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

Abstract

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. 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. Up to 24 hours after the fourth administration of ovalbumin, intense and continuous fluid signals (volume, 40-50 microL) were detected in proximal lung regions. At 72 hours after the fourth administration of ovalbumin, remaining signals (21.1 microL +/- 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. 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.