DOI:10.2214/AJR.05.0890
AJR 2006; 187:W420-W429
© American Roentgen Ray Society
Transcutaneous Contrast-Enhanced Sonography of Peripheral Lung Lesions
Christian Görg1,
Rudolf Kring1 and
Tillmann Bert1
1 All authors: Department of Internal Medicine and Department of Hematology,
Philipps-University Marburg, Marburg, Germany 35033.
Received May 25, 2005;
accepted after revision July 20, 2005.
Address correspondence to C. Görg
(goergc{at}mailer.uni-marburg.de).
WEB
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Abstract
OBJECTIVE. Transpulmonary sonography contrast agents, in conjunction
with contrast-specific imaging techniques, are increasingly accepted in
clinical use for diagnostic imaging of several organs. Anatomically, the lung
is characterized by dual blood sources, supplied from both the pulmonary and
bronchial arteries. Contrast-enhanced sonography enables us to determine
whether the pulmonary or the bronchial arteries are the source of blood to
lung lesions, depending on the time to enhancement and the extent of
enhancement after contrast agent application.
CONCLUSION. This article reports our first experience with
transcutaneous contrast-enhanced sonography for the diagnosis and differential
diagnosis of peripheral lung lesions.
Keywords: contrast-enhanced sonography • contrast media • lung • lung consolidation • lung diseases • sonography
Introduction
Transcutaneous sonography of the chest is limited because of the sound
reflection at the aerated lung. Despite of this general limitation, however,
B-mode sonographic patterns and color Doppler sonographic patterns of various
pulmonary diseases have previously been described
[1,
2].
Sonographic contrast agents, in conjunction with contrast-specific imaging
techniques, are increasingly accepted in clinical use for the diagnostic
imaging of several organs [3].
This review focuses on contrast-enhanced sonographic patterns for the
diagnosis and differential diagnosis of peripheral pleura-based lesions.
General Considerations of Contrast-Enhanced Sonography
This pictorial review is based on the contrast-enhanced sonographic
examination of 140 consecutive adult patients with pleural-based pulmonary
lesions diagnosed by B-mode sonography at an internal medical center. Informed
consent, according to legislative requirements, was obtained from each patient
for contrast-enhanced sonographic examination, and the local internal review
board was consulted and informed about the retrospective analysis. A chest
radiograph was obtained in all patients before our study. In addition, in most
cases a CT examination of the thorax had to be performed for further
diagnosis.
Contrast-enhanced sonographic studies were immediately performed after
baseline sonography with a sonography system equipped with low acoustic power
mode software (Acuson Sequoia gastrointestinal, Siemens Medical Solutions).
Curved array probes with frequencies of 3.0 and 5.0 MHz were used. We used a
sulfur hexafluoride-based microbubble second-generation contrast agent
(SonoVue, Bracco SpA) for contrast-enhanced sonographic examinations. Because
of the structure and the containment of a low-solubility gas, it is most
suitable for low-mechanical-index imaging. Low-mechanical-index techniques,
with low-solubility gas contrast agents, allow continuous real-time imaging of
all phases.
During clinical studies [3],
safety parameters (vital signs, ECG, oxygen saturation) were monitored and no
clinically meaningful change was noticed. The cost of one contrast-enhanced
sonographic examination (with 4.8 mL of SonoVue) in Europe is 
65. In the
United States, the administrative process to obtain approval of SonoVue by the
U.S. Food and Drug Administration (FDA) is not yet complete.
After baseline sonography, the contrast agent was injected IV within 2
seconds via a 20-gauge cannula. A volume of 4.8 mL was administered followed
by a 5-mL saline flush. Immediately after administering the contrast medium,
pleural lesions were observed for contrast agent uptake over a period of 5
minutes. Contrast-enhanced sonographic studies were analyzed on the basis of
review of sonographic unit-stored clips. Tissue enhancement of pleural lesions
was evaluated by using the splenic tissue enhancement as an in vivo reference
[4]. Sono-Vue, which is a
second-generation agent, is prepared within a few seconds and can be
administered immediately after baseline sonography. In our institution, we
have the contrast agent in stock at all times. In our series, the duration of
baseline sonography and contrast-enhanced sonography was a maximum of 15
minutes.
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Fig. 1B —35-year-old man with pleural effusion and compression
atelectasis. Contrast-enhanced sonography shows short time to enhancement (2
s), suggesting pulmonary arterial supply. Arrow shows marked enhanced
vessel.
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Fig. 1C —35-year-old man with pleural effusion and compression
atelectasis. During parenchymal phase (1 min), hyperechoic tissue enhancement
compared with splenic (S) enhancement (1 min) is seen.
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Fig. 2B —68-year-old man with hypernephroma and histologically proven
pleural-based metastasis. Contrast-enhanced sonography shows delayed time to
enhancement (7 s), suggesting bronchial arterial supply. Arrow shows small
enhanced vessel.
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Pathophysiologic Basics of Pulmonary Vascularity
Anatomically, the lung is characterized by a dual blood supply. In humans
the bronchial arterial system is invariably joined to the bronchial tree. This
system provides nutrition for the bronchi, pulmonary vessels, alveoli,
interstitial tissue, and visceral pleura. It also works as a hemodynamic
system with anastomoses between bronchial and pulmonary arteries. Anastomoses
between these two systems are usually closed. In case of occlusion of
pulmonary arteries or in case of hypoxia caused by lung diseases, the
anastomoses will be opened. From angiographic studies, it is known that
peripheral lung lesions such as lung cysts, pulmonary abscesses, and liquefied
pneumonia are predominantly supplied by bronchial arteries. Even lung cancer
is supplied by bronchial arteries
[5].
Pulmonary arterial vessels show a tree-like distribution. The circulation
is responsible for gas exchange. In contrast to the systemic circulation, the
pulmonary circulation system, when confronted with hypoxia, creates
vasoconstriction, called the Euler-Liljestrand mechanism. Invasion of the
pulmonary artery by a tumor has been described in 56-87% of patients suffering
from primary lung cancer [5,
6]. Especially in the center of
malignant lesions, the regular supply of vessels is completely destroyed
because of reduced vascularization by stricture or occlusion of the pulmonary
arteries [6]. Tumor
neoangiogenesis in lung cancer rises from bronchial arteries. Pulmonary
arteries seem to have no or very low capacity for neoangiogenesis
[7].
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Fig. 5B —15-year-old boy with pleurisy, suggesting pleuropneumonia.
Contrast-enhanced sonography shows isoechoic enhancement (1 min) of
infiltrated lung (LU) in early parenchymal phase compared with splenic (S)
enhancement (1 min).
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Fig. 5C —15-year-old boy with pleurisy, suggesting pleuropneumonia.
Contrast-enhanced sonography shows hyperechoic enhancement (5 min) of
infiltrated lung (LU) in late parenchymal phase compared with splenic (S)
enhancement (5 min).
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Contrast-Enhanced Sonographic Basics of Pulmonary Vascularity
The commercially available sonography contrast agents currently used in
diagnostic sonography are characterized by a microbubble structure consisting
of gas bubbles stabilized by a shell. They strongly increase the sonographic
backscatter and therefore are useful in the enhancement of blood echogenicity
for the assessment of blood flow in the vasculature. In our experience, two
different contrast-enhanced sonographic parameters are helpful for classifying
lung tissue [8].
First, because of the dual blood supply of the lung tissue by the pulmonary
artery and the bronchial arteries, a different time to enhancement is
seen in real-time examination. Tissue enhancement resulting from the pulmonary
artery supply usually starts from 2 to 6 seconds after the IV application of
contrast media (Figs. 1A,
1B, and
1C). Tissue enhancement that
results exclusively from the bronchial arterial supply usually begins from 7
to 20 seconds after application into a peripheral vein (Figs.
2A,
2B,
2C, and
2D).
Second, as described for the parenchymatous organs such as the liver and
spleen, the contrast agent remains and seems to be trapped in the lung tissue
after it has been washed out of the blood pool (in both the arterial and
venous phases). Thus, contrast-enhanced sonography can also be performed
during a delayed parenchymal phase lasting 1-5 minutes after application of
the contrast agent. We have quantified the extent of enhancement
during the arterial and parenchymal phases as anechoic, hypoechoic, isoechoic,
hyperechoic, and mixed, using the splenic tissue as an in vivo reference in
all patients. Whereas a regular dominant pulmonary arterial supply leads to
marked, predominantly hyperechoic tissue enhancement (Figs.
1A,
1B, and
1C), a regular nutritive
bronchial arterial supply without evidence of a pulmonary arterial supply is
characterized by sparse, predominantly hypoechoic tissue enhancement (Figs.
2A,
2B,
2C, and
2D).
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Fig. 7B —72-year-old man with pneumonia. Contrast-enhanced sonography
shows short time to enhancement (2 min). In parenchymal phase, hypoechoic
tissue enhancement is seen with anechoic areas caused by necrosis (N)
(arrows).
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Contrast-Enhanced Sonographic Patterns of Pulmonary Lesions
Loculated fluid, pulmonary cysts, and liquefied areas within infiltrated
pulmonary lesions do not show enhancement on contrast-enhanced sonography. In
a recent pilot study, up to 20% of pulmonary lesions had no enhancement on
contrast-enhanced sonography
[8], including patients with a
scar, pulmonary infarcts, and metastases (Figs.
3A,
3B,
3C,
4A, and
4B).
Benign lesions such as pneumonia commonly have a short time to enhancement,
and pronounced tissue enhancement is seen during the parenchymal phase (Figs.
5A,
5B,
5C,
6A, and
6B). In pneumonia, vessels
usually correspond to branches of the pulmonary artery. Because of the hypoxia
in pneumonia, a different extent of vasoconstriction occurs leading to
hypoechoic or isoechoic tissue enhancement (Figs.
7A,
7B, and
7C). In addition,
contrast-enhanced sonography allows demarcation of necrosis or abscess in the
infiltrated lung tissue (Figs.
7A,
7B, and
7C).
Benign lesions such as atelectasis commonly have a short time to
enhancement, and pronounced tissue enhancement is seen during the parenchymal
phase. In compression atelectasis caused by pleural effusion, tissue
enhancement remains markedly trapped with a hyperechoic extension compared
with the splenic tissue enhancement (Figs.
1A,
1B,
1C,
8A, and
8B)
[9]. Tumor-associated
obstructive atelectasis shows different contrast-enhanced sonographic patterns
(Figs. 9A,
9B,
9C,
10A,
10B,
11A,
11B,
12A,
12B, and
12C). In patients with
atelectasis and apparent pulmonary arterial supply, a short time to
enhancement with marked extension of tissue enhancement is seen (Figs.
9A,
9B,
9C,
10A,
10B,
11A, and
11B). Postocclusive
atelectasis caused by a central loculated tumor usually shows absent or
short-time enhancement and sparse tissue enhancement (Figs.
12A,
12B, and
12C). This pattern
characterizes the infiltration and occlusion of pulmonary arteries, which can
be seen in 96% of patients suffering from lung cancer
[5]. By means of
contrast-enhanced sonography areas of necrosis or abscess in atelectatic,
tissue can be demarcated (Figs.
10A,
10B,
11A,
11B,
12A,
12B, and
12C).
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Fig. 8B —52-year-old woman with ovarian cancer and exudative effusion
without evidence of lung metastases by CT. Contrast-enhanced sonography shows
short time to enhancement (1 min). In parenchymal phase, isoechoic tissue
enhancement compared with splenic enhancement (S) is seen.
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Fig. 10B —64-year-old man with malignant melanoma and lung metastases.
Contrast-enhanced sonography shows short time to enhancement (3 min). In
parenchymal phase, marked tissue enhancement is seen with demarcation of
hypoechoic paranchymal lesion (M).
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Fig. 11B —48-year-old man with lung cancer. Contrast-enhanced
sonography shows short time to enhancement (1 min). In parenchymal phase,
isoechoic tissue enhancement compared with spleen (S) is seen. Demarcation of
areas with anechoic enhancement suggests necrosis (N).
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Fig. 12B —53-year-old woman with fever and lung cancer.
Contrast-enhanced sonography shows delayed time to enhancement (1 min). In
parenchymal phase, reduced tissue enhancement is seen with demarcation of
anechoic area, suggesting lung abscess (A).
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Lung cancer without atelectasis as well as pulmonary metastasis is
characterized by delayed time to enhancement and sparse tissue enhancement,
suggesting bronchial arterial supply (Figs.
4A,
4B,
13A,
13B, and
13C). In subgroups of
nodules—such as metastases of hypernephroma—a pronounced bronchial
arterial tissue enhancement is found (Figs.
2A,
2B,
2C, and
2D). It should be emphasized
that subentities of lung cancer, such as bronchioloalveolar carcinoma and
adenocarcinoma, may present with a pneumonia-like contrast-enhanced
sonographic pattern because of a pulmonary arterial supply.
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Fig. 13B —31-year-old man with Kaposi sarcoma of lung.
Contrast-enhanced sonography shows short time to enhancement. In parenchymal
phase, hypoechoic tissue enhancement is seen. Demarcation of areas with
anechoic enhancement (1 min) suggests tumor necrosis (N).
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Pleurisy with pleuropneumonia has a short time to enhancement and marked
tissue enhancement similar to pneumonia as evidence of a pulmonary arterial
supply (Figs. 5A,
5B,
5C,
14A, and
14B). In a recent pilot study,
contrast-enhanced sonography allowed diagnosis or exclusion of pleuropneumonia
in patients with pleurisy and sonographically found pleural lesions (Figs.
3A,
3B,
3C,
5A,
5B, and
5C)
[8].
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Fig. 14B —73-year-old woman with pleurisy. Contrast-enhanced sonography
shows short time to enhancement (45 s). In parenchymal phase, marked tissue
enhancement is seen, suggesting pleuropneumonia.
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Pulmonary embolism and pulmonary infarct are seen on transcutaneous B-mode
sonography with a sensitivity of up to 80%
[9] and are characterized by
contrast-enhanced sonography with delayed time to enhancement and absent or
reduced tissue enhancement during the arterial and parenchymal phases,
suggesting a marginal bronchial arterial supply (Figs.
3A,
3B, and
3C). In pleural-based nodules
of unknown cause, various patterns of time to enhancement and extent of
enhancement are seen, with a predominant delayed time to enhancement
suggesting a bronchial arterial supply (Figs.
2A,
2B,
2C,
2D,
15A,
15B,
16A, and
16B).
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Fig. 16B —53-year-old woman with Hodgkin's disease and histologically
proven lung involvement. Contrast-enhanced sonography shows delayed time to
enhancement (1 min). In parenchymal phase, marked tissue enhancement is
seen.
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Conclusion
The value of sonography in chest examinations has traditionally been
limited to evaluating pleural-based lesions. Therefore, additional
radiographic studies such as chest radiography and, in most patients, CT are
strongly warranted. The inherent advantages of contrast-enhanced sonography
compared with other contrast-enhanced imaging procedures are the possibility
to assess the extent of enhancement in real-time examination during the
arterial and parenchymal phases, the ability to differentiate pulmonary
arterial from bronchial arterial vascularity by measuring the time to
enhancement, and the ability to perform repeated examinations
[10].
A limitation of our study is the small number of patients included
[8]. Larger studies are
necessary to define the role of contrast-enhanced sonography in daily clinical
practice, to determine the ability of contrast-enhanced sonography to
distinguish benign from malignant pleural-based lesions, and to reduce health
care costs by avoiding additional imaging procedures
[8].
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Abstract
Introduction
