Jason C. Woods

Diffusion MRI of hyperpolarized ³He shows that the apparent diffusion coefficient (ADC) of ³He 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 ³He gas diffusivity in explanted human lungs, and describe the relationship between ³He 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 ³He diffusion MRI. Histological measurements were made on the same specimens after they were frozen in the position of study. There is an inverse correlation between diffusivity and SA/V (and a positive correlation between diffusivity and L_m). An important result is that restricted ³He diffusivity separated normal from emphysematous lung tissue more clearly than the morphometric analyses. This effect may be due to the smaller histologic sampling size compared to the MRI voxel sizes. Magn Reson Med, 2006.

Long-range diffusivity of hyperpolarized ³He 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 ∼10 times smaller in healthy lungs (0.022 cm²/s) than the more traditionally measured D_msec, 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 cm²/s for dilute ³He 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.