Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy and one of the most prevalent visceral malignances worldwide [21]. HCC usually occurs in the setting of cirrhosis with a known cause, such as chronic viral hepatitis or alcoholism. Regarding alcoholism as a cause of cirrhosis, it is thought that alcoholism promotes hepatic malignancies indirectly via its immuno-suppressive effects. These effects facilitate the development of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Furthermore, alcoholic cirrhosis is triggered by the well-known oxidative effects that deplete the anti-oxidative defense system [35]. Whereas in Asia HCC occurs almost exclusively in patients with chronic liver damage from hepatitis, in North America many patients develop HCC without cirrhosis or known risk factors [74]. In these latter patients it is possible that steroid hormones may play a role in carcinogene-

sis, as tumors occurring in non-cirrhotic livers have been associated with the use of exogeneous steroids such as anabolic steroids and oral contraceptives, as well as with genetic factors [52]. Environmental and dietary factors are known to play major etiological roles; in this context aflatoxins, nitrosamines, and other chemical carcinogens have been implicated in non-cirrhotic HCC [18, 22]. HCC is much more common among males than females. In high-incidence countries, the male-to-female ratio may be as high as 7 or 8 : 1, but in the United States, it is approximately 2 : 1 [57]. The occurrence of HCC increases progressively with age, although again this varies by country. Thus, in high-incidence countries, the mean age at diagnosis is in the third decade of life, while in low-incidence countries, it occurs 2 to 3 decades later. HCC is well documented in childhood; most childhood cases are associated with HBV infection or metabolic diseases, such as tyrosinemia [49].

Chronic liver disease, including liver cirrhosis, is one of the most important factors in HCC, which is characterized by the development of a spectrum of nodules ranging from benign regenerative nodules to overt HCC.

In carcinogenesis of the cirrhotic liver, the first step in the development of an overt HCC may be the formation of a benign regenerative nodule which then develops in a multistep fashion through the intermediate phases of ordinary low-grade dysplastic nodule (LGDN), high-grade dys-plastic nodule (HGDN), and early HCC [90,17].

Since dysplastic nodules (DNs) containing malignant foci and early well-differentiated HCC contain a great deal of fat, it has been postulated that fat deposition in dysplastic nodules is closely related to malignancy [53]. The same author reported that 20% of liver specimens resected with the diagnosis of HCC contained DNs and 40% of those DNs were HGDNs or DNs containing foci of HCC. The presence of DNs containing foci of HCC rep resents strong evidence that DNs are premalignant lesions [53].

Microscopically, HCC is composed of malignant hepatocytes that attempt to differentiate into normal liver structures, mimicking hepatocyte growth, but are unable to form normal hepatic acini. In well-differentiated HCC, tumor cells are difficult to distinguish from normal hepatocytes or hepatocytes in hepatocellular adenoma. Malignant hepatocytes may even produce bile. In other cases, there are microscopic variations, with HCC containing fat, tumoral secretions (large amounts of watery material), fibrosis, necrosis and amorphous calcification [73].

The most frequent pattern of HCC is the trabec-ular pattern, in which the tumor cells grow in thick cords that attempt to recapitulate the cell-plate pattern seen in normal liver tissue. The trabeculae are separated by vascular spaces with very little or no supporting connective tissue. Sometimes tumor secretions are in the center of the trabeculae, giving the tumor a pseudoglandular pattern. If the trabecu-lae grow together, they produce a solid pattern [71].

Macroscopically, there are also several patterns of growth. HCC is designated single or massive when there is a solitary small or large mass, with or without a capsule. Multiple separate nodules characterize multifocal HCC, the second most common pattern. The least common pattern of diffuse or cirrhotomimetic growth is multiple small tumoral foci distributed throughout the liver, mimicking nodules of cirrhosis. HCC is described as encapsulated when it is completely surrounded by a fibrous capsule. Encapsulated HCC has better prognosis due to its greater resectability. In general, vascular invasion of intrahepatic and perihepatic vessels is common in HCC [24, 86].

The symptoms associated with HCC include malaise, fever, abdominal pain, and weight loss, while jaundice is rare [86]. Often the neoplasm is detected in asymptomatic patients, and the liver function tests are normal or slightly altered except for elevation of a-fetoprotein levels. These values are high in more than 50% of cases and generally are considered suggestive of HCC when they exceed 200 ng/ml. Proteins produced by HCC may give rise to numerous paraneoplastic syndromes such as erythrocytosis, hypercalcemia, hypoglycemia and hirsutism [49]. Several investigators [74,104] have consistently reported that HCC occurring in the non-cirrhotic liver has different features: patients are younger and are more likely to present with symptoms. Frequently, these patients have a single or dominant mass and have reduced mortality if liver resection is performed [95].

Ultrasound (US) is considered a screening method for patients at risk of HCC, and often detects neoplasms smaller than 2-3 cm (the so-called "small HCC"), even when a-fetoprotein levels are

Dialysis Patient Kidney Ultrasounds
Fig. 1. Well-differentiated hepatocellular carcinoma. Ultrasound reveals a well-defined, homogeneous, and hypoechoic lesion (asterisk)

still normal. On US scans, the echogenicity of the HCC neoplasm varies with the size of the lesion. Thus, nodules smaller than 3 cm are usually well-defined, hypoechoic, and homogeneous, with posterior acoustic enhancement (Fig. 1). Conversely, lesions larger than 3 cm are often heterogeneous, with a mosaic or mixed pattern arising from a combination of areas of necrosis, hemorrhage, fatty degeneration and interstitial fibrosis (Fig. 2). In the diffuse form, tumor infiltration tends to cause a disruption of the hepatic echo structure [16]. When visible, the capsule of an encapsulated HCC usually appears as a thin, hypoechoic, peripheral band with characteristic lateral acoustic shadows [86].

Color Doppler US sometimes reveals a "basket" pattern, which is indicative of hypervascularity and tumor shunting, and the "vessel within the tumor" pattern, with vessels that have peripheral-to-central directed flow (Fig. 3). Power Doppler US is often considered superior to color Doppler US for the depiction of vascular flow because of its high sensitivity to slow flow, lack of angle dependency, and absence of aliasing [59]. Recently, various harmonic imaging techniques, such as tissue harmonic imaging, harmonic power Doppler US, and color coded harmonic angiography, have been developed and used, also in combination with contrast media such as SonoVue, to improve the characterization of HCC.

The goal of contrast-enhanced US (CEUS) in cirrhotic patients is the differentiation of HCC from regerative nodules (RNs) and DNs (Fig. 4). On CEUS, the characteristic pattern of HCC is represented by an intense and fast peak of enhancement in the arterial phase, followed by a relatively quick wash-out (Fig. 5). Chaotic peritumoral and intralesional tortuous vessels may be seen in the arterial phase and feeding vessels can be identified in most cases [14,48,50].

Hypoechoic Nodule With Hypoechoic Rim
Fig. 2. Moderately-differentiated hepatocellular carcinoma. On ultrasound, the lesion is heterogeneous with hypoechoic and hy-perechoic areas (arrowheads). A thin, hypoechoic rim corresponding to a pseudocapsule borders the lesion (arrows)

Fig. 3. Hepatocellular carcinoma on color Doppler. Color Doppler ultrasound reveals internal vascularization and a peritumoral hy-pervascular rim giving the characteristic 'basket' pattern. The vessels flow from the periphery through the center

Answer For Liver Cancer Test

Fig. 4a-d. Dysplastic nodule with focus of hepatocellular carcinoma with SonoVue®. On the pre-contrast US scan (a), a heterogeneous isoechoic nodule is demonstrated (arrows). In the arterial phase of the dynamic evaluation after SonoVue® administration (b) the lesion (arrows) appears hypoechoic at the periphery with a hyperechoic central nodule representing a focus of hepatocellular carcinoma (asterisk). The feeding vessel supplying the hepatocellular carcinoma is also shown (arrowheadin b). The lesion becomes isoechoic in the portal-venous (c) and equilibrium (d) phases

Fig. 4a-d. Dysplastic nodule with focus of hepatocellular carcinoma with SonoVue®. On the pre-contrast US scan (a), a heterogeneous isoechoic nodule is demonstrated (arrows). In the arterial phase of the dynamic evaluation after SonoVue® administration (b) the lesion (arrows) appears hypoechoic at the periphery with a hyperechoic central nodule representing a focus of hepatocellular carcinoma (asterisk). The feeding vessel supplying the hepatocellular carcinoma is also shown (arrowheadin b). The lesion becomes isoechoic in the portal-venous (c) and equilibrium (d) phases

Sonovue Contrast
Fig. 5. Hepatocellular carcinoma on contrast-enhanced ultrasound: During the arterial phase, after the bolus injection of Sonovue®, the lesion shows intense and homogeneous enhancement, and becomes hyperechoic (arrow). Hyperechogenicity reflects the hypervascular nature of the tumor

On CT scans, the appearance of HCC depends largely on tumor size and histologic tumor grade, with low sensitivity for detection of small neoplasms that are difficult to differentiate from un-opacified vessels [38]. Unenhanced CT scans often reveal a hypodense nodule. Occasionally, central areas of lower attenuation corresponding to tumor necrosis can be seen [51]. Small HCCs have a proportionately greater arterial hepatic blood supply and, as a result, they may be visible only on hepatic arterial phase images. They tend to demonstrate hyperattenuation on early arterial phase images and rapid wash-out in the subsequent portal-venous phase (Fig. 6) [76]. In larger lesions, the portal vein may also contribute significantly to the blood supply of the HCC, enabling its visualization on portal-venous phase images as well [45]. However, because large tumors may contain areas of hemorrhage or necrosis, they may be seen as either hyper- or hypoattenuating compared with the surrounding liver tissue during the arterial phase of hepatic enhancement, and as hypoattenuating in the portal-venous phase (Fig. 7). Nodular HCCs possess a peripheral capsule in about 50 to 80% of cases (Fig. 8) [32,51,70,80].

Non-encapsulated tumors frequently appear as ill-defined, irregular, often hypervascular masses, showing a variable degree of vascular or bile duct infiltration (Fig. 9).

The role of CT in the detection of dysplastic nodules in the cirrhotic liver has been evaluated in several studies [37,61]. These studies indicate that many DNs are isoattenuating to the adjacent liver parenchyma and thus cannot be detected on CT scans because the blood supply to these nodules is similar to that of the normal liver parenchyma.

On MR imaging, DNs are usually hyperintense on T1-weighted images, and iso- to hypointense on T2-weighted images. Conversely, HCCs are often hyperintense on T2-weighted images, and hypointense on T1-weighted images. However several studies [15, 54, 70] have stated that an accurate distinction between DNs and HCCs cannot usually be made on the basis of signal intensity characteristics on unenhanced MR, because of the overlapping signal intensities from multiple nodules.

DNs, particularly LGDNs, do not usually show significant arterial enhancement after the bolus injection of gadolinium contrast agents, however in about 5% of HGDNs arterial enhancement can be detected, possibly because of neoangiogenesis (Figs. 10, 11, 12). On delayed phase images acquired after the administration of hepatobiliary contrast agents, DNs generally show a contrast agent uptake similar to that observed in the surrounding parenchyma. Since DNs contain identical or slightly increased numbers of Kupffer cells compared to the normal liver parenchyma, they are not readily seen on T2-weighted fast spin-echo images acquired after the administration of superparamagnetic iron oxide (SPIO) contrast material [62].

Contrast-enhanced dynamic MR imaging is an important tool for differentiating DNs, DNs with a focus of HCC, and overt HCC (Fig. 13). Indeed, contrast-enhanced dynamic MR is useful for the detection and characterization of HCCs in general [69]. Generally, most HCCs, because of their hy-pervascular nature, are homogeneously hyperin-tense compared to the liver in the arterial phase, and hypointense in the portal-venous and equilibrium phases. Tumors smaller than 3 cm in diameter tend to show a homogeneous enhancement (Fig. 14), and in about 20% of cases are visible mainly in the arterial phase (Fig. 15).

Irregular mosaic-like or peripheral enhancement is usually seen in larger neoplasms, depending on the internal architecture [82,106,107].

In moderately differentiated trabecular or pseudo-glandular HCCs, a peak of enhancement is usually seen during the arterial phase, followed by a rapid decrease during the subsequent portal-venous and equilibrium phases. Gradually increasing enhancement over time is found in poorly-differentiated scirrhous HCCs, whereas minimal or no contrast enhancement is seen in small, well-differentiated neoplasms. Sometimes a mixture of variably-differentiated areas may be found in large HCCs (Fig. 16).

Dynamic MR imaging is also helpful for the assessment of HCC pseudocapsules (Figs. 10, 14). When present, HCC pseudocapsules containing abundant granulation tissue usually enhance

What Eat When You Have Hypercalcemia
Fig. 6a-c. Small hepatocellular carcinoma on CT. On the unenhanced CT scan (a) the hepatic parenchyma appears homogeneous. A hypervascular nodule (arrow) can be seen in the arterial phase after the administration of contrast material (b) but is no longer seen in the portal-venous phase (c)
Large Hepatocarcinoma Mri

Fig. 7a-c. Hepatocellular carcinoma on CT. On the unenhanced CT scan (a), a large hepatocellular carcinoma (arrows) appears as a well-defined hypodense nodule with a central area of lower attenuation corresponding to tumor necrosis (arrowhead). After administration of contrast medium, the nodule is seen as hetero-geneously hyperattenuating during the arterial phase (b), becoming hypoattenu-ating compared to the surrounding parenchyma in the portal-venous phase (c)

Fig. 8a-c. Encapsulated hepatocellular carcinoma. The unenhanced CT scan (a) shows a well-defined isodense nodule (asterisk). The lesion shows discrete enhancement during the arterial phase (b) and is seen as hypodense in the portal-venous phase (c) with a peripheral hyperintense rim (arrowheads)

Fig. 9a-d. Non-encapsulated hepatocel-lular carcinoma. On the unenhanced CT scan (a) the nodule (asterisk) is seen as an ill-defined hypodense mass. The lesion enhances markedly during the arterial phase after the administration of contrast material (b) and subsequently shows right portal vein infiltration (arrow/) in the portal-venous phase (c). During the equilibrium phase (d) the lesion becomes hetero-geneously isodense

Fig. 9a-d. Non-encapsulated hepatocel-lular carcinoma. On the unenhanced CT scan (a) the nodule (asterisk) is seen as an ill-defined hypodense mass. The lesion enhances markedly during the arterial phase after the administration of contrast material (b) and subsequently shows right portal vein infiltration (arrow/) in the portal-venous phase (c). During the equilibrium phase (d) the lesion becomes hetero-geneously isodense

Fig. 10a-f. Dysplastic nodule. On the unenhanced T2-weighted image (a) the lesion (asterisk) is seen as isointense against the normal parenchyma, while on the corresponding T1-weighted image (b), it is seen as hyperintense. The lesion does not show significant enhancement on images acquired during the arterial phase after Gd-BOPTA administration (c), but reveals a thin enhancing peripheral rim during the portal-venous and equilibrium phases (d and e, respectively). In the delayed hepatobiliary phase (f) the dysplastic nodule demonstrates uptake of Gd-BOPTA

Fig. 10a-f. Dysplastic nodule. On the unenhanced T2-weighted image (a) the lesion (asterisk) is seen as isointense against the normal parenchyma, while on the corresponding T1-weighted image (b), it is seen as hyperintense. The lesion does not show significant enhancement on images acquired during the arterial phase after Gd-BOPTA administration (c), but reveals a thin enhancing peripheral rim during the portal-venous and equilibrium phases (d and e, respectively). In the delayed hepatobiliary phase (f) the dysplastic nodule demonstrates uptake of Gd-BOPTA

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Fig. 11a-f. Dysplastic nodule. On the precontrast T2-weighted image (a) the lesion is isointense compared to the normal liver parenchyma, while on the GE T1-weighted "in-phase" (b) and "out-of-phase" (c) images the nodule (arrowin b) appears hyperintense due to an increased glycogen content. The nodule enhances during the arterial phase (d) after the bolus injection of hepatobiliary contrast agent Gd-BOPTA) but shows rapid wash-out of contrast agent during the subsequent portal-venous phase (e) rapid wash-out can be observed. On a Tl-weighted fat suppressed GRE image in the delayed hepatobiliary phase (f) the lesion is isointense compared to the surrounding normal liver parenchyma

b

Normal Liver Mri Images

Fig. 12a-i. Dysplastic nodule in cirrhotic liver. On HASTE T2-weighted images (a) the liver parenchyma appears heterogeneous with a large isointense nodule (asterisk. On fat-saturated T2-weighted images (b), many hypointense nodules with variable signal intensity are detected. On GE Tl-weighted in- and out-of-phase images (c-d) the biggest lesion shows signal drop on the "out-of-phase" image due to fatty infiltration (arrow). Dynamic evaluation does not reveal significant enhancement of the nodules (e-g). On hepatobiliary phase GE Tl-weighted images with and without fat suppression acquired 1h after injection of Gd-BOPTA (h-i), many nodules show contrast agent uptake. In particular, the biggest nodule in the left liver lobe appears isointense (arrowheadin h). Note the high signal intensity in the common bile duct due to the excretion of Gd-BOPTA (arrowin i)

Liver Focus

Fig. 13a-f. Dysplastic nodule with focus of hepatocellular carcinoma. This figure shows the same case as Fig.12, on a follow-up study one year later. On the precontrast T2- weighted image (a) the nodule now contains a heterogeneous hyperintense area (arrowhead) that appears slightly hypointense on the Tl-weighted GE "out-of-phase" image (b). During the dynamic study after the bolus administration of Gd-BOPTA, the lesion shows enhancement of the internal portion in the arterial phase (c) with a "nodule within nodule" aspect. Discrete wash-out of contrast agent is apparent in the portal-venous phase (d). On the hepatobiliary phase Tl-weighted image (e) the nodule is heterogeneous in signal intensity, the hypointense area (arrowhead corresponds to a focus of hepatocellular carcinoma. A PET-CT scan (f) confirms the presence of a hot-spot area within the lesion (arrowhead

Fig. 13a-f. Dysplastic nodule with focus of hepatocellular carcinoma. This figure shows the same case as Fig.12, on a follow-up study one year later. On the precontrast T2- weighted image (a) the nodule now contains a heterogeneous hyperintense area (arrowhead) that appears slightly hypointense on the Tl-weighted GE "out-of-phase" image (b). During the dynamic study after the bolus administration of Gd-BOPTA, the lesion shows enhancement of the internal portion in the arterial phase (c) with a "nodule within nodule" aspect. Discrete wash-out of contrast agent is apparent in the portal-venous phase (d). On the hepatobiliary phase Tl-weighted image (e) the nodule is heterogeneous in signal intensity, the hypointense area (arrowhead corresponds to a focus of hepatocellular carcinoma. A PET-CT scan (f) confirms the presence of a hot-spot area within the lesion (arrowhead

Hepatocellular Carcinoma And Mri

Fig. 14a-f. Hepatocellular carcinoma. On the unenhanced T2-weighted image (a) the lesion appears hyperintense (arrow), while on the unenhanced T1-weighted image (b) the nodule is slightly hypointense with a thin hypointense peripheral rim. In the arterial phase after the bolus administration of Gd-BOPTA (c) the mass becomes heterogeneously hyperintense due to hypervascularization, whereas the peripheral rim remains hypointense. In the portal-venous phase (d) the contrast agent persists within the lesion and the pseudocapsule becomes hyperintense as well. During the equilibrium phase (e) the nodule appears slightly hyperintense and well-circumscribed by a peripheral hyperintense pseudocapsule. In the delayed hepatobiliary phase (f) the neoplasm appears homogeneously hypointense and well-delineated, since unlike normal liver hepatocytes, the malignant hepatocytes of the hepatocellular carcinoma are unable to take up the contrast agent

Fig. 14a-f. Hepatocellular carcinoma. On the unenhanced T2-weighted image (a) the lesion appears hyperintense (arrow), while on the unenhanced T1-weighted image (b) the nodule is slightly hypointense with a thin hypointense peripheral rim. In the arterial phase after the bolus administration of Gd-BOPTA (c) the mass becomes heterogeneously hyperintense due to hypervascularization, whereas the peripheral rim remains hypointense. In the portal-venous phase (d) the contrast agent persists within the lesion and the pseudocapsule becomes hyperintense as well. During the equilibrium phase (e) the nodule appears slightly hyperintense and well-circumscribed by a peripheral hyperintense pseudocapsule. In the delayed hepatobiliary phase (f) the neoplasm appears homogeneously hypointense and well-delineated, since unlike normal liver hepatocytes, the malignant hepatocytes of the hepatocellular carcinoma are unable to take up the contrast agent

Phase Liver ScanGlomerulus CalcineurinAbnormal Foot Mri Images

Fig. 15a-i. Diffuse hepatocellular carcinoma. Diffuse lesions in the liver parenchyma can be noted on T2-weighted images before (a) as well as after (b) the injection of iron oxide particles (SH U 555 A). However, the nature of the lesions remains unclear since no signs of cirrhosis are present. On unenhanced Tl-weighted images the lesions appear hypointense (c). Arterial phase images acquired after the injection of Gd-BOPTA (d) clearly reveal numerous hypervascular lesions (arrows). These lesions demonstrate rapid wash-out in the portal-venous phase (e) and hypointensity in the equilibrium phase (f). In contrast, the hypervascular nature of the lesions is not clearly depicted on dynamic imaging after the bolus injection of SH U 555 A (g, h) although the lesions are more obvious and appear hypointense on the portal-venous phase image (h), hence the differential diagnosis remains unclear. An increase of contrast between the hypointense liver lesions and surrounding normal liver tissue can be observed (i) on hepatobiliary phase Tl-weighted images after the injection of Gd-BOPTA, indicating the malignant nature of the lesions. This case shows the importance of dynamic imaging for differential diagnosis, since the only clue towards diagnosis in a patient without obvious signs of liver cirrhosis is the hypervascular nature of the lesions prominently in the portal-venous phase. Thereafter, enhancement persists with signs of wash-out into the equilibrium phase due to slow flow in the abundant blood vessels that are present in fibrous tissue (Fig. 17) [32]. With regard to the delayed phase, several authors have shown that heterogeneous delayed retention of contrast agent in HCC is not specific to particular tumors, and may correspond to abundant fibrous stroma, as found in scirrhous HCC [28,82].

In the delayed liver-specific phase after Gd-BOPTA, well-differentiated and moderately-differentiated HCCs show superior signal enhancement ratios to poorly differentiated HCCs [31, 64]. This is likely to be a consequence of the first two neo-plastic forms retaining sufficient residual hepato-cytic activity to take up Gd-BOPTA. These forms may also produce bile, which may also correlate with the degree of contrast enhancement. Nevertheless, fewer than 20% of well-differentiated and moderately-differentiated HCCs appear iso- or hy-perintense on hepatobiliary phase images after administration of Gd-BOPTA (Fig. 18); most poorly-differentiated (Fig. 19) and large HCCs are hy-pointense compared to the normal liver on delayed, hepatobiliary phase images (see also Fig. 17).

SPIO agents are helpful for detecting small HCCs in cirrhotic livers. A recent report [40] investigated the relationship between the number of Kupffer cells in HCCs and DNs and the degree of SPIO uptake. This study showed that the ratio between the number of Kupffer cells in tumorous versus non-tumorous tissue decreased with the degree of cellular differentiation. Thus, the ratio of the signal intensity of the neoplastic lesion compared with that of the non-neoplastic area on SPIO-enhanced imaging correlated well with the number of Kupffer cells present (Figs. 20, 16).

On dynamic T1-weighted imaging after the bolus administration of SH U 555 A, the hypervascu-larity of HCC nodules can be visualized in the early arterial phase as a moderate hyperintense signal due to the T1-effect of this agent. Using a dynamic T2-weighted protocol, a sudden drop-out phenomenon can be observed in hypervascular HCCs after administration of SH U 555 A, with a rapid signal loss in the perfusion phase followed by a short increase in signal intensity. On the delayed phase images after administration of SH U 555 A, poorly-differentiated HCCs generally do not show significant contrast medium uptake and thus appear hy-perintense (Fig. 21). Conversely, well-differentiated HCCs may show a variable degree of signal drop due to the presence of Kupffer cells within the lesion [34].

HCC generally do not show significant uptake of mangafodipir trisodium (Mn-DPDP) and thus appear as hypointense masses against enhanced normal parenchyma on mangafodipir-enhanced T1-weighted images [68]. However, well-differentiated HCCs may show uptake of Mn++ (Figs. 22,23). Unfortunately, considering only the hepatobiliary phase, other malignant lesions, such as metastases of neuroendocrine tumors or benign lesions, such as hepatic adenoma or FNH, may also present a similar uptake, and thus differential diagnosis may be difficult. Although mangafodipir is sometimes employed to differentiate benign hepatocellular lesions from non-hepatocellular tumors, a dynamic imaging capability usually provides important additional information for the characterization of focal liver lesions (Fig. 24). Thus, dual MR contrast agents such as Gd-BOPTA or Gd-EOB-DTPA that allow both dynamic and hepatocyte-specific imaging may be of greater benefit.

Dynamic Liver Mri

Fig. 16a-j. Hepatocellular carcinoma with different stages of differentiation. On unenhanced T2-weighted images (a) a large heteroge-neously hyperintense lesion can be noted in the right liver lobe (arrows). On the corresponding Tl-weighted image (b) the lesion again shows heterogeneous signal intensity with regions of hypo-, hyper- and isointensity. The hypervascularity of the lesion and the presence of numerous nodules is clearly depicted on arterial phase images after the bolus injection of Gd-BOPTA (c). In the portal-venous phase image (d), the more anterior aspect of the lesion demonstrates contrast agent wash-out (arrow), while the more posterior parts show contrast agent pooling. In the equilibrium phase (e) most of the lesion shows wash-out compared to normal liver tissue, thereby indicating a hepatocellular carcinoma. On arterial (f) and portal-venous (g) phase images after the injection of iron oxide particles (SH U 555 A) the hy-pervascular nature of the lesion cannot be appreciated to the same extent as after the application of a Gd-agent. In the hepatobiliary phase after the injection of Gd-BOPTA (h), parts of the lesion appear hypointense and others isointense compared to the surrounding liver tissue. This is indicative of both well-differentiated and undifferentiated areas of the hepatocellular carcinoma. The same holds true for iron oxide-enhanced Tl-weighted (i) and T2-weighted (j) images in which parts of the lesion lose signal due to uptake of contrast agent by Kupffer cells (arrow) while other parts show higher signal intensity compared to normal liver tissue due to the lack of uptake

Fig. 17 a-f. Large hepatocellular carcinoma. On T2-weighted HASTE (a) and TrueFISP (b) images the hepatocellular carcinoma (asterisk) appears as a heterogeneous, slightly hyperintense mass. Conversely, on the unenhanced GE Tl-weighted image (c) the lesion is seen as markedly hypointense. In the arterial phase, after the administration of Gd-BOPTA (d) the mass appears as heterogeneously hyperintense while in the portal-venous phase (e) it is heterogeneously hypointense with a well-defined peripheral hyperintense pseudocapsule (arrowheads). In the delayed hepatobiliary phase (f), the lesion is again hypointense due to the lack of contrast medium uptake by the malignant hepatocytes. A rim of intermediate signal intensity surrounds the lesion while central areas of necrosis show non-specific contrast agent retention (arrow)

Fig. 17 a-f. Large hepatocellular carcinoma. On T2-weighted HASTE (a) and TrueFISP (b) images the hepatocellular carcinoma (asterisk) appears as a heterogeneous, slightly hyperintense mass. Conversely, on the unenhanced GE Tl-weighted image (c) the lesion is seen as markedly hypointense. In the arterial phase, after the administration of Gd-BOPTA (d) the mass appears as heterogeneously hyperintense while in the portal-venous phase (e) it is heterogeneously hypointense with a well-defined peripheral hyperintense pseudocapsule (arrowheads). In the delayed hepatobiliary phase (f), the lesion is again hypointense due to the lack of contrast medium uptake by the malignant hepatocytes. A rim of intermediate signal intensity surrounds the lesion while central areas of necrosis show non-specific contrast agent retention (arrow)

Fig. 18a-f. Well-differentiated hepatocellular carcinoma. On the precontrast T2-weighted image (a) the nodule (arrows) appears isointense compared to the normal liver parenchyma, with a thin peripheral rim. On the corresponding precontrast GE Tl-weighted image (b) the lesion appears isointense with a hypointense rim. The lesion shows marked enhancement in the arterial phase (c) of the dynamic series after the bolus administration of Gd-BOPTA, followed by rapid wash-out of contrast agent in the portal-venous phase (d). Note that a hyperintense pseudocapsule is well demonstrated on the portal-venous phase scan. On the hepatobiliary phase GE Tl-weighted (e) and Tl-weighted fat suppressed images (f), the nodule is isointense and hyperintense respectively. This example demonstrates that the malignant cells in a well-differentiated hepatocellular carcinoma sometimes retain the ability to take up the contrast agent and to produce bile

Fig. 18a-f. Well-differentiated hepatocellular carcinoma. On the precontrast T2-weighted image (a) the nodule (arrows) appears isointense compared to the normal liver parenchyma, with a thin peripheral rim. On the corresponding precontrast GE Tl-weighted image (b) the lesion appears isointense with a hypointense rim. The lesion shows marked enhancement in the arterial phase (c) of the dynamic series after the bolus administration of Gd-BOPTA, followed by rapid wash-out of contrast agent in the portal-venous phase (d). Note that a hyperintense pseudocapsule is well demonstrated on the portal-venous phase scan. On the hepatobiliary phase GE Tl-weighted (e) and Tl-weighted fat suppressed images (f), the nodule is isointense and hyperintense respectively. This example demonstrates that the malignant cells in a well-differentiated hepatocellular carcinoma sometimes retain the ability to take up the contrast agent and to produce bile

Fig. 19a, b. Poorly-differentiated hepatocellular carcinoma. On the unenhanced GE T1-weighted image (a) and on the image acquired during the delayed hepatobiliary phase after Gd-BOPTA administration (b) the nodule is seen as hypointense compared to the liver

Fig. 20a, b. Hepatocellular carcinoma. On the unenhanced Turbo SE T2-weighted image (a) the nodule is well-defined and slightly hyperintense (arrows). On the image acquired during the delayed liver-specific phase after SPIO administration (b) the contrast-to-noise ratio is improved. The lesion does not show uptake of SPIO and remains hyperintense

Fig. 20a, b. Hepatocellular carcinoma. On the unenhanced Turbo SE T2-weighted image (a) the nodule is well-defined and slightly hyperintense (arrows). On the image acquired during the delayed liver-specific phase after SPIO administration (b) the contrast-to-noise ratio is improved. The lesion does not show uptake of SPIO and remains hyperintense

Mri Liver Hepatocellular Carcinoma

Fig. 21a-f. Poorly differentiated hepatocellular carcinoma with USPIO. On the precontrast T2-weighted image (a), a well-defined, round, slightly hyperintense nodule (arrow) is visible, while on the GRE Tl-weighted sequence the lesion appears homogeneously hypointense (b). The dynamic evaluation after bolus injection of USPIO (c-e) reveals weak uptake of contrast medium, which is slightly more evident in the equilibrium phase (e). On a T2-weighted image acquired during the delayed liver specific phase after USPIO administration (f) the hepatocellular carcinoma appears hyperintense due to the lack of Kupffer cells within the lesion

Fig. 21a-f. Poorly differentiated hepatocellular carcinoma with USPIO. On the precontrast T2-weighted image (a), a well-defined, round, slightly hyperintense nodule (arrow) is visible, while on the GRE Tl-weighted sequence the lesion appears homogeneously hypointense (b). The dynamic evaluation after bolus injection of USPIO (c-e) reveals weak uptake of contrast medium, which is slightly more evident in the equilibrium phase (e). On a T2-weighted image acquired during the delayed liver specific phase after USPIO administration (f) the hepatocellular carcinoma appears hyperintense due to the lack of Kupffer cells within the lesion

Fig. 22a-c. Hepatocellular carcinoma. The precontrast GRE T1-weighted image (a) reveals a small, well-defined hypointense nodule (arrow). The lesion (arrow) appears slightly hyperintense on the T2-weighted image (b). On the hepatobiliary phase image after Mn-DPDP administration (c) the nodule appears homogeneously hypointense compared to the surrounding normal liver parenchyma

Fig. 22a-c. Hepatocellular carcinoma. The precontrast GRE T1-weighted image (a) reveals a small, well-defined hypointense nodule (arrow). The lesion (arrow) appears slightly hyperintense on the T2-weighted image (b). On the hepatobiliary phase image after Mn-DPDP administration (c) the nodule appears homogeneously hypointense compared to the surrounding normal liver parenchyma

Hypointense Nodule Liver

Fig. 23a-c. Hepatocellular carcinoma. On both the unenhanced T2-weighted image (a) and the unenhanced Tl-weighted image (b) the nodule is slightly hypointense compared to the liver (arrows in a). The lesion is seen as strongly hyperintense on delayed phase images after mangafodipir administration (c) and no other lesions are visible

Fig. 23a-c. Hepatocellular carcinoma. On both the unenhanced T2-weighted image (a) and the unenhanced Tl-weighted image (b) the nodule is slightly hypointense compared to the liver (arrows in a). The lesion is seen as strongly hyperintense on delayed phase images after mangafodipir administration (c) and no other lesions are visible

Fig. 24a, b. Hepatocellular carcinoma. The same case as presented in Fig. 23. In the arterial phase after the bolus administration of Gd-BOPTA (a), the lesion shows intense enhancement. Another small satellite nodule can be seen only in this phase of contrast enhancement (arrowheads). In the portal-venous phase (b) the larger lesion is seen as mildly hypointense with a slightly hyperintense rim, while the smaller lesion cannot be seen

Hypophysenadenom

Fig. 24a, b. Hepatocellular carcinoma. The same case as presented in Fig. 23. In the arterial phase after the bolus administration of Gd-BOPTA (a), the lesion shows intense enhancement. Another small satellite nodule can be seen only in this phase of contrast enhancement (arrowheads). In the portal-venous phase (b) the larger lesion is seen as mildly hypointense with a slightly hyperintense rim, while the smaller lesion cannot be seen

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