Hyperpolarized129Xe MRI Membrane Uptake Associates With 12-month Changes in Lung Function in Patients With Idiopathic Pulmonary Fibrosis Initiating Therapy
Swaminathan, AC; Mummy, D; Qin, H; Salazar, C; Morrison, LD; Mammarappallil, J; Coimbra, A; Belloni, P; Driehuys, B; Tighe, RM
Published in: American Journal of Respiratory and Critical Care Medicine
RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a high mortality. Antifibrotic therapies can slow lung function decline in patients with IPF, but reliable methods to assess treatment responses are currently lacking. Hyperpolarized 129Xe MRI enables regional quantification of 129Xe uptake in the interstitium (“membrane uptake”), thus offering potential to evaluate therapeutic response. We hypothesized that in patients with IPF who start antifibrotic therapy, 129Xe membrane uptake would associate with 12-month changes in lung function. METHODS: This study enrolled patients with IPF prior to the initiation of antifibrotic therapy who underwent both 129Xe MRI and pulmonary function testing at enrollment, 3-month, and 6-month, and 12-month timepoints. For each patient, images of gas phase, interstitial tissue (membrane) uptake, and red blood cell (RBC) transfer metrics were acquired during a single breath-hold. We quantified the high membrane uptake percent (Memhigh) as the percentage of the lung where the signal was at least two standard deviations higher than a healthy reference mean. Spearman correlation was used to evaluate the association between enrollment Memhigh and forced vital capacity (FVC) as well enrollment Memhigh and 12-month change in FVC. Wilcox rank-sum test was used to compare the 12-month change in FVC among patients with enrollment Memhigh ≥ 5% vs <5%. RESULTS: This study included 21 patients with IPF who started antifibrotic therapy after enrollment. The median (Q1, Q3) Memhigh was 7.71% (0.91%, 16.12%) at enrollment, and 10.88% (0.46%, 18.17%) at 12 months of follow up. The median (Q1, Q3) FVC was 2.91 (2.37, 3.31) liters at enrollment and 2.96 (2.43, 3.48) liters at 12 months of follow up. There was no significant association between enrollment Memhigh and enrollment FVC (p= 0.60). However, we observed a positive correlation between Memhigh at enrollment and 12-month change in FVC (rho = 0.45, p = 0.04). Patients with a Memhigh ≥ 5% at enrollment had a median 12 month change in FVC of 0.14 (0.01, 0.30) liters whereas patients with Memhigh < 5% had a median 12 change in FVC of -0.10 (-0.15, 0.02) liters (p = 0.01, Figure). CONCLUSIONS: In patients with IPF, elevated 129Xe membrane uptake prior to antifibrotic initiation correlated with improvements in FVC at 12 months, whereas low 129Xe membrane uptake correlated with 12-month FVC decline. Elevated 129Xe membrane uptake may be a biomarker of patients with IPF who have an antifibrotic therapeutic response.
