Metastases

Metastases are the most common malignant focal liver lesions in the non-cirrhotic liver. However, metastases are relatively uncommon in the cirrhotic liver where HCC is more frequent. The liver is second only to regional lymph nodes as a site of metastatic disease; autopsy series of patients with primary tumors indicate that at the time of death, approximately 50% of patients have metastatic disease of the liver [78]. Although metastases can develop in the liver via hematogenous spread from most solid tumors, certain primary neoplasms are a particularly virulent cause of liver-dominant disease and often isolated liver metastases. These include colorectal cancer and neuroendocrine tumors, gastrointestinal sarcomas, uveal melanomas and other neoplasms [30].

The gross features of liver metastases vary. Lesions may be expansive, infiltrative, surface-spreading, or miliary, depending on the origin of the primary tumor. Within each of these categories, metastatic lesions may be massive, nodular, or diffuse and may range in size from less than 1 mm to many centimeters in diameter. Metastases from colon carcinoma usually appear as a few large nodules with central umbilication. Nodules from breast or lung carcinoma have an early central umbilication. Metastatic lesions of the miliary type are seen more frequently from breast, prostate or stomach cancers. Microscopically, metastases resemble the primary tumors. Fibrous reaction to the metastatic tumor is common in breast and pancreatic carcinomas, while a "fish flesh" texture is common in cellular and undiffer-entiated tumors such as small cell cancer, adeno-carcinoma of the lung, non-Hodgkin's lymphoma, some sarcomas, and melanoma [30,56]. Clinically, hepatomegaly is the most common finding, followed by ascites, jaundice, and varices [21].

On US, metastases to the liver usually take on one of the following appearances: hypoechoic, mixed echogenicity, target pattern, hyperechoic, cystic, heterogeneous or coarse echo texture without focal mass [3]. Most metastatic lesions exhibit a hypoechoic halo. This hypoechoic halo is composed of compressed normal liver parenchyma,

Coarse Texture LiverLeslie Mahaffy

Fig. 39a-g. Primary hepatic lymphoma. The pre-contrast T2-weighted TSE image (a) shows a huge, heterogeneous, well-defined, hyperintense mass (asterisk) located in the right lobe of the liver. The lesion appears hypointense on the corresponding unenhanced GE T1-weighted image (b). On VIBE images during the dynamic evaluation after the bolus administration of Gd-BOPTA the mass becomes hetero-geneously hyperintense in the arterial phase (c), with progressive enhancement and heterogeneous isointensity in the portal-venous (d) and equilibrium (e) phases. On hepatobiliary phase images (f, g) the lesion is hypointense with hyperintense fibrous septa (arrowheads)

Fig. 40a-e. Hodgkin's disease of the liver. Unenhanced T2-weighted images (a) reveal a slightly hypointense to isointense lesion (arrow) in the right liver lobe. On unenhanced T1-weighted images (b), this lesion is clearly hy-pointense compared to the surrounding liver parenchyma. On arterial phase imaging after the bolus administration of Gd-BOPTA (c) the lesion demonstrates hypovascularity with subsequent enhancement in the portal-venous phase (d). During the equilibrium phase (e) the lesion is isointense compared to surrounding liver parenchyma due to diffuse infiltration

new proliferating tumor edema, and a rim of hy-pervascularity in the periphery of the lesion (Fig.

41). In addition to a halo, metastases may take on a target or bull's-eye appearance due to alternating layers of hyper- and hypoechoic tissue (Fig.

42). These three patterns are highly suggestive for malignancy [79]. Hypoechoic metastases tend to be hypovascular, and can be secondary to lymphoma, melanoma, breast or lung carcinoma. Hy-perechoic metastases in many cases correspond to hypervascular lesions, and frequently arise from colon, renal, breast, and islet cell carcinomas (Fig.

43). Cystic metastases are rare, and include those from sarcomas, ovarian cancer (Fig. 44), colon cancer, and squamous cell carcinoma. Calcified metastases derive frequently from mucinous ade-nocarcinomas of the colon (Fig. 45), pancreas and ovary [79].

Liver metastases reveal neoangiogenetic phenomena. Microvessels are detected within the tu mor, while macrovessels are rare within the lesion but are commonly found at the periphery of the nodules. The blood supply derives predominantly from arterial vessels rather than from the portal-venous system. Vascularization in general appears to be more conspicuous in small, non-necrotic nodules.

While color and power Doppler can demonstrate peripheral circulation of the lesions, detection of vascularization within the lesion is relatively rare.

Contrast-enhanced US in the arterial filling phase reveals that virtually all secondary lesions have an inflow that varies depending on the nature of the primary tumor and the presence of necrosis. A peripheral ring-shaped enhancement occurs in the arterial and portal-venous phases in about 50% of metastases with a diameter of less than 3 cm. Virtually all metastases have a hypoechogenic appearance in the portal-venous and late phases,

Ultrasound Breast Hyperechoic Halo
Fig. 41. Metastases with halo pattern. Ultrasound reveals a hy-perechoic lesion (asterisk) surrounded by a regular hypoechoic rim (arrowheads). Another metastatic homogeneous hypoechoic nodule (arrow) coexists in the same patient

compared to the surrounding normal liver parenchyma (Fig. 46) [5].

Contrast-enhanced CT is widely used in the follow-up of secondary hepatic lesions. Since the majority of liver metastases are supplied by the hepatic artery and do not have a significant vascular supply from the portal system, most metastases are hypovascular relative to the normal liver parenchyma. These metastases nearly always demonstrate decreased attenuation compared to normal liver parenchyma on unenhanced CT scans. Non-contrast CT imaging is helpful for detecting calcifications, necrosis and hemorrhage within lesions, which occur in many types of metastases, most frequently from colon and ovarian cancers [79]. Hypovascular metastases are best seen during the portal-venous phase of contrast

Fig. 42. Metastases with bull's-eye pattern. Ultrasound reveals two large nodular lesions (asterisks) with hyper- and hypoechoic peripheral layers (arrowheads)

enhancement following the administration of contrast material when the normal liver parenchyma is maximally enhanced (Fig. 47) [55]. Hypovascu-lar metastases most commonly arise from colon, stomach, pancreas, lung, breast, and cervix neoplasms.

On the other hand, hypervascular metastases tend to be more vascular than normal liver parenchyma and are best seen during the arterial phase of contrast enhancement when they are maximally enhanced. During the portal-venous phase these lesions are often isodense compared to the normal liver and are difficult to detect (Fig. 48). Metastases of this type include those derived from renal cell carcinoma, breast carcinoma, islet cell tumors, melanoma and sarcomas, pheochromocytoma, carcinoid and thyroideal carcinoma [8].

Regardless of the hypo- or hypervascular nature of the lesion, some experts consider that arterial phase imaging is essential for the visualization of metastases smaller than 1 cm in size. This is due to the fact that the predominant blood supply derives from the hepatic artery in small lesions [38]. Since small tumors do not usually outgrow their blood supply, they generally do not have necrotic, and thus hypovascular, central areas. Furthermore, visualization of the hyperdense rim of typical hy-povascular lesions, such as colon carcinoma metastases, is frequently best achieved during the arterial phase [13]. The equilibrium phase, however, enables an evaluation of enhancement pattern and contrast wash-out and is thus important for lesion characterization. In this phase some metastases show central pooling and peripheral washout due to desmoplastic reaction and peripheral edema (Fig. 49).

The signal intensity of metastases varies con-

Melanoma Mets Haemangioma Spine Mri
Fig. 43. Hyperechoic metastases from renal cancer. A large lobu-lated, homogeneous, hyperechoic nodule simulating a hemangioma can be seen in liver segment VII (asterisk)
Nodules Liver Ultrasound

Fig. 42. Metastases with bull's-eye pattern. Ultrasound reveals two large nodular lesions (asterisks) with hyper- and hypoechoic peripheral layers (arrowheads)

Mri Images Shadow Liver
Fig. 44. Cystic metastases from ovarian cancer. An anechoic nodule with slighty irregular margins (asterisk) is surrounded by a thick hyperechoic and a thin hypoechoic rim
Fig. 45. Calcified metastases from colon cancer. Ultrasound reveals a nodular lesion with irregular margins (arrows) and numerous small calcifications with acoustic shadow
Bulls Eye Lesion Liver Ultrasound

Fig. 46a-d. Metastasis from breast cancer. The pre-contrast US scan (a) reveals a heterogeneous, slightly hypoechoic nodule (arrowheads), located in segment VII of the right liver lobe. In the arterial phase of the dynamic evaluation after SonoVue® administration (b) the lesion shows homogeneous enhancement and a thin peripheral hyperechoic rim (arrow). Conversely, the lesion appears heterogeneously hypoechoic in the portal-venous (c) and equilibrium phases (d)

Fig. 46a-d. Metastasis from breast cancer. The pre-contrast US scan (a) reveals a heterogeneous, slightly hypoechoic nodule (arrowheads), located in segment VII of the right liver lobe. In the arterial phase of the dynamic evaluation after SonoVue® administration (b) the lesion shows homogeneous enhancement and a thin peripheral hyperechoic rim (arrow). Conversely, the lesion appears heterogeneously hypoechoic in the portal-venous (c) and equilibrium phases (d)

Metastasis Arterial Venus Phase

Fig. 47a-c. Hypovascular metastases from colon cancer. On unenhanced CT (a) a large heterogeneous hypodense lesion (asterisk) can be seen clearly. Another small ill-defined slightly hypodense lesion (arrowhead) is less clearly seen. During the arterial phase (b) the lesion shows less vascularity than the surrounding liver parenchyma. The lesions appear hypodense with increased conspicuity in the portal-venous phase (c)

Fig. 47a-c. Hypovascular metastases from colon cancer. On unenhanced CT (a) a large heterogeneous hypodense lesion (asterisk) can be seen clearly. Another small ill-defined slightly hypodense lesion (arrowhead) is less clearly seen. During the arterial phase (b) the lesion shows less vascularity than the surrounding liver parenchyma. The lesions appear hypodense with increased conspicuity in the portal-venous phase (c)

Liver Arterial Phase Washout Multiple

Fig. 48a-c. Hypervascular metastases from renal cancer. On unenhanced CT (a) no lesions are detected. During the arterial phase (b) two homogeneous hypervascular nodules (arrowheads) are seen. The nodules are isodense on the portal-venous phase image (c)

siderably on MR, depending on the degree of vas-cularity, necrosis, and hemorrhage. Generally, on unenhanced T1-weighted images metastases have low signal intensity compared to the surrounding parenchyma, but may demonstrate increased signal intensity whenever intralesional hemorrhage is present. On T2-weighted images, metastases usually demonstrate high signal intensity relative to the surrounding liver parenchyma, although the signal intensity is generally lower than that typically observed in hemangiomas and cysts. The presence of coagulative necrosis, fibrous tissue or calcifications decreases the signal intensity on T2-weighted images, while colliquative necrosis or edema leads to an increase of signal intensity (Fig. 50). For metastases from adenocarcinomas, a characteristic "doughnut" or "target" sign is often seen on T2-weighted images, in which a central hy-pointense area corresponding to necrosis is surrounded by a less hypointense area corresponding to the growth margins of the tumor.

During the arterial phase after the administration of an extracellularly-distributed contrast agent, weak peripheral heterogeneous enhancement can usually be seen, while nodular or globular enhancement patterns are rarely seen (Fig. 50). A hypointense rim caused by edema may delineate the lesion in the portal-venous and equilibrium phases (Fig. 51). Often, larger metastases demonstrate heterogeneous enhancement due to the presence of non-enhancing central necrotic areas (Fig. 50). On equilibrium phase T1-weighted images, lesions are typically heterogeneously hypointense, often with a characteristic "target", "halo", "peripheral wash-out" or "doughnut" appearance (Fig. 51). Hypervascular metastases are usually hypo- to isointense on unenhanced T1-weighted images and tend to reveal strong transient enhancement in the arterial phase followed by isointensity in the portal-venous and equilibrium phases (Fig. 52) [60].

The use of contrast agents with liver-specific properties is generally considered appropriate for both the detection and diagnosis of metastases. Both positive and negative contrast agents significantly improve detection capability compared to spiral CT [12,33,85,91]. Dual contrast agents such as Gd-BOPTA and Gd-EOB-DTPA, which have both extracellular and hepatobiliary properties, enable improved characterization that can be particularly important in cases where benign and malignant lesions coexist in the same patient (Fig. 53).

On dynamic phase images the pattern of enhancement seen after Gd-BOPTA or after bolus injection of another Gd-chelate may provide useful information on the extent of tumor vasculariza-tion, and thus aid in tumor characterization (Fig. 54). Lesion detectability can also be improved on MR by the acquisition of liver-specific delayed scans after administration of Gd-BOPTA or other liver-specific contrast agents. The greatest improvement in detection has been observed for metastases smaller than 1 cm in diameter (Figs. 55,56) [89].

With mangafodipir trisodium, metastases usually appear hypointense against a strongly enhanced normal liver (Fig. 57) [101]. In some cases, it is possible to observe a rim of peripheral enhancement surrounding the metastasis, which can be useful for discriminating metastases from other liver lesions such as cysts and hemangiomas [85]. Unfortunately, metastases from neuroendocrine tumors may show enhancement after mangafodipir trisodium. Moreover, some heman-giomas may be confused with metastases, due to the low signal intensity on T2-weighted images and hypointensity on delayed hepatobiliary phase T1-weighted images (Fig. 58).

SPIO contrast agents are particularly helpful for lesion detection. Due to the absence of Kupffer cells, metastases generally do not show significant signal drop after SPIO administration and thus appear as hyperintense nodules against a darkened normal liver (Fig. 59). However, the lack of a dynamic imaging capability means that SPIO agents often present the same problem as mangafodipir trisodium when the need is to differentiate between metastases and coexisting benign lesions. To a certain extent this problem, inherent to SPIO agents, may be overcome by USPIO agents for which both dynamic and late phase imaging is possible. Dynamic T1-weighted evaluation after SH U 555 A administration may reveal enhancement of liver metastases, most frequently at the periphery on arterial phase images (Fig. 60) [33].

Central Peripheral Phenomenon
Fig. 49a, b. Metastases with central pooling from colon cancer. The unenhanced CT scan (a) shows numerous ill-defined hypodense nodules (arrows). In the equilibrium phase (b) the nodules demonstrate central contrast agent pooling and peripheral wash-out (arrowheadss)
Mri Images Liver Cancer

Fig. 50a-d. Metastases from gallbladder cancer. On the unenhanced Turbo SE T2-weighted image (a) and the GE T1-weighted image (b) the nodules (arrowheads i n a) appear heterogeneously hyperintense and hypointense, respectively. Some nodules are confluent resulting in a large mass (asterisk). During the arterial phase after contrast agent administration (c) peripheral enhancement is evident in many nodules. These nodules are more conspicuous during the portal-venous phase (d)

Fig. 50a-d. Metastases from gallbladder cancer. On the unenhanced Turbo SE T2-weighted image (a) and the GE T1-weighted image (b) the nodules (arrowheads i n a) appear heterogeneously hyperintense and hypointense, respectively. Some nodules are confluent resulting in a large mass (asterisk). During the arterial phase after contrast agent administration (c) peripheral enhancement is evident in many nodules. These nodules are more conspicuous during the portal-venous phase (d)

Mri Venous Phase

Fig. 51a-e. Hypovascular metastases from colon cancer. The unenhanced SE T2-weighted image (a) and the GE T1-weighted image (b) reveal two heterogeneous hyperintense and hypointense lesions (arrows) in segments IV and VIII. The arterial phase image (c) reveals poor and heterogeneous enhancement of the larger lesion. A low intensity peripheral rim due to hepatic parenchymal edema is also apparent. In the portal-venous phase (d), both lesions remain hypointense compared with normal liver tissue. The equilibrium phase image (e) reveals irregular enhancement in the larger lesion and peripheral enhancement of the smaller lesion

Vicarious Excretion Contrast Mri

Fig. 52a-d. Hypervascular metastases from gastrinoma. On the unenhanced Turbo SE T2-weighted image (a) the nodule (white arrow) is seen as homogeneously hyperintense with distinct borders. The GE T1-weighted image (b) reveals a sharply demarcated, hypointense lesion with homogeneous signal intensity. During the dynamic study after the administration of gadolinium contrast agent, the lesion demonstrates initial strong homogeneous hypervascularization during the arterial phase (c) followed by isointensity in the portal-venous phase (d) due to rapid wash-out

Fig. 52a-d. Hypervascular metastases from gastrinoma. On the unenhanced Turbo SE T2-weighted image (a) the nodule (white arrow) is seen as homogeneously hyperintense with distinct borders. The GE T1-weighted image (b) reveals a sharply demarcated, hypointense lesion with homogeneous signal intensity. During the dynamic study after the administration of gadolinium contrast agent, the lesion demonstrates initial strong homogeneous hypervascularization during the arterial phase (c) followed by isointensity in the portal-venous phase (d) due to rapid wash-out

Mri Images Liver Cancer

Fig. 53a-e. Detection and characterization of liver metastases from melanoma with Gd-BOPTA. On unenhanced Turbo SE T2-weighted images (a) three nodules (arrowheads) demonstrating different degrees of hyperintensi-ty can be seen. On the GE T1-weighted image (b) two of these lesions are seen as hypointense while the third small nodule (arrowhead appears slightly hyperintense. Dynamic evaluation (c, d) after Gd-BOPTA administration characterizes two lesions as hemangiomas (arrows in d), due to the presence of peripheral nodular enhancement, centripetal filling-in and complete filling-in. The metastatic lesion (arrowheadin d) shows homogeneous enhancement in the arterial phase (c) and wash-out in the equilibrium phase (d). While the metastasic lesion appears as an ill-defined hypointense nodule in the equilibrium phase, the hemangiomas are both hyperintense. Each of the lesions is seen as hypointense on the hepatobiliary phase image (e)

Fig. 53a-e. Detection and characterization of liver metastases from melanoma with Gd-BOPTA. On unenhanced Turbo SE T2-weighted images (a) three nodules (arrowheads) demonstrating different degrees of hyperintensi-ty can be seen. On the GE T1-weighted image (b) two of these lesions are seen as hypointense while the third small nodule (arrowhead appears slightly hyperintense. Dynamic evaluation (c, d) after Gd-BOPTA administration characterizes two lesions as hemangiomas (arrows in d), due to the presence of peripheral nodular enhancement, centripetal filling-in and complete filling-in. The metastatic lesion (arrowheadin d) shows homogeneous enhancement in the arterial phase (c) and wash-out in the equilibrium phase (d). While the metastasic lesion appears as an ill-defined hypointense nodule in the equilibrium phase, the hemangiomas are both hyperintense. Each of the lesions is seen as hypointense on the hepatobiliary phase image (e)

Elastofibroma Shoulder Mass

Fig. 54a-e. Hypervascular metastases from neuroendocrine pancreatic tumor. The unenhanced GE T1-weighted image (a) shows a hypointense sub-capsular nodule (arrow) with a slight retraction of the liver surface. On the HASTE T2-weighted image (b) an additional small lesion (arrows adjacent to the right hepatic vein can be depicted. Both lesions show strong homogeneous hypervascularization in the arterial phase (c) after the administration of Gd-BOPTA followed by near isointensity in the portal-venous phase (d). Hepatobiliary phase images (e) reveal much better contrast between the lesions and the surrounding parenchyma in comparison to that seen on unenhanced T1-weighted images

Fig. 54a-e. Hypervascular metastases from neuroendocrine pancreatic tumor. The unenhanced GE T1-weighted image (a) shows a hypointense sub-capsular nodule (arrow) with a slight retraction of the liver surface. On the HASTE T2-weighted image (b) an additional small lesion (arrows adjacent to the right hepatic vein can be depicted. Both lesions show strong homogeneous hypervascularization in the arterial phase (c) after the administration of Gd-BOPTA followed by near isointensity in the portal-venous phase (d). Hepatobiliary phase images (e) reveal much better contrast between the lesions and the surrounding parenchyma in comparison to that seen on unenhanced T1-weighted images

Fig. 55a-f. Metastases from endocrine tumor. A small, slightly hyperintense lesion (arrow) can be seen on the HASTE T2-weighted image (a). The lesion appears as hypointense on the unenhanced Tl-weighted image (b). On dynamic imaging after the bolus administration of Gd-BOPTA the lesion demonstrates initial enhancement during the arterial phase (c) and wash-out in the portal-venous phase (d). On the hepatobiliary phase image (e) the nodule does not show any capacity to take up Gd-BOPTA and appears hypointense. Another very small nodule (whitearrow)can be seen only in the hepatobiliary phase (f)

Fig. 55a-f. Metastases from endocrine tumor. A small, slightly hyperintense lesion (arrow) can be seen on the HASTE T2-weighted image (a). The lesion appears as hypointense on the unenhanced Tl-weighted image (b). On dynamic imaging after the bolus administration of Gd-BOPTA the lesion demonstrates initial enhancement during the arterial phase (c) and wash-out in the portal-venous phase (d). On the hepatobiliary phase image (e) the nodule does not show any capacity to take up Gd-BOPTA and appears hypointense. Another very small nodule (whitearrow)can be seen only in the hepatobiliary phase (f)

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Fig. 56a-f. Metastases from melanoma. On the unenhanced T2-weighted HASTE sequence (a) no focal lesions can be detected. Conversely, a small, well-defined hyperintense nodule with a thin hypointense rim (arrowhead) is clearly depicted on the pre-contrast GE T1-weighted "in-phase" (b) and "out-of-phase" (c) images. The nodule is isointense compared to the surrounding liver during the dynamic study after the bolus administration of Gd-BOPTA (d-e). In the hepatobiliary phase (f) the lesion (arrowhead again appears markedly hyperintense compared to the normal liver parenchyma due to presence of melanin

Fig. 56a-f. Metastases from melanoma. On the unenhanced T2-weighted HASTE sequence (a) no focal lesions can be detected. Conversely, a small, well-defined hyperintense nodule with a thin hypointense rim (arrowhead) is clearly depicted on the pre-contrast GE T1-weighted "in-phase" (b) and "out-of-phase" (c) images. The nodule is isointense compared to the surrounding liver during the dynamic study after the bolus administration of Gd-BOPTA (d-e). In the hepatobiliary phase (f) the lesion (arrowhead again appears markedly hyperintense compared to the normal liver parenchyma due to presence of melanin

Shape Liver

Fig. 58a-c. Metastases from melanoma. This figure shows the same case as Fig 53. All lesions are hypointense on the hepatobiliary phase image after the administration of mangafodipir. On the sole basis of the signal intensity on unenhanced and hepatobiliary phase images, it is difficult to distinguish metastases from hemangioma

Hypointense Nodule Liver
Fig. 59a, b. Metastases from colon cancer. Several small hyperintense nodules are demonstrated on the unenhanced Turbo SE T2-weighted image (a). After SPIO administration (b) the lesions (arrowheads) do not show a signal drop and are therefore better delineated. Additional nodules can also be seen
Mri Views Liver

Fig. 60a-f. Metastases from melanoma. On the unenhanced Turbo SE T2-weighted image (a) a small hyperintense nodule (arrow) can be seen. On the GE Tl-weighted image (b) the lesion is seen as hyperintense and well-delimited. On dynamic phase images after the bolus injection of SH U 555 A , the nodule does not show significant enhancement (c-d). On GE Tl-weighted images acquired 10 min after SH U 555 A administration (e) the signal of the parenchyma is decreased compared to that of the lesion indicating the inability of the latter to take up USPIO . On the delayed phase Turbo SE T2-weighted image (f) the lesion appears brighter and better delineated compared to the un-enhanced images

Fig. 60a-f. Metastases from melanoma. On the unenhanced Turbo SE T2-weighted image (a) a small hyperintense nodule (arrow) can be seen. On the GE Tl-weighted image (b) the lesion is seen as hyperintense and well-delimited. On dynamic phase images after the bolus injection of SH U 555 A , the nodule does not show significant enhancement (c-d). On GE Tl-weighted images acquired 10 min after SH U 555 A administration (e) the signal of the parenchyma is decreased compared to that of the lesion indicating the inability of the latter to take up USPIO . On the delayed phase Turbo SE T2-weighted image (f) the lesion appears brighter and better delineated compared to the un-enhanced images

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  • juliane
    How to read liver mri?
    2 years ago

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