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Published online before print July 22, 2008, 10.1148/radiol.2482071452
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(Radiology 2008;248:834-843.)
© RSNA, 2008

Experimental Studies

Allergen-induced Lung Inflammation in Actively Sensitized Mice Assessed with MR Imaging1

François-Xavier Blé, BSc, MSc, PhD, Catherine Cannet, BSc, MSc, Stefan Zurbruegg, BSc, Harry Karmouty-Quintana, BSc, MSc, PhD, Reinhard Bergmann, BSc, MSc, PhD, Nelly Frossard, BSc, MSc, PhD, Alexandre Trifilieff, BSc, MSc, PhD, and Nicolau Beckmann, BSc, MSc, PhD

1 From the Respiratory Diseases Department (F.X.B., A.T.), Global Imaging Group (F.X.B., C.C., S.Z., H.K., N.B.), and Developmental and Molecular Pathways Department (R.B.), Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, WSJ-386.2.09, CH-4002 Basel, Switzerland; and Faculty of Pharmacy, University Louis Pasteur-Strasbourg-1, Illkirch, France (F.X.B., N.F.). Received August 20, 2007; revision requested October 9; revision received November 19; accepted January 24, 2008; final version accepted February 19. N.B. supported by an award from the 3R Research Foundation, Münsingen, Switzerland (project 82/02). Address correspondence to N.B. (e-mail: nicolau.beckmann{at}novartis.com).

Purpose: To demonstrate the feasibility of using proton magnetic resonance (MR) imaging to noninvasively detect extravascular and luminal fluid in a murine model of allergen-induced airway inflammation.

Materials and Methods: The Basel Veterinary Authority approved this experiment. Actively sensitized female Balb/c mice received ovalbumin or saline and underwent MR imaging (a) once 24 hours after the fourth administration of ovalbumin or saline (n = 25) or (b) several times between and after ovalbumin or saline administrations (n = 22) to determine the volume of fluid signal induced by an allergen. Images were acquired in spontaneously breathing animals, without cardiac or respiratory gating. Signal detected with a gradient-echo sequence was compared with bronchoalveolar lavage (BAL) fluid parameters and with perivascular and peribronchial edema and mucus observed at histologic analysis.

Results: Up to 24 hours after the fourth administration of ovalbumin, intense and continuous fluid signals (volume, 40–50 µL) were detected in proximal lung regions. At 72 hours after the fourth administration of ovalbumin, remaining signals (21.1 µL ± 3.8) had a discontinuous texture. The number of eosinophils in the BAL fluid at 24 and 72 hours and their activation were higher in mice that received ovalbumin than in those that received saline. Histologic analysis revealed edema and secreted mucus in the early phase, whereas only mucus was encountered in the late phase.

Conclusion: These findings suggest that the main component of the early response was plasma leakage (edema), while the main component of the late response was secreted mucus. With the technique validated, the basis for pharmacologic studies in this murine model of lung inflammation with use of MR imaging as a noninvasive readout was provided.

© RSNA, 2008