Laura L. Walkup

Quantitative Magnetic Resonance Imaging of Bronchopulmonary Dysplasia in the Neonatal Intensive Care Unit Environment

RATIONALE Bronchopulmonary dysplasia (BPD) is a prevalent yet poorly characterized pulmonary complication of premature birth; the current definition is based solely on oxygen dependence at 36 weeks postmenstrual age without objective measurements of structural abnormalities across disease severity. OBJECTIVES We hypothesize that magnetic resonance imaging (MRI) can spatially resolve and quantify the structural abnormalities of the neonatal lung parenchyma associated with premature birth. METHODS Using a unique, small-footprint, 1.5-T MRI scanner within our neonatal intensive care unit (NICU), diagnostic-quality MRIs using commercially available sequences (gradient echo and spin echo) were acquired during quiet breathing in six patients with BPD, six premature patients without diagnosed BPD, and six full-term NICU patients (gestational ages, 23-39 wk) at near term-equivalent age, without administration of sedation or intravenous contrast. Images were scored by a radiologist using a modified Ochiai score, and volumes of high- and low-signal intensity lung parenchyma were quantified by segmentation and threshold analysis. MEASUREMENTS AND MAIN RESULTS Signal increases, putatively combinations of fibrosis, edema, and atelectasis, were present in all premature infants. Infants with diagnosed BPD had significantly greater volume of high-signal lung (mean ± SD, 26.1 ± 13.8%) compared with full-term infants (7.3 ± 8.2%; P = 0.020) and premature infants without BPD (8.2 ± 6.4%; P = 0.026). Signal decreases, presumably alveolar simplification, only appeared in the most severe BPD cases, although cystic appearance did increase with severity. CONCLUSIONS Pulmonary MRI reveals quantifiable, significant differences between patients with BPD, premature patients without BPD, and full-term control subjects. These methods could be implemented to individually phenotype disease, which may impact clinical care and predict future outcomes.

Translational applications of hyperpolarized 3He and 129Xe.

Clinical magnetic resonance imaging of the lung is technologically challenging, yet over the past two decades hyperpolarized noble gas (3He and 129Xe) imaging has demonstrated the ability to measure multiple pulmonary functional biomarkers. There is a growing need for non‐ionizing, non‐invasive imaging techniques due to increased concern about cancer risk from ionizing radiation, but the translation of hyperpolarized gas imaging to the pulmonary clinic has been stunted by limited access to the technology. New developments may open doors to greater access and more translation to clinical studies.

Retrospective respiratory self-gating and removal of bulk motion in pulmonary UTE MRI of neonates and adults.

To implement pulmonary three‐dimensional (3D) radial ultrashort echo‐time (UTE) MRI in non‐sedated, free‐breathing neonates and adults with retrospective motion tracking of respiratory and intermittent bulk motion, to obtain diagnostic‐quality, respiratory‐gated images.

Hyperpolarized 129Xe for investigation of mild cystic fibrosis lung disease in pediatric patients

BACKGROUND Cystic fibrosis (CF) is a genetic disease which carries high morbidity and mortality from lung-function decline. Monitoring disease progression and treatment response in young patients is desirable, but serial imaging via CT is often considered prohibitive, and detailed functional information cannot be obtained using conventional imaging techniques. Hyperpolarized 129Xe magnetic resonance imaging (MRI) can depict and quantify regional ventilation, but has not been investigated in pediatrics. We hypothesized that 129Xe MRI is feasible and would demonstrate ventilation defects in mild CF lung disease with greater sensitivity than FEV1. METHODS 11 healthy controls (age 6-16years) and 11 patients with mild CF (age 8-16years, Forced Expiratory Volume (FEV1) percent predicted >70%) were recruited for this study. Nine CF patients had an FEV1>85%. Each subject was imaged via hyperpolarized 129Xe MRI, and the ventilation defect percentage (VDP) was measured. FEV1 and VDP were compared between the groups. RESULTS FEV1 for controls was 100.3%±8.5% (mean±sd) and for CF patients was 97.9%±16.0% (p=0.67). VDP was 6.4%±2.8% for controls and 18.3%±8.6% for CF (p<0.001). When considering the 9 CF patients with normal FEV1 (>85%), the mean FEV1 was 103.1%±12.3% (p=0.57 compared to controls) and VDP was 15.4%±6.3% (p=0.002). CONCLUSIONS Hyperpolarized 129Xe MRI demonstrated ventilation defects in CF patients with normal FEV1 and more effectively discriminated CF from controls than FEV1. Thus 129Xe may be a useful outcome measure to detect mild CF lung disease, to investigate regional lung function in pediatric lung diseases, and to follow disease progression.

Pulmonary MRI of neonates in the intensive care unit using 3D ultrashort echo time and a small footprint MRI system.

To determine the feasibility of pulmonary magnetic resonance imaging (MRI) of neonatal lung structures enabled by combining two novel technologies: first, a 3D radial ultrashort echo time (UTE) pulse sequence capable of high spatial resolution full‐chest imaging in nonsedated quiet‐breathing neonates; and second, a unique, small‐footprint 1.5T MRI scanner design adapted for neonatal imaging and installed within the neonatal intensive care unit (NICU).

Quantification of neonatal lung parenchymal density via ultrashort echo time MRI with comparison to CT

To demonstrate that ultrashort echo time (UTE) magnetic resonance imaging (MRI) can achieve computed tomography (CT)‐like quantification of lung parenchyma in free‐breathing, non‐sedated neonates. Because infant CTs are used sparingly, parenchymal disease evaluation via UTE MRI has potential for translational impact.

Newer Imaging Techniques for Bronchopulmonary Dysplasia

Imaging has played a vital role in the clinical assessment of bronchopulmonary dysplasia (BPD) since its first recognition. In this review, how chest radiograph, computerized tomography (CT), nuclear medicine, and MRI have contributed to the understanding of BPD pathology and how emerging advancements in these methods, including low-dose and quantitative CT, sophisticated proton and hyperpolarized-gas MRI, influence the future of BPD imaging are discussed.

Evaluation of Neonatal Lung Volume Growth by Pulmonary Magnetic Resonance Imaging in Patients with Congenital Diaphragmatic Hernia

Objective To evaluate postnatal lung volume in infants with congenital diaphragmatic hernia (CDH) and determine if a compensatory increase in lung volume occurs during the postnatal period. Study design Using a novel pulmonary magnetic resonance imaging method for imaging neonatal lungs, the postnatal lung volumes in infants with CDH were determined and compared with prenatal lung volumes obtained via late gestation magnetic resonance imaging. Results Infants with left‐sided CDH (2 mild, 9 moderate, and 1 severe) were evaluated. The total lung volume increased in all infants, with the contralateral lung increasing faster than the ipsilateral lung (mean ± SD: 4.9 ± 3.0 mL/week vs 3.4 ± 2.1 mL/week, P = .005). In contrast to prenatal studies, the volume of lungs of infants with more severe CDH grew faster than the lungs of infants with more mild CDH (Spearmans &rgr;=‐0.086, P = .01). Although the contralateral lung volume grew faster in both mild and moderate groups, the majority of total lung volume growth in moderate CDH came from increased volume of the ipsilateral lung (42% of total lung volume increase in the moderate group vs 32% of total lung volume increase in the mild group, P = .09). Analysis of multiple clinical variables suggests that increased weight gain was associated with increased compensatory ipsilateral lung volume growth (&rgr; = 0.57, P = .05). Conclusions These results suggest a potential for postnatal catch‐up growth in infants with pulmonary hypoplasia and suggest that weight gain may increase the volume growth of the more severely affected lung.

Neonatal Pulmonary MRI of Bronchopulmonary Dysplasia Predicts Short-term Clinical Outcomes

Rationale: Bronchopulmonary dysplasia (BPD) is a serious neonatal pulmonary condition associated with premature birth, but the underlying parenchymal disease and trajectory are poorly characterized. The current National Institute of Child Health and Human Development (NICHD)/NHLBI definition of BPD severity is based on degree of prematurity and extent of oxygen requirement. However, no clear link exists between initial diagnosis and clinical outcomes. Objectives: We hypothesized that magnetic resonance imaging (MRI) of structural parenchymal abnormalities will correlate with NICHD‐defined BPD disease severity and predict short‐term respiratory outcomes. Methods: A total of 42 neonates (20 severe BPD, 6 moderate, 7 mild, 9 non‐BPD control subjects; 40 ± 3‐wk postmenstrual age) underwent quiet‐breathing structural pulmonary MRI (ultrashort echo time and gradient echo) in a neonatal ICU‐sited, neonatal‐sized 1.5 T scanner, without sedation or respiratory support unless already clinically prescribed. Disease severity was scored independently by two radiologists. Mean scores were compared with clinical severity and short‐term respiratory outcomes. Outcomes were predicted using univariate and multivariable models, including clinical data and scores. Measurements and Main Results: MRI scores significantly correlated with severities and predicted respiratory support at neonatal ICU discharge (P < 0.0001). In multivariable models, MRI scores were by far the strongest predictor of respiratory support duration over clinical data, including birth weight and gestational age. Notably, NICHD severity level was not predictive of discharge support. Conclusions: Quiet‐breathing neonatal pulmonary MRI can independently assess structural abnormalities of BPD, describe disease severity, and predict short‐term outcomes more accurately than any individual standard clinical measure. Importantly, this nonionizing technique can be implemented to phenotype disease, and has potential to serially assess efficacy of individualized therapies.

Quantitative CT scans of lung parenchymal pathology in premature infants ages 0-6 years

Bronchopulmonary dysplasia (BPD) is a common, heterogeneous disease in premature infants. We hypothesized that quantitative CT techniques could assess lung parenchymal heterogeneity in BPD patients across a broad age range and demonstrate how pathologies change over time.