Distribution of lung tissue within the chest cavity is a key contributor to delivery of both blood and air to the gas exchange regions of the lung. This distribution is multifactorial with influences from parenchyma, gravity, and level of inflation. We hypothesize that the manner in which lung inflates, for example, the primarily diaphragmatic nature of normal breathing, is an important contributor to regional lung tissue distribution. To investigate this hypothesis, we present an organ-level model of lung tissue mechanics, which incorporates pleural cavity change due to change in lung volume or posture. We quantify the changes using shape and density metrics in ten healthy subjects scanned supine at end-inspiratory and end-expiratory volumes and ten subjects scanned at both supine and prone end-inspiratory volumes. Comparing end-expiratory to end-inspiratory volume, we see primarily a change in the cranial–caudal dimension of the lung, reflective of movement of diaphragm. In the diaphragmatic region, there is greater regional lung expansion than in the cranial aspect, which is restricted by the chest wall. When moving from supine to prone, a restriction of lung was observed anteriorly, resulting in a generally reduced lung volume and a redistribution of air volume posteriorly. In general, we see the highest in lung tissue density heterogeneity in regions of the lung that are most inflated. Using our computational model, we quantify the impact of pleural cavity shape change on regional lung distribution and predict the impact on regional elastic recoil pressure.

Mechanical instability of soft tissues can either risk their normal function or alternatively trigger patterning mechanisms during growth and morphogenesis processes. Unlike standard stability analysis of linear elastic bodies, for soft tissues undergoing large deformations it is imperative to account for the nonlinearities induced by the coupling between load and surface changes at onset of instability. The related issue of boundary conditions, in context of soft tissues, has hardly been addressed in the literature, with most of available research employing dead-load conditions. This paper is concerned with the influence of imposed homogeneous rate (incremental) surface data on critical loads and associated modes in soft tissues, within the context of linear bifurcation analysis. Material behavior is modeled by compressible isotropic hyperelastic strain energy functions (SEFs), with experimentally validated material parameters for the Fung–Demiray SEF, over a range of constitutive response (including brain and liver tissues). For simplicity, we examine benchmark problems of basic spherical patterns: full sphere, spherical cavity, and thick spherical shell. Limiting the analysis to primary hydrostatic states we arrive at universal closed-form solutions, thus providing insight on the role of imposed boundary data. Influence of selected rate boundary conditions (RBCs) like dead-load and fluid-pressure (FP), coupled with constitutive parameters, on the existence and levels of bifurcation loads is compared and discussed. It is argued that the selection of the appropriate type of homogeneous RBC can have a critical effect on the level of bifurcation loads and even exclude the emergence of bifurcation instabilities.

Spiral arteries (SAs) lie at the interface between the uterus and placenta, and supply nutrients to the placental surface. Maternal blood circulation is separated from the fetal circulation by structures called villous trees. SAs are transformed in early pregnancy from tightly coiled vessels to large high-capacity channels, which is believed to facilitate an increased maternal blood flow throughout pregnancy with minimal increase in velocity, preventing damage to delicate villous trees. Significant maternal blood flow velocities have been theorized in the space surrounding the villi (the intervillous space, IVS), particularly when SA conversion is inadequate, but have only recently been visualized reliably using pulsed wave Doppler ultrasonography. Here, we present a computational model of blood flow from SA openings, allowing prediction of IVS properties based on jet length. We show that jets of flow observed by ultrasound are likely correlated with increased IVS porosity near the SA mouth and propose that observed mega-jets (flow penetrating more than half the placental thickness) are only possible when SAs open to regions of the placenta with very sparse villous structures. We postulate that IVS tissue density must decrease at the SA mouth through gestation, supporting the hypothesis that blood flow from SAs influences villous tree development.

The geometric fidelity of the inner organs on finite-element model (FEM) of the human body and the choice to use discontinuous mesh engender the appearance of empty spaces that do not reflect the real-life situation of human body cavities. The aim of this study is to assess the influence of these empty spaces on the behavior of a simplified FEM built with three different structures in interaction which properties are relevant with the abdominal cavity. This FEM is made up of a large sphere (peritoneum) containing two hemispheres (liver and spleen). The space between peritoneum and inner organs was defined with two different approaches and assessed under impact conditions. The first is a meshfree space (Mfs) approach, e.g., consider the space as a perfect gas. The second approach, meshed space (MS), entailed adding volumetric elements in the empty space. From each approach, one optimal configuration was identified regarding the recorded force versus compression, the mobility of inner organs, and the space incompressibility. This space has a considerable influence on the behavior of the FEM and mainly on the applied loadings of inner organs (difference reaching 70% according to the configuration). For the first approach, the incompressible gas is designated because it guarantees space incompressibility (vf/vi = 1) and inner organs loading with the lowest delay (for high impact velocity: Peak force = 89 N, compression 47%). For the second approach, the discontinuous volumetric mesh is preferred because it promotes space incompressibility (vf/vi = 0.94) and acceptable force reaction (for high impact velocity: Peak force = 97 N, compression 49%). The current study shows the importance of this space on the human FEMs cavities behavior and proposes two configurations able to be used in a future study including detailed FEM.

Embryo transfer (ET) is the last manual intervention after extracorporeal fertilization. After the ET procedure is completed, the embryos are conveyed in the uterus for another two to four days due to spontaneous uterine peristalsis until the window time for implantation. The role of intrauterine fluid flow patterns in transporting the embryos to their implantation site during and after ET was simulated by injection of a liquid bolus into a two-dimensional liquid-filled channel with a closed fundal end via a liquid-filled catheter inserted in the channel. Numerical experiments revealed that the intrauterine fluid field and the embryos transport pattern were strongly affected by the closed fundal end. The embryos re-circulated in small loops around the vicinity where they were deposited from the catheter. The transport pattern was controlled by the uterine peristalsis factors, such as amplitude and frequency of the uterine walls motility, as well as the synchronization between the onset of catheter discharge and uterine peristalsis. The outcome of ET was also dependent on operating parameters such as placement of the catheter tip within the uterine cavity and the delivery speed of the catheter load. In conclusion, this modeling study highlighted important parameters that should be considered during ET procedures in order to increase the potential for pregnancy success.

High-resolution numerical simulations are carried out to systematically investigate the effect of the incoming flow waveform on the hemodynamics and wall shear stress patterns of an anatomic sidewall intracranial aneurysm model. Various wave forms are constructed by appropriately scaling a typical human waveform such that the waveform maximum and time-averaged Reynolds numbers, the Womersley number ( α ) , and the pulsatility index (PI) are systematically varied within the human physiologic range. We show that the waveform PI is the key parameter that governs the vortex dynamics across the aneurysm neck and the flow patterns within the dome. At low PI, the flow in the dome is similar to a driven cavity flow and is characterized by a quasi-stationary shear layer that delineates the parent artery flow from the recirculating flow within the dome. At high PI, on the other hand, the flow is dominated by vortex ring formation, transport across the neck, and impingement and breakdown at the distal wall of the aneurysm dome. We further show that the spatial and temporal characteristics of the wall shear stress field on the aneurysm dome are strongly correlated with the vortex dynamics across the neck. We finally argue that the ratio between the characteristic time scale of transport by the mean flow across the neck and the time scale of vortex ring formation can be used to predict for a given sidewall aneurysm model the critical value of the waveform PI for which the hemodynamics will transition from the cavity mode to the vortex ring mode.

Full explanation for the pathogenesis of syringomyelia (SM), a neuropathology characterized by the formation of a cystic cavity (syrinx) in the spinal cord (SC), has not yet been provided. It has been hypothesized that abnormal cerebrospinal fluid (CSF) pressure, caused by subarachnoid space (SAS) flow blockage (stenosis), is an underlying cause of syrinx formation and subsequent pain in the patient. However, paucity in detailed in vivo pressure data has made theoretical explanations for the syrinx difficult to reconcile. In order to understand the complex pressure environment, four simplified in vitro models were constructed to have anatomical similarities with post-traumatic SM and Chiari malformation related SM. Experimental geometry and properties were based on in vivo data and incorporated pertinent elements such as a realistic CSF flow waveform, spinal stenosis, syrinx, flexible SC, and flexible spinal column. The presence of a spinal stenosis in the SAS caused peak-to-peak cerebrospinal fluid CSF pressure fluctuations to increase rostral to the stenosis. Pressure with both stenosis and syrinx present was complex. Overall, the interaction of the syrinx and stenosis resulted in a diastolic valve mechanism and rostral tensioning of the SC. In all experiments, the blockage was shown to increase and dissociate SAS pressure, while the axial pressure distribution in the syrinx remained uniform. These results highlight the importance of the properties of the SC and spinal SAS, such as compliance and permeability, and provide data for comparison with computational models. Further research examining the influence of stenosis size and location, and the importance of tissue properties, is warranted.

The alveoli are the smallest units of the lung that participate in gas exchange. Although gas transport is governed primarily by diffusion due to the small length scales associated with the acinar region ( ∼ 500 μ m ) , the transport and deposition of inhaled aerosol particles are influenced by convective airflow patterns. Therefore, understanding alveolar fluid flow and mixing is a necessary first step toward predicting aerosol transport and deposition in the human acinar region. In this study, flow patterns and particle transport have been measured using a simplified in-vitro alveolar model consisting of a single alveolus located on a bronchiole. The model comprises a transparent elastic 5/6 spherical cap (representing the alveolus) mounted over a circular hole on the side of a rigid circular tube (representing the bronchiole). The alveolus is capable of expanding and contracting in phase with the oscillatory flow through the tube. Realistic breathing conditions were achieved by exercising the model at physiologically relevant Reynolds and Womersley numbers. Particle image velocimetry was used to measure the resulting flow patterns in the alveolus. Data were acquired for five cases obtained as combinations of the alveolar-wall motion (nondeforming/oscillating) and the bronchiole flow (none/steady/oscillating). Detailed vector maps at discrete points within a given cycle revealed flow patterns, and transport and mixing of bronchiole fluid into the alveolar cavity. The time-dependent velocity vector fields were integrated over multiple cycles to estimate particle transport into the alveolar cavity and deposition on the alveolar wall. The key outcome of the study is that alveolar-wall motion enhances mixing between the bronchiole and the alveolar fluid. Particle transport and deposition into the alveolar cavity are maximized when the alveolar wall oscillates in tandem with the bronchiole fluid, which is the operating case in the human lung.

The canine nasal cavity contains a complex airway labyrinth, dedicated to respiratory air conditioning, filtering of inspired contaminants, and olfaction. The small and contorted anatomical structure of the nasal turbinates has, to date, precluded a proper study of nasal airflow in the dog. This study describes the development of a high-fidelity computational fluid dynamics (CFD) model of the canine nasal airway from a three-dimensional reconstruction of high-resolution magnetic resonance imaging scans of the canine anatomy. Unstructured hexahedral grids are generated, with large grid sizes ( ( 10 – 100 ) × 10 6 computational cells) required to capture the details of the nasal airways. High-fidelity CFD solutions of the nasal airflow for steady inspiration and expiration are computed over a range of physiological airflow rates. A rigorous grid refinement study is performed, which also illustrates a methodology for verification of CFD calculations on complex unstructured grids in tortuous airways. In general, the qualitative characteristics of the computed solutions for the different grid resolutions are fairly well preserved. However, quantitative results such as the overall pressure drop and even the regional distribution of airflow in the nasal cavity are moderately grid dependent. These quantities tend to converge monotonically with grid refinement. Lastly, transient computations of canine sniffing were carried out as part of a time-step study, demonstrating that high temporal accuracy is achievable using small time steps consisting of 160 steps per sniff period. Here we demonstrate that acceptable numerical accuracy (between approximately 1% and 15%) is achievable with practical levels of grid resolution ( ∼ 100 × 10 6 computational cells). Given the popularity of CFD as a tool for studying flow in the upper airways of humans and animals, based on this work we recommend the necessity of a grid dependence study and quantification of numerical error when presenting CFD results in complicated airways.

A detailed three-dimensional finite element model of the face is presented in this paper. Bones, muscles, skin, fat, and superficial muscoloaponeurotic system were reconstructed from magnetic resonance images and modeled according to anatomical, plastic, and reconstructive surgery literature. The finite element mesh, composed of hexahedron elements, was generated through a semi-automatic procedure with an effective compromise between the detailed representation of anatomical parts and the limitation of the computational time. Nonlinear constitutive equations are implemented in the finite element model. The corresponding model parameters were selected according to previous work with mechanical measurements on soft facial tissue, or based on reasonable assumptions. Model assumptions concerning tissue geometry, interactions, mechanical properties, and the boundary conditions were validated through comparison with experiments. The calculated response of facial tissues to gravity loads, to the application of a pressure inside the oral cavity and to the application of an imposed displacement was shown to be in good agreement with the data from corresponding magnetic resonance images and holographic measurements. As a first application, gravimetric soft tissue descent was calculated from the long time action of gravity on the face in the erect position, with tissue aging leading to a loss of stiffness. Aging predictions are compared with the observations from an “aging database” with frontal photos of volunteers at different age ranges (i.e., 20–40 years and 50–70 years).

The transport and deposition of nanoparticles, i.e., d p = 1 – 2 nm , or equivalent vapors, in the human nasal cavities is of interest to engineers, scientists, air-pollution regulators, and healthcare officials alike. Tiny ultrafine particles, i.e., d p ≤ 5 nm , are of special interest because they are most rapidly absorbed and hence have an elevated toxic or therapeutic impact when compared to larger particles. Assuming transient laminar 3-D incompressible flow in a representative human nasal cavity, the cyclic airflow pattern as well as local and overall nanoparticle depositions were computationally simulated and analyzed. The focus was on transient effects during inhalation/exhalation as compared to the steady-state assumption typically invoked. Then, an equation for a matching steady-state inhalation flow rate was developed that generates the same deposition results as cyclic inhalation. Of special interest is the olfactory region where the narrow channel surfaces receive only about one-half of a percent of the inhaled nanoparticles because the airflow bypasses these recesses located in the superior-most portions in the geometrically complex nasal cavities.

Insertion of a stent-graft into an aneurysm, especially abdominal aortic aneurysms (AAAs), is a very attractive surgical intervention; however, it is not without major postoperative complications, such as endoleaks. An endoleak is the transient accumulation of blood in the AAA cavity, which is formed by the stent-graft and AAA walls. Of the four blood pathways, a type I endoleak constitutes the major one. Thus, focusing on both proximal and distal type I endoleaks, i.e., the minute net influx of blood past the attachment points of a stent-graft into the AAA cavity, the transient three-dimensional interactions between luminal blood flow, stent-graft wall, leakage flow, and AAA wall are computationally simulated. For different type I endoleak scenarios and inlet pressure wave forms, the impact of type I endoleaks on cavity pressure, wall stress, and stent-graft migration force is analyzed. The results indicate that both proximal type I-a and distal type I-b endoleaks may cause cavity pressures close to a patient’s systemic pressure; however, with reduced pulsatility. As a result, the AAA-wall stress is elevated up to the level of a nonstented AAA and, hence, such endoleaks render the implant useless in protecting the AAA from possible rupture. Interestingly enough, the net downward force acting on the implant is significantly reduced; thus, in the presence of endoleaks, the risk of stent-graft migration may be mitigated.

Background: Implantable medical devices have increasingly large capacities for storing patient data as a diagnostic aid and to allow patient monitoring. Although these devices can store a significant amount of data, an increased ability for data storage was required for chronic monitoring in recent physiological studies. Method of Approach: Novel high capacity implantable data recorders were designed for use in advanced physiological studies of canines and free-ranging black bears. These hermitically sealed titanium encased recorders were chronically implanted and programmed to record intrabody broadband electrical activity to monitor electrocardiograms and electromyograms, and single-axis acceleration to document relative activities. Results: Changes in cardiac T-wave morphology were characterized in the canines over a 6 month period, providing new physiological data for the design of algorithms and filtering schemes that could be employed to avoid inappropriate implantable defibrillator shocks. Unique characteristics of bear hibernation physiology were successfully identified in the black bears, including: heart rate, respiratory rate, gross body movement, and shiver. An unanticipated high rejection rate of these devices occurred in the bears, with five of six being externalized during the overwintering period, including two devices implanted in the peritoneal cavity. Conclusions: High capacity implantable data recorders were designed and utilized for the collection of long-term physiological data in both laboratory and extreme field environments. The devices described were programmable to accommodate the diverse research protocols. Additionally, we have described substantial differences in the response of two species to a common device. Variations in the foreign body response of different mammals must be identified and taken into consideration when choosing tissue-contacting materials in the application of biomedical technology to physiologic research.

Flow visualization studies and supplementary numerical simulations are carried out on slow flow through a model alveolated duct. The results reveal that the type of flow that develops in the alveoli, or cavities, is controlled by the ratio of the depth to the width of the cavity and by the ratio of cavity volume to duct volume. While weak, the slowly rotating flow in the cavity is thought to be important to the convective transport of heat and mass transfer to, or from, the walls of the cavity. The relevance of these finding to particle transport and deposition deep in the lung is discussed.

A new endometrial thermal balloon ablation treatment for menorrhagia is modeled mathematically to predict its efficacy and safety. A device preheats a fluid to 173°C within a reservoir external to the uterus, and then pulses this fluid without further heating between the reservoir and the balloon for 2.1 min of treatment time. The model predicted this treatment to result in consistent immediate tissue death (coagulation) depths of 3.4±0.1 mm for uterine cavities of 7 to 26 mL, and that eventual necrosis (tissue death that would occur 1–5 days post burn) may occur to depths of 6.5±0.2 mm. Whereas, burn depths varied with uterine cavity volume when a low temperature treatment (constant 75°C for 15 min) was modeled (2.3–2.9 mm and 6.8–8.2 mm, for immediate tissue death and eventual necrosis respectively). Similarly, the high temperature, pulsed treatment was less sensitive to blood perfusion rate than the low temperature treatment. Predicted eventual necrosis depth was 1.5 mm less for the high temperature, pulsed treatment than that predicted for a low temperature treatment (constant 87°C for 7 min) for the same immediate tissue death depth (3.5 mm), indicating that the new high temperature treatment may result in less damage to non targeted tissues.

The fluid that resides within cranial and spinal cavities, cerebrospinal fluid (CSF), moves in a pulsatile fashion to and from the cranial cavity. This motion can be measured by magnetic resonance imaging (MRI) and may be of clinical importance in the diagnosis of several brain and spinal cord disorders such as hydrocephalus, Chiari malformation, and syringomyelia. In the present work, a geometric and hydrodynamic characterization of an anatomically relevant spinal canal model is presented. We found that inertial effects dominate the flow field under normal physiological flow rates. Along the length of the spinal canal, hydraulic diameter was found to vary significantly from 5 to 15 mm. The instantaneous Reynolds number at peak flow rate ranged from 150 to 450, and the Womersley number ranged from 5 to 17. Pulsatile flow calculations are presented for an idealized geometric representation of the spinal cavity. A linearized Navier–Stokes model of the pulsatile CSF flow was constructed based on MRI flow rate measurements taken on a healthy volunteer. The numerical model was employed to investigate effects of cross-sectional geometry and spinal cord motion on unsteady velocity, shear stress, and pressure gradient fields. The velocity field was shown to be blunt, due to the inertial character of the flow, with velocity peaks located near the boundaries of the spinal canal rather than at the midpoint between boundaries. The pressure gradient waveform was found to be almost exclusively dependent on the flow waveform and cross-sectional area. Characterization of the CSF dynamics in normal and diseased states may be important in understanding the pathophysiology of CSF related disorders. Flow models coupled with MRI flow measurements may become a noninvasive tool to explain the abnormal dynamics of CSF in related brain disorders as well as to determine concentration and local distribution of drugs delivered into the CSF space.

Polymer-based composites are widely used in restorative dentistry as alternatives to metals and ceramics to fill cavities in teeth. They adhere to the walls of the cavity in the tooth, thus forming a composite body consisting of dentine, enamel, and composite resin. Geometric discontinuities along the interfaces between these materials can induce singularities in the stress field, which in turn lead to premature failure of the restoration. In the present investigation, a complex stress function technique is employed to derive the order of the stress singularity. It is shown that the order of the singularity depends on both the material properties of the restorative material and the local geometry of the cavity. It is also shown that the singularity in the stress field can be avoided through careful design of the cavity shape. The results presented correlate well with experimental results reported in the literature. [S0148-0731(00)01504-1]

This paper presents measurements of the geometric shape, perimeter, and cross-sectional area of the human oral passage (from oral entrance to midtrachea) and relates them through dimensionless parameters to the depositional mass transfer of ultrafine particles. Studies were performed in two identical replicate oral passage models, one of which was cut orthogonal to the airflow direction into 3 mm elements for measurement, the other used intact for experimental measurements of ultrafine aerosol deposition. Dimensional data were combined with deposition measurements in two sections of the oral passage (the horizontal oral cavity and the vertical laryngeal–tracheal airway) to calculate the dimensionless mass transfer Sherwood number (Sh). Mass transfer theory suggests that Sh should be expressible as a function of the Reynolds numper (Re) and the Schmidt number (Sc). For inhalation and exhalation through the oral cavity (O-C), an empirical relationship was obtained for flow rates from 7.5–30.0 1 min −1 : Sh = 15.3 Re 0.812 Sc − 0.986 An empirical relationship was likewise obtained for the laryngeal–tracheal (L-T) region over the same range of flow rates: Sh = 25.9 Re 0.861 Sc − 1.37 These relationships were compared to heat transfer in the human upper airways through the well-known analogy between heat and mass transfer. The Reynolds number dependence for both the O-C and L-T relationships was in good agreement with that for heat transfer. The mass transfer coefficients were compared to extrathoracic uptake of gases and vapors and showed similar flow rate dependence. For gases and vapors that conform to the zero concentration boundary condition, the empirical relationships are applicable when diffusion coefficients are taken into consideration.

Laminar and turbulent numerical simulations of steady flow in an aneurysm model were carried out over Reynolds numbers ranging from 300 to 3600. The numerical simulations are validated with Digital Particle Image Velocimetry (DPIV) measurements, and used to study the fluid dynamic mechanisms that characterize aneurysm deterioration, by correlating them to in vitro blood platelet deposition results. It is shown that the recirculation zone formed inside the aneurysm cavity creates conditions that promote thrombus formation and the viability of rupture. Wall shear stress values in the recirculation zone are around one order of magnitude less than in the entrance zone. The point of reattachment at the distal end of the aneurysm is characterized by a pronounced wall shear stress peak. As the Reynolds number increases in laminar flow, the center of the recirculation region migrates toward the distal end of the aneurysm, increasing the pressure at the reattachment point. Under fully turbulent flow conditions (Re = 3600) the recirculation zone inside the aneurysm shrinks considerably. The wall shear stress values are almost one order of magnitude larger than those for the laminar cases. The fluid dynamics mechanisms inferred from the numerical simulation were correlated with measurements of blood platelet deposition, offering useful explanations for the different morphologies of the platelet deposition curves.

Flow visualization and pressure measurements were carried out in a single valve saphenous vein casting which was made from a saphenous vein segment obtained from a bypass patient at Cedars Sinai Medical Center. Dye was injected to understand the flow around the valve. The dye showed very complex flow patterns around the valve and in the valve sinus, and the cavity formed by a ligated branch. For steady flow, pressure drops across the valve were 0.72, 2.0 and 6.3 mmHg for the physiological flow rates of 45, 84, and 169 ml/min, respectively. Overall pressure drop across the casting (compared to Poiseuille flow for a straight tube) increased with the flow rate, being 130 to 290 percent higher over this flow rate range. In the case of pulsatile flow, pressure drops across the valve were 0.95 and 3.0 mmHg for the flow rates of 47 and 87 ml/min which were 26 and 43 percent higher than those of steady flow. Overall pressure drop was 220 and 360 percent higher for those flow rates compared to Poiseuille flow. The measured spatial pressure distributions along the casting and flow visualization indicated the global nature of the flow field with the accelerated flow through the valve separating and reattaching downstream along the wall in the pressure recovery region. Atherosclerosis may be prone to occur in the lower shear region along the wall beyond the valve tip in the reattachment region, as we have observed in vivo in rabbit experiments.