A Protocol for Coupling Volumetrically Dynamic In-Vitro Experiments to Numerical Physiology Simulation for a Hybrid Cardiovascular Model.

OBJECTIVE: The Physiology Simulation Coupled Experiment (PSCOPE) is a hybrid modeling framework that enables a physical fluid experiment to operate in the context of a closed-loop computational simulation of cardiovascular physiology. Previous PSCOPE methods coupled rigid experiments to a lumped parameter network (LPN) of physiology but are incompatible with volumetrically dynamic experiments where fluid volume varies periodically. We address this limitation by introducing a method capable of coupling multi-branch and volumetrically dynamic in-vitro experiments to an LPN. METHODS: Our proposed method utilizes an iterative weighted-averaging algorithm to identify the unique solution waveforms for a given PSCOPE model. We confirm the accuracy of these PSCOPE solutions by integrating mathematical surrogates of in-vitro experiments directly into the LPN to derive reference solutions, which serve as the gold standard to validate the solutions obtained from using our proposed method to couple the same mathematical surrogates to the LPN. Finally, we illustrate a practical application of our PSCOPE method by coupling an in-vitro renal circulation experiment to the LPN. RESULTS: Compared to the reference solution, the normalized root mean square error of the flow and pressure waveforms were 0.001%∼0.55%, demonstrating the accuracy of the coupling method. CONCLUSION: We successfully coupled the in-vitro experiment to the LPN, demonstrating the real-world performance within the constraints of sensor and actuation limitations in the physical experiment. SIGNIFICANCE: This study introduces a PSCOPE method that can be used to investigate medical devices and anatomies that exhibit periodic volume changes, expanding the utility of the hybrid framework.

In vitro validation of finite-element model of AAA hemodynamics incorporating realistic outlet boundary conditions.

The purpose of this study is to validate numerical simulations of flow and pressure in an abdominal aortic aneurysm (AAA) using phase-contrast magnetic resonance imaging (PCMRI) and an in vitro phantom under physiological flow and pressure conditions. We constructed a two-outlet physical flow phantom based on patient imaging data of an AAA and developed a physical Windkessel model to use as outlet boundary conditions. We then acquired PCMRI data in the phantom while it operated under conditions mimicking a resting and a light exercise physiological state. Next, we performed in silico numerical simulations and compared experimentally measured velocities, flows, and pressures in the in vitro phantom to those computed in the in silico simulations. There was a high degree of agreement in all of the pressure and flow waveform shapes and magnitudes between the experimental measurements and simulated results. The average pressures and flow split difference between experiment and simulation were all within 2%. Velocity patterns showed good agreement between experimental measurements and simulated results, especially in the case of whole-cycle averaged comparisons. We demonstrated methods to perform in vitro phantom experiments with physiological flows and pressures, showing good agreement between numerically simulated and experimentally measured velocity fields and pressure waveforms in a complex patient-specific AAA geometry.

Risks and Benefits of Using a Commercially Available Ventricular Assist Device for Failing Fontan Cavopulmonary Support: A Modeling Investigation.

Fontan patients often develop circulatory failure and are in desperate need of a therapeutic solution. A blood pump surgically placed in the cavopulmonary pathway can substitute the function of the absent sub-pulmonary ventricle by generating a mild pressure boost. However, there is currently no commercially available device designed for the cavopulmonary application; and the risks and benefits of implanting a ventricular assist device (VAD), originally designed for the left ventricular application, on the right circulation of failing Fontan patients is not yet clear. Moreover, further research is needed to compare the hemodynamics between the two clinically-considered surgical configurations for cavopulmonary assist, with Full and inferior vena cava (IVC) support corresponding to the entire venous return or only the inferior venous return, respectively, being routed through the VAD. In this study, we used a numerical model of the failing Fontan physiology to evaluate the Fontan hemodynamic response to a left VAD during the IVC and Full support scenarios. We observed that during Full support, the VAD improved the cardiac output while maintaining blood pressures within safe ranges, and lowered the IVC pressure to <15 mmHg; however, we found a potential risk of lung damage at higher pump speeds due to the excessive pulmonary pressure elevation. IVC support, on the other hand, did not benefit the hemodynamics in the patient cases simulated, resulting in the superior vena cava pressure increasing to an unsafe level of >20 mmHg. The findings in this study may be helpful to surgeons for recognizing the risks of a cavopulmonary VAD and developing coherent clinical strategies for the implementation of cavopulmonary support.

Target Flow-Pressure Operating Range for Designing a Failing Fontan Cavopulmonary Support Device.

Fontan operation as the current standard of care for the palliation of single ventricle defects results in significant late complications. Using a mechanical circulatory device for the right circulation to serve the function of the missing subpulmonary ventricle could potentially stabilize the failing Fontan circulation. This study aims to elucidate the hydraulic operating regions that should be targeted for designing cavopulmonary blood pumps. By integrating numerical analysis and available clinical information, the interaction of the cavopulmonary support via the IVC and full assist configurations with a wide range of simulated adult failing scenarios was investigated; with IVC and full assist corresponding to the inferior venous return or the entire venous return, respectively, being routed through the device. We identified the desired hydraulic operating regions for a cavopulmonary assist device by clustering all head pressures and corresponding pump flows that result in hemodynamic improvement for each simulated failing Fontan physiology. Results show that IVC support can produce beneficial hemodynamics in only a small fraction of failing Fontan scenarios. Cavopulmonary assist device could increase cardiac index by 35% and decrease the inferior vena cava pressure by 45% depending on the patient's pre-support hemodynamic state and surgical configuration of the cavopulmonary assist device (IVC or full support). The desired flow-pressure operating regions we identified can serve as the performance criteria for designing cavopulmonary assist devices as well as evaluating off-label use of commercially available left-side blood pumps for failing Fontan cavopulmonary support.

Hemodynamic effects of left pulmonary artery stenosis after superior cavopulmonary connection: a patient-specific multiscale modeling study.

OBJECTIVE: Currently, no quantitative guidelines have been established for treatment of left pulmonary artery (LPA) stenosis. This study aims to quantify the effects of LPA stenosis on postoperative hemodynamics for single-ventricle patients undergoing stage II superior cavopulmonary connection (SCPC) surgery, using a multiscale computational approach. METHODS: Image data from 6 patients were segmented to produce 3-dimensional models of the pulmonary arteries before stage II surgery. Pressure and flow measurements were used to tune a 0-dimensional model of the entire circulation. Postoperative geometries were generated through stage II virtual surgery; varying degrees of LPA stenosis were applied using mesh morphing and hemodynamics assessed through coupled 0-3-dimensional simulations. To relate metrics of stenosis to clinical classifications, pediatric cardiologists and surgeons ranked the degrees of stenosis in the models. The effects of LPA stenosis were assessed based on left-to-right pulmonary artery flow split ratios, mean pressure drop across the stenosis, cardiac pressure-volume loops, and other clinically relevant parameters. RESULTS: Stenosis of >65% of the vessel diameter was required to produce a right pulmonary artery:LPA flow split <30%, and/or a mean pressure drop of >3.0 mm Hg, defined as clinically significant changes. CONCLUSIONS: The effects of <65% stenosis on SCPC hemodynamics and physiology were minor and may not justify the increased complexity of adding LPA arterioplasty to the SCPC operation. However, in the longer term, pulmonary augmentation may affect outcomes of the Fontan completion surgery, as pulmonary artery distortion is a risk factor that may influence stage III physiology.

Development of A Physical Windkessel Module to Re-Create In-Vivo Vascular Flow Impedance for In-Vitro Experiments.

PURPOSE: To create and characterize a physical Windkessel module that can provide realistic and predictable vascular impedances for in-vitro flow experiments used for computational fluid dynamics validation, and other investigations of the cardiovascular system and medical devices. METHODS: We developed practical design and manufacturing methods for constructing flow resistance and capacitance units. Using these units we assembled a Windkessel impedance module and defined its corresponding analytical model incorporating an inductance to account for fluid momentum. We tested various resistance units and Windkessel modules using a flow system, and compared experimental measurements to analytical predictions of pressure, flow, and impedance. RESULTS: The resistance modules exhibited stable resistance values over wide ranges of flow rates. The resistance value variations of any particular resistor are typically within 5% across the range of flow that it is expected to accommodate under physiologic flow conditions. In the Windkessel impedance modules, the measured flow and pressure waveforms agreed very favorably with the analytical calculations for four different flow conditions used to test each module. The shapes and magnitudes of the impedance modulus and phase agree well between experiment and theoretical values, and also with those measured in-vivo in previous studies. CONCLUSIONS: The Windkessel impedance module we developed can be used as a practical tool to provide realistic vascular impedance for in-vitro cardiovascular studies. Upon proper characterization of the impedance module, its analytical model can accurately predict its measured behavior under different flow conditions.

In vitro validation of finite element analysis of blood flow in deformable models.

The purpose of this article is to validate numerical simulations of flow and pressure incorporating deformable walls using in vitro flow phantoms under physiological flow and pressure conditions. We constructed two deformable flow phantoms mimicking a normal and a restricted thoracic aorta, and used a Windkessel model at the outlet boundary. We acquired flow and pressure data in the phantom while it operated under physiological conditions. Next, in silico numerical simulations were performed, and velocities, flows, and pressures in the in silico simulations were compared to those measured in the in vitro phantoms. The experimental measurements and simulated results of pressure and flow waveform shapes and magnitudes compared favorably at all of the different measurement locations in the two deformable phantoms. The average difference between measured and simulated flow and pressure was approximately 3.5 cc/s (13% of mean) and 1.5 mmHg (1.8% of mean), respectively. Velocity patterns also showed good qualitative agreement between experiment and simulation especially in regions with less complex flow patterns. We demonstrated the capabilities of numerical simulations incorporating deformable walls to capture both the vessel wall motion and wave propagation by accurately predicting the changes in the flow and pressure waveforms at various locations down the length of the deformable flow phantoms.