Hyperpolarized ¹²⁹Xe MRI and spectroscopy of gas-exchange abnormalities in bilateral lung transplant recipients

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 ¹²⁹Xe 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.

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 ¹²⁹Xe 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.

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 (FEV₁) 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).

Patients with CLAD exhibited significant ventilation defects that correlated with FEV₁ decline, which, along with RBC transfer defects and other ¹²⁹Xe gas-exchange and hemodynamic abnormalities, could provide a promising means of early detection of physiological changes in patients with CLAD.