Reproducibility of Hyperpolarized 129Xe MRI Ventilation Defect Percent in Severe Asthma to Evaluate Clinical Trial Feasibility.

ABSTRACT

RATIONALE AND OBJECTIVES: 129Xe MRI has been developed to noninvasively visualize and quantify the functional consequence of airway obstruction in asthma. Its widespread application requires evidence of intersite reproducibility and agreement. Our objective was to evaluate reproducibility and agreement of 129Xe ventilation MRI measurements in severe asthmatics at two sites. MATERIALS AND METHODS: In seven adults with severe asthma, 129Xe ventilation MRI was acquired pre- and post-bronchodilator at two geographic sites within 24-hours. 129Xe MRI signal-to-noise ratio (SNR) was calculated and ventilation abnormalities were quantified as the whole-lung and slice-by-slice ventilation defect percent (VDP). Intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to determine intersite 129Xe VDP reproducibility and agreement. RESULTS: Whole-lung and slice-by-slice 129Xe VDP measured at both sites were correlated and reproducible (pre-bronchodilator whole-lung ICC = 0.90, p = 0.005, slice-by-slice ICC = 0.78, p < 0.0001; post-bronchodilator whole-lung ICC = 0.94, p < 0.0001, slice-by-slice ICC = 0.83, p < 0.0001) notwithstanding intersite differences in the 129Xe-dose-equivalent-volume (101 ± 15 mL site 1, 49 ± 6 mL site 2, p < 0.0001), gas-mixture (129Xe/4He site 1; 129Xe/N2 site 2) and SNR (40 ± 19 site 1, 23 ± 5 site 2, p = 0.02). Qualitative 129Xe gas distribution differences were observed between sites and slice-by-slice 129Xe VDP, but not whole-lung 129Xe VDP, was significantly lower at site 1 (pre-bronchodilator VDP whole-lung bias = -3%, p > 0.99, slice-by-slice bias = -3%, p = 0.0001; post-bronchodilator VDP whole-lung bias = -2%, p = 0.59, slice-by-slice-bias = -2%, p = 0.0003). CONCLUSION: 129Xe MRI VDP at two different sites measured within 24-hours in the same severe asthmatics were correlated. Qualitative and quantitative intersite differences in 129Xe regional gas distribution and VDP point to site-specific variability that may be due to differences in gas-mixture composition or SNR.