1H and hyperpolarized 3He magnetic resonance imaging clearly detect the preventative effect of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo

Abstract

Introduction: Proton (1H) magnetic resonance imaging (MRI) can be utilized to quantify pulmonary edema in endotoxin-induced pulmonary inflammation and hyperpolarized (HP) 3He MRI can assess pulmonary ventilation. Neither of the methods has been applied to assess the impact of a drug on endotoxin-induced pulmonary inflammation in vivo. The aim of the current study was to evaluate the capability of 1H and HP 3He MRI to assess the effects of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo. Materials and Methods: Mice were exposed to an aerosol of either saline or endotoxin (5 mg/ml) for 10 min. Half of the endotoxin-exposed mice were pretreated with a glucocorticoid (budesonide 3 mg/kg; 2 times/day) and the other half with vehicle p.o. The first budesonide treatment was administered 1 h prior to the aerosol inhalation. Forty-eight hours after the aerosol exposure, the mice were anaesthetized for subsequent imaging. Hyperpolarized 3He was administered and axial MR images of the lungs obtained. Matching 1H MR images were then acquired. The mice were sacrificed and broncho-alveolar lavage (BAL) samples were harvested to determine total and cell differential counts. Results: The lesion volume on both 1H and 3He MRI, were markedly increased by endotoxin exposure (P<0.001). Budesonide strongly reduced lesion volume ( P<0.001). The BAL cell count correlated strongly with both 3He ( P<0.001; r = 0.96) and 1H lesion volumes ( P<0.001; r = 0.97). Conclusions: Hyperpolarized 3He MRI and 1H MRI clearly visualized the preventative effect of budesonide on the impact of endotoxin on pulmonary ventilation and edema, respectively. The fact that ventilation defects on 3He MRI corresponded to findings from conventional 1H MRI, as well as to counts of BAL inflammatory cells suggests that these imaging techniques constitute promising tools for non-invasive monitoring of pulmonary inflammation in vivo.