Imaging Diagnosis of Intrahepatic Cholangiocarcinoma

1 Ultrasound Imaging Characteristics

Ultrasound examination is the first-line screening method for ICC, which is simple and economical. The ultrasound images of ICC often show irregular shapes with homogeneous low-echo lesions. As the tumor can compress or obstruct surrounding bile ducts, leading to bile accumulation, ultrasound often shows a ring or irregular hypoechoic area around the tumor. The specificity of ultrasound alone for diagnosing ICC is not high, and it is still challenging to distinguish ICC from hepatocellular carcinoma, liver abscess, etc. Ultrasound diagnosis is significantly influenced by the operator’s experience and equipment quality, as well as the tumor’s position and morphology, but clinically, ultrasound-guided multifocal puncture biopsy can be used to obtain a definitive pathological diagnosis. Additionally, contrast-enhanced ultrasound can show the tumor’s blood supply perfusion, which can assist in diagnosing ICC, but it also lacks specificity.

2 CT and MRI Characteristics

CT and MRI are still the main imaging methods for diagnosing ICC. The CT scan of ICC often shows uneven low-density lesions, with enhancement around the tumor in the arterial phase and sustained enhancement in the portal venous phase, sometimes with centripetal mild to moderate enhancement. The MRI characteristics of ICC typically show uneven low signals on T1-weighted imaging and uneven high or slightly high signals on T2-weighted imaging, with enhancement patterns similar to those of CT. The enhancement characteristics of ICC are primarily related to the infiltrative growth pattern of ICC. The tumor periphery consists of a large number of tumor cells and a small amount of fibrous tissue, resulting in relatively abundant blood supply, hence the enhancement in the arterial phase; while the tumor interior mainly consists of fibrous tissue, with some necrotic areas, causing the contrast agent to enter the fibrous stroma slowly, leading to sustained enhancement in the portal phase and delayed enhancement in the delayed phase. Both enhanced CT and MRI can clarify the relationship between the tumor and the hepatic hilum and peripheral vessels, providing a basis for clinical judgment on whether the lesion can be completely resected.

Some ICC cases are caused by long-term intrahepatic bile duct stones, and CT is relatively easier to distinguish than MRI. ICC often coexists with small foci adjacent to the main tumor, and MRI, especially in the T2-weighted phase, can display these more clearly than CT. The DWI sequence of MRI also aids in the detection of ICC and intrahepatic metastatic lesions. Reports suggest that enhanced MRI with gadoxetic acid can better detect small intrahepatic lesions of ICC.

The “shrinkage of the liver capsule” sign is a characteristic imaging manifestation of ICC, which is related to the infiltrative growth of the tumor, the presence of a large amount of fibrous tissue inside, and the pulling effect on the liver capsule. Local dilation of the bile duct around the tumor is also an important feature of ICC, often due to the tumor growing around or along the bile duct, leading to local narrowing and dilation of the bile duct lumen. Magnetic resonance T2-weighted imaging shows bile duct dilation more clearly than CT. The MRCP technique can display the entire bile duct tree, providing imaging evidence for distinguishing between extrahepatic and hilar bile duct tumors, in addition to clarifying the relationship between the tumor and surrounding bile ducts.

3 PET-CT Characteristics

PET-CT examination is a new radiological technology that combines anatomical and functional imaging. It reflects both morphological changes of the tumor and its metabolic characteristics and is increasingly used for tumor diagnosis, staging, and prognostic analysis.

Although PET-CT is not a mandatory examination item for ICC in some guidelines, more and more research results confirm its important clinical value in diagnosing ICC, as it is simple and clear, allowing even non-radiology medical staff to identify lesions effectively.

PET-CT is mainly based on the principle of increased uptake of 18F-FDG by tumor cells, primarily using standardized uptake value (SUV) for semi-quantitative analysis of attenuation-corrected images. Sabaté-Llobera et al. found a certain correlation between SUV values and CA19-9, carcinoembryonic antigen (CEA), which can assist in clarifying the diagnosis of ICC. Yoh et al. indicated that the SUVmax of ICC tumors is significantly correlated with tumor size and number, but not with the T and N staging of the American Joint Committee on Cancer (AJCC). Multivariable COX regression analysis shows that a high SUVmax predicts poor prognosis after ICC surgery.

Compared to traditional imaging examinations CT and MRI, PET-CT does not have advantages in diagnosing tumor size, subfoci, vascular cancer thrombosis, and bile duct invasion, but it has unique advantages in diagnosing lymph node and distant metastasis.

Traditional imaging techniques CT and MRI typically diagnose lymph node metastasis when the shortest diameter of the lymph node is >1 cm. The author conducted a retrospective analysis of 90 ICC surgical patients regarding the relationship between lymph node size and metastasis, finding that the proportion of large lymph nodes with metastasis significantly increased, yet some were still negative for metastasis. For lymph nodes with a shortest diameter <1 cm, nearly 10% still had metastasis. Therefore, lymph node size alone is insufficient for diagnosing metastasis. In PET-CT examinations, when the lymph node SUVmax ≥ 2.5, it is defined as positive, indicating lymph node metastasis. In this study, the accuracy of PET-CT in diagnosing ICC lymph node metastasis (86.7%) was higher than that of CT (62.2%) and MRI (68.9%). The reason is that the FDG uptake value is not affected by lymph node size, allowing for clearer imaging under high SUV conditions.

PET-CT has significant advantages over CT and MRI in diagnosing distant metastasis of ICC, as it can comprehensively display the systemic metastasis of lesions. The author analyzed the distant metastasis of 100 non-surgical ICC patients, finding that PET-CT indicated 92 cases with local lymph node metastasis. There were 23 cases with single-site distant metastasis and 77 cases with metastasis at more than two sites. Among the 100 patients, the most common distant metastasis sites were: supraclavicular lymph nodes, bone metastasis, mediastinal lymph nodes, hilar lymph nodes, and the lungs. The accuracy of PET-CT in displaying distant metastasis (98.4%) was much higher than that of CT and MRI (61.6% and 65.3%), due to: (1) PET-CT itself is a systemic examination, while CT and MRI are often limited to one area. (2) The imaging characteristics of PET-CT make it easier to indicate metastasis in lymph nodes and bones. Thus, PET-CT examination aids in the accurate clinical staging of ICC, allowing patients to receive treatment strategies different from the original plan, significantly reducing the occurrence of ineffective surgeries.

In recent years, PET-MR has also gradually been used in the clinical diagnosis and staging of tumors, but reports on its application in ICC are limited.

4 Combined Diagnosis with Multiple Imaging Techniques

Ultrasound is the first-line examination method for screening ICC. MRI has good soft tissue resolution and multi-directional imaging advantages, and its diagnostic accuracy for ICC is generally higher than that of CT; however, CT is more intuitive in displaying ICC related to intrahepatic bile duct stones. PET-CT combined with CT and MRI can improve the diagnostic accuracy of ICC and compensate for the shortcomings of CT and MRI in diagnosing regional lymph node metastases and distant metastases.

The combined diagnosis with multiple imaging techniques helps further improve the diagnostic accuracy of ICC. Among them, PET-CT should be regarded as a routine and necessary imaging examination for diagnosing ICC and should also be a standard detection method for preoperative staging of ICC.

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