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Sunday, 3 July 2011

Contrast enhanced ultrasound - CEUS

Second-generation” blood pool ultrasonographic (US) contrast media are filled with gases other than air and allow continuous real-time assessment of liver lesions at low acoustic pressure (low mechanical index).

Older Air-filled agents (first-generation US contrast media), on the other hand, can be used only with high-mechanical-index intermittent technologies because micro-bubble rupture is necessary to obtain an adequate echo signal.

1- The arterial (early) phase (15–35 seconds after injection),
2- the portal (venous) phase (35–90 seconds),
3- the sinusoidal (parenchymal or late vascular) phase (90–240 seconds).

What do we see afte injection?
Contrast medium is seen arriving in the hepatic artery and rapidly spreading through its branches. Liver parenchymal echogenicity increases consistently from the arterial to the portal phase and then decreases slightly during the sinusoidal phase. Enhancement of the branches of the hepatic artery and portal vein is readily visualized, without flow signals “bleeding” outside the vessel lumina (as happens with Doppler US). Cirrhotic liver may exhibit slightly delayed and less intense parenchymal enhancement during the portal phase.

How to describe what we see?
Echogenicity is defined with respect to the surrounding parenchymal echo levels at the same imaging time and depth. In addition, lesions can be compared with the blood pool, being hypervascular when demonstrating the same echogenicity as contrast material–enhanced vessels and hypovascular when demonstrating a lower echogenicity.


Lesion conspicuity depends on the lesion-to-parenchyma echogenicity gradient; in this case, HCC has greater conspicuity during the arterial phase and appears hyperechoic. During the portal and sinusoidal phases, the lesion is first slightly and then clearly hypoechoic relative to the surrounding parenchyma.

Enhancement may be absent (eg, cyst, small hemangioma, dysplastic nodule, or early HCC) or
may be diffuse homogeneous or diffuse heterogeneous (eg, hypervascular metastasis or atypical CCC, lymphoma, FNH).
Rim pattern manifests as peripheral, irregular but continuous arterial phase enhancement (eg, metastasis, CCC).
The globular pattern consists of discontinuous peripheral arterial phase enhancement with discrete echoic globules (eg, cavernous hemangioma). The spokelike pattern seen during the arterial phase is due to discrete arteries radiating to the periphery (eg, FNH).
The stippled pattern seen during this phase consists of discrete arteries with a chaotic distribution (eg, HCC).
The arterial phase “basket” pattern, usually seen in combination with a stippled appearance, consists of a feeding artery branching around and then within a nodule (eg, HCC).

The liver-enhancing effect of the blood pool contrast agent SonoVue (Bracco, Milan, Italy) lasts 3–5 minutes; more than 5 minutes after contrast material injection, most lesions become undetectable or have the same echogenicity as on baseline images.

Imaging techniques:
Can be divided into two main groups:(a) high-mechanical-index modalities, which allow static, intermittent imaging, and (b) low-mechanical-index modalities, which allow dynamic, continuous acquisition and require second-generation contrast media.

SonoVue: A sulfur hexafluoride–based contrast medium. This agent comes as a sterile, nonpyrogenic, lyophilized powder. A white milky suspension is obtained by adding 5 mL of 0.9% normal saline solution with an aseptic technique and vigorously shaking the mixture for 10 seconds. The reconstituted product provides 8 μL/mL of SF6 micro-bubbles, which is then administered either in its entirety (4.8 mL) or as a half dose (2.4 mL). The half dose is usually sufficient, but injecting the entire volume may be desirable in cases of liver steatosis or chronic hepatitis.

It is usually administered as a single rapid bolus injection into an antecubital vein. US is started immediately and lasts 4–5 minutes.



Liver hemangioma is a hypervascular lesion consisting of a network of vascular spaces with slow or, less commonly, rapid flow. The distribution of small arterial branches, venous lakes, and fibrosis varies. Arterial inflow is present, whereas portal afference is absent or minimal, and there is no arteriovenous fistula.

Small (<1-cm) hemangiomas are usually iso-vascular relative to the surrounding parenchyma during the arterial phase. Less commonly, a subtle, diffuse enhancement (homogeneous or heterogeneous) is seen. Larger hemangiomas (>1 cm) usually demonstrate peripheral globular pooling of contrast medium, with hyperechoic globules (nodules) becoming progressively larger and more numerous (puddle enhancement). Contrast material uptake can be fast or slow depending on intralesional circulation speed. Uncommonly, contrast material enhancement is rapid and homogeneous, simulating that of hypervascular metastases. Rarely, peripheral rimlike enhancement or diffuse homogeneous enhancement is seen (small, hypervascular hemangioma). Discrete intralesional arteries are usually not seen in hemangiomas.

(a) Baseline US image shows two homogeneously hyperechoic lesions (arrowheads) contiguous with a portal branch (arrow).

Early portal phase US image obtained 35 seconds after contrast material injection demonstrates lesion isoechogenicity. Arrow indicates an enhanced vein.

(c) Parenchymal phase US image obtained 121 seconds after injection demonstrates persistent lesion isoechogenicity.


(a) Baseline US image shows a heterogeneously hypoechoic lesion (arrow).

(b) Arterial phase US image obtained 22 seconds after contrast material injection demonstrates peripheral globular enhancement (large arrow) and a perilesional vessel (small arrow).

(c) Portal phase US image obtained 93 seconds after injection demonstrates centripetal (albeit incomplete) lesion enhancement (large arrow), which is clearly hyperechoic relative to the surrounding parenchyma. Small arrow indicates the perilesional vessel.

(d) Portal phase computed tomographic (CT) scan shows a hyperattenuating lesion with small central areas of poor enhancement (arrow).

Isovascularity persists throughout the portal and sinusoidal phases in small hemangiomas. In contrast, larger hemangiomas show progressive centripetal enlargement of peripheral hyperechoic globules with progressive filling. As the globules enlarge, they create “bridges” to the opposite side of the lesion. Centripetal filling may be absent in smaller lesions, but real-time images usually allow identification of this finding even in small, rapidly enhancing hemangiomas. Persistent strong intralesional enhancement (hyperechogenicity) is typical, although a central area or sac of persistent poor enhancement due to fibrosis may be seen in larger hemangiomas; owing to the blood pool nature of US contrast media, incomplete centripetal filling is more common at US than at CT or magnetic resonance (MR) imaging. Rarely, hemangioma shows heterogeneous hypoechogenicity (thrombosis)

Early portal phase US image obtained 43 seconds after contrast material injection shows multiple peripheral enhancing globules (large arrows) and thin enhancing septa centrally (small arrows). Although most of the lesion is hypoechoic, and was even on delayed images (not shown), the globular pattern allowed characterization.



Adenoma is a hypervascular lesion without portal tracts. Large, subcapsular tributary arteries are typical, whereas necrotic and hemorrhagic changes are frequently seen in larger masses.

Intense, rapid or slow contrast material enhancement is seen during the arterial phase. Discrete, perilesional feeding arteries manifest as enhancement around the tumor capsule; such enhancement is never seen in HCC. Heterogeneous enhancement with perfusion defects corresponding to hemorrhagic areas is present in larger masses.

More or less rapid washout is seen during the portal and sinusoidal phases, with initial hypervascularity followed by isovascularity; a hypoechoic appearance is never seen. A heterogeneous texture is seen in larger masses, with internal hypoechoic regions.

(a) Baseline US image shows a subtle hyperechoic area (arrow).

(b) Arterial phase US image obtained 21 seconds after contrast material injection demonstrates early, marked lesion enhancement (arrow). K = kidney.

(c) Portal phase US image obtained 55 seconds after injection demonstrates subtle but persistent enhancement (arrow). K = kidney.


Focal Nodular Hyperplasia - FNH

FNH is a hypervascular, hyperplastic lesion caused by preexisting vascular malformation. Patients are typically women with a history of oral contraception. FNH is not seen in patients with cirrhosis. There is usually a peripheral pseudo-capsule and a central or eccentric fibrous scar radiating to the periphery and containing arteries.

During the arterial phase, FNH manifests as a tortuous feeding artery and a central artery with very early centrifugal stellate branching (“wheel spoke” or “central spider” pattern). Immediately thereafter, during the full arterial phase, the lesion demonstrates homogeneous, intense, and very rapid contrast material enhancement. A hypoechoic central scar may be present.

(a) Baseline US image shows a slightly hypoechoic lesion (arrows).

(b) Very early arterial phase US image obtained 15 seconds after contrast material injection demonstrates rapid lesion enhancement (arrows) with discrete intralesional and perilesional arteries.

(c) Later arterial phase US image obtained 29 seconds after injection demonstrates marked homogeneous lesion enhancement (arrows).

(d) Portal phase US image obtained 49 seconds after injection demonstrates lesion isoechogenicity (arrows).

During the portal and sinusoidal phases, there is slow or, less commonly, rapid washout, with initial hypervascularity followed by isovascularity (isoechoic or hyperechoic appearance). A homogeneous texture with possible central stellate hypoechogenicity is characteristic.


(a) Baseline US image shows a homogeneous, well-defined mass (arrows) depending from the right hepatic lobe.

(b) Arterial phase US image obtained 22 seconds after contrast material injection demonstrates multiple radiating arteries within the mass (arrows).

(c) Portal phase US image obtained 56 seconds after injection demonstrates marked enhancement of the mass (white arrows), with a hypoechoic central scar (black arrow).

(d) Late arterial phase CT scan shows a markedly enhancing mass (white arrows) with central scarring (black arrow) (cf c).

The overall appearance of FNH usually allows differentiation from fibrolamellar HCC, an uncommon lesion that also contains a central scar. Fibrolamellar HCC is usually heterogeneous because of necrosis, shows internal calcification, and is hypoechoic on portal phase images.


Dysplastic Nodules and Early HCC

Dysplastic nodules are premalignant lesions within a cirrhotic liver that develop small arteries and exhibit portal tracts. Early HCC is usually a small, well-differentiated nodule with increased arterialization and gradual loss of portal vessels.

During the arterial phase, dysplastic nodules and early HCC are usually substantially isovascular with no arterial enhancement. Nevertheless, high-grade dysplastic nodules can sometimes demonstrate marked enhancement.

Dysplastic nodules and early HCC have an isoechoic or subtly hypoechogenic appearance throughout the portal and sinusoidal phases.

(a) Baseline US image shows a small, hypoechoic nodule (arrow).

(b) Arterial phase US image obtained 25 seconds after contrast material injection fails to depict any lesion.


Advanced HCC

Small to medium-sized HCC (1–5 cm) is a hypervascular lesion, with neoangiogenesis. There is little or no portal supply.
In arterial phase, advanced HCC demonstrates hyperperfusion starting immediately after enhancement of the hepatic artery. Smaller HCCs usually enhance slightly faster than larger ones.

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One or more hypertrophic feeding arteries are seen reaching lesion poles and branching intralesionally (basket pattern).

Discrete peri- and intranodular vessels are also recognizable at US, usually being dysmorphic, chaotic, and randomly stippled and having a corkscrew-shaped distribution.

Uncommon hypovascular HCC demonstrates isoperfusion or even hypoperfusion relative to the surrounding parenchyma and hence is difficult to characterize.

Areas of fatty degeneration with increased echogenicity, within the HCC do not show enhancement. Large lesions (“big” HCC) demonstrate peripheral enhancement, central hypovascular necrotic areas, and vascular lakes with hyperechoic contrast agent pooling.

During the portal and sinusoidal phases, advanced HCC demonstrates rapid washout (faster than with FNH or adenoma) and has an isovascular or, less commonly, hypovascular appearance. Transient isoechogenicity is seen on full portal phase images, eventually followed by moderate hypoechogenicity on delayed images.


Cholangiocellular Carcinoma

CCC can be hypovascular or, less commonly, hypervascular on arterial phase images, with portal phase vascularity usually being limited.

CCC demonstrates peripheral rimlike enhancement or heterogeneous enhancement during the arterial phase. Poor heterogeneous enhancement is possible, with an overall isoechoic or hypoechoic appearance.

CCC usually has a hypoechoic appearance on portal and sinusoidal phase images. Persistent subtle rim enhancement is possible. Conspicuity increases progressively, and necrotic areas with more marked hypoechogenicity may be seen. Satellite lesions may also be encountered.



Liver metastasis can be hypo- or, less commonly, hypervascular on arterial phase images depending on the organ of origin. All metastases show some degree of arterial neoangiogenesis (peripheral macrovessels and central microvessels) and lack at least a portion of the portal supply.

During the arterial phase, liver metastasis shows peripheral rimlike enhancement of varying thickness and uniformity, with an eventual target-like appearance.

There is always some kind of arterial inflow peripherally, even if subtle and heterogeneous, whereas most of the lesion is isoechoic relative to the surrounding parenchyma. Perilesional hyperemia with arterial phase–dependent enhancement of normal tissue is possible, and few discrete perilesional arteries can be found. Macroscopic arteries are usually not seen within the lesion.

There is no centripetal filling during the portal and sinusoidal phases. Subtle rim enhancement may persist. Washout is rapid; lesions are seen as filling defects that progressively increase in conspicuity relative to normal parenchymal enhancement (black holes on a bright background).

Metastases have a heterogeneously hypoechoic appearance with internal echo pollution due to microbubbles and haphazard movement within abnormal small tumor vessels (microcirculation).

Markedly hypoechoic areas within larger lesions are due to necrosis. Less commonly, hypervascular metastases may become isoechoic (undetectable) during this phase.



Primary and secondary liver lymphomas are hypercellular lesions with some degree of arterial neoangiogenesis and a poor portal supply.

Like metastasis, lymphoma demonstrates peripheral rimlike enhancement of varying thickness and uniformity during the arterial phase, with an eventual targetlike appearance. Intense, diffuse heterogeneous enhancement is rarely noted.

Like metastasis, lymphoma demonstrates no centripetal filling during the portal and sinusoidal phase. Washout is rapid, and lymphoma has a heterogeneous hypoechoic appearance with internal echo pollution (microcirculation) that progressively increases in conspicuity.



Pyogenic and amoebic liver abscesses have a variable degree of liquefaction and loculation. Their vascularity depends on the evolution stage.

Liver abscesses, especially pyogenic abscesses, have an overall coalescent appearance with a sharply defined necrotic cavity. Rim enhancement is typical. Discrete arteries are noted running along lesion margins and internal septa, with persistent enhancement of the septa. Internal enhancement is absent, and there is no microcirculation within fluid or necrotic components. Perilesional hyperemia with arterial phase–dependent enhancement of normal tissue can be seen.

During the portal and sinusoidal phases, abscesses demonstrate rapid (or sometimes slower) washout, an overall hypoechoic appearance, and marked necrotic and fluid areas internally.


Peliosis Hepatis

Peliosis hepatis is characterized by multiple blood-filled spaces ranging from 1 mm to 4–5 cm within the hepatic parenchyma.

During the arterial phase, peliosis hepatis shows a transient “fast surge” central echo enhancement that is synchronous with vessel enhancement.

During the portal and sinusoidal phases, peliosis hepatis demonstrates isoechogenicity or hypoechogenicity with no contrast material pooling or centripetal filling, allowing differentiation of this entity from hemangiomatosis.


Focal Steatosis

Focal areas of fatty infiltration may have a round, lesionlike appearance and are hyperechoic on conventional US images. Vascularity is normal.

During the arterial phase, focal steatosis demonstrates substantial isovascularity but no arterial enhancement, with normal vessels traversing the pseudolesion without mass effect.

Isovascularity persists during the portal and sinusoidal phases, with normal vessels still traversing the pseudolesion without mass effect.


Skip Area in Fatty Liver

Focal regions of spared normal parenchyma within a heterogeneously distributed steatosis may have a round, pseudolesional appearance and are hypoechoic at baseline US. The vascularity of these spared areas is normal.


Contrast-enhanced US has an 89% sensitivity and a 100% specificity in the diagnosis of hemangioma. The capability of this modality to characterize hemangiomas is approximately equal to that of MR imaging, even in small lesions. Peripheral globular enhancement with centripetal filling indicates a hemangioma, even if central enhancement is subtle or absent on portal and sinusoidal phase images. Centripetal filling is not seen in malignancies. Peripheral enhancement followed by centripetal enhancement has a 100% specificity but only an 18% sensitivity for hemangioma. Globular peripheral enhancement is found in 70%–92% of hemangiomas, rimlike peripheral enhancement in 10%–25%, and diffuse homogeneous enhancement in 5% . Peripheral nodular enhancement with contrast material filling and absence of intralesional arteries has showed an 88% sensitivity and a 99% specificity for hemangioma. Peripheral or diffuse contrast material pooling is typical for hemangioma, with a 76.5% sensitivity and a 100% specificity.

Contrast-enhanced US has a 94% sensitivity and a 93% specificity in the diagnosis of HCC and has proved sensitive in demonstrating HCC vascularity. In one series, contrast-enhanced US demonstrated vascularity in 91% of HCC nodules, CT in 93%, and angiography in 88%. Contrast-enhanced US is more sensitive than Doppler US in this setting. In one study, color Doppler US demonstrated blood flow in 87% of HCC nodules that were hypervascular at contrast-enhanced US; in another series, power Doppler US demonstrated vascularity in 69% of HCC nodules that were identified at angiography-assisted CT, whereas contrast-enhanced US showed vascularity in 96%.

HCC is typically hypervascular on arterial phase images but never exhibits rim or globular enhancement. Enhancement is homogeneous in 50% of cases and heterogeneous in 50%. Diffuse lesion enhancement on early arterial phase images indicates HCC, especially when followed by rapid washout. If a diffuse or mosaic-like arterial phase enhancement pattern or a reticular parenchymal phase enhancement pattern is regarded as indicating HCC, contrast-enhanced US has a 92% sensitivity and a 96% specificity for this entity. The presence of intratumoral vessels on arterial phase images combined with homogeneous or heterogeneous enhancement on portal phase images has a 95% sensitivity and a 94% specificity for HCC. The presence of arteries spreading into the lesion together with homogeneous hyperechoic tumor enhancement has an 83% sensitivity and a 94% specificity for HCC.

Arterial phase enhancement with slow deenhancement suggests adenoma or FNH instead of HCC. HCC and FNH can be distinguished on the basis of several distinctive morphologic features. FNH is homogeneous, even when large, whereas HCC tends to develop necrotic areas. Moreover, FNH is usually hyperechoic during the portal phase of enhancement, whereas HCC becomes iso- or hypoechoic. Central stellate enhancement has a specificity of 100% but a sensitivity of only 67% for FNH.

Contrast-enhanced US has a sensitivity of 77% and a specificity of 93% in the diagnosis of metastases. This modality is more sensitive than conventional US in detecting liver metastasis and almost as sensitive as CT or MR imaging. In one series, conventional US helped detect 59% of liver metastases seen at CT, whereas contrast-enhanced US helped detect 97%. In another study, the number of lesions detected rose from nine to 19 when contrast-enhanced US was used in addition to conventional US; contrast-enhanced US in particular allowed detection of small metastases. Contrast-enhanced US has been shown to help detect 90% of liver metastases that are visualized at ferumoxides-enhanced MR imaging.

Peripheral rim enhancement strongly suggests metastasis, especially if it is not followed by lesion filling and is not combined with a finding of intralesional vessels. Rim enhancement has been observed in 48%–70% of liver metastases. Rim enhancement, a clear parenchymal phase defect, or both can be used to diagnose metastasis or CCC with a 90% sensitivity and a 95% specificity. Of course, hypervascular metastases overlap with other benign and especially malignant hypervascular lesions, although general context and a clearly hypoechoic appearance during the portal phase generally allow differentiation.

Aside from its arterial phase appearance, a homogeneously hypoechoic lesion on portal or sinusoidal phase images should be considered malignant until proved otherwise, since benign lesions are iso- or hyperechoic during these phases. A clearly hypoechoic lesion on portal or sinusoidal phase images is usually considered to represent metastasis. The differential diagnosis of enhancement defects includes lesions such as lymphoma, CCC, HCC, dysplastic nodules in chronic liver disease (rarely), and abscess. The constellation of contrast-enhanced US findings in pyogenic abscess has been shown to be effective in differentiating this benign entity from metastasis.

In itself, the arrival time of contrast medium cannot be used to distinguish between benign and malignant lesions; early arrival is only 67% sensitive and 60% specific for malignancy.