Method for obtaining accurate geometrical coordinates of nasal airways for computer dosimetry modeling and lesion mapping

Abstract

Recently, finite-element computer simulation of airflow in rat nasal airways has been used to predict local and global xenobiotic mass transport. These computer simulations have the capability to facilitate the extrapolation of experimentat data from rats to humans for risk assessment. lmplementation of similar models of other species requires accurate and detailed geometrical coordinates of airways. This article presents a sectioning method for the acquisition of airway coordinates and morphometric data from fixed tissues. Using this method, airway tissue specimens are embedded in a frozen, contrast-enhancing medium and serially sectioned. Video imager are digitized from photographs of the block face, and image analysis is used to obtain geometrical coordinates of the nasal passage perimeters. Calibration images and embedded alignment marks are used to scale and align sequentiaf sections. Data resulting from the application of this method to a rhesus monkey specimen are reported, including a three-dimensional computer reconstruction of the data. Airway coordinates are also used to generate a set of diagrams suitable for lesion mapping for comparison w i t h local dosimetry data derived from numerical simulations. This method improves on previously reported methods. Undistorted airway geometry is obtained by photographing the cut block face. Automatic thresholding to obtain coordinates during image analysis is made possible by the contrast-enhancing medium. Automatic scaling and alignment of sections is facilitated by the use of calibration images and alignment marks. This coordinate acquisition method has applicability to other complex biological passageways.Understanding the effects of toxic agents requires knowledge of the dose delivered to the target tissue, but the dose is often difficult to quantify accurately for toxic agents that are inhaled. Time-dependent airflow patterns, mucociliary translocation, the uptake characteristics of different epithelial types, and local metabolism all have the potential to influence local xenobiotic disposition (Morgan, 1994). Recent work investigating the dosimetric

Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques

“…After decalcification, the nasal airways were transversely sectioned at 10 or 12 (based on the size of the specimen) specific anatomical locations, using gross dental and palatine landmarks ( Figure 3). This method produced nasal tissue blocks that had cross sectional profiles similar to those described by Kepler et al (1995), and has been FIGURE 3.-Photograph of the lateral wall of the nasal cavity of a 90-day-old Rhesus monkey. The location of the 12 transverse tissue blocks (T1-12) selected for light microscopic examination and morphometric analyses are indicated.…”

“…In previous reports, this has been accomplished experimentally using a sequential series of cross-sectional airway profiles covering the entire length of the nasal airways of each experimental animal. This systematic approach has been used to identify patterns of nasal toxicity to inhaled chemicals in adult monkeys (Young, 1981;Harkema et al, 1987d;Mery et al, 1994;Kepler, 1995), and relies on precise characterization and identification of the distribution of surface epithelial populations (Gross et al, 1982(Gross et al, , 1987Harkema et al, 1987a;Harkema, 1991). This type of detailed characterization, however, has not been previously reported for the developing nasal airways of infant monkeys.…”

Upper Respiratory Tract Lesions in Inhalation Toxicology

“…Publications providing key information on mapping and more precise localization of nasal lesions are available for rodents (Mery et al, 1994;Morgan, 1994;Hardisty et al, 1999) and nonhuman primates (Kepler et al, 1995). Consistent access to toxicologically important areas of the mucosal epithelium is equally important for accurate microscopic examination of the larynx.…”

Development of Methodology for the Three-Dimensional Modelling of the Metabolic Capacity of the Rat Nasal Cavity using Glutathione S-Transferase M1 as an Example

“…The production of consistently high quality frozen sections of undecalcified heads in which the structural integrity and morphology of the tissues are preserved presents considerable technical difficulties. However, Kepler et al (16) circumvented this problem by capturing images of the remaining surface of the head block rather than the sections that had been cut from the block. That method is dependent upon the natural density differences inherent in the tissue within the block to distinguish the separate tissues of the nasal cavity.…”