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

Stephan A. Carey, Kevin R. Minard, Lynn L. Trease, James G. Wagner, Guilherme J.M. Garcia, Carol A. Ballinger, Julia S. Kimbell, Charles Plopper, Richard A. Corley, Edward M. Postlethwait, Jack R. Harkema

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)27-40
Number of pages14
JournalToxicologic Pathology
Volume35
Issue number1
DOIs
StatePublished - Jan 1 2007

Fingerprint

Ozone
Nose
Haplorhini
Magnetic Resonance Imaging
Wounds and Injuries
Animals
Imaging techniques
Magnetic resonance
Linings
Extrapolation
Optical microscopy
Tissue
Geometry
Nasal Cavity
Rhinitis
Computational Biology
Macaca mulatta
Toxicology
Primates
Microscopy

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

Carey, S. A., Minard, K. R., Trease, L. L., Wagner, J. G., Garcia, G. J. M., Ballinger, C. A., ... Harkema, J. R. (2007). Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques. Toxicologic Pathology, 35(1), 27-40. https://doi.org/10.1080/01926230601072343

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 journalArticle

Carey, SA, Minard, KR, Trease, LL, Wagner, JG, Garcia, GJM, Ballinger, CA, Kimbell, JS, Plopper, C, Corley, RA, Postlethwait, EM & Harkema, JR 2007, 'Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques', Toxicologic Pathology, vol. 35, no. 1, pp. 27-40. https://doi.org/10.1080/01926230601072343
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. / Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques. In: Toxicologic Pathology. 2007 ; Vol. 35, No. 1. pp. 27-40.
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