Patent Ductus Arteriosus and Lung MRI Phenotype in Moderate and Severe Bronchopulmonary Dysplasia-Pulmonary Hypertension.

RATIONALE: A hemodynamically significant patent ductus arteriosus (hsPDA) in premature infants has been associated with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). However, these associations remain incompletely understood. OBJECTIVES: The aim was to assess the association between hsPDA duration with clinical outcomes, PH, and phenotypic differences on lung MRI. METHODS: This retrospective cohort study identified all infants with BPD <32 weeks gestation who also underwent a research lung MRI <48 weeks postmenstrual age (PMA) from 2014-2022. Clinical echocardiograms were reviewed for hsPDA, and categorized into no hsPDA, hsPDA 1-60 days, and hsPDA >60 days. Outcome variables included BPD severity, PH at 36 weeks PMA, PH after 36 weeks PMA in the absence of shunt (PH-PVD), tracheostomy or death, and lung phenotype by MRI via modified Ochiai score, indexed total lung volume (TLVI), and whole lung hyperdensity (WLH). Logistic regression and ANOVA analysis were used. MEASUREMENTS AND MAIN RESULTS: In total, 133 infants born at 26.2 ± 1.9 weeks and 776 ± 276g were reviewed (47 no hsPDA, 44 hsPDA 1-60 days, 42 hsPDA >60 days). hsPDA duration >60 days was associated with BPD severity (p<0.01), PH at 36 weeks PMA (aOR 9.7 [95% CI: 3.3-28.4]), PH-PVD (aOR 6.5 [95% CI: 2.3-18.3]), and tracheostomy or death (aOR 3.0 [95% CI: 1.0-8.8]). Duration of hsPDA > 60 days was associated with higher Ochiai score (p=0.03) and TLVI (p=0.01), but not WLH (p=0.91). CONCLUSIONS: In infants with moderate or severe BPD, prolonged exposure to hsPDA is associated with BPD severity, PH-PVD, and increased parenchymal lung disease by MRI.

Comparison of weighting algorithms to mitigate respiratory motion in free-breathing neonatal pulmonary radial UTE-MRI.

Background. Thoracoabdominal MRI is limited by respiratory motion, especially in populations who cannot perform breath-holds. One approach for reducing motion blurring in radially-acquired MRI is respiratory gating. Straightforward 'hard-gating' uses only data from a specified respiratory window and suffers from reduced SNR. Proposed 'soft-gating' reconstructions may improve scan efficiency but reduce motion correction by incorporating data with nonzero weight acquired outside the specified window. However, previous studies report conflicting benefits, and importantly the choice of soft-gated weighting algorithm and effect on image quality has not previously been explored. The purpose of this study is to map how variable soft-gated weighting functions and parameters affect signal and motion blurring in respiratory-gated reconstructions of radial lung MRI, using neonates as a model population.Methods. Ten neonatal inpatients with respiratory abnormalities were imaged using a 1.5 T neonatal-sized scanner and 3D radial ultrashort echo-time (UTE) sequence. Images were reconstructed using ungated, hard-gated, and several soft-gating weighting algorithms (exponential, sigmoid, inverse, and linear weighting decay outside the period of interest), with %Nprojrepresenting the relative amount of data included. The apparent SNR (aSNR) and motion blurring (measured by the maximum derivative of image intensity at the diaphragm, MDD) were compared between reconstructions.Results. Soft-gating functions produced higher aSNR and lower MDD than hard-gated images using equivalent %Nproj, as expected. aSNR was not identical between different gating schemes for given %Nproj. While aSNR was approximately linear with %Nprojfor each algorithm, MDD performance diverged between functions as %Nprojdecreased. Algorithm performance was relatively consistent between subjects, except in images with high noise.Conclusion. The algorithm selection for soft-gating has a notable effect on image quality of respiratory-gated MRI; the timing of included data across the respiratory phase, and not simply the amount of data, plays an important role in aSNR. The specific soft-gating function and parameters should be considered for a given imaging application's requirements of signal and sharpness.

Tracheomalacia Reduces Aerosolized Drug Delivery to the Lung.

Rationale: Neonates with respiratory issues are frequently treated with aerosolized medications to manage lung disease or facilitate airway clearance. Dynamic tracheal collapse (tracheomalacia [TM]) is a common comorbidity in these patients, but it is unknown whether the presence of TM alters the delivery of aerosolized drugs. Objectives: To quantify the effect of neonatal TM on the delivery of aerosolized drugs. Methods: Fourteen infant subjects with respiratory abnormalities were recruited; seven with TM and seven without TM. Respiratory-gated 3D ultrashort echo time magnetic resonance imaging (MRI) was acquired covering the central airway and lungs. For each subject, a computational fluid dynamics simulation modeled the airflow and particle transport in the central airway based on patient-specific airway anatomy, motion, and airflow rates derived from MRI. Results: Less aerosolized drug reached the distal airways in subjects with TM than in subjects without TM: of the total drug delivered, less particle mass passed through the main bronchi in subjects with TM compared with subjects without TM (33% vs. 47%, p = 0.013). In subjects with TM, more inhaled particles were deposited on the surface of the airway (48% vs. 25%, p = 0.003). This effect becomes greater with larger particle sizes and is significant for particles with a diameter >2 µm (2-5 µm, p ≤ 0.025 and 5-15 µm, p = 0.004). Conclusions: Neonatal patients with TM receive less aerosolized drug delivered to the lungs than subjects without TM. Currently, infants with lung disease and TM may not be receiving adequate and/or expected medication. Particles >2 µm in diameter are likely to deposit on the surface of the airway due to anatomical constrictions such as reduced tracheal and glottal cross-sectional area in neonates with TM. This problem could be alleviated by delivering smaller aerosolized particles.

Evaluation of regional lung mass and growth in neonates with bronchopulmonary dysplasia using ultrashort echo time magnetic resonance imaging.

RATIONALE: Bronchopulmonary dysplasia (BPD) is the most common long term pulmonary morbidity in premature infants and is characterized by impaired lung growth and development. We hypothesized that lung mass growth is a critical factor in determining outcomes in infants with BPD. OBJECTIVES: To measure regional lung density and mass in infants with BPD and compare to clinical variables. METHODS: We conducted a retrospective cohort study of neonates (n = 5 controls, n = 46 with BPD). Lung mass and lung density were calculated using ultrashort echo time (UTE) magnetic resonance imaging (MRI). MEASUREMENTS AND MAIN RESULTS: Lung mass increased with increasing corrected gestational age at the time of MRI in all patients. Total, right, and left lung mass in infants with BPD trended higher than control infants (65.7 vs. 49.9 g, 36.2 vs. 26.8 g, 29.5 vs. 23.1 g, respectively). Babies with BPD who survived to discharge had higher relative lung mass than control infants and infants with BPD that did not survive to discharge (21.6 vs. 15.7 g/kg, p = .01). There was a significant association between the rate of lung mass growth and linear growth at the time of MRI (p = .034). CONCLUSIONS: Infants with BPD are capable of building lung mass over time. While this lung mass growth in infants with BPD may not represent fully functional lung tissue, higher lung mass growth is associated with increased linear growth.

Olfactory loss in people with cystic fibrosis: Community perceptions and impact.

BACKGROUND: Olfactory dysfunction (OD) is prevalent in people with cystic fibrosis (PwCF) and can negatively impact quality-of-life (QOL). This study evaluated perceptions of OD, investigated how OD impacts QOL, and assessed willingness to participate in OD research among the CF community. METHODS: A 21-question survey was distributed through the CF Foundation's Community Voice program in 2023. The survey included questions on olfaction and interest in research. The Brief Questionnaire of Olfactory Disorders (BQOD), a validated person-reported outcome measure to assess QOL, was included. RESULTS: Seventy-six responses were received. Overall, 91% (69/76) reported olfactory problems. Mean BQOD score was 5.0 (standard deviation=4.8), indicating olfactory QOL impairment was present. Ninety-five percent (72/76) reported research on OD is worthwhile and were willing to participate in research. CONCLUSION: Among PwCF, OD and olfactory-specific QOL impairments are prevalent. There is strong interest and willingness to participate in OD research among the CF community.

Improved donor lung size matching by estimation of lung volumes based on chest X-ray measurements.

RATIONALE: Organ size matching is an important determinant of successful allocation and outcomes in lung transplantation. While computed tomography (CT) is the gold standard, it is rarely used in an organ-donor context, and chest X-ray (CXR) may offer a practical and accurate solution in estimating lung volumes for donor and recipient size matching. We compared CXR lung measurements to CT-measured lung volumes and traditional estimates of lung volume in the same subjects. METHODS: Our retrospective study analyzed clinically obtained CXR and CT lung images of 250 subjects without evidence of lung disease (mean age 9.9 ± 7.8 years; 129 M/121F). From CT, each lung was semi-automatically segmented and total lung volumes were quantified. From anterior-posterior CXR view, each lung was manually segmented and areas were measured. Lung lengths from the apices to the mid-basal regions of each lung were measured from CXR. Quantified CT lung volumes were compared to the corresponding CXR lung lengths, CXR lung areas, height, weight, and predicted total lung capacity (pTLC). RESULTS: There are strong and significant correlations between CT volumes and CXR lung areas in the right lung (R2 = .89, p < .0001), left lung (R2 = .87, p < .0001), and combined lungs (R2 = .89, p < .0001). Similar correlations were seen between CT volumes and CXR measured lung lengths in the right lung (R2 = .79, p < .0001) and left lung (R2 = .81, p < .0001). This correlation between anatomical lung volume (CT) and CXR was stronger than lung-volume correlation to height (R2 = .66, p < .0001), weight (R2 = .43, p < .0001), or pTLC (R2 = .66, p < .0001). CONCLUSION: CXR measures correlate much more strongly with true lung volumes than height, weight, or pTLC. The ability to obtain efficient and more accurate lung volume via CXR has the potential to change our current listing practices of using height as a surrogate for lung size, with a case example provided.

Initial feasibility and challenges of hyperpolarized 129 Xe MRI in neonates with bronchopulmonary dysplasia.

PURPOSE: The underlying functional and microstructural lung disease in neonates who are born preterm (bronchopulmonary dysplasia, BPD) remains poorly characterized. Moreover, there is a lack of suitable techniques to reliably assess lung function in this population. Here, we report our preliminary experience with hyperpolarized 129 Xe MRI in neonates with BPD. METHODS: Neonatal intensive care patients with established BPD were recruited (N = 9) and imaged at a corrected gestational age of median:40.7 (range:37.1, 44.4) wk using a 1.5T neonatal scanner. 2D 129 Xe ventilation and diffusion-weighted images and dissolved phase spectroscopy were acquired, alongside 1 H 3D radial UTE. 129 Xe images were acquired during a series of short apneic breath-holds (˜3 s). 1 H UTE images were acquired during tidal breathing. Ventilation defects were manually identified and qualitatively compared to lung structures on UTE. ADCs were calculated on a voxel-wise basis. The signal ratio of the 129 Xe red blood cell (RBC) and tissue membrane (M) resonances from spectroscopy was determined. RESULTS: Spiral-based 129 Xe ventilation imaging showed good image quality and sufficient sensitivity to detect mild ventilation abnormalities in patients with BPD. 129 Xe ADC values were elevated above that expected given healthy data in older children and adults (median:0.046 [range:0.041, 0.064] cm2 s-1 ); the highest value obtained from an extremely pre-term patient. 129 Xe spectroscopy revealed a low RBC/M ratio (0.14 [0.06, 0.21]). CONCLUSION: We have demonstrated initial feasibility of 129 Xe lung MRI in neonates. With further data, the technique may help guide management of infant lung diseases in the neonatal period and beyond.

Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a pulmonary alveolar microlithiasis lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes and other proteins suggested a role for osteoclast-like cells in the host response to microliths. While investigating the mechanisms of microlith clearance, we found that Npt2b modulates pulmonary phosphate homeostasis through effects on alternative phosphate transporter activity and alveolar osteoprotegerin, and that microliths induce osteoclast formation and activation in a receptor activator of nuclear factor-κB ligand and dietary phosphate dependent manner. This work reveals that Npt2b and pulmonary osteoclast-like cells play key roles in pulmonary homeostasis and suggest potential new therapeutic targets for the treatment of lung disease.

Short-term structural and functional changes after airway clearance therapy in cystic fibrosis.

BACKGROUND: Airway clearance therapy (ACT) with a high-frequency chest wall oscillation (HFCWO) vest is a common but time-consuming treatment. Its benefit to quality of life for cystic fibrosis (CF) patients is well established but has been questioned recently as new highly-effective modulator therapies begin to change the treatment landscape. 129Xe ventilation MRI has been shown to be very sensitive to lung obstruction in mild CF disease, making it an ideal tool to identify and quantify subtle, regional changes. METHODS: 20 CF patients (ages 20.7 ± 5.1 years) refrained from performing ACT before arriving for a single-day visit. Multiple-breath washout (MBW), spirometry, Xe MRI, and ultrashort echo-time (UTE) MRI were obtained twice-before and after patients performed ACT using their prescribed HFCWO vests (average 4.7 ± 0.5 h). UTE MRIs were scored for structural abnormalities, and standard functional metrics were obtained from MBW, spirometry, and Xe MRI-FEV1,pp, LCI2.5, and VDPN4, respectively. RESULTS: Spirometry and Xe MRI detected significant improvements in lung function post-ACT. 15/20 patients showed improvements from a baseline median of 92% FEV1,pp. Similarly, 16/20 patients showed improvements in Xe MRI from a baseline median of 15.2% VDPN4. Average individual changes were +2.6% in FEV1,pp and -1.3% in VDPN4, but without spatial correlations to easily-identifiable causative structural defects (e.g. mucus plugs or bronchiectasis) on UTE MRI. CONCLUSIONS: Lung function improved after a single instance of HFCWO-vest ACT and was detectable by spirometry and Xe MRI. The only common structural abnormalities were mucus plugs, which corresponded to ventilation defects, but ventilation defects were often present without visible abnormalities.

Intra- and Inter-visit Repeatability of 129 Xenon Multiple-Breath Washout MRI in Children With Stable Cystic Fibrosis Lung Disease.

BACKGROUND: Multiple-breath washout (MBW) 129 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. 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) 129 Xe 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.

Quantitative Imaging Metrics for the Assessment of Pulmonary Pathophysiology: An Official American Thoracic Society and Fleischner Society Joint Workshop Report.

Multiple thoracic imaging modalities have been developed to link structure to function in the diagnosis and monitoring of lung disease. Volumetric computed tomography (CT) renders three-dimensional maps of lung structures and may be combined with positron emission tomography (PET) to obtain dynamic physiological data. Magnetic resonance imaging (MRI) using ultrashort-echo time (UTE) sequences has improved signal detection from lung parenchyma; contrast agents are used to deduce airway function, ventilation-perfusion-diffusion, and mechanics. Proton MRI can measure regional ventilation-perfusion ratio. Quantitative imaging (QI)-derived endpoints have been developed to identify structure-function phenotypes, including air-blood-tissue volume partition, bronchovascular remodeling, emphysema, fibrosis, and textural patterns indicating architectural alteration. Coregistered landmarks on paired images obtained at different lung volumes are used to infer airway caliber, air trapping, gas and blood transport, compliance, and deformation. This document summarizes fundamental "good practice" stereological principles in QI study design and analysis; evaluates technical capabilities and limitations of common imaging modalities; and assesses major QI endpoints regarding underlying assumptions and limitations, ability to detect and stratify heterogeneous, overlapping pathophysiology, and monitor disease progression and therapeutic response, correlated with and complementary to, functional indices. The goal is to promote unbiased quantification and interpretation of in vivo imaging data, compare metrics obtained using different QI modalities to ensure accurate and reproducible metric derivation, and avoid misrepresentation of inferred physiological processes. The role of imaging-based computational modeling in advancing these goals is emphasized. Fundamental principles outlined herein are critical for all forms of QI irrespective of acquisition modality or disease entity.

Magnetic Resonance Imaging-Based Evaluation of Anatomy and Outcome Prediction in Infants with Esophageal Atresia.

INTRODUCTION: There is currently no validated diagnostic modality to characterize the anatomy and predict outcomes of tracheal esophageal defects, such as esophageal atresia (EA) and tracheal esophageal fistulas (TEFs). We hypothesized that ultra-short echo-time MRI would provide enhanced anatomic information allowing for evaluation of specific EA/TEF anatomy and identification of risk factors that predict outcome in infants with EA/TEF. METHODS: In this observational study, 11 infants had pre-repair ultra-short echo-time MRI of the chest completed. Esophageal size was measured at the widest point distal to the epiglottis and proximal to the carina. Angle of tracheal deviation was measured by identifying the initial point of deviation and the farthest lateral point proximal to the carina. RESULTS: Infants without a proximal TEF had a larger proximal esophageal diameter (13.5 ± 5.1 mm vs. 6.8 ± 2.1 mm, p = 0.07) when compared to infants with a proximal TEF. The angle of tracheal deviation in infants without a proximal TEF was larger than infants with a proximal TEF (16.1 ± 6.1° vs. 8.2 ± 5.4°, p = 0.09) and controls (16.1 ± 6.1° vs. 8.0 ± 3.1°, p = 0.005). An increase in the angle of tracheal deviation was positively correlated with duration of post-operative mechanical ventilation (Pearson r = 0.83, p < 0.002) and total duration of post-operative respiratory support (Pearson r = 0.80, p = 0.004). DISCUSSION: These results demonstrate that infants without a proximal TEF have a larger proximal esophagus and a greater angle of tracheal deviation which is directly correlated with the need for longer post-operative respiratory support. Additionally, these results demonstrate that MRI is a useful tool to assess the anatomy of EA/TEF.

Lung Transplantation for Bronchopulmonary Dysplasia.

BACKGROUND: Patients with bronchopulmonary dysplasia (BPD) have poor respiratory trajectories and are at increased risk of lung function decline with age. Lung transplant (LTx) is a possible treatment option for this growing patient population, but little has been published on LTx in this patient group. RESEARCH QUESTION: What are the characteristics of patients with BPD who are listed for LTx? How do waitlist and post-LTx outcomes for BPD compare with LTx for other diagnoses? STUDY DESIGN AND METHODS: The United Network for Organ Sharing (UNOS) registry was queried for patients of all ages listed for or who underwent LTx (2000-2020). Descriptive analysis, waitlist outcomes, and post-LTx survival at 1, 5, and 10 years were assessed comparing patients with BPD vs LTx patients with other diagnoses. Post-LTx survival for patients with BPD born in the pre-surfactant era (pre-SE, before 1990) and those born in the post-surfactant era (post-SE) was compared. Propensity score matching was performed to control for the risk factors and match patients with BPD with other LTx patients on a 1:1 ratio. RESULTS: BPD was reported in 65 patients, of whom 32 (49.2%) underwent LTx. Patients with BPD at listing were younger than those with other diagnoses (median age, 21 [interquartile range, 5-31] years vs 57 [45-63] years; P < .001), and more were likely to receive mechanical ventilation at listing (23% vs 3.7%; P < .001). Patients with BPD had an FEV1 of 17% compared with 34% predicted in other patients (P = .002). Patients with BPD had an overall similar post-LTx survival compared with patients with other diagnoses (P = .106), even following propensity score matching (P = .41). INTERPRETATION: LTx for BPD has increased over the last 20 years. Patients with BPD have similar post-LTx outcomes compared with those of other patient populations in the modern era. Thus, LTx could be considered for patients with BPD experiencing progressive respiratory deterioration.

Childhood to adulthood: Accounting for age dependence in healthy-reference distributions in 129 Xe gas-exchange MRI.

PURPOSE: Xenon-129 (129 Xe) gas-exchange MRI is a pulmonary-imaging technique that provides quantitative metrics for lung structure and function and is often compared to pulmonary-function tests. Unlike such tests, it does not normalize to predictive values based on demographic variables such as age. Many sites have alluded to an age dependence in gas-exchange metrics; however, a procedure for normalizing metrics has not yet been introduced. THEORY: We model healthy reference values for 129 Xe gas-exchange MRI against age using generalized additive models for location, scale, and shape (GAMLSS). GAMLSS takes signal data from an aggregated heathy-reference cohort and fits a distribution with flexible median, variation, skewness, and kurtosis to predict age-dependent centiles. This approach mirrors methods by the Global Lung Function Initiative for modeling pulmonary-function test data and applies it to binning methods widely used by the 129 Xe MRI community to interpret and quantify gas-exchange data. METHODS: Ventilation, membrane-uptake, red blood cell transfer, and red blood cell:membrane gas-exchange metrics were collected on 30 healthy subjects over an age range of 5 to 68 years. A GAMLSS model was fit against age and compared against widely used linear and generalized-linear binning 129 Xe MRI analysis schemes. RESULTS: All 4 gas-exchange metrics had significant skewness, and membrane-uptake had significant kurtosis compared to a normal distribution. Age has significant impact on distribution parameters. GAMLSS-binning produced narrower bins compared to the linear and generalized-linear binning schemes and distributed signal data closer to a normal distribution. CONCLUSION: The proposed "proof-of-concept" GAMLSS-binning approach can improve diagnostic accuracy of 129 Xe gas-exchange MRI by providing a means of modeling voxel distribution data against age.

Inter- and intravisit repeatability of free-breathing MRI in pediatric cystic fibrosis lung disease.

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.

Simulation-Based Training for Ultrasound-Guided Central Venous Catheter Placement in Pediatric Patients.

Introduction: Central venous catheter (CVC) placement in pediatric patients is lifesaving but associated with complications. To standardize training and decrease complications, we developed a simulation-based ultrasound-guided CVC placement training program for pediatric critical care providers. Methods: We implemented our CVC placement training program with several groups of learners, including pediatric critical care medicine (PCCM) fellows, pediatric emergency medicine fellows, and PCCM advanced practice providers. Learners completed prework assignments and a knowledge test before participation. The session started with group activities including a learner-led CVC site-selection debate and a team-based competition to list the steps in CVC placement. Next, the learners rotated between four stations for deliberate practice on separate components of CVC placement. Finally, they performed CVC placement on a task trainer. Evaluation included assessment of learner confidence, a knowledge test, and measurement of procedure time before and after training. Results: Twenty-seven learners participated in the training. Learner confidence in CVC placement increased significantly after participation (median confidence level: 1.5 vs. 4.0, p < .001). Learner CVC knowledge also increased significantly after participation (median test score: 68% vs. 88%, p < .001). CVC placement procedure time, a marker for skill in CVC placement, decreased significantly after participation (median procedure time: 264 seconds vs. 146 seconds, p < .001). Discussion: Our simulation-based training program effectively increased knowledge, skill, and confidence in CVC placement for a variety of learners. Future work should evaluate the optimal frequency and structure of maintenance training and the impact of training on clinical outcomes.