Modelling blood flow in patients with heart valve disease using deep learning: A computationally efficient method to expand diagnostic capabilities in clinical routine

Introduction: The computational modelling of blood flow is known to provide vital hemodynamic parameters for diagnosis and treatment-support for patients with valvular heart disease. However, most diagnosis/treatment-support solutions based on flow modelling proposed utilize time- and resource-intensive computational fluid dynamics (CFD) and are therefore difficult to implement into clinical practice. In contrast, deep learning (DL) algorithms provide results quickly with little need for computational power. Thus, modelling blood flow with DL instead of CFD may substantially enhances the usability of flow modelling-based diagnosis/treatment support in clinical routine. In this study, we propose a DL-based approach to compute pressure and wall-shear-stress (WSS) in the aorta and aortic valve of patients with aortic stenosis (AS). Methods: A total of 103 individual surface models of the aorta and aortic valve were constructed from computed tomography data of AS patients. Based on these surface models, a total of 267 patient-specific, steady-state CFD simulations of aortic flow under various flow rates were performed. Using this simulation data, an artificial neural network (ANN) was trained to compute spatially resolved pressure and WSS using a centerline-based representation. An unseen test subset of 23 cases was used to compare both methods. Results: ANN and CFD-based computations agreed well with a median relative difference between both methods of 6.0% for pressure and 4.9% for wall-shear-stress. Demonstrating the ability of DL to compute clinically relevant hemodynamic parameters for AS patients, this work presents a possible solution to facilitate the introduction of modelling-based treatment support into clinical practice

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

In-silico enhanced animal study of pulmonary artery pressure sensors: assessing hemodynamics using computational fluid dynamics

To assess whether in-silico models can be used to predict the risk of thrombus formation in pulmonary artery pressure sensors (PAPS), a chronic animal study using pigs was conducted. Computed tomography (CT) data was acquired before and immediately after implantation, as well as one and three months after the implantation. Devices were implanted into 10 pigs, each one in the left and right pulmonary artery (PA), to reduce the required number of animal experiments. The implantation procedure aimed at facilitating optimal and non-optimal positioning of the devices to increase chances of thrombus formation. Eight devices were positioned non-optimally. Three devices were positioned in the main PA instead of the left and right PA. Pre-interventional PA geometries were reconstructed from the respective CT images, and the devices were virtually implanted at the exact sites and orientations indicated by the follow-up CT after one month. Transient intra-arterial hemodynamics were calculated using computational fluid dynamics. Volume flow rates were modelled specifically matching the animals body weights. Wall shear stresses (WSS) and oscillatory shear indices (OSI) before and after device implantation were compared. Simulations revealed no relevant changes in any investigated hemodynamic parameters due to device implantation. Even in cases, where devices were implanted in a non-optimal manner, no marked differences in hemodynamic parameters compared to devices implanted in an optimal position were found. Before implantation time and surface-averaged WSS was 2.35±0.47 Pa, whereas OSI was 0.08±0.17, respectively. Areas affected by low WSS magnitudes were 2.5±2.7 cm2, whereas the areas affected by high OSI were 18.1±6.3 cm2. After device implantation, WSS and OSI were 2.45±0.49 Pa and 0.08±0.16, respectively. Surface areas affected by low WSS and high OSI were 2.9±2.7 cm2, and 18.4±6.1 cm2, respectively. This in-silico study indicates that no clinically relevant differences in intra-arterial hemodynamics are occurring after device implantation, even at non-optimal positioning of the sensor. Simultaneously, no embolic events were observed, suggesting that the risk for thrombus formation after device implantation is low and independent of the sensor position

Investigation of the Attachment of Circulating Endothelial Cells to a Cell Probe: Combined Experimental and Numerical Study

Circulating endothelial cells (CECs) are a reliable biomarker for cardiovascular diseases (CVDs). A major unresolved challenge limiting the widespread use of CECs for the diagnosis and monitoring of CVDs is their unreliable detection. This problem is mainly attributed to the low sample volume (5-10 mL) of commonly used ex vivo CEC isolation methods. To overcome this limitation, the BMProbe for the in vivo isolation of CECs is proposed. It consists of a twisted medical flat wire with a polymer-coated surface functionalized with anti-CD105 antibodies. A combined experimental and numerical study is performed to investigate which flow conditions lead to an increased cell attachment to the probe's surface. Endothelial cells are solved in a dextran solution and circulated in a flow system containing the BMProbes. Microscopic images of the attached CECs are taken. In addition, the experiments are simulated using a computational fluid dynamics (CFD) flow solver to quantify the flow conditions at the probe's surface. The microscopic images are superimposed with the CFD data to investigate the influence of wall shear rate and wall normal rate on the attachment of CECs to the probe. Most of all attached cells (85.5%) are found in areas of negative wall normal rate

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

Hemodynamic Modeling of Biological Aortic Valve Replacement Using Preoperative Data Only

Objectives: Prediction of aortic hemodynamics after aortic valve replacement (AVR) could help optimize treatment planning and improve outcomes. This study aims to demonstrate an approach to predict postoperative maximum velocity, maximum pressure gradient, secondary flow degree (SFD), and normalized flow displacement (NFD) in patients receiving biological AVR. Methods: Virtual AVR was performed for 10 patients, who received actual AVR with a biological prosthesis. The virtual AVRs used only preoperative anatomical and 4D flow MRI data. Subsequently, computational fluid dynamics (CFD) simulations were performed and the abovementioned hemodynamic parameters compared between postoperative 4D flow MRI data and CFD results. Results: For maximum velocities and pressure gradients, postoperative 4D flow MRI data and CFD results were strongly correlated (R 2 = 0.75 and R-2 = 0.81) with low root mean square error (0.21 m/s and 3.8 mmHg). SFD and NFD were moderately and weakly correlated at R 2 = 0.44 and R 2 = 0.20, respectively. Flow visualization through streamlines indicates good qualitative agreement between 4D flow MRI data and CFD results in most cases. Conclusion: The approach presented here seems suitable to estimate postoperative maximum velocity and pressure gradient in patients receiving biological AVR, using only preoperative MRI data. The workflow can be performed in a reasonable time frame and offers a method to estimate postoperative valve prosthesis performance and to identify patients at risk of patient-prosthesis mismatch preoperatively. Novel parameters, such as SFD and NFD, appear to be more sensitive, and estimation seems harder. Further workflow optimization and validation of results seems warranted