Effects of corticosteroid treatment on airway inflammation, mechanics, and hyperpolarized ³He magnetic resonance imaging in an allergic mouse model

Abstract

The purpose of this study was to assess the effects of corticosteroid therapy on a murine model of allergic asthma using hyperpolarized (3)He magnetic resonance imaging (MRI) and respiratory mechanics measurements before, during, and after methacholine (MCh) challenge. Three groups of mice were prepared, consisting of ovalbumin sensitized/ovalbumin challenged (Ova/Ova, n = 5), Ova/Ova challenged but treated with the corticosteroid dexamethasone (Ova/Ova+Dex, n = 3), and ovalbumin-sensitized/saline-challenged (Ova/PBS, n = 4) control animals. All mice underwent baseline 3D (3)He MRI, then received a MCh challenge while 10 2D (3)He MR images were acquired for 2 min, followed by post-MCh 3D (3)He MRI. Identically treated groups underwent respiratory mechanics evaluation (n = 4/group) and inflammatory cell counts (n = 4/group). Ova/Ova animals exhibited predominantly large whole lobar defects at baseline, with significantly higher ventilation defect percentage (VDP = 19 ± 4%) than Ova/PBS (+2 ± 1%, P = 0.01) animals. Such baseline defects were suppressed by dexamethasone (0%, P = 0.009). In the Ova/Ova group, MCh challenge increased VDP on both 2D (+30 ± 8%) and 3D MRI scans (+14 ± 2%). MCh-induced VDP changes were diminished in Ova/Ova+Dex animals on both 2D (+21 ± 9%, P = 0.63) and 3D scans (+7 ± 2%, P = 0.11) and also in Ova/PBS animals on 2D (+6 ± 3%, P = 0.07) and 3D (+4 ± 1%, P = 0.01) scans. Because MCh challenge caused near complete cessation of ventilation in four of five Ova/Ova animals, even as large airways remained patent, this implies that small airway (<188 μm) obstruction predominates in this model. This corresponds with respiratory mechanics observations that MCh challenge significantly increases elastance and tissue damping but only modestly affects Newtonian airway resistance.

Linking Ventilation Heterogeneity Quantified via Hyperpolarized 3He MRI to Dynamic Lung Mechanics and Airway Hyperresponsiveness

“…A majority of these defects remained persistent with time and with repeated bronchoconstriction [ 25 , 26 ]. Since then, there have been a number of advancements in HP 3 He-MRI with the emergence of quantitative methods to extract detailed structure-to-function relationships in asthma in both humans [ 23 , 24 , 30 , 32 ] and animals [ 40 – 43 ]. For example, recent efforts have calculated a characteristic index to quantify the degree of ventilation heterogeneity [ 23 , 30 , 32 ].…”

In vivo monitoring of lung inflammation in CFTR-deficient mice

“…Recently emerging non-invasive imaging technologies such as magnetic resonance imaging (MRI), micro-CT and optical imaging have been applied to longitudinal monitoring of airway remodeling and inflammation in murine models [ 11 – 14 ]. The clinical imaging system used in MRI, CT and PET, have been further adapted to murine models of asthma [ 11 , 15 – 17 ], to serve as a preclinical and translational step between basic discovery and clinical practice, whereas optical imaging technologies developed in experimental settings may also slow-down their way into the clinical practice, especially in the context of intraoperative activities [ 18 , 19 ]. Recently a mouse model transiently expressing the luciferase reporter gene under the control of a bovine IL-8 promoter has been generated [ 20 ].…”

Airway Transmural Pressures in an Airway Tree During Bronchoconstriction in Asthma

“…In contrast to homogeneous airway behavior during bronchoconstriction, imaging studies have demonstrated the emergence of VDefs in humans [1][2][3][4][35][36][37] and in animals [38][39][40]. VDefs are direct evidence for major regional differences in ventilation, airflow and parenchymal tidal expansion, which has implications for the peak transmural pressure of the airways: (1) the increase in regional tidal expansion leads to substantially higher peak transmural pressures compared to conditions with the relaxed airways, homogeneous ventilation distribution and quiet tidal breathing, and (2) increased airway resistance as well as its heterogeneity affects the intraluminal pressures in the bronchial tree.…”