Hyperpolarised gas MRI is sensitive to lung ventilation heterogeneity in early cystic fibrosis (CF) disease. However, lung microstructural changes that might accompany early lung disease in CF is less well explored. DW-MRI measurements were compared in mild CF children and age-matched healthy controls, and reassessed after a 2-year interval in the CF group. No significant difference in DW-MRI metrics (in contrast to changes in lung ventilation, VD%) was observed between healthy controls and CF children, and between baseline and 2-year follow-up visits. These results suggest that no acinar microstructural changes occur in early stage CF despite increases in ventilation heterogeneity.