Rationale: The apparent diffusion coefficient of hyperpolarized 3He in the lungs has been shown to correlate directly in animal models with the peripheral airspace size and can detect changes in lung microstructure.\ud \ud Objectives: To study in vivo the 3He apparent diffusion coefficient and to demonstrate its sensitivity to changes in lung morphometry as a result of aging, exposure to cigarette smoke, and lung inflation.\ud \ud Methods: We assessed the variation in the diffusion of hyperpolarized 3He gas in the lungs by magnetic resonance techniques. Spirometric lung volumes were recorded.\ud \ud Measurements: We measured the dependence of 3He diffusion on age and on reported cigarette smoke exposure in 32 symptom-free adults. We also measured the dependence of the apparent diffusion coefficient on the degree of lung inflation.\ud \ud Results: In healthy never-smokers, the apparent diffusion coefficient increased with age from 0.115 to 0.155 cm2 · s−1 at 20 and 70 yr, respectively, increased linearly with lung inflation and was independent of individual's lung size after correcting for age. For active and passive smokers, the apparent diffusion coefficient increased by up to 40% compared with never-smokers with mean values significantly higher (p = 0.016 and p = 0.0007, respectively).\ud \ud Conclusions: Peripheral airspace size increases with age and after exposure to smoke in healthy adults in agreement with previous histologic studies. We have confirmed in vivo that peripheral airspace size is independent of intersubject lung size
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