Acinar dysplasia is characterized by lung developmental arrest in the pseudoglandular or early canalicular phase, resulting in essentially no alveolar spaces for gas exchange. Congenital alveolar dysplasia is characterized by arrest in the late canalicular/early saccular phase, resulting in incomplete alveolarization. Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is characterized by malpositioning of the pulmonary vein branches adjacent to the pulmonary artery branches rather than within the interlobular septa, medial hypertrophy of the pulmonary arterioles, reduced alveolar capillary density, and pulmonary lobular maldevelopment. Pulmonary lymphangiectasia is also present in about one-third of cases (Dishop 2011). The misaligned pulmonary veins in ACD/MPV may actually represent anastomotic bronchial veins associated with intrapulmonary right-to-left shunting. This shunting bypasses the alveolar capillary bed and exacerbates the hypoxemia from right-to-left extrapulmonary shunting associated with persistent pulmonary hypertension of the newborn (PPHN) (Galambos et al. 2014).

The diffuse developmental disorders of the lung are associated with markedly impaired alveolar gas exchange, resulting in respiratory failure and severe PPHN within hours or days of birth in the absence of the usual causative conditions of prematurity, meconium aspiration, congenital heart disease, perinatal asphyxia, or sepsis. Death usually ensues within a few days or weeks, unless the lung involvement is patchy rather than diffuse (Chow et al. 2013), or extracorporeal membrane oxygenation (ECMO) or paracorporeal lung assist devices are available as a bridge to lung transplantation (Sen et al. 2004; Michalsky et al. 2005; Hoganson et al. 2014). Approximately 80 % of cases of ACD/MPV are associated with extrapulmonary malformations, including hypoplastic left heart syndrome, aortic coarctation, alimentary tract atresia, annular pancreas, omphalocele, midgut malrotation, and urinary tract malformation. Sporadic or familial autosomal dominant FOXF1 gene mutations have been identified as a cause of some cases of ACD/MPV (Stankiewicz et al. 2009; Sen et al. 2013).

Due the severity of the respiratory disease, imaging of patients with diffuse developmental disorders of the lung is usually limited to portable CXRs. Although the initial CXRs may be unimpressive, followup CXRs may demonstrate progressive hazy opacification of the lungs, resembling of the findings of surfactant deficiency of prematurity or genetic surfactant disorders (Fig. 1). Pneumothorax or pneumomediastinum is common and likely attributable to barotrauma (Michalsky et al. 2005; Hugosson et al. 2005; Gillespie et al. 2004; Newman and Yunis 1990).

Growth abnormalities constitute the most common cause of chronic DLD in infancy. Lung growth abnormalities are characterized histologically by impaired alveolarization manifesting as lobular simplification with deficient alveolar vascularization and septation, reduced alveolar number, and increased alveolar size resembling emphysema (Dishop 2010). As a consequence, there is diminished total alveolar surface area and reduced pulmonary diffusing capacity relative to alveolar volume (Balinotti et al. 2010). Lung growth abnormalities are often accompanied by patchy PIG or by pulmonary arterial hypertensive changes related to increased vascular resistance from a deficient capillary bed (Dishop 2011).

Lung growth abnormalities can be related to prenatal or postnatal conditions (Deutsch et al. 2007). The most common prenatal form is pulmonary hypoplasia secondary to limited intrathoracic space in utero, such as from a congenital diaphragmatic hernia, oligohydramnios, thoracic mass lesion, or skeletal dysplasia. The most frequently encountered postnatal form is chronic lung disease of infancy (CLDI) related to prematurity. This includes “new” BPD, which is characterized by impaired alveolarization, but less fibrosis and airway obstruction compared to classic BPD (Bhandari and Bhandari 2009), and Wilson-Mikity syndrome, which is characterized by slowly progressive respiratory distress and cyst-like changes of the lungs developing within the first few weeks of life despite minimal respiratory support at birth (Hoepker et al. 2008; Philip 2009). Growth abnormalities can also be observed in near-term and term infants as an idiopathic disorder or in association with congenital heart disease or certain genetic disorders (Deutsch et al. 2007; Dishop 2010).

Patients with a lung growth abnormality typically present with respiratory difficulty as a neonate, and may either improve or worsen, depending on the extent of catch-up growth of the alveoli over time and whether or not pulmonary hypertension ensues. Most alveolarization occurs by two to three years postnatal age, but recent evidence from hyperpolarized gas magnetic resonance imaging suggests that neo-alveolarization continues to occur throughout childhood and adolescence in normal individuals (Narayanan et al. 2012). Gestational age at birth is an important determinant of subsequent alveolar development (Balinotti et al. 2010), but the capacity for catch-up neo-alveolarization in those with lung growth abnormalities is currently unknown.

The chest imaging findings of infants with BPD and other lung growth abnormalities range from nearly normal to markedly abnormal, with distorted pulmonary lobules of variable shape and attenuation, perilobular reticular opacities, linear subpleural opacities, ground-glass opacities, and foci of decreased lung attenuation, often appearing as cyst-like hyperlucencies (Metwalli et al. 2011) (Fig. 2). The decreased lung attenuation is likely attributable to enlarged alveoli with reduced alveolar septation and vascularization (Mahut et al. 2007). Decreased lung attenuation on CT correlates with the clinical severity of BPD (la Tour et al. 2013). Reproducible quantitative CT scoring systems based on the extent of findings, such as decreased lung attenuation, linear opacities, and architectural distortion at a mean postmenstrual age of 39 weeks show better correlation than do CXR scores with the clinical severity of BPD, and higher CT scores predict a higher risk of rehospitalization for pneumonia (Shin et al. 2013). CT scoring systems are superior to pulmonary function testing for differentiating infants with and without a history of BPD and higher CT scores are associated with a greater number of days on supplemental oxygen (Sarria et al. 2011). Ventilation-perfusion (V/Q) single photon emission computed tomography (SPECT) performed at a mean postmenstrual age of 37 weeks commonly reveals V/Q mismatching, even in clinically mild BPD, and the degree of V/Q mismatching correlates with the duration of mechanical ventilation (Kjellberg et al. 2013). Residual pulmonary abnormalities on CT are very common in adolescent and young adult survivors of classic BPD born in the pre-surfactant era, with the most frequent findings being subpleural, triangular, and linear opacities, air trapping, and emphysema (Aukland et al. 2006; Wong et al. 2008, 2011) (Fig. 3). The imaging findings in adolescent and adult survivors of “new” BPD are not yet well described. The imaging findings of BPD are further discussed in the chapter entitled Neonatal Chest Imaging by Crotty in this book.

Down syndrome is associated with a peculiar lung growth abnormality in which the enlargement of the alveoli and alveolar ducts is particularly marked in the subpleural region, resulting in the appearance of subpleural cysts on CT (Biko et al. 2008) (Fig. 4). A lung growth abnormality should be suspected in children with Down syndrome and respiratory difficulties not attributable to congenital heart disease.

A severe progressive lung growth disorder ultimately requiring lung transplantation for survival can develop in infants with X-linked filamin A (FLNA) gene mutations. Chest imaging in these patients characteristically shows severe pulmonary hyperinflation and hyperlucency of multiple lobes of the lungs resembling emphysema along with atelectasis and airway malacia. Extrapulmonary manifestations in patients with FLNA gene mutations include periventricular nodular gray matter heterotopia, nystagmus, joint hyperextensibility, congenital heart defects, and vascular aneurysms (Guillerman 2010; Masurel-Paulet et al. 2011; de Wit et al. 2011; Guillerman et al. 2013) (Fig. 5).