Periodic Reporting for period 1 - MoDeLLiver (NUMERICAL MODELLING OF HEMODYNAMICS AND PHARMACOKINETICS FOR CLINICAL TRANSLATION)
Période du rapport: 2020-10-01 au 2022-03-31
Surgical interventions often require vascular procedures consisting in cutting vessels, removing organ parts or suturing new connections. Can we understand and predict blood flow changes due to an intervention? This is important to improve treatment outcome. MoDeLLiver aims to develop a haemodynamic mathematical model to guide interventions in particular in the lung and liver. To better predict intervention outcome, several aspects must be considered, including the local point of intervention, whole organ perfusion and function as well as their interaction with the entire circulation. The model needs to include organ interactions and remodelling due to surgery or diseases. For personalized planning, simulations must be based on patient data, both to parameterize the model and validate its prediction. Such data are however ideally non-invasive ones. Despite great advances in dynamic imaging, the link between signal and underlying tissue perfusion and function remains to be elucidated. Their better understanding will bring new data for personalised simulation.The final aim is to provide to practitioners a simulation planning tool.
We report here the publishable work of this first period. It is part of the scientific objective S1, the building block of the proposal, putting in place fundamental modelling bricks for hemodynamics. It addresses the question of how the circulatory system reacts to a component change such as a surgical act. Numerical modelling of hemodynamics in the entire circulation was carried out for two targeted surgical acts: (1) for a pulmonary hypertension palliative treatment – the Potts shunt, and (2) for a liver surgery – partial hepatectomy.
(1) Multiscale hemodynamics modelling of a pulmonary hypertension palliative treatment.
The Potts shunt (PS) was suggested as palliation for patients with suprasystemic pulmonary arterial hypertension (PAH) and right ventricular (RV) failure. The shunt is an artificial conduit that allows blood to go from the higher pressure pulmonary arteries (PA) to the lower pressure descending aorta (DAo). PS however, can result in poorly understood mortality. In [1], a patient-specific multiscale model of PAH physiology and PS was developed, with the major vessels represented in 3D coupled to a reduced model of the rest of the circulation. The results show that PS produces near-equalisation of the DAo and PA pressures, as was seen for the patient with the same PS diameter. Changes in key local and global quantities of interest were quantified for different shunt sizes. For example RV work increased but without increasing RV end-diastolic volume. Overall, this model reasonably represents patient-specific haemodynamics pre- and post-creation of the PS, providing insights into physiology of this complex condition, and presents a predictive tool that could be useful for clinical decision-making regarding suitability for PS in certain PAH patients.
(2) Hemodynamics modelling of a liver surgery at the population level.
Recently a reduced model of the cardiovascular system was proposed to simulate the hemodynamics response to partial hepatectomy and evaluate the risk of portal hypertension due to this surgery. Model parameters are tuned based on each patient data. This work [2] focuses on a global sensitivity analysis study of such model to better understand the main drivers of the clinical outputs of interest. The analysis suggested which parameters should be considered patient-specific and which can be assumed constant without losing in accuracy of the predictions. The computed results gave new insights on how to improve the calibration of some model parameters. The parameter distributions enable the creation of a sharable virtual population, that can be the basis of a fast analysis in the same spirit of [2] for other surgical interventions.
Regarding the scientific objective S2 on a zoom on organs in healthy and disease states, we have written in collaboration with Stanford U. colleagues, a bookchapter [3].
References:
[1] Pant S, et al. Multiscale modelling of Potts shunt as a potential palliative treatment for suprasystemic idiopathic pulmonary artery hypertension: a paediatric case study. Biomechanics and Modeling in Mechanobiology 2022.
[2] Sala L, et al. Sensitivity analysis of a mathematical model simulating the post-hepatectomy hemodynamics response. Subm.
[3] Yang W, et al. Modeling the Pulmonary Circulation in CHD: Clinical Concepts, Engineering Applications, and an Integrated Medico-Engineering Approach. In Modelling Congenital Heart Disease 2022
(1) Multiscale hemodynamics modelling of a pulmonary hypertension palliative treatment.
The Potts shunt (PS) was suggested as palliation for patients with suprasystemic pulmonary arterial hypertension (PAH) and right ventricular (RV) failure. The shunt is an artificial conduit that allows blood to go from the higher pressure pulmonary arteries (PA) to the lower pressure descending aorta (DAo). PS however, can result in poorly understood mortality. In [1], a patient-specific multiscale model of PAH physiology and PS was developed, with the major vessels represented in 3D coupled to a reduced model of the rest of the circulation. The results show that PS produces near-equalisation of the DAo and PA pressures, as was seen for the patient with the same PS diameter. Changes in key local and global quantities of interest were quantified for different shunt sizes. For example RV work increased but without increasing RV end-diastolic volume. Overall, this model reasonably represents patient-specific haemodynamics pre- and post-creation of the PS, providing insights into physiology of this complex condition, and presents a predictive tool that could be useful for clinical decision-making regarding suitability for PS in certain PAH patients.
(2) Hemodynamics modelling of a liver surgery at the population level.
Recently a reduced model of the cardiovascular system was proposed to simulate the hemodynamics response to partial hepatectomy and evaluate the risk of portal hypertension due to this surgery. Model parameters are tuned based on each patient data. This work [2] focuses on a global sensitivity analysis study of such model to better understand the main drivers of the clinical outputs of interest. The analysis suggested which parameters should be considered patient-specific and which can be assumed constant without losing in accuracy of the predictions. The computed results gave new insights on how to improve the calibration of some model parameters. The parameter distributions enable the creation of a sharable virtual population, that can be the basis of a fast analysis in the same spirit of [2] for other surgical interventions.
Regarding the scientific objective S2 on a zoom on organs in healthy and disease states, we have written in collaboration with Stanford U. colleagues, a bookchapter [3].
References:
[1] Pant S, et al. Multiscale modelling of Potts shunt as a potential palliative treatment for suprasystemic idiopathic pulmonary artery hypertension: a paediatric case study. Biomechanics and Modeling in Mechanobiology 2022.
[2] Sala L, et al. Sensitivity analysis of a mathematical model simulating the post-hepatectomy hemodynamics response. Subm.
[3] Yang W, et al. Modeling the Pulmonary Circulation in CHD: Clinical Concepts, Engineering Applications, and an Integrated Medico-Engineering Approach. In Modelling Congenital Heart Disease 2022
The progress beyond the state of the art of S1 is summarized for the two targeted surgical acts reported above:
(1) Clinical response to Potts shunt (PS) creation is mixed, the mechanisms of which are poorly understood. Although cardiovascular magnetic resonance imaging can provide useful insights, the full-spectrum of haemodynamic changes due to the PS creation is not accessible. In contrast, computational models that can predict the patient-specific post-procedural haemodynamic changes based upon pre-operative characteristics can prove to be a useful tool in understanding this complex condition. Except one non patient-specific study, which did not include 3D information, untill [1] there was no comprehensive computational investigation of this subject. The patient-specific multiscale model (MM) was validated and provides insights into flow features through and around the PS. The results from the computationally expensive MM were compared to the less demanding reduced model, exploring the validity of the latter in providing solutions for patient-specific parameter estimation and global assessment of such a complex condition for different PS designs. This computational model is adaptable to other patient cases.
(2) Global sensitivity analysis (GSA) for cardiovascular models has already shown its usefulness and, when combined with the polynomial chaos expansion method, its efficiency. However, GSA has rarely been applied to (closed-loop) lumped models of the entire cardiovascular system. This is the focus of [2], where by contrast to previous work, parameters of the different systemic blocks were varied. By design, the study reflects the variability of the studied population. In particular while performing the sensitivity analysis, model outputs needed to be constrained to certain physiological ranges. An innovative approach exploited the features of the polynomial chaos expansion method to reduce the overall computational cost. Although this work is focused on partial hepatectomy, the pipeline to gain insights for patient-specific parameterization and to define a physiologically relevant virtual population that can be applied to other cardiovascular hemodynamics models.
Through the MoDeLLiver project, we expect results until the end of the project on:
1) How the circulatory system reacts to a component change such as a surgical act, and how the different components of the circulatory system affect a blood-injected substance circulation.
2) Which minimal organ model is needed to predict hemodynamics and transport/function changes due to disease and intervention.
3) Understanding of the link between dynamic imaging and the underlying observed system.
4) Clinical translation.
(1) Clinical response to Potts shunt (PS) creation is mixed, the mechanisms of which are poorly understood. Although cardiovascular magnetic resonance imaging can provide useful insights, the full-spectrum of haemodynamic changes due to the PS creation is not accessible. In contrast, computational models that can predict the patient-specific post-procedural haemodynamic changes based upon pre-operative characteristics can prove to be a useful tool in understanding this complex condition. Except one non patient-specific study, which did not include 3D information, untill [1] there was no comprehensive computational investigation of this subject. The patient-specific multiscale model (MM) was validated and provides insights into flow features through and around the PS. The results from the computationally expensive MM were compared to the less demanding reduced model, exploring the validity of the latter in providing solutions for patient-specific parameter estimation and global assessment of such a complex condition for different PS designs. This computational model is adaptable to other patient cases.
(2) Global sensitivity analysis (GSA) for cardiovascular models has already shown its usefulness and, when combined with the polynomial chaos expansion method, its efficiency. However, GSA has rarely been applied to (closed-loop) lumped models of the entire cardiovascular system. This is the focus of [2], where by contrast to previous work, parameters of the different systemic blocks were varied. By design, the study reflects the variability of the studied population. In particular while performing the sensitivity analysis, model outputs needed to be constrained to certain physiological ranges. An innovative approach exploited the features of the polynomial chaos expansion method to reduce the overall computational cost. Although this work is focused on partial hepatectomy, the pipeline to gain insights for patient-specific parameterization and to define a physiologically relevant virtual population that can be applied to other cardiovascular hemodynamics models.
Through the MoDeLLiver project, we expect results until the end of the project on:
1) How the circulatory system reacts to a component change such as a surgical act, and how the different components of the circulatory system affect a blood-injected substance circulation.
2) Which minimal organ model is needed to predict hemodynamics and transport/function changes due to disease and intervention.
3) Understanding of the link between dynamic imaging and the underlying observed system.
4) Clinical translation.