CONTRAST ENHANCED ULTRASOUND

IMAGING
PRINCIPLE

• CEUS involves administration of intravenous contrast

agents containing microbubbles of perflurocarbon or
nitrogen gas
• The microbubbles affect the USG backscatter and
increase vascular contrast in a similar manner to
intravenous contrast agents used in CT and MRI
MICROBUBBLE
• Microbubble shell material determines how easily the it is
taken upper pole by the immune system
• The material for microbubble determines its time in circulation
and elasticity
• Microbubble shell is composed of albumin , galactose , lipid or
polymers
• Microbubble gas core is the most important part because it
determines the echogenicity .
• The size of microbubble is 1- 4 um
• The microbubble is nearly around the size of RBC as it should
not cross the vascular endothelium
MARKET AVAILABLE MICROBUBBLES
COMMONLY USED MICROBUBBLE

Echovist- Used in Right heart Myocardium, Liver and

gynaecological applications.

Albunex- used in Liver, Kidneys and heart contrast imaging.

• SonoVue- Most Commonly used in INDIA. Used in study of

Liver, Kidneys and Gynaecological studies.
TECHNIQUE OF CEUS

DOSE- SonoVue is a kit including 1 vial containing 25 mg of

lyophilised powder and second vial contains suspension
medium (Galactose solution)
For I.V. use dose for SonoVue is 2.4 ml (0.04ml/kg).
For renal and pancreatic evaluation low dose 1.0ml is used.
• 10ml 0.9% N.S should be flushed after the administration
of the contrast agent.
PROCEDURE-

› The suspension should be administered before 15mins after

preparation.

▸ The target organ is focused on B-mode US and then

contrast-specific imaging mode is turned on.

► On Ultrasound after the contrast is administered the tissue

is divided on basis of Perfussion i.e Hyperenhancing,
isoenhancing, hypoenhancing.
TYPES

1. Non-targeted contrast-enhanced ultrasound

2. Targeted contrast- enhanced ultrasound

Non-targeted contrast-enhance ultrasound

► More common method

► In this the microbubbles will remain in the systemic

circulation for a certain period of time. During that time,
ultrasound waves are directed on the area of interest. When
microbubbles in the blood flow past the imaging window,
the microbubbles’ compressible reflect a unique echo.
USES OF NON-TARGETED CEUS

► To enhance the contrast at the interface between the tissue

and blood. A clearer picture of the structure of an organ
▸ Evaluating the degree of blood perfusion and evaluating the
blood volume in an organ or area of interest.
► Differentiation between benign and malignant focal liver
lesions
Typical appearance of liver hemangioma (arrows). CEUS shows globular
peripheral enhancement 40 seconds after microbubble injection (A) and
progressive, centripetal fill-in after 90 seconds (B). The central portion of
the lesions remains unenhanced because of Incomplete filling .
Appearance of prostate cancer at CEUS. (A) Baseline transrectal
US of the of the prostate shows no focal abnormalities in the
peripheral portion of the gland. (B) Twenty-eight seconds after
microbubble Injection a hypervascular area is recognized in the
right prostate lobe (arrowheads). Cancer was found at biopsy
Acute splenic infarction from septic embolism in a patient with aortic valve
prosthesis infection and bacterial endocarditis. (A) No defined abnormalities
of the splenic parenchyma are seen on baseline US. (B)CEUS image obtained
30 seconds after microbubble injection shows a large, nonperfused area (*)
involving the dome of the spleen
Targeted contrast-enhanced ultrasound

▸ Contrast agents designed to bind to specific molecules, which

are then targeted at tissues expressing that substance.

► Microbubbles targeted with ligands that bind certain

molecular markers that are expressed by the area of imaging.

► Microbubbles theoretically travel through the circulatory

system, eventually finding their respective targets and binding
specifically.
USES OF TARGETED CEUS

Inflammation: Contrast agents may be designed to bind to

certain proteins that become expressed in inflammatory diseases
such as Crohn’s disease, atherosclerosis, and even heart attacks
• Thrombosis and thrombolysis: Contrast Agents specifically
bind to activated platelets and allow real-time molecular
imaging of thrombosis, such as in myocardial infarction, as
well as monitoring success or failure of pharmacological
thrombolysis.
► Cancers: If microbubbles are targeted with ligands that bind
receptors like VEGF, they can non-invasively and specifically
identify areas of cancers.

▸ Drug Delivery: drugs can be incorporated into the

microbubble’s lipid shell.

► Gene Delivery: Vector DNA can be conjugated to the

microbubbles
Complex hepatic cyst (curved arrows). (A) Baseline US showing a
heterogeneous round lesion with well- defined margins but no
defined posterior enhancement. (B) After microbubble injection the
lesion does not enhance in all vascular phases.
HOW TO REDUCE RISK AND MANAGEMENT.

► To reduce the risk Check for intolerance of any of the

components of the contrast agent

▸ Use the lowest level of acoustic output and shortest scanning

time to allow a diagnostic examination

▸ Management of Drug reactions is symptomatic.

Advantages of CEUS

› Acoustically homogeneous. Blood and surrounding

tissues have similar echogenicities, so it is also difficult to clearly
discern the degree of blood flow, perfusion, or the interface between the
tissue and blood using traditional ultrasound.

▸ Allows real-time evaluation of blood flow.

▸ Destruction of microbubbles by ultrasound in the image plane allows

absolute quantification of tissue perfusion. It does not involve radiation.
► Very cost-efficient and widely available.

▸ Since microbubbles can generate such strong signals, a lower intravenous

dosage is needed, micrograms of microbubbles are needed compared to
milligrams for other molecular imaging modalities such as MRI contrast
agents.

▸ Targeting strategies for microbubbles are versatile and modular.

› Active targeting can be increased (enhanced microbubbles adhesion) by

Acoustic radiation force using a clinical ultrasound imaging system in 2D-
mode and 3D mode
Disadvantages of CEUS
Microbubbles don’t last very long in circulation. They have low
circulation residence times because they either get taken up by
system cells or get taken up by the liver or spleen even when
they are coated with PEG.
Ultrasound produces more heat as the frequency increases.
Monitering Required.
• Microbubbles burst at low ultrasound frequencies and at high
mechanical indices (MI), which is the measure of the acoustic power
output of the ultrasound imaging system. Increasing MI increases
image quality, but there are tradeoffs with microbubble destruction.
Microbubble destruction could cause local microvasculature ruptures
and hemolysis.