Functional gas exchange measures on 129Xe MRI and spectroscopy are associated with age, sex, and BMI in healthy subjects

Introduction Hyperpolarized 129 Xe MRI and spectroscopy is a rapidly growing technique for assessing lung function, with applications in a wide range of obstructive, restrictive, and pulmonary vascular disease. However, normal variations in 129 Xe measures of gas exchange across healthy subjects are not well characterized, presenting an obstacle to differentiating disease processes from the consequences of expected physiological heterogeneity. Here, we use multivariate models to evaluate the role of age, sex, and BMI in a range of commonly used 129 Xe measures of gas exchange. Materials and methods Healthy subjects ( N = 40, 16F, age 44.3 ± 17.8 yrs., min-max 22–87 years) with no history of cardiopulmonary disease underwent 129 Xe gas exchange MRI and spectroscopy. We used multivariate linear models to assess the associations of age, sex, and body mass index (BMI) with the RBC:Membrane (RBC:M), membrane to gas (Mem:Gas), and red blood cell to gas (RBC:Gas) ratios, as well as measurements of RBC oscillation amplitude and RBC chemical shift. Results Age, sex, and BMI were all significant covariates in the RBC:M model. Each additional 10 years of age was associated with a 0.05 decrease in RBC:M ( p 0.001), each additional 10 points of BMI was associated with a decrease of 0.07 ( p = 0.02), and males were associated with a 0.17 higher RBC:M than females ( p 0.001). For Mem:Gas, male sex was associated with a decrease and BMI was associated with an increase. For RBC:Gas, age was associated with a decrease and male sex was associated with an increase. RBC oscillation amplitude increased with age and RBC chemical shift was not associated with any of the three covariates. Discussion 129 Xe MRI and spectroscopy measurements in healthy subjects, particularly the widely used RBC:M measurement, exhibit heterogeneity associated in part with variations in subject age, sex, and BMI. Elucidating the contributions of these and other factors to 129 Xe gas exchange measurements is a critical component for differentiating disease processes from expected variation in healthy subjects. Notably, the Mem:Gas and RBC chemical shift appear to be stable with aging, suggesting that unexplained deviations in these metrics may be signs of underlying abnormalities.