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.

3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:992-1000.

Intrastriatal injection of 3-nitrotyrosine, which is a biomarker for nitrating oxidants, provokes dopaminergic neuronal death in rats by unknown mechanisms. Herein, we show that extracellular 3-nitrotyrosine is transported via the L-aromatic amino acid transporter in nondopaminergic NT2 cells, whereas in dopaminergic PC12 cells, it is transported by both the l-aromatic amino acid and the dopamine transporters. In both cell lines, 3-nitrotyrosine is a substrate for tyrosine tubulin ligase, resulting in its incorporation into the C terminus of ␣-tubulin. In NT2 cells, incorporation of 3-nitrotyrosine into ␣-tubulin induces a progressive, reversible reorganization of the microtubule architecture. In PC12 cells, 3-nitrotyrosine decreases intracellular dopamine levels and is metabolized by the concerted action of the aromatic amino acid decarboxylase and monoamine oxidase. Intracellular levels of 133 mol of 3-nitrotyrosine per mole of tyrosine did not alter NT2 viability but induced PC12 apoptosis. The cell death was reversed by caspases and aromatic amino acid decarboxylase and monoamine oxidase inhibitors. 3-Nitrotyrosine induced loss of tyrosine hydroxylase-positive primary rat neurons, which was also prevented by an aromatic amino acid decarboxylase inhibitor. These findings provide a novel mechanism by which products generated by reactive nitrogen species induce dopaminergic neuron death and thus may contribute to the selective neurodegeneration in Parkinson's disease.

Rationale: Patients with bronchopulmonary dysplasia (BPD)associated pulmonary hypertension (PH) have increased morbidity and mortality. Noninvasive assessment relies on echocardiograms (echos), which are technically challenging in this population. Improved assessment could augment decisions regarding PH therapies.Objectives: We hypothesized that neonatal cardiac magnetic resonance imaging (MRI) will correlate with BPD severity and predict short-term clinical outcomes, including need for PH therapies for infants with BPD.Methods: A total of 52 infants (31 severe BPD, 9 moderate BPD, and 12 with either mild or no BPD) were imaged between 39 and 47 weeks postmenstrual age on a neonatal-sized, neonatal ICU-sited 1.5-T magnetic resonance (MR) scanner. MR left ventricular eccentricity index (EI), main pulmonary artery-to-aorta (PA/AO) diameter ratio, and pulmonary arterial blood flow were determined. Echos obtained for clinical indications were reviewed. MRI and echo indices were compared with BPD severity and clinical outcomes, including length of stay (LOS), duration of respiratory support, respiratory support at discharge, and PH therapy.Measurements and Main Results: PA/AO ratio increased with BPD severity. Increased PA/AO ratio, MR-EI, and echo-EIs were associated with increased LOS and duration of respiratory support. No correlation was seen between pulmonary arterial blood flow and BPD outcomes. Controlling for gestational age, birth weight, and BPD severity, MR-EI was associated with LOS and duration of respiratory support. Increased PA/AO ratio and MR-EI were associated with PH therapy during hospitalization and at discharge.Conclusions: MRI can provide important image-based measures of cardiac morphology that relate to disease severity and clinical outcomes in neonates with BPD.

Cystic fibrosis (CF) is the most common life-shortening autosomal recessive disorder in the Caucasian population and occurs in many other ethnicities worldwide. The daily treatment burden is substantial for CF patients even when they are well, with numerous pharmacologic and physical therapies targeting lung disease requiring the greatest time commitment. CF treatments continue to advance with greater understanding of factors influencing long-term morbidity and mortality. In recent years, in-depth understanding of genetic and protein structure-function relationships has led to the introduction of targeted therapies for patients with specific CF genotypes. With these advances, CF has become a model of personalized or precision medicine. The near future will see greater access to targeted therapies for most patients carrying common mutations, which will mandate individualized bench-to-bedside methodologies for those with rare genotypes.

Opacities, lucencies, and overall heterogeneity of lungs via quantitative CT can distinguish BPD patients from healthy controls, and these abnormalities decrease with age across BPD patients. Defining BPD severity by clinical outcomes such as respiratory support at several time points (vs a single time point, per current guidelines) may be meaningful.

Background Neuroendocrine cell hyperplasia of infancy (NEHI) is a rare pediatric interstitial lung disease (ILD). Distinct chest computed tomography (CT) define its radiographic appearance—specifically, ground‐glass (GG) opacities most prominent in the right middle lobe (RML) and lingula. We sought to quantitatively validate this description and correlate radiologic findings with clinical presentation. Methods Twenty‐one children with NEHI were identified retrospectively, alongside 10 age‐matched controls without lung disease. Clinical histories were reviewed for NEHI subjects. Semiautomated image analysis was used to measure lung volume and density. A patient‐specific Hounsfield unit threshold defining GG was developed to quantify GG and assess its distribution in each subject. Results NEHI subjects had more GG than controls (37.9 ± 11.3% vs 14.0 ± 2.7%, P < 0.0001). The proportion of GG in the RML and lingula was greater in NEHI patients compared to controls (1.43 ± 0.37 vs 0.45 ± 0.21, P < 0.0001). GG preferentially involved the RML and lingula in 20/21 NEHI subjects. There was more GG distribution in NEHI subjects who were prescribed continuous oxygen compared with those using only nocturnal oxygen (45.7 ± 8.9% vs 29.3 ± 6.1%, P = 0.003). Conclusions We confirm the previously reported finding that most patients with childhood ILD and a distinctive pattern of GG distribution on CT scan are likely to have NEHI. The amount of GG may be a biomarker for severity of respiratory disease.

The ability of lung imaging to phenotype patients, determine prognosis, and predict response to treatment is expanding in clinical and translational research. The purpose of this perspective is to describe current imaging modalities that might be useful clinical tools in patients with asthma and other lung disorders and to explore some of the new developments in imaging modalities of the lung. These imaging modalities include chest radiography, computed tomography, lung magnetic resonance imaging, electrical impedance tomography, bronchoscopy, and others.