Hyperpolarised gas MRI with ³He and ¹²⁹Xe has been established as a functional tool to image lung ventilation and detect lung microstructural changes [1]. A recent comparison of ventilation imaging and apparent diffusion coefficient (ADC) mapping with ³He and ¹²⁹Xe at 3T [2] demonstrated that comparable ventilation and microstructural information can be obtained from the two gases. In addition, ³He ADC MRI has been shown to be highly repeatable in healthy volunteers and COPD patients [3]. However, comparison of the functional sensitivity of ³He and ¹²⁹Xe lung MRI has not been performed to date at 1.5T, and the repeatability of ADC mapping MRI with ¹²⁹Xe is yet to be adequately assessed. In this work, ³He and ¹²⁹Xe ventilation and diffusion-weighted MR images were acquired at 1.5T in healthy volunteers and, at multiple time-points, in COPD patients in order to compare the functional sensitivity and assess the repeatability of MR-derived measures of ventilated volume and lung microstructure from each of the two gases.Nine healthy volunteers (with no history of lung disease) and five COPD patients were recruited for hyperpolarised ³He and ¹²⁹Xe gas MR imaging. 2D ³He and ¹²⁹Xe diffusion-weighted MR images (see e.g. [4]) were acquired for all subjects and ADC maps were calculated from the first (b=0s/cm²) and second diffusion interleaves (³He b=1.6s/cm², ¹²⁹Xe b=8.0s/cm²). In COPD patients, 3D steady-state free-precession (SSFP) images of lung ventilation were acquired with both gases using the parameters described in [5,6], and ventilation volume percentages (VV%) were calculated as described previously [5]. The whole imaging protocol was repeated in the COPD patients on three additional scan sessions (same-day, next-day and after 2 weeks) to assess the repeatability of ³He and ¹²⁹Xe MR-derived measures of ventilated volume and lung microstructure. Measurements of VV% and ADC derived from ³He and ¹²⁹Xe MRI were compared to evaluate the relative functional sensitivity of the two gases to obstructive lung disease and emphysematous microstructural changes. These metrics were also compared to pulmonary function tests (PFTs), including the diffusing capacity of carbon monoxide (TL_CO), forced expiratory volume in 1 second (FEV₁), and the ratio of FEV₁ to forced vital capacity (FVC) (FEV₁/FVC), acquired on the same day as each scan. The coefficient of variation (CoV) of each MR and PFT parameter was calculated to assess repeatability. For COPD patients, the mean values and standard deviations over all scan sessions were used for comparisons.As expected, MR images from both nuclei highlighted significant ventilation abnormalities in COPD subjects and higher global mean ADC values compared to volunteers (two-tailed t-test, p<0.001, Figure 1). VV% values were observed to be larger on average for ³He than ¹²⁹Xe (p<0.001), similar to previous observations [7], reflecting the ability of ³He to penetrate less well-ventilated lung by virtue of its higher diffusion coefficient. A strong positive correlation between ³He and ¹²⁹Xe ADC values was observed in healthy volunteers and COPD patients (Spearman’s correlation coefficient 0.982, p<0.001, Figure 2a). ADC values derived from both gases exhibited significant correlations with PFTs (Table 1), most notably TL_CO, which is in good agreement with previous findings [2,3]. Comparing VV% measurements and PFTs, only ³He VV% exhibited a significant correlation with FEV₁/FVC (p<0.05), and the relationship between ³He and ¹²⁹Xe derived VV% values was not significant (Figure 2b). The lack of observed significant correlation between VV% values of the two gases and other PFT measures can be attributed to a low number of data-points (n=5) and the absence of comparative healthy volunteer data. ADC metrics of both gases were found to be highly repeatable, with mean coefficient of variation (CoV) values (<3%) comparable to or less than those of the PFT results (Table 2). CoV values were slightly higher for VV% measures – in particular for ¹²⁹Xe, likely due to difficulty in manual segmentation of ventilation images and/or variability in ¹²⁹Xe polarisation levels. However the mean ³He and ¹²⁹Xe VV% CoV values over all subjects were still <5% and <15%, respectively, indicating good intra-subject repeatability.Preliminary experimental validation of hyperpolarised ³He and ¹²⁹Xe MR ventilation imaging and ADC mapping has been demonstrated at 1.5T in COPD patients and healthy volunteers. ADC values from both nuclei exhibited excellent agreement and significant correlations with PFT results, whilst corresponding VV% values were not as comparable due to small sample sizes. ADC and VV% metrics derived from both nuclei were repeatable, paving the way to increased use of ¹²⁹Xe as a more readily-available, cost-effective alternative to ³He for clinical lung imaging studies.