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| Surgery |

Contrast-Enhanced Ultrasonography of the Liver

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Bjørn Skjoldbye, MD BSc, Senior Consultant, Department of Surgical Gastroenterology, Herlev Hospital, University of Copenhagen, Denmark

Morten Høgholm Pedersen, MD Product Manager, Surgical Ultrasound, B-K Medical

Lisbeth Gorr Product Manager, Contrast Imaging, B-K Medical

A new B-K Medical technology enables our

transducers and ultrasound scanners to

be used for contrast-enhanced ultrasound

(CEUS) for abdominal, laparoscopic and

intraoperative applications.

New technological achievements and the

use of ultrasound contrast agents (UCA)

have given diagnostic ultrasound a new

edge. Combined with the scanner’s selective

detection of signals from the microbubbles,

the use of UCA introduces several new

advantages to the clinical use of ultrasound.

This application note discusses the uses of

CEUS in general, and its use for detecting

and characterizing focal liver lesions in

particular.

Background

Conventional B-mode ultrasound (US) is the

most commonly used imaging modality. The

sectional US images present slices of morphology

in real time without radiation hazards and with

an excellent cost-benefit ratio. Furthermore,

purpose-designed transducers have expanded the

usefulness of clinical ultrasound.

Doppler US adds important information about

vascular flow to B-mode US. However, Doppler US

is not useful for observing or quantizing blood

flow in small vessels and capillaries. It cannot

detect flow in the microvasculature because the

flow velocity there is as low as 1 mm/sec, which

is lower than the threshold of the tissue motion

filters applied in Doppler mode; the weak signals

from low velocity flow are therefore rejected.

Using a microbubble-based ultrasound contrast

agent (UCA) in combination with a dedicated

bubble-specific technology in the US scanner

makes it possible to measure flow in small

vessels and detect perfusion in capillary beds

– and extends the clinical utility of ultrasound

considerably.

Contrast-enhanced US (CEUS) has become a valuable clinical tool

Contrast-enhanced US (CEUS) has become a

valuable clinical tool to detect increased – as

well as decreased – vascularity in focal lesions as

well as in parenchymal tissue. CEUS possesses

the same virtues as conventional ultrasound,

providing a dynamic, non-invasive real-time

imaging modality for use in numerous clinical

applications.

The vascularity of tumor tissue differs from that of

normal parenchyma. Furthermore, the vascularity

of malignant lesions differs from that of benign

ones. CEUS detects these differences and may

be used to improve the sensitivity and accuracy

of detection and classification of tumors in the

parenchymal organs. Decreased vascularity in

ischemic or infarcted tissue may be visualized,

too.

The use of a UCA improves the detection of

malignant lesions in the liver by permitting the

evaluation of the contrast dynamics after infusion

of the UCA. This method is basically similar to

the procedures for performing contrast-enhanced

CT and MRI, but the CEUS analysis is done in real

time and without radiation hazards. CEUS-guided

interventions may be performed, too.

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CEUS Technology

Optimal CEUS requires a UCA and an ultrasound

system with UCA-dedicated technology, such

as the B-K Medical Pro Focus. The UCA is

administered into a larger peripheral vein using

simple intravenous access. The incident US from

the transducer interacts with the microbubbles

in the bloodstream. These generate UCA-specific

signals that can be separated from other signals,

as well as from noise, by dedicated technology in

the scanner.

Ultrasound Contrast Agents

Current ultrasound contrast agents consist of

gaseous microbubbles, surrounded by a shell,

suspended in solution. Gaseous microbubbles not

only act as strong reflectors in the bloodstream.

When they are exposed to the mechanical energy

of a US pulse, they produce, in addition to a

conventional echo, a specific response related to

their physical properties such as elasticity and

resonance frequency. Thus the bubbles contribute

a nonlinear component to the echoes that are

reflected back to the transducer. This nonlinear

response consists of harmonic signals that are

multiples of the fundamental frequency.

The microbubbles’ nonlinear response depends on

the energy of the ultrasound pulse.

A thin flexible shell preserves the microbubbles’

ability to generate harmonics. The signal

generated by the microbubbles will be strongest

when the microbubbles’ resonance frequency

coincides with the frequency of the incident US-

pulse.

Low and High MI

The acoustic pressure of the US pulse is expressed

as the mechanical index (MI). The MI is related to

the transmit power that provides the initial energy

to the ultrasound pulse.

A US pulse with low acoustic pressure (low MI)

does not rupture the microbubbles but causes

them to oscillate with a fundamental frequency

and a set of harmonics, as mentioned above.

Increasing the acoustic pressure above a certain

threshold (high MI) causes the microbubbles

to burst. When the bubbles rupture, free gas is

released. This strongly scatters the incident US.

However, free gas in the blood pool dissolves

quickly, so the increased signal from scattering is

transient.

Optimal CEUS requires an ultrasound system with UCA-dedicated technology, such as

the B-K Medical Pro Focus

UCA may occasionally be used to enhance

conventional Doppler US. Doppler US requires an

intermediate- or high-MI transmit power. However,

the present UCA-specific technology in the US

scanners uses low MI for CEUS. High MI may

be used transiently to destroy bubbles during

continuous CEUS (see below). The purpose of this

is to clear a volume of microbubbles so that a new

wash-in of microbubbles can be observed in the

volume. The dynamic behavior of UCA cannot be

observed with high-MI CEUS.

Early, Intermediate and Late Phases

After the infusion of a UCA bolus in a peripheral

vein, a timer is activated so that the time after

injection is displayed on the screen of the US

scanner. After 10-25 seconds (arterial phase), the

UCA is detected in the parenchymal arteries but

not in the central veins. During the portal phase,

30-45 seconds after administration of the UCA

bolus, the UCA is detected in the portal vein.

Finally, the late phase starts when the UCA is

detected in the central veins and parenchyma is

enhanced.

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Continuous or Transient CEUS Imaging

Continuous low-MI CEUS is the predominant

method for using UCA to evaluate focal lesions

in the liver or other parenchymal organs. It

requires a UCA designed for low-MI CEUS – such

as DEFINITY, Sonazoid or SonoVue, which produce

resonant frequencies suitable for abdominal

imaging while the MI is low enough to produce

minimal disruption of the microbubbles. Several

new UCA are on the way to the market, including

dedicated high-frequency CEUS agents. However,

their commercial availability depends on local and

regional regulations.

A UCA that consists of low solubility gases, such

as DEFINITY, Sonazoid or SonoVue, has resonance

frequencies suitable for abdominal low-MI CEUS.

Dynamic observation of such UCA for several

minutes makes real-time investigation of the

enhancement patterns of a lesion or tissue area

possible.

Levovist, a contrast agent used mainly for

ultrasound HSG (hysterosalpingography) and

ultrasonographic reflux studies of the urinary

system in children, requires higher MI settings,

so intermittent (transient) CEUS must be used

to avoid bursting the bubbles. SAE (Stimulated

Acoustic Emission) is a transient scanning

technique which may be used with Levovist to

display metastasis of the liver. SAE does not

require a CEUS-specific technology. It utilizes the

color Doppler mode but provides only transient

information. SAE is, however, widely considered

obsolete for detection and characterization of

focal lesions.

UCA is used primarily for enhancement of

microvasculature and parenchyma. Occasionally,

UCA may be used to enhance conventional

Doppler US.

Table 1 gives details of common contrast agents,

including their interior and shell substances.

Contrast-Specific Ultrasound Techniques

Because the microbubble contrast agents generate

harmonics, harmonic imaging allows CEUS to

become a very powerful diagnostic modality.

However, harmonic signals may be generated

not only by the microbubbles but also by the

tissue itself, as it expands and contracts in

Agent Manufacturer Resonance Range

Chemical Composition MI Level

DEFINITY® BMS 1.5–4 MHz Liposome/Perfluorocarbon Low < 0.4

Levovist® Schering 2–3 MHz Lipid/Air (galactose-based) High >0.6

Sonazoid® GE Healthcare 2–8 MHz Lipid/Perfluorocarbon Low < 0.4

SonoVue® Bracco 1.8–3.2 MHz Phospholipid/Sulfur hexafloride Low < 0.4

Table 1. Specifications of common ultrasound contrast agents. To find out whether a particular UCA is approved for a particular application in a particular country, contact the UCA manufacturer.

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response to the ultrasound waves. It is essential

to differentiate between harmonic signals from

the microbubbles and harmonics generated in

the tissue. The harmonic signals from the tissue

depend on the acoustical pressure (MI) of the

ultrasound pulses. At low MI, the generation of

harmonics from the tissue is negligible.

Novel low-MI multi-pulse techniques, such as

power modulation, have been developed to detect

non-linear signals from the microbubbles.

The Power Modulation Technique

The key to modern CEUS techniques is

differentiating between the signal produced by

the contrast agent’s microbubbles and the signal

reflected from tissue. New methods for this have

dramatically enhanced the image contrast-to-

tissue ratio.

B-K Medical scanners use a power modulation

technique for separating the signals. In each scan

line, the transducer emits pulses with full and half

amplitudes. These pulses are subtracted in the

scanner, to extract the nonlinear bubble signals

from the linear tissue signals. See Table 2.

Using this tissue subtraction technique provides

the best signal-to-noise ratio to differentiate

between echoes originating from the microbubbles

and those originating from the tissue.

Dynamic Enhancement Patterns

The UCA microbubbles are blood pool agents.

Observing the dynamic behavior of the

microbubbles in a lesion or tissue volume may

demonstrate the macro- and microvascular

properties of focal pathology in the liver or other

organs.

After administration of a bolus of UCA in a

peripheral vein, the microbubbles sequentially fill

the arteries, the portal veins and the parenchyma

of the liver as well as other organs. Similar to the

responses in contrast-enhanced CT and MR, the

CEUS response in the liver is generally observed in

three phases:

arterial phase (10-25 seconds after injection) -

portal phase (30-45 seconds after injection) -

late (parenchymal) phase (>120 seconds after -

injection)

As the bubbles pass through the blood vessels,

changes in the contrast-enhanced image

allow normal tissue to be differentiated from

pathological, based on the dynamics of the

different macro- and microvasculature in the

tissue types. Over time, the microbubbles are

distributed throughout the liver, so it appears

Transmit Echo from tissue Echo from bubbles

Half amplitude

Full amplitude

(2 x half ampl.) – full ampl.

1. Contrast mode before injection.

2. Contrast mode after injection.

Table 2: Principle of the power modulation technique. Linear response from the tissue is canceled by subtraction. A nonlinear response to the more powerful pulse will be different from the sum of the response to the two weaker pulses. Therefore, subtraction will give a non-zero result if a nonlinear (microbubble) response is present.

1 2

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a strong echo from the microbubbles but low

enough not to burst them. For best results, MI

must be as high as possible without bursting the

bubbles.1

The Pro Focus scanner has special contrast

imaging setups that have the MI optimized for the

transducer and the specific contrast agent being

used. With simultaneous B-mode and CEUS, the

low MI setting applies to both views.

Clinical Considerations

Before scanning with CEUS, you should make a

B-mode recording of the volume of interest.

After this, you should optimize the US scanner for

CEUS by selecting a setup appropriate for the type

of UCA and purpose of the scanning. The setup

specifies the appropriate MI levels and generally

generally contrast enhanced. Malignant lesions,

on the other hand, especially metastases which

represent non-liver tissue, appear hypoechoic.

Safety

UCA are widely considered safe and non-toxic.

Hypersensitivity may occur, but allergic reactions

are relatively rare, compared to reactions to X-ray

or MR contrast agents. Theoretically, UCA could

produce biological side effects, and the expected

clinical benefits of UCA versus the possible side

effects should always be evaluated, taking into

account the safety information provided by the

UCA manufacturer.

Methods and Equipment

Mechanical Index Is Important

The acoustic power must be sufficient to generate

CEUS Step by Step

The European Federation of Societies for Ultrasound in

Medicine and Biology (EFSUMB) recommends the following

steps for CEUS investigations.2

Note that in order to know which vascular phase an image

corresponds to, it is important to start the scanner’s timer

when you inject the contrast agent and to document the

various phases of the enhancement.

1. Perform a baseline B-mode US examination, possibly

also color and Doppler examinations.

2. Identify target lesions, and then keep the transducer

in a stable position.

3. Make sure your equipment is set for CEUS. (With

the Pro Focus, this means using one of the special

contrast setups.)

Low MI (<0.3) -

CHI-mode activated -

Simultaneous imaging activated -

4. Administer UCA.

Intravenous bolus of UCA followed by 5-10 ml saline flush -

(needle diameter not less than 20 gauge so mechanical impact does not break bubbles)

Start the timer on the scanner when you inject the UCA -

5. Scan continuously and document (see next step) the

investigation for at least 60-90 seconds to cover the

arterial and portal phases. For assessment of the

late phase, you may scan intermittently until you

observe that the UCA has disappeared from the liver

microvasculature.

6. Document the investigation on video or by storing

movie clips in the scanner. You can adjust the

length and number of clips, and you can record

continuously.

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includes a split-screen view to display the contrast

and B-mode images at the same time.

Note: Ultrasound images in this paper show

simultaneous B-mode and CEUS. Because the

MI is low, the quality of the B-mode image is

not optimal, but it is good enough to use for

orientation purposes.

In most cases, the contrast agent is administered

through a cannula in the cubital fossa and

followed by a flush of saline. A timer on the US

scanner must be activated as the UCA is injected.

Clinical Benefits

Research conducted over the past few years has

identified several potential clinical benefits of the

use of CEUS, including the following:

detection of liver metastasis -

characterization of liver lesions -

management of ablation therapy -

Detection of Liver Metastasis

Liver metastases appear hypoechoic in the portal

and late phases.

Clinical studies have shown that CEUS dramatically

improves the detection of liver metastasis

compared to what is found with conventional

US alone. Some studies even suggest that CEUS

detects lesions as well as contrast-enhanced CT.3

In conventional ultrasound examinations,

metastases may be overlooked because they

are very small or isoechoic, or because the liver

parenchyma appears heterogeneous and the

metastasis blends in with the background of the

ultrasound image.

CEUS has been found to increase the sensitivity of

detecting liver metastases from 40% to 84%.4

However, a few liver lesions localized in the

deepest regions of the parenchyma seen on other

imaging modalities will remain out of reach of

the transducer’s ultrasound beam. In these cases,

CEUS does not provide a solution.

Characterization of Liver Lesions

One of the important advantages of CEUS is the

continuous real-time information about contrast

agent uptake in the tissue. “The high reliability

is based on the markedly different contrast-

uptake patterns of the most common liver lesions

or pseudo lesions.”5 CT and MRI provide only

snapshots of information during the time period,

but contrast imaging provides the surgeon

with more information: “In our experience, the

examination of arterial inflow is very important

for lesion characterization. Due to the short time

window of arterial inflow, continuous observation

with [UCA] is superior to the one arterial image

taken with CT or MRI.”5

Differentiation between malignant and benign

lesions

When a tumor is detected, the important

distinction a surgeon needs to make is: benign

versus malignant. The perfusion kinetics

demonstrated by normal liver parenchyma and

pathological tissue seem to be key to making this

distinction.6 “Contrast-enhanced US may now offer

a definitive diagnosis for hemangiomas and FNHs

which would defer referral to more costly and/or

invasive procedures and any delay in the patient

management.”6

When a tumor is detected, the important distinction a surgeon needs to make is: benign versus malignant

A characteristic feature of malignant lesions,

particularly liver metastases, is that the

microbubbles wash out during the portal and

late phases. Hepatocellular carcinoma (HCC) can

show some enhancement in the late phase or may

appear isoenhanced.

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Being able to save film clips of the changing

ultrasound image on the scanner allows the doctor

to carefully examine the dynamic patterns by

replaying the clips.

Table 3 describes the differing contrast uptake

patterns characteristic of various lesion types

over time. The patterns described are the most

common ones. The vascular pattern that a tumor

exhibits after a contrast agent is injected will vary,

however.

Hemangiomas display a characteristic centripetal

filling pattern: the enhancement starts in the

periphery and gradually fills the lesion towards

its center. (See Case 2.) Larger cavernous

hemangiomas may be seen filling the contrast

in patchy areas situated in the periphery of the

Phase: Time after injection of contrast agent

Lesion Type Arterial phase: 10-25 sec Portal phase: 30-45 sec Late phase >120 sec

BENIGN Contrast enhancement in benign lesions tends to be hyperenhancing relative to the liver parenchyma in the late phase.

Hemangioma Peripheral nodular enhancement

Progressive centripetal enhancement

Complete enhancement

FNH (focal nodular hyperplasia)

Spoke-wheel and hyper-enhancement after few seconds

Hyper- enhancement; hypoenhanc-ing central scar in 70%

Iso- or hyper-enhancementplus hypo-enhancing central scar

MALIGNANT A characteristic feature of malignant lesions, particularly liver metastases, is that the lesions appear hypoenhanced in the late phase.

HCC (hepatocellular carcinoma

Hyperechoic rim enhance-ment with chaotic vessels

Hypo- or iso- enhancement

Hypo- enhancement

Hypovascular metastasis

Hypo- reflective lesions with typical rim enhancement

Progressive hypo- enhancement

Hypo- enhancement

Hypervascular metastasis

Brightly enhancing hyper-reflective and homogeneous

Progressive hypo- enhancement

Hypo- enhancement

Table 3. Phases of contrast enhancement of focal liver lesions after injection of contrast agents. Note that over time, the microbubbles are distributed through the liver tissue, making it appear generally contrast enhanced. (Information in table adapted from Albrecht et al 2 and Albrecht 7.

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lesion that gradually, often over several minutes,

fuse and cover all non-necrotic areas of the lesion.

The small, often capillary-laden, hemangioma may

be subject to very rapid enhancement where the

saturation of the entire lesion with the contrast

agent takes place in just a few seconds.

Malignant lesions tend to have blood primarily

supplied by arteries. This is why they may appear

more enhanced than the background parenchyma

in the arterial phase.

CEUS is a strong tool for monitoring radio frequency ablation (RFA) procedures

Management of Ablation Therapy

Various studies have indicated that CEUS is

a strong tool for monitoring radio frequency

ablation (RFA) procedures in percutaneous,

laparoscopic, or intraoperatively-guided tumor

ablations. “Contrast-enhanced US has a high

specificity and a good agreement with dynamic CT

or MRI in detecting residual viable tumoral areas.”8

“The introduction of second-generation contrast

agents in transabdominal ultrasound has

increased the sensitivity and the specificity

for detecting focal liver lesions. Their use also

allows for improved management during ablation

procedures.”9

Repeating CEUS after ablation allows the vascular

activity in the tumor and its surroundings before

and after RFA to be compared. If CEUS indicates

residual vital tumor tissue after an ablation, the

procedure may be extended or repeated until

treatment is considered sufficient.

Case Studies

An increasing body of research points to the

potential value of CEUS in connection with various

procedures, from the least invasive (percutaneous

abdominal scanning) to the most invasive

(intraoperative).

Intraoperative ultrasound has consistently been

shown to be significantly more sensitive than

other imaging techniques for detecting liver

malignancies.10, 11

Recent studies indicate that intraoperative

CEUS (CEIOUS) improves the accuracy of normal

intraoperative ultrasound (IOUS) and suggest

that it is an essential tool for use with patients

undergoing liver resection.12, 13

The following cases illustrate the spectrum of

procedures utilizing CEUS, including abdominal,

intraoperative and laparoscopic ultrasound

scannings.

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Benign Lesions

Case 1. Angioma: Percutaneous abdominal

CEUS and CE-CT

CEUS imaging of an angioma in the late phase and

the corresponding contrast-enhanced CT (CE-CT).

Investigation of the relation between the right

portal vein and the borders of a large angioma.

8820e transducer.

Case 2. Hemangioma

Characteristic centripetal filling pattern of a

hemangioma.

Late phase hyperechoic. 8820 transducer.

Case 2. Hemangioma

Figure 2a. Arterial phase. Figure 2b. Portal phase. Figure 2c. Late phase.

Case 1. Angioma

Figure 1a. CEUS view. Figure 1b. CE-CT view. Dotted rectangle shows area of CEUS view.

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Malignant Lesions

Case 3. Liver metastasis: Percutaneous

abdominal scanning

66-yr-old male with rectal cancer. Abdominal

ultrasound of the abdomen is performed, and

several solid lesions are detected in the liver.

CEUS is performed in simultaneous CHI-mode

after administration of a bolus of 2.4 ml

SonoVue. 8820 transducer.

The dynamic contrast enhancement pattern is

recorded, with t=0 when the bolus is infused

intravenously followed with a flush of 5 ml

isotonic saline.

The appearance of the lesion as vascularly active

in the arterial phase, gradually shifting to an echo-

poor appearance in the enhanced parenchyma in

the late phase, is classic for a metastasis in the

liver.

Case 4. Liver metastasis: Percutaneous

abdominal scanning

Detection and characterization of a liver

metastasis from colorectal cancer deep in the

liver, segment VII. 8820e transducer.

Case 4. Liver metastasis

Figure 4a. Early portal phase. Figure 4b. Portal phase Figure 4c. Late phase.


Figure 3a. Arterial phase. The lesion and the arteries in the liver tissue are enhanced. The liver tissue is seen without enhancement.

Figure 3b. Early portal phase. Enhancement of the portal vessels. The lesion and the liver parenchyma are seen with different enhancements.

Figure 3c. Late phase. The lesion appears echo poor in the still-enhanced parenchymal background.

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RF Ablation and Management

Case 5. CEUS monitoring of percutaneous

RF ablation

CEUS before and after US-guided percutaneous

RFA of a solitary liver metastasis in a 55-yr-old

female with breast cancer. 8820 transducer.

Case 6. Gastrointestinal stromal tumor

with RFA: Intraoperative monitoring

52-yr-old female with gastrointestinal stromal

tumor (GIST). Primary tumor in the small intestine

removed radically. New metastasis was detected

in the liver and treated with percutaneous RF

ablation 9 months later. Disease stabilized on

systemic therapy with Glivec®.

However, a new solitary metastasis was detected

in the liver two years later. IOUS with CEUS (8815

transducer) detected a small new metastasis on

the edge of the previously ablated volume (Fig 6a).

The recurrence was not seen on CT but was seen

with CEUS. The previously ablated area appears

empty of contrast activity as opposed to the active

Case 5. Percutaneous RFA monitoring

Figure 5a. Preparation for US-guided percutaneous RF ablation. In B-mode, target is seen as an echo-poor lesion on the puncture line.

Figure 5b. CEUS after 2.4 ml SonoVue administered intravenously. Markedly peripheral vascular activity (arrow) before RF treatment observed in all phases. Late phase shown here.

Figure 5c. Needle tip seen in target (arrow) during placement of RF device.

Figure 5d. Tines of the RF needle are unfolded and the treatment started.

Figure 5e. Immediately after a 19 min. RF ablation, lesion seen with heterogeneous changes in and around the lesion. Border of ablation volume cannot be clearly defined.

Figure 5f. Successful RF ablation confirmed. CEUS presents a 34 x 42 mm ablation volume (t = 38) with sharp borders and without vascular contrast activity. Ablation volume encapsulates target lesion, and no residual areas with vascular/contrast activity are defined.

Case 6. Gastrointestinal stromal tumor with RFA: Intraoperative monitoring

Figure 6a. Arterial phase Figure 6b. RFA performed. Figure 6.c. Ablation successful and complete.

Figure 7. Intraoperative CEUS identifies vascular activity on the posterior portion of primary RF-ablated metastasis on the liver. Repeated RF ablation required.

Figure 8. In B-mode (right) the ablation area appears irregular. In simultaneous CEUS, the ablation volume appears with a regular border and without internal vascular activity.

Cases 7 and 8. Intraoperative RFA monitoring

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vascular appearance of the new metastasis. IOUS-

guided RFA is performed (Fig 6b), and IOUS with

CEUS after the ablation shows a successful and

complete ablation without contrast activity.

Case 7. Recurrent liver metastasis: Intraoperative RFA monitoringCEUS performed intraoperatively identifies

vascular activity on the posterior portion and a

primary RF-ablated metastasis in the liver. 8815

transducer.

Conclusion: CEUS helped to identify subtle signs

of recurrence, enabling the surgeon to determine

an optimal and immediate course of treatment.

Case 8 CEUS after intraoperative RFA of a

liver metastasis

Follow-up CEUS 5 weeks after RFA of liver

metastasis.

Case 5. Percutaneous RFA monitoring

Figure 5a. Preparation for US-guided percutaneous RF ablation. In B-mode, target is seen as an echo-poor lesion on the puncture line.

Figure 5b. CEUS after 2.4 ml SonoVue administered intravenously. Markedly peripheral vascular activity (arrow) before RF treatment observed in all phases. Late phase shown here.

Figure 5c. Needle tip seen in target (arrow) during placement of RF device.

Figure 5d. Tines of the RF needle are unfolded and the treatment started.

Figure 5e. Immediately after a 19 min. RF ablation, lesion seen with heterogeneous changes in and around the lesion. Border of ablation volume cannot be clearly defined.

Figure 5f. Successful RF ablation confirmed. CEUS presents a 34 x 42 mm ablation volume (t = 38) with sharp borders and without vascular contrast activity. Ablation volume encapsulates target lesion, and no residual areas with vascular/contrast activity are defined.

Case 6. Gastrointestinal stromal tumor with RFA: Intraoperative monitoring

Figure 6a. Arterial phase Figure 6b. RFA performed. Figure 6.c. Ablation successful and complete.

Figure 7. Intraoperative CEUS identifies vascular activity on the posterior portion of primary RF-ablated metastasis on the liver. Repeated RF ablation required.

Figure 8. In B-mode (right) the ablation area appears irregular. In simultaneous CEUS, the ablation volume appears with a regular border and without internal vascular activity.

Cases 7 and 8. Intraoperative RFA monitoring

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Laparoscopic CEUS

Conclusion

Conclusion

CEUS is proving to be a very valuable addition to

doctors’ toolkits, helping them detect lesions and

– by letting them observe contrast-uptake patterns

over time – helping them characterize the lesions

as well. In some cases, CEUS can perhaps replace

more expensive and time consuming procedures.

B-K Medical transducers and scanners can be

used for the entire spectrum of contrast imaging:

percutaneous to laparoscopic to intraoperative.

Note: Contrast-enhanced ultrasound of the liver

has not been approved by the FDA for use in the

USA.

Case 9. Liver metastasis: Laparoscopic

scanning (LUS)

8666 transducer.

Conclusion: CE-LUS (contrast-enhanced

laparoscopic ultrasound) detects more metastases

than B-mode LUS. LUS- or CE-LUS-guided biopsy is

possible.

Figure 9a. CE-LUS after administration of 2.4 ml bolus of SonoVue. Multiple small metastases detected by CE-LUS.

Figure 9b. Biopsy from liver metastasis performed (without contrast) after CE-LUS.


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1. Tang MX, Eckersly RJ, Noble JA.Pressure-dependent attenuation with microbubbles at low mechanical index.

Ultrasound Med Biol.

2005;31(3):377–384.

2. Albrecht T et al.Guidelines for the use of contrast agents in ultrasound.

Ultraschall Med.

2004;25(4):249–256.

3. Dietrich CF et al.Assessment of metastatic liver disease in patients with primary extrahepatic tumors by contrast-enhanced sonography versus CT and MRI.

World J Gastroenterol.

2006;12(11):1699–1705.

4. Quaia E et al.Comparison of contrast-enhanced ultrasonography versus baseline ultrasound and contrast-enhanced computed tomography in metastatic disease of the liver: diagnostic performance and confidence.

Eur Radiol.

2006;16:1599–1609.

5. Rettenbacher TOur experiences using contrast-enhanced ultrasound in focal liver lesions.

Eur Radiol.

2005;15 Suppl 5:E93–97.

6. Leen EThe role of contrast-enhanced ultrasound in the characterisation of focal liver lesions.

Eur Radiol.

2001;11 Suppl 11: E27–34.

7. Albrecht TDynamic vascular pattern of focal liver lesions with contrast -enhanced ultrasound: Latest results with SonoVue.

In: Albrecht et al, eds. Contrast-

Enhanced Ultrasound in Clinical

Practice. Milan: Springer; 2005;3–22.

8. Spinazzi AEmerging clinical applications for contrast-enhanced ultrasonography.

Eur Radiol.

2001;11 Suppl 3:E7–12.

9. Siösteen A-K, Elvin AIntra-operative uses of contrast-enhanced ultrasound.

Eur Radiol.

2004;14 Suppl 8:P87–95.

10. Machi J et al.Intraoperative ultrasound.

Surg Clin North Am.

2004;84(4):1085–1111.

11. Prati U et al.Intraoperative sonography still the standard technique in hepatic surgery.

AJR 2002;179(5):1347–1348.

12. Leen E et al.Potential value of contrast-enhanced intraoperative ultrasonography during partial hepatectomy for metastases: an essential investigation before resection?

Ann Surg.

2006;243(2):236–240.

13. Torzilli G et al.Contrast-enhanced intraoperative ultrasonography during hepatectomies for colorectal cancer liver metastases.

J Gastrointest Surg.

2005;9(8):1148–153.

References

Trademarks

DEFINITY is a registered

trademark of Bristol-Myers

Squibb Medical Imaging.

Glivec is a registered trademark

of Novartis AG.

Levovist is a registered

trademark of Schering AG.

Sonazoid is a registered

trademark of GE Healthcare.

SonoVue is a registered

trademark of Bracco S.p.A.

Figure 9a. CE-LUS after administration of 2.4 ml bolus of SonoVue. Multiple small metastases detected by CE-LUS.

Figure 9b. Biopsy from liver metastasis performed (without contrast) after CE-LUS.


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World HeadquartersMileparken 34DK-2730 HerlevDenmark

Tel: +45 44 52 81 00 • Fax: +45 44 52 81 99 • www.bkmed.com

With more than 30 years of commitment to ultrasound innovation,

B-K Medical specializes in the development, manufacture and distribution

of dedicated ultrasound solutions. B-K Medical has its headquarters

in suburban Copenhagen, Denmark, and has offices and distributors

throughout the world.

A wholly owned subsidiary of Analogic Corporation

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contrast-enhanced ultrasonography of the...

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