In vivo lung morphometry with hyperpolarized ³He diffusion MRI: Reproducibility and the role of diffusion-sensitizing gradient direction

Purpose: Lung morphometry with hyperpolarized gas diffusion MRI is a highly sensitive technique for the noninvasive measurement of acinar microstructural parameters traditionally only accessible by histology. The goal of this work is to establish the reproducibility of these measurements in healthy volunteers and their dependence on the direction of the applied diffusion-sensitizing gradient. Methods: Hyperpolarized helium-3 (³He) lung morphometry MRI was performed on a total of five healthy subjects. Two subjects received duplicate imaging on the same day and three subjects received duplicate imaging after a 4-month or 27-month delay to assess reproducibility. Four subjects repeated the measurement during the same session with different diffusion-sensitizing gradient directions to determine the effect on the parameter estimates. Results: The ³He lung morphometry measurements were reproducible over the short term and long term (e.g., % coefficient of variation [CV] of mean chord length, Lm=2.1% and 2.9%, respectively) and across different diffusion gradient directions (Lm % CV=2.6%). Results also show independence of field inhomogeneity effects at 1.5T. Conclusion: ³He lung morphometry is a reproducible technique for measuring acinar microstructure and is effectively independent of the choice of diffusion gradient direction. This provides confidence for the use of this technique to compare populations and treatment efficacy.