The Role of Collateral Paths in Long-range Diffusion of ³He in Lungs

Rationale and Objectives: The hyperpolarized ³He long-range diffusion coefficient (LRDC) in lungs is sensitive to changes in lung structure due to emphysema, reflecting the increase in collateral paths resulting from tissue destruction. However, no clear understanding of LRDC in healthy lungs has emerged. Here we compare LRDC measured in healthy lungs with computer simulations of diffusion along the airway tree with no collateral connections. Materials and Methods: Computer simulations of diffusion of spatially modulated spin magnetization were performed in computer-generated, symmetric-branching models of lungs and compared with existing LRDC measurements in canine and human lungs. Results: The simulations predict LRDC values of order 0.001 cm²/sec, approximately 20 times smaller than the measured LRDC. We consider and rule out possible mechanisms for LRDC not included in the simulations: incomplete breath hold, cardiac motion, and passage of dissolved ³He through airway walls. However, a very low density of small (micron) holes in the airways is shown to account for the observed LRDC. Conclusion: It is proposed that LRDC in healthy lungs is determined by small collateral pathways.