Numerical and experimental investigation of mucociliary clearance breakdown in cystic fibrosis.

The human tracheobronchial tree surface is covered with mucus. A healthy mucus is a heterogeneous material flowing toward the esophagus and a major defense actor against local pathogen proliferation and pollutant deposition. An alteration of mucus or its environment such as in cystic fibrosis dramatically impacts the mucociliary clearance. In the present study, we investigate the mechanical organization and the physics of such mucus in human lungs by means of a joint experimental and numerical work. In particular, we focus on the influence of the shear-thinning mucus mobilized by a ciliated epithelium for mucociliary clearance. The proposed robust numerical method is able to manage variations of more than 5 orders of magnitude in the shear rate and viscosity. It leads to a cartography that allows to discuss major issues on defective mucociliary clearance in cystic fibrosis. Furthermore, the computational rheological analysis based on measurements shows that cystic fibrosis shear-thinning mucus tends to aggregate in regions of lower clearance. Yet, a rarefaction of periciliary fluid has a greater impact than the mucus shear-thinning effects.

Blood flow in the cerebral venous system: modeling and simulation.

The development of a software platform incorporating all aspects, from medical imaging data, through three-dimensional reconstruction and suitable meshing, up to simulation of blood flow in patient-specific geometries, is a crucial challenge in biomedical engineering. In the present study, a fully three-dimensional blood flow simulation is carried out through a complete rigid macrovascular circuit, namely the intracranial venous network, instead of a reduced order simulation and partial vascular network. The biomechanical modeling step is carefully analyzed and leads to the description of the flow governed by the dimensionless Navier-Stokes equations for an incompressible viscous fluid. The equations are then numerically solved with a free finite element software using five meshes of a realistic geometry obtained from medical images to prove the feasibility of the pipeline. Some features of the intracranial venous circuit in the supine position such as asymmetric behavior in merging regions are discussed.

Mathematical Model of Cardiovascular and Metabolic Responses to Umbilical Cord Occlusions in Fetal Sheep.

Fetal acidemia during labor is associated with an increased risk of brain injury and lasting neurological deficits. This is in part due to the repetitive occlusions of the umbilical cord (UCO) induced by uterine contractions. Whereas fetal heart rate (FHR) monitoring is widely used clinically, it fails to detect fetal acidemia. Hence, new approaches are needed for early detection of fetal acidemia during labor. We built a mathematical model of the UCO effects on FHR, mean arterial blood pressure (MABP), oxygenation and metabolism. Mimicking fetal experiments, our in silico model reproduces salient features of experimentally observed fetal cardiovascular and metabolic behavior including FHR overshoot, gradual MABP decrease and mixed metabolic and respiratory acidemia during UCO. Combined with statistical analysis, our model provides valuable insight into the labor-like fetal distress and guidance for refining FHR monitoring algorithms to improve detection of fetal acidemia and cardiovascular decompensation.

Temperature elevation by HIFU in ex vivo porcine muscle: MRI measurement and simulation study.

PURPOSE: High-intensity focused ultrasound is a rapidly developing medical technology with a large number of potential clinical applications. Computational model can play a pivotal role in the planning and optimization of the treatment based on the patient's image. Nonlinear propagation effects can significantly affect the temperature elevation and should be taken into account. In order to investigate the importance of nonlinear propagation effects, nonlinear Westervelt equation was solved. Weak nonlinear propagation effects were studied. The purpose of this study was to investigate the correlation between the predicted and measured temperature elevations and lesion in a porcine muscle. METHODS: The investigated single-element transducer has a focal length of 12 cm, an aperture of 8 cm, and frequency of 1.08 MHz. Porcine muscle was heated for 30 s by focused ultrasound transducer with an acoustic power in the range of 24-56 W. The theoretical model consists of nonlinear Westervelt equation with relaxation effects being taken into account and Pennes bioheat equation. RESULTS: Excellent agreement between the measured and simulated temperature rises was found. For peak temperatures above 85-90 °C "preboiling" or cavitation activity appears and lesion distortion starts, causing small discrepancy between the measured and simulated temperature rises. From the measurements and simulations, it was shown that distortion of the lesion was caused by the "preboiling" activity. CONCLUSIONS: The present study demonstrated that for peak temperatures below 85-90 °C numerical simulation results are in excellent agreement with the experimental data in three dimensions. Both temperature rise and lesion size can be well predicted. Due to nonlinear effect the temperature in the focal region can be increased compared with the linear case. The current magnetic resonance imaging (MRI) resolution is not sufficient. Due to the inevitable averaging the measured temperature can be 10-30 °C lower than the peak temperature. Computational fluid dynamics can provide additional important information that is lost using a state of the art MRI device.

Medial vascular calcification revisited: review and perspectives.

Vascular calcifications (VCs) are actively regulated biological processes associated with crystallization of hydroxyapatite in the extracellular matrix and in cells of the media (VCm) or intima (VCi) of the arterial wall. Both patterns of VC often coincide and occur in patients with type II diabetes, chronic kidney disease, and other less frequent disorders; VCs are also typical in senile degeneration. In this article, we review the current state of knowledge about the pathology, molecular biology, and nosology of VCm, expand on potential mechanisms responsible for poor prognosis, and expose some of the directions for future research in this area.

Simulation of nonlinear Westervelt equation for the investigation of acoustic streaming and nonlinear propagation effects.

This study investigates the influence of blood flow on temperature distribution during high-intensity focused ultrasound (HIFU) ablation of liver tumors. A three-dimensional acoustic-thermal-hydrodynamic coupling model is developed to compute the temperature field in the hepatic cancerous region. The model is based on the nonlinear Westervelt equation, bioheat equations for the perfused tissue and blood flow domains. The nonlinear Navier-Stokes equations are employed to describe the flow in large blood vessels. The effect of acoustic streaming is also taken into account in the present HIFU simulation study. A simulation of the Westervelt equation requires a prohibitively large amount of computer resources. Therefore a sixth-order accurate acoustic scheme in three-point stencil was developed for effectively solving the nonlinear wave equation. Results show that focused ultrasound beam with the peak intensity 2470 W/cm(2) can induce acoustic streaming velocities up to 75 cm/s in the vessel with a diameter of 3 mm. The predicted temperature difference for the cases considered with and without acoustic streaming effect is 13.5 °C or 81% on the blood vessel wall for the vein. Tumor necrosis was studied in a region close to major vessels. The theoretical feasibility to safely necrotize the tumors close to major hepatic arteries and veins was shown.

In vitro validation of computational fluid dynamic simulation in human proximal airways with hyperpolarized 3He magnetic resonance phase-contrast velocimetry.

Computational fluid dynamics (CFD) and magnetic resonance (MR) gas velocimetry were concurrently performed to study airflow in the same model of human proximal airways. Realistic in vivo-based human airway geometry was segmented from thoracic computed tomography. The three-dimensional numerical description of the airways was used for both generation of a physical airway model using rapid prototyping and mesh generation for CFD simulations. Steady laminar inspiratory experiments (Reynolds number Re = 770) were performed and velocity maps down to the fourth airway generation were extracted from a new velocity mapping technique based on MR velocimetry using hyperpolarized (3)He gas. Full two-dimensional maps of the velocity vector were measured within a few seconds. Numerical simulations were carried out with the experimental flow conditions, and the two sets of data were compared between the two modalities. Flow distributions agreed within 3%. Main and secondary flow velocity intensities were similar, as were velocity convective patterns. This work demonstrates that experimental and numerical gas velocity data can be obtained and compared in the same complex airway geometry. Experiments validated the simulation platform that integrates patient-specific airway reconstruction process from in vivo thoracic scans and velocity field calculation with CFD, hence allowing the results of this numerical tool to be used with confidence in potential clinical applications for lung characterization. Finally, this combined numerical and experimental approach of flow assessment in realistic in vivo-based human airway geometries confirmed the strong dependence of airway flow patterns on local and global geometrical factors, which could contribute to gas mixing.

Airflow modeling of steady inspiration in two realistic proximal airway trees reconstructed from human thoracic tomodensitometric images.

Detailed description of the flow field in human airways is highly important to better understand human breathing and provide a patient's customized diagnosis. An integrated numerical simulation platform is presently proposed in order to incorporate medical images into a numerical software to calculate flow field and to analyze it in terms of fluid dynamics. The platform was set up to compute steady inspiratory airflow in realistic human airways reconstructed from tomodensitometric medical images at resting breathing conditions. This morpho-functional simulation platform has been tested retrospectively with two CT-scanned patient airway morphological models: (i) a normal airway model (subject A) with no evidence of morphological alteration and (ii) a highly altered airway model (subject B) exhibiting a severe stenosis in the right main bronchus. First, various morphological aspects proper to each airway model are provided to show the performance and interest of the reconstruction method. Second, we describe the three-dimensional flow patterns associated to the global morphological features, which are mainly shared by the present realistic models and previous idealistic airway models. Finally, the flow characteristics associated to local morphological features specific to realistic airway models are discussed. The results demonstrate that the morpho-functional simulation platform is able to capture the main features of airway velocity patterns but also more specific airflow patterns which are related to customized patient morphological features such as laminar vortex formation. The present results suggest that the proposed airway functional imaging platform is adequate to provide most of functional information related to airflow and enable a patient to patient diagnosis.

Pressure field in flow through uniform straight pipes with varying wall cross curvature.

Pressure fields in rigid smooth straight tubes with an axially uniform cross section, in which an incompressible Newtonian fluid flows steadily, have been determined. Five cross section shapes are used. The reference cross section S0 is slightly elliptic (ellipticity of 1.005). Four cross section shapes, which mimic collapsed vessels in an uniformly frozen state, are defined according to the curvature of their opposite faces (the mid-face is located on the minor axis) Sq (parallel faces), St (face folding), Sc (point contact between faces) and Sl (line contact). These four selected cross shapes are characterized by large changes in both the cross sectional shape and area with respect to S0. The cross shapes are obtained from the computation of the deformation under uniform transmural pressures, without extension, of a thin-walled conduit of infinite length and of homogeneous purely elastic walls of constant thickness. The Navier-Stokes equations are solved using the finite element method for the five tubes summation operator0, summation operatorq, summation operatort, summation operatorc and summation operatorl, which are associated with S0,Sq,St,Sc and Sl, respectively. The numerical tests are performed with the same value of the volume flow rate whatever the tube configuration for three Reynolds numbers ( [See text] ). The present work is aimed at studying the pressure field for the design of the flow chamber in which endothelial cells are cultured. This field is used not only to define a new relative pressure index to determine the entry length but also to estimate the wall shear stress when the flow is fully developed.