Detection of small HCC foci in cirrhotic liver may present as a challenge, especially in the presence of regenerative nodules. Therefore, it is of the highest significance, that US should be performed by qualified and experienced personnel using optimal equipment, preferably in dedicated centers. Heterogeneous lesions may correspond to HCC with degenerative changes, while a hyperechoic focus within a larger hypoechoic mass is suggestive of development of HCC within a dysplastic nodule tumor in tumor phenomenon [ 20 ].
Large lesions often show tendency to impress on adjacent vessels and infiltrate portal vein and its branches, they may present with hypoechoic halo suggestive of expansive growth or blurred, poorly defined margins when infiltrating the surrounding parenchyma. Different features of HCC in ultrasound examination.
Small, typically hypoechoic lesion a , larger lesions with mixed echogenicity b and c. Fibrolamellar carcinoma is usually a large, solitary focus within unchanged liver parenchyma, often showing central fibrous scar and calcifications.
In comparison to conventional gray-scale US contrast-enhanced ultrasonography CEUS provides higher diagnostic efficacy in differentiation of benign and malignant focal liver lesions FLLs , often comparable to that achieved in magnetic resonance imaging MRI. The main feature differentiating benign lesions from malignancies is their level of enhancement in the late phase of the study - benign lesions are usually hyper- or isoechoic to the surrounding liver parenchyma, while malignant lesions show hypoechogenicity Fig.
Although the enhancement pattern of FLLs may be analyzed in CEUS in real time in consecutive arterial, portal venous, delayed and postvascular phases, similarly to computed tomography CT or MRI, recently, many authors discuss that different pharmacokinetic features of contrast agents used for CEUS limit the value of the examination. Sonographic contrast agents are blood pool agents, confined to the vascular space, while the majority of contrast agents used in routine CT and MRI are extracellular space agents [ 21 ]. Other limitations include the possibility of overlooking subdiaphragmatic lesions and lesions smaller than 3 mm, reduced detectability of lesions located deep in the liver parenchyma, especially in steatosis and misinterpretation of falciform ligament as a FLL [ 21 ].
Two different HCC lesions arrows in gray-scale ultrasound a,c and in late phase of contrast-enhanced ultrasound b,d.ekdeivallu.tk
Abdominal US should be performed every 6 months in high-risk patients [ 3 ]. In case of detection of a nodule smaller than 10 mm and during follow-up after resection or loco-regional treatment the interval between consecutive US examinations should be reduced to 4 months [ 3 ] Figs.
Serum AFP is the most widely used tumor biomarker in diagnosis of HCC, however its value is often considered insufficient. Therefore, AFP levels are mainly evaluated in follow-up after the treatment. AFP can be divided during electrophoresis into different isoforms. The protein is a product of abnormal carboxylation of prothrombin precursor. Other markers are also investigated, for example Golgi protein 73 GP73 [ 30 ]. In meta-analysis by Hu et al. Areas under curve for the second and the third combination of markers were significantly higher than for single markers [ 28 ].
At the time, rather a combination of laboratory tests than a single marker, should be treated more as a guidance for further diagnostics, not as a stand-alone screening test. Histopathological report should be constructed according to the International Consensus Group for Hepatocellular Neoplasia guidelines [ 31 ].
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Non-invasive diagnostic criteria, which can be applied only in cirrhotic patients, have been first established in in Barcelona [ 32 ]. The latter results directly from previously mentioned neovascularization process within developing HCC lesions, with a predominance of arterial over portal venous blood supply. According to the altered recommendations diagnosis of HCC required confirmation of the typical enhancement pattern in one of two imaging modalities multiphase CT or DCE-MRI in nodules larger than 20 mm and in both imaging modalities in case of lesions measuring 10 to 20 mm; evaluation of serum AFP levels has been removed from the diagnostic algorithm [ 33 ].
The recommendations confirmed the efficacy and maintained the other criteria for the diagnosis of HCC in imaging studies [ 3 ]. Today, HCC is the only tumor for which non-invasive diagnosis is accepted. Imaging of FLLs in CT requires the use of a multi-phase study protocol, including a phase prior to the intravascular administration of contrast agent native phase and phases obtained after intravascular administration of contrast medium - HAP, PVP and EP, obtained routinely 40, 60 and seconds post contrast administration respectively in a multi-row CT unit Fig.
EP may be also referred to as an early delay phase in comparison to the late delay phase, obtained after 10 to 15 minutes after administration of contrast medium, acquired if the imaging protocol is extended to detect lesions with a high content of fibrous tissue, such as e. An early arterial phase, acquired 20 to 30 seconds after contrast agent administration may also be performed for CT angiography reconstructions.
Native examination a , hepatic arterial phase with contrast agent in hepatic arteries and slight enhancement of portal vein b , portal venous phase c and equilibrium phase d. Iodine contrast agents CAs eliminated mainly though kidneys and showing a half-life time of 1 to 2 hours, in case of normal renal function, are administered in CT in everyday practice. Routinely CAs are administered into the median cubital vein at a dose of 1 to 2.
This is however, subject to change depending on the imaging protocol and available equipment. The value of radiation attenuation coefficient of the liver is set between 50 to 60 Hounsfield Units HU. Liver parenchyma uniformly absorbs radiation. In non-enhanced liver vessels present with lower density in comparison to surrounding parenchyma.
Proteins, fats, ferritin, lipofuscin and organelles are suspended within the hepatocyte cytoplasm. Glycogen, iron and fat determine the degree of radiation absorption. Generally, an increase of intracellular water content is observed within liver tumors, accompanied by reduction of iron and glycogen content, which leads to decrease in radiation attenuation coefficient and typically manifests as an area of low density in imaging prior to CAs administration Fig. As mentioned previously, HCCs enhance strongly in the HAP, depending on the size of the tumor and the presence of regressive changes homo- or heterogeneously.
Large tumors will typically present with heterogeneous enhancement, often with so-called mosaic pattern as opposed to small, early forms of hepatocelullar carcinomas. While planning the examination, attention should be payed to the delay of the arterial phase of approximately 10 - 15 seconds to the enhancement of the aorta. Tumors with pseudo-capsule show better prognosis.
CT axial images. HCC in hepatic arterial phase a and equilibrium phase b. Wash-out feature and enhancing tumor pseudo-capsule is visible in the latter. As shown in Fig. Schematic presentation of pattern of enhancement of HCC lesion with strong enhancement in HAP bright, hyperdense lesion in comparison to surrounding liver parenchyma and wash-out of contrast agent in subsequent PVP and EP dark, hypodense lesion.
As those foci do not meet the non-invasive diagnostic criteria of HCC, a further confirmation by means of biopsy is required [ 34 ]. If, however, a biopsy cannot verify the diagnosis, a wait and close follow-up strategy with repeat imaging is recommended [ 36 ]. Atypical hypovascular HCC focus arrow in patient after right hemihepatectomy. The lesion shows no enhancement and is invisible in hepatic arterial phase in axial CT a.
Hypovascular HCC is hypodense in portal venous phase in axial CT b and hypointense in portal venous phase in axial fat-suppressed T1-weighted image d. The lesion is hyperintense in axial T2-weighted image c.
Additional sequences like delayed post-contrast T1-weighted sequence may be included. MRI examination must cover the whole liver and multi-planar acquisition is preferred. In conventional, pre-contrast MRI sequences the majority of large HCCs show decreased signal intensity in T1-weighted and increased signal intensity in T2-weighted images Fig. However, small lesions tend to remain isointense to the adjacent liver parenchyma in T1-weighted images.
Focal or diffuse areas of high signal intensity may be observed in lesions containing fat, glycogen, copper, melanin and methemoglobin, as well as in those containing high concentration of protein or presenting with slow blood flow or thrombosis. Presence of intracellular fatty components may be easily confirmed in phase and out of phase sequences, while fat saturation sequences are used to detect extracellular fat. T1-weighted images depict hyperintense areas of bleeding methemoglobin and fat, both important features in differential diagnosis, present in HCCs and hepatic adenomas more frequently.
Decrease in signal intensity in T2-weighted images is seen in case of fibrous tissue, while areas of necrosis present especially within large foci cause an increase in signal intensity and lead to heterogenous enhancement. Copper deposits lead to a slight reduction in signal intensity, while iron deposits significantly decrease signal intensity in both T1- and T2-weighted images. Low signal intensity of regenerative nodules in T2-weighted images resulting from characteristic iron deposits, facilitate differential diagnosis with usually hyperintense HCC foci.
Pseudocapsule is hypointense in T2-weighted images and shows delayed enhancement in EP, similarly to CT. Small isointense HCC focus in T1-weighted axial image a. Another HCC focus slightly hypointense in T1-weighted coronal fat-suppressed image b.
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Same lesion in T2-weighted image is hyperintense c. Regulative nodules siderotic in T2-weighted image d in comparison. Signal intensity of proliferative lesions results from their histological and cytological features, dynamic examination after intravascular administration of contrast medium allows differentiation of lesions according to their vascularity. Small arrow and large HCC foci in T1-weighted fast-suppressed axial images: pre-contrast a , in hepatic arterial phase b and equilibrium phase c. Both lesions show enhancement in arterial phase and wash-out in equilibrium phase.
Large lesion presents with enhancing pseudo-capsule in equilibrium phase. Paramagnetic gadolinium chelates are the most commonly used contrast agents in MRI in everyday practice. They possess properties of extracellular space contrast media and therefore penetrate from intravascular space through the capillaries, into the extracellular, interstitial space, resulting in contrast enhancement of abdominal parenchymal organs, including the liver.
The recommended dose of gadolinium chelates in liver imaging is 0. CAs are excreted in the mechanism of glomerular filtration; the plasma half-life is approximately 90 minutes and increases in patients with renal failure. Gadolinium chelates are generally considered safe in low doses applied clinically. Potential adverse reactions include transient headache, nausea and vomiting, as well as pain at the injection site. In some cases of small lesions, however, the washing-out of the contrast agent may not be observed as clearly as in mature forms of HCCs.
More and more commonly used in recent years HSCAs combine pharmacological features of extracellular space agents, allowing imaging in HAP, PVP and EP with delayed uptake by hepatocytes and excretion into biliary tracts resulting in obtaining an additional imaging phase, called the HBP.