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.
Microfluidic devices can be used to explore a vast range of phenomena in biophysics and soft-matter physics. While the popularity of these devices is in part driven by the ease of soft-lithography, most research labs still depend upon expensive, clean-room fabrication of photoresist molds, which can make this technique inaccessible to the undergraduate laboratory. However, there are much simpler, if coarser, approaches to designing molds that are capable of producing surprisingly complicated devices. Here, we detail the fabrication and characterization of a microfluidic device for flow cytometry or particle sorting on a chip. Our device is a layered polydimethylsiloxane chip that uses a series of Quake valves to sort. The molds were fabricated on equipment accessible to most undergraduate labs. The techniques and physics we discuss in this manuscript can be employed to create an almost endless variety of devices for learning about complex fluid mechanics, mesoscopic, soft-matter, and biological physics.
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.
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