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.
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.
The 3He longitudinal spin-relaxation rate T1-1 is crucial for production of highly polarized 3He by spin-exchange optical pumping. We show that T1-1 is increased by a factor of 2-20 solely by exposure of spin-exchange cells to a few-kG magnetic field. The original T1-1 can be restored by degaussing the cell. The effect is attributed to magnetic surface sites and has been observed in both Pyrex and aluminosilicate-glass cells. Our results both advance the understanding of wall relaxation and demonstrate the use of 3He as an extremely sensitive probe of surface magnetism.
Perfluorinated gases, particularly C 2 F 6 , are potentially suitable alternatives to hyperpolarized noble gases for pulmonary airspace spin density and diffusion MRI. This work focuses mainly on 19 F imaging of C 2 F 6 gas in healthy and emphysematous explanted lungs, avoiding regulatory issues of human in vivo measurements. Three-dimensional gradient echo and spin echo spin density images of human lungs can be made in 10 s with adequate signal-to-noise, demonstrating the feasibility for breathing dynamics to be captured during a succession of short breath holds. As expected, the spin echo images have much smaller susceptibility artifacts than the gradient echo images.
We have observed a significant dependence of 3 He longitudinal relaxation times in glass spin-exchange optical pumping ͑SEOP͒ cells due only to the physical orientation of the cell in a 3 mT ͑30 G͒ applied magnetic field. The cells had no previous exposure to higher fields or were thoroughly degaussed prior to being measured. The presence of rubidium metal and heating of the cells associated with the SEOP process is necessary to produce this low-field orientation dependence. Our data suggest that the magnetic relaxation sites at the glass wall involved here may be the dominant cause of wall relaxation in SEOP cells at any field.Hyperpolarized ͑HP͒ noble gases ͑principally 3 He and 129 Xe) are important for a growing number of applications in physics ͓1,2͔, chemistry ͓3͔, biology ͓4͔, and medicine ͓5͔. The NMR sensitivity of HP gases depends critically on the longitudinal spin-relaxation time T 1 . The dominant contribution to T 1 is often due to wall relaxation ͑character-ized by the time T 1w ), i.e., depolarizing interactions between the gas atoms and the glass container ͑cell͒. For production of HP 3 He by spin-exchange optical pumping ͑SEOP͒ ͓6͔, in which 3 He nuclei are polarized through collisions with an optically pumped alkali-metal vapor ͑usually Rb͒, the presence of alkali metal in heated cells is required. However, even for unheated storage cells in which HP gas is introduced following either spin-exchange or metastabilityexchange optical pumping ͑MEOP͒ ͓7͔, alkali-metal coatings are often used because they are known to yield a significant increase in T 1w ͓8,9͔ as compared to bare-glass cells ͓10,11͔. The introduction of alkali metal into SEOP cells is also correlated with the appearance of ''T 1 hysteresis,'' a dependence of T 1w at a fixed low applied field on previous exposure of the cell to a much larger field ͓9͔. Multidomain magnetic sites at the glass surface were shown to strongly affect wall relaxation at 3.1 mT for cells exposed to magnetic fields between 10 mT and 1 T.We now report a dependence of T 1w on the physical orientation of cells in the low applied magnetic fields (Ϸ3 mT) typically used in SEOP. In contrast with previous work ͓9͔, these cells either have had no previous exposure to a large magnetic field ͑''pristine'' cells͒ or have been thoroughly degaussed, i.e., the cell-wall magnetization has been minimized through exposure to an alternating and gradually decreasing field. We generally observe a significant increase in T 1w , due solely to reversing the cell orientation in a 3 mT ͑30 G͒ field. This effect has been observed in cells fabricated by two separate research groups ͑University of Utah and NIST͒ using several types of glass and a wide range of cell sizes, shapes, and 3 He pressures. We expect that the magnetic relaxation sites first observed in Ref. ͓9͔ are involved here, as well. However, the heating of cells associated with SEOP also plays a crucial role in producing this low-field orientation dependence. We conclude that the effects of magnetic sites cannot be avoide...
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.
We present the results of an automated analysis of the morphometry of the pulmonary airway trees of the Sprague-Dawley rat. Our work is motivated by a need to inform lower-dimensional mathematical models to prescribe realistic boundary conditions for multiscale hybrid models of rat lung mechanics. Silicone casts were made from three age-matched, male Sprague-Dawley rats, immersed in a gel containing a contrast agent and subsequently imaged with magnetic resonance (MR). From a segmentation of this data, we extracted a connected graph, representing the airway centerline. Segment statistics (lengths and diameters) were derived from this graph. To validate this MR imaging/digital analysis method, airway segment measurements were compared with nearly 1,000 measurements collected by hand using an optical microscope from one of the rat lung casts. To evaluate the reproducibility of the MR imaging/digital analysis method, two lung casts were each imaged three times with randomized orientations in the MR bore. Diameters and lengths of randomly selected airways were compared among each of the repeated imaging datasets to estimate the variability. Finally, we analyzed the morphometry of the airway tree by assembling individual airway segments into structures that span multiple generations, which we call branches. We show that branches not segments are the fundamental repeating unit in the rat lung and develop simple mathematical relationships describing these structures for the entire lung. Our analysis shows that airway diameters and lengths have both a deterministic and stochastic character. Anat
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