gravity was resolved. Model results with an anteversion angle of 50° show successful reduction Grades 1-3, while Grade 4 failed to reduce with the PV. These results are consistent with a previous study based on a simplified anatomically-consistent synthetic model and clinical reports of very low success of the PV for Grade 4. However our model indicated that it is possible to achieve reduction of Grade 4 dislocation by hyperflexion and the resultant external rotation.

Experimental study of anisotropic stress/strain relationships of the piglet great vessels and relevance to pediatric congenital heart disease.

BACKGROUND: Determining material mechanical properties of neonatal aorta and pulmonary artery will aid understanding tissue behavior when subjected to abnormal hemodynamics of congenital heart disease. METHODS: Aorta and pulmonary arteries were harvested from 6 neonatal piglets (mean weight 3.5 kg). Tissue samples from ventral and dorsal aspects of ascending aorta (AA) and descending aorta (DA), innominate artery (IA), left subclavian artery (LScA), main pulmonary artery (MPA), and left pulmonary artery (LPA) and right pulmonary artery (RPA) were obtained in three orientations: circumferential, diagonal, and longitudinal. Samples were subjected to uniaxial tensile testing. True strain-Cauchy stress curves were individually fitted for each orientation to calibrate the Fung model, and to measure tissue stiffness (10% strain). RESULTS: All samples, for all orientations, demonstrated nonlinear hyperelastic strain-stress response to uniaxial tensile testing (Holzapfel-Gasser and fitted-Fung models R(2) > 0.95). For each vessel segment, stiffness was not significantly different among orientations. Stiffness values in all orientations, including ventral/dorsal samples, were compared between AA > MPA (p = 0.08), DA > MPA (p < 0.01), and DA > AA (p = 0.35). Comparison of circumferential orientation samples showed AA and DA are significantly stiffer than MPA (p < 0.05), and MPA stiffness was similar to that of the RPA but slightly greater than LPA. Also, dorsal circumferential samples of all segments were slightly stiffer than ventral (p = 0.21). Dorsal aspect of AA was slightly stiffer in all orientations (p = 0.248). CONCLUSIONS: The neonatal aorta and pulmonary artery exhibit hyperelastic biomechanical behavior with an anisotropic effect. Differences between aorta and pulmonary artery may play a role in native tissue behavior, ventricular and arterial mechanical coupling, and risk of deformation due to abnormal hemodynamics of congenital heard disease.

Mathematical modeling of patient-specific ventricular assist device implantation to reduce particulate embolization rate to cerebral vessels.

Stroke is the most devastating complication after ventricular assist device (VAD) implantation, with an incidence of 14%-47% despite improvements in device design and anticoagulation. This complication continues to limit the widespread implementation of VAD therapy. Patient-specific computational fluid dynamics (CFD) analysis may elucidate ways to reduce this risk. A patient-specific three-dimensional model of the aortic arch was generated from computed tomography. A 12 mm VAD outflow-graft (VAD-OG) "anastomosed" to the aorta was rendered. CFD was applied to study blood flow patterns. Particle tracks, originating from the VAD, were computed with a Lagrangian phase model and percentage of particles entering the cerebral vessels was calculated. Twelve implantation configurations of the VAD-OG and three particle sizes (2, 4, and 5 mm) were considered. Percentage of particles entering the cerebral vessels ranged from 6% for the descending aorta VAD-OG anastomosis, to 14% for the ascending aorta at 90 deg VAD-OG anastomosis. Values were significantly different among all configurations (X(2) = 3925, p < 0.0001). Shallower and more cephalad anastomoses prevented formation of zones of recirculation in the ascending aorta. In this computational model and within the range of anatomic parameters considered, the percentage of particles entering the cerebral vessels from a VAD-OG is reduced by nearly 60% by optimizing outflow-graft configuration. Ascending aorta recirculation zones, which may be thrombogenic, can also be eliminated. CFD methods coupled with patient-specific anatomy may aid in identifying the optimal location and angle for VAD-OG anastomosis to minimize stroke risk.

Mechanics of hip dysplasia reductions in infants using the Pavlik harness: a physics-based computational model.

Biomechanical factors influencing the reduction of dislocated hips with the Pavlik harness in patients of Developmental Dysplasia of the Hip (DDH) were studied using a three-dimensional computer model simulating hip reduction dynamics in (1) subluxated and (2) fully dislocated hip joints. Five hip adductor muscles were identified as key mediators of DDH prognosis, and the non-dimensional force contribution of each in the direction necessary to achieve concentric hip reductions was determined. Results point to the adductor muscles as mediators of subluxated hip reductions, as their mechanical action is a function of the degree of hip dislocation. For subluxated hips in abduction and flexion, the Pectineus, Adductor Brevis, Adductor Longus, and proximal Adductor Magnus contribute positively to reduction, while the rest of the Adductor Magnus contributes negatively. In full dislocations all muscles contribute detrimentally to reduction, elucidating the need for traction to reduce Graf IV type dislocations. Reduction of dysplastic hips was found to occur in two distinct phases: (a) release phase and (b) reduction phase.