Multi-site Analysis of Functional Gas Exchange Measures on 129Xe MRI Among Healthy Volunteers

RATIONALE: Hyperpolarized 129Xe gas exchange MRI has shown promise as a diagnostic and prognostic tool for diverse cardiopulmonary conditions, including asthma, COPD, and interstitial lung diseases. The increasing clinical use of 129Xe MRI requires a thorough characterization of the normal variation in gas exchange metrics observed in healthy individuals to differentiate expected variation from true disease processes. This study expands upon earlier models to evaluate associations between patient demographics and 129Xe gas exchange metrics in a large cohort of healthy volunteers aged 19 to 87 across three institutions. METHODS: Participants (N=134, 71F/63M, age 54±16 yrs) with no history of pulmonary disease, less than 5 pack-years smoking history, and no smoking history within the last 5 years underwent hyperpolarized 129Xe MRI. For each participant, 3D isotropic images of gas phase (airspaces) and dissolved phase (interstitial membrane tissue uptake and red blood cell transfer [RBC]) were acquired using the 1-point Dixon method at 3 Tesla during a single breath-hold. The imaging-derived metrics, membrane-to-gas ratio (M:Gas) and RBC-to-gas ratio (RBC:Gas), as well as the spectroscopy-based measure, RBC-to-membrane ratio (RBC:M), were analyzed using a multivariate linear regression model with age, sex, and BMI as covariates. Participants were included from three sites: University of Kansas Medical Center (N=27), University of British Columbia (N=58), and Duke University (N=49). Variability between the three participating institutions was assessed using ANOVA and the Tukey range test. RESULTS: Example 129Xe MRI images across a range of ages are shown in Figure 1. Multivariate regression analysis revealed that BMI and male sex were positively correlated in the M:Gas model (p=0.0001 and p=0.03 respectively). RBC:Gas signal increased in males (p=0.0002) and decreased with age (p<0.0001). Age and sex were both significant covariates in the RBC:M model (p<0.0001 and p<0.0001). Each additional 10 years of age was associated with a decrease of 0.04, and males were associated with a 0.12 higher RBC:M than females. CONCLUSION: This large cohort study demonstrates that 129Xe MRI gas exchange metrics vary as a function of patient age, sex, and BMI in healthy individuals, with sex and age playing a larger role in RBC signal whereas BMI plays the greatest role in membrane signal. The consistency of these findings across three institutions validates previous single-site models and establishes the robustness of these demographic associations. Appropriate correction factors may need to be developed to enable meaningful inter-subject comparisons and better delineate the range of expected healthy values.

Duke Scholars

Author Bastiaan Driehuys Radiology