Using Hyperpolarized Xenon-129 MRI to Quantify Early-Stage Lung Disease in Smokers

RATIONALE AND OBJECTIVES: Hyperpolarized xenon-129 magnetic resonance (MR) provides sensitive tools that may detect early stages of lung disease in smokers before it has progressed to chronic obstructive pulmonary disease (COPD) apparent to conventional spirometric measures. We hypothesized that the functional alveolar wall thickness as assessed by hyperpolarized xenon-129 MR spectroscopy would be elevated in clinically healthy smokers before xenon MR diffusion measurements would indicate emphysematous tissue destruction. MATERIALS AND METHODS: Using hyperpolarized xenon-129 MR we measured the functional septal wall thickness and apparent diffusion coefficient of the gas phase in 16 subjects with smoking-related COPD, 9 clinically healthy current or former smokers, and 10 healthy never smokers. All subjects were age-matched and characterized by conventional pulmonary function tests. 11 data sets from younger healthy never smokers were added to determine the age dependence of the septal wall thickness measurements. RESULTS: In healthy never smokers the septal wall thickness increased by 0.04 µm per year of age. The healthy smoker cohort exhibited normal pulmonary function test measures that did not significantly differ from the never-smoker cohort. The age-corrected septal wall thickness correlated well with diffusion capacity for carbon monoxide (R(2) = 0.56) and showed a highly significant difference between healthy subjects and COPD patients (8.8 µm versus 12.3 µm; p < 0.001), but was the only measure that actually discriminated healthy subjects from healthy smokers (8.8 µm versus 10.6 µm; p < 0.006). CONCLUSION: Functional alveolar wall thickness assessed by hyperpolarized xenon-129 MR allows discrimination between healthy subjects and healthy smokers and could become a powerful new measure of early-stage lung disease.