Patient-specific closed-loop model of the fontan circulation: Calibration and validation.

The Fontan circulation, designed for managing patients with a single functional ventricle, presents challenges in long-term outcomes. Computational methods offer potential solutions, yet their application in cardiology practice remains largely unexplored. Our aim was to assess the ability of a patient-specific, closed-loop, reduced-order blood flow model to simulate pulsatile blood flow in the Fontan circulation. Using one-dimensional models, we simulated the aorta, superior and inferior venae cavae, and right and left pulmonary arteries, while lumping heart chambers and remaining vessels into zero-dimensional models. The model was calibrated with patient-specific haemodynamic data from combined cardiac catheterisation and magnetic resonance exams, using a novel physics-based stepwise methodology involving simpler open-loop models. Testing on a 10-year-old, anesthetised patient, demonstrated the model's capability to replicate pulsatile pressure and flow in the larger vessels and ventricular pressure. Average relative errors in mean pressure and flow were 2.9 % and 3.6 %, with average relative point-to-point errors (RPPE) in pressure and flow at 5.2 % and 16.0 %. Comparing simulation results to measurements, mean aortic pressure and flow values were 50.7 vs. 50.4 mmHg and 41.6 vs. 41.9 ml/s, respectively, while ventricular pressure values were 28.7 vs. 27.4 mmHg. The model accurately described time-varying ventricular volume with a RPPE of 2.9 %, with mean, minimum, and maximum ventricular volume values for simulation results vs. measurements at 59.2 vs. 58.2 ml, 38.0 vs. 37.6 ml, and 76.0 vs. 74.4 ml, respectively. It provided physiologically realistic predictions of haemodynamic changes from pulmonary vasodilation and atrial fenestration opening. The new model and calibration methodology are freely available, offering a platform to virtually investigate the Fontan circulation's response to clinical interventions and explore potential mechanisms of Fontan failure. Future efforts will concentrate on broadening the model's applicability to a wider range of patient populations and clinical scenarios, as well as testing its effectiveness.

Computational study of a novel catheter for liver radioembolization.

Radioembolization (RE) is a medical treatment for primary and secondary liver cancer that involves the transcatheter intraarterial delivery of micron-sized and radiation-emitting microspheres, with the goal of improving microsphere deposition in the tumoral bed while sparing healthy tissue. An increasing number of in vitro and in silico studies on RE in the literature suggest that the particle injection velocity, spatial location of the catheter tip and catheter type are important parameters in particle distribution. The present in silico study assesses the performance of a novel catheter design that promotes particle dispersion near the injection point, with the goal of generating a particle distribution that mimics the flow split to facilitate tumour targeting. The design is based on two factors: the direction and the velocity at which particles are released from the catheter. A series of simulations was performed with the catheter inserted at an idealised hepatic artery tree with physiologically realistic boundary conditions. Two longitudinal microcatheter positions in the first generation of the tree were studied by analysing the performance of the catheter in terms of the outlet-to-outlet particle distribution and split flow matching. The results show that the catheter with the best performance is one with side holes on the catheter wall and a closed frontal tip. This catheter promotes a flow-split-matching particle distribution, which improves as the injection crossflow increases.

Computational Fluid Dynamics Modeling of Liver Radioembolization: A Review.

Yttrium-90 radioembolization (RE) is a widely used transcatheter intraarterial therapy for patients with unresectable liver cancer. In the last decade, computer simulations of hepatic artery hemodynamics during RE have been performed with the aim of better understanding and improving the therapy. In this review, we introduce the concept of computational fluid dynamics (CFD) modeling with a clinical perspective and we review the CFD models used to study RE from the fluid mechanics point of view. Finally, we show what CFD simulations have taught us about the hemodynamics during RE, the current capabilities of CFD simulations of RE, and we suggest some future perspectives.

In Vitro Model for Simulating Drug Delivery during Balloon-Occluded Transarterial Chemoembolization.

BACKGROUND: Balloon-occluded transarterial chemoembolization (B-TACE) has emerged as a safe and effective procedure for patients with liver cancer, which is one of the deadliest types of cancer worldwide. B-TACE consist of the transcatheter intraarterial infusion of chemotherapeutic agents, followed by embolizing particles, and it is performed with a microballoon catheter that temporarily occludes a hepatic artery. B-TACE relies on the blood flow redistribution promoted by the balloon-occlusion. However, flow redistribution phenomenon is not yet well understood. METHODS: This study aims to present a simple in vitro model (IVM) where B-TACE can be simulated. RESULTS: By visually analyzing the results of various clinically-realistic experiments, the IVM allows for the understanding of balloon-occlusion-related hemodynamic changes and the importance of the occlusion site. CONCLUSION: The IVM can be used as an educational tool to help clinicians better understand B-TACE treatments. This IVM could also serve as a base for a more sophisticated IVM to be used as a research tool.

A proof-of-concept study of the in-vivo validation of a computational fluid dynamics model of personalized radioembolization.

Radioembolization (RE) with yttrium-90 (90Y) microspheres, a transcatheter intraarterial therapy for patients with liver cancer, can be modeled computationally. The purpose of this work was to correlate the results obtained with this methodology using in vivo data, so that this computational tool could be used for the optimization of the RE procedure. The hepatic artery three-dimensional (3D) hemodynamics and microsphere distribution during RE were modeled for six 90Y-loaded microsphere infusions in three patients with hepatocellular carcinoma using a commercially available computational fluid dynamics (CFD) software package. The model was built based on in vivo data acquired during the pretreatment stage. The results of the simulations were compared with the in vivo distribution assessed by 90Y PET/CT. Specifically, the microsphere distribution predicted was compared with the actual 90Y activity per liver segment with a commercially available 3D-voxel dosimetry software (PLANET Dose, DOSIsoft). The average difference between the CFD-based and the PET/CT-based activity distribution was 2.36 percentage points for Patient 1, 3.51 percentage points for Patient 2 and 2.02 percentage points for Patient 3. These results suggest that CFD simulations may help to predict 90Y-microsphere distribution after RE and could be used to optimize the RE procedure on a patient-specific basis.

Estimating central blood pressure from aortic flow: development and assessment of algorithms.

Central blood pressure (cBP) is a highly prognostic cardiovascular (CV) risk factor whose accurate, invasive assessment is costly and carries risks to patients. We developed and assessed novel algorithms for estimating cBP from noninvasive aortic hemodynamic data and a peripheral blood pressure measurement. These algorithms were created using three blood flow models: the two- and three-element Windkessel (0-D) models and a one-dimensional (1-D) model of the thoracic aorta. We tested new and existing methods for estimating CV parameters (left ventricular ejection time, outflow BP, arterial resistance and compliance, pulse wave velocity, and characteristic impedance) required for the cBP algorithms, using virtual (simulated) subjects (n = 19,646) for which reference CV parameters were known exactly. We then tested the cBP algorithms using virtual subjects (n = 4,064), for which reference cBP were available free of measurement error, and clinical datasets containing invasive (n = 10) and noninvasive (n = 171) reference cBP waves across a wide range of CV conditions. The 1-D algorithm outperformed the 0-D algorithms when the aortic vascular geometry was available, achieving central systolic blood pressure (cSBP) errors ≤ 2.1 ± 9.7 mmHg and root-mean-square errors (RMSEs) ≤ 6.4 ± 2.8 mmHg against invasive reference cBP waves (n = 10). When the aortic geometry was unavailable, the three-element 0-D algorithm achieved cSBP errors ≤ 6.0 ± 4.7 mmHg and RMSEs ≤ 5.9 ± 2.4 mmHg against noninvasive reference cBP waves (n = 171), outperforming the two-element 0-D algorithm. All CV parameters were estimated with mean percentage errors ≤ 8.2%, except for the aortic characteristic impedance (≤13.4%), which affected the three-element 0-D algorithm's performance. The freely available algorithms developed in this work enable fast and accurate calculation of the cBP wave and CV parameters in datasets containing noninvasive ultrasound or magnetic resonance imaging data.NEW & NOTEWORTHY First, our proposed methods for CV parameter estimation and a comprehensive set of methods from the literature were tested using in silico and clinical datasets. Second, optimized algorithms for estimating cBP from aortic flow were developed and tested for a wide range of cBP morphologies, including catheter cBP data. Third, a dataset of simulated cBP waves was created using a three-element Windkessel model. Fourth, the Windkessel model dataset and optimized algorithms are freely available.

On the importance of spiral-flow inflow boundary conditions when using idealized artery geometries in the analysis of liver radioembolization: A parametric study.

In the last decades, the numerical studies on hemodynamics have become a valuable explorative scientific tool. The very first studies were done over idealized geometries, but as numerical methods and the power of computers have become more affordable, the studies tend to be patient specific. We apply the study to the numerical analysis of tumor-targeting during liver radioembolization (RE). RE is a treatment for liver cancer, and is performed by injecting radiolabeled microspheres via a catheter placed in the hepatic artery. The objective of the procedure is to maximize the release of radiolabeled microspheres into the tumor and avoid a healthy tissue damage. Idealized virtual arteries can serve as a generalist approach that permits to separately analyze the effect of a variable in the microsphere distribution with respect to others. However, it is important to use proper physiological boundary conditions (BCs). It is not obvious, the need to account for the effect of tortuosity when using an idealized virtual artery. We study the use of idealized geometry of a hepatic artery as a valid research tool, exploring the importance of using realistic spiral-flow inflow BC. By using a literature-based cancer scenario, we vary two parameters to analyze the microsphere distribution through the outlets of the geometry. The parameters varied are the type of microspheres injected and the microsphere injection velocity. The results with realistic inlet velocity profile showed that the particle distribution in the liver segments is not affected by the analyzed injection velocity values neither by the particle density. NOVELTY STATEMENT: In this article, we assessed the use of idealized geometries as a valid research tool and applied the use of an idealized geometry to the case of an idealized hepatic artery to study the particle-hemodynamics during radioembolization (RE). We studied three different inflow boundary conditions (BCs) to assess the usefulness of the geometry, two types of particle injection velocities and two types of commercially available microspheres for RE treatment. In recent years, the advent in computational resources allowed for more detailed patient-specific geometry generation and discretization and hemodynamics simulations. However, general studies based on idealized geometries can be performed in order to provide medical doctors with some basic and general guidelines when using a given catheter for a given cancer scenario. Moreover, using an idealized geometry can be a reasonable approach which allows us to isolate a given parameter and control other parameters, so that parameters can be independently assessed. Even though an idealized geometry does not match any patient's geometry, the use of an idealized geometry can be valid when drawing general conclusions that may be useful in patient-specific cases. However, we believe that even if an idealized hepatic artery geometry is used for the study, it is necessary to account for the upstream and downstream tortuosity of vessels through the BCs. In this work, we highlighted the need of modeling the tortuosity of upstream and downstream vasculatures through the BCs.

Liver Radioembolization: An Analysis of Parameters that Influence the Catheter-Based Particle-Delivery via CFD.

Radioembolization (RE) is a valuable treatment for liver cancer. It consists of administering radioactive microspheres by an intra-arterially placed catheter with the aim of lodging these microspheres, which are driven by the bloodstream, in the tumoral bed. Even though it is a safe treatment, some radiation-induced complications may arise. In trying to detect or solve the possible incidences that cause nontarget irradiation, simulating the particle- hemodynamics in hepatic arteries during RE by computational fluid dynamics (CFD) tools has become a valuable approach. This paper reviews the parameters that influence the outcome of RE and that have been studied via numerical simulations. In this numerical approach, the outcome of RE is regarded as successful if particles reach the artery branches that feed tumor-bearing liver segments. Up to 10 parameters have been reviewed. The variation of each parameter actually alters the hemodynamic pattern in the vicinities of the catheter tip and locally alters the incorporation of the particles into the bloodstream. Therefore, in general, the local influences of these parameters should result in global differences in terms of particle distribution in the hepatic artery branches. However, it has been observed that under some (qualitatively described) appropriate conditions where particles align with blood streamlines, the local influence resulting from a variation of a given parameter vanishes and no global differences are observed. Furthermore, the increasing number of CFD studies on RE suggests that numerical simulations have become an invaluable research tool in the study of RE.

A methodology for numerically analysing the hepatic artery haemodynamics during B-TACE: a proof of concept.

Balloon-occluded transarterial chemoembolisation (B-TACE) is an intraarterial transcatheter treatment for liver cancer. In B-TACE, an artery-occluding microballoon catheter occludes an artery and promotes collateral circulation for drug delivery to tumours. This paper presents a methodology for analysing the haemodynamics during B-TACE, by combining zero-dimensional and three-dimensional modelling tools. As a proof of concept, we apply the methodology to a patient-specific hepatic artery geometry and analyse two catheter locations. Results show that the blood flow redistribution can be predicted in this proof-of-concept study, suggesting that this approach could potentially be used to optimise catheter location.

Numerical zero-dimensional hepatic artery hemodynamics model for balloon-occluded transarterial chemoembolization.

Balloon-occluded transarterial chemoembolization (B-TACE) is a valuable treatment option for patients with inoperable malignant tumors in the liver. Balloon-occluded transarterial chemoembolization consists of the transcatheter infusion of an anticancer drug mixture and embolic agents. Contrary to conventional TACE, B-TACE is performed via an artery-occluding microballoon catheter, which makes the blood flow to redistribute due to the intra- and extrahepatic arterial collateral circulation. Several recent studies have stressed the importance of the redistribution of blood flow in enhancing the treatment outcome. In the present study, the geometries of a representative hepatic artery and the communicating arcades (CAs) are modeled. An in silico zero-dimensional hemodynamic model is created by characterizing the geometry and the boundary conditions and then is validated in vitro. The role of CAs is assessed by combining 2 cancer scenarios and 2 catheter locations. The importance of the diameter of the CAs is also studied. Results show that occluding a main artery leads to collateral circulation and CAs start to play a role in blood-flow redistribution. In summary, numerical zero-dimensional simulations permit a fast and reliable approach for exploring the blood-flow redistribution caused by the occlusion of a main artery, and this approach could be used during B-TACE planning.

The role of angled-tip microcatheter and microsphere injection velocity in liver radioembolization: A computational particle-hemodynamics study.

Liver radioembolization is a promising treatment option for combating liver tumors. It is performed by placing a microcatheter in the hepatic artery and administering radiation-emitting microspheres through the arterial bloodstream so that they get lodged in the tumoral bed. In avoiding nontarget radiation, the standard practice is to conduct a pretreatment, in which the microcatheter location and injection velocity are decided. However, between pretreatment and actual treatment, some of the parameters that influence the particle distribution in the liver can vary, resulting in radiation-induced complications. The present study aims to analyze the influence of a commercially available microcatheter with an angled tip and particle injection velocity in terms of segment-to-segment particle distribution. Specifically, 4 tip orientations and 2 injection velocities are combined to yield a set of 8 numerical simulations of the particle-hemodynamics in a patient-specific truncated hepatic artery. For each simulation, 4 cardiac pulses are simulated. Particles are injected during the first cycle, and the remaining pulses enable the majority of the injected particles to exit the computational domain. Results indicate that, in terms of injection velocity, particles are more spread out in the cross-sectional lumen areas as the injection velocity increases. The tip's orientation also plays a role because it influences the near-tip hemodynamics, therefore altering the particle travel through the hepatic artery. However, results suggest that particle distribution tries to match the blood flow split, therefore particle injection velocity and microcatheter tip orientation playing a minor role in segment-to-segment particle distribution.

Computational particle-haemodynamics analysis of liver radioembolization pretreatment as an actual treatment surrogate.

Liver radioembolization (RE) is a treatment option for patients with unresectable and chemorefractory primary and metastatic liver tumours. RE consists of intra-arterially administering via catheter radioactive microspheres that locally attack the tumours, sparing healthy tissue. Prior to RE, the standard practice is to conduct a treatment-mimicking pretreatment assessment via the infusion of 99m Tc-labelled macroaggregated albumin microparticles. The usefulness of this pretreatment has been debated in the literature, and thus, the aim of the present study is to shed light on this issue by numerically simulating the liver RE pretreatment and actual treatment particle-haemodynamics in a patient-specific hepatic artery under two different literature-based cancer scenarios and two different placements of a realistic end-hole microcatheter in the proper hepatic artery. The parameters that are analysed are the following: microagent quantity and size (accounting for RE pretreatment and treatment), catheter-tip position (near the proper hepatic artery bifurcation and away from it), and cancer burden (10% and 30% liver involvement). The conclusion that can be reached from the simulations is that when it comes to mimicking RE in terms of delivering particles to tumour-bearing segments, the catheter-tip position is much more important (because of the importance of local haemodynamic pattern alteration) than the infused microagents (i.e. quantity and size). Cancer burden is another important feature because the increase in blood flow rate to tumour-bearing segments increases the power to drag particles. These numerical simulation-based conclusions are in agreement with clinically observed events reported in the literature. Copyright © 2016 John Wiley & Sons, Ltd.

Numerical investigation of liver radioembolization via computational particle-hemodynamics: The role of the microcatheter distal direction and microsphere injection point and velocity.

Liver radioembolization is a treatment option for patients with primary and secondary liver cancer. The procedure consists of injecting radiation-emitting microspheres via an intra-arterially placed microcatheter, enabling the deposition of the microspheres in the tumoral bed. The microcatheter location and the particle injection rate are determined during a pretreatment work-up. The purpose of this study was to numerically study the effects of the injection characteristics during the first stage of microsphere travel through the bloodstream in a patient-specific hepatic artery (i.e., the near-tip particle-hemodynamics and the segment-to-segment particle distribution). Specifically, the influence of the distal direction of an end-hole microcatheter and particle injection point and velocity were analyzed. Results showed that the procedure targeted the right lobe when injecting from two of the three injection points under study and the remaining injection point primarily targeted the left lobe. Changes in microcatheter direction and injection velocity resulted in an absolute difference in exiting particle percentage for a given liver segment of up to 20% and 30%, respectively. It can be concluded that even though microcatheter placement is presumably reproduced in the treatment session relative to the pretreatment angiography, the treatment may result in undesired segment-to-segment particle distribution and therefore undesired treatment outcomes due to modifications of any of the parameters studied, i.e., microcatheter direction and particle injection point and velocity.

Computational assessment of the effects of the catheter type on particle-hemodynamics during liver radioembolization.

Radioembolization, which consist of the implantation of radioactive microspheres via intra-arterially placed microcatheter, is a safe and effective treatment for liver cancer. Nevertheless, radioembolization-related complications and side effects may arise, which are an active area of ongoing research. The catheter design has been claimed as an option in reducing these complications. In this paper, the influence of catheter type and location are investigated. The study was undertaken by numerically simulating the particle-hemodynamics in a patient-specific hepatic artery during liver radioembolization. The parameters modified were cancer scenario (30% liver involvement in the right lobe, 'scenario A', and in both lobes, 'scenario B'), catheter type (standard end-hole microcatheter, SMC, and antireflux catheter, ARC), and the location of the tip in the proper hepatic artery (in the straight part, 'inlet', and near the bifurcation, 'bifurcation'). Comparing ARC with SMC, the maximum and average (over segments) absolute difference in the percentage of particles that reached each segment were 19.62% and 9.06% when injecting near the inlet for scenario A; 3.54% and 1.07% injecting near the bifurcation for scenario A; and 18.31% and 11.85% injecting near the inlet for scenario B. It seems, therefore, that the location of the catheter tip in the artery is crucial in terms of particle distribution. Moreover, even though the near-tip blood flow was altered due to the presence of a catheter, the particle distribution matched the flow split if the distance between the injection point and the first bifurcation encountered enabled the alignment of particles with blood flow.

Liver cancer arterial perfusion modelling and CFD boundary conditions methodology: a case study of the haemodynamics of a patient-specific hepatic artery in literature-based healthy and tumour-bearing liver scenarios.

Some of the latest treatments for unresectable liver malignancies (primary or metastatic tumours), which include bland embolisation, chemoembolisation, and radioembolisation, among others, take advantage of the increased arterial blood supply to the tumours to locally attack them. A better understanding of the factors that influence this transport may help improve the therapeutic procedures by taking advantage of flow patterns or by designing catheters and infusion systems that result in the injected beads having increased access to the tumour vasculature. Computational analyses may help understand the haemodynamic patterns and embolic-microsphere transport through the hepatic arteries. In addition, physiological inflow and outflow boundary conditions are essential in order to reliably represent the blood flow through arteries. This study presents a liver cancer arterial perfusion model based on a literature review and derives boundary conditions for tumour-bearing liver-feeding hepatic arteries based on the arterial perfusion characteristics of normal and tumorous liver segment tissue masses and the hepatic artery branching configuration. Literature-based healthy and tumour-bearing realistic scenarios are created and haemodynamically analysed for the same patient-specific hepatic artery. As a result, this study provides boundary conditions for computational fluid dynamics simulations that will allow researchers to numerically study, for example, various intravascular devices used for liver disease intra-arterial treatments with different cancer scenarios. Copyright © 2016 John Wiley & Sons, Ltd.

Physiological outflow boundary conditions methodology for small arteries with multiple outlets: a patient-specific hepatic artery haemodynamics case study.

Physiological outflow boundary conditions are necessary to carry out computational fluid dynamics simulations that reliably represent the blood flow through arteries. When dealing with complex three-dimensional trees of small arteries, and therefore with multiple outlets, the robustness and speed of convergence are also important. This study derives physiological outflow boundary conditions for cases in which the physiological values at those outlets are not known (neither in vivo measurements nor literature-based values are available) and in which the tree exhibits symmetry to some extent. The inputs of the methodology are the three-dimensional domain and the flow rate waveform and the systolic and diastolic pressures at the inlet. The derived physiological outflow boundary conditions, which are a physiological pressure waveform for each outlet, are based on the results of a zero-dimensional model simulation. The methodology assumes symmetrical branching and is able to tackle the flow distribution problem when the domain outlets are at branches with a different number of upstream bifurcations. The methodology is applied to a group of patient-specific arteries in the liver. The methodology is considered to be valid because the pulsatile computational fluid dynamics simulation with the inflow flow rate waveform (input of the methodology) and the derived outflow boundary conditions lead to physiological results, that is, the resulting systolic and diastolic pressures at the inlet match the inputs of the methodology, and the flow split is also physiological.