Large-scale CFD and micro-particles simulations in a large human airways under sniff condition and drug delivery application

As we inhale, the air drawn through our nose undergoes successive accelerations and decelerations as it is turned, split, and recombined before splitting again at the end of the trachea as it enters the bronchi. Fully describing the dynamic behaviour of the airflow and how it transports inhaled particles poses a severe challenge to computational simulations. The dynamics of unsteady flow in the human large airways during a rapid and short inhalation (a so-called sniff) is a perfect example of perhaps the most complex and violent human inhalation inflow. Combining the flow solution with a Lagrangian computation reveals the effects of flow behaviour and airway geometry on the deposition of inhaled microparticles. Highly detailed large-scale computational fluid dynamics allow resolving all the spatial and temporal scales of the flow, thanks to the use of massive computational resources. A highly parallel finite element code running on supercomputers can solve the transient incompressible Navier-Stokes equations on unstructured meshes. Given that the finest mesh contained 350 million elements, the study sets a precedent for large-scale simulations of the respiratory system, proposing an analysis strategy for mean flow, fluctuations, wall shear stresses, energy spectral and particle deposition on a rapid and short inhalation. Then in a second time, we will propose a drug delivery study of nasal sprayed particle from commercial product in a human nasal cavity under different inhalation conditions; sniffing, constant flow rate and breath-hold. Particles were introduced into the flow field with initial spray conditions, including spray cone angle, insertion angle, and initial velocity. Since nasal spray atomizer design determines the particle conditions, fifteen particle size distributions were used,each defined by a log-normal distribution with a different volume mean diameter. This thesis indicates the potential of large-scale simulations to further understanding of airway physiological mechanics, which is essential to guide clinical diagnosis; better understanding of the flow and delivery of therapeutic aerosols, which could be applied to improve diagnosis and treatment.En una inhalación, el aire que atraviesa nuestra cavidad nasal es sometido a una serie de aceleraciones y deceleraciones al producirse un giros, bifurcaciones y recombinarse de nuevo antes de volver a dividirse de nuevo a la altura de la tráquea en la entrada a los bronquios principales. La descripción precisa y acurada del comportamiento dinámico de este fluido así como el transporte de partículas inhalada que entran con el mismo a través de una simulación computacional supone un gran desafío. La dinámica del fluido en las vías respiratorias durante una inhalación rápida y corta (también llamado sniff) es un ejemplo perfecto de lo que sería probablemente la inhalación en el ser humano más compleja y violenta. Combinando la solución del fluido con un modelo lagrangiano revela el comportamiento del flujo y el effecto de la geometría de las vías respiratorias sobre la deposición de micropartículas inhaladas. La dinámica de fluidos computacional a gran escala de alta precisión permite resolver todas las escalas espaciales y temporales gracias al uso de recursos computacionales masivos. Un código de elementos finitos paralelos que se ejecuta en supercomputadoras puede resolver las ecuaciones transitorias e incompresibles de Navier-Stokes. Considerando que la malla más fina contiene 350 millones de elementos, cabe señalar que el presente estudio establece un precedente para simulaciones a gran escala de las vías respiratorias, proponiendo una estrategia de análisis para flujo medio, fluctuaciones, tensiones de corte de pared, espectro de energía y deposición de partículas en el contexto de una inhalación rápida y corta. Una vez realizado el analisis anterior, propondremos un estudio de administración de fármacos con un spray nasal en una cavidad nasal humana bajo diferentes condiciones de inhalación; sniff, caudal constante y respiración sostenida. Las partículas se introdujeron en el fluido con condiciones iniciales de pulverización, incluido el ángulo del cono de pulverización, el ángulo de inserción y la velocidad inicial. El diseño del atomizador del spray nasal determina las condiciones de partículas, entonces se utilizaron quince distribuciones de tamaño de partícula, cada uno definido por una distribución logarítmica normal con una media de volumen diferente. Esta tesis demuestra el potencial de las simulaciones a gran escala para una mejor comprensión de los mecanismos fisiológicos de las vías respiratorias. Gracias a estas herramientas se podrá mejorar el diagnóstico y sus respectivos tratamientos ya que con ellas se profundizará en la comprensión del flujo que recorre las vías aereas así como el transporte de aerosoles terapéuticos

Dynamics of airflow in a short inhalation

During a rapid inhalation, such as a sniff, the flow in the airways accelerates and decays quickly. The consequences for flow development and convective trans- port of an inhaled gas were investigated in a subject geometry extending from the nose to the bronchi. The progress of flow transition and the advance of an inhaled non-absorbed gas were determined using highly resolved simulations of a sniff 0.5 s long, 1 litre per second peak flow, 364 ml inhaled volume. In the nose, the distribution of airflow evolved through three phases: (i) an initial transient of about 50 ms, roughly the filling time for a nasal volume, (ii) quasi-equilibrium over the majority of the inhalation, and (iii) a terminating phase. Flow transition commenced in the supraglottic region within 20ms, resulting in large- amplitude fluctuations persisting throughout the inhalation; in the nose, fluctuations that arose nearer peak flow were of much reduced intensity and diminished in the flow decay phase. Measures of gas concentration showed non-uniform build-up and wash-out of the inhaled gas in the nose. At the carina, the form of the temporal concentration profile reflected both shear dispersion and airway filling defects owing to recirculation regions.Comment: 15 page

Real-space density functional theory and time dependent density functional theory using finite/infinite element methods

We present a numerical approach using the finite element method to discretize the equations that allow getting a first-principles description of multi-electronic systems within DFT and TD-DFT formalisms. A strictly local polynomial function basis set is used in order to represent the entire real-space domain. Infinite elements are introduced to model the infinite external boundaries in the case of Hartree's equation. The diagonal mass matrix is obtained using a close integration rule, reducing the generalized eigenvalue problem to a standard one. This framework of electronic structure calculation is embedded in a high performance computing environment with a very good parallel behavior.Fil: Soba, Alejandro. Barcelona Supercomputing Center - Centro Nacional de Supercomputacion; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bea, Edgar Alejandro. Barcelona Supercomputing Center - Centro Nacional de Supercomputacion; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Houzeaux, Guillaume. Barcelona Supercomputing Center - Centro Nacional de Supercomputacion; EspañaFil: Calmet, Hadrien. Barcelona Supercomputing Center - Centro Nacional de Supercomputacion; EspañaFil: Cela, José María. Barcelona Supercomputing Center - Centro Nacional de Supercomputacion; Españ

Flow features and micro-particle deposition in a human respiratory system during sniffing

As we inhale, the air drawn through our nose undergoes successive accelerations and decelerations as it is turned, split and recombined before splitting again at the end of the trachea as it enters the bronchi. Fully describing the dynamic behaviour of the airflow and how it transports inhaled particles poses a severe challenge to computational simulations. In this paper we explore two aspects: the dynamic behaviour of airflow during a rapid inhalation (or sniff) and the transport of inhaled aerosols. The development of flow unsteadiness from a laminar state at entry to the nose through to the turbulent character of tracheal flow is resolved using accurate numerical models with high performance computing-based large scale simulations. Combining the flow solution with a Lagrangian computation reveals the effects of flow behaviour and airway geometry on the deposition of inhaled microparticles. Improved modelling of airflow and delivery of therapeutic aerosols could be applied to improve diagnosis and treatment

The OTree: multidimensional indexing with efficient data sampling for HPC

Spatial big data is considered an essential trend in future scientific and business applications. Indeed, research instruments, medical devices, and social networks generate hundreds of petabytes of spatial data per year. However, many authors have pointed out that the lack of specialized frameworks for multidimensional Big Data is limiting possible applications and precluding many scientific breakthroughs. Paramount in achieving High-Performance Data Analytics is to optimize and reduce the I/O operations required to analyze large data sets. To do so, we need to organize and index the data according to its multidimensional attributes. At the same time, to enable fast and interactive exploratory analysis, it is vital to generate approximate representations of large datasets efficiently. In this paper, we propose the Outlook Tree (or OTree), a novel Multidimensional Indexing with efficient data Sampling (MIS) algorithm. The OTree enables exploratory analysis of large multidimensional datasets with arbitrary precision, a vital missing feature in current distributed data management solutions. Our algorithm reduces the indexing overhead and achieves high performance even for write-intensive HPC applications. Indeed, we use the OTree to store the scientific results of a study on the efficiency of drug inhalers. Then we compare the OTree implementation on Apache Cassandra, named Qbeast, with PostgreSQL and plain storage. Lastly, we demonstrate that our proposal delivers better performance and scalability.Peer ReviewedPostprint (author's final draft

Subject-variability effects on micron particle deposition in human nasal cavities

Validated computer simulations of the airflow and particle dynamics in human nasal cavities are important for local, segmental and total deposition predictions of both inhaled toxic and therapeutic particles. Considering three, quite different subject-specific nasal airway configurations, micron-particle transport and deposition for low-to-medium flow rates have been analyzed. Of special interest was the olfactory region from which deposited drugs could readily migrate to the central nervous system for effective treatment. A secondary objective was the development of a new dimensionless group with which total particle deposition efficiency curves are very similar for all airway models, i.e., greatly reducing the impact of intersubject variability. Assuming dilute particle suspensions with inhalation flow rates ranging from 7.5 to 20 L/min, the airflow and particle-trajectory equations were solved in parallel with the in-house, multi-purpose Alya program at the Barcelona Supercomputing Center. The geometrically complex nasal airways generated intriguing airflow fields where the three subject models exhibit among them both similar as well as diverse flow structures and wall shear stress distributions, all related to the coupled particle transport and deposition. Nevertheless, with the new Stokes-Reynolds-number group, , the total deposition-efficiency curves for all three subjects and flow rates almost collapsed to a single function. However, local particle deposition efficiencies differed significantly for the three subjects when using particle diameters = 2, 10, and . Only one of the three subject-specific olfactory regions received, at relatively high values of the inertial parameter , some inhaled microspheres. Clearly, for drug delivery to the brain via the olfactory region, a new method of directional inhalation of nanoparticles would have to be implemented.The authors acknowledge Dr. Rick Corley and colleagues at Pacific Northwest National Laboratory for providing the subject B nasal surface geometry and Dr. Edgar Matida and Dr. Matthew Johnson at Carleton University for providing the subject C nasal surface geometryPeer ReviewedPostprint (published version

Numerical simulations of the flow and aerosol dispersion in a violent expiratory event: Outcomes of the "2022 International Computational Fluid Dynamics Challenge on violent expiratory events"

This paper presents and discusses the results of the "2022 International Computational Fluid Dynamics Challenge on violent expiratory events" aimed at assessing the ability of different computational codes and turbulence models to reproduce the flow generated by a rapid prototypical exhalation and the dispersion of the aerosol cloud it produces. Given a common flow configuration, a total of seven research teams from different countries have performed a total of eleven numerical simulations of the flow dispersion by solving the Unsteady Reynolds Averaged Navier-Stokes (URANS) or using the Large-Eddy Simulations (LES) or hybrid (URANS-LES) techniques. The results of each team have been compared with each other and assessed against a Direct Numerical Simulation (DNS) of the exact same flow. The DNS results are used as reference solution to determine the deviation of each modeling approach. The dispersion of both evaporative and non-evaporative particle clouds has been considered in twelve simulations using URANS and LES. Most of the models predict reasonably well the shape and the horizontal and vertical ranges of the buoyant thermal cloud generated by the warm exhalation into an initially quiescent colder ambient. However, the vertical turbulent mixing is generally underpredicted, especially by the URANS-based simulations, independently of the specific turbulence model used (and only to a lesser extent by LES). In comparison to DNS, both approaches are found to overpredict the horizontal range covered by the small particle cloud that tends to remain afloat within the thermal cloud well after the flow injection has ceasedThis study was funded by the Spanish Ministerio de Ciencia, Innovación y Universidades through the grants PID2020-113303GB-C21 and RTI2018-100907-A-I00 (MCIU/AEI/FEDER) and by the Generalitat de Catalunya through the grant 2017-SGR-1234. M. Z, V. R. and N. I. acknowledge the Super Computer Center (SCC) «Polytechnic» for providing computational resources. J.W., M.Š. and J.R. would like to thank the valuable insights given by professors Paul Steinmann and Matjaž Hriberšek and the financial support of the Deutsche Forschungsgemeinschaft, Germany under project STE 544/58-2 and the Slovenian Research Agency under project No. P2-0196Postprint (author's final draft

Large-scale CFD simulations of the transitional and turbulent regime for the large human airways during rapid inhalation

The dynamics of unsteady flow in the human large airways during a rapid inhalation were investigated using highly detailed large-scale computational fluid dynamics on a subject-specific geometry. The simulations were performed to resolve all the spatial and temporal scales of the flow, thanks to the use of massive computational resources. A highly parallel finite element code was used, running on two supercomputers, solving the transient incompressible Navier–Stokes equations on unstructured meshes. Given that the finest mesh contained 350 million elements, the study sets a precedent for large-scale simulations of the respiratory system, proposing an analysis strategy for mean flow, fluctuations and wall shear stresses on a rapid and short inhalation (a so-called sniff). The geometry used encompasses the exterior face and the airways from the nasal cavity, through the trachea and up to the third lung bifurcation; it was derived from a contrast-enhanced computed tomography (CT) scan of a 48-year-old male. The transient inflow produces complex flows over a wide range of Reynolds numbers (Re). Thanks to the high fidelity simulations, many features involving the flow transition were observed, with the level of turbulence clearly higher in the throat than in the nose. Spectral analysis revealed turbulent characteristics persisting downstream of the glottis, and were captured even with a medium mesh resolution. However a fine mesh resolution was found necessary in the nasal cavity to observe transitional features. This work indicates the potential of large-scale simulations to further understanding of airway physiological mechanics, which is essential to guide clinical diagnosis; better understanding of the flow also has implications for the design of interventions such as aerosol drug delivery.We acknowledge PRACE for awarding us access to resource FERMI based in Italy at Bologna hosted by Cineca. This work was financially supported by the PRACE project Pra04 693 (2011050693 to the Fourth PRACE regular call). The second author gratefully acknowledges support from project ‘MatComPhys’ under the European Research Executive Agency FP7-PEOPLE-2011- IEF framework. The third author was supported by the Engineering and Physical Sciences Research Council [grant number EP/ M506345/1].Peer ReviewedPostprint (author's final draft

Large-scale CFD and micro-particles simulations in a large human airways under sniff condition and drug delivery application

As we inhale, the air drawn through our nose undergoes successive accelerations and decelerations as it is turned, split, and recombined before splitting again at the end of the trachea as it enters the bronchi. Fully describing the dynamic behaviour of the airflow and how it transports inhaled particles poses a severe challenge to computational simulations. The dynamics of unsteady flow in the human large airways during a rapid and short inhalation (a so-called sniff) is a perfect example of perhaps the most complex and violent human inhalation inflow. Combining the flow solution with a Lagrangian computation reveals the effects of flow behaviour and airway geometry on the deposition of inhaled microparticles. Highly detailed large-scale computational fluid dynamics allow resolving all the spatial and temporal scales of the flow, thanks to the use of massive computational resources. A highly parallel finite element code running on supercomputers can solve the transient incompressible Navier-Stokes equations on unstructured meshes. Given that the finest mesh contained 350 million elements, the study sets a precedent for large-scale simulations of the respiratory system, proposing an analysis strategy for mean flow, fluctuations, wall shear stresses, energy spectral and particle deposition on a rapid and short inhalation. Then in a second time, we will propose a drug delivery study of nasal sprayed particle from commercial product in a human nasal cavity under different inhalation conditions; sniffing, constant flow rate and breath-hold. Particles were introduced into the flow field with initial spray conditions, including spray cone angle, insertion angle, and initial velocity. Since nasal spray atomizer design determines the particle conditions, fifteen particle size distributions were used,each defined by a log-normal distribution with a different volume mean diameter. This thesis indicates the potential of large-scale simulations to further understanding of airway physiological mechanics, which is essential to guide clinical diagnosis; better understanding of the flow and delivery of therapeutic aerosols, which could be applied to improve diagnosis and treatment.En una inhalación, el aire que atraviesa nuestra cavidad nasal es sometido a una serie de aceleraciones y deceleraciones al producirse un giros, bifurcaciones y recombinarse de nuevo antes de volver a dividirse de nuevo a la altura de la tráquea en la entrada a los bronquios principales. La descripción precisa y acurada del comportamiento dinámico de este fluido así como el transporte de partículas inhalada que entran con el mismo a través de una simulación computacional supone un gran desafío. La dinámica del fluido en las vías respiratorias durante una inhalación rápida y corta (también llamado sniff) es un ejemplo perfecto de lo que sería probablemente la inhalación en el ser humano más compleja y violenta. Combinando la solución del fluido con un modelo lagrangiano revela el comportamiento del flujo y el effecto de la geometría de las vías respiratorias sobre la deposición de micropartículas inhaladas. La dinámica de fluidos computacional a gran escala de alta precisión permite resolver todas las escalas espaciales y temporales gracias al uso de recursos computacionales masivos. Un código de elementos finitos paralelos que se ejecuta en supercomputadoras puede resolver las ecuaciones transitorias e incompresibles de Navier-Stokes. Considerando que la malla más fina contiene 350 millones de elementos, cabe señalar que el presente estudio establece un precedente para simulaciones a gran escala de las vías respiratorias, proponiendo una estrategia de análisis para flujo medio, fluctuaciones, tensiones de corte de pared, espectro de energía y deposición de partículas en el contexto de una inhalación rápida y corta. Una vez realizado el analisis anterior, propondremos un estudio de administración de fármacos con un spray nasal en una cavidad nasal humana bajo diferentes condiciones de inhalación; sniff, caudal constante y respiración sostenida. Las partículas se introdujeron en el fluido con condiciones iniciales de pulverización, incluido el ángulo del cono de pulverización, el ángulo de inserción y la velocidad inicial. El diseño del atomizador del spray nasal determina las condiciones de partículas, entonces se utilizaron quince distribuciones de tamaño de partícula, cada uno definido por una distribución logarítmica normal con una media de volumen diferente. Esta tesis demuestra el potencial de las simulaciones a gran escala para una mejor comprensión de los mecanismos fisiológicos de las vías respiratorias. Gracias a estas herramientas se podrá mejorar el diagnóstico y sus respectivos tratamientos ya que con ellas se profundizará en la comprensión del flujo que recorre las vías aereas así como el transporte de aerosoles terapéuticos.Postprint (published version