Investigating short-time diffusion of hyperpolarized 129Xe in lung air spaces and tissue: A feasibility study in chronic obstructive pulmonary disease patients

Purpose To investigate the diffusion of hyperpolarized Xe-129 in air spaces at short-time scales for determination of lung surface-to-gas-volume ratio in comparison to results from chemical shift saturation recovery, CT, and established clinical measures. Methods A pulse sequence for measurement of time-dependent diffusion of Xe-129 in air spaces at short diffusion times was developed. Gas uptake into lung tissue was measured in the same breathhold using chemical shift saturation recovery spectroscopy in the short-time regime. The potential to obtain the surface-to-gas-volume ratio using a first-order and second-order approximation of the short-time expansion of time-dependent diffusion according to Mitra et al(11) and its diagnostic relevance were tested in a study with 9 chronic obstructive pulmonary diseases patients. Results Surface-to-gas-volume ratios obtained from time-dependent diffusion were correlated with results from chemical shift saturation recovery, r = 0.840, P = .005 (first-order fits), and r = 0.923, P < .001 (second-order fits), and from CT results for second-order fits, r = 0.729, P = .026. Group means +/- SD were 75.0 +/- 15.5 cm(-1) (first-order fits) and 122.3 +/- 32.8 cm(-1) (second-order fits) for time-dependent diffusion, 125.9 +/- 43.3 cm(-1) for chemical shift saturation recovery, and 159.5 +/- 50.9 cm(-1) for CT. Surface-to-gas-volume ratios from time-dependent diffusion with first-order fits correlated significantly with carbon monoxide diffusing capacity as percent of prediction, r = 0.724, P = .028. Conclusion Time-dependent diffusion measurements of Xe-129 at short-time scales down to similar to 1 ms are feasible in chronic obstructive pulmonary patients and provide clinically relevant information on lung microstructure.