Abstract
BACKGROUND: There is currently no sensitive, noninvasive method of screening for chronic lung allograft dysfunction (CLAD), the primary barrier to long-term survival after lung transplant. Conventional pulmonary function testing is imprecise absent a sustained decline. Hyperpolarized (129)Xe magnetic resonance imaging (MRI) is a sensitive tool for 3-dimensional imaging of regional pulmonary ventilation and gas-exchange abnormalities and may aid in early detection of CLAD. METHODS: Adult patients, post bilateral lung transplant, were screened for CLAD based on the International Society for Heart and Lung Transplantation criteria. Those with established allografts (n = 10) underwent (129)Xe gas-exchange MRI and spectroscopy and were compared to results from 16 young healthy volunteers and 16 age-matched healthy volunteers. One lung transplant recipient was excluded from the final data analysis due to a concurrent lung infection found incidentally after MRI. Imaging provided quantitative maps of the ventilation defect percent (VDP), membrane high percent, and red blood cell (RBC) defect percent. Spectroscopy yielded RBC/membrane ratio, oxygenation-dependent RBC shift, and RBC oscillation amplitude. RESULTS: The analysis included 9 lung transplant recipients, 7 with CLAD and 2 without. CLAD patients exhibited VDP values consistent with their forced expiratory volume in 1 second (FEV(1)) decline (rho = 0.79, p = 0.048). Hemoglobin-corrected RBC transfer was reduced in all transplant recipients vs young healthy controls (median [first quartile-third quartile] of 13% [9%-22%] vs 2% [1.75%-3%], p = 0.003) as well as vs age-matched controls (5.5% [2%-9.25%], p = 0.039). Spectroscopy demonstrated reduced RBC/membrane signal (0.26 [0.17-0.31] vs 0.62 [0.50-0.66], p < 0.001 and vs 0.48 [0.42-0.55], p = 0.002), reduced RBC chemical shift (217.4 [217.2-217.7] ppm vs 218.2 [218.0-218.5] ppm, p = 0.009 and vs 218.3 [218.2-218.5] ppm, p = 0.003), and increased RBC oscillation amplitude vs the young healthy controls (14.1% [12.2%-16.4%] vs 11.1% [9.9%-11.9%], p = 0.003). CONCLUSIONS: Patients with CLAD exhibited significant ventilation defects that correlated with FEV(1) decline, which, along with RBC transfer defects and other (129)Xe gas-exchange and hemodynamic abnormalities, could provide a promising means of early detection of physiological changes in patients with CLAD.