Editorial for “Intra‐ and Inter‐visit Repeatability of 129Xenon Multiple‐Breath Washout MRI in Children With Stable Cystic Fibrosis Lung Disease”

Editorial for “Intraand Inter-visit Repeatability of Xenon Multiple-Breath Washout MRI in Children With Stable Cystic Fibrosis Lung Disease” Cystic fibrosis (CF) is a common inherited disease and affects the lung through abnormal mucus secretion and clearance, leading to airway plugging. Within the last decades, great improvements in both the understanding and treatment of the disease have been achieved, such that particularly younger CF patients nowadays may have apparently normal lung function as observed in spirometry. This may limit the value of spirometry as an established clinical test for treatment monitoring. More recently, the lung clearance index (LCI) obtained from multiple-breath washout measurements of an inert gas as a measure of ventilation heterogeneity has been shown to be highly sensitive to CF as well as to longitudinal changes of lung function due to treatment. It can be expected, however, that a measurement of gas concentrations after exhalation still has reduced sensitivity compared with regional measurement of gas washout, motivating the use of dynamic MRI measurements with gas agents such as hyperpolarized Xe or fluorinated gases. Hyperpolarized gases have been used for quantitative assessment of ventilation using multiple-breath protocols in a preclinical setting relatively early after the advent of hyperpolarized gas MRI, but multiple-breath Xe washout MRI has been applied in pediatric CF patients only relatively recently. MRI measurements of fractional ventilation (FV) in the washout of fluorinated inhaled gases have also recently been shown to be strongly correlated with spirometry in chronic obstructive pulmonary disease, differentiate healthy and diseased subjects, and to have good repeatability. Another recent study showed sensitivity of the fraction of the lung volume with slow washout of a fluorinated gas to CF lung disease in patients with normal spirometry. In this issue of JMRI, Alam investigated the still open but with respect to interpretation of longitudinal changes important question of intravisit and intervisit repeatability of the parameters FV and coefficient of variation of FV (CoVFV) as a heterogeneity metric derived from multiple-breath washout hyperpolarized Xe MRI in a well-performed study including pediatric CF and age-matched healthy subjects. Care was taken to obtain accurate estimates of FV by accounting for time-varying polarization decay as a detrimental effect in hyperpolarized gas MRI using previously developed methods. Good repeatability of FV and CoVFV in terms of high intraclass correlation coefficients (ICC) above 0.75 was found for intravisit assessment in both healthy and diseased subjects. Although intervisit repeatability of FV and CoVFV tended to be reduced, ICC values remained high and particularly repeatability of FV in terms of ICC and withinsubject coefficient of variation in CF was improved compared with the values for ventilation defect percentage (VDP). This may suggest this biomarker derived from multiple-breath washout MRI has advantages over VDP derived from static ventilation imaging. However, the same observation was not made in the case of intravisit repeatability and confidence intervals for ICCs are wide due to small sample size. In addition, a moderate correlation was found between the quantity of CoVFV and LCI. Taken together, these findings suggest that the method has great potential for longitudinal monitoring of CF lung disease. Yet, the fact that no significant differences in FV and CoVFV between study groups were found despite significant differences in LCI and VDP may suggest that more methodological and/or conceptual advancement is still necessary and benefits over conventional VDP quantification in static ventilation images of hyperpolarized gas MRI—sensitive to the effects of CF and changes due to treatment—may still need to be shown more clearly. Metrics probing FV heterogeneity like CoVFV or FV skewness derived from FV maps addressing potential compensatory effects of FV throughout the lung still appear to suffer from reduced robustness. Physiological gating and/or multislice acquisitions may reduce the susceptibility to artifacts associated with image misregistration. Further, the influence of Xe uptake as well as the influence of tidal volume on measured FV, for example, through gas rebreathing due to non-negligible anatomical