Lung



Lung


Mark C. Liszewski

Bernard F. Laya

Evan J. Zucker

Ricardo Restrepo

Edward Y. Lee



INTRODUCTION

Anomalies and diseases of the lung are among the most common indications that bring children to medical attention, and chest radiographs are among the most common studies interpreted by pediatric radiologists. There are myriad pediatric lung disorders, with different conditions tending to occur at different stages of development. In order to facilitate accurate diagnosis and recommend appropriate therapy, it is essential that radiologists be familiar with the full range of pediatric lung disorders.

In this chapter, a comprehensive description of lung disorders that may occur in infants and children is provided, with a focus on pathophysiology and corresponding imaging findings. First, a review of lung anatomy and embryology is presented as an essential framework. An overview of the currently available imaging modalities used to evaluate the pediatric lung—from common chest radiography to state-of-the art advanced lung MRI—is then presented. Finally, the spectrum of congenital and acquired pediatric lung disorders, including common conditions such as community-acquired pneumonia and rare disorders such as genetic syndromes, is discussed.


ANATOMY


Embryology


Lobar Anatomy

The pediatric lungs are smaller than the adult lungs, but there are no significant differences in their gross structural anatomy (Fig. 1.1). The right lung has three lobes (upper, middle, and lower), and the left lung has two lobes (upper and lower). The lobes are separated by two pleura-lined fissures on the right (the major and minor fissures) and one fissure on the left (the major fissure) (Figs. 1.1 and 1.2). The lobes are divided into 10 segments on the right and 8 segments on the left (Fig. 1.1). The right upper lobe is composed of apical, anterior, and posterior segments. The right middle lobe is composed of lateral and medial segments. The right lower lobe is composed of superior, medial basal, anterior basal, lateral basal, and posterior basal segments. The left upper lobe is composed of apicoposterior, anterior, superior lingular, and inferior lingular segments. The left lower lobe is composed of superior, anteromedial basal, posterior basal, and lateral basal segments.


Airways

Air is conducted to the lungs by a complex network of branching airways that transmit air to the respiratory bronchioles and alveoli. The large airways, including the trachea and bronchi, are discussed in detail in Section 2 (Large Airways) of this book. Bronchial branches contain cartilage within their walls to the level of the 11th generation, where they have a diameter of ˜1 mm (Fig. 1.3). The airways further branch into bronchioles, which are conducting airways that lack cartilage and extend to the level of the 16th generation (Fig. 1.3). The most distal purely conducting airway is the terminal bronchiole, which gives rise to the respiratory bronchioles (Fig. 1.4). Respiratory bronchioles are capable of gas exchange and also conduct air to the alveoli, which represent the primary site of gas exchange in the lungs.


Pulmonary Alveoli, Acini, and Secondary Pulmonary Lobules

Although the gross structural anatomy of the pediatric lung is identical to that of the adult lung, alveolar development is not complete at birth, and the number of alveoli continues to increase into early childhood. Most of the alveoli have formed by the age of 2 years, and alveolar development is complete by the age of 8 years. Alveoli range in size from

200 to 300 µm and therefore are not visible on routine radiologic imaging (Fig. 1.5). The pulmonary acinus and secondary pulmonary lobule are the smallest components of the lungs visible on radiologic imaging, and it is therefore essential that radiologists be familiar with their appearance in health and disease. The pulmonary acinus is defined as the portion of the lung that is distal to the terminal bronchiole and is composed of a respiratory bronchiole (or bronchioles) and the associated alveolar ducts and sacs. The pulmonary acinus is, therefore, the largest lung unit in which all the airways perform gas exchange.1 Each acinus contains ˜50 to 400 alveoli. The pulmonary acinus ranges in size from 6 to 10 mm in adolescence and adulthood and can be visualized on high-resolution CT (HRCT).2,3 The acinus is smaller in younger children, ranging in size from 1 to 2 mm in children under 1 year of age and therefore may not be visible.






FIGURE 1.1. Schematic diagram of lobar anatomy of the lungs.






FIGURE 1.2. Schematic diagram of the lung surrounded by the visceral and parietal pleura.






FIGURE 1.3. Schematic diagram of the lower airway branches. (Adapted from Nath J. A Short Course in Medical Terminology; 2018. Figure 8. © Wolters Kluwer, with permission.)






FIGURE 1.4. Schematic diagram of the terminal ventilation and perfusion units of the lung.






FIGURE 1.5. Schematic diagram of the pulmonary alveolus.

The secondary pulmonary lobule is the smallest unit of the lung that is separated by connective tissue septations, which are called interlobular septa (Fig. 1.6). Secondary pulmonary lobules are polyhedral in shape, have a mean diameter of 3 mm at birth, and reach a diameter of 13 to 20 mm in adulthood.2 Each secondary pulmonary lobule is composed of 3 to 24 acini, with their accompanying terminal bronchioles.4,5 Each of these terminal bronchioles arises from a central preterminal “lobular bronchiole,” which is located in the center of the secondary pulmonary lobule. Pulmonary arterial branches travel with the bronchioles in the center of the secondary pulmonary lobule. Pulmonary veins and lymphatics are located within the interlobular septa. Thickened interlobular septa may be visualized on CT outlining the polyhedral secondary pulmonary lobule or may be seen on chest radiographs as Kerley B lines (Fig. 1.7).

Collateral pathways of ventilation are structures that allow air, fluid, or other materials to pass between alveoli. Collateral pathways are interrupted by the pleura-lined fissures (unless a fissure is incomplete). Because pulmonary segments are not separated by fissures, collateral pathways connect the segments within a lobe. There are three types of collateral pathways: (1) pores of Kohn, (2) canals of Lambert, and (3) direct small airway anastomoses (Fig. 1.8). Pores of Kohn are apertures in the alveolar septa, which allow direct communication between alveoli.6 Canals of Lambert are epithelium-lined channels that connect distal bronchioles and adjacent alveoli. The collateral pathways are not fully formed in the infant and young child and do not mature until later childhood.






FIGURE 1.6. Schematic diagram of the normal secondary pulmonary lobule. (Reprinted from Elicker BM, Webb RW. Fundamentals of High-Resolution Lung CT: Common Findings, Common Patterns, Common Diseases, and Differential Diagnosis; 2013. Figure 1.11. © LWW/Wolters Kluwer, with permission.)







FIGURE 1.7. A 3-year-old girl with double outlet single right ventricle and mitral atresia, status post Norwood and Damus-Kaye-Stansel procedures. A: Axial lung window CT image shows smooth interlobular septal thickening (white arrows) due to interstitial edema. The interlobular septa outline the secondary pulmonary lobules (L). Lobular arteries (black arrow) are visualized in the centers of the secondary pulmonary lobules. B: Frontal chest radiograph demonstrates thickened interlobular septa as Kerley B lines (arrows). Also noted are tracheostomy, surgical clips, and median sternotomy wires.


Pulmonary Blood Supply and Drainage

The lung receives deoxygenated blood from the pulmonary arteries (Fig. 1.9). The pulmonary arteries travel with the bronchi and bronchioles, branching ˜28 times before reaching the capillary bed. Distal pulmonary arteries called lobular arteries can be visualized in the center of the secondary pulmonary lobule on HRCT, accompanying lobular bronchioles (Fig. 1.7A). Lobular arteries measure ˜1 mm in diameter by adulthood.4 Lobular arteries further branch into intralobular and acinar arteries within the secondary pulmonary lobule, accompanying preterminal and terminal bronchioles. Intralobular and acinar arteries range in size from 0.5 to 1 mm in diameter. Intralobular and, occasionally, acinar arteries can be visualized a few millimeters from the pleural surface.






FIGURE 1.8. Schematic diagram of collateral pathways of ventilation.

Pulmonary arteries continue to branch into smaller arterioles that are not visible on imaging studies, forming an extensive alveolar capillary network that participates in gas exchange and blood oxygenation. The very large number of alveolar capillaries form a high capacity, low resistance circuit, with a blood pressure six times lower than the systemic pressure. In this system, a large fraction of the alveolar capillaries are minimally perfused at rest. During times of demand, there is increased perfusion of these capillaries, allowing for increased blood oxygenation with minimal change in pulmonary arterial pressure. Pulmonary blood flow is mainly determined by cardiac output but is also affected by systemic pressure, pulmonary gas pressure, and gravity. Pulmonary arterial resistance is modulated by a process called hypoxic pulmonary vasoconstriction, in which smooth muscle within the pulmonary vessels constricts in direct response to hypoxia.7,8 This process shunts blood away from areas of under-ventilated lung (i.e., atelectasis) to more ventilated lung in order to help match ventilation and perfusion. In cases of global hypoxia in which a large number of pulmonary arterioles vasoconstrict, this process can contribute to pulmonary hypertension.







FIGURE 1.9. Schematic diagram of pulmonary blood supply and drainage.

Gas exchange occurs at the level of the alveolar capillaries and alveoli. The alveolus is only two cell layers thick, composed of type I respiratory epithelial cells and endothelial cells that are fused at their basal laminae. After leaving the alveolar capillaries, oxygenated blood flows into the pulmonary venules, which are located within the interlobular septa. Therefore, the veins travel separately from the bronchial arteries and bronchioles (which are located in the center of the secondary pulmonary lobule) until the level of the large pulmonary veins, which meet the main pulmonary arterial branches and bronchi at the lung hila.

The lungs receive a small amount of systemic oxygenated blood via two to four bronchial arteries, which primarily supply capillary networks within the lamina propria and submucosa of the trachea, mainstem bronchi, and pulmonary arteries9 (Fig. 1.10). Venous blood from the large airways primarily drains to systemic bronchial veins, which drain into the right side of the heart via the hemiazygos and azygos veins. Deeper in the lung, deoxygenated bronchial arteriolar blood is drained via the pulmonary venules, which empty into the left heart. The bronchial circulation normally only accounts for ˜0.5% to 1.5% of total cardiac output, and this right-to-left shunting is trivial in the healthy state.9 However, the bronchial circulation has potential to grow and expand throughout life, unlike the pulmonary arterial circulation, which does not grow after childhood. Many disease states that promote angiogenesis, including malignancy, inflammatory conditions, and congenital heart disease, cause bronchial artery proliferation that may lead to clinically significant shunting of deoxygenated blood to the left heart.


Pulmonary Lymphatic System

Many disease states affect the pulmonary lymphatics; therefore, an understanding of their location is essential (Fig. 1.11). The pulmonary lymphatic system is divided into two components: a deep plexus and a superficial plexus.9 The deep plexus travels with the pulmonary arteries and bronchi within the bronchovascular bundle and is therefore found in the center of the secondary pulmonary lobule. The superficial plexus is located within the interstitium of the interlobular septa where it travels with the pulmonary veins, as well as within the visceral pleura.4,9


Normal Development and Anatomy


Lung Development

Lung development has traditionally been divided into five main developmental phases, beginning in the 4th week of gestation and continuing after birth into early childhood. These phases include the: (1) embryonic, (2) pseudoglandular, (3) canalicular, (4) saccular, and (5) alveolar phases (Table 1.1 and Fig. 1.12).







FIGURE 1.10. Schematic diagram of thoracic bronchial arteries. (Reprinted from Moore KL, Dalley AF, Agur AMR. Clinically Oriented Anatomy. 7th ed.; 2013:117. © LWW/Wolters Kluwer, with permission.)






FIGURE 1.11. Schematic diagram of the pulmonary lymphatic system. TB, terminal bronchiole; RB, respiratory bronchiole; AD, alveolar duct; A, acinus. (Reprinted from Koeppen BM, Stanton BA. Berne and Levy Physiology. 6th ed.; 2008. © Mosby/Elsevier, with permission.)









TABLE 1.1 Prenatal Lung Development

























Embryonic period (up to 8 weeks)


Fetal period (8 to 38 weeks)


Organogenesis


Differentiation





Surfactant (25 to 38 weeks)


Embryonic (3 to 8 weeks)


Pseudoglandular (5 to 17 weeks)


Canalicular (16 to 26 weeks)


Saccular (24 to 38 weeks)


Alveolar (36 weeks to birth)




  • Formation of major airway



  • Formation of bronchial tree and portions of respiratory parenchyma



  • Birth of the acinus




  • Last generations of the lung periphery formed



  • Epithelial differentiation



  • Air-blood barrier formed




  • Expansion of air spaces



  • Surfactant detectable in amnionic fluid




  • Secondary septation



Embryonic Phase

Lung development begins early in the 4th week of gestation, when the floor of the foregut endoderm gives rise to the laryngotracheal groove. By the end of the 4th week, the caudal end of the laryngotracheal groove enlarges, forming the primordial lung, which is called the “lung bud” (Table 1.1 and Fig. 1.12). This lung bud divides into the right and left bronchial buds, beginning the embryonic phase of lung development.10 During the embryonic phase, the bronchial buds elongate and begin to extend caudally. The right bronchial bud is larger and directed more caudally than the left bronchial bud, which is directed more laterally. These typical differences in orientation between the right and left mainstem bronchi are, therefore, established in the very first stages of lung development. The bronchial buds divide as they elongate. The larger right bronchial bud divides into three branches and the smaller left bronchial bud divides into two branches by approximately day 39. These branches further divide by the end of the embryonic phase to form the pulmonary segments.

The bronchial buds are surrounded by lung mesenchyme, which is derived from splanchnic mesoderm. At the beginning of the embryonic stage, this mesenchyme lacks developed vascular structures. Vascular precursors present within the epithelium of the lung bud at the earliest phases of the embryonic stage undergo a process of vasculogenesis throughout the embryonic phase, and by the end of this phase, a vascular plexus has formed around the respiratory epithelium.11






FIGURE 1.12. Five phases of lung development. (Reprinted from Rackley CR, Stripp BR. Building and maintaining the epithelium of the lung. J Clin Invest. 2012;122(8):2724-2730. © American Society for Clinical Investigation, with permission.)


Pseudoglandular Phase

The pseudoglandular phase occurs between weeks 5 and 17 of gestation. During this phase, the pulmonary segmental branches progress through ˜20 branching generations and form the entire air-conducting portion of the lung to the level of the terminal bronchioles (Table 1.1 and Fig. 1.12). Proximal epithelial cells begin as undifferentiated columnar cells, and by the end of this phase, have differentiated into ciliated, goblet, and neuroendocrine cells. In the more distal portions of the terminal bronchioles, the epithelium is composed of cuboidal columnar cells, which form the precursors of alveolar type II cells by the end of the pseudoglandular phase. Epithelial cells begin to produce fetal lung liquid. The pulmonary vasculature continues to develop in tandem with the airway epithelium, and pulmonary venous endothelial cells give rise to pulmonary lymphatics.12


Canalicular Phase

The canalicular phase occurs between weeks 17 and 28 of gestation. During this stage, the respiratory portion of the lung begins to develop, forming respiratory bronchioles, alveolar ducts, and alveolar saccules (Table 1.1 and Fig. 1.12). The type II pneumocytes begin to contain surfactant-associated proteins and phospholipids, although do not yet secrete it. The first type I pneumocytes begin to differentiate from type II pneumocytes. There is extensive proliferation of the vasculature, leading to formation of a large capillary network and the primordial air-blood barrier. This primordial air-blood
barrier makes survival outside the uterus feasible by the end of this phase. However, capability for gas exchange remains quite immature, and survival of extremely premature infants with underdeveloped lung function depends on neonatal intensive care with surfactant replacement therapy. Largely owing to pulmonary disease, survival rates for preterm infants born at 23, 24, and 25 weeks of gestational age are low at 11%, 26%, and 44%, respectively.13


Saccular Phase

The saccular phase occurs during weeks 29 through 36 of gestation (Table 1.1 and Fig. 1.12). The sacculi that began to form in the canalicular phase proliferate and more type I pneumocytes differentiate, creating a larger surface area for gas exchange. The sacculi are surrounded by primary septa, which still contain a double layer of capillaries. The basal lamina of the distal respiratory epithelium fuses with the basal lamina of the alveolar capillary endothelium at this stage, allowing for faster diffusion of oxygen. Type II pneumocytes begin to produce increased amounts of surfactant phospholipids, which can be detected in the amniotic fluid14; nonetheless, children born during this phase often have insufficient surfactant production and suffer from respiratory distress syndrome. Survival rates for these infants have improved with the use of surfactant replacement therapy.


Alveolar Phase

The alveolar phase is the final stage of lung development, lasting from week 36 of gestation to 18 months of age (Table 1.1 and Fig. 1.12). During this phase, more sacculi form, the primary septa thin, the double capillary networks fuse, and secondary septations form millions of alveoli. This process continues after birth, with ˜50 million alveoli present in the neonatal period and 300 million present in adulthood. Extensive vascular growth occurs in tandem with the growth of the airway epithelium, providing the large expanse of alveolar and capillary surface area required to achieve sufficient gas exchange.15


Pulmonary Vascular Development

The pulmonary vasculature develops in tandem with the lung parenchyma, beginning during the embryonic phase. The truncus arteriosus divides into the pulmonary trunk and aorta at 8 weeks of gestation.16 Pulmonary arch arteries, which are derived from the 6th branchial arch arteries, connect to the pulmonary trunk. Vascular precursors within the epithelium of the lung bud undergo a process of vasculogenesis and form an extensive plexus around the respiratory epithelium.11 Preacinar vascular branching is established by 20 weeks of gestation, and intraacinar arteries continue to develop through the alveolar phase. Pulmonary veins arise within the mesenchyme separately from the arteries, eventually residing within the interlobular septa and connecting to the left atrium.17

The fetal lung is unique among organs because it does not begin functioning until birth. The lung does not participate in oxygenation during fetal life and does not receive the full cardiac output that it requires after birth. The majority of fetal cardiac output does not reach the lungs during fetal life. Blood bypasses the lungs via two right-to-left shunts: the foramen ovale and ductus arteriosus (DA). At birth, flow of oxygenated blood from the placenta stops when the umbilical cord is clamped, and the circulation pattern must rapidly transform to facilitate alveolar oxygenation. A rapid fall in pulmonary vascular resistance (PVR) at birth, caused by lung inflation and increased alveolar oxygen tension, is the key to this transition. This drop in PVR causes an 8- to 10-fold increase in pulmonary blood flow, resulting in increased left atrial pressures that functionally close the one-way valve of the foramen ovale.15 As a direct response to increased oxygen tension and the withdrawal of maternal prostaglandins, smooth muscle within the DA contracts in order to close it within the first 1 to 2 days of life.18

Because the principal trigger for this dramatic transition in blood flow is the drop in PVR that occurs at birth, conditions that result in elevated PVR can lead to persistent pulmonary hypertension of the newborn (PPHN), which causes right-toleft shunting and severe hypoxemia. PPHN is most frequently caused by underlying respiratory diseases, such as surfactant deficiency disorder (SDD), infection, meconium aspiration, or perinatal stressors including hypoglycemia and asphyxia. Less frequently, it is caused by an underlying disorder of the pulmonary vasculature, as in congenital diaphragmatic hernia or idiopathic PPHN, in which there is normal lung parenchyma with remodeled pulmonary vasculature.


Fetal Lung Fluid

The fetal lung and airways are filled with fluid until birth. Fetal lung fluid is made by respiratory epithelial cells, with production reaching ˜5 mL/kg/h near the end of gestation.19 The composition of fetal lung fluid differs from the composition of amniotic fluid, although a small amount of intermixing of fetal lung and amniotic fluid allows for assessment of lung maturation by amniotic fluid sampling.20 Clearance of fetal lung fluid after birth is essential for normal gas exchange in the newborn. Fetal lung liquid production begins to decrease in the days before delivery, and it is normally cleared by the pulmonary lymphatics and vasculature during and immediately after labor.21 In cases of cesarean section and precipitous labor, the fluid may not fully be cleared by the time of birth, and retained fetal lung fluid may cause transient respiratory distress.


Surfactant

Surfactant is a substance composed of phospholipids, proteins, neutral lipids, and cholesterol that is present in all mammalian lungs and is essential to lung function.21 Surfactant is produced by type II pneumocytes, which secrete it into the alveoli. The principal function of surfactant is to reduce surface tension within the alveoli in order to facilitate uniform alveolar expansion.22,23

Surfactant can first be detected within the lamellar bodies of the type II pneumocytes between 20 and 24 weeks of gestation.23 Lung maturity can be assessed by testing for surfactant components within the amniotic fluid. Before
35 weeks, the lung produces surfactant in smaller amounts than at term, and this surfactant is more susceptible to inactivation.24 By 35 weeks, the amount of surfactant is increased and the chemical composition is mature, containing more saturated phosphatidylcholine, phosphatidylglycerol, and surface proteins, and less phosphatidylinositol.21 The process of surfactant maturation can be slowed by insulin and can be accelerated by glucocorticoids and thyroid hormone. This hormone-mediated acceleration of surfactant maturation can be manipulated clinically, and mothers are routinely given glucocorticoids (e.g., betamethasone) 24 to 48 hours prior to preterm delivery. This reduces the incidence of the most significant complication of surfactant deficiency in preterm infants, SDD. When a preterm child is born with SDD, exogenous surfactant can be administered via an endotracheal tube to supplement the small amount of endogenous premature surfactant that is being produced. Although premature birth is the most common clinical scenario in which surfactant deficiency is seen, rare genetic mutations can also be causal. These include mutations in surfactant proteins (SPs) SP-B and SP-C as well as the intracellular transporter ABCA3.21

Surfactant production must be balanced with continuous clearance; otherwise, accumulation of excessive surfactant can interfere with oxygenation. Surfactant is constantly being recycled through endocytosis and resecretion by type II pneumocytes, and through phagocytosis and catabolism by macrophages.21 In certain disease states, disruption of this process can result in pulmonary alveolar proteinosis (PAP), a condition in which large amounts of surfactant collect within the lung and interfere with normal oxygenation. This rare condition may be caused by a mutation in granulocyte-macrophage colony-stimulating factor (GM-CSF) or its receptor, or by autoantibodies that inactivate GM-CSF.23






FIGURE 1.13. Schematic diagram of the locations of common accessory fissures. Coronal (A) and sagittal (B) diagrams of common accessory fissures. 1, right major fissure; 2, left major fissure; 3, right minor fissure; 4, azygos fissure; 5, left minor (horizontal) fissure; 6, right superior accessory fissure; 7, left superior accessory fissure; 8, right inferior accessory fissure; 9, left inferior accessory fissure. (Reprinted from Winant AJ, Cho J, Alyfei T, Lee EY. Pediatric thoracic anatomic variants: what radiologists need to know. Radiol Clin North Am. 2017;55(4):684. © Elsevier, with permission.)


Anatomic Variants

Division of the lobes of the lungs by accessory pleural fissures creates so-called “accessory lobes.” Approximately 30% to 32% of patients have at least one accessory fissure25,26,27 (Fig. 1.13). Accessory fissures include the inferior accessory fissure (12% to 21%), left minor fissure (8% to 9%), and superior accessory fissure (1% to 5%), as well as unnamed fissures between the medial and lateral segments of the right middle lobe (2% to 5%), the superior and inferior segments of the lingula (1% to 5%), and the anterobasal and lateral basal lower lobe segments (2.5% to 3%).25,26

The most common accessory fissure is the inferior accessory fissure, which surrounds the medial basal segment of the lower lobe (Fig. 1.14). The resulting accessory lobe is referred to as the inferior accessory, cardiac, retrocardiac, or infracardiac lobe and is analogous to the cardiac lobe that is present in many other mammals.28 The left minor fissure separates the lingula from the rest of the left upper lobe.28 The superior accessory fissure separates the superior segment of the lower lobe from the rest of the lower lobe, and the resulting accessory lobe is sometimes referred to as the posterior or dorsal lobe.28 The azygos fissure, which encloses the so-called azygos lobe, differs from the other accessory fissures: the azygos fissure forms when an anomalous, laterally coursing azygos vein bisects the right upper lobe, creating a reflection of both the parietal and visceral pleurae (Fig. 1.15). In contradistinction, the other fissures are composed of only visceral pleura.







FIGURE 1.14. A 6-year-old boy with an inferior accessory fissure detected on a CT obtained for abdominal pain. Axial lung window CT image shows normal bilateral major fissures (black arrows) and an inferior accessory fissure (white arrow).

Heterotaxy syndromes and situs inversus can result in abnormal lobar anatomy. Situs inversus totalis is the simplest example, in which the anatomic relationships between the left and right sides of the body (including the lungs) are transposed. In heterotaxy syndromes, both lungs may have a right-sided three-lobe configuration (right isomerism), or a left-sided two-lobe configuration (left isomerism). Left isomerism is associated with polysplenia, whereas right isomerism is associated with asplenia.29


IMAGING TECHNIQUES

Several different imaging modalities are utilized in the evaluation of the pediatric lung disorders, including radiography, ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine studies. Unlike other organs, the lung is largely filled with air, which provides both benefits and challenges. Air within the lungs and airways provides excellent inherent contrast with the adjacent soft tissues, which is particularly useful in radiography and CT. However, air within the lungs presents challenges in US, as it is unable to conduct sound waves. Air-filled lung is also a proton-poor environment, which results in significant limitations on MRI. Respiratory and cardiac motion also present unique challenges to imaging with motion-sensitive modalities such as MRI.






FIGURE 1.15. A 7-year-old boy with an azygos fissure. A: Frontal chest radiograph shows an azygos fissure (arrow) and lobe. B: Axial lung window CT image demonstrates an azygos fissure (arrow) and azygos lobe (asterisk). T, Trachea.

As imaging technology advances, it is important for radiologists and other clinicians to work together to identify and tailor imaging studies to each patient in order to find the most appropriate test that results in the least potential harm to the patient. This may include utilizing modalities that expose the patient to no or minimal ionizing radiation and adopting strategies to reduce the need for sedation whenever feasible. This section discusses the indications, contraindications, strengths, and weaknesses of each imaging modality in evaluating disorders of the pediatric lungs.


Radiography

Chest radiography is the first-line imaging test for virtually all disorders of the chest in the pediatric population. Chest radiographs are generated by projecting x-rays through the chest to create a two-dimensional image. Chest radiographs take advantage of the inherent contrast between the air-containing lung and the adjacent soft tissues. Although chest radiographs do not provide the same level of anatomic detail as cross-sectional modalities such as CT or MRI, they serve as an indispensable tool in the evaluation of the lungs.


Radiographs are relatively inexpensive and thus provide a cost-effective method suited to evaluation of many diseases of the lungs. Chest radiographs require a relatively low dose of ionizing radiation, about 0.01 to 0.02 mSv for a standard posteroanterior (PA) chest radiograph.30,31 There are currently no absolute contraindications to chest radiography. The transition from screen-film systems to computed and digital radiography systems has facilitated technical advances in image quality.32

In young children who cannot follow directions, motion artifact is a common problem. Motion artifact can be reduced through gentle immobilization of patients or image acquisition during quiet breathing.33 Although radiation doses are low in chest radiography, it is essential for radiologists and technologists to reduce unnecessary exposure through appropriate shielding.34,35 The transition from screen-film systems to computed and digital radiography has provided many benefits but does have the potential to increase patient radiation dose through a phenomenon called “dose creep.” Because it is much more difficult to recognize an overexposed radiograph on computed and digital systems that correct for image under- or overexposure, excessive radiation doses may go unnoticed. Standardized exposure indices must be adopted to reduce this risk.36,37

Standard chest radiographs consist of a frontal and lateral view. The frontal view is obtained in the anteroposterior (AP) projection in children younger than 5 and in the PA projection in children older than 5. Additional views may be obtained in certain clinical scenarios. For example, expiratory or lateral decubitus views may be obtained to assess for air trapping in cases of suspected airway obstruction.38,39,40 Lateral decubitus views may also be useful for distinguishing layering pleural fluid from loculated empyema, accentuating a small pneumothorax, or assessing shifting of an air-fluid level in a pulmonary abscess. In some cases, oblique views may be useful for evaluating questionable findings within the lung and can help to better define their relationships with adjacent structures.41


Ultrasound

Radiography, CT, and (increasingly) MRI are the most commonly utilized imaging modalities for diseases of the pediatric chest. US has received special attention as a useful tool for assessing selected pediatric lung disorders because it is portable, inexpensive, rapid, and performed without sedation. Physical properties of the lung and chest wall pose challenges to finding adequate acoustic windows. Air within the lungs and the bones of the rib cage cannot propagate sound waves. These physical properties make US unlikely to ever become a primary imaging modality for the lungs; however, it is likely to remain a useful complement to other modalities in a variety of scenarios in the pediatric population.42

The lungs of infants and young children are generally more amenable to US imaging than the lungs of adults. Young children’s ribs are less ossified than adults’, particularly the anterior costal cartilage, providing more optimal sonographic windows for viewing the lung parenchyma. In children, the relatively large thymus can also improve the sonographic window. High-quality US of the lungs may require flexibility and creativity. For example, smaller-footprint transducers may be needed to image through the smaller intercostal spaces of children. Lower-frequency transducers (<5 MHz) with better soft tissue penetration may be utilized in older children, whereas high-frequency transducers (7.5 to 15 MHz), which obtain higher-resolution images, are often preferable in younger children.

Even when an optimal sonographic window is achieved, evaluation of lung tissue deep to the peripheral surface is often quite limited due to shadowing from air within the lung. Therefore, US of the lung is most useful for evaluating abnormalities that extend to the periphery and displace air out of the lung. US may be useful for further characterization of findings that are first detected on chest radiographs.42,43,44 For example, complete opacification of one hemithorax on a chest radiograph may be due to pleural disease, a pulmonary parenchymal process, or both. Because the lung is not aerated in this scenario, US can be helpful to evaluate for pleural fluid, pulmonary parenchymal disease, and/or mass.42 Similarly, peripheral pulmonary masses can be evaluated with US to characterize solid and cystic components and internal blood flow utilizing color Doppler US imaging. Doppler US imaging can also be helpful when assessing anomalous vasculature, as is seen in pulmonary sequestration.42 Extralobar sequestration located below the diaphragm is often well visualized by US given the lack of overlying aerated lung. US can be useful for evaluating complicated pneumonia, with one series demonstrating similar performance of CT and US in detecting lung necrosis, pulmonary abscess, and loculated effusion.45

Because air within the lung causes shadowing that obscures underlying structures, most lung US is performed in conditions in which the lung is consolidated, collapsed, or replaced by a mass. However, recent research has shown some scenarios in which evaluation of US artifacts produced by aerated lung may be able to provide useful clinical information. As the sound beam interacts with the interlobular septa, it produces comet-tail artifacts, which are referred to as “B-lines.”46,47 These B-lines are increased in conditions that cause interlobular septal thickening, for instance interstitial edema caused by transient tachypnea of the newborn (TTN).48 Surfactant deficiency may cause multiple B-lines or a diffusely echogenic lung, and some studies suggest that US may be able to detect progression to chronic lung disease of infancy before radiography.42,49,50,51


Computed Tomography

Computed tomography (CT) is a highly useful tool for the evaluation of many diseases of the lungs. Although technical advances have reduced the amount of ionizing radiation utilized in routine CT of the pediatric thorax, the potential for radiation-induced cancer is a concern, particularly in children who are more radiosensitive than adults.52,53,54,55 Therefore, the first step in preparing all CT examinations should be a careful consideration of the indications and potential imaging
alternatives, which may involve less or no ionizing radiation. For example, US and MRI are being utilized with greater frequency to assess disorders of the lung and should be employed when possible. CT remains the preferred imaging modality for cross-sectional assessment of most pulmonary parenchymal disorders due to acoustic shadowing from osseous structures and aerated lung on US and issues related to motion artifact and signal dephasing on MRI. When CT is indicated, it is imperative to utilize optimized low-dose pediatric protocols, which decrease tube current or milliamperage (mA) and kilovoltage peak (kVp) based on patient size, ideally in conjunction with tube current modulation.52,56,57,58

Conventional step-and-shoot CT scanners first became widely available in the 1990s, and revolutionized the noninvasive evaluation of lung disorders. However, these early CT scanners required multiple breath-holds, were prone to artifacts from misregistration and motion, and required long scan times, which posed significant challenges when imaging children.59 These CT scanners have been essentially replaced by helical multidetector CT (MDCT) scanners, which are widely available and allow rapid imaging of the entire chest in one breath-hold. With these advances, sedation is usually not required in older children who can follow breathing instructions. Sedation is often still required in children <5 years of age, but conscious sedation can frequently be utilized as an alternative to general anesthesia.60,61

CT imaging parameters should be adjusted for each patient according to the as low as reasonably achievable (ALARA) principle in order to keep radiation dose as low as possible while maintaining diagnostic quality. Tube current should be carefully selected according to weight-based guidelines.62 A kVp of 80 kV should be utilized for patients <50 kg, and a kVp of 100 to 120 should be used in larger children or adults.61 Tube current and kVp may be further optimized using tube current modulation.57,58 Fast scan times of 1 second or less should be utilized to reduce motion artifact. In most scenarios, the field of view should cover the chest from the thoracic inlet to the diaphragm, although a larger field of view may be beneficial in certain scenarios. For example, the field of view may be extended to the level of the renal arteries to evaluate pulmonary sequestration, because the systemic arterial supply may arise from the abdominal aorta or celiac artery. The field of view may be extended to include the entire trachea in cases of pulmonary sling to evaluate for associated tracheal stenosis.61

Administration of intravenous contrast material is indicated in the majority of pediatric chest CT scans. Contrast is necessary for evaluation of vascular anatomy associated with congenital lung malformations, useful for evaluating enhancement patterns in cases of neoplasm, and helpful for evaluating mediastinal lymph nodes in cases of infection and malignancy. Lung parenchyma is generally well visualized without intravenous contrast, and a noncontrast CT examination may be preferred in cases in which evaluation of the mediastinum and vasculature is less important. Nonionic low-osmolar contrast is preferred, because it is less likely to induce side effects such as nausea and vomiting. The recommended contrast dose is usually 2 mL/kg, not to exceed 4 mL/kg or 125 mL.62 Mechanical injection is preferred to manual injection, given faster speed and greater homogeneity of contrast enhancement. Mechanical contrast injection should be performed via a 22-gauge or larger cannula within an antecubital vein. Contrast injection rates should be 1.5 to 2.5 mL/s for 22-gauge cannulas and 2.0 to 4.0 mL/s for 20-gauge cannulas. If pediatric patients have a smaller gauge intravenous cannula or a central venous catheter, then contrast should be injected manually.61,62

Modern MDCT scanners have the ability to generate thin section images of the entire lung, with greater spatial resolution and capability for routine generation of 3D and multiplanar reconstructions (MPRs). MDCT performed with thin collimation (<1 mm) produces high-resolution images with relatively prominent image noise that can be reconstructed into thicker sections (5 mm) with less image noise for routine image interpretation.41 The ability of MDCT to obtain continuous thin section CT images of the entire lung at a relatively low radiation dose has largely enabled replacement of classic HRCT technique that was developed in the 1980s, in which images with 1-mm slice thickness were obtained at 7- to 20-mm intervals.41 This technique may still be employed in selected cases, such as very-low-radiation dose follow-up CT for diffuse lung disorders including cystic fibrosis (CF) in infants and children who may require repeated CT imaging for assessment of disease progression or superimposed infectious processes.

Widespread use of MDCT has allowed MPR to become the norm in diagnostic imaging, with most centers routinely performing coronal and sagittal reconstructions on all diagnostic MDCT studies. MDCT has also allowed 3D reconstructions to become widely available. In order to create 3D reconstructions, thin section axial CT images must be reconstructed with at least 50% overlap. For example, 3-mm-thick sections can be reconstructed at 2-mm intervals, or 2-mm-thick sections can be reconstructed at 1-mm intervals. Alternatively, very thin collimation can be employed (0.5 to 1.0 mm) to create an isotropic data set that can be viewed and reconstructed in any plane. 3D volume rendering is often useful for displaying vascular or airway anatomy and depicting relationships among adjacent structures.


Magnetic Resonance Imaging

The physical properties of the lungs present challenges for MRI. Because the lungs are largely filled with air, the protonpoor environment of the chest provides low signal-to-noise ratios compared with other parts of the body. Cardiac and respiratory motion may present problems with motion artifact. The large amount of air within the chest also contributes to signal dephasing and susceptibility artifact, which can cause poor resolution. In addition to challenges related to image quality, MRI requires longer scan times than CT and more often necessitates use of sedation. Despite these challenges, recent technical advances, including parallel imaging, multichannel body-array coils, and optimized imaging protocols, have enabled use of MRI as an alternative to CT in
selected cases.63,64,65,66,67,68,69,70,71 Techniques utilizing inhaled hyperpolarized gases can increase signal within the lungs and improve image quality, although these techniques are still largely research based and not available in most clinical settings.72,73,74,75 Recently, Fourier decomposition pulmonary MRI, which is a noninvasive method for assessing ventilation and perfusion-related information, has been identified as a promising new MRI technique; however, its use is currently limited to research applications.76

There are several published protocol recommendations for basic MRI of the lungs.64,65,68,70,77,78 A basic and fundamental MRI protocol includes gradient recalled echo (GRE) localizer, coronal single-shot half-Fourier turbo spin echo (HASTE), axial 3D GRE (VIBE), coronal steady-state free precession (TrueFISP), and axial short tau inversion recovery (STIR) with optional enhanced 3D-GRE (VIBE).65,68 Sequences that are less prone to motion artifact, such as free-breathing periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER/BLADE), may be utilized in place of STIR in pediatric patients who cannot breath-hold. Although MRI has many limitations, recent investigations suggest that it may have a greater role in the evaluation of disorders of the lung parenchyma in the future. For example, Biederer et al., showed that pulmonary nodules larger than 3 to 4 mm can be detected on MRI.69 Others have shown MRI to be sensitive and specific in the evaluation of several conditions including infection, neoplasm, and interstitial lung disease.63,67 Although these results are promising, CT currently remains the preferred modality due to faster scan times and better spatial resolution.


Nuclear Medicine

For nuclear medicine studies, radiopharmaceutical agents are administered and their biodistributions are imaged. These studies often provide physiologic information that complements anatomic information attained from other radiologic studies. Nuclear medicine studies impart doses of ionizing radiation. In general, radiation doses from nuclear medicine studies are greater than doses from radiography but less than doses from CT. Nuclear medicine studies must follow the ALARA principle, and there has been much effort in recent years to set standards and recommendations for appropriate pediatric doses.79

Image acquisition times in nuclear medicine studies are longer than in radiography. Young pediatric patients may require immobilization, but sedation is only required in a small minority of cases since nuclear medicine studies are less susceptible to motion artifact than radiography, CT, or MRI. The most commonly used nuclear medicine studies for evaluation of the lung parenchyma are applied in oncologic imaging and include 111In-pentetreotide scintigraphy (Octreoscan) and 18F-fluorodeoxyglucose-positron emission tomography (FDGPET) imaging.

111In-pentetreotide is a somatostatin receptor-imaging agent, and its primary role in pediatric chest imaging is evaluation of carcinoid tumors. Octreoscan is more sensitive and accurate than enhanced CT alone and is therefore employed in initial staging and follow-up of pulmonary carcinoid tumor.80

In pediatric pulmonary imaging, FDG-PET is mainly used in the evaluation of metastatic disease but may also be utilized in rare cases of primary lung malignancy. The most common primary tumors evaluated with FDG-PET include lymphoma, rhabdomyosarcoma, osteosarcoma, and Ewing sarcoma. PET images are frequently performed along with low-dose CT, which is utilized for attenuation correction. PET and CT images are routinely fused for better anatomic localization and improved diagnostic performance.81

Due to the nature of the radiotracer, there are several considerations that must be taken into account before imaging with FDG. FDG is a glucose analog; therefore, metabolically active tissues that are utilizing glucose at the time of tracer administration demonstrate uptake. Pediatric patients must fast and not receive any form of glucose for a minimum of 4 hours prior to imaging, including intravenous fluids containing glucose. Patients should not perform any strenuous exercise the day before the scan in order to avoid excess FDG uptake by skeletal muscle. Pediatric patients are more likely than adult patients to have metabolically active brown fat, which takes up FDG and has the potential to simulate abnormal tissue.82 Brown fat uptake can be reduced by warming patients before and after radiotracer injection.83 In selected oncologic applications, FDG-PET has superior diagnostic performance compared to conventional imaging.84


SPECTRUM OF LUNG DISORDERS


Neonatal Lung Disorders

Respiratory distress due to various underlying lung disorders is commonly encountered in the neonatal intensive care setting. Familiarity with conditions that may affect the newborn lung is essential. Imaging findings and differential diagnoses in this young patient population are different than those seen in older children and adults. Prematurity-associated conditions include SDD and chronic lung disease of prematurity, while conditions affecting term newborns include TTN, meconium aspiration syndrome (MAS), and neonatal pneumonia. These conditions are currently diagnosed and monitored almost entirely with chest radiographs, and crosssectional imaging is rarely needed.


Surfactant Deficiency Disorder (Hyaline Membrane Disease)

SDD, also known as hyaline membrane disease or respiratory distress syndrome, is primarily a disorder of premature newborns and is the main cause of morbidity and mortality in this patient group. In 2011, 2.1 per 1,000 live births occurred before 27 weeks of gestation, 7.5 per 1,000 occurred at 27 through 31 weeks, and 17.3 per 1,000 occurred at 32 through 34 weeks.85 With the increased use of antenatal corticosteroids, exogenous surfactant, and improved mechanical ventilation techniques, survival rates have improved, although survival rates for extremely preterm neonates remains poor. In 2011, 0.7% born before 24 weeks, 31.2% born at 24 weeks,
59.1% born at 25 weeks, 75.3% born at 26 weeks, 93.6% born between 27 and 31 weeks, and 98.9% born between 32 and 34 weeks survived to discharge.85 SDD is twice as common in males and white patients.86

SDD occurs as a result of deficient surfactant production by immature type II pneumocytes in the preterm neonate. Surfactant reduces surface tension within alveoli, facilitating expansion during respiration. When surfactant is deficient, excessive alveolar collapse results in poor oxygenation. The surfactant-deficient lung produces eosinophilic hyaline membranes that line the respiratory bronchioles and acini and interfere with oxygenation. Hyaline membranes contain necrotic alveolar cells, fibrin, and plasma transudate and develop between 3 and 24 hours after birth. Hypoxia and respiratory acidosis trigger pulmonary arteriolar constriction, resulting in persistent pulmonary hypertension and right-to-left shunting across the patent DA, further exacerbating hypoxemia.87 At 36 to 48 hours of life, alveolar macrophages begin to clear the hyaline membranes and type II alveolar cells begin producing mature surfactant.

Treatment strategies for SDD consist of antenatal corticosteroids, exogenous surfactant administration, and supportive ventilation. Corticosteroids are administered to mothers prior to preterm delivery in order to accelerate fetal production of surfactant. At birth, exogenous surfactant is administered via an endotracheal tube as a liquid bolus and the child is turned from side to side in an attempt to distribute it uniformly throughout the lungs. Up to three or four additional doses may be administered in the first 48 hours of life.86 Infants and neonates are supported with mechanical ventilation using strategies aimed to reduce barotrauma, which has historically been a major cause of morbidity. For example, modern ventilators are triggered by the child’s spontaneous inhalations and exhalations. Alternatively, high-frequency oscillatory ventilation (HFOV), in which small tidal volumes are delivered at very high rates, is sometimes used. In patients on HFOV, projection of the diaphragm between the 8th and 10th posterior ribs on radiography indicates appropriate lung volumes.

The classic radiographic appearance of untreated SDD is diffuse granular pulmonary opacity or consolidation with air bronchograms and low lung volumes, due to acinar collapse and fluid in the alveoli from capillary leak (Fig. 1.16). Findings are typically present at birth but may not peak in severity until 12 to 24 hours of life.86 The classic radiographic appearance is rarely seen in modern practice due to the widespread use of exogenous surfactant. Surfactant is frequently administered immediately after birth, often before the first chest radiograph is obtained. Dinger et al., analyzed the chest radiographs of preterm neonates who were given surfactant and found that 38% demonstrated uniform improvement (Fig. 1.17), 35% had asymmetric improvement, 10% had no change, and 17% developed interstitial emphysema.88 Asymmetric improvement is thought to result from uneven distribution of administered exogenous surfactant within the lungs (Fig. 1.18). The asymmetric distribution may produce a radiographic appearance similar to neonatal pneumonia or meconium aspiration.86 When surfactant reaches the distal alveoli, it can cause rapid expansion of the acini, which produces small round lucencies on chest radiographs that may mimic interstitial emphysema.86 If this pattern is seen, it is essential to consider the patient’s clinical condition: patients typically decompensate in cases of pulmonary interstitial emphysema (PIE) but improve in cases of distal surfactant distribution.86






FIGURE 1.16. Male neonate born at 27 weeks of gestation who presented with respiratory distress due to surfactant deficiency disorder. Frontal chest radiograph shows diffuse granular opacities in both lungs with slightly decreased lung volumes.

Sudden increase in opacification of the lungs in patients with SDD may be due to atelectasis, pulmonary edema, or pulmonary hemorrhage. Atelectasis frequently results from changes in ventilator settings.86 Pulmonary edema may result from improved oxygenation after surfactant administration, which leads to decreased PVR and left-to-right shunting across the patent DA.86 Although the mechanism of pulmonary hemorrhage is unclear, it has been suggested that left-to-right shunting across the DA may lead to hemorrhagic pulmonary edema89 (Fig. 1.19). Neurogenic pulmonary edema may also occur in cases of large germinal matrix hemorrhage.

With the increased survival of very low-birth-weight (<1,500 g) and extremely low-birth-weight (<1,000 g) infants, a distinct radiographic pattern of lung disease has emerged. This pattern differs from the classic pattern of SDD seen in less severely premature infants. In profoundly premature infants, the chest radiograph may be normal or nearly normal in the first 2 days of life, with findings including minimal radiating perihilar opacity, diffuse fine granularity, normal lung volumes, and absent air bronchograms86,87,90 (Fig. 1.20). The biochemical profile of surfactant phospholipids in these patients is often normal, which may be related to accelerated surfactant maturation, a protective effect of intrauterine stress.90 The radiating perihilar opacities are thought to be produced by the immature thickened interstitium, and the
fine granularity is thought to correspond to excessive lung fluid. Patients with this pattern of disease do not fulfill clinical criteria for respiratory distress syndrome, and this condition has been termed “immature lung.”90 Despite the lack of chest radiographic findings, affected patients frequently have significant left-to-right shunts across the patent DA, sepsis, bradycardia, and apnea that frequently necessitates mechanical ventilation.87 At days 2 and 3 of life, the chest radiograph typically worsens, and there is development of coarse, irregularly distributed lung disease that frequently persists and evolves into a pattern of chronic lung disease.86,87






FIGURE 1.17. Male neonate born at 24 weeks of gestation who presented with respiratory distress due to surfactant deficiency disorder. A: Frontal chest radiograph shows diffuse opacities with air bronchograms in both lungs with slightly decreased lung volumes. The endotracheal tube tip is incidentally noted to be within the proximal right mainstem bronchus. B: Frontal chest radiograph obtained after administration of exogenous surfactant demonstrates uniform improvement in airspace opacities. The endotracheal tube tip is again noted to be within the proximal right mainstem bronchus.






FIGURE 1.18. Male neonate born at 25 weeks of gestation who presented with respiratory distress due to surfactant deficiency disorder, status post exogenous surfactant administration via a malpositioned endotracheal tube (ETT) placed in the proximal right mainstem bronchus. Frontal chest radiograph shows the ETT tip within the proximal right mainstem bronchus (white arrow), low lung volumes, and asymmetric granular opacities, which are greater on the left than the right. The umbilical vein catheter (black arrow) is malpositioned, with its tip located in the right atrium.

Air leak phenomena can occur in SDD due to the negative effects of mechanical ventilation on the immature lung. Manifestations include air dissecting into the pulmonary interstitium (PIE), pneumothorax, pneumomediastinum, and pneumoperitoneum. PIE is discussed in detail in a subsequent section.


Chronic Lung Disease of Infancy (Bronchopulmonary Dysplasia)

Before positive pressure ventilation and oxygen therapy were in widespread use for the treatment of SDD, premature infants who survived beyond 4 days of life typically recovered completely and chest radiographs normalized by 7 to 10 days of life.91 Infants who did not survive generally died by 3 days of life.91 This clinical course was dramatically altered when positive pressure ventilation and supplemental oxygen came into common practice. Survival rates improved, but a subset of patients developed a chronic pulmonary syndrome, which was first described by Northway in 1967.92 While “bronchopulmonary dysplasia (BPD)” was the original name of this disorder, the current preferred term is “chronic lung disease of infancy.”92







FIGURE 1.19. Male neonate born at 28 weeks of gestation who presented with respiratory distress due to surfactant deficiency disorder that was complicated by left pneumothorax and pulmonary hemorrhage. A: Frontal chest radiograph obtained at day 0 of life shows bilateral granular opacity and low lung volumes. Umbilical vein catheter (UVC; white arrow) is malpositioned within the right atrium. B: Frontal chest radiograph obtained at day 1 of life demonstrates a large left pneumothorax (P). UVC (white arrow) is malpositioned within the right atrium. C: Frontal chest radiograph obtained at day 3 of life shows left chest tube (black arrow) with interval resolution of left pneumothorax and diffuse bilateral pulmonary opacities due to pulmonary hemorrhage.

Northway described four stages of BPD. The first stage occurs from days 2 to 3 and is characterized by acute disease with diffuse granularity on chest radiographs, identical to SDD. The second stage occurs from days 4 to 10 and is characterized by near-complete opacification of the lungs. During stage II, there is repair and necrosis of the alveolar epithelium, bronchiolar necrosis with exudates in the bronchiolar lumens, and bronchiolar mucosal squamous metaplasia. By the end of stage II, respiratory compromise begins to slowly improve, and stage III is characterized by a transition to chronic disease. Stage III occurs from days 10 to 20, with chest radiographs typically demonstrating development of small cyst-like lucencies throughout hyperexpanded lungs, which correspond to admixed groups of hyperexpanded and collapsed alveoli (Fig. 1.21). Pathologically, stage III is characterized by mucous secretion, interstitial edema, and pulmonary fibrosis. Stage IV occurs after 1 month of age, with persistent cyst-like lucencies and hyperexpansion that represent more severe manifestations of the findings typically seen in stage III (Fig. 1.22). Pathology at stage IV is characterized by emphysema, atelectasis, peribronchiolar smooth muscle hypertrophy, epithelial metaplasia, and pulmonary fibrosis. Infants often develop cor pulmonale and congestive heart failure as a result of lung disease, and vascular hallmarks of pulmonary hypertension may be seen on pathology. Pulmonary oxygen toxicity from oxygen supplementation and barotrauma from mechanical ventilation were identified as the causes of BPD.

Since 1967, when chronic lung disease of infancy was originally described, there have been dramatic changes in the treatment of SDD. Widespread use of antenatal glucocorticoid therapy, exogenous surfactant, lower oxygen concentrations, and less harmful ventilation techniques have improved survival and resulted in changes in the typical clinical and radiographic features of SDD. In the original series published by Northway, the average gestational age was 34 weeks and the average birth weight was 2,235 g.92 With improvements in
therapy, it is now uncommon for SDD to develop in infants born at more than 30 weeks of gestation or with birth weight of >1,200 g.93 With improvements in treatment, a larger number of extremely low-birth-weight infants (<1,000 g) are surviving and eventually developing chronic lung disease. However, these infants often have different clinical and radiographic characteristics than the infants described by Northway. These infants frequently do not demonstrate the typical radiographic findings of RDS, but rather develop a pattern termed “immature lung,” which was described in the previous section (Fig. 1.20). Moreover, lung disease that occurs in this patient group may not be the result of high supplemental oxygen concentrations or positive pressure ventilation87 but may be
due to arrested acinar and vascular maturation instead.94 This entity has been called the “new BPD” in order to distinguish it from the classic BPD described by Northway.92,94






FIGURE 1.20. Male neonate born at 24 weeks of gestation who presented with respiratory distress due to immature lung and subsequently developed chronic lung disease of infancy. A: Frontal chest radiograph obtained at day 0 of life shows minimal granular opacities in both lungs. Umbilical vein catheter (white arrow) is malpositioned within the right atrium. B: Frontal chest radiograph obtained at day 30 of life demonstrates hyperinflated lungs with increased coarse opacities and atelectasis in the right middle lobe and bilateral lower lobes.






FIGURE 1.21. A 20-day-old girl born at 28 weeks of gestation with developing chronic lung disease of infancy. Frontal chest radiograph shows hyperinflated lungs with bilateral coarse opacities, atelectasis (white arrows), and cyst-like lucencies (black arrows).






FIGURE 1.22. A 3-month-old boy born at 26 weeks of gestation with chronic lung disease of infancy. Frontal chest radiograph shows bilateral increased coarse opacities, atelectasis (arrow), cyst-like lucencies, and hyperinflation (H).

The diagnosis of chronic lung disease of infancy or BPD was traditionally limited to infants who fulfilled several clinical and radiographic criteria, including (1) mechanical ventilation and supplemental oxygen for ≥3 days during the first 2 weeks of life, (2) respiratory distress after 28 days of life, (3) need for supplemental oxygen in order to achieve PaO2 >50 mm Hg, (4) and characteristic progression through the four radiographic stages of BPD described by Northway.92 With increased survival of very low-birth-weight infants who often had different radiographic and clinical features, this definition for BPD became less reliable. In response, a June 2000 National Institute of Child Health and Human Development/National Heart, Lung, and Blood Institute Workshop established new diagnostic criteria for BPD.93 Mild BPD was defined by a need for >21% administered O2 at 28 days but not at 36 weeks postmenstrual age (PMA). Moderate BPD was defined by a need for >21% administered O2 at 28 days and a need for <30% administered O2 at 36 weeks PMA. Severe BPD was defined by a need for >21% O2 at 28 days and a need for ≥30% O2 at 36 weeks PMA. Radiographic features were excluded from this categorization, as there were none that increased diagnostic sensitivity or specificity.95 As the radiographic features have changed from the original findings described by Northway, many have advocated for use of the term chronic lung disease of infancy to describe this entity; however, the 2000 National Institute of Child Health and Human Development/National Heart, Lung, and Blood Institute Workshop suggested keeping the term BPD because “[this entity] is clearly distinct from the multiple chronic lung diseases later in life.” Many now use the terms interchangeably.

As the clinical, epidemiological, and pathologic features of BPD have changed, the radiographic features have also changed. In 1995, Swischuk et al., described the radiographic findings in 75 premature infants who received surfactant to treat SDD.96 Infants of more advanced gestational age (mean gestational age 32 weeks) were more likely to completely clear their lungs following surfactant therapy, with subsequent normal chest radiographs. However, a different pattern emerged in more premature infants. Many went on to develop “hazy-opaque lungs” at 7 to 14 days, in a pattern that has been called “leaky lung syndrome” (LLS).96 LLS is thought to result from capillary damage, which leads to transudation of fluid into the pulmonary interstitium and pulmonary edema. Hypoxia and/or oxygen toxicity are potential causes. LLS may occur in infants who do not respond to exogenous surfactant and never clear the initial granular opacities of SDD but also may occur in infants who respond to surfactant and initially clear the granular opacities. Most patients who do not respond to surfactant therapy and develop LLS go on to develop the “bubbly lungs” described in Northway’s stage III and IV BPD. Among patients with LLS who initially responded to surfactant, 35% cleared their lungs by 21 to 28 days and did not develop the “bubbly lungs” of BPD, and the remaining 65% went on to develop “bubbly lungs.” In summary, LLS may occur at 7 to 14 days and may or may not progress to the classic radiographic appearance of BPD.

Treatment of chronic lung disease of infancy or BPD is largely supportive. The major risk factors of mechanical ventilation and high concentration oxygen supplementation are minimized to the lowest levels possible.97 Infants with chronic lung disease of infancy are more prone to developing pulmonary edema. Fluid restriction and diuretics may be utilized to manage acute respiratory distress, but they do not lower the incidence or decrease the severity of disease.98 Infants with chronic lung disease of infancy frequently have hyperactive airways with smooth muscle hypertrophy and can experience short-term improvements in respiratory status with inhaled bronchodilators including beta agonists and methylxanthines (aminophylline and caffeine).97 Although these inhaled agents often provide short-term improvements in respiratory status, there is no evidence that these therapies improve long-term outcomes.97,99

Systemic corticosteroids have been shown to improve pulmonary function and reduce the incidence of chronic lung disease of infancy.97 However, numerous clinically significant side effects occur in this patient population, the most serious being neurologic impairment and increased incidence of cerebral palsy.100,101,102 Given these risks, the American Academy of Pediatrics recommends that postnatal systemic steroids only be used in severely ill patients after a discussion of the benefits and risks with the family.102,103 Inhaled steroids have been utilized, but their effect on long-term outcomes is unclear.99 Pulmonary vasodilators including calcium channel blockers and inhaled nitric oxide have been utilized in patients with cor pulmonale and pulmonary hypertension with some short-term clinical improvement, although long-term effects and benefits have not been established.97 Optimized nutrition is a critical aspect of care, as malnutrition can stunt alveolar development and decrease respiratory muscle strength, prolonging dependence on mechanical ventilation.97


Transient Tachypnea of the Newborn

Transient tachypnea of the newborn (TTN) is also known as retained fetal lung fluid, wet lung disease, and transient respiratory distress. TTN is a condition that occurs when there is delayed clearance of fetal lung fluid, which causes respiratory distress within the first 6 hours of life, peaks at 24 hours, and typically improves by 48 to 72 hours. In utero, the lungs are filled with fetal lung fluid, which is essential for normal lung growth. During and immediately after delivery, the fluid is normally cleared via the airway (30%), lymphatics (30%), and capillaries (40%).86 This process seems to be aided by the normal vaginal delivery process, and retained fetal lung fluid is more commonly seen in infants born by cesarean section or precipitous vaginal delivery.86 The rate of TTN in infants born by cesarean section is 35.5 per 1,000 infants in cases in which labor has not occurred and 12.2 per 1,000 in cases in which labor has occurred, compared to 5.3 per 1,000 in infants born by vaginal delivery.104,105 “Thoracic squeeze” that occurs during normal vaginal delivery is often cited as the driving force
behind fetal lung fluid resorption, but this actually appears to play a very small role.106 The majority of lung fluid is cleared as a result of epithelial sodium channel activity, which is inactive in the fetal lung until adrenergic stimulation occurs at birth.107,108,109,110

The radiographic findings in TTN are similar to the findings in pulmonary edema, as fluid is retained within the pulmonary interstitium. Common findings include increased perihilar lung markings, indistinct pulmonary vasculature, pleural effusion, occasional cardiomegaly, and normal or increased lung volumes (Fig. 1.23). In some cases, the radiographic appearance can be difficult to differentiate from other neonatal lung diseases, and the addition of clinical information such as type of delivery, gestational age, and severity of symptoms is often helpful to the primary interpretation.86 Serial radiographs demonstrate rapid clearing of the lungs in the first 2 to 3 days of life, which parallels clinical improvement.


Meconium Aspiration Syndrome

Meconium aspiration syndrome (MAS) is the leading cause of morbidity and mortality in term infants and is the result of fetal meconium aspiration at or around the time of birth.111 Meconium staining of the amniotic fluid occurs in ˜10% to 15% of live births, but only ˜5% of affected neonates develop MAS, which is defined as meconium within the airway below the vocal cords.86,111,112 Aspirated meconium incites chemical pneumonitis within the lungs, inactivates surfactant, and causes small and medium size airway obstruction. Impaired oxygenation may lead to hypoxia-induced PPHN. Pneumonitis in MAS also predisposes to gram-negative bacterial infection. Meconium aspiration is more common in cases of advanced gestation (birth beyond 40 weeks).112 Clinical symptoms can range from mild respiratory distress to severe hypoxia requiring extracorporeal membrane oxygenation (ECMO).






FIGURE 1.23. A 0-day-old full-term boy born via cesarean section, with mild respiratory distress due to transient tachypnea of the newborn. Frontal chest radiograph shows mildly prominent perihilar interstitial markings and trace fluid (arrow) within the minor fissure. Follow-up chest radiograph obtained 48 hours later (not shown) showed clear lungs.

Radiographic findings in MAS include elevated lung volumes, asymmetric “ropey” or “coarse” opacities radiating from the hila, and admixed areas of hyperinflation and atelectasis (Fig. 1.24). Pneumothorax is a frequent complication, seen in 10% to 40% of cases.86,112,113 Pleural effusion is present in 10% to 20% of cases.86,113 The radiographic findings in MAS are often similar to findings in neonatal pneumonia. Because pneumonia is often difficult to exclude, and there is an increased risk of superimposed pneumonia in MAS, affected patients are often treated with antibiotics.86 In a minority of cases, chest radiographs are normal or show only pneumothorax (Fig. 1.25).86

Treatment of MAS is focused on maintaining arterial oxygen levels. Mechanical ventilation is optimized to minimize mean airway pressures and help reduce the risk of air leak phenomena, and high-frequency oscillatory or jet ventilation may be employed. Exogenous surfactant is often administered in an effort to replace endogenous surfactant that has been inactivated by meconium.112,114 Inhaled nitric oxide is frequently used to treat associated PPHN.115 ECMO may be required when severe respiratory compromise persists despite therapy but is reserved for severe cases due to associated poor neurologic outcomes.


Neonatal Pneumonia

Neonatal pneumonia can occur in utero, during labor, or shortly after delivery. The most common causal organism is group B streptococcus (GBS), although a large number of other organisms may be the cause. The most common mechanism of infection is ascending vaginal infection in the setting of prolonged rupture of membranes, although infections can also occur due to hematogenous spread via the placenta or during uneventful vaginal delivery. Signs and symptoms vary and may range from severe respiratory distress to unstable
temperature and hypothermia.116 As symptoms are nonspecific, it is often difficult to distinguish neonatal pneumonia from other causes of respiratory distress based on clinical findings.






FIGURE 1.24. A 1-day-old full-term boy who presented with respiratory distress due to meconium aspiration. Frontal chest radiograph shows coarse opacities in both lungs. The endotracheal tube tip terminates in low position, just above the carina.






FIGURE 1.25. Newborn full-term boy who presented with respiratory distress due to meconium aspiration. Frontal chest radiograph shows small bilateral pneumothoraces (arrows) and clear lungs.

The radiographic findings of neonatal pneumonia vary, and a wide spectrum of abnormalities may be seen. Haney et al., described the radiographic features in a series of 30 cases of autopsy-proven neonatal pneumonia, and the most common pattern was bilateral alveolar densities, which was seen in 77% of cases116 (Figs. 1.26 and 1.27). Findings were indistinguishable from SDD in 13% and identical to TTN in 17%, and chest radiographs were normal in 10%.114 Given the broad range of possible radiographic appearances and the crossover with findings in other causes of neonatal lung disease, definitive diagnosis is often not possible based on radiographs alone.






FIGURE 1.26. A 1-day-old full-term girl who presented with decreased oxygen saturation due to neonatal pneumonia. Frontal chest radiograph shows bilateral symmetric alveolar opacities in both lungs.






FIGURE 1.27. A 4-day-old full-term boy who presented with respiratory distress due to neonatal pneumonia. Frontal chest radiograph demonstrates bilateral asymmetric alveolar opacities, which are more severe on the right.

Group B streptococcal infection, in particular, commonly presents with low lung volumes and bilateral granular opacities, and radiographs can have an appearance identical to SDD. One potential differentiating feature is pleural effusion, which is rarely seen in SDD but not infrequent in pneumonia (Fig. 1.28). Other pathogens may cause patchy perihilar opacities with hyperinflation, an appearance that
is radiographically indistinguishable from meconium aspiration. There have been numerous reports of group B streptococcal neonatal pneumonia and sepsis associated with late-onset right-sided congenital diaphragmatic hernia.117 The appearance of the diaphragmatic defect at surgery is identical to that in cases without associated pneumonia. The mechanism for the association is currently unclear.






FIGURE 1.28. A 3-day-old boy who presented with fever and respiratory distress due to group B streptococcal pneumonia. Frontal chest radiograph shows airspace opacities (asterisks) in both lower lobes and a small right effusion (arrow).

Chlamydia trachomatis can be transmitted from the mother to the newborn during vaginal delivery. The most common neonatal chlamydia infection is conjunctivitis, and a smaller proportion of patients develop chlamydia pneumonia. The clinical and radiographic features of chlamydia pneumonia differ from those in other causes of neonatal pneumonia. Pneumonia typically presents later, usually between 2 weeks and 3 months of age.86 Signs and symptoms may include “staccato cough” and tachypnea with minimal fever and leukocytosis.118 Peripheral eosinophilia is seen in up to 50% of cases.86 Although chest radiographic findings are not specific, most radiographs demonstrate bilateral lung hyperinflation and bilateral opacities with a variety of possible patterns including interstitial opacities, atelectasis, reticulonodular opacities, and focal alveolar opacification86,119 (Fig. 1.29). Neither pleural effusion nor lobar consolidation are seen in Chlamydia pneumoniae.119 Findings are often indistinguishable from viral pneumonitis due to cytomegalovirus (CMV), respiratory syncytial virus (RSV), or adenovirus.119 Frequently, the radiographic findings in chlamydia pneumonia are more severe than might be suggested by the relatively mild symptoms.86,119

Because it can be difficult to differentiate neonatal pneumonia from other causes of neonatal respiratory distress based on both clinical and radiographic parameters, patients with suspected neonatal pneumonia are often presumptively treated with antibiotics. Diagnosis can be established in cases with positive blood or sputum culture, although cultures are often negative.120






FIGURE 1.29. A 2-month-old girl with chlamydia pneumonia who presented with conjunctivitis, fever, cough, and respiratory distress. Frontal chest radiograph shows perihilar interstitial opacities with peribronchial cuffing and hyperinflation.


Pulmonary Interstitial Emphysema

Mechanical ventilation is frequently required to maintain oxygenation in neonatal lung disease. High airway pressures (barotrauma) and airway overdistension (volutrauma) may lead to rupture of the small airways at the bronchoalveolar junctions, allowing air to dissect into the interstitial spaces of the lung, resulting in a condition called pulmonary interstitial emphysema (PIE).87 Air can further dissect through the soft tissues, leading to pneumothorax, pneumomediastinum, pneumopericardium, and/or pneumoperitoneum. Rarely, air can extend into the vasculature and cause air embolism, which is nearly always fatal.121 The most common risk factors for PIE are prematurity and SDD, although PIE can also be seen in other conditions, including MAS and neonatal pneumonia.

Radiographic features of PIE include bubbly or linear lucencies within the lung that do not conform to the shape of air bronchograms122,123 (Fig. 1.30A). Nonbranching lucencies typically extend from the hila into the periphery of the lung.122 PIE may be focal or diffuse and unilateral or bilateral.123 When unilateral, the involved lung can become enlarged and exert mass effect on the mediastinum and adjacent structures. Complications, including pneumothorax, pneumomediastinum, pneumopericardium, and pneumoperitoneum, can be detected on radiographs (Fig. 1.30B).

The bubbly lucencies of PIE can be difficult to differentiate from the bubbly lucencies that occur in chronic lung disease of infancy or BPD. Time course and patient age can be helpful in differentiating these two entities. PIE tends to occur acutely within the 1st week of life, whereas the bubbly lucencies of chronic lung disease of infancy gradually develop around the 3rd week of life and persist.96 As previously described, acinar overdistension following surfactant therapy for SDD can produce a radiographic appearance that mimics PIE. When this pattern is seen, consideration of the patient’s clinical condition is often helpful, because PIE-affected patients tend to decompensate, while SDD patients tend to improve when surfactant is successfully delivered to the acini.86

When PIE lasts for longer than 1 week, it is called persistent pulmonary interstitial emphysema (PPIE). Like PIE, PPIE can also be localized to a single lobe, or involve multiple lobes within one or both lungs124 (Fig. 1.31). The involved portion of the lung may become hyperexpanded and exert mass effect on adjacent structures. The appearance may mimic other lucent lung lesions, including congenital pulmonary airway malformation (CPAM) and congenital lobar emphysema (CLE), but in most cases, previous radiographs demonstrating PIE in the same region help to differentiate among these entities.87 In unclear cases, CT can demonstrate air-filled cystic spaces within the interstitium surrounding linear or dot-like structures that represent the bronchovascular bundles.123,124,125 This appearance is referred to as a “line-and-dot” pattern.124

When acute PIE is detected, the neonatal intensive care unit (NICU) staff should be notified immediately, because
it can be a harbinger of other air leak complications including pneumothorax. Acknowledgment of this finding often prompts a change to HFOV.123 The majority of cases of PIE resolve spontaneously, with fewer going on to develop PPIE. First-line management of PPIE is nonoperative, although surgical resection may be required in cases of hyperexpansion with significant mass effect and/or respiratory compromise.123 When surgery is considered, CT is often useful to define the lobar distribution.123,124,125






FIGURE 1.30. A 9-day-old boy born at 25 weeks of gestation who developed right pulmonary interstitial emphysema (PIE) and pneumothorax as a complication of surfactant deficiency disorder. A: Frontal chest radiograph shows diffuse granular opacities in both lungs due to surfactant deficiency disorder. Superimposed tubular lucencies in the right lung are mainly due to PIE. B: Frontal chest radiograph, obtained 6 hours later due to acute respiratory distress, demonstrates a large right-sided tension pneumothorax (asterisks) with leftward mediastinal shift. A rightsided chest tube (arrow) is malpositioned within the chest wall.






FIGURE 1.31. Newborn boy born at 29 weeks of gestation who developed pulmonary interstitial emphysema (PIE), and later, persistent pulmonary interstitial emphysema (PPIE) as complications of surfactant deficiency disorder. A: Frontal chest radiograph obtained at day 1 of life shows bilateral granular opacities due to surfactant deficiency disorder and tubular and bubbly lucencies in the left lung due to PIE. B: Frontal chest radiograph obtained at day 11 of life demonstrates tubular and bubbly lucencies involving both lungs, as well as hyperinflation due to PPIE.


Congenital Lung Malformations

Congenital lung malformations are a group of developmental anomalies that may involve the airways and lung parenchyma, vascular structures within the lung, or both. The classification of congenital lung malformations has been controversial, and several different systems have been proposed.126,127,128,129 It is helpful to consider these lesions on a spectrum, with pure pulmonary parenchymal lesions (e.g., CPAM) on one end of the spectrum and pure vascular lesions (e.g., pulmonary
arteriovenous malformation [AVM]) on the other end. These malformations can be further divided into three groups: pure airway and parenchymal lesions without vascular abnormalities, pure vascular lesions, and malformations of both lung parenchyma and the vasculature.

In classifying congenital lung malformations on the basis of airway/parenchymal and vascular involvement, it is essential to understand that lesions often exhibit features of more than one entity (termed “hybrid lesions”). For example, when meticulous microdissection techniques are used, bronchial atresia is often found as an element of other congenital lung lesions, including 100% of extralobar pulmonary sequestrations, 82% of intralobar pulmonary sequestrations, 70% of CPAMs, and 50% of CLE.130

Pathologic features of CPAM have been reported in 29% to 33% of lesions with a systemic arterial supply.131,132 Given the controversial nomenclature and considerable overlap of pathological features, radiologists are advised to describe the imaging findings of congenital lung lesions in a clear and concise manner, while avoiding pathology-based terminology that can cause confusion.61,133,134 Location, vascular supply, any communication with gastrointestinal tract, diaphragmatic involvement, and morphologic characteristics of the lesion should be carefully evaluated and reported in each case.135


Bronchial Atresia

Congenital bronchial atresia is a nonvascular congenital lung lesion caused by congenital atresia of a bronchus. Bronchial atresia may occur via one of two proposed mechanisms. According to the first theory, the developing bronchial bud is disrupted during development, and the distal bronchial bud develops normally. The second theory proposes that an ischemic event during lung development leads to stenosis and obliteration of the airway. Regardless of the underlying cause, the result is an atretic bronchus with distal lung parenchyma that does not communicate with the central bronchial tree. Atresia may be proximal, involving a mainstem or lobar bronchus, or distal, involving a segmental or subsegmental bronchus. Distal atresia is more commonly seen in clinical practice, as proximal atresia is usually lethal in the prenatal period.136

Bronchial atresia occurs most commonly in the apical or apicoposterior segments of the upper lobes.61 Normal pulmonary secretions are transported to the central airway by the movement of respiratory cilia, but secretions are unable to clear the atretic segment, leading to formation of a bronchocele. The lung distal to the atretic segment becomes hyperinflated, which is thought to be due to air drift via collateral pathways, including the pores of Kohn and canals of Lambert, or a check-valve phenomenon.136 Vascularity of the hyperinflated lung decreases as a result of hypoxia-induced vasoconstriction and stretching of vessels.

Bronchial atresia can be detected on prenatal imaging. In the fetus, amniotic fluid rather than air is trapped within the lung distal to the atretic segment. Therefore, prenatal US may demonstrate a relatively hyperechoic, hyperexpanded portion of the lung, and T2-weighted prenatal MRI may demonstrate a hyperintense, hyperexpanded region of lung due to trapped fluid.136 In the rare cases of proximal atresia, the atretic segment is more commonly found on the right. The entire lung or lobe distal to the atretic segment becomes very large, and a centrally located, fluid-filled bronchocele is typically seen.136 In proximal atresia, marked enlargement of the involved lung results in inferior vena cava (IVC) compression, hydrops, and hypoplasia of adjacent normal lung, and the condition is usually lethal in the prenatal or early postnatal period.137 In distal atresia, the involved segment is also hyperechoic on US and hyperintense on T2-weighed MRI sequences, but the involved segment is smaller, there is usually little associated mass effect, and the associated bronchocele is typically absent or too small to be visualized.136 Therefore, prenatal imaging findings in distal bronchial atresia are similar to those in bronchopulmonary sequestration and microcystic CPAM, often rendering distinction among these entities difficult.136

Chest radiography is the first-line test for postnatal evaluation of distal bronchial atresia. Early postnatal chest radiographs may demonstrate atelectasis within the lung distal to the atretic segment rather than the classic hyperexpansion and hyperlucency seen later in life. Bronchoceles are often air-filled immediately after birth and may not be seen on chest radiographs until after secretions have collected within the bronchocele, by several months of age.136 Once sufficient secretions have collected, a fluid-filled bronchocele, or mucocele, is typically seen as a perihilar round or oval opacity proximal to a lucent overinflated segment of the lung (Fig. 1.32A). The overinflated segment usually remains stable in size, and affected pediatric patients are typically asymptomatic unless superimposed infection occurs. This is an important difference between bronchial atresia and CLE, which is characterized by progressive hyperexpansion soon after birth, which typically causes symptoms such as respiratory distress.136

When bronchial atresia is detected on prenatal imaging or chest radiographs, cross-sectional imaging is often indicated for further evaluation and characterization of the underlying lesion. CT is the preferred modality, given its excellent contrast and spatial resolution in air-filled lung. CT typically shows the mucocele as a tubular central opacity, which may have an air-fluid level. The lung distal to the atretic segment is more lucent than adjacent normally aerated lung due to hyperinflation and decreased vascularity (Fig. 1.32B). Use of MRI has been described in the evaluation of bronchial atresia and typically demonstrates the tubular mucocele as hyperintense on T1- and T2-weighted MR images.138,139 MRI does not demonstrate hyperinflation and decreased vascularity within the lung beyond the atretic bronchus as well as CT, given the relatively signal-poor environment of the lung parenchyma.65

Surgical lobectomy or segmentectomy is the current standard treatment in symptomatic patients. CT is typically performed for surgical planning. Management of small, asymptomatic foci of bronchial atresia is more controversial. Some advocate resection of asymptomatic, radiographically diagnosed bronchial atresia given risk of future infection and frequent discovery of CPAM elements on pathology.140,141 However, large scale studies are currently needed to establish evidence-based guidelines for treatment of these patients.136







FIGURE 1.32. An 11-month-old girl with bronchial atresia detected on imaging studies obtained for evaluation of pneumonia. A: Frontal chest radiograph shows regional hyperinflation (H) in the left lower lobe. B: Coronal lung window CT image demonstrates a hyperinflated posterior left lower lobe with impacted mucus in a bronchocele (arrow).


Congenital Lobar Emphysema

CLE is a nonvascular lesion that is caused by obstruction of a lobar bronchus. Other names for CLE include congenital lobar hyperinflation and infantile lobar emphysema. CLE occurs when there is hyperexpansion of a lobe of the lung due to narrowing of a lobar bronchus from extrinsic compression, intrinsic narrowing, and/or bronchial cartilage deficiency. CLE has a lobar predilection: left upper lobe > right middle lobe > right upper lobe > right or left lower lobe.142 There are two main forms of CLE: the classic form and polyalveolar form. The classic form of CLE is characterized by a normal or decreased number of alveoli within the hyperinflated segment. In the polyalveolar form, the number of alveoli within the hyperinflated segment is increased.143

The majority of newborns with CLE have symptoms of respiratory distress within the first 6 hours of life. CLE may first be detected on prenatal imaging. Prenatal US may demonstrate a hyperexpanded lobe, which is hyperechoic due to increased trapped fetal fluid, and MRI may show a hyperintense, hyperexpanded lobe on T2-weighted MR imaging.144,145 Differentiating CLE from bronchial atresia on fetal imaging is often difficult because the imaging findings are similar.144 After birth, on the first radiographs, the affected lobe of the lung is typically radiopaque due to entrapped fetal lung fluid. As this fluid is absorbed by the pulmonary lymphatic system, the fluid is replaced with air, and the affected lung becomes hyperlucent. Subsequent radiographs show progressive hyperinflation, which often exerts significant mass effect on the adjacent lung, mediastinum, and diaphragm (Fig. 1.33).

Mass effect frequently results in symptoms, and lobectomy is the current treatment of choice. CT is often performed prior to surgery and is useful for defining the lobar anatomy and depicting the degree of mass effect on adjacent lung and mediastinal structures61 (Fig. 1.34).


Foregut Duplication Cyst (Bronchogenic Cyst, Esophageal Duplication Cyst, and Neurenteric Cyst)

A variety of congenital cysts can arise from the primitive foregut early in fetal development, including bronchogenic cysts, esophageal duplication cysts, and neurenteric cysts. Foregut duplication cysts are uncommon, accounting for <5% of mediastinal masses in the pediatric population.146 Small foregut duplication cysts are frequently asymptomatic and identified incidentally. Symptoms can occur when cysts are large and exert mass effect on adjacent structures or in the context of superinfection.

Developmentally, bronchogenic cysts occur due to abnormal budding of the ventral lung bud or abnormal branching of the tracheobronchial tree. Bronchogenic cysts are initially closely related to the tracheobronchial tree, but with growth, this continuity may be lost.146 The majority of bronchogenic cysts are located within the mediastinum, typically adjacent to the trachea or bronchi, although ˜15% are located within the lung parenchyma.147 Esophageal duplication cysts may be derived from a diverticulum of the dorsal bud of the primitive foregut or caused by aberrant recanalization of the gut. They are usually closely apposed to the esophagus, but like bronchogenic cysts, they can migrate away from their organ of origin during development.146 Neurenteric cysts occur when there is incomplete separation of the endoderm and notochord, resulting in development of a diverticulum that may form into a posterior mediastinal cyst.146 Distinction between bronchogenic, esophageal, and neurenteric cysts is artificial, as these congenital cysts often contain elements of more than one foregut structure. For example, cysts attached to the esophagus may contain respiratory epithelium, and cysts attached to the trachea or bronchus may contain squamous epithelium.

Foregut duplication cysts may be detected during prenatal imaging. In cases of bronchogenic cyst, prenatal US most commonly demonstrates a unilocular, centrally located anechoic cyst (Fig. 1.35A) and T2-weighted fetal MRI typically shows a hyperintense cyst with a thin hypointense wall (Fig. 1.35B).145,148,149 Postnatally, foregut duplication cysts typically appear on chest radiographs as middle or posterior mediastinal masses. Bronchogenic cysts, in particular, are
typically located within the middle mediastinum and, less commonly, within the lung parenchyma (Fig. 1.36A). On CT, foregut duplication cysts are typically circumscribed, round, or ovoid nonenhancing lesions with homogeneous fluid attenuation between 0 and 20 Hounsfield units and a thin wall, although density can be higher if there are proteinaceous contents61 (Fig. 1.36B). On MRI, foregut duplication cysts are typically high in signal on T2-weighted MR images, variable in intensity on T1-weighted MR images depending on the nature of the cyst contents, and lacking enhancing solid components142 (Fig. 1.36C and D). While mediastinal bronchogenic cysts rarely communicate with the airway, intrapulmonary bronchogenic cysts often do communicate with the airway, increasing the risk of superimposed infection.150 In cases of superinfection, air-fluid levels may develop and the wall may become thickened, with associated hyperenhancement and adjacent inflammatory changes135 (Fig. 1.37).






FIGURE 1.33. Newborn boy with congenital lobar emphysema (CLE) in the left upper lobe who presented with progressively worsening respiratory distress. A: Frontal chest radiograph obtained at day 8 of life shows hyperinflation (H) of the left upper lobe. B: Frontal chest radiograph obtained at day 9 of life demonstrates increased hyperinflation (H) with progressive rightward mediastinal shift. C: Frontal chest radiograph obtained at day 10 of life after left upper lobectomy shows improved mediastinal shift with postoperative changes including a left chest tube, left upper lung atelectasis, and subcutaneous air in the left chest.

Symptomatic foregut duplication cysts are treated with surgical resection. Asymptomatic foregut duplication cysts detected in children are also generally surgically resected.135 Management of asymptomatic foregut duplication cysts detected in adults is more controversial. An analysis by Kirmani et al., suggests that asymptomatic bronchogenic cysts detected in adults may be managed conservatively according to patient preference, but patients should be advised that ˜45% of patients with asymptomatic lesions eventually go on to develop symptoms. Symptoms may be severe and make later surgery necessary, and there is an estimated 0.7% chance of malignancy.151







FIGURE 1.34. A 20-day-old girl with congenital lobar emphysema (CLE) in the left upper lobe who presented with irritability and desaturation. Axial lung window CT image shows a hyperinflated left upper lobe with rightward mediastinal shift.


Congenital Pulmonary Airway Malformation

Congenital pulmonary airway malformations (CPAMs), formerly known as congenital cystic adenomatoid malformations (CCAMs), are a group of congenitally malformed cystic and solid lung lesions, which are associated with bronchiolar overgrowth and communication with an abnormal bronchial tree that lacks cartilage.135,150 Most CPAMs have conventional pulmonary vascular anatomy, with arterial supply from the pulmonary artery and venous drainage via pulmonary veins.61 However, pathologic features of CPAM are present in 29% to 33% of lesions with a systemic arterial supply.131,132 With pathological analysis, features of CPAM are frequently seen in other congenital lung lesions.130,134,152 For example, Riedlinger et al., found features of CPAM in 91% of extralobar sequestrations, 91% of intralobar sequestrations, and 50% of CLE lesions.130






FIGURE 1.35. Second trimester fetus with a foregut duplication cyst that was surgically resected after birth. A: Prenatal coronal fetal ultrasound shows a round anechoic cyst (asterisk) in the mediastinum. B: Sagittal prenatal T2-weighted MRI confirms a hyperintense cyst (arrow).

There is a fair amount of controversy surrounding the classification of CPAMs, especially as more studies have shown significant overlap between these and other congenital lung lesions.128,130,131,135,150 In 1977, Stocker et al., proposed a classification system that is still used by many.153 The original Stocker classification described three types of CCAM: (1) type 1 lesions, characterized by one or more cyst(s) of presumed bronchial or bronchiolar origin measuring larger than 2 cm; (2) type 2 lesions, composed of one or more cysts of presumed bronchiolar origin measuring smaller than 2 cm; and (3) type 3 lesions, which appear macroscopically solid but contain microcysts (<0.5 cm) of presumed bronchiolar origin.

In 2001, Stocker proposed an expansion of this system to include type 0 lesions, which were previously called acinar dysplasia (a condition that is incompatible with life), and type 4 lesions, which are composed of large peripheral lung cysts of presumed distal acinar origin that are often associated with pneumothorax.154 Although this classification system is widely used, it is not universally accepted.128 The term CPAM is now widely preferred to CCAM because macroscopic cysts are only present in types 1, 2, and 4, and adenomatoid proliferation is only present in type 3. CPAM can be radiographically and clinically indistinguishable from cystic type I pleuropulmonary blastoma (PPB),155,156,157,158 and there is increasing evidence that type 4 CPAM and type I PPB may represent the same or overlapping conditions.128,152,157,159,160 Many cite the classification system proposed by Langston as an alternative to the Stocker system, in which Stocker type 1 CPAMs are called the “large cyst type,” Stocker type 2 CPAMs are called the “small cyst type,” and Stocker type 3 lesions are considered a type of pulmonary hyperplasia rather than a type of CPAM.128

Type 1 CPAMs account for 60% to 65% of all CPAMs. Large type 1 CPAMs may cause mass effect on the adjacent lung and mediastinum and can be symptomatic
soon after birth.133,144,155 Smaller type 1 CPAMs may only become symptomatic later in life if superimposed infection occurs or in rare cases of associated malignancy.155 Type 2 CPAMs account for ˜20% of all CPAMs, and ˜50% of type 2 CPAMs are accompanied by additional congenital anomalies, including cardiovascular malformations, extralobar pulmonary sequestration, tracheoesophageal fistula, renal agenesis, intestinal atresia, and congenital diaphragmatic hernia, leading to poorer prognosis than type 1 CPAMs.155,161 Type 3 CPAMs account for ˜5% to 10% of all CPAMs and typically present as a solid mass involving an entire lobe. Type 3 CPAMs may be associated with polyhydramnios, fetal hydrops, and significant respiratory symptoms soon after birth.162 The entity described as type 4 CPAM, which has significant overlap with type I PPB, accounts for ˜10% of CPAMs and may be symptomatic in the newborn period or may present with pneumothorax in older children, a feature which is unusual for other CPAMs.155






FIGURE 1.36. A 16-year-old asymptomatic girl with a foregut duplication cyst that was incidentally detected on chest radiography obtained because of a positive PPD (purified protein derivative) test for tuberculosis. A: Frontal chest radiograph shows an opacity (arrow) in the left hilar region. B: Axial enhanced CT image demonstrates a nonenhancing cyst (asterisk) within the mediastinum and left hilum. C: Axial T2-weighted, fat-suppressed MRI shows a hyperintense cyst (asterisk) within the mediastinum and left hilum. D: Axial enhanced T1-weighted, fat-suppressed MRI demonstrates a nonenhancing cyst (asterisk) within the mediastinum and left hilum.






FIGURE 1.37. A 13-year-old boy with an infected foregut duplication cyst who presented with fever and leukocytosis. Axial enhanced CT image shows a large low attenuation cyst (asterisk) containing a small amount of air (arrow), with a thickened and enhancing wall and adjacent inflammatory changes.

CPAMs are often first detected on screening prenatal US and appear as heterogeneous hyperechoic lesions within the lung, often containing cysts of varying number and size.144 On T2-weighted fetal MRI, CPAMs are hyperintense to the adjacent lung due to retained fluid within the abnormal lung tissue, and cysts may also be visualized.144 On fetal imaging, CPAMs are typically categorized as macrocystic cysts (≥5 mm) or microcystic cysts (<5 mm),133 with macrocystic lesions corresponding to Stocker type 1 lesions and microcystic lesions
corresponding to Stocker type 2 lesions.135,144 In lesions without visible cysts, as in some Stocker type 2 lesions and all Stocker type 3 lesions, the hyperechoic, hyperintense lung lesion may be indistinguishable from other congenital lung lesions such as bronchopulmonary sequestration and CLE.144 CPAMs may be large and can exert mass effect on the adjacent lung and mediastinum.144 CPAMs most commonly affect a single lobe, although multilobar and bilateral lesions rarely occur.155 Prenatally diagnosed CPAMs are usually first detected in the 2nd trimester, typically increase in size between 20 and 25 weeks of gestation, and stabilize in size by the end of the 2nd trimester.144 Twenty to fifty percent decrease in size during the 3rd trimester, but complete involution is rare.144,163,164






FIGURE 1.38. A 2-year-old boy with type 1 congenital pulmonary airway malformation in the right lower lobe that was detected on a chest radiograph obtained for evaluation of pneumonia. The lesion was surgically resected. A: Frontal chest radiograph shows an air-filled cystic lesion (arrow) in the medial right lower lobe. B: Axial lung window CT image demonstrates a large air-filled cyst (asterisk) and smaller adjacent cysts (arrowheads) in the right lower lobe.

The postnatal imaging appearance of CPAM depends on the type and whether there is superimposed infection or associated mass effect. Given the controversial classification of these lesions, it is best for imaging reports to provide a detailed description of the anatomy, including size, location, number of cysts, size of the largest cyst, relationship with the pulmonary hilum, communication with the bronchial tree, and degree of aeration.61,133,135 The large cyst type 1 lesions contain at least one cyst that is >2 cm in diameter and may have additional smaller cysts (Fig. 1.38). At birth, cysts are initially filled with lung fluid that is replaced with air supplied via the bronchial tree.133 On CT, type 1 lesions appear as one or more large cyst(s), which are typically air-filled, although occasionally contain air-fluid levels61 (Fig. 1.38B). Septations and nonaerated lung typically separate the cysts of multicystic lesions.135 Type 2 lesions typically appear as multicystic, partially air-filled masses or areas of consolidation with cysts smaller than 2 cm61,135 (Fig. 1.39). Stocker type 3 CPAMs, referred to as pulmonary hyperplasia by Langston, are composed of microscopic cysts and, therefore, appear as solid, enhancing masses on CT and MRI (Fig. 1.40). Radiographically, type 3 CPAMs are seen as opacities that are often large and associated with mass effect.61,135 So-called Stocker type 4 CPAMs are composed of large, peripherally located cysts and are radiographically indistinguishable from Stocker type 1 lesions and type I PPB. Type 4 lesions can present with pneumothorax.155,157

CPAMs may present later in life with superinfection, and a small number develop malignancy. When infected, CPAMs typically demonstrate consolidation with associated air-fluid levels on chest radiography and a thick, enhancing rim with adjacent parenchymal airspace disease on CT or MRI.61,135,150 In addition to the association between Stocker type 4 CPAM and type I PPB described earlier, a small number of Stocker type 1 CPAMs reportedly develop bronchoalveolar carcinoma.159 Rare cases of blastomas, malignant mesenchymomas, and rhabdomyosarcomas arising from CPAMs have also
been reported165,166,167,168; however, it has been proposed that these cases represent low-grade PPBs rather than CPAMs with malignant degeneration.128






FIGURE 1.39. A 1-month-old boy with type 2 congenital pulmonary airway malformation in the right lung. Axial lung window CT image shows two multicystic lung lesions (arrows).






FIGURE 1.40. A 2-week-old boy with a prenatally diagnosed focal lung lesion that was found to represent a type 3 congenital pulmonary airway malformation. A: Axial enhanced CT image shows an enhancing lesion (arrow) in the right lower lobe. B: Three-dimensional reformatted CT image effectively excludes sequestration by demonstrating no anomalous artery arising from the descending aorta and no anomalous vein draining from the congenital pulmonary airway malformation.

Surgical resection is indicated in symptomatic CPAMs, but surgical resection of asymptomatic lesions is more controversial.169 Many support surgical resection of asymptomatic lesions due to the risks of superimposed infection and malignancy.135,150,156,160 However, others do not advocate surgical resection on account of the low incidence of these complications.170 Presence of the DICER1 gene mutation, which is present in 66% of cases of PPB, also helps guide decisions about surgical resection versus nonoperative management.171


Pulmonary Sequestration

The classic definition of pulmonary sequestration, as first laid forth by Pryce in 1946, is a “disconnected bronchopulmonary mass or cyst with an anomalous arterial supply.”172 Pulmonary sequestration was later subdivided into two main types: intralobar and extralobar pulmonary sequestration.

Intralobar pulmonary sequestration accounts for 75% of pulmonary sequestrations and is classically defined as a portion of nonfunctioning lung that does not communicate with the tracheobronchial tree, has a systemic arterial supply (typically from the descending thoracic aorta or upper abdominal aorta or one of its branches), contains veins that drain to the pulmonary veins, and shares a visceral pleural covering with the adjacent lung.61,135,150 The lung tissue in classic intralobar pulmonary sequestration resembles a CPAM lesion, containing cystic spaces that have been linked to the “bronchial atresia sequence.”130 Intralobar pulmonary sequestration was traditionally thought to be an acquired lesion that occurred after a chronic inflammatory process recruited systemic blood vessels from the aorta or its branches, but with improved prenatal imaging, a large number of prenatally diagnosed cases of intralobar pulmonary sequestration have challenged this view.133 Intralobar pulmonary sequestration is most commonly isolated, without associated congenital anomalies.150

Extralobar pulmonary sequestration accounts for the other 25% of pulmonary sequestrations and is defined as nonfunctioning lung tissue that does not communicate with the tracheobronchial tree and has a systemic arterial supply (typically from the descending aorta or one of its branches); however, unlike intralobar pulmonary sequestration, extralobar sequestration has systemic venous drainage (typically to the azygos, hemiazygos, portal, internal mammary, or subclavian veins, or the IVC) and has its own pleural covering separate from that of the adjacent lung.61,135,150 Extralobar pulmonary sequestrations are most commonly located within the lower lung, more commonly on the left. Less often, they can occur in the mediastinum or pericardium or below the diaphragm. Features of type 2 CPAM are seen in up to 50% of extralobar pulmonary sequestrations. These combination lesions are termed “hybrid lesions.”173 Unlike intralobar pulmonary sequestrations, extralobar pulmonary lesions are frequently associated with additional congenital abnormalities including congenital heart disease and diaphragmatic hernia.150

The classification and description of pulmonary sequestration has had shortcomings from the time the entity was first described. Four of the original seven cases first described by Pryce did not fit his strict definition, and he proposed three variants, including abnormal artery supplying lung with abnormal tracheobronchial connection, abnormal artery supplying lung with normal and abnormal tracheobronchial connection, and abnormal artery supplying lung with a normal tracheobronchial connection.174 Others have broadened the definition to include normal lung with systemic arterial supply and abnormal lung tissue that maintains a normal bronchial connection but has a systemic arterial supply.175 Given the shortcomings of the Pryce
categorization, alternative classification systems have been proposed. For example, Clements and Warner created a comprehensive system, using the term “pulmonary malinosculation” to describe “a congenitally abnormal connection or opening of one or more components of the bronchopulmonary vascular complex.”126 Another approach described by Langston points out that many different lung malformations may have a systemic arterial supply; on the basis of this fact, the author considers that abnormal systemic arterial supply is an attribute rather than a defining characteristic and encourages use of a descriptive approach.128,131 Despite the existence of valid and widely cited competing classification systems, the terms “intralobar” and “extralobar” pulmonary sequestration seem to be deeply entrenched, and familiarity with the classic definitions and their limitations is essential. As with all congenital lung lesions, the radiologist is advised to focus on imaging features, including location, vascular supply, and appearance of the lesion, and avoid descriptors that may be unclear.






FIGURE 1.41. A 17-month-old asymptomatic boy with pulmonary sequestration that was initially detected on prenatal ultrasound (US). The lesion was surgically resected. A: Axial fetal US obtained at 33 weeks gestation shows a focal hyperechoic lesion (calipers) in the right lower lung. B: Axial postnatal lung window CT image demonstrates a lucent lesion (black arrow) located in the medial right lower lobe. C: Sagittal maximum intensity projection CT image shows an anomalous systemic artery (white arrow) supplying the lesion. This feeder artery arises from a branch of the left gastric artery (arrowhead).

With the wide availability of fetal imaging, pulmonary sequestration is now often first detected prenatally. On prenatal US with Doppler overlay, pulmonary sequestration typically appears as a homogeneous, hyperechoic pulmonary mass with an abnormal systemic arterial supply133 (Fig. 1.41A). On T2-weighted prenatal MRI, sequestration is commonly seen as a homogeneous lesion that is hyperintense compared to the adjacent lung.176 Abnormal arterial supply can sometimes be visualized on MRI as a flow void extending from the aorta or one of its branches. If the abnormal arterial supply is not visualized, the imaging findings are identical to other congenital lung lesions, including bronchial atresia, CPAM, and CLE.133,144,176 Similar to CPAMs, pulmonary sequestrations generally increase in size from the 20th to the 28th week and then decrease in size during the 3rd trimester.135 In the 3rd trimester, lesions become much more difficult to detect due to decreased size and a normal increase in the echogenicity and signal intensity of the adjacent lung.135
Although many lesions seem to disappear during the 3rd trimester, complete regression is very unusual and followup postnatal cross-sectional imaging is recommended in all cases because radiographs may not detect small lesions.144,177

The most common postnatal imaging appearance of pulmonary sequestration is a lung mass within one of the lower lobes (seen in 98% of cases).61 Although extralobar pulmonary sequestration can occur anywhere from the neck to below the diaphragm, the most common finding on chest radiography is a solid mass within the left lower lobe. Intralobar pulmonary sequestration also tends to occur in the lower lobes, and depending on its internal composition and the presence or absence of superinfection, it can appear as a solid mass, cystic lesion, or consolidation on chest radiographs.135

CT or MR angiography with 2D and 3D reformations is recommended in cases of suspected pulmonary sequestration to ensure that associated anomalous vessels are accurately detected61,65 (Fig. 1.41B and C). A study that compared the preoperative diagnostic accuracy of axial, multiplanar (2D), and 3D MDCT images in the evaluation of congenital lung malformations in pediatric patients showed that supplemental multiplanar and 3D images add diagnostic value for lesions associated with anomalous veins178 (Fig. 1.42). Extralobar pulmonary sequestrations classically appear as solid, enhancing masses with systemic arterial supply and systemic venous drainage. Intralobar pulmonary sequestrations typically become air-filled after fetal lung fluid has cleared.133 The mechanism of aeration is presumably collateral air drift because lesions have an abnormal tracheobronchial connection.135 As many as 50% to 90% of pulmonary sequestrations contain elements of CPAM on pathology. Therefore, it is not surprising that cystic elements are frequently identified on cross-sectional imaging.130,173 In cases with superimposed
infection, findings may include consolidation, air-fluid levels, and increased cyst formation in chronically infected lesions.61






FIGURE 1.42. An 11-month-old boy with intralobar pulmonary sequestration that was initially detected on prenatal ultrasound. The patient subsequently underwent surgical resection. A: Axial enhanced CT image shows an anomalous artery (arrow) arising from the descending aorta (DA). B: Three-dimensional reformatted CT image confirms the presence of the anomalous artery (arrow). C: Three-dimensional reformatted CT image demonstrates two anomalous veins (arrows) draining into inferior right pulmonary veins. The anomalous veins were not clearly visualized on axial CT images.






FIGURE 1.43. A 5-month-old asymptomatic boy with a hybrid congenital lung lesion that consisted of congenital pulmonary airway malformation and pulmonary sequestration. The lesion was resected. A: Axial enhanced lung window CT image shows a left lower lobe multicystic lesion (arrowheads) with a large feeding systemic artery (arrow). B: Sagittal oblique maximum intensity projection CT image demonstrates the anomalous systemic artery (arrow) arising from the descending aorta (DA).

The standard treatment for symptomatic pulmonary sequestration is surgical resection. Management for asymptomatic lesions continues to be somewhat controversial. Many recommend elective resection of intralobar pulmonary sequestration due to risks of future superimposed infection, pneumothorax, bleeding, and malignant transformation.179,180 Extralobar pulmonary sequestrations have a lower rate of complications than intralobar pulmonary sequestrations, and thus, management is more debatable. Extrathoracic extralobar pulmonary sequestration is often managed conservatively without treatment, but intrathoracic lesions are often surgically resected.135 Arterial embolization has been reported as a potential alternative to surgery in both intralobar and extralobar pulmonary sequestration in selected cases.181,182


Hybrid Congenital Lung Lesions

Elements of bronchial atresia, CPAM, and CLE often coexist within the same lesion, and hybrid or overlap lesions are often seen126,128,130,131,134,144 (Figs. 1.43 and 1.44). Langston has proposed that all congenital lung malformations are the consequence of in utero airway obstruction and represent a spectrum of lesions rather than distinct pathological entities with different underlying pathogenetic processes.128 Based on this theory, it is not surprising that hybrid lesions are often seen. To determine the frequency of overlap lesions, Riedlinger et al., used a dissection microscope to examine pathologic specimens from 47 congenital lung lesions and found atresia of a bronchus in 100% of extralobar pulmonary sequestrations, 82% of intralobar sequestrations, 70% of CPAMs, and 50% of CLE lesions and found parenchymal changes of CPAM in 91% of extralobar pulmonary sequestrations, 91% of intralobar pulmonary sequestrations, and 50% of CLE lesions.130 The high incidence of overlapping histopathologic features emphasizes that the radiologist can be most helpful by providing a description of the congenital lung malformation, focusing on location, airway or GI tract communication, vascular supply, and internal characteristics, rather than attempting to provide a specific diagnosis.


Infectious Lung Disorders

Pneumonia and other lower respiratory tract infections are the most common causes of illness in the pediatric population, with a worldwide incidence of 150 million cases per year
in children under the age of 5, ˜20 million of which lead to hospitalization.183 Acute lower respiratory infection, defined as infection that affects the airway below the glottis, is a rare cause of mortality in Western countries (<1 per 1,000 per year)184 but is the leading cause of childhood mortality in the world overall.183






FIGURE 1.44. A 2-month-old girl with a hybrid congenital lung lesion that consisted of congenital pulmonary airway malformation (CPAM) and congenital lobar emphysema (CLE). Coronal lung window CT image depicts areas of CLE as hyperinflation (asterisks) in the right upper and lower lobes. Two areas of CPAM appear as small cystic lesions (arrows).

A large number of pathogens may cause pneumonia, including viruses, bacteria, fungi, and other microorganisms. Certain age groups are more susceptible to different forms of pneumonia. Maternal antibodies confer passive immunity to newborns in the first months of life. As a result, bacterial pneumonia is more common in neonates and viral pneumonia is rare.185 As maternal antibodies wane and childhood antibodies are yet to be developed, viral pneumonia becomes more common, with a peak from 2 months to 2 years of age.185 After 2 years of age, bacterial pneumonia becomes more common, a trend that continues into adulthood.

Chest radiography has not been shown to change outcomes in routine cases of acute lower respiratory infection in children.186,187 However, the clinical diagnosis of pneumonia can be challenging, particularly in young children. Chest radiography is the primary imaging test performed to help confirm or exclude pneumonia in most cases.188 There is debate regarding the utility of the lateral chest radiograph, since the frontal radiograph is frequently sufficient to diagnose pneumonia.188,189,190,191 However, many advocate for its continued use, as certain important findings, such as hyperinflation and hilar adenopathy, may be better seen on the lateral view.191,192

Many different pathogens can cause lower respiratory tract infections. Although certain radiographic patterns are more typical with particular pathogens, considerable overlap precludes identification of a single causal organism based on chest radiographic findings alone. Frequently, radiographs are regarded as more clinically useful in differentiating between viral and bacterial pneumonia, as bacterial pneumonia requires antibiotics and viral pneumonia does not. Studies, however, have shown that viral and bacterial pneumonia cannot be reliably differentiated based on chest radiography alone.193,194,195 Separately, clinical and radiographic criteria both overestimate the prevalence of bacterial pneumonia.193 However, combined use of radiographic and clinical parameters has a high negative predictive value.193 Therefore, when combined radiographic and clinical features are not compatible with bacterial pulmonary infection, pediatric patients are unlikely to benefit from antibiotic treatment.188

Although there is considerable overlap in the radiographic features of different lower respiratory tract infections, several pathogens may present with characteristic patterns. These patterns and pertinent clinical factors for each pathogen are discussed in the following sections.


Viral Infection

Viral lower respiratory tract infections, which include bronchiolitis and pneumonia, occur via spread of airborne droplets.196 Viruses primarily infect the respiratory mucosa of the lower respiratory tract. As a result, infected cells become inflamed and necrotic, leading to bronchial wall edema and thickening. Mucus is also produced in response to inflammation. Because children’s airways are relatively smaller than adults’, and children tend to produce more mucus in response to viral infection, they are relatively more susceptible to air trapping and atelectasis due to airway narrowing and mucous plugging. This leads to the typical radiographic findings of pediatric viral respiratory infection, which include symmetric perihilar and peribronchial opacities, bronchial wall thickening, hyperinflation, and atelectasis.188 It is important to recognize that atelectasis caused by viral infection is frequently misinterpreted as focal consolidation due to bacterial pneumonia.193,197

A variety of viral pathogens may cause respiratory infection in children—pathogens that are most often encountered in clinical practice are discussed in the following section.


RNA Viruses


Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants and young children. RSV can have a variable clinical course, ranging from mild coryza to severe respiratory distress. RSV infection accounted for 24% of hospitalizations for children <5 years old in the United States from 1997 to 2006.198 Hospitalization rates are highest among infants <3 months old (48.9 per 1,000).198 Several conditions predispose children to RSV infection and more severe disease course, such as chronic lung disease, congenital airway anomalies, trisomy 21, and history of prematurity.199,200 Mortality is ˜69 to 120 per 100,000 hospitalizations in children without risk factors, but 18.8 times higher in highrisk children with RSV infection.200

Chest radiographs in RSV infection may be normal or demonstrate perihilar interstitial opacities and/or bronchial wall thickening, hyperinflation, and atelectasis201,202 (Fig. 1.45). Several laboratory tests aid in the diagnosis of RSV infection, including antigen tests, PCR assays performed on respiratory specimens, and serologic tests. The majority of children with RSV infection require only supportive treatment. Bronchodilators have been shown to have little, if any, benefit203,204 and the American Academy of Pediatrics (AAP) recommends against their routine use.205 There is also little evidence that corticosteroid treatment confers a benefit, and the AAP also recommends against its routine use.205 Antibiotics should not be given prophylactically, but rather reserved for cases complicated by superimposed bacterial infection.205 Ribavirin is the only treatment approved for children with RSV infection, although randomized controlled studies showing its benefits are small and some studies have shown no benefit. Therefore, the AAP recommends that ribavirin should not be used routinely in RSV infection.205


Human Metapneumovirus

Human metapneumovirus (HMPV) is an RNA virus from the Pneumovirinae subfamily of the Paramyxoviridae family, the same subfamily as RSV.206 HMPV was identified as a cause of viral infection relatively recently and was first isolated from children with respiratory tract infection in 2001207; however, retrospective sampling has identified the virus in samples
from as early as 1958.207 HMPV causes a lower respiratory tract infection with highly similar clinical manifestations to RSV. HMPV is primarily an infection of children, with 77% of the population becoming seropositive by age 5, 91% by age 10, and 96% by age 20.208 Like RSV, infections from HMPV are usually self-limited, although severe symptoms in a subset of pediatric patients can require hospitalization. As in RSV, children with comorbidities including chronic lung disease, prematurity, and immunodeficiency are more likely to have severe disease207 (Fig. 1.46).






FIGURE 1.45. A 4-month-old girl with respiratory syncytial virus infection who presented with cough and wheezing. Frontal chest radiograph shows perihilar interstitial opacities with peribronchial cuffing and hyperinflation.

Radiographic features of HMPV infection are similar to those of RSV infection and may include bronchial wall thickening, hyperinflation, and focal opacification.209 Laboratory tests for acute HMPV infection include RT-PCR, shell vial culture, and immunofluorescence assays. Serologic tests are also available, although have limited clinical utility given the high rate of seropositivity in the general population. No safe and effective antiviral treatment has been developed, and current treatment is largely focused on supportive measures and prevention using contact precautions and handwashing.207 Several case reports have described successful use of ribavirin,210,211,212,213 and further clinical studies are needed to investigate its possible role.


Parainfluenza Virus

There are five types of human parainfluenza virus (hPIV), serotypes 1, 2, 3, 4a, and 4b. Types 1 to 3 are the most common and, among children <5 years of age, are responsible for 16,000 to 100,000 hospitalizations per year, with 9,000 to 52,000 of those hospitalizations due to hPIV-3 infection.214 hPIV-3 affects a younger age group, with most infections occurring before 12 months of age, while hPIV-1 and -2 tend to affect children from 2 to 5 years of age.215






FIGURE 1.46. An 18-month-old girl born at 29 weeks of gestation who developed human metapneumovirus infection superimposed on underlying chronic lung disease of infancy. Frontal chest radiograph shows a tracheostomy and bilateral perihilar interstitial opacities with peribronchial cuffing and hyperinflation. Underlying coarse opacities represent chronic lung disease of infancy.

Clinical manifestations of hPIV infection depend on the serotype. hPIV-1 infection causes upper respiratory infection in 46%, croup in 31%, lower respiratory infection in 5%, and other manifestations in 18%.216 hPIV-2 infection causes croup in 45%, upper respiratory infection in 40%, lower respiratory infection in 2%, and other manifestations in 13%.216 hPIV-3 infection causes upper respiratory infection in 64%, lower respiratory infection in 9%, croup in 9%, and other manifestations in 18%.216

Pediatric patients with croup due to hPIV infection typically have symptoms of low-grade fever, barking cough, stridor, nasal flaring, and dyspnea.217 The diagnosis of croup should be made clinically, but radiographs of the airway may be obtained for confirmation or to assess for alternative diagnoses.217 Frontal radiography may demonstrate a “steeple sign” due to symmetric subglottic narrowing, although this finding can be absent in up to 50% of cases218 (Fig. 1.47A). Lateral radiography may show distention of the hypopharynx (Fig. 1.47B). Less than 10% of patients with croup develop viral pneumonitis causing hypoxemia,215 and chest radiographs in these cases may demonstrate findings similar to other viral lower respiratory infections, including perihilar interstitial opacities, bronchial wall thickening, and atelectasis (Fig. 1.48).

Laboratory diagnosis may be sought when symptoms are not specific. Available laboratory tests include RT-PCR assays and viral culture, which may be used in the acute phase of the illness, and serologic assays, which can determine whether the patient has been previously exposed.215 The majority of hPIV infections require no treatment. Management of croup caused by hPIV is largely supportive and may include nebulized racemic epinephrine and corticosteroids in severe cases.215







FIGURE 1.47. A 2-year-old girl with laryngotracheobronchitis (also known as croup) who presented with barking cough and stridor. A: Frontal radiograph of the neck shows a “steeple sign” (arrow) due to narrowing of the subglottic trachea. B: Lateral radiograph of the neck demonstrates distension of the hypopharynx (arrowheads) and narrowing of the subglottic airway (arrow).


Rhinovirus

Human rhinoviruses (HRVs) are RNA viruses from the Enterovirus genus, which also includes polioviruses, coxsackieviruses, and echoviruses. HRVs are one of the causes of the common cold and among the most common viral diseases worldwide.219 The average child has one HRV infection per year and infection rates are highest in the fall.220 Infection most commonly occurs via inhalation of respiratory droplets.219 Typically, symptoms are consistent with the common cold, and infection may cause asthma exacerbation. Lower respiratory tract infection by HRV can produce a similar radiographic pattern to that seen in other viral infections221 (Fig. 1.49). HRV can cause serious and sometimes fatal lower respiratory infection in children, particularly in very young infants with coinfection by other viruses or bacteria and/or other underlying illnesses.222,223,224






FIGURE 1.48. An 8-week-old boy with a parainfluenza lower respiratory tract infection who presented with severe respiratory distress requiring intubation. Frontal chest radiograph shows perihilar interstitial opacities with multifocal atelectasis, mainly in the upper lobes and left lower lobe.


Influenza

Influenza is a highly contagious infection of the respiratory tract that is caused by the influenza virus. Influenza is common in children, with the highest rates among children younger than 2 years of age, especially those with chronic medical conditions.225 Among children younger than 5 years of age, influenza infection has an annual hospitalization rate of 0.9 per 1,000, an annual emergency department visit rate of 6 to 27 per 1,000, and an annual clinic visit rate of 50 to 95 per 1,000.226 Clinical evaluation is insensitive, and influenza is only diagnosed in ˜28% of hospitalized patients and 17% of outpatients with the infection.226

Influenza infects the respiratory epithelium and can produce severe pneumonia. Chest radiographs may demonstrate pulmonary opacities, which are frequently bilateral and diffuse in children with influenza-associated lower respiratory infection227 (Fig. 1.50). Pneumonia can be due to the virus itself or secondary bacterial pneumonia, typically due to
Streptococcus pneumoniae or Staphylococcus aureus infection.228 Seasonal influenza epidemics typically occur annually, for instance, usually between October and May in the United States.229 In recent years, several contagious outbreaks of infection by novel influenza strains have resulted in high mortality and morbidity. A highly virulent avian-origin virus, H5N1, crossed over to humans in 1997, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) resulted in a worldwide outbreak in 2002, a swine-origin H1N1 virus caused a pandemic in 2009, and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) spread to 27 countries in 2016. These variants are discussed further below.






FIGURE 1.49. A 4-year-old boy with rhinovirus lower respiratory tract infection who presented with fever and asthma exacerbation. Frontal chest radiograph shows prominent interstitial opacities and atelectasis (asterisk) in the left lower lobe.






FIGURE 1.50. A 5-year-old boy with influenza B lower respiratory tract infection who presented with fever and cough. Frontal chest radiograph shows bilateral peribronchial thickening and atelectasis (asterisk) in the left lower lobe.


Avian-Origin Influenza (H5N1) Virus

In the past several years, there have been reports of human illness caused by avian influenza viruses after direct contact with infected poultry. In 1997, there were 18 human cases, with a 33% mortality rate.206 From 2003 to 2007, there were 379 cases, with a 63% mortality rate.206 Symptoms typically begin with mild respiratory complaints, which rapidly progress to severe pneumonia and acute respiratory distress syndrome206 (Fig. 1.51). Although definite human-to-human transmission has not been demonstrated, there is concern that genetic assortment could occur and lead to a pandemic caused by a highly virulent influenza strain.


Severe Acute Respiratory Syndrome Coronavirus

In 2002, a new severe respiratory illness due to a coronavirus emerged in Guangdong Province, China, and led to a 9-month long worldwide outbreak, infecting 8,098 people and causing 774 deaths.230 The virus, called SARS-CoV, was likely transmitted to humans from civet cats. Respiratory failure requiring mechanical ventilation occurred in 10% to 20% of infected adult patients, but pediatric patients had more mild symptoms and no deaths were reported among affected children.206,231 Radiographic findings in children with SARS are not specific and may include consolidation (45.2%), which is often peripheral and multifocal (22.6%), and bronchial wall thickening (14.5%)232 (Fig. 1.52). In a substantial proportion of cases, radiographs are normal (35.5%).232 The outbreak was declared to be over in July 2003, and since then, only a few laboratory-associated cases have been reported.206






FIGURE 1.51. A 15-year-old boy with avian-origin influenza (H5N1) virus infection who presented with severe respiratory distress requiring intubation. Frontal chest radiograph shows diffuse bilateral airspace opacities with air bronchograms.







FIGURE 1.52. A 6-year-old girl with fever, cough, and respiratory distress due to severe acute respiratory syndrome coronavirus (SARSCoV) infection. Frontal chest radiograph shows bilateral, multifocal consolidations (asterisks).


Swine-Origin Influenza A (H1N1) Virus

In 2009, a novel influenza A (H1N1) virus emerged from a swine reservoir and caused a worldwide pandemic. The virus is now referred to as 2009 pandemic influenza A (H1N1). Symptoms ranged from self-limited febrile respiratory infection to severe illness.233 In the United States, in 2009, ˜61 million illnesses occurred, resulting in 274,000 hospitalizations and 12,400 deaths.225 Rates of hospitalization were highest among infants and young children.229 In 2009, 317 children in the United States died as a result of infection and complications. Sixty-eight percent had an underlying medical condition that put them at greater risk.234 The virus was associated with high rates of diffuse alveolar damage (DAD), viral pneumonia, and superimposed bacterial pneumonia, with >25% of fatal cases showing evidence of bacterial pneumonia caused by S aureus, S pneumoniae, or S pyogenes.235

In a study of hospitalized patients with 2009 pandemic influenza A (H1N1) infection, 64% of children had pulmonary opacification on chest radiography, which was bilateral in 64% of cases where it was present227 (Fig. 1.53). Whereas pulmonary opacification tended to be peripheral in adults, it was more commonly diffuse in children.227 Another study of 108 pediatric patients with microbiologically confirmed influenza A (H1N1) infection showed that initial chest radiographs were often normal or showed prominent peribronchial markings with hyperinflation in affected pediatric patients with a mild and self-limited clinical course of influenza A (H1N1) infection. However, bilateral, symmetric, and multifocal areas of consolidation, often associated with ground-glass opacities, were seen in pediatric patients with a more severe clinical course236 (Fig. 1.54).






FIGURE 1.53. A 3-year-old boy who presented with fever and shortness of breath due to swine-origin influenza A (H1N1) virus infection. Frontal chest radiograph shows perihilar interstitial opacities, mild peribronchial cuffing, and atelectasis in the left lower lobe.


Middle East Respiratory Syndrome Coronavirus

Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012 and, as of 2016, had spread to 27 countries. Of 1,728 laboratory-confirmed cases, 624 have resulted in death.237 Clinical manifestations are variable and may include fever, chills, rigors, headache, cough, dyspnea, myalgia, coryza, sore throat, nausea, vomiting, dizziness, sputum production, diarrhea, abdominal pain, progressive
pneumonitis with respiratory failure, diffuse alveolar damage (DAD), septic shock, and multiorgan failure.238 Children are more likely to have mild disease, with cough and fever being the most commonly reported symptoms.238 Mortality is much less common in children than in adult patients, except in cases in which there is an underlying medical condition.238






FIGURE 1.54. A 10-year-old girl with fever and worsening cough due to swine-origin influenza A (H1N1) virus infection. Frontal chest radiograph shows bilateral, multifocal consolidations (asterisks).

Of all patients with MERS-CoV infection (children and adults), 83% present with abnormal chest radiographs, with findings including ground-glass opacity (66%), consolidation (18%), and irregular linear-type airspace disease (9%).238,239 Findings are more often unifocal (69%) than multifocal (30%).239 Initially, opacities tend to be peripheral and located within the mid to lower lungs, followed by progression to involve the central and upper lungs.238 Chest radiographic findings are often pronounced in cases of severe disease, and severity of chest radiographic findings is an independent predictor of mortality in adults.239 Pleural effusion and pneumothorax are more common in patients who do not survive.239 In the first week of the illness, chest CT findings include groundglass opacity (53%), consolidation (20%), combined groundglass opacity and consolidation (33%), and interlobular septal thickening (26%)238 (Fig. 1.55). Chest CT findings in the 2nd and 3rd weeks may include a “crazy-paving” pattern, cavitation, tree-in-bud opacities, centrilobular nodules, constrictive obliterative bronchiolitis, bronchiolitis obliterans (BO), peribronchiolar air trapping, thickened peripheral bronchioles, and organizing pneumonia.238


Measles

Measles is seen less frequently in the modern era due to vaccination, although it is still encountered in immunosuppressed and nonvaccinated children. Measles is highly contagious among those without immunity and is spread via aerosolized respiratory droplets. Infection is characterized by fever, cough, coryza, conjunctivitis, Koplik spots, and maculopapular rash. Children with typical measles may develop pneumonia, with a broad range of reported incidence from 5% to 55%, and acute respiratory distress syndrome may occur in a subset of these patients as a severe complication.240,241,242 Chest radiographs in measles pneumonia typically show hyperinflation with bilateral perihilar opacification, which is similar to the pattern seen in other viral infections.242 However, measles may also cause lobar or segmental pneumonia, pneumothorax, pleural effusion, and empyema.241 Chest CT may detect pulmonary abnormalities more frequently than radiographs.243 Findings on CT may include multiple ground-glass opacities, nodular densities, or consolidations243 (Fig. 1.56). Superimposed bacterial infection may occur in up to 30% of cases.244 Severe respiratory symptoms are rare in young infants and children with measles, and most children recover without complications.240,241






FIGURE 1.55. A 17-year-old girl with Middle East respiratory syndrome coronavirus (MERS-CoV) infection who presented with fever, chills, headache, cough, and diarrhea. Axial lung window CT image shows multiple areas of ground-glass opacity (arrows) and consolidation (asterisks).


Human Immunodeficiency Virus

Human immunodeficiency virus (HIV) is an RNA retrovirus that primarily infects CD4+ T lymphocytes and leads to acquired immunodeficiency syndrome (AIDS). Most HIV infections in children are the result of mother-to-child transmission, and most adolescent cases are the result of transmission during sexual activity or intravenous drug use.245 There are numerous pulmonary manifestations of HIV infection, but the three most common are lymphoid interstitial pneumonitis/pulmonary lymphoid hyperplasia (LIP/PLH), Pneumocystis jiroveci infection, and bacterial pneumonia. Common causes of viral pneumonia in HIV infection include RSV, parainfluenza virus, influenza virus, adenovirus, CMV, and HSV. The most common causal agents of bacterial pneumonia in HIV include S pneumoniae, S aureus, Haemophilus influenzae type b, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. Fungal pneumonias also occur in HIV, most commonly Candida albicans, Cryptococcus neoformans, and Histoplasma capsulatum infections. Each of these entities is discussed in detail in the following sections.


DNA Viruses


Adenovirus

Adenoviruses are nonenveloped double-stranded DNA viruses that are most commonly associated with respiratory tract infection
and gastroenteritis but may also cause keratoconjunctivitis, cardiac infection, genitourinary infection, and lymphatic infection. Adenovirus can cause a variety of respiratory tract infections, including otitis media, pharyngitis, tonsillitis, croup, bronchiolitis, bronchitis, pneumonia, and pleural effusion. Up to 20% of pneumonias occurring in children <5 years of age are due to adenovirus.246 Types 3, 7, and 21 have been associated with the most severe disease, and fatalities have been reported with these types and several others.247






FIGURE 1.56. A 5-year-old girl with measles who presented with fever, cough, and maculopapular rash. Axial lung window CT image shows multiple small bilateral pulmonary nodules.






FIGURE 1.57. An 8-month-old boy with adenovirus lower respiratory tract infection who presented with fever and cough. Frontal chest radiograph shows perihilar interstitial and hazy opacities.

Radiographic findings in adenovirus pneumonia may include patchy or diffuse confluent pulmonary opacities, bronchial wall thickening, peribronchial linear opacities, and occasional pleural effusion246,248 (Figs. 1.57 and 1.58). Long-term sequelae develop in a subset of affected pediatric patients and may include bronchiectasis and BO.247,248,249,250






FIGURE 1.58. A 2-year-old boy with adenovirus lower respiratory tract infection who presented with severe respiratory distress requiring intubation. Frontal chest radiograph shows extensive bilateral airspace opacities and bilateral pleural effusions (arrows).


Cytomegalovirus

Cytomegalovirus (CMV) is a double-stranded DNA virus from the β-herpesvirus group. CMV is the most common congenital infection in the United States and is a cause of opportunistic infection in pediatric patients with decreased T-cell function, including organ transplant recipients and pediatric patients with AIDS. Infections in the fetus and immunosuppressed children may involve the CNS, liver, and lungs and can lead to petechial hemorrhage, purpura, and hemolytic anemia. Infection in children and adults without immunodeficiency is most commonly asymptomatic, although can cause pharyngitis, tonsillitis, a mononucleosis syndrome characterized by fever, headache, and malaise, or occasionally, pneumonia.251 CMV pneumonia in immunocompetent hosts is usually benign and self-limited, but it is a very serious illness with a high mortality rate in immunosuppressed patients.251 Infection can occur in the perinatal period and is usually asymptomatic in full-term neonates, although can cause lymphadenopathy, hepatosplenomegaly, hepatitis, or pneumonitis in up to one-third of cases.252 Perinatal CMV pneumonia may occur in premature neonates and can cause protracted severe pneumonitis and subsequent chronic lung disease of infancy.252,253

Radiographic findings in CMV pneumonia are often similar to those seen in other viral infections, including hyperinflation with diffuse interstitial or peribronchial opacification (Fig. 1.59).254 Findings on CT may include centrilobular nodules, ground-glass opacities, and consolidation.255,256,257 CMV pneumonia can be complicated with superinfection by gramnegative enteric bacteria and fungi in transplant patients and P jiroveci infection in AIDS patients.251






FIGURE 1.59. Newborn boy with cytomegalovirus lower respiratory tract infection who presented with desaturation and irritability. Frontal chest radiograph shows extensive multifocal ground-glass opacities and consolidations in both lungs, more severe on the right.







FIGURE 1.60. A 13-year-old boy on chronic immunosuppressive therapy for renal transplant, who presented with cough and wheeze due to varicella-zoster infection. A: Frontal chest radiograph shows multiple small, poorly defined pulmonary nodules in both lungs. B: Axial lung window CT image demonstrates multiple small pulmonary nodules with surrounding ground-glass opacities and a small left pleural effusion (asterisk).


Varicella-Zoster Virus

Varicella-zoster virus (VZV) is an alpha herpesvirus that causes varicella (chickenpox) and zoster (shingles). Varicella occurs during primary infection, most often in childhood, and is characterized by fever and pruritic rash. Zoster occurs when latent VZV reactivates within the dorsal root ganglia and causes unilateral skin infection in a dermatomal distribution or other manifestations. Zoster is primarily a disease of adults but can occur in children, particularly in the setting of immunodeficiency. Although rare in children, VZV can cause serious pneumonia in adults.258,259

Chest radiographs in VZV pneumonia typically demonstrate multiple 5- to 10-mm poorly defined nodules260 (Fig. 1.60). On CT, nodules may be coalescent and demonstrate a groundglass halo, or patchy ground-glass opacities may be seen. In the majority of cases, pulmonary nodules and opacities resolve within a week of disappearance of rash but may persist longer in cases of severe disease.260 Nodules may calcify and appear as numerous 2 to 3 mm calcifications that persist after infection has resolved260 (Fig. 1.61).


Epstein-Barr Virus

Epstein-Barr virus (EBV) is a very common double-stranded DNA virus from the herpesvirus family. It is commonly associated with infectious mononucleosis but also plays a central role in the development of numerous lymphoproliferative disorders and malignancies. Rare cases of infectious mononucleosis can have pulmonary involvement, which may be characterized by alveolar opacifications or consolidation that may be diffuse and confluent in severe cases261 (Fig. 1.62). Lymphadenopathy and pleural effusions can also be seen.261,262,263 EBV may also lead to pulmonary manifestations in cases of EBV-associated hemophagocytic lymphohistiocytosis, chronic active EBV infection, LIP in HIV infection, posttransplant lymphoproliferative disorder (PTLD), and pulmonary lymphoma.264


Herpes Simplex Viruses

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are double-stranded DNA viruses in the human herpesvirus family, which also includes CMV, EBV, VZV, and human herpesviruses (HHV) types 6A, 6B, 7, and 8. HSV is ubiquitous, and clinical manifestations range from no symptoms or mild “fever blisters” to life-threatening disseminated infection in neonates.265 HSV pneumonia is uncommon but has been described in neonates266,267 and may occur in immunocompromised patients.260,265 HSV pneumonia may occur due to extension of oropharyngeal infection into the lower respiratory tract or from hematogenous spread.260 HSV pneumonia is characterized by alveolar necrosis and ulceration on pathology.260

Radiographic findings in reported neonatal cases include diffuse interstitial and alveolar opacifications as well as
bilateral pleural effusions266,267 (Fig. 1.63). Imaging findings in immunocompromised older patients with HSV pneumonia include patchy segmental and subsegmental consolidation, ground-glass opacities, atelectasis, centrilobular nodules, and pleural effusion.268,269,270 HSV-1 pneumonias are frequently associated with coexisting bacterial pneumonia.260






FIGURE 1.61. A 40-year-old female with a prior history of varicella pneumonia. Frontal chest radiograph shows multiple small, calcified pulmonary nodules in both lungs.






FIGURE 1.62. A 5-year-old girl who presented with fever and cough due to Epstein-Barr virus lung infection. Frontal chest radiograph shows multifocal consolidations (asterisks) involving the right middle and left lower lobes.


Bacterial Infection

Bacterial pneumonias have three main radiographic appearances: (1) focal consolidation, (2) bronchopneumonia, and (3) atypical pneumonia. It is important to recognize that these patterns are often not seen in young children and are virtually always absent in neonates.188






FIGURE 1.63. A 4-day-old girl who presented with fever and respiratory distress due to herpes simplex virus infection. Frontal chest radiograph shows right upper lobe atelectasis with patchy subsegmental ground-glass opacities in both lungs and more confluent airspace opacity (arrow) in the right midlung.






FIGURE 1.64. A 2-year-old boy who presented with fever, cough, and elevated white blood cell count due to lobar bacterial pneumonia. Frontal chest radiograph shows a dense consolidative opacity (asterisk) with an internal air bronchogram expanding the right upper lobe and causing bulging of the minor fissure (arrow).

The typical imaging appearance of pulmonary consolidation occurs due to filling of alveoli with exudate, inflammatory cells, and fibrin.196 Consolidation may be lobar, or can take on a spherical shape in children, causing “round pneumonia”271,272 (Figs. 1.64 and 1.65). Children are predisposed to developing round pneumonia due to underdeveloped pores of Kohn and
canals of Lambert, and resultant centrifugal spread of infection within the lung leads to spherical consolidation with sharp margins. The mean age for round pneumonia is 5 years, with 75% occurring before 8 years of age and 90% occurring before 12 years of age.271






FIGURE 1.65. A 3-year-old boy who presented with fever and cough due to bacterial round pneumonia. Frontal chest radiograph shows a round opacity (arrow) with an internal air bronchogram in the right upper lobe, as well as bibasilar subsegmental atelectasis. Follow-up chest radiograph obtained after treatment (not shown) showed complete resolution.

Bronchopneumonia is a term used to describe a different form of bacterial pneumonia that is characterized by peribronchial inflammation, which involves the airways in multiple segments or lobes and then spreads to the adjacent parenchyma, resulting in patchy consolidation.196

Atypical pneumonia describes an infection in which nonpulmonary symptoms, including headache, sore throat, and pharyngeal exudates, are the major clinical features. Chest radiographs typically demonstrate reticular or band-like opacities in a patchy distribution without a focal region of consolidation.185

Although certain patterns of bacterial pneumonia are seen more commonly with particular pathogens, there is considerable overlap in the radiographic findings in different bacterial pneumonias. Pertinent clinical and imaging features of the most commonly encountered bacterial pneumonias in the pediatric population are discussed below.


Streptococcus pneumoniae

Streptococcus pneumoniae is the leading cause of bacterial pneumonia in children under 5 years of age. S pneumoniae is a gram-positive, catalase-negative, facultative anaerobic bacterium that grows in pairs (diplococci) and short chains. S pneumoniae is ubiquitous and can be found in the nasopharynges of up to 30% of children in Western countries and up to 80% of children in developing countries.273 Symptoms of pneumococcal pneumonia typically begin with a prodrome similar to a viral respiratory tract infection, followed by high fever, rigors, dyspnea, pleuritic chest pain, and cough with rust-colored sputum.274 S pneumoniae is a common cause of pneumonia in otherwise healthy children. Several risk factors are associated with increased incidence and complications of pneumococcal pneumonia, including immunocompromise, chronic heart and lung disease, diabetes mellitus, sickle cell disease (SCD), asplenia, and renal failure, and pneumococcal vaccine is recommended in patients with these conditions.275 Preceding viral infection, particularly with influenza, is also a risk factor for pneumococcal pneumonia.228

The typical radiographic appearance of pneumococcal pneumonia is airspace consolidation with air bronchograms involving a single lobe. In a minority of cases, consolidation may take on a round appearance in young children (round pneumonia) (Fig. 1.65) or may involve multiple lobes. Pneumococcal pneumonia can be complicated by pleural effusion, empyema, or lung necrosis in <30% of cases (Fig. 1.66). The imaging evaluation of uncomplicated pneumococcal pneumonia is usually limited to chest radiographs. Chest US is playing an increasing role in the evaluation of pneumonia, particularly pneumonia complicated by pleural disease such as empyema.42,45 Enhanced chest CT may be performed in selected cases of complicated pneumonia but is not indicated in the routine evaluation of uncomplicated cases.


Streptococcus pyogenes (Group A Streptococcus)

Streptococcus pyogenes, also known as group A β-hemolytic streptococcus (GAS), is a gram-positive coccus that causes a wide range of infections in pediatric patients. Notably, this organism can cause the postinfectious sequelae of rheumatic fever and poststreptococcal glomerulonephritis. Although the majority of streptococcal infections are relatively benign, severe invasive infections, including necrotizing fasciitis and streptococcal toxic shock syndrome, may occur. Respiratory infections more commonly involve the upper respiratory tract and are relatively benign, typically including pharyngitis and tonsillitis. Pneumonia and empyema are less common invasive GAS infections276,277,278 (Fig. 1.67). GAS pneumonia may be lobar or bronchocentric, with a bilateral pattern sometimes seen in bronchocentric disease.279 Necrotizing pneumonia with pulmonary abscess is a rare complication.280,281


Streptococcus agalactiae (Group B Streptococcus)

Streptococcus agalactiae, also known as group B streptococcus (GBS), is a gram-positive coccus. GBS is a common cause of pneumonia and sepsis in newborns and is discussed in detail in the previous section describing neonatal lung disorders and neonatal pneumonia.


Staphylococcus aureus

Staphylococcus aureus is a gram-positive coccus that groups in pairs, chains, and clusters. S aureus can cause a large number of infections, including pneumonia. Pneumonia can occur due to inhalation of the organism or hematogenous seeding of the lungs in the setting of bacteremia. Pneumonia due to inhalation typically manifests as a progressive bronchopneumonia, which begins as patchy multifocal opacifications that later coalesce to form consolidations.

Methicillin-resistant strains are increasingly common. Methicillin-sensitive S aureus (MSSA) and methicillinresistant S aureus (MRSA) pneumonia may both cause pneumonia in pediatric patients, although findings can differ. Eredem et al., describe a series of pediatric patients with S aureus pneumonia and report that 65% had MRSA and 35% had MSSA, MRSA patients were younger on average (65% were younger than 1 year of age), consolidation was more often unilateral in MRSA (62%) and more often bilateral in MSSA (79%), pneumatoceles occurred in 50% of MRSA cases and 21% of MSSA cases, and pleural effusions occurred in 85% of MRSA and 64% of MSSA cases.282 Necrotizing pneumonia and abscess can also occur283 (Figs. 1.68 and 1.69).

In cases of hematogenous pulmonary infection from S aureus, the imaging findings typically include multiple bilateral nodular densities that often cavitate and form abscesses with air-fluid levels. If a pattern of hematogenous infection is seen within the lungs, a search for the infectious source is essential. Common sites of primary infection include cellulitis, septic arthritis, and osteomyelitis.


Haemophilus influenzae

Haemophilus influenzae is a gram-negative coccobacillus that was first isolated in the 1889 influenza pandemic and was originally believed to be the cause of influenza. This was later
disproven, but the organism was given the species name of influenzae to reflect this historical association. H influenzae type B (HiB) is a particularly virulent strain and was the most common cause of bacterial meningitis in children under 5 years in the United States and a common cause of several other infections including pneumonia, empyema, epiglottitis, pericarditis, cellulitis, and septic arthritis before 1990.284 Since the introduction of a conjugate vaccine in 1988, the incidence of HiB infection in the United States has fallen by more than 95%.285 Before widespread vaccination, children with underlying medical conditions, including SCD, asplenia, HIV infection, and malignancy, were at increased risk. H influenzae infection is now relatively rare in countries with widespread vaccination but can still be seen in nonimmunized children and in children with poor antibody response to vaccination, including those with underlying immunodeficiency.286






FIGURE 1.66. A 4-year-old boy who presented with fever and cough due to Streptococcus pneumoniae pneumonia. A: Frontal chest radiograph obtained at initial presentation shows consolidation (asterisk) in the left lower lobe. B: Frontal chest radiograph obtained 4 days later demonstrates a cystic cavity (black arrowhead) within the left lower lobe due to necrosis. A chest tube (black arrow) was placed for treatment of a complicated effusion. C: Axial enhanced CT image obtained 10 days after initial presentation shows a loculated empyema with pleural enhancement (white arrows) and multiple cystic cavities (white arrowheads) in the left lower lobe due to necrosis.

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May 8, 2019 | Posted by in PSYCHOLOGY | Comments Off on Lung
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