Verification Study of in Silico Computed Intracardiac Blood Flow With 4D Flow MRI.

OBJECTIVE: Major challenges for clinical applications of in silico medicine are limitations in time and computational resources. Computational approaches should therefore be tailored to specific applications with relatively low complexity and must be verified and validated against clinical gold standards. METHODS: This study performed computational fluid dynamics simulations of left ventricular hemodynamics of different complexity based on shape reconstruction from steady state gradient echo magnetic resonance imaging (MRI) data. Computed flow results of a rigid wall model (RWM) and a prescribed motion fluid-structure interaction (PM-FSI) model were compared against phase-contrast MRI measurements for three healthy subjects. RESULTS: Extracted boundary conditions from the steady state MRI sequences as well as computed metrics, such as flow rate, valve velocities, and kinetic energy show good agreement with in vivo flow measurements. Regional flow analysis reveals larger differences. CONCLUSION: Basic flow structures are well captured with RWM and PM-FSI. For the computation of further biomarkers like washout or flow efficiency, usage of PM-FSI is required. Regarding boundary-near flow, more accurate anatomical models are inevitable. SIGNIFICANCE: These results delineate areas of application of both methods and lay a foundation for larger validation studies and sensitivity analysis for healthy and diseased cases, being an essential step upon clinical translations.

Circulatory efficiency in patients with severe aortic valve stenosis before and after aortic valve replacement.

BACKGROUND: Circulatory efficiency reflects the ratio between total left ventricular work and the work required for maintaining cardiovascular circulation. The effect of severe aortic valve stenosis (AS) and aortic valve replacement (AVR) on left ventricular/circulatory mechanical power and efficiency is not yet fully understood. We aimed to quantify left ventricular (LV) efficiency in patients with severe AS before and after surgical AVR. METHODS: Circulatory efficiency was computed from cardiovascular magnetic resonance (CMR) imaging derived volumetric data, echocardiographic and clinical data in patients with severe AS (n = 41) before and 4 months after AVR and in age and sex-matched healthy subjects (n = 10). RESULTS: In patients with AS circulatory efficiency was significantly decreased compared to healthy subjects (9 ± 3% vs 12 ± 2%; p = 0.004). There were significant negative correlations between circulatory efficiency and LV myocardial mass (r = - 0.591, p < 0.001), myocardial fibrosis volume (r = - 0.427, p = 0.015), end systolic volume (r = - 0.609, p < 0.001) and NT-proBNP (r = - 0.444, p = 0.009) and significant positive correlation between circulatory efficiency and LV ejection fraction (r = 0.704, p < 0.001). After AVR, circulatory efficiency increased significantly in the total cohort (9 ± 3 vs 13 ± 5%; p < 0.001). However, in 10/41 (24%) patients, circulatory efficiency remained below 10% after AVR and, thus, did not restore to normal values. These patients also showed less reduction in myocardial fibrosis volume compared to patients with restored circulatory efficiency after AVR. CONCLUSION: In our cohort, circulatory efficiency is reduced in patients with severe AS. In 76% of cases, AVR leads to normalization of circulatory efficiency. However, in 24% of patients, circulatory efficiency remained below normal values even after successful AVR. In these patients also less regression of myocardial fibrosis volume was seen. Trial Registration clinicaltrials.gov NCT03172338, June 1, 2017, retrospectively registered.

Synthetic Database of Aortic Morphometry and Hemodynamics: Overcoming Medical Imaging Data Availability.

Modeling of hemodynamics and artificial intelligence have great potential to support clinical diagnosis and decision making. While hemodynamics modeling is extremely time- and resource-consuming, machine learning (ML) typically requires large training data that are often unavailable. The aim of this study was to develop and evaluate a novel methodology generating a large database of synthetic cases with characteristics similar to clinical cohorts of patients with coarctation of the aorta (CoA), a congenital heart disease associated with abnormal hemodynamics. Synthetic data allows use of ML approaches to investigate aortic morphometric pathology and its influence on hemodynamics. Magnetic resonance imaging data (154 patients as well as of healthy subjects) of aortic shape and flow were used to statistically characterize the clinical cohort. The methodology generating the synthetic cohort combined statistical shape modeling of aortic morphometry and aorta inlet flow fields and numerical flow simulations. Hierarchical clustering and non-linear regression analysis were successfully used to investigate the relationship between morphometry and hemodynamics and to demonstrate credibility of the synthetic cohort by comparison with a clinical cohort. A database of 2652 synthetic cases with realistic shape and hemodynamic properties was generated. Three shape clusters and respective differences in hemodynamics were identified. The novel model predicts the CoA pressure gradient with a root mean square error of 4.6 mmHg. In conclusion, synthetic data for anatomy and hemodynamics is a suitable means to address the lack of large datasets and provide a powerful basis for ML to gain new insights into cardiovascular diseases.

Towards improving the accuracy of aortic transvalvular pressure gradients: rethinking Bernoulli.

The transvalvular pressure gradient (TPG) is commonly estimated using the Bernoulli equation. However, the method is known to be inaccurate. Therefore, an adjusted Bernoulli model for accurate TPG assessment was developed and evaluated. Numerical simulations were used to calculate TPGCFD in patient-specific geometries of aortic stenosis as ground truth. Geometries, aortic valve areas (AVA), and flow rates were derived from computed tomography scans. Simulations were divided in a training data set (135 cases) and a test data set (36 cases). The training data was used to fit an adjusted Bernoulli model as a function of AVA and flow rate. The model-predicted TPGModel was evaluated using the test data set and also compared against the common Bernoulli equation (TPGB). TPGB and TPGModel both correlated well with TPGCFD (r > 0.94), but significantly overestimated it. The average difference between TPGModel and TPGCFD was much lower: 3.3 mmHg vs. 17.3 mmHg between TPGB and TPGCFD. Also, the standard error of estimate was lower for the adjusted model: SEEModel = 5.3 mmHg vs. SEEB = 22.3 mmHg. The adjusted model's performance was more accurate than that of the conventional Bernoulli equation. The model might help to improve non-invasive assessment of TPG. Graphical abstract Processing pipeline for the definition of an adjusted Bernoulli model for the assessment of transvalvular pressure gradient. Using CT image data, the patient specific geometry of the stenosed AVs were reconstructed. Using this segmentation, the AVA as well as the volume flow rate was calculated and used for model definition. This novel model was compared against classical approaches on a test data set, which was not used for the model definition.

Effect of daptomycin and vancomycin on Staphylococcus epidermidis biofilms: An in vitro assessment using fluorescence in situ hybridization.

Colonization of in-dwelling catheters by microbial biofilms is a major concern in patient health eventually leading to catheter-related blood stream infections. Biofilms are less susceptible to standard antibiotic therapies that are effective against planktonic bacteria. Standard procedure for the detection of microorganisms on the catheter tip is culture. However, viable but non-culturable cells (VBNCs) may be missed. The aim of this study was to evaluate the use of fluorescence in situ hybridization (FISH) as an indicator to visualize and quantify the effect of the antibiotics daptomycin and vancomycin on biofilms in situ. We established an in vitro catheter biofilm model of Staphylococcus epidermidis biofilms on polyurethane catheters. Biofilm activity was measured by FISH and correlated to colony forming units (CFU) data. Digital image analysis was used for quantification of total biofilm mass and the area of the FISH positive biofilm cells. FISH showed a pronounced effect of both antibiotics on the biofilms, with daptomycin having a significantly stronger effect in terms of both reduction of biofilm mass and number of FISH-positive cells. This supports the anti-biofilm capacity of daptomycin. Interestingly, neither antibiotic was able to eradicate all of the FISH-positive cells. In summary, FISH succeeded in visualization, quantification, and localization of antibiotic activity on biofilms. This technique adds a new tool to the arsenal of test systems for anti-biofilm compounds. FISH is a valuable complementary technique to CFU since it can be highly standardized and provides information on biofilm architecture and quantity and localization of survivor cells.

Publisher Correction: Model-Based Therapy Planning Allows Prediction of Haemodynamic Outcome after Aortic Valve Replacement.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Model-Based Therapy Planning Allows Prediction of Haemodynamic Outcome after Aortic Valve Replacement.

Optimizing treatment planning is essential for advances in patient care and outcomes. Precisely tailored therapy for each patient remains a yearned-for goal. Cardiovascular modelling has the potential to simulate and predict the functional response before the actual intervention is performed. The objective of this study was to proof the validity of model-based prediction of haemodynamic outcome after aortic valve replacement. In a prospective study design virtual (model-based) treatment of the valve and the surrounding vasculature were performed alongside the actual surgical procedure (control group). The resulting predictions of anatomic and haemodynamic outcome based on information from magnetic resonance imaging before the procedure were compared to post-operative imaging assessment of the surgical control group in ten patients. Predicted vs. post-operative peak velocities across the valve were comparable (2.97 ± 1.12 vs. 2.68 ± 0.67 m/s; p = 0.362). In wall shear stress (17.3 ± 12.3 Pa vs. 16.7 ± 16.84 Pa; p = 0.803) and secondary flow degree (0.44 ± 0.32 vs. 0.49 ± 0.23; p = 0.277) significant linear correlations (p < 0.001) were found between predicted and post-operative outcomes. Between groups blood flow patterns showed good agreement (helicity p = 0.852, vorticity p = 0.185, eccentricity p = 0.333). Model-based therapy planning is able to accurately predict post-operative haemodynamics after aortic valve replacement. These validated virtual treatment procedures open up promising opportunities for individually targeted interventions.

[Numerical flow simulation : A new method for assessing nasal breathing]. / Numerische Strömungssimulation : Eine neue Methode zur Beurteilung der Nasenatmung.

The current options for objective assessment of nasal breathing are limited. The maximum they can determine is the total nasal resistance. Possibilities to analyze the endonasal airstream are lacking. In contrast, numerical flow simulation is able to provide detailed information of the flow field within the nasal cavity. Thus, it has the potential to analyze the nasal airstream of an individual patient in a comprehensive manner and only a computed tomography (CT) scan of the paranasal sinuses is required. The clinical application is still limited due to the necessary technical and personnel resources. In particular, a statistically based referential characterization of normal nasal breathing does not yet exist in order to be able to compare and classify the simulation results.

Is MRI-based CFD able to improve clinical treatment of coarctations of aorta?

Pressure drop associated with coarctation of the aorta (CoA) can be successfully treated surgically or by stent placement. However, a decreased life expectancy associated with altered aortic hemodynamics was found in long-term studies. Image-based computational fluid dynamics (CFD) is intended to support particular diagnoses, to help in choosing between treatment options, and to improve performance of treatment procedures. This study aimed to prove the ability of CFD to improve aortic hemodynamics in CoA patients. In 13 patients (6 males, 7 females; mean age 25 ± 14 years), we compared pre- and post-treatment peak systole hemodynamics [pressure drops and wall shear stress (WSS)] vs. virtual treatment as proposed by biomedical engineers. Anatomy and flow data for CFD were based on MRI and angiography. Segmentation, geometry reconstruction and virtual treatment geometry were performed using the software ZIBAmira, whereas peak systole flow conditions were simulated with the software ANSYS(®) Fluent(®). Virtual treatment significantly reduced pressure drop compared to post-treatment values by a mean of 2.8 ± 3.15 mmHg, which significantly reduced mean WSS by 3.8 Pa. Thus, CFD has the potential to improve post-treatment hemodynamics associated with poor long-term prognosis of patients with coarctation of the aorta. MRI-based CFD has a huge potential to allow the slight reduction of post-treatment pressure drop, which causes significant improvement (reduction) of the WSS at the stenosis segment.

The impact of MRI-based inflow for the hemodynamic evaluation of aortic coarctation.

Aortic coarctation (CoA) accounting for 3-11% of congenital heart disease can be successfully treated. Long-term results, however, have revealed decreased life expectancy associated with abnormal hemodynamics. Accordingly, an assessment of hemodynamics is the key factor in treatment decisions and successful long-term results. In this study, 3D angiography whole heart (3DWH) and 4D phase-contrast magnetic resonance imaging (MRI) data were acquired. Geometries of the thoracic aorta with CoAs were reconstructed using ZIB-Amira software. X-ray angiograms were used to evaluate the post-treatment geometry. Computational fluid dynamics models in three patients were created to simulate pre- and post-treatment situations using the FLUENT program. The aim of the study was to investigate the impact of the inlet velocity profile (plug vs. MRI-based) with a focus on the peak systole pressure gradient and wall shear stress (WSS). Results show that helical flow at the aorta inlet can significantly affect the assessment of pressure drop and WSS. Simplified plug inlet velocity profiles significantly (p < 0.05) overestimate the pressure drop in pre- and post-treatment geometries and significantly (p < 0.05) underestimate surface-averaged WSS. We conclude that the use of the physiologically correct but time-expensive 4D MRI-based in vivo velocity profile in CFD studies may be an important step towards a patient-specific analysis of CoA hemodynamics.

Reproducibility of image-based analysis of cerebral aneurysm geometry and hemodynamics: an in-vitro study of magnetic resonance imaging, computed tomography, and three-dimensional rotational angiography.

BACKGROUND AND STUDY AIMS: Image-based computational fluid dynamics (CFD) provides a means for analysis of biofluid mechanical parameters of cerebral aneurysms. This may enable patient-specific rupture risk analysis and facilitate treatment decisions. Application of different imaging methods may, however, alter the geometrical basis of these studies. The present study compares geometry and hemodynamics of an aneurysm phantom model acquired by means of magnetic resonance imaging (MRI), computed tomography (CT), and rotational angiography (3DRA). MATERIALS AND METHODS: The phantom model of a basilaris artery aneurysm was fabricated based on data generated by CT angiography. This model underwent imaging by means of CT, MRI, and 3DRA. We compared the geometrical reconstructions using the original dataset with those obtained from CT, MRI, and 3DRA. Similarly, CFD analyses were performed using the four reconstructions (3DRA, MRI, CT, and original dataset). RESULTS: MRI and the 3DRA-based reconstructions yield mean reconstruction errors of 0.097 mm and 0.1 mm, which are by a factor of 2.5 better than the CT reconstruction. The maximal error for the aneurysm radius (7.11 mm) measurement was found in the 3DRA reconstruction and was 3.8% (0.28 mm). A comparison of calculated time-averaged wall shear stress (WSS) shows good correlations for the entire surface and, separately, for the surface of the aneurysmal sack. The maximal error of 8% of the mean WSS calculation of the whole surface was found for the CT reconstruction. The calculations of the aneurysmal sack mean WSS from the MRI reconstruction were estimated to have a maximal error of 7%. CONCLUSION: All three imaging techniques (CT, MRI, 3DRA) adequately reproduce aneurysm geometry and allow meaningful CFD analyses.

Flow field of a novel implantable valveless counterpulsation heart assist device.

Flow fields are one of the key factors associated with the life threatening formation of thrombi in artificial organs. Therefore, knowledge of flow field is crucial for the design and optimization of a long-term blood pump performance. The blood chamber flow of a novel counterpulsation heart assist device (CPD) has been investigated using laser Doppler velocimetry (LDV), particle image velocimetry (PIV), and near-wall PIV (wall-PIV). The wall-PIV is an in-house developed technique assessing wall shear rates (WSR). These experimental techniques analyzed complex transient three-dimensional (3D) flow fields including major and secondary structures during the whole CPD cycle (ejection, filling, and hold time). PIV measurements in the central plane investigated an evolution (development and destruction) of the blood chamber fully filling vortex as the major CPD flow structure. The wall-PIV measurements identified areas of blood stagnation (vortex center and jet impingements) and quantified WSR at the front housing. Maximal mean WSR of 2,045 ± 605 s(-1) were found at the end of the filling. The LDV, which identified helical flow structure at the outer region of the pump, was used to complete 3D flow analysis and to combine PIV and wall-PIV results. The results suggest good washing behavior of the CPD regarding thrombus formation.

Statistical wall shear stress maps of ruptured and unruptured middle cerebral artery aneurysms.

Haemodynamics and morphology play an important role in the genesis, growth and rupture of cerebral aneurysms. The goal of this study was to generate and analyse statistical wall shear stress (WSS) distributions and shapes in middle cerebral artery (MCA) saccular aneurysms. Unsteady flow was simulated in seven ruptured and 15 unruptured MCA aneurysms. In order to compare these results, all geometries must be brought in a uniform coordinate system. For this, aneurysms with corresponding WSS data were transformed into a uniform spherical shape; then, all geometries were uniformly aligned in three-dimensional space. Subsequently, we compared statistical WSS maps and surfaces of ruptured and unruptured aneurysms. No significant (p > 0.05) differences exist between ruptured and unruptured aneurysms regarding radius and mean WSS. In unruptured aneurysms, statistical WSS map relates regions with high (greater than 3 Pa) WSS to the neck region. In ruptured aneurysms, additional areas with high WSS contiguous to regions of low (less than 1 Pa) WSS are found in the dome region. In ruptured aneurysms, we found significantly lower WSS. The averaged aneurysm surface of unruptured aneurysms is round shaped, whereas the averaged surface of ruptured cases is multi-lobular. Our results confirm the hypothesis of low WSS and irregular shape as the essential rupture risk parameters.

Flow dynamics of a novel counterpulsation device characterized by CFD and PIV modeling.

BACKGROUND: Historically, single port valveless pneumatic blood pumps have had a high incidence of thrombus formation due to areas of blood stagnation and hemolysis due to areas of high shear stress. METHODS: To ensure minimal hemolysis and favorable blood washing characteristics, particle image velocimetry (PIV) and computational fluid dynamics (CFD) were used to evaluate the design of a new single port, valveless counterpulsation device (Symphony). The Symphony design was tested in 6-h acute (n=8), 5-day (n=8) and 30-day (n=2) chronic experiments in a calf model (Jersey, 76 kg). Venous blood samples were collected during acute (hourly) and chronic (weekly) time courses to analyze for temporal changes in biochemical markers and quantify plasma free hemoglobin. At the end of the study, animals were euthanized and the Symphony and end-organs (brain, liver, kidney, lungs, heart, and spleen) were examined for thrombus formations. RESULTS: Both the PIV and the CFD showed the development of a strong moving vortex during filling phase and that blood exited the Symphony uniformly from all areas during ejection phase. The laminar shear stresses estimated by CFD remained well below the hemolysis threshold of 400 Pa inside the Symphony throughout filling and ejection phases. No areas of persistent blood stagnation or flow separation were observed. The maximum plasma free hemoglobin (<10mg/dl), average platelet count (pre-implant = 473 ± 56 K/µl and post-implant = 331 ± 62 K/µl), and average hematocrit (pre-implant = 31 ± 2% and post-implant = 29 ± 2%) were normal at all measured time-points for each test animal in acute and chronic experiments. There were no changes in measures of hepatic function (ALP, ALT) or renal function (creatinine) from pre-Symphony implantation values. The necropsy examination showed no signs of thrombus formation in the Symphony or end organs. CONCLUSIONS: These data suggest that the designed Symphony has good washing characteristics without persistent areas of blood stagnation sites during the entire pump cycle, and has a low risk of hemolysis and thrombus formations.

In vitro study of near-wall flow in a cerebral aneurysm model with and without coils.

BACKGROUND AND PURPOSE: Coil embolization procedures change the flow conditions in the cerebral aneurysm and, therefore, in the near-wall region. Knowledge of these flow changes may be helpful to optimize therapy. The goal of this study was to investigate the effect of the coil-packing attenuation on the near-wall flow and its variability due to differences in the coil structure. MATERIALS AND METHODS: An enlarged transparent model of an ACA aneurysm was fabricated on the basis of CT angiography. The near-wall flow was visualized by using a recently proposed technique called Wall-PIV. Coil-packing attenuation of 10%, 15%, and 20% were investigated and compared with an aneurysmal flow without coils. Then the flow variability due to the coil introduction was analyzed in 10 experiments by using a packing attenuation of 15%. RESULTS: A small packing attenuation of 10% already alters the near-wall flow significantly in a large part of the aneurysmal sac. These flow changes are characterized by a slow flow with short (interrupted) path lines. An increased packing attenuation expands the wall area exposed to the altered flow conditions. This area, however, depends on the coil position and/or on the 3D coil structure in the aneurysm. CONCLUSIONS: To our knowledge, this is the first time the near-wall flow changes caused by coils in an aneurysm model have been visualized. It can be concluded that future hydrodynamic studies of coil therapy should include an investigation of the coil structure in addition to the coil-packing attenuation.

Novel non-dimensional approach to comparison of wall shear stress distributions in coronary arteries of different groups of patients.

BACKGROUND: Local wall shear stress (WSS) has an impact on local remodelling of the vessel wall. WSS in turn strongly depends on local geometry. Our aim was to characterize patterns of local wall shear stress associated with distinct types of remodelling in coronary arteries. Vessel size and flow rates are different between patients, however. To compare distribution patterns of WSS in analogy to fluid-dynamic modelling, non-dimensional WSS/area functions are calculated. METHODS: Right coronary arteries from seven controls, five patients with coronary artery disease (CAD) and five patients with aneurysmatic CAD (AnCAD) were analyzed. Flow simulations were performed in three-dimensionally reconstructed coronary vessels from biplane angiographic projections. Local WSS was normalized as percentage of maximum value in a histogram (100 classes) and corresponding area was expressed as percentage of total area. RESULTS: The normalized WSS distribution was characterized by a single peak with a large lower tie in controls, a loss of the single peak and a stochastic distribution in AnCAD and a narrowing of the lower tie in CAD. Correct classification of 16/17 coronary arteries was feasible by Fisher's discriminant functions based on median WSS, mean diameter, percentage of area with WSS or=15 Pa. CONCLUSION: Normalized WSS distribution might be an efficient tool in comparing wall shear stress between different patient groups. Whether normalized WSS distribution curves are apt to grade severity of disease remains to be investigated.

Particle image velocimetry of a flow at a vaulted wall.

The assessment of flow along a vaulted wall (with two main finite radii of curvature) is of general interest; in biofluid mechanics, it is of special interest. Unlike the geometry of flows in engineering, flow geometry in nature is often determined by vaulted walls. Specifically the flow adjacent to the wall of blood vessels is particularly interesting since this is where either thrombi are formed or atherosclerosis develops. Current measurement methods have problems assessing the flow along vaulted walls. In contrast with conventional particle image velocimetry (PIV), this new method, called wall PIV, allows the investigation of a flow adjacent to transparent flexible surfaces with two finite radii of curvature. Using an optical method which allows the observation of particles up to a predefined depth enables the visualization solely of the boundary layer flow. This is accomplished by adding a specific dye to the fluid which absorbs the monochromatic light used to illuminate the region of observation. The obtained images can be analysed with the methods of conventional PIV and result in a vector field of the velocities along the wall. With wall PIV, the steady flow adjacent to the vaulted wall of a blood pump was investigated and the resulting velocity field as well as the velocity fluctuations were assessed.

Mathematical model of platelet deposition under flow conditions.

Platelet deposition in resting blood is well researched and understood. However, the influence of hemodynamic parameters such as wall shear rate is less clear. Clinical experience and experiments show an interaction between flow and platelet deposition. But a complete understanding of the flow influence and hence a quantification has not yet been achieved. A well defined experiment of flow dependant platelet depositions is the stagnation point flow. This kind of flow is ubiquitous in the circulatory system, to be found in every bifurcation and recirculation region. These are the areas where thrombus formations are likely to occur if other conditions are also met. First, experiments were performed in a stagnation point flow chamber. A simplified blood model, platelet rich plasma, was used as a test fluid. With a microscope the platelet deposition was observed and recorded. Platelets deposit in a characteristic pattern showing the influence of the flow. An analysis of this pattern is the objective of this study and is achieved with the help of a numerical model, which is based on a convective diffusive transport. The model results in a platelet deposition pattern, which in its shape and temporal development is very similar to experimental results. Hence it is concluded that the assumed transport processes are causal for platelet depositions and thrombus formation.

Trileaflet valve for VAD use with purged sinus.

Clinical applications of ventricle assist devices continue to be problematic due to thromboembolic complications. The problem originates mainly at the valves, which are usually made of an antithrombogenic material, such as cross-linked bovine pericardium. However, wherever the blood flow is stagnant or forms a recirculation region, a thrombus is likely to form. A similar blood flow is found in the space between the housing of the valve and the leaflets, the so-called valve sinus. Consequently, thrombi are often generated in this region. The novel valve design presented in this article avoids the formation of stagnant flow in the valve sinus during systole by a purge flow. This flow is taken from the main flow through the valve and is directed into each sinus region. The effect is achieved by perforation of the valve sinus with a small orifice at the bottom of the sinus. The purge flow effect is investigated with the computational fluid dynamics (CFD) method. The simulation shows that the purge flow effectively increases flow in the valve sinuses.