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CME Article

Diagnosis of Focal Liver Masses

on Ultrasonography
Comparison of Unenhanced and
Contrast-Enhanced Scans
Stephanie R. Wilson, MD, Hyun-Jung Jang, MD,
Tae Kyoung Kim, MD, Peter N. Burns, PhD

Objective. The purpose of this study was to compare the diagnostic accuracy, confidence level, and rec-
ommended management of focal liver masses after contrast-enhanced ultrasonography (CEUS) com-
pared with unenhanced ultrasonography alone. Methods. One hundred sixty-seven patients were
referred for CEUS to characterize a focal liver mass. A 2-person blind read determined benignancy or
malignancy, comparative diagnosis, and accuracy on both ultrasonography and CEUS. Results were
compared with the final diagnoses. Results. The 2 readers could not determine benignancy or malig-
nancy in 77 (46.1%) and 46 (27.5%) of 167 unenhanced scans compared with 2 (1.2%) and 1 (0.6%)
of 167 CEUS scans. The confidence level increased from 0 responses in the 2 highest grades (4 and 5)
on the unenhanced scans to 135 (81.8%) and 132 (79.5%) of 167 at level 5 for CEUS. Regarding the
diagnosis, the confidence level was lowest (grade 1) on the unenhanced scans in 128 (82.1%) and 79
(65.3%) of 167 for the 2 readers and improved to the highest (grade 5) in 110 (65.9%) and 113
(68.1%) of 167. Regarding diagnostic accuracy, the unenhanced scans agreed with the correct diagno-
sis in 85 (50.9%) and 63 (37.7%) of 167, and CEUS agreed with the correct diagnosis in 133 (79.6%)
and 142 (85%) of 167 for readers 1 and 2, respectively. Recommendations for further imaging
decreased from 166 (99.4%) and 147 (88%) of 167 on the unenhanced scans to 30 (18%) and 5 (3%)
of 167 on CEUS for readers 1 and 2. Conclusions. Contrast-enhanced ultrasonography improves the
accuracy and confidence of diagnosis of focal liver lesions and reduces recommendations for further
investigations. Key words: contrast agents; liver neoplasms; microbubbles; ultrasonography.

U
Abbreviations
CEUS, contrast-enhanced ultrasonography; CT, comput-
ed tomographic; FNH, focal nodular hyperplasia; HCC,
hepatocellular carcinoma; MI, mechanical index; MR,
magnetic resonance
Received February 5, 2007, from the Department of
Medical Imaging, Toronto General Hospital and
University of Toronto, Toronto, Ontario, Canada
(S.R.W., H.-J.J., T.K.K.); and Departments of Medical
Biophysics and Medical Imaging, University of
Toronto, and Imaging Research, Sunnybrook Health
Sciences Centre, Toronto, Ontario, Canada (P.N.B.).
Revision requested February 20, 2007. Revised
manuscript accepted for publication March 1, 2007.
This work was supported in part by the Terry Fox
Program of the National Cancer Institute of Canada.
Address correspondence to Stephanie R. Wilson,
MD, Toronto General Hospital, 585 University Ave,
Toronto ON M5G 2N2, Canada.
E-mail: stephanie.wilson@uhn.on.ca
CME Article includes CME test
nenhanced ultrasonography has excellent spa-
tial and contrast resolution and may therefore
provide useful information regarding the liver
and liver masses without the use of contrast
agents. Liver cysts can be identified and confidently diag-
nosed, and a variety of appearances of solid masses may
suggest a specific diagnosis.1 Recognition of a hypoe-
choic halo or rim surrounding an echogenic or isoechoic
liver mass, for example, suggests probable malignancy,2
and masses with this morphologic characteristic would
always provoke confirmatory imaging with either com-
puted tomographic (CT) or magnetic resonance (MR)
scans. Multiple hypoechoic masses in the liver most often
suggest metastases.3 By comparison, the common
appearance of hemangioma as a solid, uniformly
echogenic mass, possibly showing increased enhance-
ment deep to the mass, is so well recognized that in a
patient without risk of hepatocellular carcinoma (HCC)

© 2007 by the American Institute of Ultrasound in Medicine • J Ultrasound Med 2007; 26:775–787 • 0278-4297/07/$3.50
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Diagnosis of Focal Liver Masses on Ultrasonography

or metastases, identification of such a mass pre-
cludes the need for further imaging.4 However, in
patients at risk for HCC or for a variety of metas-
tases, there is recognition that small, uniformly
echogenic hemangiomalike masses may repre-
sent malignant liver tumors,5 and confirmation
of all such masses in high-risk patients with
either CT or MR scans is recommended. This
extreme reliance on clinical information has
become part of our practice standard but
emphasizes the lack of specificity of convention-
al ultrasonography. With knowledge of the
patient’s history and demographics, therefore,
two different interpretations may result from an
identical ultrasonographic appearance. In the
case of a hemangiomalike mass, this type of
interpretation tends to work relatively well in
clinical practice, although it illustrates the lack of
a methodological basis on which the interpreta-
tions can be made in the absence of clinical
information (Figure 1). In many other cases, a
mass seen on ultrasonography is referred for
contrast-enhanced CT or MR imaging for a con-
fident diagnosis.

Figure 1. Agreement of unenhanced imaging and CEUS

regarding both diagnosis and determination of malignancy in
a young woman with no risk factors and with a small classic
hemangioma. A, Baseline sonogram shows a focal solitary
echogenic mass in the liver suggesting hemangioma in the
absence of known risk factors. B, Arterial phase CEUS image
shows enhancement of the liver. There are small bright
peripheral nodules of contrast around the periphery of the
lesion. C, Portal phase CEUS image shows sustained enhance-
ment. On the real-time examination, there was centripetal
progression of the enhancement classic for hemangioma.
Contrast-enhanced ultrasonography enables a definitive diag-
nosis regardless of risk factors.

B C

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The introduction of contrast-enhanced ultra-
sonography (CEUS) has provided the opportu-
nity for ultrasonography to play a role in the
noninvasive diagnosis of focal liver masses, an
area previously dominated by contrast-
enhanced CT and MR imaging. Studies have
shown accurate diagnosis of commonly encoun-
tered liver masses with CEUS6–10 and also a high
level of agreement of enhancement patterns
between CEUS and contrast-enhanced CT.11,12
Nonetheless, the actual impact of the perfor-
mance of CEUS in terms of patient treatment
remains unclear. In this study, we used a blind
read to compare the diagnosis, confidence level,
and recommended management of focal liver
masses after a standard unenhanced sonogram
with examinations of the same patients using
CEUS. These were judged against a final, inde-
pendent diagnosis for each studied lesion.
Materials and Methods
Patients
This prospective study had approval of the
Institutional Research and Ethics Board. Patients
gave informed consent. Nonconsecutive patients
with solid liver masses visible on routine ultra-
sonography were recruited for CEUS at the time
of their ultrasound examination. The study pop-
ulation comprised 156 patients with 167 liver
masses referred to our department for character-
ization. Two masses were evaluated in 11
patients: in each case, the masses were in differ-
ent locations in the liver and were reviewed in a
blind read format without visualization of both
lesions at the same time. There were 68 men and
88 women (age range, 19–86 years; mean age, 51
years). Confirmed liver masses comprised 50
HCCs, 16 metastases, 42 hemangiomas, 47 focal
nodular hyperplasias (FNH), and 12 others (3
cholangiocarcinomas, 3 adenomas, 4 regenera-
tive nodules, 1 lymphoma, and 1 lipoma).
The mean size of the malignant lesions was 5.5
cm (range, 1–12 cm). Pathologic confirmation of
the diagnosis was obtained in 62 of 70 malignant
lesions: 45 HCCs, 13 metastases, 3 cholangiocar-
cinomas, and 1 lymphoma, the last 2 lesions cat-
egorized with “other lesions.” Three patients
with known extrahepatic primary cancer had
widespread metastases on medical imaging in
J Ultrasound Med 2007; 26:775–787
Wilson et al
the liver, lung, and bones with disease progres-
sion over a 3-year follow-up. Three patients with
HCC had an α-fetoprotein level of greater than
4000 ng/mL, and 1 patient with HCC had diag-
nosis only on medical imaging.
The mean size of the benign lesions was 4.3 cm
(range, 0.7–11 cm). Pathologic confirmation was
obtained in 12 of 97 benign lesions including the
single lipoma, 3 of 4 regenerative nodules, 2 of 3
adenomas, 5 of 47 FNHs, and 1 hemangioma. All
other benign lesions were confirmed by CT or
MR imaging or technetium-labeled red blood
cell scintigraphy. Benign diagnoses were estab-
lished by continued imaging and clinical obser-
vation over a mean period of more than 4 years
(mean, 50 months; range, 31–70 months).
Imaging Technique
Ultrasound scans were performed by a single
physician and one of the authors (S.R.W.) with
more than 25 years of experience in liver ultra-
sonography. Contrast-specific imaging was used:
pulse inversion imaging on an HDI 5000 system
(Philips Medical Systems, Bothell, WA; n = 145)
and contrast pulse sequence imaging on an
Acuson Sequoia system (Siemens Medical
Solutions, Santa Clara, CA; n = 22). All examina-
tions included a thorough scan before liver
enhancement, including identification of the
lesion and determination of its size and mor-
phologic characteristics. Curvilinear transduc-
ers were used with a center frequency of 1.1 to
2.2 MHz. The ultrasound contrast agent com-
prised gas-filled perflutren lipid microspheres
(Definity; Bristol-Myers Squibb, Billerica, MA)
administered intravenously by multiple small
boluses (range, 3–6; median, 4; aliquot dose
range, 0.1–0.4 mL; median, 0.2 mL), followed by
a saline flush, to a maximum total dose of 10
µL/kg. Injections were separated by an interval
of greater than 5 minutes to minimize any cumu-
lative effect of the contrast agent. The scanning
technique used was low-mechanical index (MI
<0.1), real-time imaging, which preserves the
microbubble population and allows evaluation
of lesional vessels as well as lesion and liver
enhancement. The transmit focal zone was
always positioned distal to the lesion of interest.
The image frame rate was typically 10 to 15 Hz.
The region of interest was observed continuous-
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Diagnosis of Focal Liver Masses on Ultrasonography

ly from the time of injection for about 5 minutes.
The arterial phase was timed for 45 seconds after
the completion of the flush, after which we
defined an “extended portal venous phase,”
encompassing the commonly described inter-
val from 45 to 70 seconds after injection, as well
as the remainder of the observation period.
Because the contrast microbubbles are purely
intravascular, there is no interstitial or equilibri-
um phase: enhancement in the extended portal
phase shows progressive decay over about 3 min-
utes until the baseline appearance is again
observed.
Blind Read
A 2-person blind read was conducted to docu-
ment the interpretation of the lesion as benign or
malignant, as well as the diagnosis, together with
a confidence level and recommended manage-
ment. The procedure was carried out on the
ultrasonographic and CEUS images for each
patient. Both readers were authors (H.-J.J. and
T.K.K.) who had no prior exposure to the images
before the blind read. They had 5 and 3 years
experience with the performance and interpreta-
tion of CEUS, respectively. The readers were
blinded to all clinical and demographic informa-
tion. The image file included a single unen-
hanced image followed by several images from
the CEUS scan, including the baseline image, an
arterial phase image, a portal venous phase
image, and a cine clip of the wash-in of the con-
trast agent to the peak of arterial phase enhance-
ment. The arterial and portal venous phase
images were chosen to show the maximum dif-
ference between the enhancement of the mass
and the enhancement of the adjacent liver.
Reader Training
Readers relied on their own experience and the
commonly acknowledged features for determi-
nation of malignancy and the diagnosis for
unenhanced ultrasonography and CEUS, sum-
marized below and in Tables 1 and 2.
On unenhanced ultrasonography, malignancy
was suggested by identification of a hypoechoic
halo around a solid mass as well as the presence
of hypoechoic or multiple masses.
Criteria for the differential diagnosis of a focal
mass on unenhanced ultrasonography, as much

Table 1. Diagnostic Criteria of Benignancy and Malignancy on Unenhanced Ultrasonography and CEUS
Tumor Type Imaging Findings
Benign Unenhanced Homogeneous hyperechogenicity
Hypoechogenicity with hyperechoic rind
Posterior sonic enhancement
CEUS No wash-out during portal phase
Malignant Unenhanced Hypoechoic halo
Target appearance
Hypoechoic
CEUS Wash-out during portal venous phase regardless of arterial vascularity

Table 2. Suggestive Features of Common Focal Liver Lesions Based on CEUS Enhancement Patterns
Diagnosis Unenhanced Ultrasonography CEUS
HCC Varied Diffuse arterial enhancement
Portal phase wash-out
Hemangioma Homogeneous hyperechogenicity Peripheral nodular enhancement
Hypoechoic with hyperechoic rind Centripetal progression
Posterior sonic enhancement Sustained enhancement
FNH Subtle lesion with mass effect Brisk homogeneous enhancement
Central spoke wheel artery
Nonenhancing scar
Sustained enhancement
Metastasis Hypoechoic Rim enhancement
Nonhomogeneous echogenicity Rapid and complete wash-out
Hypoechoic halo

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as they were available,1,2 included a uniformly
echogenic4 or a hypoechoic mass with an
echogenic rim for hemangioma,13 a subtle isoe-
choic mass often with a mass effect or contour
bulge for FNH,14 single, diffuse, or multifocal
masses of varying echogenicity for HCC, and a
hypoechoic halo surrounding a solid mass2 or a
hypoechoic mass for metastases.3
On CEUS, criteria for malignancy were based
on published guidelines,15 combined with other
reports in the literature.8,16,17 A major require-
ment for the determination of malignancy or
benignancy was the appearance of the mass in
the portal venous phase relative to the liver.8,16,18
A mass that appeared more enhanced or of
greater echogenicity was interpreted as showing
sustained enhancement, commonly encoun-
tered with benign lesions. Malignant lesions, in
comparison, tend to show wash-out or hypoe-
chogenicity relative to the enhanced liver.
Additional arterial phase enhancement charac-
teristics used to make a diagnosis included
identification of peripheral nodular enhance-
ment with centripetal progression for heman-
gioma and stellate vascularity for FNH.
Hepatocellular carcinoma shows more variabili-
ty in its enhancement pattern, with arterial
phase hypervascularity and wash-out that may
be less complete and later than that seen for
nonhepatocyte malignancy.19,20 Metastases may
show some variation of their arterial phase
enhancement but are characterized by rapid
wash-out within the time frame traditionally
defined as the arterial phase.21
Reader Questions
The same questions were asked after assessment
of the unenhanced ultrasonographic images
and the CEUS images. The responses based on
the unenhanced images were completed
before evaluation of the CEUS. The first ques-
tion was the determination of benignancy or
malignancy, with 3 possible responses: benign,
malignant, or do not know. The confidence
level for this interpretation was graded from 1
(lowest confidence) to 5 (highest confidence).
The second question addressed the most likely
diagnosis, with choices comprising FNH,
hemangioma, HCC, metastases, other, and do
not know, also with a confidence level. The
J Ultrasound Med 2007; 26:775–787
Wilson et al
third question addressed differential diagnos-
tic possibilities, with the same choice of
answers as for the diagnosis. The last question
was the recommendation for further manage-
ment: nothing, biopsy, nuclear medicine scan,
CT, MR imaging, or follow-up ultrasonography.
A single answer was required for each of these
questions except the last, where multiple selec-
tions were permitted.
Analysis
The blinded read end points comprised an
assessment of benign/malignant, specific diag-
nosis, diagnostic confidence, differential diagno-
sis, and recommendation for management.
Descriptive statistics were calculated for each
question showing the number and percentage
of cases with specific question responses.
Inferential statistics were used to compare the
performance of the CEUS and unenhanced
imaging, performed for individual readers and
with a combined analysis to evaluate an overall
effect and reader effect. For benign/malignant
classification, the evaluations were compared
by the overall proportion of correct assessments.
The analysis of the benign/malignant classifica-
tion was completed assuming cases in which no
assessment was possible as nonagreement and
for only cases in which an assessment was made
for both imaging sets. Similarly, the ability to
make a correct diagnosis was compared assum-
ing the cases in which no diagnosis could be
made as failure and using only the cases in
which a diagnosis was made for both imaging
sessions. The need for additional procedures
was analyzed as a binary variable, using the
Fisher exact test for comparisons within a read-
er and a repeated measures model to incorpo-
rate both readers. In the case of specific
diagnoses, the overall number of diagnoses, dif-
ferential diagnosis, and cases in which no diag-
nosis was possible were summarized. The
homogeneity of the 3 levels and the dichoto-
mous outcome of single versus multiple or no
diagnosis cases were also compared with a
Fisher exact test for each reader and with a
repeated measures logistic model to incorporate
both readers. P < .05 was regarded as significant.
Analysis was performed with SAS statistical soft-
ware (SAS Institute Inc, Cary, NC).
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Diagnosis of Focal Liver Masses on Ultrasonography

Results the unenhanced scans to 135 (81.8%) of 167 at

Results from the read are tabulated in Table 3.
Each reader was asked whether the lesion was
benign or malignant or to note whether he or she
was unable to determine whether the lesion was
benign or malignant (Figure 2). There were sig-
nificant differences between correct assessments
in the unenhanced and CEUS images for both
readers, with the 2 readers answering “do not
know” in 77 (46.1%) and 46 (27.5%) of 167 unen-
hanced scans compared with only 2 (1.2%) and 1
(0.6%) of 167 CEUS studies. The confidence level
for the responses increased from 0 responses in
the 2 highest grades (4 and 5) for each reader on
level 5 and 132 (79.5%) of 167 for CEUS for read-
ers 1 and 2, respectively. The mean diagnostic
confidence increased from 1.45 to 4.7 on CEUS
(Figures 3 and 4). In addition, there were far fewer
cases in which the readers were unable to reach a
determination of benign or malignant status for
the CEUS studies.
The results of the readers making a specific
diagnosis are also presented in Table 3, which
shows the agreement rates for each reader com-
paring unenhanced and CEUS imaging with the
final diagnosis. The agreement rates for exact
diagnosis were significantly higher in the assess-
ments of CEUS studies, with 85 (50.9%) and 63

Table 3. Results of Blind Read

Reader 1 Reader 2
Parameter Unenhanced Enhanced Unenhanced Enhanced
Total images read 167 167 167 167
Benign or malignant, n (%)
Do not know 77 (46.1) 2 (1.2) 46 (27.5) 1 (0.6)
Benign 42 (25.1) 106 (63.5) 49 (29.3) 99 (59.3)
Malignant 48 (28.7) 59 (35.3) 72 (43.1) 67 (40.1)
Agreed with diagnosis of benign/malignant 75 (44.9) 153 (91.6)* 90 (53.9) 158 (94.6)*
Benign/malignant confidence, n (%)
1 (lowest) 65 (72.2) 0 62 (51.2) 0
2 23 (25.6) 4 (2.4) 46 (38) 2 (1.2)
3 2 (2.2) 12 (7.3) 13 (10.7) 13 (7.8)
4 0 14 (8.5) 0 19 (11.4)
5 (highest) 0 135 (81.8) 0 132 (79.5)
Mean (SD) 1.3 (0.51) 4.7 (0.71) 1.6 (0.68) 4.7 (0.67)
Lesion diagnosis, n (%)
Do not know 11 (6.6) 0 46 (27.5) 1 (0.6)
Other 3 (1.8) 14 (8.4) 0 2 (1.2)
FNH 38 (22.8) 54 (32.3) 3 (1.8) 54 (32.3)
Hemangioma 41 (24.6) 40 (24) 46 (27.5) 43 (25.7)
Metastasis 16 (9.6) 19 (11.4) 8 (4.8) 12 (7.2)
HCC 58 (34.7) 40 (24) 64 (38.3) 55 (32.9)
Agreed with final lesion diagnosis 85 (50.9) 133 (79.6)† 63 (37.7) 142 (85)†
Confidence in diagnosis, n (%)
1 (lowest) 128 (82.1) 0 79 (65.3) 0
2 24 (15.4) 9 (5.4) 34 (28.1) 4 (2.4)
3 4 (2.6) 21 (12.6) 8 (6.6) 22 (13.3)
4 0 27 (16.2) 0 27 (16.3)
5 (highest) 0 110 (65.9) 0 113 (68.1)
Total 156 167 121 166
Mean (SD) 1.2 (0.46) 4.4 (0.91) 1.4 (0.61) 4.5 (0.81)
Differential diagnosis, n (%)
None 1 (0.6) 106 (63.5) 0 115 (68.9)
Other 87 (52.1) 24 (14.4) 49 (29.3) 9 (5.4)
FNH 80 (47.9) 11 (6.6) 137 (82) 8 (4.8)
Hemangioma 67 (40.1) 4 (2.4) 99 (59.3) 2 (1.2)
Metastasis 85 (50.9) 7 (4.2) 156 (93.4) 13 (7.8)
HCC 91 (54.5) 22 (13.2) 96 (57.5) 25 (15)
*P < .0001, model analysis of variance tests (contrast effect).
†P < .0001, McNemar test for each reader comparison.

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Wilson et al

(37.7%) correct diagnoses for the unenhanced
scans and 133 (79.6%) and 142 (85%) correct
diagnoses for the CEUS scans for readers 1 and 2
(Figure 2).
The readers were then asked what they would
recommend as the next step in the patient’s diag-
nostic workup. As can be seen in Table 4, in every
case, neither reader was confident enough in the
unenhanced diagnosis to not recommend an
additional diagnostic procedure (Figures 3 and
5). For the CEUS studies, the 2 readers were con-
fident enough in their diagnosis to recommend
no additional diagnostic testing in 118 (70.7%)
and 113 (67.7%) cases, respectively (Figure 6).

Figure 2. Agreement of unenhanced imaging and CEUS for determination of malignancy in a young woman with hepatitis B virus
and HCC. A, Unenhanced sonogram of the right lobe of the liver shows an expansive, somewhat exophytic mass with a faint hypoe-
choic halo. The image suggests a malignant mass, either metastasis or HCC. B, Arterial phase image shows extensive dysmorphic
vascularity. C, At the peak of arterial phase enhancement, the lesion is enhanced more than the liver. D, In the portal venous phase,
the lesion has washed out. The diagnosis was HCC on CEUS.

A B

C D

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Diagnosis of Focal Liver Masses on Ultrasonography

Specific recommendations for CT decreased from required were accompanied by an improvement

166 (99.4%) of 167 on the unenhanced scans to 30 in the readers’ diagnostic accuracy. When the
(18%) of 167 on CEUS for reader 1 and 147 (88%) readers recommended no further testing after
of 167 to 5 (3%) of 167 for reader 2. Cases in which CEUS, their sensitivity and specificity were 98%,
the readers specified that no further testing was 100.0%, 95%, and 99%, respectively.

Figure 3. Unenhanced scan suggests malignancy; CEUS definitively shows benign FNH. A, Unenhanced sagittal scan of the left lobe
shows a grossly fatty liver with a focal hypoechoic mass. With or without clinical information, this is suggestive of malignancy. Further
imaging would be recommended on the basis of this scan. B, Arterial phase image shows faint evidence of a stellate pattern to
enhancement. C, At peak arterial phase enhancement, the lesion is homogeneous and hypervascular. D, In the portal venous phase,
the lesion is completely isovascular, and there is a nonenhancing scar.

A B

C D

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Wilson et al

Discussion Interpretation of an unenhanced ultrasound

The improvement in the confidence level for
determination of benignancy or malignancy as
well as for diagnosis averaged over 3 points on a
5-level grading system. Surprisingly, the readers
were correct in predicting the correct diagnosis
in almost half the cases on unenhanced scans
alone, even in the absence of any information.
However, the marked increase in correct predic-
tion of diagnosis with CEUS is clear, occurring in
a further 84 (50%) and 70 (42%) of 167 cases.
image without the essential contribution of clin-
ical information is extremely difficult, and, as the
results show, readers were neither accurate nor
confident in the interpretation of unenhanced
ultrasound images presented outside a clinical
context. This included the determination of
benignancy or malignancy as well as the diagno-
sis. Interpretation of images without demograph-
ic or clinical information does not reproduce
clinical reality, and undoubtedly, in the real
world of liver mass diagnosis, experienced sono-

Figure 4. Characterization of a very small indeterminate mass

with CEUS confirms metastatic hypervascular metastasis from a
small-bowel gastrointestinal stromal tumor. A, Oblique unen-
hanced sonogram of the right lobe shows a small hypoechoic
mass in the liver with slight increased through-transmission dis-
tally. B, An arterial phase CEUS image shows that the mass is
hypervascular. C, In the portal venous phase, there is wash-out of
the lesion, which again appears black.

B C

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Diagnosis of Focal Liver Masses on Ultrasonography

Table 4. Recommendation for Next Test to Diagnosis

Reader 1 Reader 2
Recommendation Unenhanced Enhanced Unenhanced Enhanced
Nothing, n (%) 0 118 (70.7) 0 113 (67.7)
Biopsy, n (%) 0 9 (5.4) 0 18 (10.8)
Nuclear medicine, n (%) 0 0 0 0
CT, n (%) 166 (99.4) 30 (18) 147 (88) 5 (3)
MR imaging, n (%) 6 (3.6) 19 (11.4) 158 (94.6) 33 (19.8)
Follow-up ultrasonography, n (%) 0 1 (0.6) 0 0
Total 167 167 167 167

Figure 5. Unenhanced scan is indeterminate even as to the pres-

ence of a liver mass(es). Contrast-enhanced ultrasonography
allows diagnosis of multiple metastases. A, Unenhanced trans-
verse sonogram shows very subtle nonfocal hypoechogenicity in
the liver, raising the possibility of a liver mass. This indeterminate
scan would motivate further imaging, including CT or MR imag-
ing. B, Arterial phase sonogram shows hypovascular masses with
rim enhancement throughout the liver. C, These were confirmed
on a portal venous phase image.

B C

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Wilson et al

graphers, aware of the patient’s sex, age, clinical
presentation, and results of other imaging tests,
would perform much better than did the readers
in this study. The addition of CEUS, however,
improved all aspects of the liver mass diagnosis
despite the continued absence of clinical and
demographic information. This attests to a con-
siderable improvement in both diagnostic accu-
racy and specificity provided by the addition of
contrast to an ultrasound examination per-
formed for the characterization of a focal liver
mass. Furthermore, recommendations for fur-
ther imaging and biopsy were also significantly
reduced on CEUS when compared with the

Figure 6. Giant hemangioma is indeterminate on an unenhanced scan but is definitively diagnosed on CEUS. A, Unenhanced sagit-
tal sonogram of the right lobe of the liver shows a very large lobulated and somewhat heterogeneous mass, suggestive of possible
malignancy. Such a large mass would always be investigated further with either CT or MR imaging. B, Early arterial phase image shows
multiple peripheral puddles of contrast. C and D, Over subsequent frames, there is progressive centripetal progression of enhance-
ment, classic for hemangioma.

A B

C D

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Diagnosis of Focal Liver Masses on Ultrasonography
unenhanced scans. The use of CEUS to provide an
immediate diagnosis of a mass detected on unen-
hanced ultrasonography would, therefore, have a
substantial benefit to management in terms of
reduction of hospital visits, a shorter time to diag-
nosis, and also the initiation of proper treatment.
For diagnosis of benign lesions, such as heman-
giomas, the reduction in referral for further imag-
ing such as CT or MR imaging is also important for
both radiation risk and reduction in costs.
Clinical information is so imperative for liver
mass diagnosis that competent imagers will not
interpret images without it.22 Knowledge of risk
factors for HCC, such as positive serologic results
for hepatitis B or C or known cirrhosis, has a
strong impact on the interpretation of imaging
studies. Hepatocellular carcinoma may be con-
sidered in preference to other diagnoses, even in
the absence of the classic diagnostic enhance-
ment features. Similarly, a history of malignancy
makes every identified liver mass a possible
metastasis until proven otherwise.
Previous investigators have compared the per-
formance of CEUS with that of unenhanced
ultrasonography. Bryant et al23 documented the
positive impact of CEUS performed with Levovist
(SH U 508A; Schering AG, Berlin, Germany), an
air-filled microbubble contrast agent, scanned
with high MI imaging. Although their results
were positive, the necessity to use a high MI with
this agent precluded real-time imaging, the cur-
rently preferred method. Subsequent investiga-
tors24,25 described the more significant impact of
CEUS with the second-generation perfluorocar-
bon agent SonoVue (Bracco SpA, Milan, Italy),
similar to that used in this current study. Leen et
al24 showed a reduction in indeterminate scans
in 127 focal liver masses and also a reduced need
for further imaging, in agreement with our
results. In a larger series of 452 liver lesions,
Quaia et al25 also showed results similar to our
own, with improved differentiation of benign
from malignant lesions and a similar improve-
ment in both diagnostic accuracy and confi-
dence level. Xu et al,26 evaluating the difficult
problem of determining benignancy or malig-
nancy in 200 liver lesions of less than 3 cm in
diameter, many in patients with chronic liver dis-
ease, also showed a considerable improvement
of CEUS over unenhanced ultrasonography.
786
Although many of the patients in our study did
have chronic liver disease, we have not addressed
that specific problem in this present investiga-
tion.
Contrast-enhanced ultrasonography has the
advantages of safety, with no radiation exposure
and a very low incidence of adverse events,27 ease
of performance, and relatively low cost. The
examination is performed in real time and shows
lesional enhancement similar to that of contrast-
enhanced CT and MR scans together with vessel
morphologic characteristics. A clear improve-
ment associated with CEUS for determination of
malignancy and provision of the correct diagno-
sis is evident. As experienced sonographers
working with CEUS, we think that the addition of
contrast enhancement allows ultrasound to
occupy a reliable role in the noninvasive diagno-
sis of liver masses.
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