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

Journal Article · Thu Mar 01 04:00:00 EST 2007 · Toxicologic Pathology, 35(1):27-40

DOI:https://doi.org/10.1080/01926230601072343· OSTI ID:902662

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

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.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 902662
• Report Number(s): PNWD-SA-7576
• Journal Information: Toxicologic Pathology, 35(1):27-40, Journal Name: Toxicologic Pathology, 35(1):27-40 Journal Issue: 1 Vol. 35; ISSN TOPADD; ISSN 0192-6233
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BIOLOGICAL EFFECTS
DOSE-RESPONSE RELATIONSHIPS
INJURIES
MAGNETIC RESONANCE
MAPPING
MONKEYS
NECROSIS
NOSE
OZONE
computational gluid dynamics
magnetic resonance imaging
morphometry
nasal toxicology
ozone