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.
Multiple-breath washout (MBW)
Xe 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.
To assess intravisit and intervisit repeatability of MBW Xe-MRI in healthy and CF children.
Prospective, longitudinal cohort study.
A total of 18 pediatric subjects (7 healthy, 11 CF).
A 3 T/2D coronal hyperpolarized (HP)
Xe images using GRE sequence.
All subjects completed MBW Xe-MRI, pulmonary function tests (PFTs) (spirometry, nitrogen N
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 (CoV
) 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 CoV
map distributions was also assessed.
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.
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. CoV
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). CoV
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. CoV
correlated significantly with LCI (R = 0.56). Skewness of FV distributions significantly distinguished between cohorts at baseline.
MBW Xe-MRI had high intravisit and intervisit repeatability in healthy and stable CF subjects. CoV
correlated with LCI, suggesting the importance of ventilation heterogeneity to early CF.
1.
Stage 2.
Many knowledge gaps in the nature of early chronic obstructive pulmonary disease (COPD) still exist, mainly because COPD has always been considered a disease of the elderly. Little attention has been ...paid to the pathologic changes in the lungs of young adults with risk factors for COPD, such as bronchopulmonary dysplasia. One major limitation is the current lack of noninvasive ways to sensitively measure or image functional declines from subjects who are at risk for COPD but haven't yet developed more significant clinical symptoms of the disease.
We report the use of lung magnetic resonance imaging with hyperpolarized gas in the diagnostic workup for bronchopulmonary dysplasia with underlying chronic airflow limitation in presence of spirometry criteria that meet the diagnosis of early-onset COPD.
In the postsurfactant era, where more young adults will be spirometrically diagnosed with COPD, patients should be classified not only on the basis of their airflow limitation, but also on lung abnormalities identified with safe, comprehensive imaging technologies that allow regular, longitudinal follow-up.
Pulmonary MRI can now provide high‐resolution images that are sensitive to early disease and specific to inflammation in cystic fibrosis (CF) lung disease. With specificity and function limited via ...computed tomography (CT), there are significant advantages to MRI. Many of the modern MRI techniques can be performed throughout life, and can be employed to understand changes over time, in addition to quantification of treatment response. Proton density and T1/T2 contrast images can be obtained within a single breath‐hold, providing depiction of structural abnormalities and active inflammation. Modern radial and/or spiral ultrashort echo‐time (UTE) techniques rival CT in resolution for depiction and quantification of structure, for both airway and parenchymal abnormalities. Contrast perfusion MRI techniques are now utilized routinely to visualize changes in pulmonary and bronchial circulation that routinely occur in CF lung disease, and noncontrast techniques are moving closer to clinical translation. Functional information can be obtained from noncontrast proton images alone, using techniques such as Fourier decomposition. Hyperpolarized‐gas MRI, increasingly using 129Xe, is now becoming more widespread and has been demonstrated to have high sensitivity to early airway obstruction in CF via ventilation MRI. The sensitivity of 129Xe MRI promises future use in personalized medicine, management of early CF lung disease, and in future clinical trials. By combining structural and functional techniques, with or without hyperpolarized gases, regional structure–function relationships can be obtained, giving insight into the pathophysiology of disease and improved clinical management. This article reviews the modern MRI techniques that can routinely be employed for CF lung disease in nearly any large medical center.
Level of Evidence: 4
Technical Efficacy Stage: 5
J. Magn. Reson. Imaging 2019.
Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD) pathogenesis. Iron accumulation has been implicated in ...oxidative stress in other diseases, such as Alzheimer's and Parkinson's diseases, but little is known about iron accumulation in COPD. We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these correlate with airway obstruction. Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL) cells were obtained from non-smokers, healthy smokers, and GOLD 1-3 COPD subjects. Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor), storage (ferritin) and export (ferroportin) genes was examined by real-time RT-PCR assay. Percentage of iron-positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV.sub.1) and the ratio between FEV.sub.1 and forced vital capacity (FEV.sub.1 /FVC)). The alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues. Futhermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity. The mRNA expression of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively). In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin correlated with airway obstruction. These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative stress.
Adolescent idiopathic scoliosis (AIS) is associated with decreased respiratory quality of life and impaired diaphragm function. Recent hyperpolarized helium (HHe) MRI studies show alveolarization ...continues throughout adolescence, and mechanical forces are known to impact alveolarization. We therefore hypothesized that patients with AIS would have alterations in alveolar size, alveolar number, or alveolar septal dimensions compared to adolescents without AIS, and that posterior spinal fusion (PSF) might reverse these differences. We conducted a prospective observational trial using HHe MRI to test for changes in alveolar microstructure in control and AIS subjects at baseline and one year. After obtaining written informed consent from subjects' legal guardians and assent from the subjects, we performed HHe and proton MRI in 14 AIS and 16 control subjects aged 8-21 years. The mean age of control subjects (12.9 years) was significantly less than AIS (14.9 years, p = 0.003). At baseline, there were no significant differences in alveolar size, number, or alveolar duct morphometry between AIS and control subjects or between the concave (compressed) and convex (expanded) lungs of AIS subjects. At one year after PSF AIS subjects had an increase in alveolar density in the formerly convex lung (p = 0.05), likely reflecting a change in thoracic anatomy, but there were no other significant changes in lung microstructure. Modeling of alveolar size over time demonstrated similar rates of alveolar growth in control and AIS subjects in both right and left lungs pre- and post-PSF. Although this study suffered from poor age-matching, we found no evidence that AIS or PSF impacts lung microstructure. Trial registration: Clinical trial registration number NCT03539770.
Computational fluid dynamics (CFD) simulations of respiratory airflow have the potential to change the clinical assessment of regional airway function in health and disease, in pulmonary medicine and ...otolaryngology. For example, in diseases where multiple sites of airway obstruction occur, such as obstructive sleep apnea (OSA), CFD simulations can identify which sites of obstruction contribute most to airway resistance and may therefore be candidate sites for airway surgery. The main barrier to clinical uptake of respiratory CFD to date has been the difficulty in validating CFD results against a clinical gold standard. Invasive instrumentation of the upper airway to measure respiratory airflow velocity or pressure can disrupt the airflow and alter the subject's natural breathing patterns. Therefore, in this study, we instead propose phase contrast (PC) velocimetry magnetic resonance imaging (MRI) of inhaled hyperpolarized 129Xe gas as a non-invasive reference to which airflow velocities calculated via CFD can be compared. To that end, we performed subject-specific CFD simulations in airway models derived from 1H MRI, and using respiratory flowrate measurements acquired synchronously with MRI. Airflow velocity vectors calculated by CFD simulations were then qualitatively and quantitatively compared to velocity maps derived from PC velocimetry MRI of inhaled hyperpolarized 129Xe gas. The results show both techniques produce similar spatial distributions of high velocity regions in the anterior-posterior and foot-head directions, indicating good qualitative agreement. Statistically significant correlations and low Bland-Altman bias between the local velocity values produced by the two techniques indicates quantitative agreement. This preliminary in vivo comparison of respiratory airway CFD and PC MRI of hyperpolarized 129Xe gas demonstrates the feasibility of PC MRI as a technique to validate respiratory CFD and forms the basis for further comprehensive validation studies. This study is therefore a first step in the pathway towards clinical adoption of respiratory CFD.
Premature birth affects millions of neonates each year, placing them at risk for respiratory disease due to prematurity. Bronchopulmonary dysplasia is the most common chronic lung disease of infancy, ...but recent data suggest that even premature infants who do not meet the strict definition of bronchopulmonary dysplasia can develop adverse pulmonary outcomes later in life. This post-prematurity respiratory disease (PPRD) manifests as chronic respiratory symptoms, including cough, recurrent wheezing, exercise limitation, and reduced pulmonary function. This document provides an evidence-based clinical practice guideline on the outpatient management of infants, children, and adolescents with PPRD.
A multidisciplinary panel of experts posed questions regarding the outpatient management of PPRD. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations.
The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations were developed for or against three common medical therapies and four diagnostic evaluations in the context of the outpatient management of PPRD.
The panel developed recommendations for the outpatient management of patients with PPRD on the basis of limited evidence and expert opinion. Important areas for future research were identified.
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