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In this study, hyperpolarized ¹²⁹Xe MR ventilation and ¹H anatomical images were obtained from three subject groups: young healthy volunteers (HVs), subjects with chronic obstructive pulmonary disease (COPD) and age‐matched controls (AMCs). Ventilation images were quantified by two methods: an expert reader‐based ventilation defect score percentage (VDS%) and a semi‐automated segmentation‐based ventilation defect percentage (VDP). Reader‐based values were assigned by two experienced radiologists and resolved by consensus. In the semi‐automated analysis, ¹H anatomical images and ¹²⁹Xe ventilation images were both segmented following registration to obtain the thoracic cavity volume and ventilated volume, respectively, which were then expressed as a ratio to obtain the VDP. Ventilation images were also characterized by generating signal intensity histograms from voxels within the …