Neonatal Pulmonary Magnetic Resonance Imaging of Bronchopulmonary Dysplasia Predicts Short-Term Clinical Outcomes

Abstract

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.

Keywords: bronchopulmonary dysplasia; magnetic resonance imaging; neonatal lung disease; outcome prediction modeling; prematurity.

Figure 1.

Representative axial gradient echo (GRE) and ultrashort echo time (UTE) magnetic resonance imaging (MRI) demonstrating the range of bronchopulmonary dysplasia (BPD) severity. The level of respiratory support at neonatal ICU discharge and MRI scores are provided for each subject. Owing to its relatively short TE value, the UTE sequence can visualize hypodense tissue with intensity above the noise floor, whereas, in the same tissue, the GRE image is reconstructed with intensity near that of noise, even when non-zero density is present and apparent on UTE (for example, in the deceased severe BPD case at far right). In this way, UTE contrast weighting yields density-like intensities between various pulmonary tissues. On the other hand, with its relatively long TE value, the GRE sequence can yield improved contrast between fibrotic/interstitial/soft tissues and normal/hypodense parenchymal tissues, even though it does not represent accurate density measures of tissue with rapid effective transverse relaxation time decay.

Figure 2.

Correlation between magnetic resonance imaging (MRI) score and bronchopulmonary dysplasia (BPD) disease severity (National Institute of Child Health and Human Development [NICHD]/NHLBI definition). Notably, MRI scores of preterm subjects without BPD and term control subjects did not significantly differ, and there is a large standard deviation in MRI scores of patients with moderate and severe BPD, reflective of the broad range of outcomes observed in these severity groups. Plot elements are represented as follows: mean (circle); median (horizontal line); interquartile range (gray box); and 9–91% data (whiskers).

Figure 3.

Correlations of National Institute of Child Health and Human Development (NICHD) bronchopulmonary dysplasia (BPD) severity (mild, moderate, severe, and deceased due to lung disease) to magnetic resonance imaging (MRI) score (A; P < 0.0001), birth weight (B; P < 0.0001), and gestational age (C; P = 0.13) (ANOVA). Plot elements are represented as follows: mean (circle); median (horizontal line); interquartile range (gray box); and 9–91% data (whiskers).

Figure 4.

Correlations of respiratory support at neonatal ICU (NICU) discharge (room air, oxygen, ventilator, and deceased due to lung disease) to magnetic resonance imaging (MRI) score (A; P < 0.0001), birth weight (B; P = 0.007), and gestational age (C; P = 0.12) (ANOVA). Plot elements are represented as follows: mean (circle); median (horizontal line); interquartile range (gray box); and 9–91% data (whiskers). BPD = bronchopulmonary dysplasia.

Figure 5.

Correlations of respiratory support at 40-weeks postmenstrual age (PMA) (room air, oxygen/flow, and ventilator) to magnetic resonance imaging (MRI) score (A; P < 0.0001), birth weight (B; P < 0.0001), and gestational age (C; P = 0.04) (ANOVA). Plot elements are represented as follows: mean (circle); median (horizontal line); interquartile range (gray box); and 9–91% data (whiskers). BPD = bronchopulmonary dysplasia.