title: Lung inflammation and vascular remodeling after repeated allergen challenge detected noninvasively by MRI.
abstract: 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 microm revealed by histology. Angiogenesis of vessels smaller than 30 microm 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.
authors.affiliation: Discovery Technologies Department, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Tigani
authors.forename: Catherine
authors.initials: C
authors.lastname: Cannet
authors.forename: Harry
authors.initials: H
authors.lastname: Karmouty-Quintana
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Blé
authors.forename: Stefan
authors.initials: S
authors.lastname: Zurbruegg
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schaeublin
authors.forename: John R
authors.initials: JR
authors.lastname: Fozard
authors.forename: Nicolau
authors.initials: N
authors.lastname: Beckmann
mesh_terms: D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000098:blood supply / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability / Q000187:drug effects; D005456:Fluorescent Dyes; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D010047:Ovalbumin / Q000008:administration & dosage*; D011654:Pulmonary Edema / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D011914:Rats, Inbred BN; D012130:Respiratory Hypersensitivity / Q000503:physiopathology
chemical_list: D000485:Allergens; D005456:Fluorescent Dyes; D010047:Ovalbumin