High-resolution CT of pediatric lung disease

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HIGH-RESOLUTION CT OF THE LUNG II

HIGH-RESOLUTION CT OF PEDIATRIC LUNG DISEASE Jerald P. Kuhn, MD, and Alan S. Brody, MD

Since a review in 1993 of high-resolution CT (HRCT) in children,43 the technique has become more widely used, but there is still limited experience with many of the uncommon and rare childhood pulmonary diseases. Even with the common diseases, such as asthma, cystic fibrosis, bronchopulmonary dysplasia (BPD), and infection, there is no consensus regarding when and how to use HRCT. This article provides a foundation for differential diagnosis based on an approach using anatomic categories of disease defined by CT findings. CT findings have been organized into those suggesting disease of the large and small airways; alveolar disorders, both interstitial and air-space; and diseases involving the peripheral (septal) interstitial tissues. Also discussed are diseases associated with pulmonary nodules, vascular disorders, pulmonary fibrosis, and fatal neonatal lung diseases. INDICATIONS The most common indications for pediatric HRCT are listed in Table 1. Virtually any time a child has a pulmonary parenchymal abnormality requiring CT, a relatively thin-slice technique should be used in combination with the edge-enhancing algorithm. For some conditions, such as metastatic disease, all of both lungs need to be imaged. For other con-

ditions, such as an anomaly or localized mass, it may be possible to restrict the examination to the region of interest to limit radiation to the patient. Although these are not strictly HRCT studies, and are not discussed, the principles of interpretation are the same. TECHNIQUE Image Quality Four components impact on the quality of HRCT images in children: (1) motion, (2) lung Table 1. INDICATIONS FOR PEDIATRIC HRCT 1. Normal chest radiograph with serious or unexplained symptom Fever in an immune compromised patient Unexplained dyspnea, wheezing, or severe or atypical asthma 2. Abnormal but nonspecific chest radiograph Ill-defined nodules, opacities or suspicion of interstitial disease Guide for biopsy 3. Detection of bronchiectasis 4. Detection of sequelae of infection Bronchiolitis obliterans or bronchiectasis 5. Cystic fibrosis Staging Evaluation of therapy Research 6. Bronchopulmonary dysplasia Evaluation of severity of disease

From the Department of Radiology, State University of New York at Buffalo School of Medicine, Buffalo, New York (JPK); and Departments of Radiology and Pediatrics, Children’s Hospital Medical Center, Cincinnati, Ohio (ASB)

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volume, (3) patient size, and (4) CT technical factors. Technique should be chosen after consideration of the first three factors. Although technique is the primary determinant of dose, it has the least impact on image quality. Motion. The greatest impediment to obtaining high-quality CT studies in children is respiratory and gross body motion. In children who cannot follow instructions, typically those under 3 years old, motion must be controlled by using restraints, sedation, and the shortest possible scan time available. Sedation is used in varying degrees in different departments and many protocols are in use.17 With a 0.1-second scan time of electron beam CT (EBCT)43 and the speed of the new multisection helical CT scanners, sedation is not usually necessary.68 Sedation is still required in many uncooperative children between the ages of 6 months and 6 years. Children less than 6 months old usually lie still, frequently falling asleep after a feeding. Sedation is rarely required in children over 6 years old. Chloral hydrate is frequently used in children less than 2 years old. Pentobarbital is a commonly used drug in older children. In most cases young children are imaged during quiet respiration. Posterior atelectasis is usually less striking than in adults,74 but is present in nearly all patients undergoing general anesthesia. 74, 77 Prone imaging is rarely necessary. Lung Volume Lung volume during quiet respiration is lower than during maximum inflation, but the appearance during quiet breathing is closer to a full inspiratory image than an expiratory image. No comparison between breathing and breath-hold images has been performed with HRCT, but for helical CT an experimental study with pathologic correlation found comparable image quality.12 Inspiratory and expiratory images are very helpful in evaluating abnormal lung attenuation in children and adults. With EBCT a dynamic scan can be obtained during the course of a normal respiratory cycle (Fig. 1).43 If a child is too young to cooperate, a decubitus scan can serve to evaluate possible air trapping on the dependent side.48 By about 6 years of age, most children can cooperate to produce a good quality inspiratory and expiratory HRCT. This degree of cooperation usually requires preparation and a member of the CT team in the scan room. Practicing inspiratory

and expiratory maneuvers before entering the scan room is helpful. Parents can sometimes be enlisted to help their child cooperate. It is unusual for a child to follow verbal instructions from the control room for HRCT with inspiratory and expiratory images until about 12 years old. CT Technique The factors varied in pediatric HRCT are slice thickness, scan time, tube kilovoltage, and tube current. Slice thickness is usually the thinnest available. Slice spacing should be chosen based on the suspected pathology. If chest radiographs are normal, and a diffuse interstitial process is suspected, four or five slices may be sufficient. If the detection of a few small cysts is of diagnostic importance, more slices should be obtained. In general the authors use 10-mm slice spacing in children over 10 years old, 7-mm spacing in children from 2 to 10 years old, and 5-mm spacing for children less than 2 years of age. Early reports of HRCT emphasized the potentially high radiation dose from this technique.60 Since that time it has been recognized that HRCT can be done using a lower patient dose than conventional CT.57 Low-dose techniques have further reduced HRCT dose.2 The authors have calculated that in infants, four images at 40 mA can be obtained using the same dose as a two-view chest radiograph. Dose is directly proportional to the product of scan time and tube current. The dose increase caused by increasing kilovoltage is not linear, and is greater than often appreciated. An increase from 120 to 140 kilovoltage (peak) increases dose by approximately 40%. Pediatric patients are rarely large enough to warrant the use of increased kilovoltage (peak). Scan time can be shortened by more rapid gantry rotation or by decreasing beam rotation to less than a full 360. In general, the fastest scan time that uses full rotation should be used. The use of partial scans should be evaluated at each site. As long as full scanner rotation is used, the effect of decreasing scan time is the same as an equal decrease in tube current. Tube current should be adjusted to provide the lowest dose consistent with adequate diagnostic quality. Several authors have advocated doses as low as 20 to 40 mA for HRCT in adults.57, 90 Because of their smaller size, the potential for decreasing dose is particularly

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Figure 1. Dynamic electron beam CT (EBCT) study in a 5-year-old boy with bronchiolitis obliterans. The image shows marked air-trapping and mosaic perfusion pattern. The graph shows virtually no air exchange in the hyperlucent lung regions (A). The ground-glass regions (B and C) show a normal variation of approximately 150 Hounsfield units (H) between inspiration and expiration.

great in children. A technique chart that relates tube current to weight is appropriate. Forty mA provides good quality images in infants. Children rarely require more than 100 mA.2 Other Considerations A high-frequency reconstruction algorithm (bone or lung) should be used to increase edge enhancement and improve visualization of parenchymal detail. The authors routinely also reconstruct images using a standard (soft tissue) reconstruction algorithm to review mediastinal structures. The use of the smallest

field of view possible optimizes spatial resolution. SPECIAL HIGH-RESOLUTION CT TECHNIQUES Electron Beam CT Electron beam CT allows routine use of a 0.1-second scan time that is short enough to stop respiratory motion artifact. Drawbacks include spatial resolution inferior to that of helical scanners and the lack of widespread availability of EBCT.

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Stop Ventilation Technique HRCT in young children is limited both by patient motion and by an inability to obtain inspiratory and expiratory images. The stop ventilation technique uses conscious sedation and mask ventilation to provide motion-free images at inspiration and expiration.47 If a sedated child is given several deep breaths, the child’s respiration pauses for 8 to 15 seconds. During this pause inspiratory images are obtained by administering positive pressure. Expiratory images are obtained by allowing the elastic recoil of the lung to decrease lung volume when the airway is open to atmospheric pressure. Using this technique high-quality HRCT images can be obtained in young children (Fig. 2). Expertise in respiratory management and additional experience are required to make this technique reliable and effective. HIGH-RESOLUTION CT SIGNS OF DISEASE Airways Investigation of diseases of the pediatric airways is perhaps the most important use of HRCT because this group of diseases is so common in children. HRCT signs of diseases involving the airways are listed in Table 2. Diseases primarily affecting the bronchi are diagnosed by finding bronchial wall thickening or bronchiectasis. The abnormalities can range from subtle and equivocal to grossly obvious. Minimal bronchial wall thickening, whether caused by infection, infiltration, or edema, can be difficult to diagnose with certainty on CT. Similarly, distinguishing between mild, reversible bronchial dilatation and minimal cylindric bronchiectasis is difficult. Many cases can be recognized using the criteria for bronchiectasis used in adults but equivocal cases do exist. Recognition of more marked bronchial dilatation is simple but there can be inconsistency in trying to decide if the bronchiectasis is cylindric or varicose or when varicose, if it is severe enough to be considered cystic. Despite these limitations, it is generally agreed that CT is the most accurate imaging procedure for the study of bronchiectasis. Diseases associated with pediatric bronchiectasis13 are listed in Table 3. Bronchial dilatation and bronchiectasis are uncommon in

childhood asthma, although their true incidence is not known. In cystic fibrosis, disease begins in the small airways, but bronchiectasis is almost invariably present as the child ages.26 Bronchiectasis is typically worse in the upper lobes than in the lower lungs and often more severe on the right than on the left side. The HRCT findings in cystic fibrosis are well documented and include not only progressively more severe bronchiectasis, but evidence of small airway disease including focal and generalized air trapping and centrilobular opacities (Figs. 3 and 4).25, 26, 32 Mucoid impaction of bronchi and bronchioles can be widespread but is often reversible. The role of HRCT in cystic fibrosis is still undergoing study,72 but CT can document the presence and extent of disease earlier and more accurately than chest radiography. Long,46 using the stop ventilation technique and careful measurements, showed early bronchial wall thickening and airway dilatation in a group of young (mean age 2.5) children with cystic fibrosis. CT scoring systems have been developed to quantitate the severity of disease52 and have been shown to correlate well with pulmonary function tests.61 It has been shown that CT can evaluate response to therapy and should be considered as an accurate way to evaluate efficacy of experimental therapies.10 Signs of bronchiolar (small airway) disease are in Table 2. The presence of air trapping suggests disease in the smaller airways. In infancy, these tiny airways easily become obstructed by inflammatory edema or exudate and contribute disproportionately to airway resistance resulting in marked air trapping that can be either focal or diffuse.20 Diffuse air trapping can be easily overlooked because the lungs are uniformly involved. In a child breathing quietly or breathholding at less than total vital capacity, visible anterior or posterior junction lines indicate that significant air trapping is present.43 Attenuation of the lung is lower than normal, often with values in the 900 H range, rather than 600 to 750 H,84 but unless actually measured can escape visual detection. Focal air trapping is more easily recognized, but requires a dynamic or expiratory scan for optimal diagnosis.48 Focal air trapping is often accompanied by a mosaic perfusion pattern that results when blood is shunted from a hyperinflated, hypoxic region to adjacent normal lung.86 Air trapping occurs in diseases that affect the smaller airways: bronchiolitis, asthma,

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Figure 2. A, A 4-month-old patient who had postgastric pull-up surgery and chronic aspiration pneumonia. A 10-mm helical CT slice at 240 milliampere-second (mAs) was made at an outside hospital. A dilated, fluidfilled esophagus is present, but no pulmonary abnormalities are evident. Compare with B. B, Image using a ‘‘stop ventilation’’ technique with a 1mm slice at 80 mAs. This image shows numerous, small, centrilobular opacities caused by chronic aspiration. Also a number of normal bronchi are visible that are not seen on the other study. This image was obtained with about one-tenth the dose of the outside study.

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Table 2. HRCT SIGNS OF PEDIATRIC AIRWAY DISORDERS Bronchial disease Bronchial wall thickening Compare with other regions of lung Visibility of bronchus further peripheral than normal Bronchiectasis Bronchus larger than accompanying vessel Lack of tapering Bronchus visible within 1 cm of pleural surface Bronchiolar disease Diffuse air trapping Decreased lung attenuation Prominent anterior and posterior junction lines Focal air trapping Low attenuation accentuated on expiration Decrease vessel size Mosaic perfusion pattern Bronchial wall thickening or bronchiectasis Centrilobular opacities Strongly suggest infection

cystic fibrosis, and viral lower respiratory infection. Other causes of generalized hyperinflation include large left-to-right shunts, diabetic acidosis, aspirin intoxication, and other causes of metabolic acidosis. There is no indication to image these conditions with CT unless a complication or an unusual associated finding is present. Bronchiolitis is a common viral lower respiratory tract infection that is most frequent in infancy. In some cases wheezing is the only symptom, but respiratory distress can be severe and, in rare instances, death can result. The only indication for CT is to exclude some other cause for the infant’s respiratory distress. CT shows findings of hyperaeration and focal disturbances in aeration and a mosaic perfusion pattern.43 Bronchial asthma is a common, recurrent pulmonary disease characterized by wheez-

Table 3. CAUSES OF PEDIATRIC BRONCHIECTASIS Cystic fibrosis Ciliary dyskinesia Allergic bronchopulmonary aspergillosis Infection Chronic, recurrent infection Aspiration syndromes AIDS Other immune deficiency syndromes Sequelae of infection Bronchiolitis obliterans Obstruction Foreign body Neoplasm (rare) Congenital anomaly Williams-Campbell syndrome

ing, paroxysmal cough, and dyspnea caused by hyperreactivity of the tracheobronchial airways resulting in increased resistance to airflow. CT scans are rarely obtained in children with uncomplicated asthma. The authors have examined a few such children who were suspected of having other conditions and found peribronchial thickening and focal, peripheral regions of air trapping, a pattern similar to that described in bronchiolitis obliterans. Asthmatic children with superimposed infection often have segmental or subsegmental regions of centrilobular opacities not apparent on chest radiography.43 CT may be indicated in some cases of atypical or refractory asthma. Occasionally, an unsuspected cause for wheezing is diagnosed. The authors have encountered BPD, bronchiectasis, bronchiolitis obliterans, and congenital pulmonary anomalies in children thought clinically to be asthmatic.43 In a series of 16 children with atypical asthma examined by HRCT, Nuhoglu et al64 found nine with minor abnormalities (mostly fibrotic scars and linear atelectasis) and three with major pathology including bronchiectasis and right middle lobe atelectasis. CT is also useful to diagnose allergic bronchopulmonary aspergillosis that is an infrequent complication of long-standing asthma.78 It has been shown that HRCT can assess airway reactivity29 in addition to diagnosing small airways disease, so it is likely that CT will have use as a research tool and for more accurate clinical diagnosis in atypical asthma. In addition to having generalized air trapping, patients with asthma, bronchiolitis, and viral lower respiratory infection have focal air trapping that resolves between bouts of illness. Constrictive or obliterative bronchiolitis (OB), however, is characterized by irreversible focal air trapping. OB is diagnosed pathologically by the presence of concentric fibrosis of the submucosal and peribronchial tissues of the terminal and respiratory bronchioles resulting in bronchial obliteration or severe narrowing.19 OB is commonly present distal to areas of bronchiectasis but it is not clear whether it is a cause or a result of bronchiectasis, or merely a related condition. 24 During childhood, there are two important causes of OB. The first is a complication of organ transplantation particularly lung and heart-lung transplants, although it has also been associated with bone marrow transplantation.73 Bronchiolitis obliterans is a late complication thought to represent a form of

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Figure 3. A 9-year old patient with minimal changes of cystic fibrosis. The lungs are slightly hyperexpanded and of decreased attenuation. Slight bronchial wall thickening is present.

Figure 4. An 18-year-old patient with advanced cystic fibrosis. Changes of cystic bronchiectasis with air–fluid levels are obvious in the right lower lobe as well as diffuse bilateral bronchiectasis of all degrees, mucoid impaction, centrilobular opacities, air-trapping, and mosaic perfusion in the left lower lobe. On the right, there is a chest tube and subcutaneous emphysema from an earlier pneumothorax.

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chronic rejection. It has a prevalence of about 50% and is a leading post-transplant cause of morbidity and mortality. It rarely develops sooner than 3 months after surgery and in most cases does not appear until near the end of the first postoperative year. Plain radiographic findings are not helpful in establishing the diagnosis. Transbronchial biopsy is diagnostic but often is falsly negative because of the patchy nature of the abnormality. HRCT is an important diagnostic aid with a reported sensitivity of 74% to 91% and a specificity of 67% to 94%. The most useful findings are dilatation of lower lobe bronchi, focal air trapping on expiratory CT, and mosaic perfusion pattern.44, 45, 87 The second important cause of OB in childhood is infection. Prior pneumonia, early in life with adenovirus, especially types 21 and 7, has been shown to be an important cause of this condition.11 Kim et al36 reported that 38% of children hospitalized with mycoplasma pneumonia were shown to have sequelae on CT that were consistent with OB. Other predisposing causes of OB include measles, influenzal viral infections, rheumatoid arthritis, systemic lupus erythematosus, and inhalation of toxic gases. Interestingly, OB has not been noted as a complication of respiratory syncytial viral infection.55 The true prevalence of OB following pulmonary infection in infancy or early childhood is not known, but the authors see several cases a year with typical CT findings, although lung biopsy is rarely performed. The article by Kim et al36 suggests that OB may be a fairly common complication of mycoplasma infection. It is apparent that infection in early life can scar the lungs much as it does the kidney; what is still unknown is how often this sequence of events occurs. The clinical findings of OB are nonspecific but include prolonged recovery from an initial infection with recurrent bouts of wheezing, pneumonia, and atelectasis. Fixed airway obstruction is often detected if pulmonary function tests can be performed. Chest radiograph is normal in less severe cases but shows intermittent pneumonia, hyperinflation, and peribronchial thickening in the sicker infants. Unilateral hyperlucent lung (Swyer-James syndrome) is a unique manifestation of OB with involvement asymmetric enough to allow initial recognition by radiography. When CT is performed on these children, bilateral changes of OB are found in about 50% of cases.40, 49, 54

CT findings of OB are those of small airways disease including focal air trapping, especially on expiration; mosaic perfusion pattern; bronchial wall thickening; and bronchiectasis (Figs. 1 and 5). 50, 81, 89 These CT findings suggest a diagnosis of OB, but unless air trapping and bronchiectasis are both present, the findings have to be interpreted with caution because reactive airways disease, bronchiolitis, and acute viral pneumonia also produce focal areas of air trapping and a mosaic perfusion pattern. If bronchiectasis is not present, a follow-up CT study showing no change in the areas of air trapping after an interval of 6 months to a year strongly suggests the diagnosis. The last CT finding to be discussed as an indication of small airway disease is the presence of centrilobular opacities (CLO). These result when the terminal bronchiole becomes dilated and fluid-filled allowing it to become visible on CT. CLOs are described as having a ‘‘tree-in-bud appearance’’ or branching Ys or dots in the center of the secondary pulmonary lobule.4 Their presence strongly suggests bronchiolar infection.21, 50 The authors have noted this pattern frequently in children with mycoplasma pneumonia, aspiration pneumonia (see Fig. 2B), cystic fibrosis (see Fig. 4), and occasionally in asthmatics. Bronchial wall disease, focal air trapping, ground-glass opacities (GGO), and consolidation are frequent concomitant abnormalities (Fig. 6). CLOs are rarely found uniformly throughout both lungs and their presence should be suspected if one sees too many dots near the lung periphery. Usually, comparison with other lung regions confirms the suspected focal pathology. Alveolar Disorders Disease at the alveolar level is manifest by the presence of GGO. GGO is defined as an increase in normal lung attenuation that does not obscure the underlying parenchymal detail (Figs. 1 and 5B). As discussed previously, GGO may occur in normal lung from shunting of blood from adjacent hypoxic or oligemic segments. GGO is also produced by alveolar disease. This is either the result of thickening of the alveolar septal walls; a reflection of interstitial disease; or opacification of alveolar air-spaces with fluid, exudate, or hemorrhage conditions often associated with frank areas of consolidation. GGOs are non-

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Figure 5. A 5-year-old boy with biopsy-proved bronchiolitis obliterans from pneumonia in infancy. A, Inspiration reveals loss of volume on the right with upper lobe atelectasis and markedly decreased attenuation and vascularity in the right lung. Bronchial wall thickening is noted on the left with a barely perceptible mosaic perfusion pattern. B, Expiration reveals left sided air-trapping, and mosaic perfusion pattern is much more apparent.

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Figure 6. A 3-mm 0.1-second EBCT image reveals centrilobular opacities and marked bronchial wall thickening are seen throughout the right upper lobe in this 9-year-old girl with mycoplasma pneumonia. Incidental note is made of the azygos vein abutting the right paravertebral surface.

specific and their presence can implicate airway, vascular, air-space, or interstitial disease from a wide range of causes (Table 4). Presence of diffuse, relatively uniform GGO suggests diffuse interstitial disease. Focal GGOs are more often caused by air-space disease or vascular redistribution. Often the clinical picture or associated CT findings, such as the crazy paving pattern of pulmonary alveolar proteinosis (PAP) (Fig. 7) helps to narrow the differential diagnosis, but it is not unusual that biopsy or bronchoalveolar lavage (BAL) is required to determine the underlying cause. Pulmonary hemorrhage produces GGOs that tend to be poorly marginated, somewhat fluffy or micronodular in appearTable 4. CAUSES OF GROUND-GLASS OPACITY IN CHILDHOOD Interstitial diseases associated with GGO in children Chronic pneumonitis of infancy Desquamative interstitial pneumonitis Nonspecific interstitial pneumonitis Air-space disorders associated with GGO Diffuse alveolar damage (ARDS) Hemorrhage Vasculitis Exudate (pneumonias) Pneumocystis carinii pneumonia Pulmonary edema Pulmonary alveolar proteinosis (both types) Lymphocytic interstitial pneumonia Leukemic infiltrate Alveolar capillary dysplasia

ance, and usually multifocal. Patients present with anemia, hemoptysis, or sudden onset of cough or dyspnea. Hemorrhage and pulmonary edema are widespread in diffuse alveolar damage, typified by acute respiratory distress syndrome (ARDS). Less common diseases causing pulmonary hemorrhage include idiopathic pulmonary hemorrhage (hemosiderosis); Goodpasture’s syndrome; systemic lupus erythematosus; and, less commonly, the other collagen vascular diseases. Diseases associated with pulmonary vasculitis and hemorrhage include Wegener’s granulomatosis and Churg-Strauss syndrome. The most common pulmonary presentation of Wegener ’s granulomatosis in childhood seems to be ill-defined, bilateral nodules that may cavitate (Fig. 8). Imaging of these disorders is nonspecific and diagnosis requires BAL, immunologic tests, or biopsy. The idiopathic, diffuse interstitial lung diseases that are so often diagnostic dilemmas in adults are much less common in children. There is still controversy about the classification of these rare disorders in children and only a few reports of their CT appearances. 39, 51 Katzenstein et al 35 described an entity called chronic pneumonitis of infancy (CPI). This condition develops at an average age of about 4 months in infants who are normal at birth. Most cases have a progressive downhill course. They believe many childhood cases of what were previously labeled usual interstitial pneumonia or desquamative interstitial pneumonia actually repre-

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Figure 7. Pulmonary alveolar proteinosis in a 12-year-old girl. A 6-mm 0.1-second EBCT image reveals bilateral ground-glass opacities and a marked, smooth interlobular septal thickening (crazy-paving) appearance.

Figure 8. Wegener’s granulomatosis in 15-year-old boy presenting with renal failure and pulmonary opacities. A 6-mm EBCT 0.1-second image reveals bilateral nodules, several of which have margins of ground-glass attenuation suggestive of vasculitis. Several cavitated lesions were noted on other images.

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Figure 9. A 3-mm 0.1-second EBCT image of a 4-week-old patient with chronic pneumonitis of infancy. Diffuse, severe, ground-glass opacities are present without apparent septal thickening.

sented CPI. The authors have seen one proved case in which CT showed initially diffuse GGO (Fig. 9) with progressive changes of severe, chronic interstitial fibrosis, which resulted in the death of the infant following attempted lung transplantation. Katzenstein et al35 believe most of the remaining cases of idiopathic interstitial pneumonias of childhood fit in the category they call nonspecific interstitial pneumonitis, which is characterized pathologically by mild chronic inflammatory changes in the alveolar septum and a lack of an intralveolar exudate. The CT appearances of this condition, which may have multiple causes, have not been fully described. Desquamative interstitial pneumonia in childhood is still poorly understood. Some cases may represent chronic pneumonitis of infancy and there is some apparent overlap with surfactant B deficiency and congenital alveolar proteinosis. Reported CT findings of desquamative interstitial pneumonia 51 include diffuse GGO with progression to pulmonary fibrosis. Usual interstitial pneumonitis either does not exist in children or is extremely rare.62 Signs of diseases affecting the peripheral portion of the interstitium of the lung are listed in Table 5. The first is interlobular septal thickening. The interlobular septa are part of the peripheral interstitium of the lung and form the margins of the secondary pulmonary lobule.85 They contain pulmonary lymphatics and venous structures, are best developed in the periphery of the lung anteriorly, and are usually not visualized on a normal

pediatric chest radiograph. A few septa may normally be visible on chest CT. As septae become thickened, they are recognized as Kerley B lines on a radiograph and on CT as thin, 1- to 2-cm lines, generally perpendicular to the pleural surface. When numerous they form a fine mesh-like pattern of lines (Fig. 10). They are contiguous with the interlobar septa (the pleural fissures) and the bronchovascular bundles, and often these structures become thickened, making recognition of septal pathology more obvious. Thickening of the septa may be either smooth, nodular, or irregular.33 Smooth septal thickening is much more common in children. Conditions causing smooth septal thickening are listed in Table 6. Because many of these disorders are associated with either engorged veins, lymphatics or interstitial edema, areas of GGO are often also present. Cardiogenic pulmonary edema is not studied by CT for diagnostic purposes, but may be detected serendipitously as may edema related to renal disease or iatrogenic fluid overload. Early edema is Table 5. HRCT SIGNS OF PERIPHERAL INTERSTITIAL (SEPTAL) DISORDERS Smooth septal thickening Reticular pattern Regular bronchovascular bundle thickening Prominent interlobular septal (fissural thickening) Nodular septal thickening May be associated with pulmonary nodules Irregular or nodular bronchovascular bundle thickening

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Figure 10. Unilateral, (right-sided) smooth, interlobular septal thickening in a 12-year-old girl who has right-sided partial anomalous pulmonary venous return.

manifest by slight increase in lung attenuation, GGO, and septal thickening.30 One of the most striking causes of septal thickening is pulmonary alveolar proteinosis. This condition, which may present in childhood, is of unknown cause.1 Pathologic examination reveals that alveoli are filled with a periodic acid–Schiff (PAS)-positive material, perhaps from type 2 pneumocytes. Interstitial fibrosis is absent in early cases, although septal edema is present and may be striking on CT (see Fig. 7). Pulmonary lymphangiomatosis (lymphangiectasia) can be limited to one lung and is associated with marked septal and bronchovascular bundle thickening. Patients often also have a pleural effusion and a mediastinal mass or infiltration.82, 88 Other rare con-

Table 6. CAUSES OF SMOOTH SEPTAL THICKENING Fluid overload Cardiac, renal, or iatrogenic Diabetic keto-acidosis Pulmonary vein atresia or obstruction Pulmonary lymphangiectasia (lymphangiomatosis) Associated with mediastinal mass or pleural effusion Rare diseases Pulmonary alveolar proteinosis Pulmonary capillary hemangiomatosis Pulmonary alveolar microlithiasis Pulmonary hemosiderosis Gaucher disease Niemann-Pick disease

ditions presenting with septal thickening are pulmonary alveolar microlithiasis, pulmonary capillary hemangiomatosis, and pulmonary hemosiderosis.16, 27, 39, 51, 75 These conditions usually also have a small, nodular component. Nodular septal thickening is usually associated with an infiltrative process, often malignant, that spreads along the pulmonary lymphatics resulting not only in nodular septal thickening but thickening of the bronchovascular bundle and often with pulmonary nodules, masses, or areas of consolidation. Diseases associated with this pattern include metastatic sarcomas; lymphoma, (especially large cell); and rarely neuroblastoma. In most cases the nature of the underlying disease is already well established clinically. Large cell lymphoma is one condition that can present relatively suddenly with an abnormal chest film before the diagnosis is apparent (Fig. 11). Irregular septal thickening is associated with pulmonary fibrosis and is discussed later.

DISORDERS ASSOCIATED WITH PULMONARY NODULES OR SMALL MASSES Pulmonary nodules can be classified in a number of ways: by attenuation that may be

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Figure 11. Histiocytic (large cell) lymphoma in a 17-year-old boy. Axial EBCT scan with 3-mm collimation through the upper lung zones shows a marked interlobular septal pattern and nodular thickening of the bronchovascular bundles, present bilaterally, but much more marked in the left upper lobe.

ground-glass, soft tissue, calcific, or air-containing; by size; or by location (Table 7). It can be difficult to determine if a CT image showing too many dots is caused by multiple small nodules, vessels, or CLOs. Using a slightly thicker slice (3 to 5 mm) allows easier recognition of vessels. Nodules tend to be diffuse and CLOs tend to be localized, associated with bronchial wall thickening, and possess a branching or Y pattern not observed with nodules.

Table 7. PULMONARY NODULES IN CHILDHOOD Small, ill-defined centrilobular nodules Hypersensitivity pneumonia LIP Pulmonary capillary hemangiomatosis Pulmonary hemosiderosis Follicular bronchiolitis Small soft tissue nodules Metastatic disease Miliary tuberculosis Granulomatous and fungal infections Langerhans’ cell histiocytosis Pulmonary hemosiderosis Larger nodules or masses Metastases Recurrent respiratory papillomatosis Lymphoma Lymphomatoid granulomatosis Fungal infection Bronchiolitis obliterans with organizing pneumonia Vasculitis Septic emboli Arteriovenous malformations Pulmonary artery aneurysms

Ill-defined centrilobular nodules of groundglass attenuation are associated with hypersensitivity pneumonitis, which in children is usually acute and caused by exposure to one of many bird antigens. Vasculitis can produce similar appearances, although the nodules usually are larger. Similar nodules have also been described in pulmonary capillary hemangiomatosis.16 Small soft tissue nodules occur in pulmonary lymphoid hyperplasia, including AIDS-associated LIP and rarely follicular bronchiolitis. LIP is an AIDS-defining illness if it occurs in a child under 13 years. Up to 30% to 40% of children with AIDS develop LIP. Reticulonodular infiltrates and nodules from miliary to a few millimeters in size, GGO, and bronchovascular bundle thickening are characteristic. Hilar adenopathy and thymic cysts are other common findings. Small cysts and areas of bronchiectasis occur and may be related to partial bronchiole obstruction from lymphocytic infiltration.18, 53 Follicular bronchiolitis is characterized by the presence of enlarged lymphoid aggregates along distal bronchi and bronchioles. This condition is also thought to be part of the spectrum of pulmonary lymphoid proliferation. It usually has its onset before 6 months of age and is characterized on CT by small nodules, bronchial wall thickening, and sometimes by striking findings of focal air trapping suggestive of bronchiolitis obliterans (Fig. 12).38, 66, 71 Langerhans’ cell histiocytosis presents with small, soft tissue, centrilobular

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Figure 12. A 2-year-old patient with biopsy-proved follicular bronchiolitis. Wide-spread air-trapping and mosaic perfusion pattern. Nodules have been reported in this condition but are not apparent in this patient.

nodules some of which coalesce and cavitate (Fig. 13). Thymic cysts and calcifications are associated findings sometimes present on CT.9, 39, 79, 80 Pulmonary involvement occurs in from 10% to 50% of cases, but lung disease has not been shown to have an adverse prognostic effect. 22 As this disease progresses,

however, large pulmonary cysts can form and produce pneumothoraces or progressive pulmonary failure. Miliary tuberculosis has innumerable 1- to 3-mm soft tissue nodules scattered diffusely throughout both lungs. 37 Pulmonary alveolar microlithiasis is a rare familial disease characterized by micronodu-

Figure 13. A 3-mm EBCT image at 0.1 second reveals a 16-month-old patient with Langerhans’ cell histiocytosis. Multiple, small, thin-walled cysts and scattered, small soft tissue nodules are noted throughout both lungs.

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lar calcifications, septal thickening, and GGOs. Punctate and linear pleural calcifications are also present.27, 75 Surprisingly, these nodules do not always appear calcified on CT51 Larger, more sharply defined pulmonary nodules can result from metastatic disease. Wilms’ tumor and the sarcomas are the most frequent causes, but lymphoma and rarely neuroblastoma may also develop nodules. It is unusual to have pulmonary metastases as the initial manifestation of a pediatric malignancy. Lymphomatoid granulomatosis is a rare angiocentric, angiodestructive lymphoproliferative disorder that may be a precursor of T-cell lymphoma.34 Its pulmonary presentations range from a solitary nodule34 to large, bilateral conglomerate opacities69 Other soft tissue nodules that tend to be large and may cavitate include (1) septic emboli, a unique variant of which is Lemierre syndrome, which is pharyngitis, jugular venous thrombosis, and septic emboli15, 42; (2) fungal infection, especially with candida and aspergillus, which can produce multiple peripheral nodules; and (3) recurrent respiratory papillomatosis,6, 42 previously called juvenile laryngeal papillomatosis, which can seed down the airway from its origin in the larynx and present as pulmonary nodules, which often cavitate. Vasculitis, especially Wegener’s granulomatosis, can produce multiple pulmo-

nary nodules, often with ground-glass margins and occasional cavitation (see Fig. 8).14, 23, 59 Bronchiolitis obliterans with organizing pneumonia (BOOP), also called cryptogenic organizing pneumonia, is one of the lung’s most common, nonspecific, reparative reactions. Pathologic examination reveals a sharply demarcated cellular fibrotic reaction that plugs the air spaces and small airways. BOOP is uncommon in children but has been seen in patients recovering from malignancy and as a manifestation of drug reaction, especially bleomycin toxicity.28, 56 CT demonstrates a subpleural distribution of opacities that are often nodular in nature and may be accompanied by ground-glass attenuation (Fig. 14). BOOP is often reversible and may respond to steroid therapy.

Vascular Disorders Diseases affecting the pulmonary circulation are listed in Table 8. Secondary signs of vascular disease have been discussed previously and include septal thickening (pulmonary venous engorgement); GGO (capillaritis or edema), mosaic perfusion pattern (oligemia and vascular redistribution); and nodules (vasculitis). Primary signs of vascular diseases include visualization of vessels in an

Figure 14. Biopsy-proved bronchiolitis obliterans with organizing pneumonia (BOOP) in an 18-year-old patient with post–bone marrow transplant for leukemia. Large, ill-defined soft tissue masses are present primarily in the periphery of the right lower lobe.

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Table 8. PULMONARY VASCULAR DISORDERS Large vessels Anomalies Anomalous venous return Aberrant arterial supply Left to right shunt Congestive failure Pulmonary hypertension Aneurysms Associated with tetrology of Fallot with absent valve Behc¸et’s syndrome Hepatopulmonary syndrome Decreased vessel size Right-to-left shunt Acute chest syndrome in sickle cell disease Bronchiolitis obliterans Pulmonary embolism Secondary signs Smooth interlobular septal thickening Mosaic perfusion pattern Nodules and small masses

anomalous position, such as total or partial anomalous pulmonary venous return. Abnormalities of size include a pulmonary artery that may be absent, hypoplastic, or rarely aneurysmally dilated. The pulmonary arteries are larger than their accompanying bronchus if there is a left to right shunt, vascular redistribution, or pulmonary hypertension. Pulmonary arteriovenous malformation occur mainly in patients with Osler-Weber-Rendu disease and may manifest as a single large mass or multiple small nodules.70 They are bilateral in about two thirds of cases. Hepatopulmonary syndrome is associated with right to left shunting but prominent pulmonary vascularity, especially in the lower lobes.58 Behc¸et’s syndrome is a rare systemic vasculitis that can manifest with large pulmonary artery aneurysms.65 Atresia or obstruction of pulmonary veins presents with smooth interlobular septal thickening, and in more severe cases with areas of GGO. Decreased vessel size can be seen in acute chest syndrome in patients with sickle cell disease.7 Pulmonary thromboembolism is uncommon in children but has the same CT appearances as described in adults. Pulmonary embolism in children usually is associated with an indwelling catheter,3 malignancy, sepsis, or other predisposing factor.

Pulmonary Fibrosis End stage pulmonary fibrosis is fortunately rare in children. Findings of fibrosis include

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honeycombing, cysts, traction bronchiectasis, and parenchymal bands. Large cysts form in end-stage cystic fibrosis; most are caused by cystic bronchiectasis, but large subpleural bullae and pneumatoceles can also develop.83 Extensive cysts can occur in end-stage Langerhans’ cell histiocytosis particularly in the upper lung zones. BPD can range in appearance from a few subpleural areas of hyperlucency, possibly caused by small airways disease, to extensive lung destruction, generally more severe anteriorly and in the upper lobes.5, 31, 43, 67 Frequent findings include parenchymal bands, multifocal areas of decreased attenuation, and perfusion. Reduced bronchial caliber has been reported,31 but bronchial dilatation also occurs (Fig. 15). Similar changes develop in pediatric survivors of ARDS. Interstitial fibrosis can occur in collagen vascular disease, particularly systemic sclerosis.76 Interstitial fibrosis progressing to end-stage pulmonary fibrosis is unusual in children but can be seen in chronic pneumonitis of infancy (Fig. 16), and nonspecific interstitial pneumonitis. Focal areas of hyperlucency, usually associated with a mass or disturbance of normal pulmonary anatomy, occur with congenital malformations, such as bronchial atresia, sequestration, and congenital cystic adenomatoid malformation (CCAM). Postinfectious pneumatoceles and loculated interstitial pulmonary emphysema are transient causes of what initially might seem to be destructive lung disease.32, 41 FATAL NEONATAL LUNG DISORDERS Surfactant B deficiency has been identified as a cause of congenital pulmonary alveolar proteinosis.95 This condition presents at birth with radiographic findings similar to respiratory distress syndrome. The CT appearance in two cases was similar to that described in the adult form of alveolar proteinosis described previously with diffuse GGO and marked septal thickening (Fig. 17).61a This disease also is usually fatal unless lung transplantation is performed. A second rare neonatal condition that has a recognizable CT pattern is alveolar capillary dysplasia. In this disorder there is apparent malalignment of the pulmonary vessels with the capillaries. Clinical presentation is marked pulmonary hypertension. CT shows diffuse GGO with ‘‘dark bronchus’’ sign. Finally, there is a newly reported condition,

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Figure 15. A 3-mm EBCT image shows bronchopulmonary dysplasia in a 6-year-old patient. A, Section through the lung bases reveals hyperaerated lower lobes especially on the left. Mild bronchial dilatation is noted. This condition had developed since an earlier study at age 4. B, On a higher level there are typical changes of bronchopulmonary dysplasia with linear, fibrotic changes medially, some loss of upper lobe lung volume, and primarily peripheral areas of air-trapping. Small, triangular, pleural-based opacities are present at both levels.

HIGH-RESOLUTION CT OF PEDIATRIC LUNG DISEASE

Figure 16. End stage pulmonary fibrosis in the same patient as Figure 9 now at age 4 months. The lungs are essentially destroyed with severe small honeycomb cysts and marked septal thickening throughout. The patient died following a lung transplant.

Figure 17. A 3-mm EBCT image showing congenital alveolar proteinosis caused by surfactant B deficiency in a 3-week-old patient. Note the similarity in appearance to Figure 7 with ground-glass opacities and smooth interlobular septal thickening.

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Figure 18. Persistent tachypnea of infancy. A 3-month-old infant with tachypnea since birth. Chest radiography revealed nonspecific central haziness. A, HRCT shows findings of bilateral GGO in a somewhat dependent distribution. Biopsy revealed pulmonary neuroendocrine cell hyperplasia. B, Follow-up HRCT 15 months later using stop-ventilation technique shows improvement, although the basic pattern of GGO persists. (Courtesy of Dr. R. Cohen, Oakland, CA.)

persistent tachypnea of infancy, that still is poorly defined.15a, 71a These patients present in infancy with chronic tachypnea and hypoxemia. Radiographic findings are nonspecific and may be normal or show mild interstitial disease and peribronchial thickening. Some CT scans have been normal, others (Fig. 18) show GGO suggestive of edema. Pathologic findings characteristically include pulmonary neuroendocrine cell hyperplasia. Affected infants show gradual improvement over a course of months to years. SUMMARY High-resolution CT in children remains a technically challenging procedure, both to perform optimally and to interpret correctly. Although much remains to be learned about its optimal application, it is apparent that often confusing or nonspecific chest radiographs are clarified and a much clearer understanding is being gained about the diagnosis and evolution of both common and unusual pediatric lung diseases. As new therapies become available for these disorders, and CT becomes faster and easier to perform, it will become increasingly used not only for more accurate diagnosis but also for better evaluation of effects of therapy.

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