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

Abstract

ABSTRACT Age-related changes in gross and microscopic structure of the nasal cavity can alter local tissue susceptibility as well as the dose of inhaled toxicant delivered to susceptible sites. This article describes a novel method for the use of magnetic resonance imaging, 3-dimensional airway modeling, and morphometric techniques to characterize the distribution and magnitude of ozone-induced nasal injury in infant monkeys. Using this method, we are able to generate age-specific, 3-dimensional, epithelial maps of the nasal airways of infant Rhesus macaques. The principal nasal lesions observed in this primate model of ozone-induced nasal toxicology were neutrophilic rhinitis, along with necrosis and exfoliation of the epithelium lining the anterior maxilloturbinate. These lesions, induced by acute or cyclic (episodic) exposures, were examined by light microscopy, quantified by morphometric techniques, and mapped on 3-dimensional models of the nasal airways. Here, we describe the histopathologic, imaging, and computational biology methods developed to efficiently characterize, localize, quantify, and map these nasal lesions. By combining these techniques, the location and severity of the nasal epithelial injury were correlated with epithelial type, nasal airway geometry, and local biochemical and molecular changes on an individual animal basis. These correlations are critical for accurate predictive modeling of exposure-dose-response relationshipsmore » in the nasal airways, and subsequent extrapolation of nasal findings in animals to humans for developing risk assessment.« less

Authors:
; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
902662
Report Number(s):
PNWD-SA-7576
Journal ID: ISSN 0192-6233; TOPADD; TRN: US200718%%46
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Toxicologic Pathology, 35(1):27-40
Additional Journal Information:
Journal Volume: 35; Journal Issue: 1; Journal ID: ISSN 0192-6233
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; MONKEYS; NOSE; MAGNETIC RESONANCE; NECROSIS; OZONE; BIOLOGICAL EFFECTS; MAPPING; INJURIES; DOSE-RESPONSE RELATIONSHIPS; magnetic resonance imaging; nasal toxicology; ozone; computational gluid dynamics; morphometry

Citation Formats

Carey, Stephen A, Minard, Kevin R, Trease, Lynn L, Wagner, James G, Garcia, Guilherme M, Ballinger, Carol A, Kimbell, Julia, Plopper, Charles G, Corley, Rick A, Postlewait, Ed, and Harkema, Jack R. Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques. United States: N. p., 2007. Web. doi:10.1080/01926230601072343.
Carey, Stephen A, Minard, Kevin R, Trease, Lynn L, Wagner, James G, Garcia, Guilherme M, Ballinger, Carol A, Kimbell, Julia, Plopper, Charles G, Corley, Rick A, Postlewait, Ed, & Harkema, Jack R. Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques. United States. https://doi.org/10.1080/01926230601072343
Carey, Stephen A, Minard, Kevin R, Trease, Lynn L, Wagner, James G, Garcia, Guilherme M, Ballinger, Carol A, Kimbell, Julia, Plopper, Charles G, Corley, Rick A, Postlewait, Ed, and Harkema, Jack R. 2007. "Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques". United States. https://doi.org/10.1080/01926230601072343.
@article{osti_902662,
title = {Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques},
author = {Carey, Stephen A and Minard, Kevin R and Trease, Lynn L and Wagner, James G and Garcia, Guilherme M and Ballinger, Carol A and Kimbell, Julia and Plopper, Charles G and Corley, Rick A and Postlewait, Ed and Harkema, Jack R},
abstractNote = {ABSTRACT Age-related changes in gross and microscopic structure of the nasal cavity can alter local tissue susceptibility as well as the dose of inhaled toxicant delivered to susceptible sites. This article describes a novel method for the use of magnetic resonance imaging, 3-dimensional airway modeling, and morphometric techniques to characterize the distribution and magnitude of ozone-induced nasal injury in infant monkeys. Using this method, we are able to generate age-specific, 3-dimensional, epithelial maps of the nasal airways of infant Rhesus macaques. The principal nasal lesions observed in this primate model of ozone-induced nasal toxicology were neutrophilic rhinitis, along with necrosis and exfoliation of the epithelium lining the anterior maxilloturbinate. These lesions, induced by acute or cyclic (episodic) exposures, were examined by light microscopy, quantified by morphometric techniques, and mapped on 3-dimensional models of the nasal airways. Here, we describe the histopathologic, imaging, and computational biology methods developed to efficiently characterize, localize, quantify, and map these nasal lesions. By combining these techniques, the location and severity of the nasal epithelial injury were correlated with epithelial type, nasal airway geometry, and local biochemical and molecular changes on an individual animal basis. These correlations are critical for accurate predictive modeling of exposure-dose-response relationships in the nasal airways, and subsequent extrapolation of nasal findings in animals to humans for developing risk assessment.},
doi = {10.1080/01926230601072343},
url = {https://www.osti.gov/biblio/902662}, journal = {Toxicologic Pathology, 35(1):27-40},
issn = {0192-6233},
number = 1,
volume = 35,
place = {United States},
year = {Thu Mar 01 00:00:00 EST 2007},
month = {Thu Mar 01 00:00:00 EST 2007}
}