Ultrashort‐TE MRI longitudinal study and characterization of a chronic model of asthma in mice: inflammation and bronchial remodeling assessment

Abstract

Asthma is a chronic disease characterized by bronchial hyperresponsiveness (BHR), bronchial inflammation and remodeling. The great improvements in (1)H MRI ultrashort-TE (UTE) sequences in the last decade have allowed lung images with high-resolution and good signal-to-noise ratio to be obtained in parenchymal tissues. In this article, we present a UTE (1)H MRI high-resolution study of a chronic model of asthma in mice with the aim to longitudinally assess the main features of asthma using a fully noninvasive approach. Balb/c mice (n = 6) were sensitized with ovalbumin over a period of 75 days. The control group (n = 3) received normal saline on the same days. MRI acquisitions were performed on days 0, 38 and 78 to study the inflammatory volumes and bronchial remodeling (peribronchial signal intensity index, PBSI). Plethysmographic studies were performed on days 0, 39 and 79 to assess BHR to methacholine using the enhanced pause (Penh) ratio. The average inflammatory volume measured by MRI in the ovalbumin group (15.6 ± 2.4 μL) was increased significantly relative to control mice (-0.3 ± 0.7 μL) on day 38. The inflammatory volume was larger (34.2 ± 3.1 μL) on day 78 in the ovalbumin group. PBSI was significantly higher in the ovalbumin group on day 78 (1.53 ± 0.08) relative to the control group (1.16 ± 0.10), but not on day 38. After sensitization, asthmatic mice presented BHR to methacholine on days 39 and 79. Penh ratios correlated significantly with the inflammatory volume on day 39 and with the PBSI on day 79. This study shows, for the first time, that high-resolution UTE (1)H MRI of the lungs may allow the noninvasive quantification of peribronchial eosinophilic inflammation with airways occlusion by mucus and of bronchial remodeling in a murine asthma model that correlates with functional parameters.