title: A robust protocol for regional evaluation of methacholine challenge in mouse models of allergic asthma using hyperpolarized 3He MRI.
abstract: Hyperpolarized (HP) (3)He magnetic resonance imaging has been recently used to produce high-resolution images of pulmonary ventilation after methacholine (MCh) challenge in mouse models of allergic inflammation. This capability presents an opportunity to gain new insights about these models and to more sensitively evaluate new drug treatments in the pre-clinical setting. In the current study, we present our initial experience using two-dimensional (2D), time-resolved (3)He MRI of MCh challenge-induced airways hyperreactivity (AHR) to compare ovalbumin-sensitized and challenged (N = 8) mice to controls (N = 8). Imaging demonstrated that ovalbumin-sensitized and challenged animals exhibited many large ventilation defects even prior to MCh challenge (four out of eight) compared to no defects in the control animals. Additionally, the ovalbumin-sensitized and challenged animals experienced a greater number of ventilation defects (4.5 +/- 0.4) following MCh infusion than did controls (3.3 +/- 0.6). However, due to variability in MCh delivery that was specific to the small animal MRI environment, the difference in mean defect number was not statistically significant. These findings are reviewed in detail and a comprehensive solution to the variability problem is presented that has greatly enhanced the magnitude and reproducibility of the MCh response. This has permitted us to develop a new imaging protocol consisting of a baseline 3D image, a time-resolved 2D series during MCh challenge, and a post-MCh 3D image that reveals persistent ventilation defects.
authors.affiliation: Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Abraham C
authors.initials: AC
authors.lastname: Thomas
authors.forename: Erin N
authors.initials: EN
authors.lastname: Potts
authors.forename: Ben T
authors.initials: BT
authors.lastname: Chen
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Slipetz
authors.forename: W Michael
authors.initials: WM
authors.lastname: Foster
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Driehuys
mesh_terms: D000818:Animals; D001249:Asthma / Q000473:pathology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000187:drug effects; D002452:Cell Count; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006339:Heart Rate / Q000187:drug effects; D006371:Helium / Q000737:chemistry*; D021621:Imaging, Three-Dimensional; D007260:Infusion Pumps; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D016210:Methacholine Chloride / Q000008:administration & dosage* / Q000494:pharmacology*; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage; D012123:Pulmonary Ventilation / Q000187:drug effects; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D016210:Methacholine Chloride; D006371:Helium; D010047:Ovalbumin