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1.
Ultrasonics ; 127: 106854, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36215762

RESUMEN

Recent years have seen a substantial increase in the application of machine learning (ML) for automated analysis of nondestructive examination (NDE) data. One of the applications of interest is the use of ML for the analysis of data from in-service inspection of welds in nuclear power and other industries. These types of inspections are performed in accordance with criteria described in the ASME Boiler and Pressure Vessel Code and require the use of reliable NDE techniques. The rapid growth in ML methods and the diversity of possible approaches indicate a need to assess the current capabilities of ML and automated data analysis for NDE and identify any gaps or shortcomings in current ML technologies as applied to the automated analysis of NDE data. In particular, there is a need to determine the impact of ML on the NDE reliability. This paper discusses the findings from a literature survey on the current state of ML for the automated analysis of data from ultrasonic NDE of weld flaws. It discusses an overview of ultrasonic NDE as used for weld inspections in nuclear power and other industries. Data sets and ML models used in the literature are summarized, along with a generally applicable workflow for ML. Findings on the capabilities, limitations and potential gaps in feature selection, data selection, and ML model optimization are discussed. The paper identified several needs for quantifying and validating the performance of ML methods for ultrasonic NDE, including the need for common data sets.

2.
Anat Rec (Hoboken) ; 299(7): 853-68, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27145450

RESUMEN

The rabbit is commonly used as a laboratory animal for inhalation toxicology tests and detail knowledge of the rabbit airway morphometry is needed for outcome analysis or theoretical modeling. The objective of this study is to quantify the morphometric dimension of the nasal airway of a New Zealand white rabbit and to relate the morphology and functions through analytical and computational methods. Images of high-resolution MRI scans of the rabbit were processed to measure the axial distribution of the cross-sectional areas, perimeter, and complexity level. The lateral recess, which has functions other than respiration or olfaction, was isolated from the nasal airway and its dimension was quantified separately. A low Reynolds number turbulence model was implemented to simulate the airflow, heat transfer, vapor transport, and wall shear stress. Results of this study provide detailed morphological information of the rabbit that can be used in the studies of olfaction, inhalation toxicology, drug delivery, and physiology-based pharmacokinetics modeling. For the first time, we reported a spiral nasal vestibule that splits into three paths leading to the dorsal meatus, maxilloturbinate, and ventral meatus, respectively. Both non-dimensional functional analysis and CFD simulations suggested that the airflow in the rabbit nose is laminar and the unsteady effect is only significantly during sniffing. Due to the large surface-to-volume ratio, the maxilloturbinate is highly effective in warming and moistening the inhaled air to body conditions. The unique anatomical structure and respiratory airflow pattern may have important implications for designing new odorant detectors or electronic noses. Anat Rec, 299:853-868, 2016. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Aire Acondicionado , Cavidad Nasal/anatomía & histología , Cavidad Nasal/fisiología , Respiración , Olfato/fisiología , Animales , Simulación por Computador , Femenino , Imagen por Resonancia Magnética , Ventilación Pulmonar , Conejos
3.
Inhal Toxicol ; 28(4): 192-202, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26986954

RESUMEN

CONTEXT: Computational fluid dynamics (CFD) simulations of airflows coupled with physiologically based pharmacokinetic (PBPK) modeling of respiratory tissue doses of airborne materials have traditionally used either steady-state inhalation or a sinusoidal approximation of the breathing cycle for airflow simulations despite their differences from normal breathing patterns. OBJECTIVE: Evaluate the impact of realistic breathing patterns, including sniffing, on predicted nasal tissue concentrations of a reactive vapor that targets the nose in rats as a case study. MATERIALS AND METHODS: Whole-body plethysmography measurements from a free-breathing rat were used to produce profiles of normal breathing, sniffing and combinations of both as flow inputs to CFD/PBPK simulations of acetaldehyde exposure. RESULTS: For the normal measured ventilation profile, modest reductions in time- and tissue depth-dependent areas under the curve (AUC) acetaldehyde concentrations were predicted in the wet squamous, respiratory and transitional epithelium along the main airflow path, while corresponding increases were predicted in the olfactory epithelium, especially the most distal regions of the ethmoid turbinates, versus the idealized profile. The higher amplitude/frequency sniffing profile produced greater AUC increases over the idealized profile in the olfactory epithelium, especially in the posterior region. CONCLUSIONS: The differences in tissue AUCs at known lesion-forming regions for acetaldehyde between normal and idealized profiles were minimal, suggesting that sinusoidal profiles may be used for this chemical and exposure concentration. However, depending upon the chemical, exposure system and concentration and the time spent sniffing, the use of realistic breathing profiles, including sniffing, could become an important modulator for local tissue dose predictions.


Asunto(s)
Modelos Biológicos , Respiración , Fenómenos Fisiológicos Respiratorios , Sistema Respiratorio/metabolismo , Acetaldehído/farmacocinética , Animales , Femenino , Hidrodinámica , Pletismografía Total , Ratas Sprague-Dawley
4.
Inhal Toxicol ; 28(2): 80-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26895308

RESUMEN

Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.


Asunto(s)
Carbunco/transmisión , Modelos Animales de Enfermedad , Exposición por Inhalación , Conejos , Microbiología del Aire , Animales , Bacillus anthracis , Pulmón/microbiología , Modelos Biológicos , Sistema Respiratorio/anatomía & histología
5.
Toxicol Sci ; 146(1): 65-88, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25858911

RESUMEN

Computational fluid dynamics (CFD) modeling is well suited for addressing species-specific anatomy and physiology in calculating respiratory tissue exposures to inhaled materials. In this study, we overcame prior CFD model limitations to demonstrate the importance of realistic, transient breathing patterns for predicting site-specific tissue dose. Specifically, extended airway CFD models of the rat and human were coupled with airway region-specific physiologically based pharmacokinetic (PBPK) tissue models to describe the kinetics of 3 reactive constituents of cigarette smoke: acrolein, acetaldehyde and formaldehyde. Simulations of aldehyde no-observed-adverse-effect levels for nasal toxicity in the rat were conducted until breath-by-breath tissue concentration profiles reached steady state. Human oral breathing simulations were conducted using representative aldehyde yields from cigarette smoke, measured puff ventilation profiles and numbers of cigarettes smoked per day. As with prior steady-state CFD/PBPK simulations, the anterior respiratory nasal epithelial tissues received the greatest initial uptake rates for each aldehyde in the rat. However, integrated time- and tissue depth-dependent area under the curve (AUC) concentrations were typically greater in the anterior dorsal olfactory epithelium using the more realistic transient breathing profiles. For human simulations, oral and laryngeal tissues received the highest local tissue dose with greater penetration to pulmonary tissues than predicted in the rat. Based upon lifetime average daily dose comparisons of tissue hot-spot AUCs (top 2.5% of surface area-normalized AUCs in each region) and numbers of cigarettes smoked/day, the order of concern for human exposures was acrolein > formaldehyde > acetaldehyde even though acetaldehyde yields were 10-fold greater than formaldehyde and acrolein.


Asunto(s)
Aldehídos/metabolismo , Modelos Biológicos , Humo , Aldehídos/farmacocinética , Animales , Humanos , Ratas , Nicotiana
6.
Exp Lung Res ; 41(3): 135-45, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25513951

RESUMEN

PURPOSE: Computer models for inhalation toxicology and drug-aerosol delivery studies rely on ventilation pattern inputs for predictions of particle deposition and vapor uptake. However, changes in lung mechanics due to disease can impact airflow dynamics and model results. It has been demonstrated that non-invasive, in vivo, 4DCT imaging (3D imaging at multiple time points in the breathing cycle) can be used to map heterogeneities in ventilation patterns under healthy and disease conditions. The purpose of this study was to validate ventilation patterns measured from CT imaging by exposing the same rats to an aerosol of fluorescent microspheres (FMS) and examining particle deposition patterns using cryomicrotome imaging. MATERIALS AND METHODS: Six male Sprague-Dawley rats were intratracheally instilled with elastase to a single lobe to induce a heterogeneous disease. After four weeks, rats were imaged over the breathing cycle by CT then immediately exposed to an aerosol of ∼ 1 µm FMS for ∼ 5 minutes. After the exposure, the lungs were excised and prepared for cryomicrotome imaging, where a 3D image of FMS deposition was acquired using serial sectioning. Cryomicrotome images were spatially registered to match the live CT images to facilitate direct quantitative comparisons of FMS signal intensity with the CT-based ventilation maps. RESULTS: Comparisons of fractional ventilation in contiguous, non-overlapping, 3D regions between CT-based ventilation maps and FMS images showed strong correlations in fractional ventilation (r = 0.888, p < 0.0001). CONCLUSION: We conclude that ventilation maps derived from CT imaging are predictive of the 1 µm aerosol deposition used in ventilation-perfusion heterogeneity inhalation studies.


Asunto(s)
Aerosoles/metabolismo , Pulmón/diagnóstico por imagen , Ventilación Pulmonar/fisiología , Administración por Inhalación , Animales , Imagenología Tridimensional/métodos , Pulmón/metabolismo , Pulmón/fisiología , Masculino , Microesferas , Ratas , Ratas Sprague-Dawley , Respiración , Tomografía Computarizada por Rayos X/métodos
7.
Inhal Toxicol ; 26(9): 524-44, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25055841

RESUMEN

While inhalation toxicological studies of various compounds have been conducted using a number of different strains of rats, mechanistic dosimetry models have only had tracheobronchial (TB) structural data for Long-Evans rats, detailed morphometric data on the alveolar region of Sprague-Dawley rats and limited alveolar data on other strains. Based upon CT imaging data for two male Sprague-Dawley rats, a 15-generation, symmetric typical path model was developed for the TB region. Literature data for the alveolar region of Sprague-Dawley rats were analyzed to develop an eight-generation model, and the two regions were joined to provide a complete lower respiratory tract model for Sprague-Dawley rats. The resulting lung model was used to examine particle deposition in Sprague-Dawley rats and to compare these results with predicted deposition in Long-Evans rats. Relationships of various physiologic variables and lung volumes were either developed in this study or extracted from the literature to provide the necessary input data for examining particle deposition. While the lengths, diameters and branching angles of the TB airways differed between the two Sprague-Dawley rats, the predicted deposition patterns in the three major respiratory tract regions were very similar. Between Sprague-Dawley and Long-Evans rats, significant differences in TB and alveolar predicted deposition fractions were observed over a wide range of particle sizes, with TB deposition fractions being up to 3- to 4-fold greater in Sprague-Dawley rats and alveolar deposition being significantly greater in Long-Evans rats. Thus, strain-specific lung geometry models should be used for particle deposition calculations and interspecies dose comparisons.


Asunto(s)
Modelos Biológicos , Material Particulado/farmacocinética , Fenómenos Fisiológicos Respiratorios , Sistema Respiratorio/anatomía & histología , Administración por Inhalación , Animales , Exposición por Inhalación , Masculino , Modelos Animales , Tamaño de la Partícula , Ratas , Ratas Long-Evans , Ratas Sprague-Dawley , Sistema Respiratorio/metabolismo
8.
BMC Med Imaging ; 14: 1, 2014 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-24393332

RESUMEN

BACKGROUND: Assessing heterogeneity in lung images can be an important diagnosis tool. We present a novel and objective method for assessing lung damage in a rat model of emphysema. We combined a three-dimensional (3D) computer graphics method-octree decomposition-with a geostatistics-based approach for assessing spatial relationships-the variogram-to evaluate disease in 3D computed tomography (CT) image volumes. METHODS: Male, Sprague-Dawley rats were dosed intratracheally with saline (control), or with elastase dissolved in saline to either the whole lung (for mild, global disease) or a single lobe (for severe, local disease). Gated 3D micro-CT images were acquired on the lungs of all rats at end expiration. Images were masked, and octree decomposition was performed on the images to reduce the lungs to homogeneous blocks of 2 × 2 × 2, 4 × 4 × 4, and 8 × 8 × 8 voxels. To focus on lung parenchyma, small blocks were ignored because they primarily defined boundaries and vascular features, and the spatial variance between all pairs of the 8 × 8 × 8 blocks was calculated as the square of the difference of signal intensity. Variograms-graphs of distance vs. variance-were constructed, and results of a least-squares-fit were compared. The robustness of the approach was tested on images prepared with various filtering protocols. Statistical assessment of the similarity of the three control rats was made with a Kruskal-Wallis rank sum test. A Mann-Whitney-Wilcoxon rank sum test was used to measure statistical distinction between individuals. For comparison with the variogram results, the coefficient of variation and the emphysema index were also calculated for all rats. RESULTS: Variogram analysis showed that the control rats were statistically indistinct (p = 0.12), but there were significant differences between control, mild global disease, and severe local disease groups (p < 0.0001). A heterogeneity index was calculated to describe the difference of an individual variogram from the control average. This metric also showed clear separation between dose groups. The coefficient of variation and the emphysema index, on the other hand, did not separate groups. CONCLUSION: These results suggest the octree decomposition and variogram analysis approach may be a rapid, non-subjective, and sensitive imaging-based biomarker for characterizing lung disease.


Asunto(s)
Enfisema/diagnóstico por imagen , Imagenología Tridimensional/métodos , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Animales , Modelos Animales de Enfermedad , Enfisema/patología , Pulmón/patología , Masculino , Interpretación de Imagen Radiográfica Asistida por Computador , Ratas , Ratas Sprague-Dawley , Sensibilidad y Especificidad
9.
Acad Radiol ; 20(10): 1264-71, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24029058

RESUMEN

RATIONALE AND OBJECTIVES: To investigate the ability of variogram analysis of octree-decomposed computed tomography (CT) images and volume change maps to detect radiation-induced damage in rat lungs. MATERIALS AND METHODS: The lungs of female Sprague-Dawley rats were exposed to one of five absorbed doses (0, 6, 9, 12, or 15 Gy) of gamma radiation from a Co-60 source. At 6 months postexposure, pulmonary function tests were performed and four-dimensional (4D) CT images were acquired using a respiratory-gated microCT scanner. Volume change maps were then calculated from the 4DCT images. Octree decomposition was performed on CT images and volume change maps, and variogram analysis was applied to the decomposed images. Correlations of measured parameters with dose were evaluated. RESULTS: The effects of irradiation were not detectable from measured parameters, indicating only mild lung damage. Additionally, there were no significant correlations of pulmonary function results or CT densitometry with radiation dose. However, the variogram analysis did detect a significant correlation with dose in both the CT images (r = -0.57, P = .003) and the volume change maps (r = -0.53, P = .008). CONCLUSION: This is the first study to use variogram analysis of lung images to assess pulmonary damage in a model of radiation injury. Results show that this approach is more sensitive to detecting radiation damage than conventional measures such as pulmonary function tests or CT densitometry.


Asunto(s)
Algoritmos , Imagenología Tridimensional/métodos , Neumonitis por Radiación/diagnóstico por imagen , Neumonitis por Radiación/etiología , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/efectos adversos , Tomografía Computarizada por Rayos X/métodos , Animales , Femenino , Dosis de Radiación , Radiometría/métodos , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
10.
Exp Lung Res ; 39(6): 249-57, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23786464

RESUMEN

The use of anatomically accurate, animal-specific airway geometries is important for understanding and modeling the physiology of the respiratory system. One approach for acquiring detailed airway architecture is to create a bronchial cast of the conducting airways. However, typical casting procedures either do not faithfully preserve the in vivo branching angles or produce rigid casts that when removed for imaging are fragile and thus easily damaged. We address these problems by creating an in situ bronchial cast of the conducting airways in rats that can be subsequently imaged in situ using three-dimensional micro-CT imaging. We also demonstrate that deformations in airway branch angles resulting from the casting procedure are small, and that these angle deformations can be reversed through an interactive adjustment of the segmented cast geometry. Animal work was approved by the Institutional Animal Care and Use Committee of Pacific Northwest National Laboratory.


Asunto(s)
Bronquios/anatomía & histología , Molde por Corrosión/métodos , Imagenología Tridimensional/métodos , Microtomografía por Rayos X/métodos , Animales , Artefactos , Broncografía , Masculino , Ratas , Ratas Sprague-Dawley
11.
PLoS One ; 8(6): e65874, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23799057

RESUMEN

Changes in the shape of the lung during breathing determine the movement of airways and alveoli, and thus impact airflow dynamics. Modeling airflow dynamics in health and disease is a key goal for predictive multiscale models of respiration. Past efforts to model changes in lung shape during breathing have measured shape at multiple breath-holds. However, breath-holds do not capture hysteretic differences between inspiration and expiration resulting from the additional energy required for inspiration. Alternatively, imaging dynamically--without breath-holds--allows measurement of hysteretic differences. In this study, we acquire multiple micro-CT images per breath (4DCT) in live rats, and from these images we develop, for the first time, dynamic volume maps. These maps show changes in local volume across the entire lung throughout the breathing cycle and accurately predict the global pressure-volume (PV) hysteresis. Male Sprague-Dawley rats were given either a full- or partial-lung dose of elastase or saline as a control. After three weeks, 4DCT images of the mechanically ventilated rats under anesthesia were acquired dynamically over the breathing cycle (11 time points, ≤100 ms temporal resolution, 8 cmH2O peak pressure). Non-rigid image registration was applied to determine the deformation gradient--a numerical description of changes to lung shape--at each time point. The registration accuracy was evaluated by landmark identification. Of 67 landmarks, one was determined misregistered by all three observers, and 11 were determined misregistered by two observers. Volume change maps were calculated on a voxel-by-voxel basis at all time points using both the Jacobian of the deformation gradient and the inhaled air fraction. The calculated lung PV hysteresis agrees with pressure-volume curves measured by the ventilator. Volume maps in diseased rats show increased compliance and ventilation heterogeneity. Future predictive multiscale models of rodent respiration may leverage such volume maps as boundary conditions.


Asunto(s)
Enfisema/diagnóstico por imagen , Tomografía Computarizada Cuatridimensional/métodos , Ventilación Pulmonar , Animales , Enfisema/fisiopatología , Hidrodinámica , Pulmón/diagnóstico por imagen , Pulmón/patología , Pulmón/fisiopatología , Masculino , Interpretación de Imagen Radiográfica Asistida por Computador , Ratas , Ratas Sprague-Dawley , Respiración
12.
Int J Numer Method Biomed Eng ; 29(1): 1-16, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23293066

RESUMEN

Geometries for organ scale and multiscale simulations of organ function are now routinely derived from imaging data. However, medical images may also contain spatially heterogeneous information other than geometry that are relevant to such simulations either as initial conditions or in the form of model parameters. In this manuscript, we present an algorithm for the efficient and robust mapping of such data to imaging-based unstructured polyhedral grids in parallel. We then illustrate the application of our mapping algorithm to three different mapping problems: (i) the mapping of MRI diffusion tensor data to an unstructured ventricular grid; (ii) the mapping of serial cyrosection histology data to an unstructured mouse brain grid; and (iii) the mapping of computed tomography-derived volumetric strain data to an unstructured multiscale lung grid. Execution times and parallel performance are reported for each case.


Asunto(s)
Algoritmos , Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Imagenología Tridimensional/métodos , Animales , Fenómenos Biomecánicos , Ratones , Radiografía
13.
Inhal Toxicol ; 24(13): 869-99, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23121298

RESUMEN

The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 µm in size were examined for endotracheal and and up to 5 µm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.


Asunto(s)
Macaca mulatta/anatomía & histología , Modelos Animales , Modelos Biológicos , Sistema Respiratorio/anatomía & histología , Administración por Inhalación , Algoritmos , Animales , Femenino , Humanos , Macaca mulatta/fisiología , Masculino , Tamaño de la Partícula , Material Particulado/metabolismo , Fenómenos Fisiológicos Respiratorios , Sistema Respiratorio/metabolismo
14.
J Magn Reson ; 221: 129-38, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22771528

RESUMEN

Phase-contrast (PC) magnetic resonance imaging (MRI) with hyperpolarized ³He is potentially useful for developing and testing patient-specific models of pulmonary airflow. One challenge, however, is that PC-MRI provides apparent values of local ³He velocity that not only depend on actual airflow but also on gas diffusion. This not only blurs laminar flow patterns in narrow airways but also introduces anomalous airflow structure that reflects gas-wall interactions. Here, both effects are predicted in a live rat using computational fluid dynamics (CFD), and for the first time, simulated patterns of apparent ³He gas velocity are compared with in vivo PC-MRI. Results show (1) that correlations (R²) between measured and simulated airflow patterns increase from 0.23 to 0.79 simply by accounting for apparent ³He transport, and (2) that remaining differences are mainly due to uncertain airway segmentation and partial volume effects stemming from relatively coarse MRI resolution. Higher-fidelity testing of pulmonary airflow predictions should therefore be possible with future imaging improvements.


Asunto(s)
Pulmón/fisiología , Imagen por Resonancia Magnética/métodos , Ventilación Pulmonar/fisiología , Algoritmos , Animales , Benchmarking , Calibración , Análisis de Fourier , Helio , Procesamiento de Imagen Asistido por Computador , Masculino , Fantasmas de Imagen , Ratas , Ratas Sprague-Dawley , Respiración Artificial
15.
Toxicol Sci ; 128(2): 500-16, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22584687

RESUMEN

Computational fluid dynamics (CFD) models are useful for predicting site-specific dosimetry of airborne materials in the respiratory tract and elucidating the importance of species differences in anatomy, physiology, and breathing patterns. We improved the imaging and model development methods to the point where CFD models for the rat, monkey, and human now encompass airways from the nose or mouth to the lung. A total of 1272, 2172, and 135 pulmonary airways representing 17±7, 19±9, or 9±2 airway generations were included in the rat, monkey and human models, respectively. A CFD/physiologically based pharmacokinetic model previously developed for acrolein was adapted for these anatomically correct extended airway models. Model parameters were obtained from the literature or measured directly. Airflow and acrolein uptake patterns were determined under steady-state inhalation conditions to provide direct comparisons with prior data and nasal-only simulations. Results confirmed that regional uptake was sensitive to airway geometry, airflow rates, acrolein concentrations, air:tissue partition coefficients, tissue thickness, and the maximum rate of metabolism. Nasal extraction efficiencies were predicted to be greatest in the rat, followed by the monkey, and then the human. For both nasal and oral breathing modes in humans, higher uptake rates were predicted for lower tracheobronchial tissues than either the rat or monkey. These extended airway models provide a unique foundation for comparing material transport and site-specific tissue uptake across a significantly greater range of conducting airways in the rat, monkey, and human than prior CFD models.


Asunto(s)
Fenómenos Fisiológicos Respiratorios/efectos de los fármacos , Acroleína/farmacocinética , Acroleína/farmacología , Anciano , Anciano de 80 o más Años , Animales , Femenino , Humanos , Macaca mulatta , Masculino , Ratas , Ratas Sprague-Dawley , Distribución Tisular
16.
Anat Rec (Hoboken) ; 295(6): 1027-44, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22528468

RESUMEN

We examine a previously published branch-based approach for modeling airway diameters that is predicated on the assumption of self-consistency across all levels of the tree. We mathematically formulate this assumption, propose a method to test it and develop a more general model to be used when the assumption is violated. We discuss the effect of measurement error on the estimated models and propose methods that take account of error. The methods are illustrated on data from MRI and CT images of silicone casts of two rats, two normal monkeys, and one ozone-exposed monkey. Our results showed substantial departures from self-consistency in all five subjects. When departures from self-consistency exist, we do not recommend using the self-consistency model, even as an approximation, as we have shown that it may likely lead to an incorrect representation of the diameter geometry. The new variance model can be used instead. Measurement error has an important impact on the estimated morphometry models and needs to be addressed in the analysis.


Asunto(s)
Bronquios/anatomía & histología , Macaca mulatta/anatomía & histología , Modelos Anatómicos , Ratas Sprague-Dawley/anatomía & histología , Animales , Imagen por Resonancia Magnética , Masculino , Ratas , Reproducibilidad de los Resultados , Tomografía Computarizada por Rayos X
17.
PLoS One ; 6(11): e27577, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22087338

RESUMEN

Pulmonary computational fluid dynamics models require that three-dimensional images be acquired over multiple points in the dynamic breathing cycle without breath holds or changes in ventilatory mechanics. With small animals, these requirements can result in long imaging times (∼90 minutes), over which lung mechanics, such as compliance, may gradually change if not carefully monitored and controlled. These changes, caused by derecruitment of parenchymal tissue, are manifested as an upward drift in peak inspiratory pressure (PIP) or by changes in the pressure waveform and/or lung volume over the course of the experiment. We demonstrate highly repeatable mechanical ventilation in anesthetized rats over a long duration for dynamic lung x-ray computed tomography (CT) imaging. We describe significant updates to a basic commercial ventilator that was acquired for these experiments. Key to achieving consistent results was the implementation of periodic deep breaths, or sighs, of extended duration to maintain lung recruitment. In addition, continuous monitoring of breath-to-breath pressure and volume waveforms and long-term trends in PIP and flow provide diagnostics of changes in breathing mechanics.


Asunto(s)
Hidrodinámica , Pulmón/fisiología , Modelos Biológicos , Respiración , Animales , Imagenología Tridimensional , Ratas , Tomografía Computarizada por Rayos X
18.
J Comput Assist Tomogr ; 34(5): 773-9, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20861785

RESUMEN

OBJECTIVE: To evaluate the use of inflation-fixed lung tissue for emphysema quantification with computed tomography (CT) and He magnetic resonance (MR) diffusion imaging. METHODS: Fourteen subjects representing a range of chronic obstructive pulmonary disease severity who underwent complete or lobar lung resection were studied. Computed tomographic measurements of lung attenuation and MR measurements of the hyperpolarized 3He apparent diffusion coefficient (ADC) in resected specimens fixed in inflation with heated formalin vapor were compared with measurements obtained before fixation. RESULTS: The mean (SD) CT emphysema indices were 56% (17%) before and 58% (19%) after fixation (P = 0.77; R = 0.76). Index differences correlated with differences in lung volume (R = 0.47). The mean (SD) 3He ADCs were 0.40 (0.15) cm/s before and 0.39 (0.14) cm/s after fixation (P = 0.03, R = 0.98). The CT emphysema index and the 3He ADC were correlated before (R = 0.89) and after fixation (R = 0.79). CONCLUSIONS: Concordance of CT and 3He MR imaging measurements in unfixed and inflation-fixed lungs supports the use of inflation-fixed lungs for quantitative imaging studies in emphysema.


Asunto(s)
Enfisema/diagnóstico , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano , Enfisema/diagnóstico por imagen , Enfisema/cirugía , Femenino , Helio , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Neumonectomía , Dosis de Radiación
19.
J Magn Reson Imaging ; 31(5): 1091-9, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20432343

RESUMEN

PURPOSE: To investigate the ability of proton ((1)H) magnetic resonance imaging (MRI) to distinguish between pulmonary inflammation and fibrosis. MATERIALS AND METHODS: Three groups of Sprague-Dawley rats (n = 5) were instilled intratracheally with bleomycin (2.5 U/kg or 3.5 U/kg) in saline or with saline only. Rats were imaged at 2.0 Tesla using a multi-slice Carr-Purcell-Meilboom-Gill (CPMG) sequence with 6 ms echo spacing. Signal intensity (S(0)) and T(2) were calculated on a pixel-by-pixel basis using images collected before dosing and 1, 2, 4, and 7 weeks after. At each time point, data from dosed animals were compared with controls, and bivariate statistical analysis was used to classify image pixels containing abnormal tissue. At week 7, pulmonary function tests were performed, then all rats were killed, left lungs were formalin fixed and tri-chrome stained for histological analysis of collagen content, and right lungs were used to measure water and hydroxyproline (collagen) content. RESULTS: The product S(0)xT(2) significantly correlated with water and collagen content in the high-dose group (P = 0.004 and P = 0.03, respectively). However, S(0) and T(2) of abnormal tissue were correlated for all time points (r = 0.93, P < 0.001), and could not distinguish inflammation from fibrosis. CONCLUSION: MRI can be used to confidently localize pulmonary inflammation and fibrosis, but it lacks specificity.


Asunto(s)
Bleomicina , Modelos Animales de Enfermedad , Imagen por Resonancia Magnética/métodos , Neumonía/inducido químicamente , Neumonía/diagnóstico , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/diagnóstico , Animales , Humanos , Masculino , Protones , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
20.
J Magn Reson Imaging ; 30(4): 801-8, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19787725

RESUMEN

PURPOSE: To characterize the effect of diffusion time on short-range hyperpolarized (3)He magnetic resonance imaging (MRI) diffusion measurements across a wide range of emphysema severity. MATERIALS AND METHODS: (3)He diffusion MRI was performed on 19 lungs or lobes resected from 18 subjects with varying degrees of emphysema using three diffusion times (1.6 msec, 5 msec, and 10 msec) at constant b value. Emphysema severity was quantified as the mean apparent diffusion coefficient (ADC) and as the percentage of pixels with ADC higher than multiple thresholds from 0.30-0.55 cm(2)/sec (ADC index). Quantitative histology (mean linear intercept) was obtained in 10 of the lung specimens from 10 of the subjects. RESULTS: The mean ADCs with diffusion times of 1.6, 5.0, and 10.0 msec were 0.46, 0.40, and 0.37 cm(2)/sec, respectively (P < 0.0001, analysis of variance [ANOVA]). There was no relationship between the ADC magnitude and the effect of diffusion time on ADC values. The mean linear intercept correlated with ADC (r = 0.91-0.94, P < 0.001) and ADC index (r = 0.78-0.92, P < 0.01) at all diffusion times. CONCLUSION: Decreases in ADC with longer diffusion time were unrelated to emphysema severity. The strong correlations between the ADC at all diffusion times tested and quantitative histology demonstrate that ADC is a robust measure of emphysema.


Asunto(s)
Imagen de Difusión por Resonancia Magnética/métodos , Enfisema Pulmonar/patología , Anciano , Análisis de Varianza , Femenino , Helio , Humanos , Técnicas In Vitro , Isótopos , Masculino
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