In vivo lung morphometry with hyperpolarized 3He diffusion MRI: theoretical background.

MRI-based study of (3)He gas diffusion in lungs may provide important information on lung microstructure. Lung acinar airways can be described in terms of cylinders covered with alveolar sleeve [Haefeli-Bleuer, Weibel, Anat. Rec. 220 (1988) 401]. For relatively short diffusion times (on the order of a few ms) this geometry allows description of the (3)He diffusion attenuated MR signal in lungs in terms of two diffusion coefficients-longitudinal (D(L)) and transverse (D(T)) with respect to the individual acinar airway axis [Yablonskiy et al., PNAS 99 (2002) 3111]. In this paper, empirical relationships between D(L) and D(T) and the geometrical parameters of airways and alveoli are found by means of computer Monte Carlo simulations. The effects of non-Gaussian signal behavior (dependence of D(L) and D(T) on b-value) are also taken into account. The results obtained are quantitatively valid in the physiologically important range of airway parameters characteristic of healthy lungs and lungs with mild emphysema. In lungs with advanced emphysema, the results provide only "apparent" characteristics but still could potentially be used to evaluate emphysema progression. This creates a basis for in vivo lung morphometry-evaluation of the geometrical parameters of acinar airways from hyperpolarized (3)He diffusion MRI, despite the airways being too small to be resolved by direct imaging. These results also predict a rather substantial dependence of (3)He ADC on the experimentally-controllable diffusion time, Delta. If Delta is decreased from 3 ms to 1 ms, the ADC in normal human lungs may increase by almost 50%. This effect should be taken into account when comparing experimental data obtained with different pulse sequences.