Fast apparent transverse relaxation (short T 2 *) is a common obstacle when attempting to perform quantitative 1 H MRI of the lungs. While T 2 * times are longer for pulmonary hyperpolarized (HP) gas functional imaging (in particular for gaseous 129 Xe), T 2 * can still lead to quantitative inaccuracies for sequences requiring longer echo times (such as diffusion weighted images) or longer readout duration (such as spiral sequences). This is especially true in preclinical studies, where high magnetic fields lead to shorter relaxation times than are typically seen in human studies. However, the T 2 * of HP 129 Xe in the most common animal model of human disease (mice) has not been reported. Herein, we present a multi-echo radial flyback imaging sequence and use it to measure HP 129 Xe T 2 * at 7 T under a variety of respiratory conditions. This sequence mitigates the impact of T 1 relaxation outside the animal by using multiple gradient-refocused echoes to acquire images at a number of effective echo times for each RF excitation. After validating the sequence using a phantom containing water doped with superparamagnetic iron oxide nanoparticles, we measured the 129 Xe T 2 * in vivo for 10 healthy C57Bl/6 J mice and found T 2 *~5 ms in the lung airspaces. Interestingly, T 2 * was relatively constant over all experimental conditions, and varied significantly with sex, but not age, mass, or the O 2 content of the inhaled gas mixture. These results are discussed in the context of T 2 * relaxation within porous media. K E Y W O R D S129

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 3 He, it has never been validated in mice for 129 Xe. Here, we examine the effect of cardiac motion on diffusion imaging and validate 129 Xe 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 (dualgating: ADC = 0.020 cm 2 /s, single-gating: ADC = 0.020 cm 2 /s; P = .38). Diffusion-morphometry-generated maps of ADC (mean, 0.0165 ± 0.0001 cm 2 /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 129 Xe ADC measurements in mice, arguing its impact will be similarly minimal in humans, where relative cardiac

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