Abstract
Age-related changes in gross and microscopic structure of the nasal cavity may 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 generated 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 precisely 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 determining risk.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 27-40 |
| Number of pages | 14 |
| Journal | Toxicologic Pathology |
| Volume | 35 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2007 |
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Keywords
- computational fluid dynamics
- Magnetic resonance imaging
- morphometry
- nasal toxicology
- ozone
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Molecular Biology
- Toxicology
- Cell Biology
Cite this
Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques. / Carey, Stephan A.; Minard, Kevin R.; Trease, Lynn L.; Wagner, James G.; Garcia, Guilherme J.M.; Ballinger, Carol A.; Kimbell, Julia S.; Plopper, Charles; Corley, Richard A.; Postlethwait, Edward M.; Harkema, Jack R.
In: Toxicologic Pathology, Vol. 35, No. 1, 01.01.2007, p. 27-40.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques
AU - Carey, Stephan A.
AU - Minard, Kevin R.
AU - Trease, Lynn L.
AU - Wagner, James G.
AU - Garcia, Guilherme J.M.
AU - Ballinger, Carol A.
AU - Kimbell, Julia S.
AU - Plopper, Charles
AU - Corley, Richard A.
AU - Postlethwait, Edward M.
AU - Harkema, Jack R.
PY - 2007/1/1
Y1 - 2007/1/1
N2 - Age-related changes in gross and microscopic structure of the nasal cavity may 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 generated 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 precisely 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 determining risk.
AB - Age-related changes in gross and microscopic structure of the nasal cavity may 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 generated 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 precisely 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 determining risk.
KW - computational fluid dynamics
KW - Magnetic resonance imaging
KW - morphometry
KW - nasal toxicology
KW - ozone
UR - http://www.scopus.com/inward/record.url?scp=33847312157&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33847312157&partnerID=8YFLogxK
U2 - 10.1080/01926230601072343
DO - 10.1080/01926230601072343
M3 - Article
C2 - 17325970
AN - SCOPUS:33847312157
VL - 35
SP - 27
EP - 40
JO - Toxicologic Pathology
JF - Toxicologic Pathology
SN - 0192-6233
IS - 1
ER -