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 [Lm] = 74 µm) that agreed well with conventional histology (h = 45 µm, R = 108 µm, Lm = 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.