Purpose: To investigate the prognostic power of hyperpolarized-Â¹Â²â?¹Xe pulmonary gas exchange MRI in predicting clinical progression of subjects with idiopathic pulmonary fibrosis (IPF).
Methods: Twelve IPF patients underwent hyperpolarized-Â¹Â²â?¹Xe MRI to obtain 3D quantitative measures of Â¹Â²â?¹Xe both dissolved interstitially in the lung alveolar tissue (namely â€œbarrier uptakeâ€?) and transferred to red blood cells (â€œRBC transferâ€?). Based on comparison to a previously published healthy reference cohort, we calculated the percentage of lung voxels exhibiting high barrier uptake (Barrier-High) and low RBC transfer (RBC-Low). In a given subject, percent-volumes of Barrier-High and RBC-Low were considered abnormal if they exceeded the mean of the healthy reference cohort by more than 2 standard deviations. This stratified each subject into one of three groups: 1) abnormal RBC-Low; 2) abnormal Barrier-High; and 3) both abnormal RBC-Low and Barrier-High. Prospective clinical information, including baseline CT fibrosis score, periodic measures of lung function (FVC and DLCO), drug therapies, and death or lung transplant, was collected over a median follow-up time of 38, 31, and 33 months for each group, respectively. Kaplan Meier analysis was employed to determine whether transplant-free survival was different between the three groups.
Results: Baseline Â¹Â²â?¹Xe MRI categorized two subjects into group 1, and five subjects into both group 2 and group 3. There was overlap between groups in the baseline clinical metrics of FVC, DLCO, CT fibrosis scores, or GAP scores, with the exception of group 1, which exhibited higher FVC than other groups. No deaths or transplants were observed in groups 1 or 2. However, 80% of subjects (4/5) in group 3 proceeded to death (2) or transplant (2), with a median transplant-free survival of 21 months (P=0.04).
Conclusion: This small pilot study suggests that Â¹Â²â?¹Xe MRI may present new and unique prognostic information for stratifying IPF subjects and predicting clinical outcomes.
Funding Support, Disclosures, and Conflict of Interest: B. Driehuys is a founder of and shareholder in Polarean Imaging, outside the submitted work, and has a patent (US 9625550 B2) receiving royalties paid by Polarean Imaging. This work was supported by the following grants: NIH/NHLBI R01 HL105643, NIH/NHLBI R01HL126771, NIH/NIEHS R01 ES027574 and Gilead Sciences.