Longitudinal Assessment of Children with Mild Cystic Fibrosis Using Hyperpolarized Gas Lung Magnetic Resonance Imaging and Lung Clearance Index

Abstract

IntroductionImproving life expectancy in patients with cystic fibrosis (CF) alongside annual rates of decline in FEV1 as low as 1-2% predicted per year (1), poses challenges for the use of spirometry as a measurement of longitudinal change. Spirometry is also insensitive to early changes in the CF lung, and lung clearance index (LCI) derived from multiple breath washout (MBW) has emerged as a promising alternative in patients with well-preserved spirometry, including children (2).Recently the potential of LCI in the longitudinal assessment of CF lung disease has been highlighted (3), though there are still questions with regards to the mechanisms behind the mixed LCI response seen in intervention studies (4-6).As a global metric however, LCI offers little information as to the location of any abnormality and the associated pathophysiology.Hyperpolarised gas ventilation magnetic resonance imaging (ventilation MRI) is a sensitive imaging technique that reveals the distribution of ventilation within the lung in exquisite detail, allowing regional ventilation heterogeneity to be assessed. Ventilation MRI has been shown to be highly sensitive to early lung function abnormalities in CF and other obstructive airways diseases before changes are manifested in spirometry (7-9).We have previously reported cross-sectional data on a cohort of 19 children with mild CF lung disease where ventilation MRI demonstrated lung defects when abnormality was often not detectable on either CT or LCI (8). The aim of the present study was to re-assess these children at a second time point 1-2 years 3 following the baseline visit and describe any observed longitudinal changes in lung function or ventilation MRI. Some of the results of these studies have been previously reported in the form of abstracts (10-12). Methods14 children with CF from the cohort previously reported (8) were re-assessed at a second time point between 1.3-2.0 years after baseline using helium-3 ( 3 He) ventilation MRI, MBW, spirometry and body plethysmography using the same methods as previously described (8). Patients were clinically stable for at least 4 weeks prior to both visits (free from exacerbation and needing no new treatments) and were on stable chronic medical regimens according to national guidelines. From the ventilation images two indices were calculated; (i) the ventilation defect percentage (VDP), which quantifies the fraction of the lung volume that is not ventilated, and (ii) the mean co-efficient of variance of ventilated image signal intensity (CVmean), a metric of ventilation heterogeneity.The percentage change from baseline to visit two was calculated for all metrics. Wilcoxon matched-pairs signed rank test and Spearman correlations were performed due to the small sample size. ResultsPatient demographics, lung function and MRI metrics at baseline and visit two are presented in Table 1. At baseline all children with CF had visible ventilation 4 defects, and VDP and CVmean were greater in CF patients than healthy controls (as reported previousl...

Assessing the feasibility of hyperpolarized 129Xe multiple‐breath washout MRI in pediatric cystic fibrosis

“…7 Ventilation defect percent is reproducible over short time periods (i.e., up to a few weeks) in patients with CF with stable health, 8 and longitudinal imaging (i.e., up to a few years) can identify functional changes that are not reflected in PFTs. 9,10 In addition, VDP is strongly correlated with LCI, and this result has been confirmed using HP 129 Xe 11,12 and 3 He MRI. 13 It has been suggested that both VDP and LCI probe similar physiology, as VDP visualizes the spatial heterogeneity of ventilation during a static breath-hold at a single time-point following a single HP gas inhalation, and LCI measures the temporal heterogeneity of the tracer gas washout (i.e., nitrogen [N 2 ] or sulfur hexafluoride [SF 6 ]) during multiple exhalations.…”

“…Ventilation defect percent is reproducible over short time periods (i.e., up to a few weeks) in patients with CF with stable health, and longitudinal imaging (i.e., up to a few years) can identify functional changes that are not reflected in PFTs . In addition, VDP is strongly correlated with LCI, and this result has been confirmed using HP 129 Xe and 3 He MRI .…”

Modelling structural determinants of ventilation heterogeneity: a perturbative approach

“…More broadly, these results suggest that elevated MBW indices induced by airway constrictions are more variable in general, which is observed experimentally in CF and asthma patients through the increased sensitivity of LCI to posture [36,37], as well increased inter-patient variability [38].…”

“…More broadly, these results suggest that elevated MBW indices induced by airway constrictions are more variable in general, which is observed experimentally through the increased variance in LCI measured in CF and asthma patients [46], as well as an increased sensitivity of LCI to posture which affects the distribution of ventilation due to gravity [47,48]. This latter affect can be understood by perturbing acinar elastance, which affects their rate of ventilation.…”

19F MRI of the Lungs Using Inert Fluorinated Gases: Challenges and New Developments

“…As researchers and clinicians consider the potential applications of inert fluorinated gas MRI, rigorous reproducibility and validation studies will be required. HP gas MRI technology is maturing, and instead of focusing on developing new acquisition approaches, investigators are now focusing on longitudinal imaging 77 and interventional trials with novel therapeutics. 78 19 F MRI technology is not currently as well-developed as HP gases, but there is a strong potential for using it in similar applications in the future.…”