Abstract
BACKGROUND:
To investigate the accuracy of contrast-enhanced ultrasonography, CT-enhancement and MRI in the diagnosis of liver-occupying lesions.
METHODS:
176 patients with suspected liver lesions in our hospital were retrospectively studied from July 2014 to July 2016. All of the 176 patients were diagnosed by contrast-enhanced ultrasonography, enhanced CT and MRI, and the pathological examination was performed. The results of pathological examination were regarded as the results of the diagnosis. The diagnostic accuracywas then compared among contrast-enhanced ultrasound, enhanced CT and MRI of these patients.
RESULTS:
The results of contrast-enhanced ultrasonography showed that 164 of the 176 patients had liver-occupying lesions, and the accuracy of the diagnosis was 95.35%, which was significantly higher than that of CT enhancement and MRI (80.23% 84.30%). The accuracy of contrast-enhanced ultrasonography, in the diagnosis of primary liver cancer was significantly higher than that of CT enhancement and MRI (P < 0.05), and the difference was significant difference (P < 0.05).
CONCLUSIONS:
The examination of contrast-enhanced ultrasonography is relatively simple, and the patients can get duplicateexamination, so we should choose the contrast-enhanced ultrasonography as the preferred method of diagnosis in liver mass, especially primary liver cancer.
Introduction
Liver lesions are a common and frequently-occurring disease which can be caused by a variety of diseases and brings very serious threat to the human body, such as malignant tumors, benign tumors or tumor-like lesions. As lack of specificity early clinical manifestations of liver lesions, imaging is the main means in the detection of liver disease [1, 2]. Although the treatment for liver metastasis have made great progress than in the past and the current main clinical treatments are surgical treatment, transcatheter arterial chemoembolization, radiofrequency ablation and liver transplantation and so on, early detection and diagnosis is still the key to improve the quality of life and the prognosis of patients [3]. Liver benign focal lesions include hemangioma, liver abscess, focal nodular hyperplasia, of which hepatic cavernous hemangioma is the most common intrahepatic benign tumor which is a typical liver hemangioma easy to diagnose. But a small number of small lesions and lack of blood supply of hemangioma need to identify with primary liver cancer. At present, the diagnosis of liver lesions in patients mainly by color Doppler ultrasound, enhanced CT, MRI and fine needle aspiration biopsy. Color Doppler ultrasonography has a certain value for localization diagnosis, but there are still some difficulties in qualitative diagnosis of the lesion. Detection rate of enhanced CT and enhanced MRI of liver cancer can reach 80% or more, but each imaging range of these imaging methods is more limited, and only the morphology examination of the tumor and cannot evaluate the systemic invasion and its biological behavior. Although CT plain scan and enhanced imaging have improved the diagnosis and localization of hepatic mass-occupying lesion, the examination of some special populations is restricted because of poor reproducibility, invasive and nephrotoxicity. MRI can clearly show whether the surrounding organs were invaded and whether the retroperitoneal lymph nodes were under enlargement, but it lacks an intuitive and effective assessment for the benign and malignant tumor [4, 5]. In addition, invasive examination such as liver biopsy can get clear cytology and histopathology pathology, but the sensitivity depends on the patient’s physical condition, tumor size, location, and skill level of the operator. And this invasive examination not only exists more surgical contraindications, may also lead to a series of postoperative complications. Therefore, in clinical practice, a non-invasive method of examination with early diagnosis and accurate staging is more needed.
Since 1990s, many new ultrasonic techniques have emerged, among which the most influential of medical ultrasound that can further enhance its position in modern imaging technology is ultrasound contrast imaging, which by means of intravenous contrast agent and ultrasound imaging harmonic imaging technology can clearly show the microvascular and tissue perfusion and increase the contrast resolution of the image, which greatly improve the sensitivity and specificity of ultrasound detection of lesions. Ultrasound microbubble contrast has better tolerance and higher safety than enhanced CT and MRI [6, 7]. Nowadays ultrasound contrast imaging not only further develops the clinical application range, but also improves the diagnosis level of conventional gray-scale color Doppler ultrasound, and has good development prospect in targeted therapy. In conclusion, ultrasound contrast imaging has brought revolutionary in the development of ultrasound imaging technology.
In order to further explore the best method for the diagnosis of liver occupying lesions, we collected 176 patients with hepatic resection from July, 2014 to July, 2016, who underwent pathology. The results of the pathological examination were regarded as the results of the diagnosis. Then, the accuracy of contrast-enhanced ultrasonography, enhanced CT and MRI were compared. The clinical value of contrast-enhanced ultrasonography, enhanced CT and MRI in the diagnosis of hepatic space-occupying lesion were compared and provide theoretical basis for early diagnosis and early treatment to hepatic lesion.
Material and methods
General information
176 cases of patients with liver lesions under surgical resection were admitted in this study from July 2014 to July 2016 in our hospital and the liver space-occupying lesions resected from the patients were taken for pathological examination. The results of pathological examination are considered as the result of the diagnosis. Of the 176 patients, 107 were male and 69 were female. Their age ranged from 32 to 71 years, with a median age of 51.9±8.6 years. All of the patients were examined by contrast-enhanced ultrasonography, CT-enhanced and MRI.
Inclusion criteria: The Affiliated Hospital of Jining Medical University ethics committee approved this study and all patients had signed written informed consent. The relevant diagnostic criteria of liver lesions were abnormal echo area or low density area in the liver parenchyma under B ultrasound and CT. Patients with kidney and other serious disease history, incomplete information, iodine allergy and mental illness history were excluded. Of all the176 cases of patients, 147 cases were single lesions and 29 cases were multiple lesions. The 176 patients were confirmed by surgery or biopsy after histopathology. There were no significant differences in sex, age and lesion diameter among the 176 patients (P > 0.05).
Diagnosis method
All 176 cases were diagnosed by contrast-enhanced ultrasonography and contrast-enhanced CT or contrast-enhanced ultrasonography and MRI, and underwent surgery or biopsy, and the two checks are separated by a week. The method of Ultrasound contrast examination: Firstly, the instrument of the whole digital ultrasound system (Philips IU22 color Doppler ultrasound system with 3.5 MHz probe) was used in the study. Secondly, patients with supine position, left lateral position or right anterior oblique, and its liver site was fully exposed. Thirdly, the frequency of the ultrasonic probe is set to 3.0∼3.5 MHz and we conduct a comprehensive scan to the patient’s liver to observe and record the location, size, shape and internal echo of the lesion and at the same time we also observed the lesion and peripheral blood flow conditions. Last, 2.4 ml contrast agent was injected into the elbow vein of the patient’s, and then scanned the lesion that was recorded before to observe the changes in the sonographic situation. The method of enhance CT examination: Firstly, the instrument of the 64-slice spiral CT (XVISION/GX)was used in the study. Secondly, patients with supine position and conducted a comprehensive scan of their liver. Thirdly, 50 ml contrast agent was injected in the elbow vein of the patient and take enhanced CT after five seconds of the injection. The method of MRI examination: Firstly, MRI was performed using a GE SignaHDx 3.0T superconducting magnetic resonance imager and an eight-channel phased array abdominal coil. Secondly, Respiratory training was performed before the scan. Asked the patient to take supine position and conducted comprehensive scan of their liver. The injection of Gd-DTPA was performed in the vein of the elbow. The injection volume was 15 ml. The injection rate was 3 ml/s. The arterial phase of T1WI FS was scanned 15 s after the injection. The portal vein phase was scanned 50s–60s later. The delayed phase was scanned 90s after the injection. In the study, we choose clinical experience of physicians to read the film (Fig. 2).

MR imaging in the diagnosis of primary liver cancer. Figure 2 shows T1WI liver tumor is low signal, the signal is not uniform with clear boundary and visible pseudocapsule; T2WI shows tumor is slightly higher signal, in which scattered the spot-like high signal shadow with clear border and the pseudocapsule is high signal; Dynamic enhancement of arterial lesions is significantly uneven enhancement and dynamic enhancement of portal vein showed significant reduction in tumor signal intensity.
The data of each group were analyzed by SPSS18.0 software. One-way ANOVA and z-test were used to analyze the differences between the two groups. P < 0.05 was considered statistically significant. All data were expressed as (x±s). In the case of obeying the normal distribution, single factor ANOVA was used and LSD-t test for pairs of two comparison was used when the difference was statistically significant.
Results
Comparison of contrast-enhanced ultrasonography and pathologic examination in the detection of hepatic space-occupying lesions
Compared with pathologic examination, the accuracy of contrast-enhanced ultrasonography in the diagnosis of hepatic hemangioma, FNH, hepatic cyst and hepatic abscess had no significant difference (P > 0.05), but there was no significant difference between contrast-enhanced ultrasonography and pathologic examination in the detection rate of hepatic space-occupying lesion. The accuracy of diagnosis of primary liver cancer and liver metastases was significantly lower than that of pathologic examination (P < 0.05). (Table 1)
Comparison of contrast ultrasonography and pathologic examination in the detection of hepatic space-occupying lesions (n = 172)
Comparison of contrast ultrasonography and pathologic examination in the detection of hepatic space-occupying lesions (n = 172)
Reference: LC-Liver cancer, LMC- Liver metastatic carcinoma, LH- Liver hemangioma, FNH- Focal nodular hyperplasia, LCY- Liver cyst, LA- Liver abscess.
Compare CT enhanced and pathological examination in the detection rate of the liver lesions, we found that there was no significant difference between CT enhancement and pathological examination in the diagnosis of liver cysts and liver abscess (P > 0.05) while CT enhancement were significantly lower than pathological examination in the diagnosis of primary liver cancer, liver metastases, hepatic hemangioma and FNH (P < 0.05). (Table 2)
Comparison of CT enhancement and pathological examination in the detection rate of liver lesions (n = 172)
Comparison of CT enhancement and pathological examination in the detection rate of liver lesions (n = 172)
Reference: LC-Liver cancer, LMC- Liver metastatic carcinoma, LH-Liver hemangioma, FNH-Focal nodular hyperplasia, LCY-Liver cyst, LA-Liver abscess.
Compared with MRI and pathological examination in the detection rate of liver lesions, we found that there was no significant difference in the diagnosis of hepatic hemangioma, liver cysts, liver abscess accuracy (P > 0.05) while MRI was significantly lower than that of pathologic examination in the diagnosis of primary liver cancer, liver metastases and FNH (P < 0.05). (Table 3)
Comparison of MRI and pathological examination in the detection rate of liver lesions (n = 172)
Comparison of MRI and pathological examination in the detection rate of liver lesions (n = 172)
Reference: LC-Liver cancer, LMC- Liver metastatic carcinoma, LH-Liver hemangioma, FNH- Focal nodular hyperplasia, LCY-Liver cyst, LA-Liver abscess.
The accuracy of contrast-enhanced ultrasonography was significantly higher than that of enhanced CT and MRI in the diagnosis of primary liver cancer and the difference was statistically significant (P < 0.05). There was no significant difference among the three groups in the diagnosis of metastatic carcinoma, hepatic hemangioma, FNH, hepatic cyst and liver abscess (P > 0.05). (Table 4)
Comparison of contrast ultrasonography, enhanced CT, MRI and pathologic examination of hepatic space-occupying lesions (n = 172)
Comparison of contrast ultrasonography, enhanced CT, MRI and pathologic examination of hepatic space-occupying lesions (n = 172)
Reference: LC-Liver cancer, LMC-Liver metastatic carcinoma, LH-Liver hemangioma, FNH-Focal nodular hyperplasia, LCY-Liver cyst, LA-Liver abscess.
There are three phases in the course of hepatic contrast echocardiography, namely arterial phase, portal phase and delayed phase. In the course of contrast-enhanced ultrasonography, the forms of liver blood supply and the nature of liver-occupying disease were different at different time which can be differentiated liver lesions [8–10]. Hepatic hemangiomas is a more common hepatic space-occupying disease whose essence is a liver benign tumor, and mostly are cavernous hemangioma. Routine ultrasound could show intrahepatic homogeneous, hyperechoic lesions, the border was mostly clear, or lesions of strong hypoechoic echo with irregular low echo and the lesions can show the expansion of sinusoids. Generally strong echo is easy to distinguish from other diseases while lesions of strong hypoechoic echo with irregular low echo is hard to distinguish among liver malignancy and fatty infiltration and other diseases. Contrast-enhanced ultrasonography can be a good solution to this problem, mainly due to the result of lump or ring enhancement around the early lesions under arterial phase and portal vein phase of contrast-enhanced ultrasound of hepatic hemangioma, of which contrast agent slowly enhanced from the periphery to the center and to form a typical circular enhancement signal to the heart. The result of contrast-enhanced ultrasonography of heterogeneous hepatic fatty infiltration was generally characterized by the centrifugal spoke-shaped enhancement, while the major feature of malignant tumors was even hypoechoic phase under delayed phase (Fig. 1). These can be used as the distinction points among hepatic hemangioma, hepatic malignant tumors and fatty infiltration.

Contrast-enhanced ultrasonography in the diagnosis of primary liver. Figere1 shows the result of contrast-enhanced ultrasonography of hepatic malignant tumors is homogeneous low echo under delay phase.
Contrast-enhanced ultrasound (CEUS) is a typical representative of new ultrasound technology, which can enhance the color Doppler signal and two-dimensional ultrasound images to observe and reflect the different organizations of the blood perfusion. The most widely used ultrasound contrast agent is the European Sonovue. The main component of ultrasound contrast agent is microbubbles. The microbubbles are usually surrounded by a shell containing a variety of low-solubility composite gases. Microbubble may image under low-power mode which can reduce the microbubble damage and to achieve real-time imaging [11–14]. Results of the relative study showed that the CT images of patients with liver-occupying lesion were characterized by a round or oval shape with a low density and a clear boundary, and the arterial phase was often intensified. Low-density ring was around the high-density nodules ring and liver-occupying lesion was low-density under the portal vein phase and delayed phase (Fig. 3) [15–18]. Resent study shows that contrast-enhanced ultrasound imaging features of liver lesions in patients are as follows: Firstly, the enhancement is rapid under arterial phase and the portal phase and delayed phase subsided quickly of patients with hepatocellular carcinoma. Secondly, the enhancement is rapid under arterial phase of liver metastases while with low enhancement under the portal phase and its echo located in the normal tissue near the lesion was enhanced. Thirdly, there are different characteristics the arterial phase and portal phase depending on the presence of blood supply of patients with hepatic pseudo tumor. Forth, hepatic focal nodular hyperplasia is enhanced radially from the central to the around lesion under the arterial phase, the portal phase is highly enhanced and the delayed phase is the presence of low echo area in the hypoechoic lesion. Last, hepatic hemangioma is lump or ring enhancement around the early lesions under arterial phase and portal vein phase, of which contrast agent slowly enhanced and the portal phase part or the entire lesion is centripetalecho enhancement [19–22]. Liver tissue perfusion phase can be clearly observed in liver lesions of contrast-enhanced ultrasound examination which can significantly enhance the liver of the audio and video features and can improve its sensitivity and specificity of diagnosis [23–26]. Therefore, contrast-enhanced ultrasound has been carried out as the main means in conducting the census in patients with liver lesions.

CT enhancement imaging in the diagnosis of primary liver cancer. Figure 3 shows tumor in the arterial phase is abnormal strengthening focal with clear state and low-density ring area around the lesion; the edge of the lesion was partially enhanced under portal vein phase.
Our study shows that compared with pathologic examination, the accuracy of contrast-enhanced ultrasonography in the diagnosis of hepatic hemangioma, FNH, hepatic cyst and hepatic abscess had no significant difference (P > 0.05), but there was no significant difference between contrast-enhanced ultrasonography and pathologic examination in the detection rate of hepatic space-occupying lesion. The accuracy of diagnosis of primary liver cancer and liver metastases was significantly lower than that of pathologic examination (P < 0.05). Compared with CT enhanced and pathological examination in the detection rate of the liver lesions, we found that there was no significant difference between CT enhancement and pathological examination in the diagnosis of liver cysts and liver abscess (P > 0.05) while CT enhancement were significantly lower than pathological examination in the diagnosis of primary liver cancer, liver metastases, hepatic hemangioma and FNH (P < 0.05). Compared with MRI and pathological examination in the detection rate of liver lesions, we found that there was no significant difference in the diagnosis of hepatic hemangioma, liver cysts, liver abscess accuracy (P > 0.05) while MRI was significantly lower than that of pathologic examination in the diagnosis of primary liver cancer, liver metastases and FNH (P < 0.05).The accuracy of contrast-enhanced ultrasonography was significantly higher than that of enhanced CT and MRI in the diagnosis of primary liver cancer and the difference was statistically significant (P < 0.05). There was no significant difference among the three groups in the diagnosis of metastatic carcinoma, hepatic hemangioma, FNH, hepatic cyst and liver abscess (P > 0.05).
In the present study a very high diagnostic accuracy was achieved, much higher than in the big multicenter DEGUM study [27]. This difference may be related to our insufficient sample size to some extent, so subsequent studies with larger sample size are needed. Using CEUS the differentiation of adenoma, atypical hemangioma, CCC and HCC is difficult, and we need to find better ways to diagnose. Also, the differentiation of HCC lesions less than 15 mm from regenerative nodules is difficult considering the LIRADS classification, we need to collect more data and conduct follow-up studies to solve this problem.
In summary, contrast-enhanced ultrasound has a certain advantage in the differential diagnosis of liver lesions and can real-time display contrast enhancement model within the lesion and thereby can improve the sensitivity and accuracy of disease diagnosis which can be applied to predict and evaluate the therapeutic effect of the disease and can also provide assistance and reference for patients to recover as soon as possible. Using CEUS the differentiation of adenoma, atypical hemangioma, CCC and HCC is difficult. Contrast-enhanced ultrasound examination is relatively simple and can be repeated when necessary, so we should take this method as the preferred method for diagnosis in patients with liver lesions.
Author contributions
All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.
Footnotes
Acknowledgments
Not applicable.
Availability of data and material
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Ethics approval and consent to participate
All experiments and animal care procedures were done following institutional guidelines.
Consent for publication
Not applicable.
Funding
Not applicable.
