Purpose The purpose of this study is to assess the intra‐ and interscan repeatability of free‐breathing phase‐resolved functional lung (PREFUL) MRI in stable pediatric cystic fibrosis (CF) lung disease in comparison to static breath‐hold hyperpolarized 129‐xenon MRI (Xe‐MRI) and pulmonary function tests. Methods Free‐breathing 1‐hydrogen MRI and Xe‐MRI were acquired from 15 stable pediatric CF patients and seven healthy age‐matched participants on two visits, 1 month apart. Same‐visit MRI scans were also performed on a subgroup of the CF patients. Following the PREFUL algorithm, regional ventilation (RVent) and regional flow volume loop cross‐correlation maps were determined from the free‐breathing data. Ventilation defect percentage (VDP) was determined from RVent maps (VDPRVent), regional flow volume loop cross‐correlation maps (VDPCC), VDPRVent ∪ VDPCC, and multi‐slice Xe‐MRI. Repeatability was evaluated using Bland–Altman analysis, coefficient of repeatability (CR), and intraclass correlation. Results Minimal bias and no significant differences were reported for all PREFUL MRI and Xe‐MRI VDP parameters between intra‐ and intervisits (all P > 0.05). Repeatability of VDPRVent, VDPCC, VDPRVent ∪ VDPCC, and multi‐slice Xe‐MRI were lower between the two‐visit scans (CR = 14.81%, 15.36%, 16.19%, and 9.32%, respectively) in comparison to the same‐day scans (CR = 3.38%, 2.90%, 1.90%, and 3.92%, respectively). pulmonary function tests showed high interscan repeatability relative to PREFUL MRI and Xe‐MRI. Conclusion PREFUL MRI, similar to Xe‐MRI, showed high intravisit repeatability but moderate intervisit repeatability in CF, which may be due to inherent disease instability, even in stable patients. Thus, PREFUL MRI may be considered a suitable outcome measure for future treatment response studies.
Background Multiple‐breath washout (MBW) 129Xe MRI (MBW Xe‐MRI) is a promising technique for following pediatric cystic fibrosis (CF) lung disease progression. However, its repeatability in stable CF needs to be established to use it as an outcome measure for novel therapies. Purpose To assess intravisit and intervisit repeatability of MBW Xe‐MRI in healthy and CF children. Study Type Prospective, longitudinal cohort study. Subjects A total of 18 pediatric subjects (7 healthy, 11 CF). Field Strength/Sequence A 3 T/2D coronal hyperpolarized (HP) 129Xe images using GRE sequence. Assessment All subjects completed MBW Xe‐MRI, pulmonary function tests (PFTs) (spirometry, nitrogen [N2] MBW for lung clearance index [LCI]) and ventilation defect percent (VDP) at baseline (visit 1) and 1‐month after. Fractional ventilation (FV), coefficient of variation (CoVFV) maps were calculated from MBW Xe‐MRI data acquired between intervening air washout breaths performed after an initial xenon breath‐hold. Skewness of FV and CoVFV map distributions was also assessed. Statistical Tests Repeatability: intraclass correlation coefficients (ICC), within‐subject coefficient of variation (CV%), repeatability coefficient (CR). Agreement: Bland–Altman. For correlations between MBW Xe‐MRI, VDP and PFTs: Spearman's correlation. Significance threshold: P < 0.05. Results For FV, intravisit median [IQR] ICC was high in both healthy (0.94 [0.48, 0.99]) and CF (0.83 [0.04, 0.97]) subjects. CoVFV also had good intravisit ICC in healthy (0.92 [0.42, 0.99]) and CF (0.79 [0.02, 0.96]) subjects. Similarly, for FV, intervisit ICC was high in health (0.94 [0.68, 0.99]) and CF (0.89 [0.61, 0.97]). CoVFV also had good intervisit ICC in health (0.92 [0.42, 0.99]) and CF (0.78 [0.26, 0.94]). FV had better intervisit repeatability than VDP. CoVFV correlated significantly with LCI (R = 0.56). Skewness of FV distributions significantly distinguished between cohorts at baseline. Data Conclusion MBW Xe‐MRI had high intravisit and intervisit repeatability in healthy and stable CF subjects. CoVFV correlated with LCI, suggesting the importance of ventilation heterogeneity to early CF. Evidence Level 1. Technical Efficacy Stage 2.
Hyperpolarized 129Xe MRI (Xe-MRI) yielding VDP has shown advantages over conventional PFT’s for assessing paediatric CF lung disease but is only a static “snapshot” of a dynamic process. Xe-MRI can be conducted in a MBW fashion to yield temporal/spatial heterogeneity of the gas during respiration, resulting in regional maps of fractional ventilation (r), a measure of percent gas clearance per breath. This work assessed the within-visit and inter-visit repeatability of MBW Xe-MRI between baseline and one-month follow-up in paediatric subjects with stable CF and found strong intra- and inter-visit repeatability. Significant correlations between MBW Xe-MRI and LCI were also found.
Free-breathing lung MRI has been shown to be a responsive measure to CF pulmonary exacerbations treatments but have not been used to track stable disease progression longitudinally. In this study we determined the intra- and inter-scan reproducibility of free-breathing lung MRI in healthy and stable pediatric CF across 2 visits and compared to hyperpolarized Xenon MRI (Xe-MRI). Xe-MRI and free-breathing lung show a high intra-scan reproducibility in stable CF subjects, but free-breathing lung MRI showed a low inter-scan reproducibility. However, free-breathing lung MRI significantly correlated with Xe-MRI suggesting that it may be an alternative to expensive, and less wide-spread Xe-MRI.
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