Scale-Resolving Simulations of Steady and Pulsatile Flow Through Healthy and Stenotic Heart Valves.

Blood-flow downstream of stenotic and healthy aortic valves exhibits intermittent random fluctuations in the velocity field which are associated with turbulence. Such flows warrant the use of computationally demanding scale-resolving models. The aim of this work was to compute and quantify this turbulent flow in healthy and stenotic heart valves for steady and pulsatile flow conditions. Large eddy simulations (LESs) and Reynolds-averaged Navier-Stokes (RANS) simulations were used to compute the flow field at inlet Reynolds numbers of 2700 and 5400 for valves with an opening area of 70 mm2 and 175 mm2 and their projected orifice-plate type counterparts. Power spectra and turbulent kinetic energy were quantified on the centerline. Projected geometries exhibited an increased pressure-drop (>90%) and elevated turbulent kinetic energy levels (>147%). Turbulence production was an order of magnitude higher in stenotic heart valves compared to healthy valves. Pulsatile flow stabilizes flow in the acceleration phase, whereas onset of deceleration triggered (healthy valve) or amplified (stenotic valve) turbulence. Simplification of the aortic valve by projecting the orifice area should be avoided in computational fluid dynamics (CFD). RANS simulations may be used to predict the transvalvular pressure-drop, but scale-resolving models are recommended when detailed information of the flow field is required.

The impact of shape uncertainty on aortic-valve pressure-drop computations.

Patient-specific image-based computational fluid dynamics (CFD) is widely adopted in the cardiovascular research community to study hemodynamics, and will become increasingly important for personalized medicine. However, segmentation of the flow domain is not exact and geometric uncertainty can be expected which propagates through the computational model, leading to uncertainty in model output. Seventy-four aortic-valves were segmented from computed tomography images at peak systole. Statistical shape modeling was used to obtain an approximate parameterization of the original segmentations. This parameterization was used to train a meta-model that related the first five shape mode coefficients and flowrate to the CFD-computed transvalvular pressure-drop. Consequently, shape uncertainty in the order of 0.5 and 1.0 mm was emulated by introducing uncertainty in the shape mode coefficients. A global variance-based sensitivity analysis was performed to quantify output uncertainty and to determine relative importance of the shape modes. The first shape mode captured the opening/closing behavior of the valve and uncertainty in this mode coefficient accounted for more than 90% of the output variance. However, sensitivity to shape uncertainty is patient-specific, and the relative importance of the fourth shape mode coefficient tended to increase with increases in valvular area. These results show that geometric uncertainty in the order of image voxel size may lead to substantial uncertainty in CFD-computed transvalvular pressure-drops. Moreover, this illustrates that it is essential to assess the impact of geometric uncertainty on model output, and that this should be thoroughly quantified for applications that wish to use image-based CFD models.

Unmixing multi-spectral photoacoustic sources in human carotid plaques using non-negative independent component analysis.

Multi-spectral photoacoustic imaging (MSPAI) is promising for morphology assessment of carotid plaques; however, obtaining unique spectral characteristics of chromophores is cumbersome. We used MSPAI and non-negative independent component analysis (ICA) to unmix distinct signal sources in human carotid plaques blindly. The feasibility of the method was demonstrated on a plaque phantom with hemorrhage and cholesterol inclusions, and plaque endarterectomy samples ex vivo. Furthermore, the results were verified with histology using Masson's trichrome staining. Results showed that ICA could separate recent hemorrhages from old hemorrhages. Additionally, the signatures of cholesterol inclusion were also captured for the phantom experiment. Artifacts were successfully removed from signal sources. Histologic examinations showed high resemblance with the unmixed components and confirmed the morphologic distinction between recent and mature hemorrhages. In future pre-clinical studies, unmixing could be used for morphology assessment of intact human plaque samples.

Perfusion dynamics assessment with Power Doppler ultrasound in skeletal muscle during maximal and submaximal cycling exercise.

PURPOSE: Assessment of limitations in the perfusion dynamics of skeletal muscle may provide insight in the pathophysiology of exercise intolerance in, e.g., heart failure patients. Power doppler ultrasound (PDUS) has been recognized as a sensitive tool for the detection of muscle blood flow. In this volunteer study (N = 30), a method is demonstrated for perfusion measurements in the vastus lateralis muscle, with PDUS, during standardized cycling exercise protocols, and the test-retest reliability has been investigated. METHODS: Fixation of the ultrasound probe on the upper leg allowed for continuous PDUS measurements. Cycling exercise protocols included a submaximal and an incremental exercise to maximal power. The relative perfused area (RPA) was determined as a measure of perfusion. Absolute and relative reliability of RPA amplitude and kinetic parameters during exercise (onset, slope, maximum value) and recovery (overshoot, decay time constants) were investigated. RESULTS: A RPA increase during exercise followed by a signal recovery was measured in all volunteers. Amplitudes and kinetic parameters during exercise and recovery showed poor to good relative reliability (ICC ranging from 0.2-0.8), and poor to moderate absolute reliability (coefficient of variation (CV) range 18-60%). CONCLUSIONS: A method has been demonstrated which allows for continuous (Power Doppler) ultrasonography and assessment of perfusion dynamics in skeletal muscle during exercise. The reliability of the RPA amplitudes and kinetics ranges from poor to good, while the reliability of the RPA increase in submaximal cycling (ICC = 0.8, CV = 18%) is promising for non-invasive clinical assessment of the muscle perfusion response to daily exercise.

Patient Specific Wall Stress Analysis and Mechanical Characterization of Abdominal Aortic Aneurysms Using 4D Ultrasound.

OBJECTIVES: The aim of this study was to perform wall stress analysis (WSA) using 4D ultrasound (US) in 40 patients with an abdominal aortic aneurysm (AAA). The geometries and wall stress results were compared with computed tomography (CT) in seven patients. Additionally, the WSA models were calibrated using 4D motion estimation, resulting in patient specific material parameters that were compared among patients. METHODS: 4D-US images were acquired for 40 patients (AAA diameter 27-52 mm). Patient specific AAA geometries and wall motion were extracted from the 4D-US. WSA was performed and corresponding patient specific material properties were derived. For seven patients, CT data were available and analyzed for geometry and wall stress comparison. RESULTS: The 4D-US based 99th percentile wall stress ranged from 198 to 390 kPa. Regression analysis showed no significant relation between wall stress and diameter of the AAA. The similarity indices between US and CT were very good and ranged between 0.90 and 0.96, and the 25th, 50th, 75th, and 95th percentile wall stresses of the US and CT data were in agreement. The characterized patient specific shear modulus had a median of 1.1 MPa (interquartile range, 0.7-1.4 MPa). Based on the maximum AAA diameter, the AAAs were divided in a small, medium, and large diameter groups. The largest AAAs revealed an increased wall stiffness compared with the smallest AAAs. CONCLUSIONS: 4D ultrasound is applicable for wall stress analysis of AAAs, and offers the opportunity to perform wall stress analysis over time, also for AAAs who do not qualify for a CT or magnetic resonance imaging. Moreover, the patient specific material properties can be determined, which could possibly improve risk assessment.

A novel passive left heart platform for device testing and research.

Integration of biological samples into in vitro mock loops is fundamental to simulate real device's operating conditions. We developed an in vitro platform capable of simulating the pumping function of the heart through the external pressurization of the ventricle. The system consists of a fluid-filled chamber, in which the ventricles are housed and sealed to exclude the atria from external loads. The chamber is connected to a pump that drives the motion of the ventricular walls. The aorta is connected to a systemic impedance simulator, and the left atrium to an adjustable preload. The platform reproduced physiologic hemodynamics, i.e. aortic pressures of 120/80 mmHg with 5 L/min of cardiac output, and allowed for intracardiac endoscopy. A pilot study with a left ventricular assist device (LVAD) was also performed. The LVAD was connected to the heart to investigate aortic valve functioning at different levels of support. Results were consistent with the literature, and high speed video recordings of the aortic valve allowed for the visualization of the transition between a fully opening valve and a permanently closed configuration. In conclusion, the system showed to be an effective tool for the hemodynamic assessment of devices, the simulation of surgical or transcatheter procedures and for visualization studies.

A mock circulation model for cardiovascular device evaluation.

The aim of this study was to develop an integrated mock circulation system that functions in a physiological manner for testing cardiovascular devices under well-controlled circumstances. In contrast to previously reported mock loops, the model includes a systemic, pulmonary, and coronary circulation, an elaborate heart contraction model, and a realistic heart rate control model. The behavior of the presented system was tested in response to changes in left ventricular contractile states, loading conditions, and heart rate. For validation purposes, generated hemodynamic parameters and responses were compared to literature. The model was implemented in a servo-motor driven mock loop, together with a relatively simple lead-lag controller. The pressure and flow signals measured closely mimicked human pressure under both physiological and pathological conditions. In addition, the system's response to changes in preload, afterload, and heart rate indicate a proper implementation of the incorporated feedback mechanisms (frequency and cardiac function control). Therefore, the presented mock circulation allows for generic in vitro testing of cardiovascular devices under well-controlled circumstances.

Intra-aortic balloon counterpulsation in acute myocardial infarction: old and emerging indications.

BACKGROUND: Recent evidence questions the role of intra-aortic balloon counterpulsation (IABP) in the treatment of acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). An area of increasing interest is the use of IABP for persistent ischaemia (PI). We analysed the use of IABP in patients with AMI complicated by CS or PI. METHODS: From 2008 to 2010, a total of 4076 patients were admitted to our hospital for primary percutaneous coronary intervention (PCI) for AMI. Out of those, 239 patients received an IABP either because of CS or because of PI. Characteristics and outcome of those patients are investigated. RESULTS: The mean age of the study population was 64 ± 11 years; 75 % were male patients. Of the patients, 63 % had CS and 37 % had PI. Patients with CS had a 30-day mortality rate of 36 %; 1-year mortality was 41 %. Patients with PI had a 30-day mortality rate of 7 %; 1-year mortality was 11 %. CONCLUSIONS: Mortality in patients admitted for primary PCI because of AMI complicated by CS is high despite IABP use. Outcome in patients treated with IABP for PI is favourable and mandates further prospective studies.

Complex flow patterns in a real-size intracranial aneurysm phantom: phase contrast MRI compared with particle image velocimetry and computational fluid dynamics.

The aim of this study was to validate the flow patterns measured by high-resolution, time-resolved, three-dimensional phase contrast MRI in a real-size intracranial aneurysm phantom. Retrospectively gated three-dimensional phase contrast MRI was performed in an intracranial aneurysm phantom at a resolution of 0.2 × 0.2 × 0.3 mm(3) in a solenoid rat coil. Both steady and pulsatile flows were applied. The phase contrast MRI measurements were compared with particle image velocimetry measurements and computational fluid dynamics simulations. A quantitative comparison was performed by calculating the differences between the magnitude of the velocity vectors and angles between the velocity vectors in corresponding voxels. Qualitative analysis of the results was executed by visual inspection and comparison of the flow patterns. The root-mean-square errors of the velocity magnitude in the comparison between phase contrast MRI and computational fluid dynamics were 5% and 4% of the maximum phase contrast MRI velocity, and the medians of the angle distribution between corresponding velocity vectors were 16° and 14° for the steady and pulsatile measurements, respectively. In the phase contrast MRI and particle image velocimetry comparison, the root-mean-square errors were 12% and 10% of the maximum phase contrast MRI velocity, and the medians of the angle distribution between corresponding velocity vectors were 19° and 15° for the steady and pulsatile measurements, respectively. Good agreement was found in the qualitative comparison of flow patterns between the phase contrast MRI measurements and both particle image velocimetry measurements and computational fluid dynamics simulations. High-resolution, time-resolved, three-dimensional phase contrast MRI can accurately measure complex flow patterns in an intracranial aneurysm phantom.

Real time, non-invasive assessment of leaflet deformation in heart valve tissue engineering.

In heart valve tissue engineering, most bioreactors try to mimic physiological flow and operate with a preset transvalvular pressure applied to the tissue. The induced deformations are unknown and can vary during culturing as a consequence of changing mechanical properties of the engineered construct. Real-time measurement and control of local tissue strains are desired to systematically study the effects of mechanical loading on tissue development and, consequently, to design an optimal conditioning protocol. In this study, a method is presented to assess local tissue strains in heart valve leaflets during culturing. We hypothesize that local tissue strains can be determined from volumetric deformation. Volumetric deformation is defined as the amount of fluid displaced by the deformed heart valve leaflets in a stented configuration, and is measured, non-invasively, using a flow sensor. A numerical model is employed to relate volumetric deformation to local tissue strains in various regions of the leaflets (e.g. belly and commissures). The flow-based deformation measurement method was validated and its functionality was demonstrated in a tissue engineering experiment. Tri-leaflet, stented heart valves were cultured in vitro and during mechanical conditioning, realistic values for volumetric and local deformation were obtained.

Assessment of endoleak significance after endovascular repair of abdominal aortic aneurysms: a lumped parameter model.

The outcome of endovascular repair of abdominal aortic aneurysms (AAAs) is greatly compromised by the possible occurrence of endoleak. Previously, the causes and effects of endoleak on a patient-specific basis have mainly been investigated in experimental studies. In order to both reconcile and physically substantiate the various experimental findings, a lumped parameter model of an incompletely excluded AAA was developed. After experimental validation, the model was applied to study the effects on the intrasac pressure of the degree of endoleak, the degree of stent-graft compliance, and the resistance of a possible outflow tract formed by a branching vessel. It is concluded that the presence of endoleak leads to elevated intrasac pressure, the mean of which is mainly governed by the outflow tract resistance, while the pulse pressure is governed by both the endoleak resistance and the stent-graft compliance. Based on the agreement of the current results with previous findings, it is further concluded that the lumped parameter modelling method provides a useful numerical tool for validating experimental endoleak studies.

Patient-specific initial wall stress in abdominal aortic aneurysms with a backward incremental method.

Patient-specific wall stress simulations on abdominal aortic aneurysms may provide a better criterion for surgical intervention than the currently used maximum transverse diameter. In these simulations, it is common practice to compute the peak wall stress by applying the full systolic pressure directly on the aneurysm geometry as it appears in medical images. Since this approach does not account for the fact that the measured geometry is already experiencing a substantial load, it may lead to an incorrect systolic aneurysm shape. We have developed an approach to compute the wall stress on the true diastolic geometry at a given pressure with a backward incremental method. The method has been evaluated with a neo-Hookean material law for several simple test problems. The results show that the method can predict an unloaded configuration if the loaded geometry and the load applied are known. The effect of incorporating the initial diastolic stress has been assessed by using three patient-specific geometries acquired with cardiac triggered MR. The comparison shows that the commonly used approach leads to an unrealistically smooth systolic geometry and therefore provides an underestimation for the peak wall stress. Our backward incremental modelling approach overcomes these issues and provides a more plausible estimate for the systolic aneurysm volume and a significantly different estimate for the peak wall stress. When the approach is applied with a more complex material law which has been proposed specifically for abdominal aortic aneurysm similar effects are observed and the same conclusion can be drawn.

Electrospinning versus knitting: two scaffolds for tissue engineering of the aortic valve.

Two types of scaffolds were developed for tissue engineering of the aortic valve; an electrospun valvular scaffold and a knitted valvular scaffold. These scaffolds were compared in a physiologic flow system and in a tissue-engineering process. In fibrin gel enclosed human myofibroblasts were seeded onto both types of scaffolds and cultured for 23 days under continuous medium perfusion. Tissue formation was evaluated by confocal laser scanning microscopy, histology and DNA quantification. Collagen formation was quantified by a hydroxyproline assay. When subjected to physiologic flow, the spun scaffold tore within 6 h, whereas the knitted scaffold remained intact. Cells proliferated well on both types of scaffolds, although the cellular penetration into the spun scaffold was poor. Collagen production, normalized to DNA content, was not significantly different for the two types of scaffolds, but seeding efficiency was higher for the spun scaffold, because it acted as a cell impermeable filter. The knitted tissue constructs showed complete cellular in-growth into the pores. An optimal scaffold seems to be a combination of the strength of the knitted structure and the cell-filtering ability of the spun structure.

A patient-specific computational model of fluid-structure interaction in abdominal aortic aneurysms.

It is generally believed that knowledge of the wall stress distribution could help to find better rupture risk predictors of abdominal aortic aneurysms (AAAs). Although AAA wall stress results from combined action between blood, wall and intraluminal thrombus, previously published models for patient-specific assessment of the wall stress predominantly did not include fluid-dynamic effects. In order to facilitate the incorporation of fluid-structure interaction in the assessment of AAA wall stress, in this paper, a method for generating patient-specific hexahedral finite element meshes of the AAA lumen and wall is presented. The applicability of the meshes is illustrated by simulations of the wall stress, blood velocity distribution and wall shear stress in a characteristic AAA. The presented method yields a flexible, semi-automated approach for generating patient-specific hexahedral meshes of the AAA lumen and wall with predefined element distributions. The combined fluid/solid mesh allows for simulations of AAA blood dynamics and AAA wall mechanics and the interaction between the two. The mechanical quantities computed in these simulations need to be validated in a clinical setting, after which they could be included in clinical trials in search of risk factors for AAA rupture.