Diffusion MRI of hyperpolarized 3He shows that the apparent diffusion coefficient (ADC) of 3 He gas is highly restricted in the normal lung and becomes nearly unrestricted in severe emphysema. The nature of this restricted diffusion provides information about lung structure; however, no direct comparison with histology in human lungs has been reported. The purpose of this study is to provide information about 3 He gas diffusivity in explanted human lungs, and describe the relationship between 3 He diffusivity and the surface area to lung volume ratio (SA/V) and mean linear intercept (L m ) measurements-the gold standard for diagnosis of emphysema. Explanted lungs from patients who were undergoing lung transplantation for advanced COPD, and donor lungs that were not used for transplantation were imaged via

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-Long-range diffusivity of hyperpolarized 3 He gas was measured from the decay rate of sinusoidally modulated longitudinal nuclear magnetization in three normal donor and nine severely emphysematous explanted human lungs. This (long-range) diffusivity, which we call D sec, is measured over seconds and centimeters and is ϳ10 times smaller in healthy lungs (0.022 cm 2 /s) than the more traditionally measured Dmsec, which is measured over milliseconds and submillimeters. The increased restriction of D sec reflects the complex, tortuous paths required to navigate long distances through the maze of branching peripheral airways. In emphysematous lungs, D sec is substantially increased, with some regions showing nearly the unrestricted value of the self-diffusion coefficient (0.88 cm 2 /s for dilute 3 He in air, a 40-fold increase). This suggests the presence of large collateral pathways opened by alveolar destruction that bypass the airways proper. This destruction was confirmed by comparison with histology in seven lungs and by removal of trapped gas via holes in the pleural surface in five lungs. emphysema; diffusivity; airways; transplant surgery; alveolar destruction IN RECENT YEARS,3 He magnetic resonance imaging has been shown to be an effective tool for characterizing lung ventilation and microstructure. Maps of 3 He spin density have been used to identify ventilation defects in a variety of lung diseases (11,15), and measurements of restricted diffusion over millisecond time scales have been a powerful probe of emphysema (3,4,20,21,29). Air space expansion and tissue destruction due to emphysema result in fewer and larger air spaces; alveolar walls, which normally restrict gas diffusion, are absent, giving rise to an increase in gas diffusivity (19,25). During a typical experimental diffusion time of 2 ms, most 3 He atoms cannot diffuse from one acinar airway (e.g., an alveolar duct) to its neighbor; thus the results are sensitive only to the size and geometry of alveoli and individual alveolar-lined airways within the acinus (8, 29).Measurements of 3 He diffusion over longer times and distances are possible with spatially modulated longitudinal magnetization, because the time constant for relaxation of longitudinal magnetization (T 1 ) is much longer than the time constant for transverse magnetization (T * 2 ): in humans at 1.5 T, T 1 of 3 He in lung is Ն20 s and T * 2 is 20 ms (11). Spatial modulation of longitudinal magnetization has been used to monitor cardiac or thoracic motion (1, 7, 17); in the air spaces of lungs as used here, the motion of 3 He is stochastic (diffusive) and results in attenuation of the spatial modulation (16). Diffusion averages across the spatially modulated magnetization, so the diffusivity may be determined from the decay rate of the amplitude of the modulation. Recently, experiments of 3 He diffusion over seconds and centimeters via magnetization tagging have shown that the long-range diffusivity (D sec ) is very restricted in healthy human and canine lungs: 0.015-0.02 cm 2 /s (...

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