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Radiología. 2010;52(2):144-152
ISSN: 0033-8338
RADIOLOGÍA
RADIOLOGÍA
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ORIGINAL
Usefulness of contrast-enhanced ultrasonography in daily clinical
practice: A multicenter study in Spain
C. Nicolau Molinaa,*, T. Fontanilla Echevesteb, J.L. Del Cura Rodríguezc,
F. Cruz Villalónd, T. Ripollés Gonzáleze, B. Baudet Naverosf, Ma.J. Velasco Marcosg,
C. Garre Sánchezh, R. Huertas Arroyoi, L. Hernández Garcíaj, S.J. Pitti Reyesk,
R.A. Gómez Rodríguezl, Ma.J. Calvo Lópezm, A. Maroto Genovern, G. Álvarez Bustos°,
M. Poch Zatarainp and A. Talegón Meléndezq
Radiology Department, Barcelona Clinic Hospital, Barcelona, Spain
Radiology Department, Puerta De Hierro Hospital, Madrid, Spain
c
Radiology Department, Basurto Hospital, Bilbao, Spain
d
Radiology Department, Reina Sofía Hospital, Córdoba, Spain
e
Radiology Department, Dr. Peset Hospital, Valencia, Spain
f
Radiology Department, Nuestra Señora Candelaria Hospital, Sta. Cruz de Tenerife, Spain
g
Radiology Department, Río Hortega Hospital, Valladolid, Spain
h
Digestive Department, Virgen de la Arrixaca Hospital, Murcia, Spain
i
Neurology Department, La Mancha Centro General Hospital, Ciudad Real, Spain
j
Radiology Department, León Hospital, León, Spain
k
Radiology Department, Canarias La Laguna University Hospital, Sta. Cruz de Tenerife, Spain
l
Digestive Department, Virgen de la Salud Hospital, Toledo, Spain
m
Radiology Department, Puerta Del Mar Hospital, Cádiz, Spain
n
Radiology Department, Josep Trueta Hospital, Girona, Spain
o
Radiology Department, Carlos Haya Hospital, Málaga, Spain
p
Radiology Department, Donostia Hospital, San Sebastián, Spain
q
Radiology Department, Virgen Del Rocío Hospital, Sevilla, Spain
a
b
Received 19 June 2009; accepted 3 November 2009
Available on Internet 30 December 2009
KEYWORDS
Ultrasonography;
Contrast agents;
Contrast-enhanced
ultrasonography
Abstract
Objectives: We aimed to determine whether the use of ultrasonographic contrast agents
improves the diagnostic accuracy of ultrasonography (US).
Material and methods: We carried out a prospective multicenter study in 42 hospitals. We
included 1786 patients with inconclusive US; 84.9 % of the inconclusive studies were abdominal
US (including studies of the liver, kidneys, spleen, and other sites), 6.2 % were studies of the
*Corresponding author.
E-mail: [email protected] (C. Nicolau Molina).
0033-8338/$ - see front matter © 2009 SERAM. Published by Elsevier España, S.L. All rights reserved.
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Usefulness of contrast-enhanced ultrasonography in daily clinical practice: A multicenter study in Spain
145
peripheral vessels, 4.3 % were breast studies, and 4.6 % were other studies. We evaluated the
type of contrast-enhanced US (color Doppler or contrast-specific method), type of contrast
agent, dose and number of doses, and type of administration (bolus or infusion). We evaluated
whether the findings at contrast-enhanced US improved the diagnostic accuracy of unenhanced
US and whether they enabled a conclusive diagnosis to be reached.
Results: The contrast agent SonoVue was used in 99.9 % of the studies; a single dose of contrast
agent was used in 84.8 %, and the contrast agent was administered in bolus in 98.5 %.
Contrast-enhanced US improved the diagnostic accuracy in 91.6 % of cases and enabled a
conclusive diagnosis in 69.2 %. The best diagnostic accuracy was obtained in the supraaortic
vessels, where a definitive diagnosis was reached in 95.4 % of cases, followed by the abdominal
area, with a conclusive diagnosis in 72.6 % of cases.
Conclusions: The use of contrast-enhanced US significantly improved the diagnostic accuracy of
US and enabled a conclusive diagnosis in most cases.
© 2009 SERAM. Published by Elsevier España, S.L. All rights reserved.
PALABRAS CLAVE
Ecografía;
Medios de contraste;
Ecografía con
contraste
Utilidad de la ecografía con contraste en la práctica clínica diaria.
Estudio multicéntrico español CEUS
Resumen
Objetivos: El objetivo de este estudio multicéntrico ha sido evaluar si la ecografía con contraste
permite aumentar el rendimiento diagnóstico de la ecografía basal.
Material y métodos: En este estudio prospectivo multicéntrico realizado en 42 hospitales se
incluyeron 1.786 pacientes con estudios ecográficos considerados como no concluyentes. El
84,9 % fueron ecografías abdominales (incluyendo estudios hepáticos, renales, esplénicos y de
otras localizaciones), el 6,2 % fueron estudios vasculares periféricos, el 4,3 % fueron estudios
mamarios y el 4,6 % fueron estudios de otras localizaciones. Se evaluó el tipo de ecografía con
contraste (Doppler color o método específico de contraste), el tipo de contraste, la dosis y el
número de dosis y el tipo de administración (en forma de bolo o infusión). Sobre los hallazgos
obtenidos en la ecografía con contraste se valoró si conseguía aumentar el rendimiento
diagnóstico de la ecografía basal y si permitía un diagnóstico concluyente.
Resultados: El 99,9 % de los estudios se realizó con SonoVue, con una dosis de contraste (84,8 %)
y en forma de bolo (98,5 %). En el 91,6 % de los casos la ecografía con contraste aumentó el
rendimiento diagnóstico de la ecografía basal, y en el 69,2 % permitió un diagnóstico de certeza.
El mayor rendimiento diagnóstico se obtuvo en los estudios de troncos supraaórticos con un
diagnóstico definitivo en el 95,4 % de los casos, seguido por el área abdominal con resultado
concluyente en el 72,6 % de los casos.
Conclusiones: El uso de la ecografía con contraste aumentó significativamente el rendimiento
diagnóstico de la ecografía basal, y se obtuvo un resultado concluyente en la mayoría de los
casos.
© 2009 SERAM. Publicado por Elsevier España, S.L. Todos los derechos reservados.
Introduction
Ultrasound is an imaging technique that is most frequently
used to evaluate abdominal, musculoskeletal and vascular
diseases. However, in a radiology department daily
practice, ultrasound findings are not specific enough to
make a definitive diagnosis. Duplex Doppler ultrasound
provides valuable information on vascularization, 1 since it
permits confirmation of vascular patency, the direction and
velocity of flow, and may, ocasionally, contribute to the
characterization of focal lesions. 2 However, its usefulness in
detection of slow flow or flow in deep vascular structures is
limited, and it cannot be used to adequately detect tumor
or parenchymal microvasculature. 1,3 When ultrasound does
not permit a conclusive diagnosis, it is usually necessary to
use other imaging techniques, such as computed tomography
(CT) or magnetic resonance imaging (MRI), or to perform a
biopsy or needle aspiration to reach a definitive diagnosis.
For both CT and MRI, administration of intravenous contrast
enables evaluation of the microvascular characteristics of
the organs and potential tumors; an assessment of the type
of uptake is required to make a final diagnosis.4-6
The appearance of ultrasound contrast agents composed
of gaseous micro-bubbles stabilized with other substances,
has revolutionized ultrasound diagnosis for many diseases.7-9
In Europe, two contrast agents are approved for radiological
use: Levovist (Schering, Germany), which is made up of
air with galactose and palmitic acid as surfactant agents,
and SonoVue (Bracco, Italy), which is composed of sulfur
hexafluoride in a phospholipid capsule. The low solubility
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146
and greater stability of sulfur hexafluoride (SonoVue)
allow studies to be performed in real time, when used
gently to avoid destruction of the micro-bubbles. 8 Its
primary use is in characterizing focal liver lesions, 10-12
follow-up of tumors after percutaneous treatment, 13,14
and evaluating parenchymal perfusion of different organs,
including trauma, infection, and ischemic conditions. 15-19
Various multicenter studies with large patient cohorts have
already demonstrated the excellent diagnostic accuracy of
contrast ultrasound for characterization of focal hepatic
lesions, 20-22 but to our knowledge, no multicenter study has
yet evaluated the usefulness and diagnostic accuracy of
contrast ultrasound for general practice. The objective of
this study is to describe how contrast ultrasound is routinely
used in Spain and to evaluate whether contrast sonography
increases the diagnostic accuracy of baseline ultrasound
studies as well as their capacity to yield a definitive
diagnosis.
Materials and methods
Patients. In this multicenter study performed in 42 Spanish
hospitals, which we called the CEUS study, 1,786 patients
were included; of those patients, 886 were men (53.6 %) and
767 were women (46.4 %), with an average age of 59.8 years
(range, 14-93 years). Only patients with a non-diagnostic
or inconclusive baseline ultrasound were included. Of
these patients, a contrast ultrasound study was performed
on 1,683 patients (94.2 %). The rest (103 patients) did not
undergo contrast ultrasound for the following reasons:
performance of another diagnostic technique (83 patients,
80.6 %), patient’s decision (16 patients, 15.5 %), or
contraindications (10 patients, 9.7 %, due to severe heart
or respiratory disease). The study did not require specific
informed consent because only patients who had received
a contrast ultrasound according to the normal diagnostic
guidelines and protocols of each center were included.
Ultrasound. All patients who participated in the study
underwent an ultrasound with intravenous contrast
administration. The ultrasound studies were performed
with Toshiba equipment in 46 % of cases (Aplio platform in
37.6 %, Xario in 8.4 %), Siemens equipment in 21 % of cases
(Sequoia in 11 %, Antares in 7.1 %, and others in 2.9 %),
Philips equipment in 20.9 % of the cases (IU22 in 9.7 %, HDI
5000 in 8.4 %, and others in 2.8 %), General Electric in 11.9 %
of cases (Logic 7 in 7.2 %, Logic 9 in 4.7 %), and Esaote in
0.2 % of cases.
Variables analyzed. The following variables were analyzed
on baseline ultrasound: characteristics of the structures
explored and why the initial ultrasound was not conclusive
(multiple-choice questionnaire). On contrast ultrasound,
the following parameters were evaluated: type of contrast
ultrasound (color Doppler or specific contrast method),
type of contrast used, dosage and number of doses, type
of administration (bolus or infusion), and time needed to
perform the study. From the results obtained by contrast
ultrasound, we evaluated whether it had higher diagnostic
accuracy compared to the baseline ultrasound, yielded
a definitive or conclusive diagnosis and detected more
lesions. When evaluating whether the contrast exam was
conclusive, we only included patients with histologically or
C. Nicolau Molina et al
cytologically confirmed diagnoses, with a diagnosis achieved
with some other imaging modality (CT or MRI) considered
“gold standard”, or with contrast ultrasound studies that
met the criteria of enhancement previously accepted as
conclusive in the medical literature. 23 Finally, the operator’s
and patient’s satisfaction with the scan were evaluated, on
a scale of 0 to 3, where 0 = bad, 1 = fair, 2 = good, and
3 = very good.
Data analysis. All the analysis were performed using
the SPSS 12.0 statistical program (SPSS, Chicago, IL).
Descriptive analysis was performed for both qualitative and
quantitative variables. Qualitative variables were analyzed
using absolute and percent frequencies, while quantitative
variables were studied using the mean, medium, standard
deviation, minimum, maximum, and confidence intervals.
To compare groups, the Student’s t-test was used for
normally distributed variables (Mann-Whitney U test for
non-parametric variables), and the chi-square test or
Fisher’s exact test were used for discrete variables. The
significance level was established at p < 0.05.
Results
Initial baseline ultrasound. Concerning to the initial baseline
ultrasound, table 1 lists the area or structures explored,
with the abdominal area being the most frequent (84.9 %
of cases), especially the liver (71.2 % of cases), followed
by the kidney (10 % of cases). Regarding the reasons that
made ultrasound examination not conclusive, the most
frequent cause was the presence of a lesion that could not
be definitively identified by ultrasound (23.1 % of cases),
followed by non-evaluable or inconclusive vascularization
(table 2).
Contrast ultrasound. Technique. Regarding the type of
contrast ultrasound, the results were as follows: in 93.3 %
of cases (1,514 patients) a “specific contrast mode” was
used, while in 6.7 % (109 patients), color Doppler ultrasound
was used (the type used for 60 patients is unknown). The
contrast used was SonoVue in 99.9 % of cases. In the only case
in which SonoVue was not used, Levovist was administered,
and a color Doppler ultrasound was used to evaluate
vascular patency. The most frequently used dosages were
2.4-2.5 ml (64.9 %) and 4.8-5.0 ml (18.2 %). For the majority
of patients (84.8 %), only one dose was administered. For
15 %, two doses were administered, and for the remaining
patients (0.2 %), more than two doses were injected. The
two most frequent reasons for using two or more doses were
to study several lesions (59.4 %) and an inconclusive study
with one dose (33.1 %). In 98.5 % of patients, the method of
administration was through a contrast bolus, vs. infusion for
the remaining (1.5 %). The average time used to complete
the ultrasound study was seven minutes.
Contrast ultrasound. Findings. In table 3, we show the
definitive diagnoses obtained in the study; the most frequent
lesions were hepatocarcinomas (20 %), metastasis (17.1 %),
and hepatic hemangiomas (13.3 %). In studies of focal lesions,
contrast ultrasound allowed for better characterization of
the lesion in 87.9 % of cases, better delineation of the lesion
in 83.9 % of cases and generation of a differential diagnosis in
84.9 % of cases. Contrast ultrasound was also able to detect
more lesions as well as smaller lesions (fig. 1). Regarding its
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Usefulness of contrast-enhanced ultrasonography in daily clinical practice: A multicenter study in Spain
Table 1 The anatomical areas examined in the patients
included in the study
Area
Abdomen
Liver
Pancreas
Spleen
Portal vein
Kidney
Renal artery
Abdominal aorta
Other
Breast
Neurological
Extracranial carotid artery
Intracranial carotid artery
Peripheral artery
Other
Other areas
Lymph nodes
Other
Total
Frequency
1,516
1,272
17
35
17
179
3
2
38
77
111
99
91
2
5
82
57
25
1,786
%
84.9
71.2
1.0
2.0
1.0
10.0
0.2
0.1
2.1
4.3
6.2
5.5
5.1
0.1
0.3
4.6
3.2
1.4
100.0
Table 2 Cause for study inclusion and reason for which
the baseline ultrasound was inconclusive (multiple options
were permitted)
Frequency
Ultrasonographically non-specific
lesion
The lesion identified in another test
was not identified by ultrasound
Small lesion
Isoechoic lesion
Poorly delineated margin
of the lesion
Non-evaluable or inconclusive
vascularization
Fatty infiltration
Obesity
Suspicion of vascular occlusion
Small veins
Insufficient temporal bone window
Depth of the veins
Other
%
1,281
71.7
115
6.4
216
158
372
12.1
8.8
20.8
413
23.1
123
60
43
27
81
5
137
6.9
3.4
2.4
1.5
4.5
0.3
7.7
usefulness, in 91.6 % of cases, contrast ultrasound increased
the accuracy of the baseline ultrasound. This increase in
accuracy was greater for neurological studies (98.2 %),
followed by the abdomen (92.8 %), lymph nodes (84.8 %), and
to a lesser extent, the breast (66.7 %) (table 4). In addition,
in 69.2 % of cases, contrast ultrasound enabled to make a
definitive diagnosis with certainty; without it, a conclusive
diagnosis could be reached in only 30.8 % of cases. When the
results were analyzed with respect to the anatomical areas
most frequently explored (table 5), we found that 95.4 % of
147
Table 3 Diagnoses obtained in the study
Diagnoses
Hepatocellular carcinoma
Hemangioma
Focal nodular hyperplasia
Adenoma
Metastasis
Hepatic steatosis
Regenerative nodule
Cyst
Portal vein thrombosis
Cerebral artery stenosis
Extracranial carotid artery stenosis
Cerebral artery occlusion
Extracranial carotid artery occlusion
Other diagnosis
Normal test
Complete response to treatment
Benign renal lesion
Abscess
Malignant renal tumor
Malignant nodule(s)
Malignant adenopathy
Benign splenic lesion
Benign adenopathy
Benign pancreatic involvement
Post-surgical changes
Temporal artery stenosis
Malignant mammary lesion
Lymphoma
Vascular thrombosis
Malignant pancreatic tumor
Hepatic artery occlusion
Cerebral vascular involvement
Impaired hepatic perfusion
Temporal arteritis
Benign mammary lesion
Renal artery occlusion
Other
Frequency
230
153
42
5
196
77
22
55
19
22
7
5
9
362
97
81
28
26
23
12
5
5
3
3
3
3
3
3
3
2
2
2
1
1
1
1
46
neurological studies obtained a conclusive diagnosis, as well
as 73.6 % of abdominal scans (73.6 % hepatic, 71.6 % kidney
(fig. 2), 61.5 % spleen, and 59.3 % pancreas). However, a
conclusive diagnosis was obtained in only 20.4 % of lymph
node studies and in 13.2 % of breast studies.
Finally, when degree of satisfaction was examined, in
85.5 % of studies, the operator’s degree of satisfaction was
good or very good, while in 98.2 % of cases, the patient’s
satisfaction with the exam was also good or very good.
Discussion
Our study shows that contrast ultrasound resolves the
majority of inconclusive ultrasound studies, not merely
increasing diagnostic accuracy, but also yielding a
conclusive diagnosis, as occurred with 69.2 % of the patients
included in our study. Reaching a definitive diagnosis
using contrast ultrasound has advantages over using other
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148
C. Nicolau Molina et al
Figure 1 A patient with hepatocellular carcinoma (HCC) for one year. a) On the baseline control ultrasound, two focal lesions
were found in the right lobe that were suspicious for HCC, but this did not allow for a definitive diagnosis (arrows). b) Contrast
ultrasonography showed enhancement in the arterial phase (arrows) in both lesions that was typical of HCC, and enabled detection
of another tumor that was not shown in the baseline ultrasound (broken arrow). c) In the late phase, contrast had washed out of all
three lesions, all of which appeared hypoechoic. The lesion in the anterior segment is shown (arrow). Findings were confirmed by
CT and MRI (not shown).
Table 4 Increase in diagnostic accuracy with respect
to the baseline ultrasound exam
Table 5 Conclusive diagnosis depending on the area
examined
Area examined and increase in accuracy of the ultrasound
Area studied and diagnosis
Area examined
Abdomen
Area studied
Breast
Brain
Other
Abdomen
Breast
Brain
Other
Increase in accuracy
Yes
1,307 (92.8 %) 50 (66.7 %) 107 (98.2 %) 67 (84.8 %)
No
101 (7.2 %) 25 (33.3 %)
2 (1.8 %) 12 (15.2 %)
Total 1,408 (100 %) 75 (100 %) 109 (100 %) 79 (100 %)
Conclusive diagnosis
Yes
1,013 (72.6 %) 10 (13.2 %) 104 (95.4 %) 21 (26.6 %)
No
383 (27.4 %) 66 (86.8 %)
5 (4.6 %) 58 (73.4 %)
Total 1,396 (100 %) 76 (100 %) 109 (100 %) 79 (100 %)
imaging techniques; these advantages include availability,
few contraindications (only patients with severe cardiac
disease), absence of ionizing radiation, no contraindication
for patients with nephropathy, and reduction of time to
diagnosis. 8,24,25
The most frequent indications for contrast ultrasound
in our study were characterization of focal hepatic lesions
and evaluation of the response to percutaneous treatment
of focal hepatic lesions. 8,26 Because of its high sensitivity
for detecting microvasculature, contrast ultrasound
identifies the enhancement patterns of the most frequently
focal hepatic lesions, as has been described in other
studies. 27,28 In two recent multicenter studies in which 1,328
and 1,034 hepatic nodules were studied using contrast
ultrasound21,22 to differentiate between benign and malignant
tumors, a sensitivity of 95.8 % and specificity of 83.1 % were
reached by Strobel et al., 22 and a sensitivity of 79.4 % and
specificity of 88.1 % were reported by Tranquart et al. 21.
Furthermore, contrast ultrasound was more accurate to
establish whether a percutaneously treated lesion showed
residual tumor (persistent enhancement) or a complete
response (absence of enhancement) (fig. 3). 14,29,30
However, we have obtained better diagnostic accuracy
in ultrasonographic studies of the supra-aortic vessels, and
we have replicated the excellent results obtained by other
studies (fig. 4), 31,32 as well as for the suspicion of occlusion
of the internal carotid artery. 33 With duplex Doppler
ultrasound, it is very difficult to evaluate the arteries of
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Usefulness of contrast-enhanced ultrasonography in daily clinical practice: A multicenter study in Spain
149
Figure 2 A patient with multiple renal cysts and back pain. a) The baseline ultrasound scan showed a cystic lesion in the left kidney
partially occupied by dense material that prevented to discard an intracystic neoformation. b) The contrast ultrasound confirmed
the absence of intracystic uptake in all phases and was consistent with a complicated cyst without intracystic neoformation.
Figure 3 A patient with hepatocarcinoma (HCC) in the left hepatic lobe, treated with radiofrequency ablation. a) In a control
ultrasound scan, the tumor was visualized with difficulty, and it was impossible to determine whether tumor was still present or
if ablation had been completely successful. b) The contrast ultrasound study showed a lack of tumor enhancement in the arterial
phase (arrow) and in all other phases, consistent with complete response.
the circle of Willis or to detect very low flow or velocities in
sub-occlusive carotid stenosis, especially in obese patients
or those with short necks. Contrast administration enables
the detection of vascular patency and can confirm occlusion
via color Doppler and specific contrast methods. In addition,
it avoids the necessity for more invasive diagnostic tests
such as angiography. 33,34
Our study also supports the expansion of ultrasonography
into other diagnostic areas. In our study the third indication
has been suspicion of renal disease, fundamentally for
complicated cysts and control of pyelonephritis, obtaining
results similar to other studies. 15,16,35,36
Despite the significantly increased use of contrast
ultrasonography in all of the areas we examined, its
diagnostic accuracy does not permit a conclusive diagnosis
in some areas, particularly in the breast and lymph nodes
(fig. 5). Few published studies have described the different
enhancement patterns of contrast in the breast and lymph
nodes, in part due to the recent incorporation of highfrequency transducers compatible with the specific contrast
programs. 37,38 Our results are in agreement with findings
from other studies that found that contrast ultrasonography
can detect tumor microvasculature but cannot differentiate
between different tumors. Thus, in the breast, some initial
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150
C. Nicolau Molina et al
Figure 4 A patient suspected of having cerebrovascular disease. Color Doppler transcranial ultrasonography was used to visualize
the circle of Willis. a) In the baseline color Doppler study, the midbrain and perimesencephalic cisterns could be seen, but the
window was insufficient to obtain an adequate color Doppler. b) By administering contrast and slightly adjusting the return and
position of the transducer, the middle cerebral artery (M1 trajectory and part of the M2 trajectory) and the anterior cerebral artery
(A1 trajectory and part of the A2 trajectory) were isolated. c) Using pulse-Doppler, we were able to measure the flow velocity in the
arteries in question and to adequately see with color Doppler the trajectory of the individual arteries.
Figure 5 Adenopathy in a patient with a history of malignant
melanoma. a) Hilar node. Displacement of hilar vascularization
through power Doppler. b) Contrast enhancement showed
a no-uptake zone, consistent with a tumor implant; this was
subsequently confirmed by histology.
studies investigated the usefulness of duplex Doppler
contrast ultrasonography and reported that malignant
lesions more frequently exhibited hypervascularization (95 %
of malignant compared to 21 % of benign lesions, according
to Moon et al., 39 or 78.1 % of malignant lesions compared
to 35.3 % of benign lesions, according to Martinez et al. 40).
The emergence of a second generation of contrast agents
and improvements in ultrasound technology including
the incorporation of specific methods of contrast has
enabled not only the detection of vascularization, but also
identification of the type of vascularization. Balleyguier et
al. 38 have reported that vascularization in malignant lesions
is more prominent, that vessels are tortuous and irregular
and, if uptake curves are obtained, that malignant lesions
have earlier uptake and faster washout.
A theoretical limitation of our study is that no
standardization for this technology exists, since different
ultrasound equipment from different companies were used,
with different dosages of contrast and different contrast
protocols. Nevertheless, this theoretical limitation supports
the contention that contrast ultrasonography can provide
good results even with different techniques and dosages.
In addition, our objective was to evaluate the diagnostic
accuracy of contrast ultrasonography in the daily reality
of the different hospitals that participated in the study.
Another limitation was that not all of the focal lesions
were confirmed through histology. However, diagnoses for
the lesions that were included were confirmed using the
established, accepted diagnostic criteria based on various
imaging techniques.
In conclusion, we found that contrast ultrasonography
significantly increased the diagnostic accuracy of ultrasound
studies when the baseline study did not permit a definitive
diagnosis, and a conclusive result was obtained in the
majority of cases.
Conflict of interest
The CEUS study was sponsored by Laboratorios Farmacéuticos
Rovi S. A. The authors of the study had total freedom
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Usefulness of contrast-enhanced ultrasonography in daily clinical practice: A multicenter study in Spain
to access data and total independence to develop the
manuscript. None of them maintain any professional
relationship with Laboratorios Farmacéuticos Rovi S. A.
Acknowledgements
A complete list of the participating centers and investigators
in the CEUS study: Puerta de Hierro Hospital of Madrid
(Rafael Pérez Arangüena, Teresa Fontanilla Echeveste,
Cristina Cortés León), Virgen de la Salud Hospital of
Toledo (Rafael Ángel Gómez Rodríguez, Tomás Artaza
Varasa, Concepción González de Frutos), La Paz Hospital
of Madrid (Sonia Martín Chavarri, José María Segura Cabral,
Carmen Comas Redondo), Clinic Hospital of Madrid (Julián
Hernández Montero, Susana Martín Garre), Doce de Octubre
Hospital of Madrid (Fernando Granados Caballero), Alcorcón
Hospital (Ángel Bueno Horcajadas, Raúl de la Cruz Burgos,
Teresa Hernández Cabrero, Miguel Ángel Trapero García,
Silvia Pérez Rodrigo, Mónica Rebollo), Clinic Hospital of
Valladolid (José M Herrero Izquierdo, José M Duro Roca), Río
Hortega Hospital of Valladolid (María Jesús Velasco Marcos,
Marcelino Mendo González), Segovia General Hospital (Diana
Oquillas Izquierdo), Hospital of León (Leonor Hernández
García), Virgen de la Arrixaca Hospital of Murcia (Manuel
Reus Pintado, Carmen Garre Sánchez), Morales Meseguer
Hospital of Murcia (José Ramón Olalla Muñoz, Juan Antonio
López Corbalán, Enrique Girela Baena), Reina Sofía Hospital
of Córdoba (Marisa Vignote Alguacil, Juan Francisco de Dios
Vega, Antonio Reyes López, Fernanda Cruz Villalón, Marina
Álvarez Benito, María José García Ortega, María Cara García,
José Luis Raya Povedano, Ana Luz Santos Romero), Marqués
de Valdecilla Hospital of Santander (Francisco José González
Sánchez, Martín Silván Delgado), Basurto Hospital of Bilbao
(José Luis del Cura Rodríguez, Rosa Zabala Landa), Donostia
Hospital of San Sebastián (Montserrat Poch Zatarain),
Txagorritxu Hospital of Vitoria (Mariano Juste Carmé),
Juan Canalejo Hospital of A Coruña (Francisco Javier Pérez
Fontán, Maximino Lago Novoa), Central Hospital of Asturias
(Ana Montes, David Calvo Temprano, Belinda Fernández
Mariño, Valle Cadahira Rodrigo), Orense Hospital (Elena
Otero Gutiérrez), Xeral Calde Hospital of Lugo (Jorge
González Ramírez, José Manuel Bermúdez Cancedo, Manuel
Crespo), Nuestra señora Candelaria Hospital of Santa Cruz
de Tenerife (Beatriz Baudet Naveros, Mercedes Quintero
Quintero), University Hospital Universitario of Canarias-La
Laguna de Sta. Cruz de Tenerife (Julián Fernández Ramos,
Sergio Juan Pitti Reyes), Carlos Haya Hospital of Málaga (Eva
Briceño García, Guillermo Álvarez Bustos, Antonio Gómez
Pardal, María del Mar Molinero Casares), General Hospital of
Ciudad Real (Miguel Ángel Zarca Díaz de la Esquina, Antonio
Pinar Ruiz), La Mancha Centro General Hospital of Ciudad
Real (Rafael Huertas Arroyo), Bellvitge University Hospital
of Barcelona (Carlos Valls Durán), Josep Trueta Hospital of
Girona (Albert Maroto Genover, Jordi Soriano Viladomiu),
Germans Trias i Pujol Hospital of Badalona (José Ángel
Giménez Lasanta, Laura Castro Frías, Juan Carlos Quintero
Rivera, Eva Barluenga Torres), Parc Taulí Hospital of Sabadell
(Jordi Puig Domingo), Vall d?Hebrón Hospital of Barcelona
(Xavier Serres Creixams), Vega Baja Hospital of Orihuela,
Alicante (Jesús Antonio Belda Serrano), Puerta del Mar
Hospital of Cádiz (María José Calvo López), Virgen del Rocío
151
Hospital of Sevilla (Antonio Talegón Meléndez), San Juan de
Dios Hospital of Sevilla (María Angustias Ortiz Flores, Esther
Ruíz García, Fernando Romero Gallego), Puerto Real Hospital
of Cádiz (Antonio Escribano Moriana), Dr. Peset Hospital of
Valencia (Tomás Ripollés González, María Jesús Martínez
Pérez), General Hospital Alicante (Ana Pampliega Pérez).
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