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HOT TOPICS IN RESPIRATORY MEDICINE: Issue 3, 2007
Chronic obstructive pulmonary disease: definition, epidemiology and diagnostic procedures
Imaging in chronic obstructive pulmonary disease
Saher Burhan Shaker
Correspondence to:
Saher Burhan Shaker - MD, PhD
Dept. of Respiratory Medicine
Gentofte University Hospital
Hellerup, Denmark
E-mail: saher @dadlnet.dk
DOI:


Full text


Chronic obstructive pulmonary disease (COPD) is classically subdivided into pulmonary emphysema and chronic bronchitis (CB). Emphysema is defined patho-anatomically as "permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls, and without obvious fibrosis" [1]. These lesions are readily identified and quantitated using computed tomography (CT), and the accompanying hyperinflation is easily detected on plain chest x-rays especially in advanced disease. The diagnosis of CB is clinical and relies on the presence of productive cough for 3 months in 2 or more successive years. The pathological changes of mucosal inflammation and bronchial wall thickening have been difficult to identify with available imaging modalities; however, the rapid advances in CT technology using multidetector row CT (MDCT) provide a better chance to identify and assess airwall thickening.

IMAGING TECHNIQUES

Plain chest radiography

For the majority of patients with COPD, chest radiography is the first, and probably the only, imaging procedure required. A chest radiograph is usually performed when the diagnosis is made, but repeated chest radiography is not recommended in stable disease. The severity of COPD is assessed by measuring lung function tests (LFT), and the main purpose of chest radiographs is to exclude comorbidities such as bronchogenic carcinoma, left ventricular failure, and bronchiectasis. Chest radiographs also provide a rough estimate of the degree of hyperinflation.
A major advance in the last decade has been the introduction of digital chest radiography. The conventional film is replaced by a reusable photostimulable phosphor plate, selenium drum, or selenium plate. Studies have shown that selenium radiography is superior to phosphor radiography [2] and conventional chest radiography [3].
Even with an optimally exposed image, almost half the area of the lung is obscured by overlying structures [4]. The detection of pulmonary nodules can be improved by using single-shot dual-energy imaging, using a double-layer phosphor plate separated by a copper film. This technique allows digital subtraction of bony structure to reveal the underlying lung [5]. In addition, dual-energy subtraction generates bone-selective images allowing better detection of calcified lung and pleural nodules [6]. This technique is yet to gain wider acceptance by radiologists and clinicians as it competes with CT for the same indications.
The combination of digital radiography with a picture archiving and communication system (PACS) allows rapid dissemination of the images and provides flexible image storage and transport compared to conventional hard copies. Transfer of images to expert radiologists across medical centers offers a real opportunity to facilitate diagnosis and improve treatment.

Computed tomography

CT has two major advantages over plain radiography: the true cross-sectional anatomical image provided without superimposition of organs, and higher contrast, because neighboring or superimposed structures have no or very little influence on the contrast resolution of structures [7]. These advantages help to detect subtle differences in lung density and allow direct visualization of lung destruction and evaluation of its severity. The rapid development of CT technology; the emergence of multidetector (or multislice) scanners capable of making 4 to 64 slices at one rotation; and reduced rotation time below 0.5 s make it possible to scan the whole chest in 5 to 10 s; that is, within a single breathhold even in patients with severe COPD. These technical advances have led to improvement in image quality, with the possibility of multiplanar reconstruction, together with reduction in radiation exposure, an inherent disadvantage of radiology [7].
Loss of lung tissue and, hence, loss of density are the pathological correlates of emphysema; therefore, CT has greatly improved the diagnosis of emphysema, but also provided an objective method to quantitate its severity. In 1978, Rosenblum et al [8] described the CT features of emphysema; they found that patients with emphysema had lower mean lung density compared to healthy individuals and, even more striking, had large zones of extremely low density scattered throughout the lung. To my knowledge this was the first description of low attenuation areas-pathognomonic to parenchymal destruction in emphysema. In subsequent years, investigators found good correlation between the extent of emphysema on CT and in resected lobes or lungs [9-11]. This correlation improved over time with improved spatial resolution, faster scan times, and thinner collimation. At present, CT and, more specifically, high-resolution CT (HRCT), are the imaging methods of choice to diagnose emphysema in living patients. As a result of decreased volume averaging and higher spatial resolution, HRCT is superior to conventional CT for visual identification of small areas of emphysema [11]. The HRCT technique aims at optimizing the demonstration of lung anatomy. Collimation of 1 to 2 mm is essential, together with the use of the high-spatial frequency algorithm (called bone, sharp or hard depending on the scanner manufacturer). With current scanners that have a rotation time of less than 0.5 s, scan techniques of 120 to 140 kV and tube current of 200 to 250 mA have proved satisfactory. A window level of -700 Hounsfield units (HU) and a width of 1500 HU are optimal for lung structures.
In clinical practice, CT is rarely used to diagnose emphysema and assess its severity, and its use is limited to research settings; nevertheless, expected advances in the medical and surgical treatment of emphysema will increase the use of CT to assess the efficacy of these treatments.

PULMONARY EMPHYSEMA

Emphysema is a major constituent of lung pathology in COPD and is the major determinant of clinically recognized severe airflow obstruction. It is relatively uncommon to find severe airway obstruction with little or no emphysema [12]. The incidence of emphysema in patients with chronic productive cough is more than 70% [12]. High incidence of emphysema has been reported in smokers undergoing lobe resection for nodules, even in the absence of symptoms and airway obstruction [13].
Four morphological subtypes of emphysema have been described:

1. Centrilobular emphysema (CLE) is characterized by destruction of the central part of the secondary lung lobule, initially with predilection for the upper lobes. It is the most frequent subtype in smokers.
2. Paraseptal emphysema (PSE) involves the distal part of the secondary lung lobule adjacent to the interlobar septa and pleura. PSE usually coexists with CLE in smokers.
3. Panlobular emphysema (PLE) is the pathological subtype associated with α1-antitrypsin deficiency (A1AD). In PLE, the secondary lung lobule is more or less uniformly destroyed from the respiratory bronchiole to the terminal distal alveoli. The lesions are characteristically more predominant in the lower lobes.
4. Irregular airspace enlargement is not the result of direct parenchymal destruction, but is caused by associated fibrosis of other lung diseases such as sarcoidosis, tuberculosis, and idiopathic pulmonary fibrosis [1]. The combination of fibrosis and airspace enlargement is easily detected on chest radiographs and CT.

Plain chest radiography in emphysema

Destruction of the alveolar septa and vascular structures can be radiologically detected as areas of low density with poor vascularity. Loss of elastic tissue results in features of airway obstruction and hyperinflation. Vascular changes and hyperinflation are the most important signs of emphysema on chest radiographs.
Rapid attenuation of the peripheral pulmonary arteries results in arterial deficiency in the outer half of the lung fields [14,15]. Arterial deficiency refers to the reduced number and size of pulmonary vessels and their branches. The vessels are distorted and have increased branching angles. These signs are subject to inter- and intraobserver variations and are less reliable than are the signs of hyperinflation.
Hyperinflation is reflected physiologically as a marked increase in residual volume. Radiologically, the most reliable sign of hyperinflation is a low, flattened diaphragm (Figure 1).

HTRM - 3 : Resp.Med. 26-2 Shaker fig. 1_th.jpg  Figure 1. Chest radiograph (frontal and lateral view) of a 63-year-old woman with tobacco-induced emphysema showing the signs of hyperinflation and poor vascularity at the lung periphery. The patient had severe airway obstruction, forced expiratory
volume in 1 s (FEV1) = 0.8 L (32% of predicted).


The diaphragm is considered low if the border of the right hemidiaphragm in the midclavicular line lies at or below the anterior end of the seventh rib. Flattening of the diaphragm contour is best detected on lateral projections by drawing a line between the costophrenic and the cardiophrenic angles. Perpendicular height of less than 1.5 cm indicates flattening. This sign correlates well with the degree of airway obstruction [14,16]. Increase in the retrosternal airspace of more than 2.5 cm between the sternum and the ascending aorta is also supportive of the presence of emphysema [15]. Other signs include increased length of the lung (>30 cm) [16], small heart, and obtuse costophrenic angle.
Saber-sheath trachea is also considered a sign of hyperinflation and is present in some patients with COPD. It is evident on both radiography and CT. The trachea is normal down to the level of the thoracic inlet. In its thoracic course, the trachea becomes narrowed in the coronal plane, possibly due to air trapping in the upper lobes related to CLE. The ratio of the coronal to sagittal tracheal diameters measured 1 cm above the aortic arch is termed the tracheal index. An index below 0.7 cm is diagnostic of saber-sheath trachea. In a study of 60 patients with sabersheath trachea, Greene found that 57 had clinical evidence of COPD, as compared with 11 of 60 control patients with a normal tracheal index [17].
In general, the sensitivity of chest radiography is low, especially in mild to moderate disease. Thurlbeck and Simon found that only 41% of patients with severe pathologically proven emphysema could be diagnosed correctly by plain radiography [15].
Bullae are readily detected on chest radiographs as avascular round or oval areas greater than 1 cm in diameter surrounded by a pencil-thin or invisible wall. Usually bullae are associated with other signs of emphysema on chest radiography, yet they might be present without other radiological signs of emphysema, particularly in an apical paraseptal location. Bullae are often asymmetrical with one lung more severely involved. Chest radiography markedly underestimates the extent of bullous changes compared to CT [18]. Furthermore, CT allows the distinction between localized bullous disease amenable to surgical resection from bullous changes associated with diffuse severe emphysema, thus offering help with selecting patients for bullectomy [19]. In addition, CT can, in few difficult instances, distinguish bullous disease from pneumothorax.
Idiopathic bullous emphysema is sometimes referred to as vanishing lung syndrome and usually occurs in both smoker and nonsmoker, young male patients. It is a rare entity resulting in large, progressive bullous changes associated with compression or relaxation atelectasis of the surrounding lung tissue. The bullae have a typical upper, asymmetrical distribution and occupy at least one third of a hemithorax (Figure 2) [20].

HTRM - 3 : Resp.Med. 26-2 Shaker fig. 2_th.jpg  Figure 2. Severe bullous emphysema of the right upper lobe. A smaller bulla and a combination of centrilobular and paraseptal emphysema can be seen in the left upper lobe. 

Computed tomography in emphysema

CT is the imaging modality of choice to detect emphysema and assess its severity in vivo, given its high contrast and spatial resolution. Areas of low attenuation are readily detected as dark areas without a visible wall located in the center of the secondary lung lobule surrounded by apparently normal lung parenchyma. During the1980s, several studies showed good correlation between visual grading on CT scans and the pathological extent of emphysema with correlation coefficients between 0.7 to 0.9 [9,10,21]. It was suggested that HRCT is able to distinguish normal lungs from emphysematous lungs and to detect even the mildest degrees of CLE [10,21]. This finding was challenged by Miller et al [11], who found that CT is insensitive in detecting the earliest lesions of emphysema because most lesions <5 mm in diameter were missed. The group also reported that CT consistently underestimated the extent of CLE and PLE. Despite that, they found a good correlation between CT score and pathological score (r = 0.81) with the use of 10-mm slices, and an even better correlation (r = 0.85) with the use of 1.5-mm slices. Similar conclusions were reached by Spouge et al [22], who determined the value of CT in assessing the presence and extent of pathologically proved PLE.
CLE is the most common subtype of emphysema and is caused by smoking in the vast majority of cases. The lesions usually have an upper lobe predilection (Figure 3). This distribution might be the explanation for the late onset of dyspnea in patients with emphysema. It has been estimated that in CLE, 30% of the lung must be destroyed before symptoms or changes in lung function become evident [23]. Areas of ground-glass opacities and centrilobular micronodules are common findings in cigarette smokers, indicating the presence of respiratory bronchiolitis [24]. It has been proposed that these lesions are the precursors of CLE in smokers. Data in support of this hypothesis are scarce [25], but repeated CT scans in smokers attending lung cancer screening programs are expected to promote our understanding of the natural history of CLE in smokers.

HTRM - 3 : Resp.Med. 26-2 Shaker fig. 3_th.jpg  Figure 3. High-resolution computed tomography (HRCT) section
at the level of the carina showing centrilobular emphysema with
areas of low attenuation scattered throughout the lung,
clustered around a centrilobular pulmonary arteriole, and
surrounded by apparently normal lung tissue. 


PSE usually coexists with CLE in smokers. It is characterized by involvement of the distal wall of the pulmonary lobule. It has typical distribution adjacent to pleural surfaces and interlobar fissures (Figure 4). The walls of the lesions are often thicker than CLE and PLE and might resemble honeycombing; however, honeycombing is usually arranged in multiple rows, whereas PSE is typically confined to a single row. When the lesions are >1 cm in diameter, they are most appropriately termed bullae. Rupture of these bullae might be the cause of idiopathic spontaneous pneumothorax [26]. Lesur and colleagues [27] found that CT demonstrated emphysema with apical distribution in 17 of 20 young patients with idiopathic spontaneous pneumothorax. Subpleural distribution was found in 16 patients [27].

HTRM - 3 : Resp.Med. 26-2 Shaker fig. 4_th.jpg  Figure 4. High-resolution computed tomography section at the level of the carina showing paraseptal emphysema consisting of a single row of lesions with a distinct wall. 


PLE is the morphological subtype associated with A1AD and is characterized by uniform destruction of the pulmonary lobule, leading to widespread areas of abnormally low attenuation without visible walls (Figure 5). In contrast to CLE, the destruction is generalized and more prominent in the lower lobes [28]. Pulmonary vessels in the affected lung are fewer and smaller than normal. These changes are easily distinguished from healthy lungs in severe PLE; however, in mild to moderate PLE they can be very subtle and difficult to detect [11]. PSE is an uncommon accompanying lesion, and bullae are not considered a major feature of the disease [28]. Bronchiectasis and bronchial wall thickening are frequently reported in A1AD and are probably the result of frequent infection and damage of the airways [28]. In cigarette smokers with a normal A1AD level, PLE may be seen in conjunction with CLE, but it is not the dominant morphologic abnormality and as emphysema worsens it becomes difficult to distinguish PLE from CLE both pathologically and radiologically.

HTRM - 3 : Resp.Med. 26-2 Shaker fig. 5_th.jpg  Figure 5. High-resolution computed tomography through the lung bases in a patient with panlobular emphysema due to α1-antitrypsin deficiency after single lung transplantation (right). The left lung shows uniform destruction of the pulmonary lobule associated with fewer and smaller pulmonary vessels and mild varicose bronchiectasis. 


Radiation exposure is an inherent limitation of the use of CT in the clinical setting. The radiation exposure in conventional CT is 7 mSv, compared to 0.05 mSv for a chest radiograph [29]. Nevertheless, several years ago the concept of low-dose CT was introduced. It was found that CT images acquired at 20 mA were not inferior in quality to those acquired at the conventional dose of 200 mA, and yielded similar anatomical information [30]. Low-dose protocol reduces the radiation dose below 1 mSv, permitting the use of repeated quantitative CT to monitor the progression of emphysema without considerable reduction in image quality [31].

CT quantitation of emphysema

The extent of emphysema can be assessed from CT scans by both visual and computer-assisted methods. Visual quantitation is performed by assessing each CT section for the severity of emphysema, thus obtaining a rough estimate of the area involved by emphysema. Comparative CT-pathological studies have shown good correlation between visual scores of CT scans and pathological specimens [9,11,21,22]. HRCT is the technique of choice for visual assessment of emphysema. Nevertheless, visual scoring is subjective and has therefore large intra- and interobserver variations, a clear limitation for its use in longitudinal and interventional studies. Conversely, objective quantitation has been studied extensively and is a promising method for the evaluation of the severity and progression of emphysema.
Because of their digital nature, CT images lend themselves to objective computer analysis. The analysis consists of 3 steps: segmentation of the lung using a soft tissue lung interface threshold of -200 to -500 HU; generation of the histogram of pixel attenuation (density) values; and calculation of the densitometric parameters. Several parameters have been explored (Figure 6), but 2 have been widely applied in CT quantitative studies: the relative area of emphysema (RA; also called emphysema index) and the percentile density (PD) [32].

  
HTRM - 3 : Resp.Med. 26-2 Shaker fig. 6_th.jpg
Figure 6. Computed-tomography-derived lung density histogram of a patient with smoker's emphysema. Four densitometric parameters are depicted: the mean lung density; the mode; the fifteenth percentile density in Hounsfield units (HU; PD15 is calculated by adding 1000 = 56 g/L); and the relative area of emphysema (RA-910), which is the shaded area below the threshold of -910 HU (= 34%).


Müller and associates [33] applied the density mask software introduced on General Electric scanners in the late 1980s to objectively quantitate the severity of emphysema. Pixels with values below -910 HU (RA-910) were highlighted and their percentage calculated as an index of the severity of emphysema. The highest correlation with pathology was obtained using a threshold of -910 HU. Using HRCT, Gevenois et al [34,35] found that at a threshold of -950 HU, there was no significant difference between the radiological and pathological extent of emphysema. Although HRCT improves the visual assessment of emphysema, the combination of thin sections and hard reconstruction algorithms results in poor density resolution and should be avoided in densitometric studies. Relative area is an extensively used index to quantitate emphysema from CT scans; thresholds in the range of -856 to -960 HU have been suggested for this purpose [36].
The nth percentile density is derived from the histogram as the density in Hounsfield units at which n% of pixels have lower densities. Percentile density can be converted into grams per liter by adding 1000 (Figure 6). Gould et al [37] found good correlation between the area of the distal airspaces and the fifth percentile density of the density histogram. Dirksen et al [38] showed that percentiles in the range of 10 to 30% were most pertinent because they showed the strongest time trend in a longitudinal study of CT lung density assessment in emphysema. The fifteenth percentile (PD15) was chosen to monitor the progression of emphysema in a subsequent study by the same group [39].
Several investigators have used different quantitative CT parameters and found good correlation with the diffusion capacity [40-42], correlations ranging from poor to good with airway obstruction [40-43], good correlation with exercise capacity [44], and good correlation with the health-related quality of life [40].
The main confounder to lung densitometry is lung volume changes depending on the depth of inspiration during scanning. Investigators have tried to overcome this limitation by spirometric gating; nevertheless, even under these conditions patients with COPD were less able to reproduce the same lung volume in repeated scans [45]. Lung volume can be calculated from volumetric scans and thus lung density can be volume-adjusted by statistical modelling [38]. Using this method, there was high reproducibility of RA-910 and PD15 in repeated scans of patients with COPD [31]. Together with the use of low-dose protocol, the high sensitivity and reproducibility of lung density parameters provide good tools to monitor the progression of emphysema and to monitor the effect of current and future treatments.
Standardization of the protocol of image acquisition, reconstruction, and analysis is extremely important in quantitative CT. In addition to reducing the variation in lung density measurement and improving the sensitivity of the technique, it allows comparison of results from different studies [36]. The need for standardization of CT densitometry in a manner similar to standardization of LFT is well recognized, and efforts have been made to achieve this [36,46]; yet the radiological and respiratory societies have to work together to produce a common recommendation regarding the optimal CT acquisition protocol and analysis procedure for the quantitation of emphysema.
Lung densitometry has been studied in patients undergoing lung volume reduction surgery to assess the extent of emphysema in pre- and postoperative CT scans. Such studies have typically shown a significant post-operative reduction in RA. Dirksen et al [39] used densitometric parameters in a randomized trial of the effect of augmentation therapy in patients with A1AD. They found a trend of protective effect of augmentation therapy that did not reach statistical significance because of the small sample size. This study suggested that CT densitometry is twice more sensitive than LFT (forced expiratory volume in 1 s [FEV1] and diffusion capacity) for detecting the progression of emphysema in patients with A1AD [39]. RA-910 was also used as an end point in a pilot study to evaluate the feasibility of all-trans-retinoic acid in emphysema [47]. No significant difference was observed between the active and placebo groups, but the treatment was well tolerated to encourage trials with higher doses or longer duration.
The discussed density parameters provide not only a global measure of emphysema, but can be further divided into upper, middle, and lower zones and inner core and outer rind. Further refinement of the method to segment the anatomical lung lobes will be an important improvement. However, density measurement does not provide information about the subtype of emphysema and other associated pathological elements. Uppaluri et al [48] used texture analysis of lung parenchyma by a method called adaptive multiple feature method. This computer-aided method of pattern recognition showed excellent sensitivity and reproducibility in identifying areas of emphysema, ground-glass opacity, and fibrosis.

CHRONIC BRONCHITIS

CB is defined, using clinical criteria, by a productive cough on most days for at least 3 months for 2 or more consecutive years, when other pulmonary or cardiac causes are excluded. The pathological changes in obstructive CB include, in addition to hyperplasia and hypertrophy of the mucus glands, structural obstruction of the small airways due to inflammation and fibrosis [49].

Plain chest radiography

In the absence of accompanying emphysema and hyperinflation, the majority of patients with CB have a normal chest radiograph. Two radiographic features have been described in CB: bronchial wall thickening and increased lung markings. The signs of bronchial wall thickening are ring shadows [50] and parallel line shadows, also known as tramline opacities. These signs are largely subjective, with marked overlap in normal subjects, and might merely reflect the presence of accompanying bronchiectasis [51]. Increased lung markings or "dirty" lung in smokers refer to small ill-defined opacities in the lung parenchyma. This sign has been regarded as useful evidence in support of the presence of CB; however, the relationship of CB to dirty lung has not been pathologically validated.
Pulmonary hypertension and cor pulmonale are recognized complications of COPD, characterized on chest radiographs by enlargement of the right ventricle and the central pulmonary arteries. On posteroanterior films, the transverse diameter of the right descending pulmonary artery is <17 mm and the left descending pulmonary artery <18 mm. Greater values indicate enlargement and support the presence of pulmonary hypertension [52].

Computed tomography

There are no specific signs of CB on CT. Remy-Jardin and colleagues found that 33% of healthy smoking volunteers with normal LFT tests had proximal and distal bronchial wall thickening as compared to 18% of control subjects [24]. In a subsequent CT-pathological correlation study in a group of heavy smokers, the same authors found bronchial wall thickening in 39% of patients. This finding correlated pathologically with smooth muscle hyperplasia, bronchial wall inflammation, and peribronchial fibrosis [13]. Thus HRCT has provided new insights into the morphological changes in smokers' lung; however, there are still a number of unresolved issues about the exact histopathological nature of dirty lung [51].

Quantitative CT of the airways

There have been reviews of quantitation of airways by CT [53,54], and the use of CT to measure airway dimensions has received much attention in the last decade. This happened parallel to the rapid advances in CT technology, particularly the introduction of MDCT in the late 1990s. Volume scans of the lungs with 0.5- to 1-mm sections can now be obtained in less than 10 s, that is, within a single breathhold. MDCT produces a true isotropic voxel with good image quality and unlimited capacity for multiplanar reconstructions.
Initial CT studies relied on manual tracing of the airways [54]. This method is tedious, time-consuming, and has poor reproducibility. Instead, studies applied automatic image analysis using the full-width-at-half-maximum technique, which implies the evaluation of voxel attenuation values along an x-ray beam that projects from the center of the lumen toward the parenchyma [55]. The clinical applications of CT airway measurement have been limited, as the major focus has been on studying the parenchyma. Nakano et al [55] measured the dimensions of the right upper lobe segmental bronchus in 114 smokers and found that airwall thickness correlated with measures of airflow obstruction [55]. Airwall thickness was increased in COPD patients with symptoms of CB compared to more severely obstructed patients without symptoms of CB [56].
The main criticism of measuring large airway dimensions is that the major site of pathology in COPD is the small airways [49]. Measuring small airways with CT is still associated with large variations. However, there are data suggesting that measuring large airways provide an estimate of small airway pathology [57]. It has been shown that FEV1 % pred correlates with CT-derived wall area percent. More interestingly, this correlation improved as the airways became smaller in size from the third to the sixth generation [58].
While quantitative CT of the lung parenchyma have been applied in longitudinal and interventional studies, further research is needed to validate quantitation of the airways, regarding image acquisition, adjustment for lung volume, analysis procedure, and reproducibility, before its use as an end point in clinical trials.

OTHER IMAGING TECHNIQUES

Ventilation-perfusion scintigraphy

Several types of scintigraphs have been used in patients with COPD. Ventilation-perfusion lung scintigraphy is abnormal in symptomatic patients with COPD. Most patients with emphysema have multiple, bilateral, patchy, matched defects of ventilation and perfusion; however, a subgroup of patients show ventilation-perfusion mismatch quite similar to that seen in pulmonary embolism [59].
Usually ventilation-perfusion scintigraphy is performed to exclude lung embolism in patients with COPD presenting with acute exacerbations of symptoms. Unfortunately, the results are frequently inconclusive because of the preexisting perfusion defects [60]. Tomographic imaging using single photon emission computed tomography (SPECT) has improved the sensitivity and specificity of ventilation-perfusion scintigraphy in detecting lung embolism to a level comparable with MDCT [61]; nevertheless, evidence is lacking for the advantage of SPECT over multislice CT in patients with emphysema [60].
Ventilation-perfusion scintigraphy traditionally has been used in selecting patients for surgical treatment of emphysema in lung volume reduction surgery (LVRS) and lung transplantation. The National Emphysema Treatment Trial (NETT) study has shown improved survival in a subgroup of patients with upper lobe distribution of emphysema and low exercise capacity [62]. CT provides subjective (visual) and objective (quantitative) assessment of the severity of emphysema and its regional distribution [63] and is mandatory for patient selection for LVRS. CT was found superior to ventilation-perfusion scintigraphy in defining the heterogeneous distribution of emphysema as a predictor for improvement after LVRS [64]. However, ventilation-perfusion scintigraphy is complementary to CT by providing functional mapping of the lung lobes pathoanatomically assessed by CT [59].

Magnetic resonance imaging

Currently, CT is the imaging modality of choice to diagnose and assess lung pathology in COPD, yet many investigators have explored magnetic resonance imaging (MRI) as a possible alternative or suppliant, obviously because MRI does not rely on ionizing radiation. Functional imaging of the lung is currently conducted using radionucleotide studies of ventilation and perfusion; however, MRI is a promising tool in the assessment of ventilation and can be superior to scintigraphic ventilation studies [65]. Conventional MRI of the lung is difficult because of the abundance of fine air-soft tissue interfaces, low proton density of the lung, and the noise induced by cardiac and diaphragmatic motion [66]. The rapid decay of MR signals can be overcome by inhalation of hyperpolarized inert noble gases such as helium-3 (3He) or xenon-129 (129Xe). Hyperpolarized MRI was first reported in humans in 1996 [67].
Mainly four imaging sequences have undergone continuous refinement in the last decade:

1. Ventilation imaging. Is the most straightforward use of MRI, where static imaging of the lungs is made while a patient inhales hyperpolarized 3He or 129Xe. It can be performed during a single breathhold (Figure 7).
2. Dynamic ventilation. Rapid sequences of MR can be employed to produce dynamic ventilation images. Studies in patients with COPD have shown regional inhomogeneous and delayed ventilation [68].
3. Diffusion weighted images. The apparent diffusion coefficient (ADC) of 3He reflects the size of the distal airspaces. Expectedly, studies have shown that ADC is increased in patients with emphysema compared to that in healthy patients [69].
4. Oxygen-enhanced MRI. Employs the measurement of the rate of decay of 3He polarization, providing an indirect measurement of the local oxygen concentration [70]. Preliminary studies have shown that oxygen-enhanced MRI correlates to the functional and HRCT extent of emphysema [71,72].

HTRM - 3 : Resp.Med. 26-2 Shaker fig. 7_th.jpg  Figure 7. Ventilation magnetic resonance imaging sequences using hyperpolarized helium-3 (3He): A. In healthy individual showing uniform ventilation; B. In a patient with smoker's emphysema showing patchy ventilation defects; C. In a patient with α1-antitrypsin deficiency showing the ventilation defect mainly in the lower lobes.

Bronchography

Bronchographic findings in COPD are of historic interest, as the investigation no longer has a place in the clinical diagnosis and follow-up of COPD. Bronchography has contributed to our understanding of the structural changes of the airways in COPD, but during the last 20 years this modality has been totally replaced by CT.

Echocardiography

Echocardiography is used to assess noninvasively right ventricular pressure by measurement of right ventricular and atrial dimensions and by measurement of the pressure gradient across the tricuspid valve. Echocardiography is twice as sensitive as clinical parameters in detecting cor pulmonale [73]. It is essential for monitoring the severity of pulmonary hypertension and response to treatment. In addition, echocardiography can assess the presence of associated left ventricular disease, a common comorbidity in patients with tobacco-induced COPD [74]. Technical difficulties might be encountered in patients with hyperinflation because of poor transmission of sound waves by the increased retrosternal airspace; however, adequate examination can be achieved in the majority of patients.
There have been many advances in imaging modalities of COPD in the last two decades. Clearly, our understanding of the pathogenesis, natural history, and phenotypes of COPD mainly will be promoted by imaging.

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