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Imaging in Chronic Obstructive Pulmonary Disease

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Hot Topics in Respiratory Medicine 2007;3:19-27 - Downloaded from www.hottopicsin.com -
Imaging in chronic obstructive
pulmonary disease
❯ Saher Burhan Shaker
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 co-
morbidities such as bronchogenic carcinoma, left
ventricular failure, and bronchiectasis. Chest radiographs
also provide a rough estimate of the degree of hyper-
inflation.
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
Hot Topics in Respiratory Medicine n. 3 - 2007
© FBCommunication - Modena (Italy)
Imaging in chronic obstructive pulmonary disease
Author: Saher Burhan Shaker
Email: saher@dadlnet.dk
Copyright © 2007 FBCommunication s.r.l. a socio unico
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 resolu-
tion, HRCT is superior to conventional CT for visual
identification of small areas of emphysema [11]. The HRCT
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Imaging in chronic obstructive pulmonary disease
 Hot Topics in Respiratory Medicine 2007;3:19-27 - Downloaded from www.hottopicsin.com - Copyright © 2007 FBCommunication s.r.l. a socio unico

technique aims at optimizing the demonstration of lung Hyperinflation is reflected physiologically as a marked
anatomy. Collimation of 1 to 2 mm is essential, together increase in residual volume. Radiologically, the most
with the use of the high-spatial frequency algorithm reliable sign of hyperinflation is a low, flattened diaphragm
(called bone, sharp or hard depending on the scanner (Figure 1).
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 A
(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. B
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 Figure 1. Chest radiograph (frontal and lateral view) of a 63-
number and size of pulmonary vessels and their branches. year-old woman with tobacco-induced emphysema showing the
The vessels are distorted and have increased branching signs of hyperinflation and poor vascularity at the lung periphery.
angles. These signs are subject to inter- and intraobserver The patient had severe airway obstruction, forced expiratory
variations and are less reliable than are the signs of volume in 1 s (FEV1) = 0.8 L (32% of predicted).
hyperinflation.

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Chronic obstructive pulmonary disease: definition, epidemiology, and diagnostic procedures
Hot Topics in Respiratory Medicine 2007;3:19-27 - Downloaded from www.hottopicsin.com - Copyright © 2007 FBCommunication s.r.l. a socio unico

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 Figure 2. Severe bullous emphysema of the right upper lobe. A
course, the trachea becomes narrowed in the coronal smaller bulla and a combination of centrilobular and paraseptal
plane, possibly due to air trapping in the upper lobes emphysema can be seen in the left upper lobe.
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 saber-
sheath 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,
Figure 3. High-resolution computed tomography (HRCT) section
particularly in an apical paraseptal location. Bullae are
at the level of the carina showing centrilobular emphysema with
often asymmetrical with one lung more severely involved.
areas of low attenuation scattered throughout the lung,
Chest radiography markedly underestimates the extent of
clustered around a centrilobular pulmonary arteriole, and
bullous changes compared to CT [18]. Furthermore, CT
surrounded by apparently normal lung tissue.
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, challenged by Miller et al [11], who found that CT is
CT can, in few difficult instances, distinguish bullous dis- insensitive in detecting the earliest lesions of emphysema
ease from pneumothorax. because most lesions <5 mm in diameter were missed. The
Idiopathic bullous emphysema is sometimes referred to group also reported that CT consistently underestimated the
as vanishing lung syndrome and usually occurs in both extent of CLE and PLE. Despite that, they found a good
smoker and nonsmoker, young male patients. It is a rare correlation between CT score and pathological score
entity resulting in large, progressive bullous changes (r = 0.81) with the use of 10-mm slices, and an even better
associated with compression or relaxation atelectasis of correlation (r = 0.85) with the use of 1.5-mm slices. Similar
the surrounding lung tissue. The bullae have a typical conclusions were reached by Spouge et al [22], who
upper, asymmetrical distribution and occupy at least one determined the value of CT in assessing the presence and
third of a hemithorax (Figure 2) [20]. 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
Computed tomography in emphysema lesions usually have an upper lobe predilection (Figure 3).
This distribution might be the explanation for the late onset
CT is the imaging modality of choice to detect emphysema of dyspnea in patients with emphysema. It has been
and assess its severity in vivo, given its high contrast and estimated that in CLE, 30% of the lung must be destroyed
spatial resolution. Areas of low attenuation are readily before symptoms or changes in lung function become
detected as dark areas without a visible wall located in the evident [23]. Areas of ground-glass opacities and
center of the secondary lung lobule surrounded by centrilobular micronodules are common findings in cigarette
apparently normal lung parenchyma. During the1980s, smokers, indicating the presence of respiratory bronchiolitis
several studies showed good correlation between visual [24]. It has been proposed that these lesions are the
grading on CT scans and the pathological extent of precursors of CLE in smokers. Data in support of this
emphysema with correlation coefficients between 0.7 to 0.9 hypothesis are scarce [25], but repeated CT scans in
[9,10,21]. It was suggested that HRCT is able to distinguish smokers attending lung cancer screening programs are
normal lungs from emphysematous lungs and to detect even expected to promote our understanding of the natural
the mildest degrees of CLE [10,21]. This finding was history of CLE in smokers.

21
Imaging in chronic obstructive pulmonary disease
 Hot Topics in Respiratory Medicine 2007;3:19-27 - Downloaded from www.hottopicsin.com -
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].
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
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.
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.
22
Chronic obstructive pulmonary disease: definition, epidemiology, and diagnostic procedures
Copyright © 2007 FBCommunication s.r.l. a socio unico
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.
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
15th percentile density = -944 HU
25000 The mode = -897 HU
Mean lung density = -859 HU
20000
Frequency
15000
10000
5000
0
50 00 50 00 50 00 50 00 50 00 50 00 50 00
-10 -10 -9 -9 -8 -8 -7 -7 -6 -6 -5 -5 -4 -4
Pixel attenuation values
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%).
Hot Topics in Respiratory Medicine 2007;3:19-27 - Downloaded from www.hottopicsin.com -
have been widely applied in CT quantitative studies: the
relative area of emphysema (RA; also called emphysema
index) and the percentile density (PD) [32].
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 assess-
ment 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 (see 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 den-
sitometry 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 recom-
mendation 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-
Copyright © 2007 FBCommunication s.r.l. a socio unico
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 pro-
gression 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 in-
formation 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
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Imaging in chronic obstructive pulmonary disease
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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 appli-
cations 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 dimen-
sions 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
24
Chronic obstructive pulmonary disease: definition, epidemiology, and diagnostic procedures
Copyright © 2007 FBCommunication s.r.l. a socio unico
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 hy-
perpolarized 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].
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.
Hot Topics in Respiratory Medicine 2007;3:19-27 - Downloaded from www.hottopicsin.com -
A B
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.
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
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