Imaging of Emphysema Overview

Conventional chest radiography is generally the first imaging procedure performed in patients with respiratory symptoms, and frontal and lateral chest radiographs may reveal changes of emphysema. A chest radiograph is universally available, noninvasive, and inexpensive, and it poses an acceptable radiation exposure.[1, 2, 3] For further information, see the Medscape Reference topics Imaging in Congenital Lobar Emphysema, Imaging in Emphysematous Pyelonephritis, and Imaging in Pulmonary Interstitial Emphysema. High-resolution computed tomography (HRCT) scanning is more sensitive than chest radiography in diagnosing emphysema and in determining its type and extent of disease. [4] HRCT also has a high specificity for diagnosing emphysema with virtually no false-positive diagnoses. However, in clinical practice, more reliance is placed on patient history, lung function tests, and abnormal chest radiographs to diagnose emphysema. However, some patients with early emphysema, particularly those with early disease, may present with atypical symptoms, and it is in these patients that an HRCT is most rewarding. If significant emphysema is found on HRCT, no further workup is necessary; specifically, lung biopsy is not needed. Studies are under way to assess the role of computed tomography (CT) in the early detection of lung cancer in patients with COPD and in predicting response to lung-volumereduction surgery (LVRS).[5] Radionuclide scanning and MRI have a potential role in patients being assessed for LVRS. Images of emphysema are displayed below.

Chest radiograph of an emphysematous patient shows hyperinflated lungs with reduced vascular markings. Pulmonary hila are prominent, suggesting some degree of pulmonary hypertension (Corra da Silva, 2001).

CT densitovolumetry in a heavy smoker with emphysema revealed compromise of about 22% of the lung parenchyma (Corra da Silva, 2001).

CT densitovolumetry in a patient with lung cancer. Three-dimensional (3D) image shows that the cancer is in the portion of the right lung that was less affected by emphysema in a patient with poor pulmonary function (Corra da Silva, 2001).

Ballile and Laennec described the anatomopathology of emphysema in 1793 and in 1826, respectively. After that, Lynne Reid published one of the landmark works in our understanding of emphysema, The Pathology of Emphysema (Reid, 1967) ,which provided a detailed description of the anatomy of the lung units and of the anatomopathology and pathophysiology of emphysema, broadening the view of this complex disease.[6, 7] Various changes have happened since then, especially the advent of the high-resolution CT (HRCT) of the chest. Pulmonary emphysema is defined as the permanent enlargement of airspaces distal to the terminal bronchioles and the destruction of the alveolar walls. Pathology reveals a marked increase in the size of the airspaces, resulting in labored breathing and an increased susceptibility to infection. It can be caused by irreversible expansion of the alveoli or by the destruction of alveolar walls. Fibrosisis not associated with this condition. Pulmonary emphysema and chronic bronchitis are important components ofchronic obstructive pulmonary disease (COPD). Emphysema often coexists with chronic bronchitis in the COPD population, and from a clinical point of view, they are generally considered as one entity. Although a tissue diagnosis of emphysema is possible, in advanced cases it can usually be confidently diagnosed on the basis of the patient's history, physical findings, pulmonary function, and imaging results.

Limitations of techniques
Chest radiographic findings are not good indicators of the severity of disease and do not help in identifying patients with COPD without clinically significant emphysema. Imaging information from HRCT does not alter the management of emphysema; therefore, HRCT has no place in the day-today care of patients with COPD. In their early stages, the 3 forms of emphysema can be distinguished morphologically by using HRCT. However, as the disease becomes more extensive, the distinction becomes difficult or impossible, both radiographically and pathologically.

Radiography
In moderate-to-severe emphysema, chest radiographic findings include bilaterally hyperlucent lungs of large volume, flattened hemidiaphragms with widened costophrenic angles, horizontal ribs, and a narrow mediastinum. The peripheral vascular markings are attenuated, but the markings become prominent when the patient has pulmonary hypertension and right-sided heart failure. A lateral view shows increased retrosternal airspace and flattening of the anterior diaphragmatic angle. In addition, bullae and an irregular distribution of the lung vasculature may be present. When pulmonary hypertension develops, the hilar vascular shadows become prominent, with filling of the lower retrosternal airspace due to right ventricular enlargement. (See the images below.)

Chest radiograph of an emphysematous patient shows hyperinflated lungs with reduced vascular markings. Pulmonary hila are prominent, suggesting some degree of pulmonary hypertension (Corra da Silva, 2001).

Schematic representation of 1 criterion for defining flattening of the diaphragm on the lateral chest radiograph: drawing a line from the posterior to anterior costophrenic angles and measuring the distance from this line to the apex of the diaphragm. If the height is less than 1.5 cm, the criterion of flattening is fulfilled (Corra da Silva, 2001).

Schematic representation of another criterion for defining flattening of the diaphragm on the lateral chest radiograph. When the angle formed by the contact point between the diaphragm and the anterior thoracic wall is more than or equal to 90, the criterion is fulfilled (Corra da Silva, 2001).

Schematic representation of another sign of emphysema on the lateral chest radiograph. When the retrosternal space (defined as the space between the posterior border of the sternum and the anterior wall of the mediastinum) is larger than 2.5 cm, it is highly suggestive of overinflated lungs. This radiograph is from a patient with pectus carinatum, an important differential diagnosis to consider when this space is measured (Corra da Silva, 2001).

Close-up image shows emphysematous bullae in the left upper lobe. Note the subpleural, thin-walled, cystlike appearance (Corra da Silva, 2001).

A, Frontal posteroanterior (PA) chest radiograph shows no abnormality of the pulmonary vasculature, with normal intercostal spaces and a diaphragmatic dome between the 6th and 7th anterior ribs on both sides. B, Image in a patient with emphysema demonstrating reduced pulmonary vasculature resulting in hyperlucent lungs. The intercostal spaces are mildly enlarged, and the diaphragmatic domes are straightened and below the extremity of the seventh rib (Corra da Silva, 2001).

A, Lateral radiograph of the chest shows normal pulmonary vasculature, a retrosternal space within normal limits (< 2.5 cm), and a normal angle between the diaphragm and the anterior thoracic wall. B, Lateral view of the chest shows increased pulmonary transparency, increased retrosternal space (>2.5 cm), and an angle between the thoracic wall and the diaphragm >90. Straightening of the diaphragm can be more evident in this projection than on others (Corra da Silva, 2001).

Degree of confidence
In clinical practice, reliance is placed on the patient's history, lung function, and abnormal chest radiographs to diagnose emphysema. Chest radiographic findings generally cannot establish the diagnosis of mild emphysema; however, when emphysema is fully established, classic radiographic findings are typically observed. Findings on routine chest radiographs can suggest emphysema, but this is not a sensitive technique for diagnosis. However, chest radiography is useful to look for complications during acute exacerbations and to exclude other pathologies, such as superadded infection or lung cancer. The chest radiograph is not a good indicator of the severity of disease and does not help in identifying patients with COPD without significant emphysema. Thurlbeck and Simon found that only 41% of those with moderately severe emphysema and two thirds of those with severe emphysema had evidence of disease on chest radiography.[8]

Computed Tomography
CT scanning of the chest, especially high-resolution CT (HRCT), has a much greater sensitivity and specificity than those of plain chest radiography in diagnosing and assessing the severity of emphysema (see the images below). CT can depict surgically treatable areas of bullous disease that are not evident on plain chest radiography. CT is also useful in predicting the outcome of surgery. HRCT may be useful in diagnosing subclinical or mild emphysema, and HRCT can be used to differentiate the pathologic types of emphysema. However, CT scanning is not yet used to routinely evaluate patients with COPD. Instead, it is being reserved for patients in whom the diagnosis is in doubt, to look for coexistent pathologies, and to assess their suitability for surgical intervention. [9, 10, 11, 12,
13, 14, 4, 15, 16]

High-resolution CT (HRCT) in a patient after viral bronchiolitis obliterans demonstrates areas of airtrapping, which is predominant in the inferior lobes and associated with bronchiectasis in the left lower lobe. Note that the decreased attenuation caused by the airtrapping can simulate emphysema (Corra da Silva, 2001).

Pediatric high-resolution CT (HRCT) shows a hyperinflated right lung with large pulmonary bullae due to congenital lobar emphysema (Corra da Silva, 2001).

High-resolution CT (HRCT) demonstrates areas of centriacinar emphysema. Note the low attenuation areas without walls due to destruction of the alveoli septae centrally in the acini. Red element shows the size of a normal acinus (Corra da Silva, 2001).

High-resolution CT (HRCT) shows large bullae in both inferior lobes due to uniform enlargement and destruction of the alveoli walls causing distortion of the pulmonary architecture (Corra da Silva, 2001).

Hruban et al[17] and Bergin C et al[18] have shown an excellent correlation between HRCT and histologic findings. They used low-resolution (10 mm) scans and were still able to show that CT findings were better predictors of emphysema than results of pulmonary function tests. Semiautomated assessment of emphysema by using HRCT data is possible and can help eliminate interobserver and intraobserver variability and provide a reproducible assessment of the percentage of lung affected. Gould et al[19]measured the mean density in vivo of the lowest fifth percentile of the distribution of pixels and compared it with a computed quantification of emphysema on the

subsequently excised lungs and showed a strong correlation between lung attenuation and distal airspace size. Mller et al[20] and Kinsella et al[21] used a CT attenuation mask to highlight voxels in a given attenuation range to quantitate emphysema and define areas of abnormally low attenuation. They compared different masks, mean lung attenuations, and visual appearances and pathologic grades of emphysema in 28 patients undergoing lung resection for tumor. In each patient, a single representative CT image was compared with corresponding pathologic specimens. They found good correlation between the extent of emphysema as assessed by using the attenuation mask and the pathologic grade. Such methods not only eliminate interobserver and intraobserver variability but also enable reproducible assessment of the percentage of lung that is affected. Although quantitative CT measurements have problems, these methods hold real promise for improving our understanding of lung function.[22] Kuwano et al[23] visually quantified emphysema on 1- and 5-mm HRCT scans by using resected specimens. They found an excellent correlation; however, as expected, the 5-mm sections tended to cause underestimation of the degree of emphysema. They concluded that HRCT scans could depict mild emphysema in patients without clinical evidence of airflow limitation and that they could be used to exclude emphysema in patients with moderate or severe airflow limitation. Miller et al[24] found that CT can cause underestimation of the extent of emphysema when lesions are less than 0.5 cm. However, in their study, the inflation pressures of the fixed lung specimens were not controlled, and a number of their patients had only thick-section (10 mm) studies. Mild-to-moderate degrees of centrilobular emphysema are depicted on HRCT as small, round areas of low attenuation, several millimeters in diameter, grouped near the center of secondary pulmonary lobules, with no discernible walls in many cases. Although the centrilobular location of these lucencies cannot always be appreciated on HRCT, lung parenchymal changes are diagnostic of emphysema. [25] Alpha 1-PI deficiency is classically associated with panlobular emphysema, though panlobular emphysema may also be seen in smokers without alpha 1-PI deficiency, in the elderly, and in people with distal bronchial and bronchiolar obliteration. It is almost always most severe in the lower lobes. In severe panlobular emphysema, the characteristic HRCT appearance is that of decreased lung attenuation, with few visible pulmonary vessels in the abnormal regions; bullae or cysts are characteristically absent. Mild and even moderately severe panlobular emphysema can be subtle and difficult to detect.[26] Paraseptal emphysema usually involves the distal part of the secondary lobule and is therefore most obvious in subpleural regions. Paraseptal emphysema may be seen in isolation or in combination with centrilobular emphysema. It is often asymptomatic, but it can be associated with spontaneous pneumothorax in young adults. As demonstrated in the image below, HRCT shows the bullae or air cysts associated with paraseptal emphysema well despite their thin walls.

High-resolution CT (HRCT) shows subpleural bullae consistent with paraseptal emphysema. Red mark shows the size of a normal acinus (Corra da Silva, 2001).

Bullous emphysema is generally seen in association with centriacinar emphysema and paraseptal emphysema.[27] Although a bullous emphysema is not a specific pathologic entity, a syndrome of giant bullous emphysema or vanishing lung syndrome has been described on the basis of clinical and radiologic features. Giant bullous emphysema is often seen in young men in association with large, progressive upper-lobe bullae that occupy a considerable volume of a hemithorax. Most patients with giant bullous emphysema smoke cigarettes, but this entity may also occur in nonsmokers.

Helical CT
Because of the great variability of the machines, with single helical scanners and several models of multisection CT scanners, no technique has been standardized, and the detection rate of emphysema varies with the technique. Even with thick sections, the detection and quantification of emphysema is better than it is with conventional radiography and pulmonary function tests. The great advantage of helical CT is that the whole chest can be scanned in a single acquisition of less than 20 seconds. For the visual detection of emphysema, use of a high-definition algorithm (bone or lung settings) is helpful. However, for the automatic detection of emphysema by computer, the standard algorithm is probably best. High-definition filters affect the attenuation measured by the computer, deviating from the values from the real Hounsfield scale and generally increasing the attenuation to variable degrees depending on the air-lung-tissue proportion. This effect is even more important when the attenuation of the lungs is compared for high-definition processing with scanners from different suppliers. To enhance the margins of adjacent structures with different attenuations, processing artificially changes the original attenuation of the interface planes between the adjacent high- and lowattenuating structures, as in the case of the lung parenchyma and the air content of the lungs. This phenomenon is more obvious in the lung and skin than in solid viscera. This is probably why thresholds for discriminating emphysema differ in the current literature. The authors' personal experience suggests that the threshold -950 HU, as Gevenois suggested, with the standard algorithm without edge enhancement is the most appropriate method. This method may be most consistent and reliable for measuring the lung attenuation by using different machines. Various authors have been investigating volumetric quantification of emphysema based on the Hounsfield scale by using CT pulmonary densitovolumetry (shown in the images below). Some have suggested that precocious detection with quantification and 3-dimensional (3D) demonstration of the extension and distribution of emphysema could be helpful in smoking cessation programs or in risk assessments for occupational exposures.

CT densitovolumetry of a nonsmoker, healthy young patient shows normal lungs. Less than 0.35% of lungs have attenuations below -950 HU (Corra da Silva, 2001).

CT densitovolumetry in a patient with lung cancer. Three-dimensional (3D) image shows that the cancer is in the portion of the right lung that was less affected by emphysema in a patient with poor pulmonary function (Corra da Silva, 2001).

CT densitovolumetry shows the attenuation mask. Green areas are those with attenuation below the selected threshold (here, -950 HU to evaluate emphysema), and pink areas are those with attenuations above the threshold. Area outside the patient is highlighted in green because of air (Corra da Silva, 2001).

Degree of confidence
HRCT is more sensitive than standard chest radiography. [28] HRCT is useful in the workup of smokers with new-onset or progressive dyspnea. The severity of emphysematous change may be underestimated on conventional radiography, whereas HRCT depicts combined fibrosis and emphysema. Patients with these conditions may have relatively normal lung volumes and spirometric results, but they may have severe dyspnea and a reduced diffusing capacity. In healthy nonsmokers aged 19-40 years, a maximum of 0.35% of the area of emphysema can be detected by means of CT quantification.[29] Using 1.5- and 10-mm collimation scans, Miller et al[24] showed that the extent of centriacinar and panacinar emphysema was consistently underestimated with CT, because it missed most lesions less than 0.5 cm in diameter. They concluded that CT is insensitive in detecting the earliest lesions of emphysema. However, the inflation pressures of the fixed lung specimens were not controlled, and a number of their patients had only thick-section (10 mm) studies.

Magnetic Resonance Imaging

Hyperpolarized gases are contrast agents that, when inhaled, provide images of the lung airspaces with high temporal and spatial resolution. The availability of these gases has great potential in the study of diffuse lung disease, particularly emphysema.[30] Ley et al assessed emphysematous enlargement of distal airspaces and concomitant large- and small-airway disease by using diffusion-weighted helium MRI, high-resolution CT (HRCT), and lung function tests. Helium MRI and HRCT scanning results agreed better than did HRCT scanning results and functional characterizations of emphysema in terms of hyperinflation and large- and small-airway disease, as assessed on lung function tests.[31] Sergiacomi et al[32] used lung-perfusion 2-dimensional (2D) dynamic breath-hold technique in patients with severe emphysema and found a high sensitivity (86.7%) and good specificity (80.0%) in detecting perfusion defects. They observed low peak signal intensities in emphysematous regions and concluded that lung perfusion MRI is a potential alternative to nuclear medicine study in the evaluation of severe pulmonary emphysema.

Nuclear Imaging
Functional evaluation of the lungs can be carried out by using xenon-133 (133 Xe) lung ventilation scintigraphy before and after lung-volumereduction surgery (LVRS) in patients with pulmonary emphysema. Xenon-133 washout curves during lung scintigraphy exhibit a biphasic pattern: (1) the first component of the washout curve, m(r), corresponds to an initial rapid phase in washout that reflects emptying of the large airways, and (2) the second component, m(s), reflects a slower phase of washout that is attributed to gas elimination in the small airways.[33, 34] Radionuclide ventilation scans enable a useful assessment of lung function before and after LVRS. Travaline et al[35] demonstrated that small-airway ventilation in lung regions that were surgically treated and also in those areas that were not surgically treated in the same patient were associated with increased improvement in lung function after LVRS.