Connective tissue disease-associated lung disease in children.

Connective tissue diseases are a heterogeneous group of autoimmune diseases that can affect a variety of organ systems. Lung parenchymal involvement is an important contributor to morbidity and mortality in children with connective tissue disease. Connective tissue disease-associated lung disease in children often manifests as one of several radiologic-pathologic patterns of disease, with certain patterns having a propensity to occur in association with certain connective tissue diseases. In this article, key clinical, histopathologic, and computed tomography (CT) features of typical patterns of connective tissue disease-associated lung disease in children are reviewed, with an emphasis on radiologic-pathologic correlation, to improve recognition of these patterns of lung disease at CT and to empower the pediatric radiologist to more fully contribute to the care of pediatric patients with these conditions.

Endemic mycoses in children in North America: a review of radiologic findings.

Clinically significant endemic mycoses (fungal infections) in the United States (U.S.) include Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides immitis/posadasii. While the majority of infections go clinically unnoticed, symptomatic disease can occur in immunocompromised or hospitalized patients, and occasionally in immune-competent individuals. Clinical manifestations vary widely and their diagnosis may require fungal culture, making the rapid diagnosis a challenge. Imaging can be helpful in making a clinical diagnosis prior to laboratory confirmation, as well as assist in characterizing disease extent and severity. In this review, we discuss the three major endemic fungal infections that occur in the U.S., including mycology, epidemiology, clinical presentations, and typical imaging features with an emphasis on the pediatric population.

Childhood interstitial lung disease more prevalent in infancy: a practical review.

Childhood interstitial lung disease (chILD) is a heterogeneous group of uncommon, mostly chronic pediatric pulmonary disorders characterized by impaired gas exchange and diffuse abnormalities on imaging. A subset of these diseases occurs more frequently in infants and young children than in older children and teenagers. Some of these disorders occur in certain clinical scenarios and/or have typical imaging features that can help the radiologist recognize when to suggest a possible diagnosis and potentially spare a child a lung biopsy. We review the clinical, histopathological and computed tomography features of chILD more prevalent in infancy, including diffuse developmental disorders, growth abnormalities, specific conditions of undefined etiology, and surfactant dysfunction mutations and related disorders, to familiarize the pediatric radiologist with this group of disorders.

Pulmonary lymphoproliferative disorders in children: a practical review.

Pulmonary lymphoproliferative disorders represent an uncommon spectrum of proliferation of lymphoid tissue in the lung parenchyma ranging from benign hyperplasia to malignancy. They tend to occur in certain clinical situations and have typical imaging features that together can be used by the radiologist to suggest these entities as part of the differential diagnosis. We review key clinical, histopathological and computed tomography features of pulmonary lymphoproliferative disorders in children including follicular bronchiolitis, lymphoid interstitial pneumonia, granulomatous-lymphocytic interstitial lung disease, lymphoma and post-transplant lymphoproliferative disorder to familiarize the pediatric radiologist with this group of disorders.

Case 262: Isolated Left Ventricular Apical Hypoplasia.

History A 17-year-old white male adolescent was re-evaluated for a withheld cardiac condition initially detected during prenatal imaging at an outside institution. He had previously experienced intermittent episodes of shortness of breath, chest pain, and palpitations with exertion, but more recently he had been asymptomatic. He had no other comorbidities and no family history of congenital heart disease, cardiomyopathy, arrhythmia, or sudden cardiac death. At physical examination, the patient had a grade II/IV rumbling systolic murmur best heard at the left upper sternal border. Otherwise, cardiovascular and other physical examination findings were normal. An electrocardiogram showed sinus bradycardia and nonspecific T wave changes. A graded exercise stress test was normal. Cardiac MRI was performed without and with gadolinium-based contrast material. Multiple echocardiograms obtained since birth, cardiac MR images obtained 2 and 4 years earlier, and nongated CT images obtained with iodinated contrast material to evaluate trauma 8 years prior showed findings similar to those of the current examination. Prior chest radiographs (not shown) were normal, and angiography performed when the patient was 4 years old revealed normal coronary arteries.

Neonatal Pulmonary Magnetic Resonance Imaging 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.

Respiratory motion in children and young adults undergoing liver magnetic resonance imaging with intravenous gadoxetate disodium contrast material.

BACKGROUND: Gadoxetate disodium, utilized in hepatobiliary magnetic resonance (MR) imaging, has been associated with transient respiratory motion during the arterial phase in adults. OBJECTIVE: The purpose of this study was to determine the presence and severity of this phenomenon in children imaged awake versus under general anesthesia. MATERIALS AND METHODS: This retrospective cohort study was approved by the institutional review board; informed consent was waived. One hundred thirty exams of children ≤18 years old who underwent dynamic liver MR imaging with gadoxetate disodium between October 2010 and January 2018 were reviewed. Three pediatric radiologists scored respiratory motion artifacts on all imaging phases using a 5-point Likert scale. Differences in mean motion scores were assessed with analysis of variance and Tukey's multiple comparisons test, and multivariable regression was used to identify predictors of arterial phase motion in awake patients. RESULTS: One hundred thirty patients (50% [n=65] female; mean age: 9.8±3.7 years, 48.5% [n=63] awake) were included. There were significant differences in mean motion scores between phases in the awake cohort (P<0.0001) but not in the general anesthesia cohort (P=0.051). In the awake cohort, arterial phase motion score (mean: 3.52±0.83) was significantly higher than mean motion score in all other phases (P≤0.0003). There were no significant patient-specific predictors of arterial phase motion score in the awake cohort. CONCLUSION: Significantly increased arterial phase respiratory motion artifact in awake children undergoing dynamic liver MR imaging with gadoxetate disodium suggests that transient respiratory motion occurs in children. General anesthesia may suppress this phenomenon.

Case 262.

History A 17-year-old white male adolescent was re-evaluated for a withheld cardiac condition initially detected during prenatal imaging at an outside institution. He had previously experienced intermittent episodes of shortness of breath, chest pain, and palpitations with exertion, but more recently he had been asymptomatic. He had no other comorbidities and no family history of congenital heart disease, cardiomyopathy, arrhythmia, or sudden cardiac death. At physical examination, the patient had a grade II/IV rumbling systolic murmur best heard at the left upper sternal border. Otherwise, cardiovascular and other physical examination findings were normal. An electrocardiogram showed sinus bradycardia and nonspecific T wave changes. A graded exercise stress test was normal. Cardiac MRI was performed without and with gadolinium-based contrast material ( Figs 1 - 3 ). Multiple echocardiograms obtained since birth, cardiac MR images obtained 2 and 4 years earlier ( Fig 4 ), and nongated CT images obtained with iodinated contrast material to evaluate trauma 8 years prior ( Fig 5 ) showed findings similar to those of the current examination. Prior chest radiographs (not shown) were normal, and angiography performed when the patient was 4 years old revealed normal coronary arteries. [Figure: see text][Figure: see text][Figure: see text][Figure: see text][Figure: see text][Figure: see text][Figure: see text].

Hoverboards: spectrum of injury and association with an uncommon fracture.

BACKGROUND: Self-balancing electric scooters, commonly known as hoverboards, are a new and popular consumer item with recognized fall hazards. The spectrum of injuries associated with hoverboard use has not been studied. OBJECTIVE: The purpose of this study is to determine the spectrum of radiologically apparent injuries associated with hoverboard use. MATERIALS AND METHODS: We retrospectively reviewed all imaging studies interpreted at our institution for hoverboard-related injuries during an 8-month period. We recorded patient demographics and injury characteristics. RESULTS: Thirty-two of the 47 pediatric patients imaged for hoverboard-related injury had radiologically detectable injuries, all fractures. Fifty percent of these 32 patients were female and 50% were male, with a mean age of 12.4 years. There were 42 fractures total, all involving the appendicular skeleton, with 74% in the upper extremities and 26% in the lower extremities. Thirty-eight percent of the fractures involved the physis. A distinct injury pattern was seen in three patients who sustained open distal phalanx juxta-epiphyseal fractures. CONCLUSION: Most of the fractures sustained during hoverboard use are commonly seen in everyday pediatric radiology practice, with an overall pattern paralleling that reported in association with skateboard use. However an otherwise uncommon fracture, the distal phalanx juxta-epiphyseal fracture, was identified in association with hoverboard use, and this finding has important treatment implications including need for irrigation and debridement, antibiotic therapy, and potential surgical fixation.

Extensive heterotopic gastric mucosa of the small intestine: imaging with 99mTc-sodium pertechnetate SPECT/CT enterography.

Extensive heterotopic gastric mucosa of the small intestine is a rare, but potentially life-threatening condition characterized by multifocal or long-segment heterotopic gastric mucosa within the bowel lumen that is often associated with other anomalies including malrotation and annular pancreas. Although the imaging findings are characteristic, this entity may be unrecognized due to its unusual imaging appearance and rarity. CT or MR enterography and 99mTc-sodium pertechnetate scintigraphy can provide complementary information that enables specific diagnosis and accurate assessment of disease extent. We present a case of extensive heterotopic gastric mucosa of the small intestine imaged by simultaneous, combined 99mTc-sodium pertechnetate single photon-emission computed tomography (SPECT)/CT enterography to both familiarize the reader with the condition and describe an imaging strategy that enables specific diagnosis and assists with treatment planning.

Lung Ultrasound in Children With Systemic Juvenile Idiopathic Arthritis-Associated Interstitial Lung Disease.

OBJECTIVE: Systemic juvenile idiopathic arthritis (JIA) associated with lung disease (JIA-LD) is a potentially life threating complication in children with systemic JIA. Although high-resolution computed tomography (HRCT) is considered the gold standard imaging modality for evaluating interstitial lung disease (ILD), lung ultrasound (US) has shown utility for ILD screening in adults with connective tissue diseases at lower cost and without using ionizing radiation. The goals of this pilot study were to describe lung US features in children with known systemic JIA-LD and to assess the feasibility of lung US in this population. METHODS: Children age <18 years with systemic JIA-LD and healthy controls were enrolled. Lung US acquisition was performed at 14 lung positions. Demographic, clinical, and HRCT data were collected and reviewed. Feasibility was assessed through patient surveys. Lung US findings were qualitatively and semiquantitatively assessed and compared to HRCT findings. RESULTS: Lung US was performed in 9 children with systemic JIA-LD and 6 healthy controls and took 12 minutes on average to perform. Lung US findings in systemic JIA-LD included focal to diffuse pleural irregularity, granularity, and thickening, with associated scattered or coalesced B-lines, and subpleural consolidations. Lung US findings appeared to correspond to HRCT findings. CONCLUSION: Lung US in systemic JIA-LD reveals highly conspicuous abnormalities in the pleura and subpleura that appear to correlate with peripheral lung findings on HRCT. Lung US is a feasible imaging tool in children even from an early age. This study suggests a potential role of lung US in systemic JIA-LD screening, diagnosis, and/or prognostication.

Tracheostomy prediction model in neonatal bronchopulmonary dysplasia via lung and airway MRI.

RATIONALE: Clinical management of neonatal bronchopulmonary dysplasia (BPD) is often imprecise and can vary widely between different institutions and providers, due to limited objective measurements of disease pathology severity. There is critical need to improve guidance on the application and timing of interventional treatments, such as tracheostomy. OBJECTIVES: To generate an imaging-based clinical tool for early identification of those patients with BPD who are likely to require later tracheostomy and long-term mechanical ventilation. METHODS: We conducted a prospective cohort study of n = 61 infants (55 BPD, 6 preterm non-BPD). Magnetic resonance imaging (MRI) scores of lung parenchymal disease were used to create a binomial logistic regression model for predicting tracheostomy requirement. This model was further investigated using clinical variables and MRI-quantified tracheomalacia (TM). MEASUREMENTS AND MAIN RESULTS: A model for predicting tracheostomy requirement was created using MRI parenchymal score. This model had 89% accuracy, 100% positive predictive value (PPV), and 85% negative predictive value (NPV), compared with 84%, 60%, and 83%, respectively, when using only relevant clinical variables. In a subset of patients with airway MRI (n = 36), a model including lung and TM measurements had 83% accuracy, 92% PPV, and 78% NPV. CONCLUSIONS: MRI-based measurements of parenchymal disease and TM can be used to predict need for tracheostomy in infants with BPD, more accurately than clinical factors alone. This prediction model has strong potential as a clinical tool for physicians and families for early determination of tracheostomy requirement.

Machine Learning for Detection of Correct Peripherally Inserted Central Catheter Tip Position from Radiology Reports in Infants.

BACKGROUND: In critically ill infants, the position of a peripherally inserted central catheter (PICC) must be confirmed frequently, as the tip may move from its original position and run the risk of hyperosmolar vascular damage or extravasation into surrounding spaces. Automated detection of PICC tip position holds great promise for alerting bedside clinicians to noncentral PICCs. OBJECTIVES: This research seeks to use natural language processing (NLP) and supervised machine learning (ML) techniques to predict PICC tip position based primarily on text analysis of radiograph reports from infants with an upper extremity PICC. METHODS: Radiographs, containing a PICC line in infants under 6 months of age, were manually classified into 12 anatomical locations based on the radiologist's textual report of the PICC line's tip. After categorization, we performed a 70/30 train/test split and benchmarked the performance of seven different (neural network, support vector machine, the naïve Bayes, decision tree, random forest, AdaBoost, and K-nearest neighbors) supervised ML algorithms. After optimization, we calculated accuracy, precision, and recall of each algorithm's ability to correctly categorize the stated location of the PICC tip. RESULTS: A total of 17,337 radiographs met criteria for inclusion and were labeled manually. Interrater agreement was 99.1%. Support vector machines and neural networks yielded accuracies as high as 98% in identifying PICC tips in central versus noncentral position (binary outcome) and accuracies as high as 95% when attempting to categorize the individual anatomical location (12-category outcome). CONCLUSION: Our study shows that ML classifiers can automatically extract the anatomical location of PICC tips from radiology reports. Two ML classifiers, support vector machine (SVM) and a neural network, obtained top accuracies in both binary and multiple category predictions. Implementing these algorithms in a neonatal intensive care unit as a clinical decision support system may help clinicians address PICC line position.

Elevated lung volumes in neonates with bronchopulmonary dysplasia measured via MRI.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity defined by requirement for respiratory support at 36 weeks postmenstrual age (PMA), but structural sequelae like lung hyperinflation are often not quantified. Quiet-breathing, nonsedated magnetic resonance imaging (MRI) allows tomographic quantification of lung volumes and densities. We hypothesized that functional residual capacity (FRC) and intrapleural volume (IV) are increased in BPD and correlate with qualitative radiological scoring of hyperinflation. METHODS: Ultrashort echo time (UTE) MRI of 17 neonates (acquired at ~39 weeks PMA) were reconstructed at end-expiration and end-inspiration via the time course of the k0 point in k-space. Images were segmented to determine total lung, tidal, parenchymal tissue, and vascular tissue volumes. FRC was calculated by subtracting parenchymal and vascular tissue volumes from IV. Respiratory rate (RR) was calculated via the UTE respiratory waveform, yielding estimates of minute ventilation when combined with tidal volumes (TVs). Two radiologists scored hyperinflation on the MR images. RESULTS: IV at FRC increased in BPD: for control, mild, and severe (patients the median volumes were 32.8, 33.5, and 50.9 mL/kg, respectively. TV (medians: 2.21, 3.64, and 4.84 mL/kg) and minute ventilation (medians: 493, 750, and 991 mL/min) increased with increasing severity of BPD (despite decreasing RR, medians: 75.6, 63.0, and 56.1 breaths/min). FRC increased with increasing severity of BPD (39.3, 38.3, and 56.0 mL, respectively). Findings were consistent with increased hyperinflation scored by radiologists. CONCLUSIONS: This study demonstrates that UTE MRI can quantify hyperinflation in neonatal BPD and that lung volumes significantly increase with disease severity.

Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease: Characterization and Risk Factors.

OBJECTIVE: Systemic juvenile idiopathic arthritis (JIA) is associated with a recently recognized, albeit poorly defined and characterized, lung disease (LD). The objective of this study was to describe the clinical characteristics, risk factors, and histopathologic and immunologic features of this novel inflammatory LD associated with systemic JIA (designated SJIA-LD). METHODS: Clinical data collected since 2010 were abstracted from the medical records of patients with systemic JIA from the Cincinnati Children's Hospital Medical Center. Epidemiologic, cellular, biochemical, genomic, and transcriptional profiling analyses were performed. RESULTS: Eighteen patients with SJIA-LD were identified. Radiographic findings included diffuse ground-glass opacities, subpleural reticulation, interlobular septal thickening, and lymphadenopathy. Pathologic findings included patchy, but extensive, lymphoplasmacytic infiltrates and mixed features of pulmonary alveolar proteinosis (PAP) and endogenous lipoid pneumonia. Compared to systemic JIA patients without LD, those with SJIA-LD were younger at the diagnosis of systemic JIA (odds ratio [OR] 6.5, P = 0.007), more often had prior episodes of macrophage activation syndrome (MAS) (OR 14.5, P < 0.001), had a greater frequency of adverse reactions to biologic therapy (OR 13.6, P < 0.001), and had higher serum levels of interleukin-18 (IL-18) (median 27,612 pg/ml versus 5,413 pg/ml; P = 0.047). Patients with SJIA-LD lacked genetic, serologic, or functional evidence of granulocyte-macrophage colony-stimulating factor pathway dysfunction, a feature that is typical of familial or autoimmune PAP. Moreover, bronchoalveolar lavage (BAL) fluid from patients with SJIA-LD rarely demonstrated proteinaceous material and had less lipid-laden macrophages than that seen in patients with primary PAP (mean 10.5% in patients with SJIA-LD versus 66.1% in patients with primary PAP; P < 0.001). BAL fluid from patients with SJIA-LD contained elevated levels of IL-18 and the interferon-γ-induced chemokines CXCL9 and CXCL10. Transcriptional profiling of the lung tissue from patients with SJIA-LD identified up-regulated type II interferon and T cell activation networks. This signature was also present in SJIA-LD human lung tissue sections that lacked substantial histopathologic findings, suggesting that this activation signature may precede and drive the lung pathology in SJIA-LD. CONCLUSION: Pulmonary disease is increasingly detected in children with systemic JIA, particularly in association with MAS. This entity has distinct clinical and immunologic features and represents an uncharacterized inflammatory LD.