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At least 1,153 records · Page 64Linked to original sources

Estimation of patient dose from radiopharmaceuticals using voxel models.

The aim of this study was to demonstrate the advantages of patient dosimetry using voxel models and to present sets of dose estimates for patients of different gender and size. These models offer greater realism with respect to organ shape and topology than the well-established Medical Internal Radiation Dose (MIRD)-type mathematical models. At the National Research Centre for Environment and Health (GSF), specific absorbed fractions have been previously calculated for 4 male and 3 female voxel models, representing different age and stature, for a wide range of source organs. For this study, estimates both for established and new radiopharmaceuticals were performed using biokinetic data from International Commission on Radiological Protection (ICRP). The above calculations allowed for comparison to the MIRD technique in relation to the resulting absorbed organ and effective doses. Furthermore, data sets representing a range of voxel phantoms were investigated. It was found that dose differences among the voxel models can amount up to a factor of 3.

Adult↗

Isotonic and hypertonic saline droplet deposition in a human upper airway model.

The evaporative and hygroscopic effects and deposition of isotonic and hypertonic saline droplets have been simulated from the mouth to the first four generations of the tracheobronchial tree under laminar-transitional-turbulent inspiratory flow conditions. Specifically, the local water vapor transport, droplet evaporation rate, and deposition fractions are analyzed. The effects of inhalation flow rates, thermodynamic air properties and NaCl-droplet concentrations of interest are discussed as well. The validated computer simulation results indicate that the increase of NaCl-solute concentration, increase of inlet relative humidity, or decrease of inlet air temperature may reduce water evaporation and increase water condensation at saline droplet surfaces, resulting in higher droplet depositions due to the increasing particle diameter and density. However, solute concentrations below 10% may not have a very pronounced effect on droplet deposition in the human upper airways.

Administration, Inhalation↗

Comparison of SPECT aerosol deposition data with a human respiratory tract model.

Three-dimensional (3D) radionuclide imaging provides detailed information on the distribution of inhaled aerosol material within the body. Analysis of the data can provide estimates of the deposition per airway generation. In this study, two different nebulizers have been used to deliver radiolabeled aerosols of different particle size to 12 human subjects. Medical imaging has been used to assess the deposition in the body. The deposition pattern has also been estimated using the International Commission on Radiological Protection (ICRP) empirical model and compared to values obtained by experiment. The results showed generally good agreement between model and experiment for both aerosols for the deposition in the extrathoracic and conducting airways. However, there were significant differences in the fate of the remainder of the aerosol between the amount deposited in the alveolar region and that exhaled. The inter-subject variability of deposition predicted by the model was significantly less than that measured, for all regions of the body. The model predicted quite well the differences in deposition distribution pattern between the two aerosols. In conclusion, this study has shown that the ICPR model of inhaled aerosol deposition shows areas of good agreement with results from experiment. However, there are also areas of disagreement, which may be explained by hygroscopic particle growth and individual variation in airway anatomy.

Administration, Inhalation↗

Aerosol deposition in the upper airways of a child.

In a small child, normally only a small amount of inhaled aerosol particles reaches the lungs because the majority deposits in the upper airways. In this study, the upper airways of a 9- month-old child, based on computed tomography (CT) data, are modeled to serve as input for a computational fluid dynamics package (CFX). Verification of the validity of aerosol deposition calculations by this package is accomplished by evaluating two test cases, which also can be solved analytically. The numerically found sedimentation fraction in a horizontally placed straight pipe shows deviations from the exact solution for small particle sizes (less than 3 micron) due to small velocities generated by the use of an unstructured mesh. Although these velocities are small compared to the mainstream velocity, they are comparable with the terminal settling velocity of such a particle. Also the test case for inertial impaction in a bend pipe demonstrated the same problem. With this in mind, the aerosol deposition of 3.7-micron particles in the upper airway model of the child (SAINT-model) was calculated. Results were compared with experimentally found results in the literature. For small tidal volumes and flow rates, the computational results matched the experimentally measured results. However, large deviations were found for higher flow rates and small particle sizes. Most probably the incompletely modeled entrance at the nose and inertial effects due to turbulence might be responsible.

Administration, Inhalation↗

Analysis of particle deposition in the turbinate and olfactory regions using a human nasal computational fluid dynamics model.

The human nasal passages effectively filter particles from inhaled air. This prevents harmful pollutants from reaching susceptible pulmonary airways, but may leave the nasal mucosa vulnerable to potentially injurious effects from inhaled toxicants. This filtering property may also be strategically used for aerosolized nasal drug delivery. The nasal route has recently been considered as a means of delivering systemically acting drugs due to the large absorptive surface area available in close proximity to the nostrils. In this study, a computational fluid dynamics (CFD) model of nasal airflow was used with a particle transport and deposition code to predict localized deposition of inhaled particles in human nasal passages. The model geometry was formed from MRI scan tracings of the nasal passages of a healthy adult male. Spherical particles ranging in size from 5 to 50 microm were released from the nostrils. Particle trajectories and deposition sites were calculated in the presence of steady-state inspiratory airflow at volumetric flow rates of 7.5, 15, and 30 L/min. The nasal valve, turbinates, and olfactory region were defined in the CFD model so that particles depositing in these regions could be identified and correlated with their release positions on the nostril surfaces. When plotted against impaction parameter, deposition efficiencies in these regions exhibited maximum values of 53%, 20%, and 3%, respectively. Analysis of preferential deposition patterns and nostril release positions under natural breathing scenarios can be used to determine optimal particle size and flow rate combinations to selectively target drug particles to specific regions of the nose.

Administration, Inhalation↗

Three-dimensional computational fluid dynamics simulations of particle deposition in the tracheobronchial tree.

Simulation of the dynamics and disposition of inhaled particles within human lungs is an invaluable tool in both the development of inhaled pharmacologic drugs and the risk assessment of environmental particulate matter (PM). The goal of the present focused study was to assess the utility of three-dimensional computational fluid dynamics (CFD) models in studying the local deposition patterns of PM in respiratory airways. CFD models were validated using data from published experimental studies in human lung casts. The ability of CFD to appropriately simulate trends in deposition patterns due to changing ventilatory conditions was specifically addressed. CFD simulations of airflow and particle motion were performed in a model of the trachea and main bronchi using Fluent Inc.'s FIDAP CFD software. Particle diameters of 8 microm were considered for input flow rates of 15 and 60 L/min. CFD was able to reproduce the observed spatial heterogeneities of deposition within the modeled bifurcations, and correctly predicted the "hot-spots" of particle deposition on carinal ridges. The CFD methods also predicted observed differences in deposition for high-versus-low flow rates. CFD models may provide an efficient means of studying the complex effects of airway geometry, particle characteristics, and ventilatory parameters on particle deposition and therefore aid in the design of human subject experiments.

Administration, Inhalation↗

Three-dimensional computer-assisted analysis of graded contusion lesions in the spinal cord of the rat.

Histological analysis of spinal cord injury in experimental animals has focused primarily on the microanatomy of damaged tissue. The current study presents an analysis of the three-dimensional structure of lesion sites in the spinal cord of rats contused with an injury device which produces consistent lesions. Three levels of injury were produced by systematically varying the cord displacement and the duration of the displacement during impact. The resulting groups of subjects exhibited mild, moderate, and severe neurological deficits. Comparisons of equivalent mild impacts made at thoracic versus lumbar spinal cord levels were also made. The results indicate that the overall shape of the lesions is generally biconical, with extensions in the base of the dorsal funiculus, irrespective of the degree of damage or the spinal level of the injury. Lower displacement injuries yielded shorter lesions rostrocaudally with less spread into the white matter. Similar impacts in the lumbar versus thoracic spinal cord produced shorter, more truncated lesion sites at lumbar levels with less involvement of the white matter than in the thoracic lesions. Three-dimensional analyses can can provide additional information about the lesion beyond that available from conventional histopathological measures. Such information could be useful in assessing the results of posttraumatic manipulations which are directed at reducing tissue damage or tissue replacement via transplantation.

Animals↗

On the mechanics of impact neurotrauma: a review and critical synthesis.

A computational modeling technique for the simulation of head impact mechanics is proposed as a tool for the study of traumatic brain injury (TBI). The capabilities, limitations, and consequently the utilities of this technique are discussed in light of the current computing and imaging technologies and their prospective advancement. A significant portion of the mechanics, relevant to head impact simulation, has been incorporated into this computational technique resulting in automated devices that ease the technical burden of biomechanical analysis of TBI mechanisms. A brief exposition of the concepts utilized in these devices is given and their basis in experiment is discussed.

Biomechanical Phenomena↗

The influence of different boundary conditions on the response of the head to impact: a two-dimensional finite element study.

The objective of the present study is to gain a better understanding of the possible importance of skull-brain interface conditions, boundary conditions at the head-neck junction, and brain material properties when modeling the response of the human head to transient loadings. To that end, a two-dimensional plane strain finite element model of a para-sagittal section of a human head has been developed. The model comprises the brain and the skull, with the foramen magnum represented by a force-free opening. The model geometry was obtained from MRI data. The material properties used were adopted from the literature and are homogeneous and isotropic. In all analyses the skull bone was modeled as a linearly elastic material. First, to enable a comparison between simulation results and experiments reported in the literature, the loading conditions, realized in experiments reported in literature, were used as input to the completely linearly elastic model without a kinematic constraint at the head-neck junction. This was done for both rigid coupling and no coupling at the skull-brain interface. Next, various versions of the model were constructed by using different combinations of the following features: linear elastic or viscoelastic brain material properties, different contact conditions at the skull-brain interface, and incorporation of a neck constraint. The results show that both coup and contrecoup pressures are much more sensitive to the type of skull-brain interface condition than to the presence or absence of a force-free foramen magnum. A neck constraint proves to be an important modeling assumption, because of its effect upon the deformation of the brain. The use of different time-dependent deviatoric material parameters for the brain did not significantly change the head's response.

Biomechanical Phenomena↗

Vascular progenitor cells: origin and mechanisms of mobilization, differentiation, integration, and vasculogenesis.

The recent discovery of progenitor cells in peripheral blood that can differentiate into endothelial or vascular smooth muscle cells has led to the re-evaluation of many traditionally held beliefs about vascular biology. Most notably, concepts of vascular regeneration and repair, previously considered limited to the proliferation of existing differentiated cells within vascular tissue, have been expanded to include the potential for postnatal vasculogenesis. These cells have since been identified in the bone marrow, heart, skeletal muscle, and other peripheral tissues, including the vasculature itself. The significance of these cells lies not only in developing our understanding of normal vascular biology, but also in the insights they may provide into vascular diseases such as atherosclerosis. In addition, a potential role in therapeutics has already been explored in early clinical trials in humans. The mechanisms underlying the mobilization, target tissue integration, differentiation, and the observed therapeutic benefits of these cells are now being elucidated. It is these mechanisms, and the current understanding of the lineage of these cells, that constitutes the focus of this review.

Animals↗

Formalization of mouse embryo anatomy.

MOTIVATION: The Edinburgh Mouse Atlas and Gene Expression Database project has developed a digital atlas of mouse development to provide a spatio-temporal framework for spatially mapped data such as in situ gene expression and cell lineage. As part of this database, a mouse embryo anatomy ontology has been created. A formalization of this anatomy is required to document its precise semantics and how it is used in the context of the Mouse Atlas. RESULTS: The paper describes the existing anatomy ontology and formalizes aspects of it using a predicate logic based approach. It therefore provides a guide for users of the current version of the ontology, as well as the basis for a description of the anatomy using an ontology language, such as OWL, thus enabling future work on reasoning about the Mouse Atlas in the context of an intelligent gene expression bioinformatics workflow system. The logic has been implemented in a Prolog prototype. AVAILABILITY: The Mouse Atlas is available on-line at http://genex.hgu.mrc.ac.uk

Algorithms↗

A model lung with direct representation of respiratory muscle activity.

We describe the theory, construction and testing of an active model lung. This is designed so that when it is connected to a ventilator, the interaction between spontaneous ventilatory activity in the patient and the pressures and flows generated by the ventilator are reproduced faithfully. A waveform of negative pressure, pmus, equivalent to the action of the respiratory muscles, is applied indirectly to the compliance unit of a conventional model lung. It is shown that, when the compliance and resistance of a subject have been measured, the waveform of pmus can be determined. This was undertaken in three volunteers breathing under various conditions, including connection to a ventilator operating in different modes. When these conditions were reproduced with the lung model replacing, but matched to, each subject, the original waveforms of flow and pressure at the mouth were reproduced.

Adult↗

Retinotopic organization in human visual cortex and the spatial precision of functional MRI.

A method of using functional magnetic resonance imaging (fMRI) to measure retinotopic organization within human cortex is described. The method is based on a visual stimulus that creates a traveling wave of neural activity within retinotopically organized visual areas. We measured the fMRI signal caused by this stimulus in visual cortex and represented the results on images of the flattened cortical sheet. We used the method to locate visual areas and to evaluate the spatial precision of fMRI. Specifically, we: (i) identified the borders between several retinotopically organized visual areas in the posterior occipital lobe; (ii) measured the function relating cortical position to visual field eccentricity within area V1; (iii) localized activity to within 1.1 mm of visual cortex; and (iv) estimated the spatial resolution of the fMRI signal and found that signal amplitude falls to 60% at a spatial frequency of 1 cycle per 9 mm of visual cortex. This spatial resolution is consistent with a linespread whose full width at half maximum spreads across 3.5 mm of visual cortex.

Brain Mapping↗

Constant and variable aspects of axonal phenotype in cerebral cortex.

In order to determine to what extent the terminal arbors of phylogenetically and functionally distant axons are constructed according to common rules, we have compared visual callosal axons in cats (CCC axons) with thalamocortical axons to the whisker representation in mice (MTC axons). Both similarities and differences were found. Maximal order of branching, branching angles, topological distribution of branches and boutons are similar for all axons, indicating strong constraints in arbor formation. CCC and MTC axons are indistinguishable for total arbor length and number of branches, although these parameters can vary across individual axons of each group. MTC axons have longer and bouton-richer end-branches (the 'transmission compartment') while, in CCC axons, proximal, boutonless branches (the 'conduction compartment') predominate. Therefore, the two classes of axons appear to be specialized for performing different types of operations, in agreement with the available electrophysiological data and computer simulations. Differences in the length of branches were also observed between MTC axons of normal and 'barrelless' mice, suggesting that this parameter can be regulated by conditions at the terminal sites.

Animals↗