Validating in vivo hyperpolarized ¹²⁹Xe diffusion MRI and diffusion morphometry in the mouse lung

Purpose: Diffusion and lung morphometry imaging using hyperpolarized gases are promising tools to quantify pulmonary microstructure noninvasively in humans and in animal models. These techniques assume the motion encoded is exclusively diffusive gas displacement, but the impact of cardiac motion on measurements has never been explored. Furthermore, although diffusion morphometry has been validated against histology in humans and mice using ³He, it has never been validated in mice for ¹²⁹Xe. Here, we examine the effect of cardiac motion on diffusion imaging and validate ¹²⁹Xe diffusion morphometry in mice. Theory and Methods: Mice were imaged using gradient-echo-based diffusion imaging, and apparent diffusion-coefficient (ADC) maps were generated with and without cardiac gating. Diffusion-weighted images were fit to a previously developed theoretical model using Bayesian probability theory, producing morphometric parameters that were compared with conventional histology. Results: Cardiac gating had no significant impact on ADC measurements (dual-gating: ADC = 0.020 cm²/s, single-gating: ADC = 0.020 cm²/s; P =.38). Diffusion-morphometry–generated maps of ADC (mean, 0.0165 ± 0.0001 cm²/s) and acinar dimensions (alveolar sleeve depth [h] = 44 µm, acinar duct radii [R] = 99 µm, mean linear intercept [L_m] = 74 µm) that agreed well with conventional histology (h = 45 µm, R = 108 µm, L_m = 63 µm). Conclusion: Cardiac motion has negligible impact on ¹²⁹Xe ADC measurements in mice, arguing its impact will be similarly minimal in humans, where relative cardiac motion is reduced. Hyperpolarized ¹²⁹Xe diffusion morphometry accurately and noninvasively maps the dimensions of lung microstructure, suggesting it can quantify the pulmonary microstructure in mouse models of lung disease.