The influence of lung airways branching structure and diffusion time on measurements and models of short-range 3He gas MR diffusion.

Hyperpolarized (3)He diffusion experiments have been shown to be sensitive to changes in acinar structure due to emphysematous lung disease. Extracting quantitative information about lung microstructure from the diffusion signal is complicated due its dependence on a number of factors including diffusion time and the complex branching acinar geometry. A theoretical model (cylinder model) has been proposed as a means of estimating acinar airway dimensions from measured diffusivities. This model assumes that the effects of acinar branching geometry and finite airway length upon (3)He diffusion behaviour are negligible. In this work, we use finite element simulations of diffusion in a model of branching alveolar ducts to investigate in detail the effects of acinar branching structure and finite airway length on short-range (3)He diffusion measurements. The results show that branching effects have a significant influence upon (3)He diffusivity, even at short diffusion times. The expressions of the cylinder model theory do not account for significant dependences upon diffusion time, branching geometry and airway length, as a consequence of the oversimplified geometrical model used. The effect of diffusion time on (3)He ADC was also investigated through experiments with healthy human volunteers. The results demonstrate that the cylinder model can produce inaccurate estimates of the airway dimensions as a consequence of incompletely accounting for the diffusion-time dependence in the model equations and confirmed the predicted limitations of the cylinder model for reliable lung morphometry measurements. The results and models presented in this work may help in the development of a more realistic theoretical framework for 'in vivo lung morphometry' using (3)He diffusion MR.