Hyperpolarized (3)He and (129)Xe magnetic resonance imaging apparent diffusion coefficients: physiological relevance in older never‐ and ex‐smokers

Noble gas pulmonary magnetic resonance imaging (MRI) is transitioning away from (3)He to (129)Xe gas, but the physiological/clinical relevance of (129)Xe apparent diffusion coefficient (ADC) parenchyma measurements is not well understood. Therefore, our objective was to generate (129)Xe MRI ADC for comparison with (3)He ADC and with well‐established measurements of alveolar structure and function in older never‐smokers and ex‐smokers with chronic obstructive pulmonary disease (COPD). In four never‐smokers and 10 COPD ex‐smokers, (3)He (b = 1.6 sec/cm(2)) and (129)Xe (b = 12, 20, and 30 sec/cm(2)) ADC, computed tomography (CT) density‐threshold measurements, and the diffusing capacity for carbon monoxide (DL(CO)) were measured. To understand regional differences, the anterior–posterior (AP(G)) and superior–inferior (∆SI) ADC differences were evaluated. Compared to never‐smokers, COPD ex‐smokers showed greater (3)He ADC (P = 0.006), (129)Xe ADC(b12) (P = 0.006), and ADC(b20) (P = 0.006), but not for ADC(b30) (P > 0.05). Never‐smokers and COPD ex‐smokers had significantly different AP(G) for (3)He ADC (P = 0.02), (129)Xe ADC(b12) (P = 0.006), and ADC(b20) (P = 0.01), but not for ADC(b30) (P > 0.05). ∆SI for never‐ and ex‐smokers was significantly different for (3)He ADC (P = 0.046), but not for (129)Xe ADC (P > 0.05). There were strong correlations for DL(CO) with (3)He ADC and (129)Xe ADC(b12) (both r = −0.95, P < 0.05); in a multivariate model (129)Xe ADC(b12) was the only significant predictor of DL(CO) (P = 0.049). For COPD ex‐smokers, CT relative area <−950 HU (RA(950)) correlated with (3)He ADC (r = 0.90, P = 0.008) and (129)Xe ADC(b12) (r = 0.85, P = 0.03). In conclusion, while (129)Xe ADC(b30) may be appropriate for evaluating subclinical or mild emphysema, in this small group of never‐smokers and ex‐smokers with moderate‐to‐severe emphysema, (129)Xe ADC(b12) provided a physiologically appropriate estimate of gas exchange abnormalities and alveolar microstructure.