Regional aerosol deposition in the human airways: the SimInhale benchmark case and a critical assessment of in silico methods

Regional deposition effects are important in the pulmonary delivery of drugs intended for the topical treatment of respiratory ailments. They also play a critical role in the systemic delivery of drugs with limited lung bioavailability. In recent years, significant improvements in the quality of pulmonary imaging have taken place, however the resolution of current imaging modalities remains inadequate for quantifying regional deposition. Computational Fluid-Particle Dynamics (CFPD) can fill this gap by providing detailed information about regional deposition in the extrathoracic and conducting airways. It is therefore not surprising that the last 15 years have seen an exponential growth in the application of CFPD methods in this area. Survey of the recent literature however, reveals a wide variability in the range of modelling approaches used and in the assumptions made about important physical processes taking place during aerosol inhalation. The purpose of this work is to provide a concise critical review of the computational approaches used to date, and to present a benchmark case for validation of future studies in the upper airways. In the spirit of providing the wider community with a reference for quality assurance of CFPD studies, in vitro deposition measurements have been conducted in a human-based model of the upper airways, and several groups within MP1404 SimInhale have computed the same case using a variety of simulation and discretization approaches. Here, we report the results of this collaborative effort and provide a critical discussion of the performance of the various simulation methods. The benchmark case, in vitro deposition data and in silico results will be published online and made available to the wider community. Particle image velocimetry measurements of the flow, as well as additional numerical results from the community, will be appended to the online database as they become available in the future

Low-mass e+e- pair production in 158 A GeV Pb-Au collisions at the CERN SPS, its dependence on multiplicity and transverse momentum

We report a measurement of low-mass electron pairs observed in 158 GeV/nucleon Pb-Au collisions. The pair yield integrated over the range of invariant masses 0.2 < m < 2.0 GeV is enhanced by a factor of 3.5 +/- 0.4 (stat) +/- 0.9 (syst) over the expectation from neutral meson decays. As observed previously in S-Au collisions, the enhancement is most pronounced in the invariant-mass region 300-700 MeV. For Pb-Au we find evidence for a strong increase of the enhancement with centrality. In addition, we show that the enhancement covers a wide range in transverse momentum, but is largest at the lowest observed pt.Comment: 17 pages, 4 figures, submitted to Phys.Lett.

Semi-Hard Scattering Unraveled from Collective Dynamics by Two-Pion Azimuthal Correlations in 158 A GeV/c Pb + Au Collisions

Elliptic flow and two-particle azimuthal correlations of charged hadrons and high-$p_T$ pions ($p_T>$ 1 GeV/$c$) have been measured close to mid-rapidity in 158A GeV/$c$ Pb+Au collisions by the CERES experiment. Elliptic flow ($v_2$) rises linearly with $p_T$ to a value of about 10% at 2 GeV/$c$. Beyond $p_T\approx$ 1.5 GeV/$c$, the slope decreases considerably, possibly indicating a saturation of $v_2$ at high $p_T$. Two-pion azimuthal anisotropies for $p_T>$ 1.2 GeV/$c$ exceed the elliptic flow values by about 60% in mid-central collisions. These non-flow contributions are attributed to near-side and back-to-back jet-like correlations, the latter exhibiting centrality dependent broadening.Comment: Submitted to Phys. Rev. Letters, 4 pages, 5 figure

Recent results from Pb-Au collisions at 158 GeV/c per nucleon obtained with the CERES spectrometer

During the 1996 lead run time, CERES has accumulated 42 million events, corresponding to a factor of 5 more statistics than in 1995 and 2.5 million events of a special photon-run. We report on the results of the low-mass e$^+$e$^-$-pair analysis. Since the most critical item is the poor signal-to-background ratio we also discuss the understanding of this background, in absolute terms, with the help of a detailed Monte Carlo simulation. We show preliminary results of the photon analysis and summarize the results of the hadron analysis preliminarily reported on already at QM'97Comment: 10 pages, 9 figures, Proceedings of the XIV Int. Conf. on Nucleus-Nucleus Collisions,Quark Matter 99, Torino, Italy, May 10 - 15, 199

e+e--pair production in Pb-Au collisions at 158 GeV per nucleon

We present the combined results on electron-pair production in 158 GeV/n {Pb-Au} ($\sqrt{s}$= 17.2 GeV) collisions taken at the CERN SPS in 1995 and 1996, and give a detailed account of the data analysis. The enhancement over the reference of neutral meson decays amounts to a factor of 2.31$\pm0.19 (stat.)\pm0.55 (syst.)\pm0.69 (decays)$ for semi-central collisions (28% $\sigma/\sigma_{geo}$) when yields are integrated over $m>$ 200 MeV/$c^2$ in invariant mass. The measured yield, its stronger-than-linear scaling with $N_{ch}$, and the dominance of low pair $p_t$ strongly suggest an interpretation as {\it thermal radiation} from pion annihilation in the hadronic fireball. The shape of the excess centring at $m\approx$ 500 MeV/$c^2$, however, cannot be described without strong medium modifications of the $\rho$ meson. The results are put into perspective by comparison to predictions from Brown-Rho scaling governed by chiral symmetry restoration, and from the spectral-function many-body treatment in which the approach to the phase boundary is less explicit.Comment: 39 pages, 40 figures, to appear in Eur.Phys.J.C. (2005

Computational and experimental model of electroporation for human aorta

Purpose: In this study the computational and experimental electroporation model with human aorta tissue is made in order to examine the reduction of smooth muscle cells. Methods. The segments in native state of the aorta are treated by electroporation method through a series of electrical impulses from 50 V/cm to 2500 V/cm. For each patient we analyzed one sample with and one sample without electroporation as a control. In the computational study, electrical field distribution is solved by the Laplace equation. The Pennes Bioheat equation without metabolism and blood perfusion heating is used to solve heat transfer problems. Different conductivity values are used in order to fit the experimental results. Results: Experimental histology has shown us that there are a smaller number of vascular smooth muscle cells (VSMC) nuclei at the tunica media, while the elastic fibre morphology is maintained 24 h after electroporation. In the computational model, heat generation coupled with electrical field is included. The fitting procedure is applied for conductivity values in order to make material properties of the aorta tissue. The fitting procedure gives tissue conductivity of 0.44 [S/m] for applied electrical field of 2500 V/cm. Conclusions: Future studies are necessary for investigation of a new device for in-vivo ablation with electroporation of plaque stenosis. It will open up a new avenue for stenosis treatment without stent implantation

Three-Dimensional Computer Model of Benign Paroxysmal Positional Vertigo in the Semi-Circular Canal

© 2018 Zarko Milosevic et al. Benign Paroxysmal Positional Vertigo (BPPV) is the most common vestibular disorder. In this paper we tried to investigate a model of the semi-circular canal (SCC) with parametrically defined dimension and full 3D three SCC from patient-specific 3D reconstruction. Full Navier-Stokes equations and continuity equations are used for fluid domain with Arbitrary-Lagrangian Eulerian (ALE) formulation for mesh motion. Fluid-structure interaction for fluid coupling with cupula deformation is used. Particle tracking algorithm has been used for particle motion. Velocity distribution, shear stress and force from endolymph side are presented for one parametric SCC and three patient-specific SCC. All models are used for correlation with the same experimental protocols with head moving and nystagmus eye tracking

Three-dimensional biomechanical model of benign paroxysmal positional vertigo in the semi-circular canal

© 2017, Strojarski Facultet. All rights reserved. Benign Paroxysmal Positional Vertigo (BPPV) is one of the most common vestibular disorders occuring due to the presence of basophilic particles in the semicircular canals (SCC). Three-dimensional biomechanical model of the SCC is described with full 3D fluid-structure interaction of particles, wall, cupula deformation and endolymph fluid flow. The model of the SCC with parametric defined dimension and fully 3D three SCC from patient specific 3D reconstruction is presented. Navier-Stokes equations with continuity equations described fluid flow while Arbitrary-Lagrangian Eulerian (ALE) formulation is used for mesh motion. Fluid-structure interaction for fluid coupling with cupula deformation is used. Particle tracking algorithm has been used for particle motion. Different size and number of particles with their full interaction between themselves, wall and cupula deformation are used. Velocity distribution, shear stress and force from endolymph side are presented for parametric one SCC and patient specific three SCC. All the models are used for correlation with the same experimental protocols with head moving and nystagmus eye tracking. Full fluid-structure interaction of otoconia particles, wall, cupula deflection and endolymph flow in three-dimension give more details and understanding of the pathology of the specific patient in standard clinical diagnostic and therapy procedure for BPPV

Computer simulation of thromboexclusion of the complete aorta in the treatment of chronic type B aneurysm

The purpose of this computational study was to examine the hemodynamic parameters of the velocity fields, shear stress, pressure and drag force field in the complex aorta system, based on a case of type B aortic dissection. The extra-anatomic reconstruction of the complete aorta and bipolar exclusion of the aneurysm was investigated by computational fluid dynamics. Three different cases of the same patient were analyzed: the existing preoperative condition and two alternative surgical treatment options, cases A and B, involving different distal aorto-aortic anastomosis sites. The three-dimensional Navier-Stokes equations and the continuity equation were solved with an unsteady stabilized finite element method. The aorta and large tube graft geometries were reconstructed based on CT angiography images to generate a patient-specific 3D finite element mesh. The computed results showed velocity profiles with smaller intensity in the aorta than in the graft tube in the postoperative case. The shear stress distribution showed low zones around 0.5Pa in the aneurysm part of the aorta for all three cases. Pressure distribution and, particularly, drag force had much higher values in the preoperative aneurysm zones (7.37N) than postoperatively (2.45N), which provides strong evidence of the hemodynamic and biomechanical benefits of this type of intervention in this specific patient. After assessing the outcome obtained with each of the two alternatives A and B, for which we found no significant difference, it was decided to use option A to treat the patient. In summary, computational studies could complement surgical preoperative risk assessment and provide significant insight into the benefits of different treatment alternatives. © 2013 Informa UK Ltd All rights reserved

Computer simulation of cervical tissue response to a hydraulic dilator device

Background: Classical mechanical dilators for cervical dilation are associated with various complications, such as uterine perforation, cervical laceration, infections and intraperitoneal hemorrhage. A new medical device called continuous controllable balloon dilator (CCBD) was constructed to make a significant reduction in all of the side effects of traditional mechanical dilation. Method. In this study we investigated numerically the cervical canal tissue response for Hegar and CCBD using our poroelastic finite element model and in-house software development. Boundary conditions for pressure loading on the tissue for both dilators in vivo were measured experimentally. Material properties of the cervical tissue were fitted with experimental in vivo data of pressure and fluid volume or balloon size. Results: Obtained results for effective stresses inside the cervical tissue clearly showed higher stresses for Hegar dilator during dilation in comparison with our CCBD. Conclusion: This study opens a new avenue for the implementation of CCBD device instead of mechanical dilators to prevent cervical injury during cervical dilation. © 2013 Filipovic et al.; licensee BioMed Central Ltd