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 Contrast-enhanced ultrasound (CEUS)
involves the administration of intravenous
contrast agents containing microbubbles of
perfluorocarbon or nitrogen gas.
 The microbububbles affect ultrasound
backscatter and increase vascular contrast in
a similar manner to intravenous contrast
agents used in CT and MRI
 Microbubble shell material determines how
easily the microbubble is taken up by
the immune system.
 The material for microbubble determines its
time in circulation and elasticity.
 Microbubble shells are composed
of albumin, galactose, lipid, or polymers
 Microbubble gas core is the most important
part because it determines the echogenicity.
 Size of Microbubble is around 1 - 4 μm.
 The Microbubble is nearly around the size of
RBCs as it should not cross the vascular
endothelium.
Air (Nitrogen) Perfluorocarbon Sulfur hexafluoride
Albunex (Mallinckrodt) BR14 (Bracco) SonoVue (Bracco)e
Echovist (Shering) Definity (Bristol–Myers
Squibb Medical
Imaging)
Levovist (Shering) Echogen (Sonus
Pharmaceuticals)
Myomap (Quadrant) Imagent–Imavist
(Alliance)
Quantison (Quadrant) Optison (GE
Healthcare)
 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.
 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.
1.Non-targeted
contrast-enhanced
ultrasound
2.Targeted contrast-
enhanced 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.
 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 in.
 Appearance of prostate cancer at CEUS. (A) Baseline transrectal
US 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
 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.
 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.
ADVERSE EVENT FREQUENCY
0.5-5 %
FREQUENCY
<1%
SYSTEMIC HEADACHE
HYPERSENSITIVITY
ABDOMINAL PAIN
WEAKNESS
CHEST PAIN, BACK
PAIN.
CARDIOVASCULAR HYPERTENSION ATRIAL FIBRILATION
PALPITATION,
TACHYCARDIA
DIGESTIVE SYSTEM NAUSEA ANOREXIA , DIARRHEA,
DYSPEPSIA
MSK, CNS DIZINESS, DRYMOUTH,
VASODILATATION
LEG CRAMPS,
PARESTHESIA
RESPIRATORY, SKIN DYSPNOEA, SWEATING,
RASH, PRURITUS
SPECIAL SENSES ALTERED TASTE, SMELL.
 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.
 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.
 Microbubbles don’t last very long in circulation.
They have low circulation residence times
because they either get taken up by immune
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.
 Targeting ligands can be immunogenic, since
current targeting ligands used in preclinical
experiments are derived from animal culture.
 Low targeted microbubble adhesion
efficiency. This is main reasons that targeted
contrast-enhanced ultrasound remains in the
preclinical development stages.
Contrast enhanced ultrasound

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Contrast enhanced ultrasound

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  • 2.  Contrast-enhanced ultrasound (CEUS) involves the administration of intravenous contrast agents containing microbubbles of perfluorocarbon or nitrogen gas.  The microbububbles affect ultrasound backscatter and increase vascular contrast in a similar manner to intravenous contrast agents used in CT and MRI
  • 3.  Microbubble shell material determines how easily the microbubble is taken up by the immune system.  The material for microbubble determines its time in circulation and elasticity.  Microbubble shells are composed of albumin, galactose, lipid, or polymers  Microbubble gas core is the most important part because it determines the echogenicity.
  • 4.  Size of Microbubble is around 1 - 4 μm.  The Microbubble is nearly around the size of RBCs as it should not cross the vascular endothelium.
  • 5. Air (Nitrogen) Perfluorocarbon Sulfur hexafluoride Albunex (Mallinckrodt) BR14 (Bracco) SonoVue (Bracco)e Echovist (Shering) Definity (Bristol–Myers Squibb Medical Imaging) Levovist (Shering) Echogen (Sonus Pharmaceuticals) Myomap (Quadrant) Imagent–Imavist (Alliance) Quantison (Quadrant) Optison (GE Healthcare)
  • 6.  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.
  • 7.  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.
  • 8.  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.
  • 10.  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.
  • 11.  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
  • 12. 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 in.
  • 13.  Appearance of prostate cancer at CEUS. (A) Baseline transrectal US 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
  • 14.  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
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  • 16.  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.
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  • 18.  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.
  • 19.  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
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  • 21. 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.
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  • 23.
  • 24. ADVERSE EVENT FREQUENCY 0.5-5 % FREQUENCY <1% SYSTEMIC HEADACHE HYPERSENSITIVITY ABDOMINAL PAIN WEAKNESS CHEST PAIN, BACK PAIN. CARDIOVASCULAR HYPERTENSION ATRIAL FIBRILATION PALPITATION, TACHYCARDIA DIGESTIVE SYSTEM NAUSEA ANOREXIA , DIARRHEA, DYSPEPSIA MSK, CNS DIZINESS, DRYMOUTH, VASODILATATION LEG CRAMPS, PARESTHESIA RESPIRATORY, SKIN DYSPNOEA, SWEATING, RASH, PRURITUS SPECIAL SENSES ALTERED TASTE, SMELL.
  • 25.  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.
  • 26.  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.
  • 27.  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.
  • 28.  Microbubbles don’t last very long in circulation. They have low circulation residence times because they either get taken up by immune 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.
  • 29.  Targeting ligands can be immunogenic, since current targeting ligands used in preclinical experiments are derived from animal culture.  Low targeted microbubble adhesion efficiency. This is main reasons that targeted contrast-enhanced ultrasound remains in the preclinical development stages.