3He MRI in mouse models of asthma

In the study of asthma, a vital role is played by mouse models, because knockout or transgenic methods can be used to alter disease pathways and identify therapeutic targets that affect lung function. Assessment of lung function in rodents by available methods is insensitive because these techniques lack regional specificity. A more sensitive method for evaluating lung function in human asthma patients uses hyperpolarized (HP) 3He MRI before and after bronchoconstriction induced by methacholine (MCh). We now report the ability to perform such 3He imaging of MCh response in mice, where voxels must be ∼3000 times smaller than in humans and 3He diffusion becomes an impediment to resolving the airways. We show three‐dimensional (3D) images that reveal airway structure down to the fifth branching and visualize ventilation at a resolution of 125 × 125 × 1000 μm3. Images of ovalbumin (OVA)‐sensitized mice acquired after MCh show both airway closure and ventilation loss. To also observe the MCh response in naive mice, we developed a non‐slice‐selective 2D protocol with 187 × 187 μm2 resolution that was fast enough to record the MCh response and recovery with 12‐s temporal resolution. The extension of 3He MRI to mouse models should make it a valuable translational tool in asthma research. Magn Reson Med 58:893–900, 2007. © 2007 Wiley‐Liss, Inc.