I. Indications
1. Qualitative diagnosis of focal liver lesions (FLLs), such as
(1) Lesions found incidentally during routine ultrasound examination or physical examination. Xu Qing, Department of Ultrasound, Yueqing People’s Hospital
(2) Lesions found during routine ultrasound screening for chronic hepatitis and liver cirrhosis.
(3) Lesions found during regular ultrasound follow-up with a history of malignant tumors.
(4) Emboli in the intrahepatic vasculature (portal vein/hepatic vein/inferior vena cava/bile duct), the nature of which cannot be clarified.
(5) Complex cysts or cystic solid masses.
2. If a lesion is suspected on conventional ultrasound, or if other imaging studies reveal a lesion but conventional ultrasound does not show it or does not show it well, CEUS can improve the sensitivity of detection and make further qualitative diagnosis, or perform tissue biopsy or intervention under CEUS guidance.
3. In transplanted livers, CEUS is used to comprehensively assess the anatomy and patency of the recipient and donor vessels, as well as abnormal lesions that appear in the liver during follow-up.
4. for liver trauma (see “Guidelines for Clinical Use of Ultrasonography in Abdominal Substantial Organ Trauma” for details)
5. Application of CEUS in ablative treatment of liver tumors.
(1) Define the nature, size, location, number and blood supply status of the tumor before treatment.
(2) Guided localization during treatment. When the lesion is not clearly shown on conventional ultrasound or the boundary is blurred, or when the tumor remains or local recurrence is difficult to be distinguished from the original ablation site, CEUS can be used to guide the targeted puncture to achieve precise treatment.
(3) To determine the effectiveness of ablation immediately after the treatment or the next day to determine whether additional treatment is needed.
(4) To determine the effectiveness of local treatment of the tumor during follow-up.
(6) Evaluation of the efficacy of Transcatheter hepatic arterial chemoembolization (TACE), local radiotherapy, drug injection therapy and targeted therapy for hepatocellular carcinoma.
II. Preparation before examination
1. preparation of contrast agent and injection requirements refer to the general theory.
2. Establish peripheral venous access to the patient. 3.
3. understand the clinical information (medical history, laboratory and other imaging examinations) and the purpose of the examination, determine whether the examination is suitable for CEUS, and exclude contraindications (see General); and obtain informed consent.
III. Examination method
There are 3 steps in the following order.
1. routine ultrasound examination
2. Contrast condition setting.
Enter the imaging mode and adjust the imaging conditions (see General for the method).
3. Implementation of imaging.
The probe section is placed in the area of interest, with the target lesion in the middle of the image if possible. The contrast agent is injected via the anterior vein of the elbow (see General), and the conventional recommended dosage is 2.4 ml, which can be increased to 4.8 ml for patients with obesity or severe cirrhosis or fatty liver. The storage function is activated in the imaging, and the dynamic images are stored according to the predetermined scheme according to the purpose of the examination.
IV. Observation content
1. Temporal phase of CEUS
(1) Hepatic arterial phase: From the beginning of contrast injection to 30 seconds thereafter, the enhancement of liver tissue in this phase mainly originates from microbubbles of hepatic arterial blood flow (Table 1).
(2) Portal phase: from 31 to 120 seconds after the injection, the enhancement mainly originates from microbubbles of portal blood flow.
(3) Delayed phase: 121 seconds to 6 minutes after injection, with enhancement originating from microvesicles remaining in the portal vein as well as in the hepatic sinusoids.
Table 1: Temporal phases of hepatic CEUS
Time phase
Time after contrast injection (sec)
Start
End
Arterial phase
10-15
30
Portal phase
31
120
Delayed phase
121
360
2. Performance of CEUS
Four aspects were observed in terms of enhancement onset time, enhancement level, contrast agent distribution characteristics and enhancement pattern.
(1) Time of enhancement onset refers to the time when enhancement begins to appear in the lesion and liver tissue, respectively.
(2) Enhancement level refers to the gray-scale intensity of the echo. The enhancement level of a lesion is defined by the level of enhancement of the adjacent liver tissue as a reference, and can be defined as four levels of no, low, equal and high enhancement, i.e., no, low, equal and high echogenicity compared with the echogenicity of the liver tissue, respectively. If the same lesion has both different levels of enhancement, the highest level is defined. For example, if a lesion has both high enhancement and low or no enhancement, the lesion can be defined as high enhancement and then combined with the contrast distribution characteristics.
(3) Contrast distribution characteristics refer to the distribution of contrast agent within the lesion, and there are several main types as follows: ① Homogeneous enhancement: the enhancement level is homogeneous and uniform. (2) inhomogeneous enhancement: the level of enhancement within the lesion is variable and the shape is irregular. (③) Peripheral nodular enhancement: nodular enhancement of variable size protrudes medially around the edge of the lesion, and the central part is mostly non-enhancing. (iv) Peripheral thick ring-like enhancement: the edge of the lesion shows homogeneous, regular thick ring-like enhancement, and the central part is mostly without enhancement, also known as the facial circle sign. (⑤) Peripheral irregular band enhancement: the edge of the lesion shows ring-shaped band enhancement, and the thickness and shape of the ring band are irregular, and the central part is low or no enhancement. (6) Multi-room-like or foveal enhancement: Within the low- or no-enhancing lesion, linear enhancement is seen to separate the lesion into several small rooms.
(4) Enhancement pattern refers to the change in enhancement level and contrast distribution characteristics during the arterial phase after the lesion exhibits a certain level of enhancement and contrast distribution characteristics, followed by the portal phase and delayed phase. The most common enhancement patterns are: (1) enhancement in the arterial phase with continuous enhancement in the portal/delayed phase. (ii) Enhancement in the arterial phase with significant fading of enhancement in the portal/delayed phase. (iii) No enhancement in all three vascular phases.
V. Clinical application
The clinical application of hepatic CEUS is relatively mature. Based on the reference of domestic and international literature, especially the results of a multicenter study in China, this guideline makes the following recommendations.
1. Qualitative diagnosis of FLLs
Based on the manifestation of CEUS, the qualitative diagnosis of lesions can be made by combining the clinical data of the subject, including the background of liver disease, medical history and symptoms, laboratory tests (e.g. tumor markers, blood picture), other imaging tests (e.g. CECT/CEMRI), etc.
(1) Enhanced performance of common malignant FLLs
Malignant FLLs generally show high enhancement in the arterial phase and fade to low enhancement in the portal/delayed phase.
1) Hepatocellular carcinoma (HCC)
Tumors in the arterial phase begin to enhance earlier than the liver parenchyma, and some tumor vessels and envelope enhancement can be seen. Nearly 70% of lesions < 5 cm in diameter are uniformly enhancing (85% uniform enhancement in < 2 cm) and 30% are inhomogeneously enhancing; most lesions over 5 cm in diameter (about 76%) are inhomogeneously enhancing.
The typical pattern of enhancement in HCC on CEUS is: high enhancement in the arterial phase, fading to hypoenhancement in the portal or delayed phase. 89% of HCC show this typical enhancement pattern, with most of them (about 70%) fading to hypoenhancement in the portal phase. The presence of a typical enhancement pattern was not significantly related to the presence or absence of cirrhosis, but there were significant differences between tumors of different sizes. The typical enhancement pattern was found in 76% of lesions < 2 cm in diameter and 24% of atypical ones, while more than 90% of tumors > 2 cm in diameter showed a typical enhancement pattern.
Therefore, a lesion >2 cm in diameter with the above-mentioned typical enhancement pattern and other enhancement features, combined with positive hepatitis virus infection or cirrhosis, should be highly suspicious of HCC, and the diagnosis can be further confirmed if it is accompanied by elevated serum alpha-fetoprotein (AFP). However, it must be differentiated very carefully from intrahepatic cholangiocarcinoma (see below).
A small number of HCCs (< 10%) present atypically, such as hyperenhancement in the arterial phase, persistent isoenhancement in the portal/delayed phase, or hypo- or isoenhancement in all three phases. Most often seen in smaller or more pathologically differentiated lesions.
2) Intrahepatic cholangiocarcinoma (ICC)
Eighty-three percent of ICC show a typical enhancement pattern similar to that of HCC, i.e. high enhancement in the arterial phase with fading to low enhancement in the portal or delayed phase. Of the lesions with a typical enhancement pattern, 63% showed peripheral irregular band enhancement, and the rest had homogeneous or heterogeneous enhancement. Peripheral irregular band enhancement was seen in 46% of lesions < 5 cm in diameter and 69% of lesions over 5 cm in diameter.
The typical enhancement patterns of ICC and HCC overlap with each other, making the differential diagnosis difficult. Peripheral irregular band enhancement is an important feature of ICC, which accounts for only 1% of HCC, and thus can be considered a key point in the differential diagnosis. A few patients with ICC may also have positive hepatitis virus infection or cirrhosis or even positive AFP, but mostly elevated levels of ICC-related tumor markers (e.g., CEA, CA19-9, CA125) can be detected. The correct diagnosis can be reached in most cases based on CEUS manifestations combined with clinical data. For some cases with difficult differential diagnosis (mostly small lesions), tissue biopsy is recommended.
3) Metastatic liver cancer (MLC)
MLC is characterized by rapid fading of enhancement, with hypoenhancement in the portal phase or even in the late arterial phase, and some lesions become hypoenhanced and anechoic in the delayed phase.
4) Other rare malignant FLLs
Although their performance is different, they basically conform to the enhancement pattern of malignant FLLs.
(2) Enhancement of common benign FLLs
Benign FLLs generally show high or equal enhancement in the arterial phase, unchanged or equal enhancement in the portal/delayed phase, or no enhancement in all three phases.
1) Hemangioma (hepatic hemangioma)
The typical presentation: the enhancement in the arterial phase is early or equal to that of the liver parenchyma, with more than 90% showing peripheral nodular hyperenhancement and centripetal filling of contrast in the portal and delayed phases, with some achieving whole-tumor enhancement; the enhancement level remains high or isoenhancement. 8% of lesions (mostly below 2 cm in diameter) show uniform whole-tumor hyperenhancement in the arterial phase.
If the enhancement is typical and combined with clinical data, a preliminary diagnosis can be made; if there is no significant change in the follow-up period of 1 year, a definite diagnosis can be made.
2) Hepatic adenoma (Adenoma)
The enhancement in the arterial phase is earlier than that in the liver parenchyma, with uniform hyperenhancement, and non-enhanced areas can be seen in larger lesions. The portal phase and delayed phase still show persistent high or equal enhancement, and some lesions with delayed phase enhancement fade to hypoenhancement.
3) Focal nodular hyperplasia (FNH)
In 70%-75% of the lesions, the portal and delayed phases are still hyper- or iso-enhancing, and some of the lesions have a “central scar” with low or no enhancement.
The diagnosis can be obtained in most cases by combining the clinical data. It should be noted that 25-30% of the lesions fade in the delayed phase, mostly in those with combined fatty liver.
4) Regenerating nodule
Most of them enhance simultaneously with the liver parenchyma, and all three stages are isoenhancing. In a few larger lesions, the arterial phase enhances a little later than the parenchyma, and the enhancement level is slightly lower, while the portal and delayed phases are isoenhanced.
5) Dysplastic nodule
Dysplastic nodule is a precancerous lesion of HCC, with complex enhancement pattern of benign or malignant FLLs, which is related to the degree of tissue differentiation.
6) Focal fatty change or sparing of the liver
Simultaneous enhancement and regression with the liver parenchyma, with isoenhancement in all three stages.
7) Liver cyst
It shows no enhancement in all three stages with clear borders.
8) Liver abscess
The arterial phase shows heterogeneous or predominantly peripheral hyperenhancement, and the internal partitioned enhancement can be seen, with a non-enhancing necrotic liquefied area between the partitions. The portal and delayed phases show fading or isoenhancement. A special sign is the regional patchy enhancement of the surrounding liver parenchyma, mostly wedge-shaped, seen in the early arterial phase in some cases.
The enhancement pattern of hepatic abscess has the characteristics of malignant FLLs, and the combination of clinical information such as pain, fever, and elevated peripheral blood leukocytes can help in the differential diagnosis, and if necessary, puncture can be tried to clarify the diagnosis.
(9) Inflammatory Focal Lesions)
Inflammatory focal lesions (such as inflammatory pseudotumors, tuberculosis, fungal infections, etc.) are a rare group of benign lesions, and the enhancement characteristics can be summarized as follows: ① enhancement starts earlier than or synchronized with liver tissue; ② more than 85% of the arterial phase shows high or equal enhancement; ③ contrast distribution characteristics are diverse, and may show uniform, heterogeneous or irregular peripheral ring enhancement; ④ more than 70% of the portal phase and delayed phase fade to low enhancement . The enhancing manifestations of inflammatory focal lesions are easily confused with malignant lesions, and clinical data such as medical history and laboratory examination often do not show any special findings, which mostly require puncture biopsy to determine the diagnosis.
(3) Enhancement of intrahepatic vascular or bile duct emboli
1) Tumor thrombus
High enhancement in the arterial phase and fading enhancement in the portal or delayed phase.
2) Thrombus
No enhancement in three phases.
2. Detection of FLLs
(1) Application purposes.
1) To improve the sensitivity of detection of micro FLLs.
2) Detection of lesions detected by CECT/CEMRI but not revealed by conventional ultrasound.
3) Application in the field of interventional medicine (see below).
(2) Examination methods
1) In general, the whole liver is scanned in a sequential manner after contrast injection, without missing every segment or dead space, until the scan is considered adequate or the contrast is cleared.
2) For lesions that have been detected by CECT/CEMRI, the location of the lesion is determined against the images of CECT/CEMRI or by using fusion imaging, and then contrast is injected to locate the lesion and observe its enhancement performance.
3. Applications in the field of interventional therapy
(1) Guided targeted puncture
1) Application purposes.
① For lesions that are not clearly shown under conventional ultrasound or have unclear boundaries, a puncture biopsy under CEUS guidance can clearly show the target lesion, improve the accuracy of biopsy and reduce the number of puncture needles.
② After ablation or other local treatment of hepatocellular carcinoma, residual or locally progressed tumors that are difficult to be identified by conventional ultrasound can be detected by CEUS and accurately punctured under CEUS guidance to supplement treatment.
③ After hepatocellular carcinoma by hepatic artery embolization chemotherapy (TACE), detect surviving tumors that are difficult to identify by conventional ultrasound and CECT by CEUS, and combine ablation therapy under CEUS guidance to improve local efficacy.
2) Guidance method.
Cases to be punctured for biopsy refer to the image localization of CECT/CEMRI. For cases requiring supplementary treatment after ablation and TACE, firstly, local disinfection and towel laying, local anesthesia, preparation of puncture needle set, then injection of contrast agent, and puncture when the tumor extent shows the largest and tumor boundary is the clearest.
(2) Monitoring of liver tumor ablation therapy
1) Application purpose.
① To assess whether the technique is successful.
② To finally judge the local efficacy.
2) Methods and observations.
① The assessment of technical success is performed after the disappearance of strong echogenic masses in the ablation foci. Thermal ablation is usually performed 15-30 minutes after the end of the treatment, and for those who have slow disappearance of strong echogenic masses in alcohol ablation lesions, they can be examined on the next day. The sign of successful technique is that the ablation scope covers the tumor without deviation and the third stage is no enhancement. If coverage is incomplete or if the tumor remains, it shows irregular or nodular hyperenhancement in the arterial phase, with fading enhancement in the portal and delayed phases. This enhancement pattern is similar to the congestive response band usually seen after thermal ablation, but the latter is a more regular circumferential enhancement around the ablation focus, which should be distinguished.
② The time to determine local efficacy is usually 1 month after treatment. Complete ablation shows no enhancement in all three phases, and incomplete ablation shows local nodular hyperenhancement in the arterial phase and hypoenhancement in the portal or delayed phase of decompensation.
(3) Conventional CEUS examination only obtains two-dimensional tomographic images, which is difficult to grasp the enhancement performance of the whole lesion, and even if multi-sectional transformation sweep is used, it is inevitable to miss.
(3) Evaluation of the efficacy of TACE for liver tumors
There is no unanimous opinion on the timing of CEUS implementation, and the criteria for judging the efficacy are the same as those for ablation therapy.
4. Perioperative evaluation of liver transplantation
(1) Purpose of application.
1) Pre-transplantation: to understand the patency of liver vessels, to further clarify the diagnosis of tumor lesions, to exclude contraindications to liver transplantation, and to select a suitable recipient or donor (living liver transplantation).
2) Post-transplantation: timely detection of hepatic vascular and biliary complications. Evaluate the efficacy after stenting for hepatic artery thrombosis or stenosis.
(2) Methods and what is seen
1) CEUS of the transplanted liver is performed as before. Lower contrast dosage (e.g., 0.5-1 ml/time) is recommended for assessing vascular status, multiple injections can be observed, real-time follow-up sweeps along the vascular pathway, and microangiography or high MI blast mode is used to show the vessels if necessary.
2) Post-transplant arterial complications.
① Hepatic artery thrombosis: In the early stage of hepatic artery thrombosis, no arterial perfusion is visualized in the liver in the arterial phase, and only portal venous perfusion is seen. In combination with local hepatic infarction, it shows as a wedge-shaped non-enhanced area in the liver; in the late stage, it is easy to form collateral branches and shows fine reticular or lamellar enhancement in the portal part of the liver in the arterial phase.
② Hepatic artery stenosis: The early arterial phase can directly show the hepatic artery and its alignment, morphology and stenosis and other lesions. Hepatic artery stenosis mostly presents as localized stenosis of the anastomosis, segmental or multiple segmental stenosis, and rarely as diffuse thinning stenosis of the hepatic artery.
3) Hepatic artery pseudoaneurysm: a round or semicircular contrast-filled area adjacent to the hepatic artery in the early arterial phase and connected to the hepatic artery.
3) Post-transplant complications of the portal and vena cava systems: enhanced manifestations of thrombosis and carcinoma emboli are described previously. CUES can directly show the site and extent of stenosis of the portal or inferior vena cava anastomosis.
4) Biliary complications after transplantation.
① Biliary stenosis: For those who need to do percutaneous transhepatic perforator bile duct placement for drainage, 10-30 ml of diluted UCA can be injected through the drainage tube. CEUS imaging mode can obtain similar effect as X-ray cholangiography, showing the morphology of the proximal dilated bile duct and stenotic segment, accurately determining the site of biliary stenosis and distinguishing anastomotic stenosis from non-anastomotic stenosis.
② Ischemic cholangitis: transvenous CEUS can reflect the perfusion of the bile duct wall in the hilar region more sensitively. Ischemic cholangitis (even early in the course of the disease) may present with no or low enhancement of the hilar bile duct wall in the arterial phase. In addition, transvenous CEUS is more likely to show bile tumors and dilated bile ducts that are difficult to show with conventional ultrasound.
5) Recurrence of hepatocellular carcinoma after transplantation:
The method of CEUS examination and enhancement performance are described in the previous section “Hepatocellular carcinoma of the liver”.
Limitations
The limitations of ultrasound are mainly due to the inherent limitations of the diagnostic technique.
In cases such as obesity, interference from gastrointestinal gas or pulmonary gas, high and deep lesion location, or poor breathing coordination, CEUS may not be able to clearly show the lesion.
2. CEUS obtains local tomographic images, which cannot show the whole liver in a more complete way as CECT/CEMRI. When there are more lesions or they are more dispersed, it is often necessary to repeat the contrast injection for scanning in different sections.
3. Conventional CEUS is a two-dimensional image, which makes it difficult to grasp the stereoscopic enhancement performance of the lesion and may affect the accuracy of the determination of the local efficacy of tumor ablation.
VII. Reporting content and requirements
First of all, the findings of conventional ultrasound examination should be reported.
The content of the report about CEUS examination should include.
1. lesion location, number, size and morphology.
2. the onset of enhancement of the lesion faster or slower than the surrounding liver tissue, or equal.
3. the enhancement performance (enhancement level, contrast distribution characteristics) of the arterial stage lesion.
4. Changes in enhancement performance of portal phase lesions.
5. Variation in enhancement performance of delayed phase lesions.
In case of multiple lesions, those with the same enhancement performance can be described together, otherwise they should be described separately; those with the same enhancement performance in the portal and delayed phases can be described together, otherwise they should also be described separately.