Contrast echocardiography Sruthi Meenaxshi Post Doc Fellow VMCRH

1. Contrast Echocardiography
DR.S.R.Sruthi Meenaxshi MBBS, MD,
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2. Contrast Echocardiography
• Contrast echocardiography is a technique for improving echocardiographic
resolution and providing real time assessment of intracardiac blood flow.
• Agitated saline contrast provides contrast in the right heart and enables
detection of right to left shunts.
• Opacification of the left ventricular (LV) cavity by contrast agents
developed to traverse the pulmonary vasculature permits improved
endocardial border detection
• In a 2018 update to the American Society of Echocardiography (ASE)
Guidelines, an alternative name for echocardiographic contrast agents as
ultrasound enhancing agents (UEAs) was proposed to help patients and
providers distinguish these agents from other iodinated contrast agents
and gadolinium

3. US FDA APPROVED INDICATION
• cardiac imaging is for LV opacification via an
intravenous injection.
• off label uses of UEAs,
• stress echocardiography,
• enhancement of Doppler signal,
• Assess myocardial perfusion and viability
• intracoronary injection during alcohol septal
ablation for hypertrophic cardiomyopathy
patients

4. MICROBUBBLE CONTRAST AGENTS
• Mechanism of contrast:
• As sound travels from one medium to another, the
change in density (known as acoustic impedance) at
the interface causes the reflection of sound waves .
• The greater the difference in the media densities, the
more echogenic the interface.
• Gas is an excellent contrast agent since it is 100,000
times less dense than blood.

5. AGITATED SALINE CONTRAST
• Agitated saline solution administered via intravenous
injection provides air microbubble contrast in the right
heart.
• The air microbubbles are short-lived and diffuse into the
lungs when traversing the pulmonary circulation.
• Therefore the microbubbles enter the left heart only in the
presence of a right to left intracardiac or extracardiac
(pulmonary arteriovenous) shunt.
• Saline microbubbles are therefore helpful in examining the
right heart and identifying shunts.

6. Contrast agents for LV opacification
• To allow left heart evaluation , ideal contrast microbubble
must be small and durable
• However, a small bubble size (diameter ≤10 µm) is required
for successful transpulmonary passage
• Contrast agents must meet the following requirements:
❖ safe
❖ metabolically inert
❖ long lasting
❖ strong reflector of ultrasound
❖ small enough to pass through capillaries

7. Other agents
• Indocyananine green dye
• Polysaccharide or gelatin encapsulated air
• Albunex – First US FDA approved myocardial
contrast agent ( use 5 % human albumin
solution – limited utility due to microbubble
air loss which results in large decrease in
echogenicity)

8. SECOND GENERATION CONTRAST
AGENTS
• Gas Diffusion decreased by use of inert gases
(eg.perflurocarbons) to form microbubbles.
• Improved bubble surface stability was
attained through use of innovative colloidal
suspensions or emulsions

9. SGA From December 2019 ,
commercially available worldwide for
cardiac imaging
❖ PERFLUTREN PROTEIN TYPE A (Optison) – A human albumin-based
shell enclosing octafluoropropane gas (perflutren) This agent is FDA
approved and is also available in Canada.
❖ PERFLUTREN LIPID MICROSPHERES (Definity) – A phospholipid
shell enclosing octafluoropropane gas (perflutren) This agent is FDA
approved and is also available in Europe (known as Lumity), Canada,
Australia, and in parts of Asia.
❖ Sulfur hexafluoride lipid microsphere (Lumason) – A phospholipid
shell enclosing sulfur hexafluoride gas. This agent is FDA approved
and is available in Canada, Europe, and some Latin American and
Asian countries.

16. Adverse effect
• Limited data on children and adolescents
• chest pain, fatigue, back/neck pain, headache, dizziness, or shortness of breath) lasting less than 60
seconds during contrast administration, and none of the 113 patients were found to have had an
adverse event within 24 hours of perflutren lipid microsphere (Definity) administration
• Another study included 20 patients (ages 9 to 18 years) who underwent transthoracic
echocardiography with perflutren protein A (Optison) echocontrast. There were no adverse
hemodynamic effects, changes in taste, or flushing episodes. Three patients experienced transient
headaches
• Sulfur hexafluoride lipid microsphere (Lumason) was initially FDA approved for noncardiac imaging
in pediatric patients (eg, liver imaging, evaluation of vesicoureteral reflux); as of December 2019,
the FDA has also approved the use of sulfur hexafluoride lipid microsphere (Lumason) for cardiac
imaging in pediatric patients
• This is based on a study of 12 pediatric patients (ages 9 to 17 years) with suspected cardiac disease
and suboptimal noncontrast echocardiography who received Lumason in one prospective
multicenter clinical trial. No adverse effects were reported.

17. OPTIMAL ECHOCARDIOGRAPHIC
SETTINGS
• Contrast agent durability is dependent upon
both bubble composition and ultrasonic
characteristics.
• Alterations in the echocardiographic settings
can therefore optimize both microbubble
durability and contrast intensity.

18. Equipment setup and contrast agent administration 2008
American Society of Echocardiography (ASE) consensus
statement on contrast agents in echocardiography
• Harmonic detection — Second harmonic detection systems
improve the signal-to-noise ratio of contrast images
• Microbubbles resonate (shake) with exposure to ultrasound energy
at frequencies that are multiples of the ultrasound frequency
emitted from the transducer.
• This results in the emission of fundamentals (same frequency) and
harmonics (multiples) of the frequency to which they are exposed
• By setting the imaging frequency of the echo system to a harmonic
of the emitted frequency, the system "filters" out all returning
fundamental frequencies from the myocardium and enhances the
microbubble signal.

19. • The contrast intensity improves two to three times using
second harmonics
• Other advantages to harmonic imaging include decreased
artifact and shadowing, as well as enhanced contrast
detection in areas of low microbubble concentration
• Harmonic imaging also improves endocardial tracking even
without echocardiographic contrast
• However, the ejection fraction obtained by harmonic
imaging along with contrast echocardiography provides the
closest correlation with the radionuclide ejection fraction

20. Intermittent or transient imaging
When a sound wave interacts with a microbubble, some of the energy
is reflected, but a portion actively destroys the microbubbles.
As a result, continuous ultrasound imaging results in depletion of the
microbubble population, giving a suboptimal signal-to-noise ratio .
• Increased microbubble durability may be accomplished with
intermittent or transient response imaging .
• Ultrasound that is emitted only once per cardiac cycle, or as
infrequently as every 5 to 10 beats, improves microbubble contrast
intensity inversely with bubble transit velocity

21. Low mechanical index imaging
❖ Another technique to decrease the destruction of
microbubbles is low mechanical index imaging.
❖ If a very low acoustic power is transmitted, fewer bubbles
will be destroyed even with continuous imaging.
❖ Commercial echocardiographic machines now have this
"real time" contrast imaging and studies assessing its utility
are ongoing.
❖ Images may also be enhanced using Doppler technology
with power-Doppler imaging and/or ultrasound pulse
inversion technology

22. Mode of contrast injection —
• The mode of contrast injection can affect
image quality.
• Steady state infusions offer an advantage
over single or multiple bolus injections of
agents
• Allows titration to an optimal and uniform
image and extending the duration of LV
opacification, allowing for time to assess
multiple anatomic views

23. CLINICAL APPLICATIONS OF CONTRAST
ECHOCARDIOGRAPHY
• Shunt detection — The first clinical use of contrast
echocardiography was for detection of right-to-left
shunts
• Agitated saline given intravenously is well suited for
this purpose because microbubbles of air formed from
agitating saline persist long enough to opacify the right
heart chambers and diffuse into the lungs when
traveling through the pulmonary circulation.
• Therefore, microbubbles will not gain access to the left
heart chambers unless a right-to-left intracardiac or
extracardiac shunt is present.

25. Agitated saline contrast to detect
intracardiac shunt and pulmonary
arteriovenous shunting
• This technique is used most often for the detection of
1. patent foramen ovale
2. atrial septal defects
3. ventricular septal defects
4. arteriovenous shunts in the pulmonary vasculature.
• The appearance of bubbles in the left heart early (within three to
five beats) after right chamber opacification suggests an
intracardiac shunt
• Later appearance of bubbles in the left heart (>5 beats after first
seeing bubbles in the right atrium) suggests pulmonary
arteriovenous shunting.

26. • Microbubble contrast agents such as
• Optison ,
• Definity and
• Lumason (sulfur hexafluoride lipid
microsphere) that traverse the pulmonary
vasculature are NOT designed for shunt
detection.

28. Doppler signal enhancement
❖AGITATED SALINE (and other ultrasound
contrast agents) may be used to enhance
tricuspid Doppler signals for use in assessment
of transvalvular velocity
❖to estimate right ventricular systolic pressure.

29. DIAGNOSIS OF PERSISITENT LEFT
SUPERIOR VENA CAVA
• Agitated saline (or other ultrasound) contrast can help confirm the diagnosis of persistent left
superior vena cava (SVC).
• This venous anomaly is usually detected incidentally
• A persistent left SVC is suspected when a dilated coronary sinus is detected in the absence of a
cause for elevated right atrial pressure.
•
• A persistent left superior vena cava drains directly into the coronary sinus leading to a characteristic
sequence of contrast appearance: following injection of contrast into a left arm vein, contrast
appears in the coronary sinus before appearing in the right atrium
• Upon intravenous injection of contrast into the right arm, there is normal transit of contrast with
right atrial opacification before appearance of contrast in the coronary sinus.
• The presence of a left SVC may complicate transvenous placement of pulmonary artery (Swan-
Ganz) catheters, pacemaker or implantable cardioverter-defibrillator leads, as well as retrograde
cardioplegia

30. CLINICAL APPLICATIONS FOR
MICROBUBBLE CONTRAST AGENTS
• ENDOCARDIAL BORDER DEFINITION:
• The second generation microbubble contrast agents
Definity ,Optison and Lumason (Sulfur hexafluoride lipid
microsphere), which are available in most countries)
traverse the pulmonary vasculature and are indicated for LV
opacification and LV endocardial border definition in
patients with technically suboptimal.
• In the 2011 ASE/AHAA Appropriate Use Criteria for
Echocardiography, the use of contrast is considered
appropriate when >2 contiguous LV segments are not seen
on noncontrast images

32. Rest echocardiography
▪ Contrast opacification of the LV cavity enhances
border detection, decreasing the variability in the
interpretation of regional wall motion
abnormalities, LV volumes and remodeling, and
the ejection fraction (EF)
▪ It is an accurate and cost-effective method for
evaluating LV function in situations where
obtaining a study is technically difficult, such as in
the intensive care unit

34. 2008 American Society of
Echocardiography (ASE) guidelines
●Difficult to image patients presenting for rest
echocardiography with reduced image quality
•To enable improved endocardial visualization and
assessment of LV structure and function when ≥2
contiguous segments are not seen on non-contrast images
•To reduce variability and increase accuracy in LV volume and
LVEF measurements by 2D echocardiography
•To increase the confidence of the interpreting clinician in LV
functional, structure, and volume assessments

35. ●To confirm or exclude the echocardiographic diagnosis of the following LV
structural abnormalities, when nonenhanced images are suboptimal for
definitive diagnosis:
•Apical variant of hypertrophic cardiomyopathy
•LV noncompaction
•Apical thrombus
•Complications of myocardial infarction, such as LV aneurysm,
pseudoaneurysm, and myocardial rupture
●To assist in the detection and correct classification of intracardiac masses,
including tumors and thrombi
●For imaging in the intensive care unit (ICU) when standard tissue harmonic
imaging does not provide adequate cardiac structural definition

36. Apical LV thrombus

37. STRESS ECHOCARDIOGRAPHY
• Diagnostic exercise and pharmacologic stress echocardiography depend
upon the accurate assessment of segmental wall motion and thickening.
• Echocardiographic contrast administration during stress echocardiography
is commonly performed to better define endocardial borders in patients
with suboptimal echocardiographic images (to enhance the detection of
wall motion abnormalities).
• Additionally, the administration of echocardiographic contrast can be
performed for the concurrent assessment of myocardial perfusion.
• When perfusion imaging is combined with contrast assessment of wall
motion abnormalities, the process is typically referred to as real-time
myocardial contrast echocardiography (RTMCE).

38. • The 2008 ASE guidelines suggest contrast
echocardiography for difficult to image
patients presenting for stress
echocardiography with suboptimal image
quality
●To obtain diagnostic assessment of segmental
wall motion and thickening at rest and stress

40. ALCOHOL SEPTAL ABLATION
• Contrast echocardiography can be used to guide alcohol septal ablation used as a treatment
to diminish LV outflow obstruction in patients with hypertrophic cardiomyopathy
• Injection of one of the second-generation echocardiographic contrast agents into the
proposed target septal arteries to determine the territory supplied by them is key to the
success of the procedure, as defined by at least a 50 percent reduction in left ventricular
outflow tract (LVOT) gradient
• After the target septal perforator is identified, a balloon catheter is advanced into the vessel
and inflated. One to 2 mL of a diluted echocardiographic contrast agent is injected through
the balloon catheter during continuous echocardiographic imaging.
• A well-demarcated area with increased echodensity in the basal septum will be noted
• Myocardial contrast echocardiography (MCE) can accurately delineate the size of the septal
vascular territory prior to ethanol injection and can predict the infarct size that results from
ethanol infusion

41. • Optison(perflutren protein type A) has been used for this purpose.
• DEFINITY and LUMASON is contraindicated by FDA regulations
• The 2011 ASE clinical recommendations for multimodality
cardiovascular imaging of patients with hypertrophic
cardiomyopathy do endorse the use of MCE during alcohol septal
ablation, and list the following advantages:
• shorter intervention time, shorter fluoroscopy time, fewer occluded
vessels, smaller amount of ethanol used, smaller infarct size, lower
likelihood of heart block, and higher likelihood of success .

42. MYOCARDIAL PERFUSION
• Portable real-time, noninvasive assessment of
myocardial perfusion may become possible
with improved contrast echocardiography
agents and detection algorithms
• Controlled investigations with newer, second
generation agents have shown that routine
intravenous injection accurately identifies
myocardial perfusion

43. MYOCARDIAL VIABILITY
• Myocardial viability assessment, particularly in the high risk patient with LV
dysfunction, has had increasing importance in patient management and
decision making.
• Current techniques used to determine myocardial viability include SPECT
imaging, positron emission tomography scanning, nuclear magnetic imaging,
and low-dose dobutamine echocardiography.
• Provides simultaneous LV function and perfusion information via a single
modality
• The identification of
❖ subnormal flow (heterogeneous contrast effect)
❖ no flow (fixed contrast defect)
❖ normal flow (homogeneous contrast) within dysfunctional myocardium
predicts long-term recovery of function following the restoration of normal blood
supply

45. STUNNED MYOCARDIUM
• Dysfunctional segments of the LV following an ischemic
insult may represent either infarcted or stunned tissue.
• Contrast echocardiography may be helpful in differentiating
these two patterns of myocardial dysfunction.
• Stunned myocardium has homogeneous myocardial
contrast, representing normal blood flow with an intact
microvasculature.
• Such a pattern implies either that the decrease in perfusion
was not lethal or that reperfusion (either spontaneous or as
a result of intervention) occurred prior to necrosis.

49. HIBERNATING MYOCARDIUM
• Hibernating myocardium — Hibernation is the
metabolic adaptation and downregulation that occurs
following a chronic ischemic insult.
• As with stunned myocardium, necrotic transformation
is avoided and microvascular integrity is maintained,
but blood flow and systolic function remain
suboptimal. In this setting, findings obtained via
contrast echocardiography may be informative.
• The degree of contrast homogeneity may be
proportional to the extent of functional recovery

50. INTRAVENTRICULAR FLOW PATTERNS
• In addition to improving endocardial border detection by LV opacification
• The intraventricular dynamics of contrast exhibits characteristic flow
patterns during the cardiac cycle, which may be associated with LV
segmental or global function.
• Two different flow patterns were identified
●A swift, vertical, and homogeneous flow towards the apex; 91 percent of
patients with this pattern had normal LV segmental function and 93 percent
had normal global LV function
●A distinctly protracted, swirling, and heterogeneous pattern; 99 percent of
patients with this pattern had one or more wall motion abnormality and 83
percent had various degrees of LV dysfunction

51. Swift , vertical homogenous pattern to
the apex – normal global LV function

52. Swirling pattern , left ventricular
dyssynergy and reduced global function

53. Local drug delivery
• Utilizing known ultrasonic destruction of microbubbles, local drug
delivery of agents (contained within the shell) could be performed
with well-controlled end-organ targeting
• As an example, enhancement of thrombolysis may be possible
within a specific vascular area using targeted contrast agent
destruction.
• Characterization of the effects of microbubble destruction on the
endothelium has stimulated investigation into techniques for
endothelial-directed drug therapy
• Genetic elements capable of stimulating angiogenesis or inhibiting
neointimal proliferation following balloon injury could potentially
be deposited at specific sites.

54. THANKYOU