Potential technology for studying dosimetry and response to airborne chemical and biological pollutants

Abstract

Advances in computational, and imaging techniques have enabled the rapid development of three-dimensional (3-D) models of biological systems in unprecedented detail. Using these advances, 3-D models of the lungs and nasal passages of the rat and human are being developed to ultimately improve predictions of airborne pollutant dosimetry. Techniques for imaging the respiratory tract by magnetic resonance imaging (MRI) were developed to improve the speed and accuracy of geometric data collection for mesh reconstruction. The MRI resolution is comparable to that obtained by manual measurements but at much greater speed and accuracy. Newly developed software (NWGrid) was utilized to translate imaging data from MR into 3-D mesh structures. Together, these approaches significantly reduced the time to develop a 3-D model. This more robust airway structure will ultimately facilitate modeling gas or vapor exchange between the respiratory tract and vasculature as well as enable linkages of dosimetry with cell response models. The 3-D, finite volume, viscoelastic mesh structures form the geometric basis for computational fluid dynamics modeling of inhalation, exhalation and the delivery of individual particles (or concentrations of gas or vapors) to discrete regions of the respiratory tract. The ability of these 3-D models to resolve dosimetry at such a high level of detail will require new techniques to measure regional airflows and particulate deposition for model validation.

Computational fluid dynamics simulations of submicrometer and micrometer particle deposition in the nasal passages of a Sprague-Dawley rat

“…The model consisted of the complete nasal passages (i.e., left and right nasal passages), nasopharyngeal duct, larynx, trachea, and several generations of the lung. Further details regarding the development of the model can be found in Minard et al (2006) and Timchalk et al (2001). For this study, the model was truncated at the anterior trachea to focus on particle deposition in the upper respiratory tract and to be consistent with the geometries of nasal replica molds that were used in earlier in vitro particle deposition experiments and are used for model validation (Fig.…”

“…A three-dimensional model of the rat respiratory tract was previously developed from magnetic resonance (MR) images of an adult male Sprague-Dawley rat weighing approximately 600 g (Minard et al, 2006;Timchalk et al, 2001). The model consisted of the complete nasal passages (i.e., left and right nasal passages), nasopharyngeal duct, larynx, trachea, and several generations of the lung.…”

Development of a Zealand white rabbit deposition model to study inhalation anthrax

“…Briefly, the lung cast of TB airways of a male, New Zealand white rabbit weighing 3.7 kg was made and subsequently imaged at 50 micron resolution using aμCT scanner. The lung cast data were segmented using the method of Timchalk et al (2001) and Carson et al (2010). The iso-surfaces of the segmented geometry were extracted and used to construct the airway centerlines from which airway dimensions (length and diameter) and orientations (bifurcation and gravity angles) were obtained (Kabilan et al, 2016).…”

Magnetic resonance imaging and computational fluid dynamics (CFD) simulations of rabbit nasal airflows for the development of hybrid CFD/PBPK models

“…Rabbits were imaged using an adaptation of methods previously developed in this laboratory for rats (Timchalk et al, 2001; Minard et al, 2006). In this study, magnetic resonance (MR) imaging was performed using a 2.0-tesla horizontal-bore magnet, a Varian Unity Plus console (Varian, Inc., Palo Alto, CA), and a custom, in-house fabricated linearly polarized birdcage coil with an 8-cm inner diameter.…”