Category
:
Prospective Study
Title
:
Utilization of 4-Dimensional
Ultrasound in the Detection of
Neoplastic Liver Mass
Topic
:
Liver
Utilization of 4D Ultrasound in the Detection of Liver Mass
DA Payawal, RL Fernan, IA Lapus, RR Reyes
Section of Gastroenterology, Cardinal Santos Medical Center
Abstract
Background: Significant advances have been introduced in various fields of
medical technology. The 4-Dimensional Ultrasound (4-D US) is a new trend in
imaging. Objective: To determine the sensitivity and specificity as well the
likelihood ratio of 4D-US in the detection of neoplastic liver mass. Methodology:
A prospective study done at Cardinal Santos Medical Center. Patients with liver
mass or suspicious liver mass on 2D-US underwent MRI and 4D-US.
Tumor
morphology and intralesional vascular involvement were noted. Histopathologic
correlation was done to all patients. Results: Seventeen patients had liver mass
or suspicious liver mass on 2D-US. Similar number of patients with neoplastic
mass and non-neoplastic mass were seen on 2D-US and 4D-US. On MRI
findings, more patients were seen to have neoplastic mass. When correlated
histopathologically, sensitivity and specificity of 4D-US were 92% and 75% with a
likelihood ratio of 3.7 and 0.11 for positive and negative test. 2D-US had 85%
and 50% sensitivity and specificity with a likelihood ratio of 1.7 and 0.3 for
positive and negative test. MRI showed 100% sensitivity and 75% specificity
with a likelihood ratio of 4 and 0 for a positive and negative test. Intralesional
involvement was seen only seen on 4D-US. Conclusion: 4D-US is superior to
2D-US and is almost comparable with MRI in the detection of neoplastic liver
mass.
INTRODUCTION
Significant advances have been recently introduced into various fields of medical
technology. In the field of imaging techniques for the detection of liver mass,
several non-invasive modalities are being utilized. Recent progression of
noninvasive imaging technology includes various techniques of harmonic
ultrasound (US) imaging with several kinds of US contrast agents, multi-slice
helical computed tomography (CT) and rapid high-quality magnetic resonance
(MR) technique with new tissue specific contrast agents. These techniques seem
to have a strong potential to improve detection and characterization of
hepatocellular carcinoma (1). At present, the use of state-of-the art hepatic
Magnetic Resonant Imaging techniques is being used as the gold standard in the
detection of hepatic mass with a reported sensitivity of 75%-100% (2).
The use of technologically advance ultrasound machine like the ThreeDimensional Ultrasound (3-D US) permits volume imaging methods to be
incorporated in interactive manipulation of volume using rendering, rotation and
zooming in on localized features. Integration of views obtained over a region of a
patient with 3-D US may permit better visualization in these situations and allow
a more accurate diagnosis (3). Several investigations concluded the superiority
of 3D-US as compared to Two-Dimensional Ultrasound (2-D US) in volume
rendering of the liver (4), usefulness in procedures of ablation for liver cancers
(5) and in imaging vascularity in hepatocellular carcinoma (6) concluded the
superiority of 3D US.
The Four-Dimensional Ultrasound (4D-US) is the latest in ultrasonographic
imaging. It is a 3-D US with an element of real-time. It is exclusive to GE
(General Electric). Its advantages are that it allows the operator to visualize
internal anatomy moving in real-time and increases the accuracy in US-guided
biopsy. Compared with standard two-dimensional ultrasonographically guided
biopsy of hepatic masses, four-dimensional ultrasonography provides improved
visualization of biopsy devices and more perceptible information on the spatial
relationships between the biopsy needle and the target lesion (7).
Currently
however, there is a limited study of the usefulness of this new imaging
technology in the detection of liver mass and majority of its utilization is on
images of fetus in an expectant mother. Could 4-D US be utilized as a diagnostic
tool in the detection of neoplastic liver mass?
In this study, we aimed to determine the sensitivity and specificity as well the
likelihood of 4D-ultrasound in the detection of neoplastic liver mass.
METHODOLOGY
This was a prospective study done at Cardinal Santos Medical Center for a
period of one year (2004). Patients with liver mass or suspicious liver mass on 2D US were recruited in the study. Two-dimensional ultrasounds of different
patients were done in different hospitals or diagnostic clinics and findings were
read by different utlrasonologist. Consent to be included in the diagnostic study
was given by all the patients. All patients underwent imaging of the liver using
Siemens high field 1.5 Tesla Magnetic Resonance Imaging (MRI) with
Gadolinium enhancement and General Electric Voluson 730 Expert Diamond 4-D
US. The MRI served as the gold standard of diagnostic imaging in our study. A
single radiologist from each diagnostic imaging modality interpreted the findings.
The radiologists were unaware of the patient’s clinical diagnosis and to the
findings of the other diagnostic imaging modalities. The tumor size, number and
intralesional vascular involvement were noted. The tumor size was classified as
to greater or less the 5 cm which was based on Barcelona Clinic Liver Cancer
Classification (BCLC). Tumor frequency was classified as uninodular or
multinodular (≥2) and this was based on CLIP classification. Classification of
tumor size was based on Barcelona Clinic Liver Cancer Classification scoring of
the On ultrasound findings, the following criteria were used to evaluate HCC: all
focal solid lesions (8), a homogeneous or heterogeneous hypoechoic lesion,
heterogeneous hyperechoic lesion, target lesion (a solid lesion with a hypoechoic
halo), or lesion with internal color Doppler flow (9). The criteria for malignancy on
MRI were as follows: a mass demonstrating homogenous, heterogeneous, or
ring enhancement during the hepatic arterial phase (HAP) and hyperintensity on
T2 weighted images (10). A bulls-eye lesion which is a common description of
metastasis was classified as neoplastic. Non-enhancing lesions after contrast
material
administration
were
considered
as
non-neoplastic.
To
verify
histopathologically the findings on images, all patients underwent ultrasound
guided needle core biopsy (U.S. Biopsy gauge 20, 19 cm) except for one patient
who underwent diagnostic paracentesis.
The sensitivity and specificity with
likelihood ratio for a positive and a negative test
of the different imaging
modalities for the detection of neoplastic liver mass were done on a per patient
basis.
RESULTS
Seventeen patients with liver mass or suspicious mass on bimodal ultrasound
were included in the study. Fifteen patients were male and the mean age of the
seventeen patients were 63.8 years with the youngest age at 42 years and oldest
age at 76 years. Of the seventeen patients, seven were known to have hepatitis
B, five were known alcoholics, one with ascites, one was to rule out an
abdominal malignancy and three underwent routine ultrasound as part of checkup.
Thirteen patients have neoplastic mass consideration on bimodal ultrasound. The
he neoplastic mass findings were solid mass and heterogeneous hypoechoic
nodule and, heterogeneous hyperechoic nodule. The other four patients have
non-neoplastic mass findings on 2-D US findings. Findings were regenerating
nodule, nodular echo pattern and liver cirrhosis. Size of mass lesion ranges from
1.3 cm to 15.4 cm and frequency ranges from 1 to 2 lesions. No intralesional
vascular finding was noted. Table 1 showed the summary of 2-D US findings.
Table 1. Summary of 2-D US findings
2-DIMENSIONAL ULTRASOUND FINDING
NUMBER OF PATIENTS
Liver cirrhosis/nodular pattern
4
Solid Mass/Nodule
13
Hyperechoic/Hypoechoic Nodule
Number of Solid Mass
Size of Mass
Solitary
11
≥2
2
≤ 5 cm
8
≥5 cm
5
Intralesional vascular involvement
0
Histopathologic correlation showed that of the 13 patients with neoplastic masses
and nodules, 11 patients have hepatocellular carcinoma, 1 with chronic hepatitis
and 1 with abscess.
Two patients with non-neoplastic consideration had
adenocarcinoma on biopsy.
Two patients with liver cirrhosis had the same
histopathologic finding. Sensitivity and specificity on per patient basis of 2dimensional ultrasound was 85% and 50% respectively. Likelihood ratio for a
positive test was 1.7 and for a negative test was 0.3.
Table 5 showed the
summary of histopathologic findings in correlation to the 2D-ultrsound findings.
On 4-D US, thirteen patients have consideration of neoplastic mass while 3
patients have liver cirrhosis and one has nodular echopattern with focal
hypoechogenecity.
Neoplastic mass was described by the ultrasonologist as
solid mass and irregular heterogeneous mass with intralesional vascular
involvement. Size of mass lesion ranges from 1.6 cm to 16 cm and frequency
ranges from 1 to 2 lesions. Seven of these patients had intralesional vascular
lesion. Table 2 showed the summary of 4D-UTZ findings.
Table 2. Summary of 4D-US findings.
4D-ULTRASOUND FINDING
NUMBER OF PATIENTS
Fatty liver with focal sparing
1
Nodular echopattern
1
Liver cirrhosis
2
Solid mass
13
Irregular heterogeneous mass
Number of Solid Mass
Size of Mass
Solitary
10
≥2
3
≤ 5 cm
8
≥5 cm
5
Intralesional vascular involvement
7
On histologic correlation, one patient with finding of solid mass turned out to be
an abscess. The other 10 patients have hepatocellular carcinoma and two with
adenocarcinoma. Liver cirrhosis on imaging correlated well with histopathology.
Chronic hepatitis was the histopathologic finding for fatty liver with focal sparing.
The patient sensitivity and specificity for 4-D US were 92% and 75% respectively
with a likelihood ratio of 3.68 for positive test and 0.11 for negative test. Table 5
showed the summary of histopathologic findings in correlation to the 4-D US
findings
Fourteen
patients have neoplastic liver mass findings on magnetic resonance
imaging. Neoplastic masses were described as enhancing mass, bull’s eye
lesion, hyperintense mass on T1 and T2–W and multiple contrasts enhancing
peritoneal surface nodule. Three patients have findings of non-neoplastic lesions.
Non-neoplastic findings were abscess, liver cirrhosis and conglomeration of
poorly enhancing masses. The mass lesion size ranges from 1 cm to 18 cm and
frequency ranges from one to three lesions per patient.
findings were shown in table 3.
Summary of MRI
Table 3. Summary of MRI findings.
MRI FINDINGS
NUMBER OF PATIENTS
Liver cirrhosis
1
Large complex mass/abscess
1
Conglomerate of small poorly enhancing masses
1
Enhancing Mass/Hepatocellular Ca/Bull’s eye lesion
14
Peritoneal carcinomatosis/neoplasm
Number of Mass
Size of Mass
Solitary
10
≥2
3
≤ 5 cm
7
≥5 cm
6
On histopathologic correlation, one patient with solid hepatic mass on 4-D US
and 2-D US was read as an abscess on MRI and this was confirmed by biopsy.
The two other non-neoplastic findings on MRI showed histologic findings of liver
cirrhosis and chronic hepatitis. In one patient with ascites wherein MRI findings
showed an abnormal enhancement of the peritoneal lining and multiple contrasts
enhancing peritoneal surface nodule on right subdiapraghmatic region, MRI
considerations were peritoneal carcinomatosis, primary peritoneal neoplasm and
inflammatory process. This patient underwent diagnostic paracentesis instead of
liver biopsy and cell block showed malignant cells. Further investigation revealed
an ovarian carcinoma.
One patient with a subtle mildly enhancing lesion
measuring 2.0 x 3.0 cm in which considerations were
a focus of inflammation,
benign or malignant neoplasm had a histopathologic finding of chronic hepatitis.
One patient whose consideration was regenerating or dysplastic nodules or
hepatocellular carcinoma due to the MRI findings of diffuse micronodular liver
cirrhosis and a 3.2 cm mass at the posterior segment with hyperintensity on both
T1 and T2–W examinations and non-visualized vascularity revealed a
histopathologic finding of hepatocellular carcinoma. The same mass showed
intralesional vascular involvement on 4-D US and was interpreted as
hepatocellular carcinoma. On 2-D US, liver finding of the same patient was liver
parenchymal disease with hepatic nodule. Summary of histologic correlation with
MRI findings were shown in table 4. Overall, patient’s sensitivity and specificity
for MRI were 100% and 75% respectively with a likelihood ratio of 4 for positive
test and 0 for negative test.
Table 4. Summary of histopathologic findings in correlation to the imaging findings
2D-UTZ
4D-UTZ
MRI
Solid mass
Avascular
Solid mass
Vascular
Solid mass
Avascular
Solid masses
Vascular
Solid nodule
Vascular
Solid mass
Vascular
Solid mass
Vascular
Solid mass
Avascular
Liver Cirrhosis
Histopathology
1
Solid mass
2
Solid mass
3
Solid mass
4
Solid masses
5
6
Solid
Irregular
Nodule
Solid mass
7
Solid mass
8
Solid mass
9
Liver cirrhosis
10
Nodular echo
pattern
11
Liver cirrhosis
12
Solid mass
13
Heterogenously
Hypoechoic
illdefined mass
14
Heterogenously
Hyperechoic
nodule
Solid
Vascular
mass
15
Regenerating
nodule
Solid
Vascular
mass
16
Solid mass
Focal
Ill-defined mildly Chronic hepatitis
hypoechogenicity enhancing lesion
Avascular
Nodular echo
pattern
Avascular
Liver Cirrhosis
Solid mass
Avascular
Heterogeneous
mass
Vascular
Abscess
Abscess
Enhancing mass
Hepatocellular Ca
Enhancing mass
Hepatocellular Ca
Cluster of
enhancing mass
Enhancing mass
Adenocarcinoma
Enhancing mass
Hepatocellular Ca
Enhancing mass
Hepatocellular Ca
Multiple enhancing
mass
Nodular
liver
margins
Multiple
contrast
enhancing nodule
Hepatocellular Ca
Conglomeration of
small masses
Small enhancing
nodules
Hypoenhancing
liver lesion and
hyperenhancing
liver lesion
Regenerating
or
dysplastic nodule
or hepatocellular
Ca
Bulls-eye lesion
Chronic hepatitis
Hepatocellular Ca
Liver cirrhosis
Peritoneal malignancy
Hepatocellular Ca
Hepatocellular Ca
Hepatocellular Ca
Adenocarcinoma
17
Solid mass
Solid mass
(vascular)
Large enhancing Hepatocellular Ca
mass
DISCUSSION
Over the past few years, ultrasound imaging has made tremendous progress in
obtaining important diagnostic information for patients in a rapid, non-invasive
manner. The inherent flexibility of ultrasound imaging, its moderate cost, nonradiation, includes real time imaging and no known bioeffects give ultrasound a
vital role in the diagnostic process and important advantages compared with MRI
and CT scan. In the clinical field, hepatocellular carcinoma (HCC) represents the
fifth most common cancer in the world and the third cause of cancer-related
death (11). Local data however, has shown that HCC represents the third most
common cancer in the Philippines and ranks 2nd among males. The early
detection of hepatocellular carcinoma is critical to patient treatment and survival
in this era of surgical techniques for resection and transplantation and new
alternative therapeutic options such as transchatheter chemoembolization or
radiofrequency ablation (12). Therefore, imaging has an important role to play
and the accuracy of sonography in the detection of hepatocellular carcinoma is
very important. However, reported sensitivities of ultrasonography ranges from
33% to 96 % (13).
With the advent of a revolutionary technology in ultrasonography, which is the
four- dimensional ultrasound, we investigated its accuracy in detecting mass
lesions of the liver as compared to the two-dimensional ultrasound and magnetic
resonance imaging. Our result showed that 4-D US had a slightly better patient’s
sensitivity (92%) than 2-D US (85%). Two malignant lesions were missed on 2-D
ultrasound while one lesion which was a peritoneal neoplasm was missed on 4-D
US.
The only neoplastic lesion missed by 4-D US was the small peritoneal
neoplasm with ascites. As a gold standard, patient’s sensitivity to MRI in our
study is 100%. The specificity based on our results was similar with 4-D US and
MRI (75%) unlike with 2-D US (50%). With a near difference in sensitivity and
similar specificity, and considering the cost of undergoing an MRI, 4-D -US can
be an option as an imaging technique in the detection of liver mass.
One
limitation of our study that could have affected the sensitivity of the 2-DUS was
that the radiologist was not blinded to the patient’s clinical condition unlike the
radiologist of 4-D US and MRI. Another aspect for determining the accuracy of
4D-US was the assessment of lesion sensitivity. This was not done since its
measurement of accuracy would need the gross liver specimen for a lesion per
lesion analysis. Despite of a better sensitivity of
4-D US to 2-D US, the added
feature of real-time imaging is not useful in detecting liver mass since the lesion
is just stationary. Eliminating the real-time feature of 4-D US makes it a 3-D US
and will yield the same sensitivity result. The machine’s real time feature can find
its value in ultrasound guided biopsy of hepatic mass (7). In conclusion, 4-D US
is superior to
2-D US and is almost comparable with MRI in the detection of
neoplastic liver mass. The real-time feature of the machine is not useful in
detecting liver mass.
REFERENCES
1. Choi, BI, The Current Status of Imaging Diagnosis of HCC. Department of
Radiology, Seoul National University Hospital.
2. Peterson MS, et al . Hepatic malignancies: usefulness of acquisition of
multiple arterial venous phase images at gadolinium-enhacned MR imaging,
Radiology 1996; 201: 337-345
3. Pretorius DH, et al. 3-Dimensional ultrasound imaging in patient diagnosis
and management: the future. Ultrasound Obstet Gynecol 1991; 1(6):381-382
4. Hui-Xiong Xu, et al. Three dimensional Power Doppler Imaging in depicting
vascularity in HCC. J Ultrasound Med 22: 1147-1154
5. Hui-Xiong Xu. Et al. Three-dimensional Gray scale volume rendering of the
liver prelimenary clinical experience. J Ultrasound Med 21:961-970
6. Hui-Xiong Xu. Et al. Usefulness of three-dimensional sonography in
procedures of ablation of liver cancers. J Ultrasound Med.
7. Hyung Jim Won, et al. Value of Four –dimensional Ultrasonography in
Ultrasonographically Guided Biopsy of Hepatic masses.
8. Genevieve, L. et al. Sonographic Detection of HCC and dysplastic nodules in
cirrhosis; Correlation pf Pretransplantation Sonography and Liver Explant
Pathology in 2000 Patients. American Journal of Radiology. 2002; 179:75-80
9. Ihab R., et al. Imaging Evaluation of HCC. Journal of Vascular and
Interventional Radiology 2002;13:S173-S184
10 Earls J, Rofsky NR, DeCorato D, Krinsky G, Weinreb JC. Arterial-phase
dynamic gadolinium-enhanced MR imaging: optimization with a test
examination and a power injector. Radiology 1997; 202:268-273
11. Parkin DM, et al, Estimating the world cancer burden: GLOBOCAN 2000. Int J
Cancer 2001; 94:153-156
12. Trinchet JC, Beaugrand M. Treatment of hepatocellular carcinoma in patients
with cirrhosis. J Hepatol 1997;25:259 -262 10.
13. Tanaka S, Kitamura T, Nakanishi K, et al. Effectiveness of periodic checkup
by ultrasonography for the early diagnosis of hepatocellular carcinoma.
Cancer 1990;66:2210 -2214[Medline]