ObjectivesThe objective of this work was to apply quantitative and semi-quantitative dynamic contrast enhanced MRI (DCE-MRI) methods to evaluate lung perfusion in idiopathic pulmonary fibrosis (IPF).Materials and MethodsIn this prospective trial 41 subjects, including healthy control (control) and IPF subjects, were studied using DCE-MRI at baseline. IPF subjects were then followed for 1 year, progressive IPF (IPFprog) were distinguished from stable IPF (IPFstable) subjects based on a decline in percent predicted FVC (FVC%p) or DLCO (DLCO%p) measured during followup visits. 35/41 subjects were retained for final baseline analysis at (control: N=15; IPFstable: N=14; IPFprog: N=6). Seven measures and their coefficients of variation (CV) were derived using temporally resolved DCE-MRI. Two sets of global and regional comparisons were made: control versus IPF groups, and control versus IPFstableversus IPFprog groups, using linear regression analysis. Each measure was compared to FVC%p, DLCO%p, and the lung clearance index (LCI%p) using a Spearman rank correlation.ResultsDCE-MRI identified regional perfusion differences between control and IPF subjects using first moment transit time (FMTT), contrast uptake slope (SLOPE), and pulmonary blood flow (PBF) (p≤0.05), while global averages did not. FMTT was shorter for IPFprog compared to both IPFstable (p=0.004) and control groups (p=0.023). Correlations were observed between PBF CV and DLCO%p (rs=−0.48, p=0.022) and %LCI (rs=+0.47, p=0.015). Significant group differences were detected in age (p<0.001), DLCO%p (p<0.001), FVC%p (p=0.001), and LCI%p (p=0.007).ConclusionsGlobal analysis obscures regional changes in pulmonary hemodynamics in IPF using DCE-MRI in IPF. Decreased FMTT may be a candidate marker for IPF progression.

No abstract

Progression of idiopathic pulmonary fibrosis (IPF) is highly variable [1] and it is clinically challenging to effectively manage care and tailor treatment regimens using antifibrotic medications, such as nintedanib and pirfenidone, on a patient-specific basis [2]. Clinical evaluation of the functional response to these treatments is limited largely to pulmonary function tests (PFTs) (e.g. forced vital capacity (FVC), percentage predicted forced expiratory volume in 1 s (FEV 1 ), diffusing capacity of the lung for carbon monoxide (D LCO ) [3] and/or progression-free survival [4]). The development of more sensitive biomarkers that can provide longitudinal evaluation of regional treatment response would have meaningful clinical utility. Hyperpolarised (HP) xenon-129 ( 129 Xe) magnetic resonance imaging (MRI) has shown potential for evaluating both regional ventilation and gas exchange, with a strong focus on applications in IPF [5][6][7]. Specifically, HP 129 Xe MRI spectroscopy measures of red blood cell (RBC) 129 Xe uptake across the lung tissue and plasma barrier (hereafter "membrane") from the alveolar space, called the RBC-to-membrane ratio, has been shown to be a possible biomarker of future IPF disease progression [8].In this work, we investigate our hypothesis that IPF patients treated with antifibrotic medications will show improved longitudinal trajectories in this candidate biomarker over the course of 1 year. These results have been introduced previously in abstract form [9]. The study was Health Insurance Portability and Accountability Act compliant and informed consent was obtained in accordance with approved institutional review board (UW IRB 2013-0266 and UW IRB 2014-1572) and investigational new drug (United States Food and Drug Administration IND# 118077) protocols. 25 participants with IPF were recruited prospectively, 21 of whom (19 males, mean±SD age 70.1±8.5 years) underwent HP 129 Xe MRI ventilation and spectroscopic imaging at baseline and at 1-year follow-up. Criteria for study inclusion were outpatients aged >18 years with clinical diagnosis of IPF by established means. Potential participants were excluded for any of the following reasons: respiratory illness within 30 days of MRI; oxygen saturation on room air <90%; history of ventricular cardiac arrhythmia; cardiac arrest within the past year; pregnancy; or unable to maintain 15-s breath-hold. All 21 participants underwent treatment for IPF according to the standard of care such that a subgroup was treated with antifibrotic medication ("antifibrotic" group; n=12, 11 males, age 68.1±7.7 years), while the remaining patients were treated with alternative therapies ("no-antifibrotic" group; n=9, eight males, age 72.8±9.2 years). Participants were considered part of the antifibrotic group if they received antifibrotic medication at any point during the study ( pirfenidone: n=8 for full year, n=2 for part of year; nintedanib: n=1 for full year, n=1 for part of year). Patients receiving only partial treatment were medicated as follows: two wer...