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Hemodynamic assessment of the development and rupture of intracranial aneurysms using computational simulations.

Intracranial aneurysms manifest themselves as sacculations within a weakened region of the vessel wall and pose substantial neurological risks upon rupture. A primary factor in the development and rupture stages of an aneurysm is hemodynamics and its degrading effects on the aneurysm wall. Wall dynamics and hemodynamics within a fully developed aneurysm were investigated using computational simulation techniques. To study wall dynamics, the aneurysm was modeled as a thing spherical shell with linearly elastic and plastic (viscoelastic) wall behavior. The sensitivity of this model to the biophysical parameters which describe it will assist in the quantitative assessment of factors predisposing to aneurysm rupture and subarachnoid hemorrhage. Flow dynamics simulations were performed for spherical aneurysms with rigid walls. We observed the development and motion of an annular vortex within the lateral sacculation. We also simulated a ruptured aneurysm by placing a tear near the neck of the aneurysm. Flow patterns showed blood flowing out during the initial stages of the flow, but displayed an inflow of blood soon thereafter, as the internal pressure dropped. These results are substantiated by the clinical observations that turbulent flow is observed within the aneurysm as evidenced by reduced bruits.

Aneurysm, Ruptured↗

The shape of the proximal isovelocity surface area varies with regurgitant orifice size and distance from orifice: computer simulation and model experiments with color M-mode technique.

The hemispheric proximal isovelocity surface area method for quantification of mitral regurgitant flow (i.e., Qc = 2 pi r2v), where 2 pi r2 is the surface area and v is the velocity at radius r, was investigated as distance from the orifice was increased. Computer simulations and steady flow model experiments were performed for orifices of 4, 6, and 8 mm. Flow rates derived from the centerline velocity and hemispheric assumption were compared with true flow rates. Proximal isovelocity surface area shape varied as distance from each orifice was increased and could only be approximated from the hemispheric equation when a certain distance was exceeded: > 7, > 10, and > 12 mm for the 4, 6, and 8 mm orifices, respectively. Prediction of relative error showed that the best radial zone at which to make measurements was 5 to 9, 6 to 14 and 7 to 17 mm for the 4, 6, and 8 mm orifices, respectively. Although effects of a nonhemispheric shape could be compensated for by use of a correction factor, a radius of 8 to 9 mm can be recommended without the use of a correction factor over all orifices studied if a deviation in calculated as compared with true flow of 15% is considered acceptable. These measurements therefore have implications for the technique in clinical practice.

Blood Flow Velocity↗

Computer simulation of occlusal discrepancies resulting from different mounting techniques.

The effect of arbitrary mounting of maxillary casts on occlusal relationships was investigated in this study. Maxillary casts of 31 volunteers were mounted on an articulator by use of two split cast bases. This mounting was done first with the arbitrary face bow and second with a hinge bow. Three reference points were defined and measured on each maxillary cast with a three-dimensional digitizer. The measurements were taken from the arbitrarily mounted cast and from the cast mounted according to the hinge axis. Opening and closing movements that were transferred according to the hinge axis. Opening and closing movements that were transferred from the articulator to the mouth of the patient were simulated by a computer based on measurements of the reference points. The results revealed that the use of an arbitrary face bow causes a deviation of the hinge-axis points from the precise axis of more than 5 mm in 77% of the cases. Resulting occlusal errors depended on the angles between the arbitrary and precise axes and the direction of the axis shifts. The occlusal error is roughly proportional to the shift or tilting of the hinge axis in millimeters or degrees. For a given deviation of the arbitrary and precise axes, the occlusal error is proportional to the record height. For a record height of 2 mm or more, an occlusal error of more than 0.1 mm will occur. An average occlusal error of more than 0.1 mm would most likely lead to the necessity of extensive selective grinding of occlusal discrepancies in the patient's mouth.

Adult↗

Computer simulation and experimental validation of the electrophoretic behavior of proteins.

A mathematical model of the electrophoretic behavior of proteins is presented. The Debye-Hückel-Henry theory is used for the description of protein mobility, which has the important result of making net mobility a function of ionic strength. A net charge vs pH relationship and a diffusion coefficient are required to describe a specific protein. The model is employed for the computer simulation of three distinct electrophoretic modes: isoelectric focusing, isotachophoresis, and zone electrophoresis. The validity of the model is tested by comparing simulation with experimental data. Excellent qualitative agreement was found.

Computer Simulation↗

Computer simulation and sled test validation of a powerbase wheelchair and occupant subjected to frontal crash conditions.

The Americans with Disabilities Act (ADA) has led to an increased number of wheelchair users seeking transportation services. Many of these individuals are unable to transfer to a vehicle and are instead required to travel seated in their wheelchairs. Unfortunately, wheelchairs are not typically designed with the same occupant protection features as motor vehicle seats, and wheelchair seated occupants may be at higher risk for injury in a crash. To study the effects of crash level forces on wheelchairs and their occupants, it is useful to simulate crash conditions using computer modeling. This study has used a dynamic lumped mass crash simulator, in combination with sled impact testing, to develop a model of a secured commercial powerbase and restrained occupant subjected to a 20 g/30 mph frontal motor vehicle crash. Time histories profiles of simulation-generated wheelchair kinematics, occupant accelerations, tiedown forces and occupant restraint forces were compared to sled impact testing for model validation. Validation efforts for this model were compared to validation results found acceptable for the ISO/SAE surrogate wheelchair model. This wheelchair-occupant simulation model can be used to investigate wheelchair crash response or to evaluate the influence of various factors on occupant crash safety.

Accidents↗

Computer simulation of rat heart metabolism after adding glucose to the perfusate.

An experiment where perfused rat hearts receiving no substrate are suddenly given glucose with insulin in the perfusate is simulated with a computer model of cardiac energy metabolism. Mitochondrial metabolism is quantitatively reorganized under cytoplasmic control, with fatty acid oxidation undergoing a two-step decrease. There is an unspanning of the Krebs cycle (different reactions going at different rates) due primarily to slowing of alpha-ketoglutarate dehydrogenase; this ends when cytoplasmic glucose reaches a new steady state. Mitochondria in vitro are known to have higher pH than their surroundings; it is found here that this also holds in situ. Under these conditions, glycolysis is coherently substrate controlled, as is phosphofructokinase, usually considered the typical example of an allosteric enzyme. Limitations on simple methods of analyzing metabolic data of this type, e.g., use of lactate/pyruvate ratios to calculate NADH/NAD ratios, are discussed. Here a large volume of enzyme and other biochemical information has been integrated into a physiologically meaningful system.

Amino Acids↗

Cardiopulmonary resuscitation by intrathoracic pressure variations--in vivo studies and computer simulation.

The effect of intrathoracic pressure variations on the hemodynamics of dogs with cardiac arrest were studied experimentally and simulated on a computer. High intrathoracic pressure (up to 90 mm Hg) was generated by lung inflation with passive and active modes of external fixation. Abdominal binding was found to be essential for the generation of high intrathoracic pressure. Remarkable Doppler flow signals were detected over the femoral artery with each lung inflation. Blood gases measured after 30 minutes of cardiac fibrillation in dogs together with intrathoracic pressure variations showed well oxygenated arterial blood with metabolic acidosis. A computer model was used to explore the effects of intrathoracic pressure variations over a large range of parameters. For intrathoracic pressure of 50/0 mm Hg. the mathematical model predicted maximal flow of 663 ml/min, occurring at a rate of 115 cpm, with a duty cycle of 58%. The heart showed only minor volume changes during the cycle, indicating its main function as a passive conduit during cardiopulmonary resuscitation. The data show that intrathoracic pressure variation with no direct heart compression can cause systemic blood flow of the magnitude occurring in most cardiopulmonary resuscitation techniques.

Animals↗

Estimation of metabolic flux rates in liver purine catabolism of tumour-bearing mice by computer simulation of radioactive tracer experiments.

Mouse hepatocytes from healthy control mice and from Ehrlich ascites tumour-bearing mice were used for tracer-kinetic studies of purine catabolism of liver cells during different periods of tumour growth. The dynamics of the radioactive tracers were modelled mathematically by a system of differential equations. Computer simulations, i.e. direct fitting of numerical solutions of these equations to the observed time-courses of metabolites and specific radioactivities, enables one to estimate unknown kinetic parameters of a simplified model of pathways of hepatic purine catabolism in tumour-bearing mice. There occurred great differences of metabolic flux rates between control hepatocytes, hepatocytes of mice during the proliferating period of tumour growth (6th day after inoculation of the tumour) and hepatocytes of mice during the resting period of tumour growth (12th day after inoculation of the tumour). The final purine degradation of hepatocytes prepared during the proliferating period was lower in comparison with that of control hepatocytes, but it was markedly higher in hepatocytes prepared during the resting period of tumour growth. The changes in hepatocyte purine catabolism during the proliferating period of tumour growth argue for transitions which aim at the maintenance of high purine nucleotide levels in the liver itself rather than for an increased nucleoside and nucleobase supply for the tumour. This suggestion is in accordance with the increased ATP level of the liver during the proliferating phase of tumour growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Structural mechanics of the blowout fracture: numerical computer simulation of orbital deformation by the finite element method.

Blowout fractures most frequently involve the orbital floor. The contour of the orbit has been postulated as one of the factors responsible for this phenomenon, but only a few studies have been carried out. The present study was planned to determine the effect of the contour of the orbit when intraorbital pressure is raised to simulate the hydraulic mechanism of blowout fracture. The profile of the orbit was estimated from five dry human skulls, and the measurements were approximated to frame models. The deformation of these models by raised intraorbital pressure was calculated by computer simulation using the finite element method. In all of the orbital models, the deformation of the orbital floor was significantly greater than that of the roof. These findings verified that the orbital roof has a higher resistance than the floor against raised intraorbital pressure. We suspect that this resistance is due to the arched shape of the orbital roof, whereas the floor is rather flat.

Computer Simulation↗

Computer simulation in sport and industry.

The last several decades have brought decreases in the specific cost of computer memory and increases in processor throughput. As a result simulation has become correspondingly more important as a component of industrial design and as a method for the study of general biomechanics and sports techniques. This paper illustrates, by way of examples, several of the more important aspects of the application of computer simulation to dynamic problems. Topics include (1) the ideas of suitable model complexity and its tradeoff with interpretability; (2) the sequential and iterative nature of model building and the importance of experimental data in the modelling and validation process; (3) the essential role of user-friendly software and graphical interfaces in the interchange of information between simulation programs and the users; and 4) the role of computer simulation in learning feedback loops, both in the field and in the computer laboratory. Most industrial use of simulation is in the design process. A similar approach is equally valid in biomechanics and sport applications through the incorporation of design variables, which may be easily changed in the model experiment.

Biomechanical Phenomena↗

Using computer simulations to compare pertussis vaccination strategies in Australia.

High levels of notified pertussis in adolescents and adults, persisting severe disease (hospitalization and deaths) in infants despite high childhood immunization coverage, together with the availability of adult-formulated pertussis vaccines, have made alternate strategies for vaccine control of pertussis an important issue in Australia. An age-structured computer simulation model was used to compare the likely effects of adopting different vaccination strategies in Australia on pertussis transmission by age group over a 50 year time period. Epidemiological parameters and vaccination coverage in Australia were estimated from previous pertussis modeling studies and existing data. In the simulations, replacing the pertussis booster at 18 months with a booster dose for adolescents at an age between 12 and 17 years, assuming 80% coverage, led to decreases in pertussis cases of 30% in children of ages 0-23 months (who have the highest complication rates) and of 25% in adolescents, but an increase of 15% in cases in 2-4-year-old children. The simulations did not suggest any shift of pertussis cases into the adult child-bearing years. Varying parameter values in the simulations in a series of sensitivity analyses showed the model predictions to be robust over a plausible range. The results of these simulations suggest that the recent change in the Australian pertussis vaccination schedule, replacing the 18 month dose with a pertussis booster in 15-17-year-old adolescents, is very likely to reduce overall pertussis incidence in Australia without increasing the cost of the current vaccine program.

Adolescent↗

Neurite branching pattern formation: modeling and computer simulation.

A model for nerve cell pattern formation is proposed in this paper. The model is based on some experimental results and an assumption that there is a kind of inhibitive interaction between growing neurites on the same nerve cell. In this paper, this interaction is termed lateral inhibition. A group of ordinary differential equations are used to describe the elongation of the terminal neurite segments of individual nerve cells. Computer simulation and comparison of it with in vitro studies are also made in this paper.

Animals↗

[Analysis by computer simulation of double breathing during pressure support ventilation].

BACKGROUND: Pressure support ventilation (PSV) usually provides good patient-ventilator synchrony, but asynchrony is sometimes encountered. Double breathing is one form of asynchrony in which the ventilator assists two or more times during a single inspiration of the patient. METHODS: Double breathing was analyzed using a computer simulation. RESULTS: In an obstructive lung model, inspiratory support was terminated just after the beginning of the inspiration lasting until inspiratory effort triggering the ventilator again. One of the causes of this premature termination was that the compressed and consumed volume in the circuit created a high peak inspiratory flow setting. The other cause was oscillation of the airway pressure. Reducing the circuit volume, slowing the inspiratory rise time, or decreasing the termination criteria could prevent this phenomenon. In a restrictive lung model, the time-constant of the lung was so short that the inspiratory flow finished early and double breathing occurred. It was difficult to prevent this phenomenon by adjusting the circuit assembly or respiratory parameters. CONCLUSIONS: Double breathing during PSV was considered to be closely associated with obstructive or restrictive lung. If the problem arises and cannot be resolved by adjusting ventilatory parameters, the ventilatory mode must be changed.

Airway Resistance↗

A new glucose-clamp algorithm--theoretical considerations and computer simulations.

The commonly used setup of an automatic glucose-clamp was analyzed as a control system, modeling the measuring device and the patient in a simple but effective way. Strict limits in response time, parasitic oscillation amplitude, and accuracy were defined in order to approach the physician's requirements. We developed a new control algorithm and defined the gain coefficients which can lead the system within these limits. Computer simulations with model parameters from literature (patient) and from experimental data (measuring device) are presented. Preliminary in vivo trials are also presented.

Algorithms↗

A general method for the computer simulation of biological systems interacting with fluids.

At this Symposium on Biological Fluid Dynamics, it is appropriate to ask whether there is any common theme that unites the diverse problems that arise in the study of living systems interacting with fluids. The answer that immediately comes to mind is this: biological fluid dynamics invariably involves the interaction of elastic flexible tissue with viscous incompressible fluid. (In many cases the tissue is not only elastic, it is also active, i.e. capable of doing work on the fluid). This paper describes the immersed boundary method, which is a general framework for the computer simulation of biofluid dynamic systems. This method has already been applied to blood flow in the heart (including the computer-assisted design of prosthetic cardiac valves), platelet aggregation during blood clotting, aquatic animal locomotion, wave propagation along the basilar membrane of the inner ear, and flow in collapsible tubes. In the immersed boundary method, the elastic (and possibly active) biological tissue is treated as a part of the fluid in which additional forces (derived from the tissue stresses) are applied. Because the tissue is represented in terms of its force field, the method remains straightforward, even when the geometry of the biological tissue is complicated, dynamic and not known in advance.

Animals↗

Computer simulation analysis of the effects of countermeasures for reentry orthostatic intolerance.

Fluid loading is a countermeasure currently in routine use to improve the g-tolerance of crewmembers during reentry and return of Shuttle flights. However, its effectiveness diminishes with mission duration. Countermeasures that will be effective on long-duration flights are needed and are presently under development. This paper discusses the application of computer simulation in the analysis of the effects of countermeasures for reentry orthostatic intolerance. The results suggest improvements upon the fluid loading countermeasure currently in use.

Blood Volume↗