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This Article Full Text Full Text (PDF) All Versions of this Article: 292/3/L644    most recent 00122.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Tigani, B. Articles by Beckmann, N. Search for Related Content PubMed PubMed Citation Articles by Tigani, B. Articles by Beckmann, N.

Lung inflammation and vascular remodeling after repeated allergen challenge detected noninvasively by MRI

¹Discovery Technologies and ²Respiratory Diseases Research Department, Novartis Institutes for BioMedical Research, Basel, Switzerland; ³Sackler Institute of Pulmonary Pharmacology, King's College London, London, United Kingdom; and ⁴Faculty of Pharmacy, University Louis Pasteur-Strasbourg-I, Illkirch, France

Submitted 3 April 2006 ; accepted in final form 31 October 2006

Magnetic resonance imaging (MRI) has been used previously to follow noninvasively inflammatory processes in rat acute models of lung inflammation. Here the technique was applied to a model involving repeated intratracheal administration of ovalbumin (OA). Anatomical MRI was performed at different time points with respect to a single or multiple OA challenges in Brown Norway rats actively sensitized to the allergen. Vascular permeability was assessed using dynamic contrast-enhanced MRI (DCE-MRI). Bronchoalveolar lavage (BAL) fluid analysis and histology were performed to validate the MRI data. The time course of MRI signals after a single OA challenge reached a maximum at 48 h and decreased significantly at 96 h. After the second and subsequent challenges, the maximum signal occurred at 6 h with a time-dependent decline over the remainder of the time course. A reduction of the inflammatory response following repeated administration of OA was also detected by BAL fluid analysis. The decrease in vascular permeability assessed by DCE-MRI in repeatedly OA-challenged rats was consistent with the thickening of the vascular wall for vessels of diameter up to 300 µm revealed by histology. Angiogenesis of vessels smaller than 30 µm was also detected histologically. These results suggest that MRI can be used to detect the inflammatory response and vascular remodeling associated with chronic airway inflammation in rat models involving repeated administration of allergen. As the contrast agent used in the DCE-MRI experiments is approved for clinical use, there is potential to translate the approach to patients.

angiogenesis; asthma; chronic inflammation; magnetic resonance imaging; vessel remodeling

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