A proof-of-concept pipeline to guide evaluation of tumor tissue perfusion by dynamic contrast-agent imaging: Direct simulation and inverse tracer-kinetic procedures.

Dynamic contrast-enhanced (DCE) perfusion imaging has shown great potential to non-invasively assess cancer development and its treatment by their characteristic tissue signatures. Different tracer kinetics models are being applied to estimate tissue and tumor perfusion parameters from DCE perfusion imaging. The goal of this work is to provide an model-based pipeline to evaluate how these DCE imaging parameters may relate to the true tissue parameters.

Assessing Early Cardiac Outflow Tract Adaptive Responses Through Combined Experimental-Computational Manipulations.

Mechanical forces are essential for proper growth and remodeling of the primitive pharyngeal arch arteries (PAAs) into the great vessels of the heart. Despite general acknowledgement of a hemodynamic-malformation link, the direct correlation between hemodynamics and PAA morphogenesis remains poorly understood. The elusiveness is largely due to difficulty in performing isolated hemodynamic perturbations and quantifying changes in-vivo.

A whole lung in silico model to estimate age dependent particle dosimetry.

Anatomical and physiological changes alter airflow characteristics and aerosol distribution in the developing lung. Correlation between age and aerosol dosimetry is needed, specifically because youth are more susceptible to medication side effects. In this study, we estimate aerosol dosages (particle diameters of 1, 3, and 5 [Formula: see text]m) in a 3 month-old infant, a 6 year-old child, and a 36 year-old adult by performing whole lung subject-specific particle simulations throughout respiration.

Simulation of a detoxifying organ function: Focus on hemodynamics modeling and convection-reaction numerical simulation in microcirculatory networks.

When modeling a detoxifying organ function, an important component is the impact of flow on the metabolism of a compound of interest carried by the blood. We here study the effects of red blood cells (such as the Fahraeus-Lindqvist effect and plasma skimming) on blood flow in typical microcirculatory components such as tubes, bifurcations and entire networks, with particular emphasis on the liver as important representative of detoxifying organs. In one of the plasma skimming models, under certain conditions, oscillations between states are found and analyzed in a methodical study to identify their causes and influencing parameters.

Predicting the risk of post-hepatectomy portal hypertension using a digital twin: A clinical proof of concept.

Background & Aims: Despite improvements in medical and surgical techniques, post-hepatectomy liver failure (PHLF) remains the leading cause of postoperative death. High postoperative portal vein pressure (P) and portocaval gradient (PCG), which cannot be predicted by current tools, are the most important determinants of PHLF. Therefore, we aimed to evaluate a digital twin to predict the risk of postoperative portal hypertension (PHT).

Verification of the coupled-momentum method with Womersley's Deformable Wall analytical solution.

In this paper, we perform a verification study of the Coupled-Momentum Method (CMM), a 3D fluid-structure interaction (FSI) model which uses a thin linear elastic membrane and linear kinematics to describe the mechanical behavior of the vessel wall. The verification of this model is done using Womersley's deformable wall analytical solution for pulsatile flow in a semi-infinite cylindrical vessel. This solution is, under certain premises, the analytical solution of the CMM and can thus be used for model verification.

Cohort-based multiscale analysis of hemodynamic-driven growth and remodeling of the embryonic pharyngeal arch arteries.

Growth and remodeling of the primitive pharyngeal arch artery (PAA) network into the extracardiac great vessels is poorly understood but a major source of clinically serious malformations. Undisrupted blood flow is required for normal PAA development, yet specific relationships between hemodynamics and remodeling remain largely unknown. Meeting this challenge is hindered by the common reductionist analysis of morphology to single idealized models, where in fact structural morphology varies substantially.

Closed-Loop Lumped Parameter Modeling of Hemodynamics During Cirrhogenesis in Rats.

Objective: Cirrhosis is the common end stage of any given chronic liver disease, developing after persistent destruction and regeneration of parenchymal liver cells. The associated architectural distortion increases the intrahepatic vascular resistance, leading to portal hypertension and systemic circulatory disorders. This study investigates the impact of the changing vascular resistances on the hepatic and global circulation hemodynamics during cirrhogenesis.

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 atrioventric-ular valve regurgitation (AVVR) in babies born with an already very challenging heart condition, i.e., with single ventricle physiology.

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

The 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 spectroscopy enables to assess hepatic ICG concentration over time in the liver tissue.

Computational simulation of postoperative pulmonary flow distribution in Alagille patients with peripheral pulmonary artery stenosis.

Background: Up to 90% of individuals with Alagille syndrome have congenital heart diseases. Peripheral pulmonary artery stenosis (PPS), resulting in right ventricular hypertension and pulmonary flow disparity, is one of the most common abnormalities, yet the hemodynamic effects are ill-defined, and optimal patient management and treatment strategies are not well established. The purpose of this pilot study is to use recently refined computational simulation in the setting of multiple surgical strategies, to examine the influence of pulmonary artery reconstruction on hemodynamics in this population.

Benchmark problems for numerical treatment of backflow at open boundaries.

In computational fluid dynamics, incoming velocity at open boundaries, or backflow, often yields unphysical instabilities already for moderate Reynolds numbers. Several treatments to overcome these backflow instabilities have been proposed in the literature. However, these approaches have not yet been compared in detail in terms of accuracy in different physiological regimes, in particular because of the difficulty to generate stable reference solutions apart from analytical forms.

Tumor Cell Load and Heterogeneity Estimation From Diffusion-Weighted MRI Calibrated With Histological Data: an Example From Lung Cancer.

Diffusion-weighted magnetic resonance imaging (DWI) is a key non-invasive imaging technique for cancer diagnosis and tumor treatment assessment, reflecting Brownian movement of water molecules in tissues. Since densely packed cells restrict molecule mobility, tumor tissues produce usually higher signal (a.k.

Modulating Portal Hemodynamics With Vascular Ring Allows Efficient Regeneration After Partial Hepatectomy in a Porcine Model.

Objective: To investigate safety and efficacy of temporary portal hemodynamics modulation with a novel percutaneously adjustable vascular ring (MID-AVR) onto a porcine model of 75% hepatectomy.

Background: Postoperative liver failure is a leading cause of mortality after major hepatectomy. Portal flow modulation is an increasingly accepted concept to prevent postoperative liver failure.

Inverse problems in reduced order models of cardiovascular haemodynamics: aspects of data assimilation and heart rate variability.

Inverse problems in cardiovascular modelling have become increasingly important to assess each patient individually. These problems entail estimation of patient-specific model parameters from uncertain measurements acquired in the clinic. In recent years, the method of data assimilation, especially the unscented Kalman filter, has gained popularity to address computational efficiency and uncertainty consideration in such problems.

Partial hepatectomy hemodynamics changes: Experimental data explained by closed-loop lumped modeling.

The liver function may be degraded after partial liver ablation surgery. Adverse liver hemodynamics have been shown to be associated to liver failure. The link between these hemodynamics changes and ablation size is however poorly understood.

Aerosol transport throughout inspiration and expiration in the pulmonary airways.

Little is known about transport throughout the respiration cycle in the conducting airways. It is challenging to appropriately describe the time-dependent number of particles entering back into the model during exhalation. Modeling the entire lung is not feasible; therefore, multidomain methods must be used.

Inferring Growth Control Mechanisms in Growing Multi-cellular Spheroids of NSCLC Cells from Spatial-Temporal Image Data.

We develop a quantitative single cell-based mathematical model for multi-cellular tumor spheroids (MCTS) of SK-MES-1 cells, a non-small cell lung cancer (NSCLC) cell line, growing under various nutrient conditions: we confront the simulations performed with this model with data on the growth kinetics and spatial labeling patterns for cell proliferation, extracellular matrix (ECM), cell distribution and cell death. We start with a simple model capturing part of the experimental observations. We then show, by performing a sensitivity analysis at each development stage of the model that its complexity needs to be stepwise increased to account for further experimental growth conditions.

Adaptive outflow boundary conditions improve post-operative predictions after repair of peripheral pulmonary artery stenosis.

Peripheral pulmonary artery stenosis (PPS) is a congenital abnormality resulting in pulmonary blood flow disparity and right ventricular hypertension. Despite recent advance in catheter-based interventions, surgical reconstruction is still preferred to treat complex PPS. However optimal surgical strategies remain unclear.

Aerosols in healthy and emphysematous in silico pulmonary acinar rat models.

There 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 (Oakes et al.

Data assimilation and modelling of patient-specific single-ventricle physiology with and without valve regurgitation.

A closed-loop lumped parameter model of blood circulation is considered for single-ventricle shunt physiology. Its parameters are estimated by an inverse problem based on patient-specific haemodynamics measurements. As opposed to a black-box approach, maximizing the number of parameters that are related to physically measurable quantities motivates the present model.

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 outflow tract (RVOT). Due to this pathological anatomy, available transcatheter valves are usually too small to be deployed there. To avoid surgical valve replacement, an alternative consists in implanting a reducer prior to or in combination with the valve.