Model and methods to assess hepatic function from indocyanine green fluorescence dynamical measurements of liver tissue

International audienceThe indocyanine green (ICG) clearance, presented as plasma disappearance rate is, presently, a reliable method to estimate the hepatic " function ". However, this technique is not instantaneously available and thus cannot been used intra-operatively (during liver surgery). Near-infrared spec-troscopy enables to assess hepatic ICG concentration over time in the liver tissue. This article proposes to extract more information from the liver intensity dynamics by interpreting it through a dedicated pharmacokinetics model. In order to account for the different exchanges between the liver tissues, the proposed model includes three compartments for the liver model (sinusoids, hepa-tocytes and bile canaliculi). The model output dependency to parameters is studied with sensitivity analysis and solving an inverse problem on synthetic data. The estimation of model parameters is then performed with in-vivo measurements in rabbits (El-Desoky et al. 1999). Parameters for different liver states are estimated, and their link with liver function is investigated. A nonlinear (Michaelis-Menten type) excretion rate from the hepatocytes to the bile canaliculi was necessary to reproduce the measurements for different liver conditions. In case of bile duct ligation, the model suggests that this rate is reduced, and that the ICG is stored in the hepatocytes. Moreover, the level of ICG remains high in the blood following the ligation of the bile duct. The percentage of retention of indocyanine green in blood, which is a common test for hepatic function estimation, is also investigated with the model. The impact of bile duct ligation and reduced liver inflow on the percentage of ICG retention in blood is studied. The estimation of the pharmacokinetics model parameters may lead to an evaluation of different liver functions

Outflow boundary conditions for 3D simulations of non-periodic blood flow and pressure fields in deformable arteries

The simulation of blood flow and pressure in arteries requires outflow boundary conditions that incorporate models of downstream domains. We previously described a coupled multidomain method to couple analytical models of the downstream domains with 3D numerical models of the upstream vasculature. This prior work either included pure resistance boundary conditions or impedance boundary conditions based on assumed periodicity of the solution. However, flow and pressure in arteries are not necessarily periodic in time due to heart rate variability, respiration, complex transitional flow or acute physiological changes. We present herein an approach for prescribing lumped parameter outflow boundary conditions that accommodate transient phenomena. We have applied this method to compute haemodynamic quantities in different physiologically relevant cardiovascular models, including patient-specific examples, to study non-periodic flow phenomena often observed in normal subjects and in patients with acquired or congenital cardiovascular disease. The relevance of using boundary conditions that accommodate transient phenomena compared with boundary conditions that assume periodicity of the solution is discussed

A reduced-order modeling for efficient design study of artificial valve in enlarged ventricular outflow tracts

A computational approach is proposed for efficient design study of a reducer stent to be percutaneously implanted in enlarged right ventricular outflow tracts (RVOT). The need for such a device is driven by the absence of bovine or artificial valves which could be implanted in these RVOT to replace the absent or incompetent native valve, as is often the case over time after Tetralogy of Fallot repair. Hemodynamics are simulated in the stented RVOT via a reduce order model based on proper orthogonal decomposition (POD), while the artificial valve is modeled as a thin resistive surface. The reduced order model is obtained from the numerical solution on a reference device configuration, then varying the geometrical parameters (diameter) for design purposes. To validate the approach, forces exerted on the valve and on the reducer are monitored, varying with geometrical parameters, and compared with the results of full CFD simulations. Such an approach could also be useful for uncertainty quantification

Efficient blood flow simulations for the design of stented valve reducer in enlarged ventricular outflow tracts

Tetralogy of Fallot is a congenital heart disease characterized over time, after the initial repair, by the absence of a functioning pulmonary valve, which causes regurgitation, and by progressive enlargement of the right ventricle and pulmonary arteries. Due to this pathological anatomy, available transcatheter valves are usually too small to be deployed in the enlarged right ventricular outflow tracts (RVOT). To avoid surgical valve replacement, an alternative consists in implanting a reducer prior to or in combination with a transcatheter valve. We describe a computational model to study the effect of a stented valve RVOT reducer on the hemodynamics in enlarged ventricular outflow tracts. To this aim, blood flow in the right ventricular outflow tract is modeled via the incompressible Navier--Stokes equations coupled to a simplified valve model, numerically solved with a standard finite element method and with a reduced order model based on Proper Orthogonal Decomposition (POD). Numerical simulations are based on a patient geometry obtained from medical imaging and boundary conditions tuned according to measurements of inlet flow rates and pressures. Different geometrical models of the reducer are built, varying its length and/or diameter, and compared with the initial device-free state. Simulations thus investigate multiple device configurations and describe the effect of geometry on hemodynamics. Forces exerted on the valve and on the reducer are monitored, varying with geometrical parameters. Results support the thesis that the reducer does not introduce significant pressure gradients, as was found in animal experiments. Finally, we demonstrate how computational complexity can be reduced with POD

Aerosols in Healthy and Emphysematous In Silico Pulmonary Acinar Rat Models

International audienceThere has been relatively little attention given on predicting particle deposition in the respiratory zone of the diseased lungs despite the high prevalence of chronic obstructive pulmonary disease (COPD). Increased alveolar volume and deterioration of alveolar septum, characteristic of emphysema, may alter the amount and location of particle deposition compared to healthy lungs, which is particularly important for toxic or therapeutic aerosols. In an attempt to shed new light on aerosol transport and deposition in emphysematous lungs, we performed numerical simulations in models of healthy and emphysematous acini motivated by recent experimental lobar-level data in rats~\citep{OakesEmp}. Compared to healthy acinar structures, models of emphysematous subacini were created by removing inter-septal alveolar walls and enhancing the alveolar volume in either a homogeneous or heterogeneous fashion. Flow waveforms and particle properties were implemented to match the experimental data. The occurrence of flow separation and recirculation within alveolar cavities was found in proximal generations of the healthy zones, in contrast to the radial-like airflows observed in the diseased regions. In agreement with experimental data, simulations point to particle deposition concentrations that are more heterogeneously distributed in the diseased models compared with the healthy one. Yet, simulations predicted less deposition in the emphysematous models in contrast to some experimental studies, a likely consequence due to the shallower penetration depths and modified flow topologies in disease compared to health. These spatial-temporal particle transport simulations provide new insight on deposition in the emphysematous acini and shed light on experimental observations

A Lumped Parameter Model to Study Atrioventricular Valve Regurgitation in Stage 1 and Changes Across Stage 2 Surgery in Single Ventricle Patients

Goal: This manuscript evaluates atrioventricular valve regurgitation (AVVR) in babies born with an already very challenging heart condition, i.e. with single ventricle physiology. Although the second surgery that single ventricle patients undergo is thought to decrease AVVR, there is much controversy in the clinical literature about AVVR treatment. Methods: The effect of atrioventricular valve regurgitation (AVVR) on Stage 1 haemodynamics and resulting acute changes from conversion to Stage 2 circulation in single ventricle patients are analysed through lumped parameter models. Several degrees of AVVR severity are analysed, for two types of valve regurgitation: incomplete leaflet closure and valve prolapse. Results: The models show that increasing AVVR in Stage 1 induces the following effects: i) higher stroke volume and associated decrease in ventricular end-systolic volume; ii) increase in atrial volumes with V-loop enlargement in pressure-volume curves; iii) pulmonary venous hypertension. The Stage 2 surgery results in volume unloading of the ventricle thereby driving a decrease in AVVR. However, this effect is offset by an increase in ventricular pressures resulting in a net increase in regurgitation fraction (RF) of approximately 0.1 (for example, in severe AVVR, the pre-operative RF increases from ~60% to ~70% post-operatively). Moreover, despite some improvements to sarcomere function early after Stage 2 surgery, it may deteriorate in cases of severe AVVR. Conclusion: In patients with moderate to severe AVVR, restoration of atrioventricular valve competence prior to, or at the time of, Stage 2 surgery would likely lead to improved haemodynamics and clinical outcome as the models suggest that uncorrected AVVR can worsen across Stage 2 surgery. This was found to be independent of the AVVR degree and mechanisms

A cohort longitudinal study identifies morphology and hemodynamics predictors of abdominal aortic aneurysm growth

International audienceAbdominal aortic aneurysms (AAA) are localized, commonly occurring aortic dilations. Following rupture only immediate treatment can prevent morbidity and mortality. AAA maximal diameter and growth are the current metrics to evaluate the associated risk and plan intervention. Although these criteria alone lack patient specificity, predicting their evolution would improve clinical decision. If the disease is known to be associated with altered morphology and blood flow, intraluminal thrombus deposit and clinical symptoms, the growth mechanisms are yet to be fully understood. In this retrospective longitudinal study of 138 scans, morphological analysis and blood flow simulations for 32 patients with clinically diagnosed AAAs and several follow-up CT-scans, are performed and compared to 9 control subjects. Several metrics stratify patients between healthy, low and high risk groups. Local correlations between hemodynamic metrics and AAA growth are also explored but due to their high inter-patient variability, do not explain AAA heterogeneous growth. Finally, high-risk predictors trained with successively clinical, morphological, hemodynamic and all data, and their link to the AAA evolution are built from supervise learning. Predictive performance is high for morphological, hemodynamic and all data, in contrast to clinical data. The morphology-based predictor exhibits an interesting effort-predictability tradeoff to be validated for clinical translation

A poroelastic model valid in large strains with applications to perfusion in cardiac modeling

National audienceSee http://hal.archives-ouvertes.fr/docs/00/59/26/88/ANNEX/r_5H9QH1SR.pd

Aerosols in the lung: multi-domain transport and coupling

International audienceIn this paper, we present a framework that couples three-dimensional (3D) to one-dimensional (1D) transport models to predict particle deposition in the respiratory airways throughout respiration. During respiration, the time dependent flow rate and particle concentration can be passed between the domains (inspiration: 3D to 1D, expiration: 1D to 3D). This framework enables us to predict particle transport and deposition in the whole lung and throughout both inspiration and expiration

Modified Navier-Stokes equations for the outflow boundary conditions in hemodynamics

International audienceWe present a new approach for the outflow boundary conditions of Navier-Stokes equations in hemodynamics. We first describe some existing 3D-0D coupling methods and highlight benefits and disadvantages of each of them. We then introduce a new method that consists in adding a 3D artificial part where the Navier-Stokes equations are modified to obtain an equivalent energy balance to a standard coupling with a 3-element Windkessel model. We investigate theoretically the stability of the system and compare it to previously introduced methods. Finally we compare these coupling methods for numerical simulations of blood flow in three patient-specific models, which represent different flow regimes in the pulmonary and systemic circulations. The new method, especially in its hybrid form, is a possible alternative to existing methods. It can be in particular convenient in codes that do not allow users to implement non-standard boundary conditions