Evaluation of allergic lung inflammation by computed tomography in a rat model in vivo

The ability of micro-computed tomography (CT) to noninvasively evaluate allergic pulmonary inflammation in an experimental model was investigated. In addition, two image segmentation methods and the value of respiratory gating were investigated in the context of this model. Brown Norway rats were exposed to one of four doses of house dust mite (HDM) extract (0, 0.15, 15 or 150 μg) delivered intratracheally every 24 h for 10 days. CT scanning was performed at baseline and after several longitudinal HDM exposures. Both thoracic- and lung-segmentation methods yielded similar results when standardisation practices were employed. While tissue histology correlated well with CT images, cell counts from bronchoalveolar lavage depicted greater inflammation than did density measures from CT images. Evidence from representative CT slices and transaxial density distribution indicated that inflammation was primarily associated with major airways and extended into the periphery from these focal points. Respiratory gating demonstrated that images of the inspiratory state provided greater contrast of inflammatory processes. Lastly, decreases in tidal volumes indicated significant mechanical respiratory changes in animals exposed to both 15 and 150 μg. In summary, CT image segmentation can extract pertinent data on in vivo allergic airway/lung inflammation. Furthermore, respiratory gating provides additional contrast and insight into these quantification practices.

[1]  M. Jordana,et al.  Intranasal Exposure of Mice to House Dust Mite Elicits Allergic Airway Inflammation via a GM-CSF-Mediated Mechanism1 , 2004, The Journal of Immunology.

[2]  T. Herlin,et al.  Energy metabolism of human neutrophils during phagocytosis. , 1982, The Journal of clinical investigation.

[3]  T. Farncombe,et al.  Journal of Translational Medicine Comparison between Conventional and "clinical" Assessment of Experimental Lung Fibrosis , 2008 .

[4]  C. Haslett,et al.  In vivo measurement of neutrophil activity in experimental lung inflammation. , 1994, American journal of respiratory and critical care medicine.

[5]  J. Fozard,et al.  Pulmonary edema induced by allergen challenge in the rat: Noninvasive assessment by magnetic resonance imaging , 2001, Magnetic resonance in medicine.

[6]  F. Korosec,et al.  Noninvasive mapping of regional response to segmental allergen challenge using magnetic resonance imaging and [F‐18]fluorodeoxyglucose positron emission tomography , 2005, Magnetic resonance in medicine.

[7]  M. Jordana,et al.  House dust mite facilitates ovalbumin-specific allergic sensitization and airway inflammation. , 2005, American journal of respiratory and critical care medicine.

[8]  D. Warburton,et al.  Three-dimensional computed tomography imaging in an animal model of emphysema , 2007 .

[9]  J. Fozard,et al.  Lung inflammation and vascular remodeling after repeated allergen challenge detected noninvasively by MRI. , 2007, American journal of physiology. Lung cellular and molecular physiology.

[10]  J. Bates,et al.  Airway hyperresponsiveness in allergically inflamed mice: the role of airway closure. , 2007, American journal of respiratory and critical care medicine.

[11]  R. E. Wiley,et al.  Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling. , 2004, American journal of respiratory and critical care medicine.

[12]  Kennita A Johnson Imaging Techniques for Small Animal Imaging Models of Pulmonary Disease: Micro-CT , 2007, Toxicologic pathology.

[13]  Brett A. Simon,et al.  Non-Invasive Imaging of Regional Lung Function using X-Ray Computed Tomography , 2004, Journal of Clinical Monitoring and Computing.

[14]  Daniel A Low,et al.  Computed tomography studies of lung mechanics. , 2005, Proceedings of the American Thoracic Society.

[15]  N. Morrell,et al.  In vivo assessment of lung inflammatory cell activity in patients with COPD and asthma , 2003, European Respiratory Journal.

[16]  J. Fozard,et al.  Resolution of the oedema associated with allergic pulmonary inflammation in rats assessed noninvasively by magnetic resonance imaging , 2003, British journal of pharmacology.

[17]  T H Farncombe Software-based respiratory gating for small animal conebeam CT. , 2008, Medical physics.

[18]  N L Müller,et al.  Computed tomographic imaging of the airways: relationship to structure and function , 2005, European Respiratory Journal.

[19]  G Allan Johnson,et al.  3He MRI in mouse models of asthma , 2007, Magnetic resonance in medicine.

[20]  S. Raoof,et al.  The role of chest radiography and computed tomography in the diagnosis and management of asthma , 2007, Current opinion in pulmonary medicine.

[21]  D. Schuster,et al.  Imaging pulmonary inflammation with positron emission tomography: a biomarker for drug development. , 2006, Molecular pharmaceutics.

[22]  T. Jones,et al.  Imaging allergen-invoked airway inflammation in atopic asthma with [18F]-fluorodeoxyglucose and positron emission tomography , 1996, The Lancet.