(a) MR images illustrate signal intensity buildup during repeated hyperpolarized gas breaths in healthy nonsmoker (top), asymptomatic smoker (middle), and patient with COPD (bottom) and show progression of nonuniform ventilation and apparent resolution of some (but not all) defects during an extended breathing sequence. Image sets used six breaths with an accelerated 6 × 48 × 64 image acquired after each inhalation, necessitating 1.02 seconds. (b) Signal intensity buildup during repeated hyperpolarized gas breaths for the entire subject box plotted for each cohort. Note that whole-lung values in each breath are integration of signal intensities in all voxels in lung. For better comparison, whole-lung sum of signal intensities in each breath for each subject is normalized by maximum signal intensity observed in that subject during course of imaging (ie, breath with the highest signal intensity has a value of 1.0). AS = asymptomatic smokers, HN = healthy nonsmokers.