Role of Contrast Enhanced
Ultrasonography in Characterization
of Hepatic Diseases
DR MUHAMMAD BIN ZULFIQAR
PGR III FCPS Services institute of Medical
Sciences/ Services Hospital Lahore
AIMS
• To assess whether characterization of solid
focal liver lesions could be improved by CEUS
as compared with lesion with preliminary Gray
Scale and Color Doppler US.
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in Focal Liver Lesions at
Microbubble-enhanced US. RadioGraphics 2004; 24:921–935
Contrast Agents
• US contrast agents consist of microbubbles of air
or perfluorocarbon gas stabilized by a protein,
lipid, or polymer shell (1).
• The bubbles are sufficiently small and stable to
traverse the pulmonary and cardiac circulations
following peripheral venous injection.
• The bubbles are approximately the same size as
red blood cells and cannot move through the
vascular endothelium into the interstitium, even
after an extended period of time (2)
(1)Solbiati L, Martegani A, Leen E, Correas JM, Burns PN, Becker D. Contrast-enhanced ultrasound of liver diseases. Milan, Italy: Springer, 2003
(2).Becher H, Burns PN. Handbook of contrast echocardiography. Berlin, Germany: Springer, 2000. Available at:
http://www.sunnybrook.utoronto.ca/EchoHandbook/.
Dose of Contrast Agent
• A typical contrast material dose for an adult
patient consists of 0.2–2 mL of a suspension of
bubbles in saline solution. This dose is
manually injected into an arm vein, followed
by a flush of 5 mL of saline solution.
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in Focal Liver Lesions at
Microbubble-enhanced US. RadioGraphics 2004; 24:921–935
Bubble Specific Imaging
• Bubbles respond to the sound emitted by the imaging
transducer by changing their size in sympathy with the
US pressure wave, which results in their radial
oscillation at the US frequency.
• Bubbles have a natural or resonant frequency, at which
their response is greatly enhanced.
• Bubbles of the size range (diameter of 3–5 um)
resonate at diagnostic US frequencies and are required
for transpulmonary passage following intravenous
injection
• It is this phenomenon that makes contrast-specific
imaging possible.
Powers JE, Burns PN, Souquet J. Imaging instrumentation for ultrasound contrast agents. In: Nanda NC, Schlief R, Goldberg
BB, eds. Advances in echo imaging using contrast enhancement. 2nd ed. Dubai, United Arab Emirates: Kluwer Academic
Publishers, 1997; 139–170.
• Graph illustrates
microbubble behavior in
an acoustic field. Bubbles
respond asymmetrically
to high-intensity sound
waves, stiffening when
compressed and yielding
when expanded, a
nonlinear response that
produces harmonics in
the scattered wave.
Burns PN, Wilson SR, Hope Simpson D. Pulse inversion imaging of liver blood flow: improved method for characterizing focal
masses with microbubble contrast. Invest Radiol 2000; 35:58–71.
Principles of CEUS Imaging
• Harmonic Imaging (rarely used)
– Frequencies that are multiples of the driving
frequency
• Pulse Inversion / Phase Inversion Imaging /
Coherent Contrast Imaging (commonly used)
– the echo from tissue is suppressed and that from
the microbubble contrast material is enhanced
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in
Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004; 24:921–935
MI (Mechanical Index)
• (the MI is the ratio of the peak rarefactional
pressure to the square root of the frequency
and is related to the tendency of the sound to
induce bubble motion.
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in
Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004; 24:921–935
Low Mechanical Index <0.2
• At a low MI (less than about 0.2, depending
on the agent used), bubbles are stimulated
into harmonic motion and can be imaged in
real time,
• shows vessel morphology and the evolution of
the vascular volume over time.
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in
Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004; 24:921–935
High Mechanical Index >0.3
• Higher MI (greater than about 0.3, again depending on
the agent), the oscillation of the bubbles becomes so
pronounced that the bubbles can be disrupted by the
sound beam used to image them.
• So they emit a strong, highly nonlinear echo that is
relatively easy to detect.
• Highly sensitive “vascular volume” image.
• this “disruption” method of imaging does not allow
real-time frame rates, yet it is the most sensitive means
of evaluating the vascular volume in tissue.
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in
Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004; 24:921–935
Combination of MI Values
• Both High(>0.3) and Low(<0.2) MI values are used in
combination in to image capillary flow in
myocardium (1), liver (2) and other organs (3) .
(1) Becher H, Burns PN. Handbook of contrast echocardiography. Berlin, Germany: Springer, 2000. Available at:
http://www.sunnybrook.utoronto.ca/ EchoHandbook/.
(2) Wilson SR, Burns PN. Liver mass evaluation with ultrasound: the impact of microbubble contrast agents and pulse
inversion imaging. Semin Liver Dis 2001; 21:147–159.
(3) Missouris CG, Allen CM, Balen FG, Buckenham T, Lees WR, MacGregor GA. Non-invasive screening for renal artery
stenosis with ultrasound contrast enhancement. J Hypertens 1996; 14:519–524.
• Baseline conventional US image obtained with a high
mechanical index (MI) of 1.2 [1]) shows a large, highly
echogenic focal mass with a hypoechoic rim. The
echogenicity of the lesion is related to its tissue
properties. (b) Pulse inversion US image (MI 0.1)
shows suppression of the tissue echoes. The entire
image now appears black
Continued
•
On an arterial phase US image obtained moments after a small (0.1-mL) bolus
injection of a suspension of microbubbles into a peripheral vein, the lesion
enhances far more than the adjacent liver, a finding that is consistent with a
hypervascular mass. The microbubbles within the vasculature now account for the
echogenicity of the lesion. (d) Portal venous phase US image shows enhancement
of the liver parenchyma. The lesion is less echogenic than the liver (ie, has
“washed out”), a finding that is consistent with a hypervascular malignancy.
Hepatocellular carcinoma (HCC) was confirmed at biopsy.
CEUS in Hepatocellular Carcinoma
• Although many malignant liver tumors are readily
seen at US, surveillance US can be difficult in
patients with chronically diseased livers who are
at risk for HCC.
• In addition, nonenhanced US has low specificity
because a variety of nonmalignant lesions such as
hemangioma, FNH, and regenerative nodules
may appear similar to HCC.
• In many cases, CT or MR imaging is required for
further characterization.
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in
Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004; 24:921–935
CEUS in Hepatocellular Carcinoma
• The addition of microbubble contrast agents
has greatly improved the ability to diagnose
HCC with US. Hypervascularity with frequent
vessel dysmorphology and washout during the
portal venous phase are characteristic
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in
Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004; 24:921–935
Pitfalls
• Problems with adequately scanning the entire
cirrhotic liver because of its small size.
• Difficulty in differentiating regenerative
nodularity from malignant tumors,
• Problems related to the alteration of liver blood
flow in cirrhosis, including increased relative
hepatic arterial supply.
• All these are also encountered in MRI and CT
Hepatobiliary Imaging.
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in
Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004; 24:921–935
• (Right) Arterial phase US image shows a lesion
whose echogenicity exceeds that of the liver, a
finding that is consistent with a hypervascular mass.
There is a central nonenhancing area that suggests
scar or necrosis. (Left) On a portal venous phase US
image, the lesion is washed out, appearing less
echogenic than the adjacent liver.
Continued
• Arterial phase (right) and portal venous phase
(Left) CT scans show the hypervascular mass
with necrosis and with washout on the portal
venous phase image.
• This was proved to be HCC
• Small HCC. (Right) Arterial phase US image
shows a hypervascular lesion with avid
enhancement. (Left) On a portal venous phase
US image, the lesion is hypoechoic relative to the
enhanced background liver. This washout is
strongly suggestive of the malignant nature of the
mass.
CEUS in Metastasis
• Contrast-enhanced US shows lesion blood flow in
metastases as a reflection of the vascularity of the
primary tumor.
• Considerable variation is seen during the arterial phase
of enhancement.
– Hypovascular
– Hypervascular
• Regardless of their appearance during the arterial
phase, however, metastases have consistently shown
less enhancement than the liver during the portal
venous phase of contrast-enhanced US.
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in
Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004; 24:921–935
Hpovascular Metastasis
• Hypovascularity and rim enhancement (Fig 9),
both typical of metastatic lesions, including
those from the breast, lung, and colon.
• Tumor enhancement may be inhomogeneous
because of necrosis.
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in
Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004; 24:921–935
• Figure 9. Metastasis from primary carcinoma of
the anal canal with rim enhancement. Baseline
US (right) image shows an expansive mass in the
left lobe of the liver. (mid) Arterial phase US
image demonstrates the mass with rim
enhancement. (Left) On a portal venous phase
US image, the lesion is completely washed out
and appears black.
• Figure 9. Metastasis from primary carcinoma of the anal canal
with rim enhancement. (a, b) Baseline US (a) and CT (b) images
show an expansive mass in the left lobe of the liver. (c, d) Arterial
phase US (c) and CT (d) images demonstrate the mass with rim
enhancement. (e) On a portal venous phase US image, the lesion is
completely washed out and appears black. (f) Portal venous phase
CT scan shows continued rim enhancement of the tumor, a finding
that probably represents interstitial contrast material.
Hypervascualr Metastasis
• Hypervascular primary tumors, including
those from the kidney and thyroid gland and
those of neuroendocrine origin, show
hypervascular metastases with enhancement
features that overlap with those of HCC (Fig
10
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in
Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004; 24:921–935
• Hypervascular metastases from carcinoid tumor. (Right)
Baseline US image shows the liver with high fat content
and hypoechoic lesions. (Mid) On an arterial phase US
image, the lesions enhance avidly, appearing more
echogenic than the adjacent liver. (Left) On a portal venous
phase US image, the liver remains brightly enhanced, and
the lesions have washed out and appear hypoechoic. The
patient was allergic to iodinated contrast material.
Wilson SR, Burns PN. Liver mass evaluation with ultrasound: the impact of microbubble contrast agents and
pulse inversion imaging. Semin Liver Dis 2001; 21:147–159.
Hemangioma
• Hemangioma is the most frequently encountered benign liver
tumor and is reported to occur in 5%–20% of the population.
• Contrast enhanced US use to confirm the nature of a
hemangioma that is incidentally detected at nonenhanced US.
• Lesions show peripheral puddles and pools of enhancement
that expand in a centripetal pattern during the portal venous
phase and beyond, often progressing to complete fill-in of the
lesion (Fig 11).
• Sustained enhancement, in which the lesion has an
echogenicity equal to or greater than that of the liver through
the portal venous phase and beyond is requisite to confident
diagnosis.
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in
Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004; 24:921–935
• Hemangioma. (Right) Baseline conventional US
image shows a heterogeneous, bulbous, slightly
exophytic lesion that extends from the posterior
right lobe. (Left) Early arterial phase vascular US
image shows no linear vessels. There is peripheral
nodular enhancement.
Continued
• (Right) Late arterial phase US image shows
centripetal progression of the enhancement.
(Left) On a portal venous phase US image, the
lesion appears uniformly enhanced and brighter
than the background liver. This sustained
enhancement is consistent with a benign
condition
• Rapidly enhancing hemangioma in a patient with
known neuroendocrine tumor. Baseline US failed to
show a mass that had been detected previously at CT
performed as part of a metastasis survey. Sequential
arterial phase US images obtained over a 2-second
interval show a thin rim of marginal enhancement
(right), peripheral nodular enhancement (Left) and Continued
• Centripetal progression of enhancement to
complete fill in the lesion (Right). (Left) Arterial
phase CT scan shows a brightly enhancing mass.
Both images showing a hypervascular mass. The
peripheral nodular enhancement and the
centripetal progression of enhancement are
appreciated only on the US images.
• Hemangioma. Arterial phase US image (right)
and CT scan (left) show classic features of
hemangioma, with bright peripheral nodules
and a typical bridge across the lesion with
pools of contrast material along its margins.
Focal Nodular Hyperplasia
• FNH is not a tumor but a hyper plastic liver lesion.
• FNH differentials include hypervascular masses such as
HCC and its fibrolamellar variety.
• Noninvasive confirmation of FNH without the need for
liver biopsy is important.
• Like HCC, FNH manifests as a hypervascular liver mass
during the arterial phase of contrast-enhanced US.
• However, the specific morphologic features of these
two entities during the arterial phase are often
different. FNH is uniformly enhanced without the
frequent occurrence of necrosis and heterogeneity
seen in HCC.
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow
Patterns in Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004;
24:921–935
Continued
• Figure 14. FNH. (a) Sagittal conventional US
image shows a fatty liver with an expansive
hypoechoic mass in the caudate lobe. (b)
Arterial phase US image shows a
hypervascular mass with a stellate vascular
pattern
• (Right) On a portal venous phase US image, the
lesion remains equal in enhancement to the liver
and contains a central nonenhancing scar. (left)
Confirmatory portal venous phase CT scan also
demonstrates sustained enhancement of the
lesion and the nonenhancing scar.
Focal Nodular Hyperplasia
• FNH shows stellate lesion vascularity and, frequently, a
central nonenhancing scar.
• A tortuous feeding artery is also commonly seen with
FNH.
• Portal venous phase imaging is critical to confident
confirmation of the diagnosis. As opposed to HCC, in
which washout is generally seen, FNH continues to
show enhancement equal to or greater than that of the
adjacent liver into the portal venous phase and
beyond.
• This phenomenon constitutes a major criterion for
diagnosis of FNH, without which we still recommend
further evaluation with CT or MR imaging.
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in
Focal Liver Lesions at Microbubble-enhanced US. RadioGraphics 2004; 24:921–935
• FNH. (right) Baseline conventional US image of the
right lobe shows a subtle echogenic mass. (middle)
Arterial phase US image shows a hypervascular mass
with some stellate vascularity, a small nonenhancing
scar (arrow), and a typical tortuous feeding artery.
(left) Confirmatory arterial phase CT scan also
demonstrates the hypervascular mass and
nonenhancing scar (arrow).
CEUS in Adenoma
• Hepatic adenoma benign liver lesion. This
hepatocytic tumor frequently manifests with
spontaneous rupture and hemorrhage.
• Malignant potential has been documented, and
diagnosis is therefore important.
• These lesions have been vascular during the
arterial phase.
• The documentation of portal venous behavior
has been complicated by the higher baseline
echogenicity of these tumors, which commonly
contain a significant volume of fat.
• Adenoma in a young female. (A) Gray scale
sonogram shows an oval hypoechoic lesion in
liver. (B) CEUS-arterial phase shows
• diffuse heterogeneous enhancement, which
on portovenous phase (C) is isoechoic to liver
parenchyma.
Shruti Thakur, Anupam Jhobta, D.S. Dhiman, R.G. Sood, Arun Chauhan,Charu S. Thakur. Role of contrast enhanced
ultrasound in characterization of focal liver lesions. The Egyptian Journal of Radiology and Nuclear Medicine (2014) 45, 7–17
A
B
C
D
• Contrast-enhanced ultrasound images of a hepatic adenoma
(HA) in a 23- year old asymptomatic man with no history of
hormone use. (A) Hypoechoic HA visualized in twodimensional sonography; lines ‘A’ and ‘B’ were used to
measure diameter in the maximum section. (B) Hypervascular
enhancement of HA with contrast ‘fast-in’ in the arterial
phase. (C) Lesion (arrow) appearing isoechoic or slightly
hyperechoic compared with normal-surrounding liver
parenchyma in the portal venous phase. (D) Lesion (arrow)
showing persistent enhancement with slight washing out and
visualization of the borderline in the delayed phase
XL ZHU1,*, P CHEN2,*, H GUO3,*, N ZHANG3, WJ HOU4, XY LI1 AND Y XU1. Contrast-enhanced Ultrasound
for the Diagnosis of Hepatic Adenoma. The Journal of International Medical Research 2011; 39: 920 – 928
Imaging
Phase
HCC
Hypovascular
Metastasis
Hypervascula
r Metastasis
Hemangioma
FNH
Arterial
(vascular
pattern)
Hypervascular,
dysmorphic
vessels
Hypovascular,
marginal
vessels
Hypervascular
Marginal
vessels,
peripheral
puddles and
pools, no linear
vessels
Hypervascular,
stellate
vessels,
tortuous
feeding
artery
Enhancement
Arterial
Greater than
that of liver,
diffuse, often
heterogeneous
Less than that
of liver,
marginal,
often
heterogeneous
More than
that of liver
Greater than
that
of liver,
peripheral
nodules,
often
heterogeneous
Greater than
that of
liver, diffuse
and
homogeneous,
nonenhancing
scar
Portal venous–
late
Less than that
of
liver
Less than that
of liver
Less than that
of liver
Equal to or
greater
than that of
liver, centripetal
progression
Greater than or
equal to that of
liver,
nonenhancing
scar
Change in
enhancement
over time
Washout
Washout
Washout
Sustained
enhancement
Sustained
enhancement
Margot Brannigan, MD, Peter N. Burns, PhD,Stephanie R. Wilson, MD. Blood Flow Patterns in Focal Liver Lesions at Microbubble-enhanced US.
RadioGraphics 2004; 24:921–935
Characteristics pattern in Other
Lesions
Jae Young Jang, et al. Current consensus and guidelines of contrast enhanced ultrasound for the
characterization of focal liver lesions. Clinical and Molecular Hepatology 2013;19:1-16
Role in Cholangiocarcinoma
• The enhancement patterns of ICC correlate with
tumor size. That is, most small ICCs (≤ 3 cm) are
homogeneously enhancing, while those > 3 cm
enhance heterogeneously or show a peripherally
enhancing rim.
• In portal and late phase on CEUS, most ICCs show
up as hypo-enhancing, which is a prominent
feature of malignancy on CEUS.
• However, on enhanced CT or MRI, most ICCs
show delayed hyper-enhancement in the late
phase.
Xu HX. Contrast-enhanced ultrasound in the biliary system: Potential uses and indications. World
J Radiol 2009 December 31; 1(1): 37-44
• Intrahepatic cholangiocarcinoma. (right)
Baseline ultrasound shows an isoechoic mass
in segment 5 of the liver; (left): The lesion
shows peripheral rim-like hyper-enhancement
26 s after contrast agent injection on CEUS;
• (Right) The lesion becomes hypo-enhanced 52
s after contrast agent injection; (left) The
lesion continues to be hypo-enhanced 121 s
after contrast agent injection.
Characteristics of malignant lesions of
the liver in CEUS
Jae Young Jang, et al. Current consensus and guidelines of contrast enhanced ultrasound for
the characterization of focal liver lesions. Clinical and Molecular Hepatology 2013;19:1-16
CEUS in Hepatic Abscess
• Hepatic abscess shows perilesional vascularity on
arterial phase, ring enhancement on portal
venous phase and retained their enhancement
pattern on late parenchymal phase.
• Hepatic abscess shows dense rim of opacification
with a persistent hypoechoic center.
• Both the external and internal margins became
sharper after contrast administration
Shruti Thakur, Anupam Jhobta, D.S. Dhiman, R.G. Sood, Arun Chauhan,Charu S. Thakur. Role of contrast enhanced
ultrasound in characterization of focal liver lesions. The Egyptian Journal of Radiology and Nuclear Medicine (2014) 45, 7–17
http://dx.doi.org/10.3350/cmh.2013.19.1.1
• Hepatic abscess in a 22-year-old man. (right)
Gray scale shows a well defined heterogeneous
hypoechoic lesion in right lobe. (left) Color
Doppler shows no vascularity.
Continued
• (Right) CEUS-arterial phase shows intense
peritumoral enhancement. (Left) CEUS-portal
venous phase shows persisting rim
enhancement.
Take Home Message
Microbubble enhanced US of the liver provides
enhancement information comparable to that
provided by contrast enhanced CT and MR
imaging, along with real-time morphologic
evaluation of lesion vascularity.
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