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Current role of contrast echo-recent advances & clinical
applications
Dr Malleswara Rao
blood appears ‘black-Why?
• not because blood produces no echo
• sound scattered by RBCs is very weak,
1,000–10,000 times weaker than that from
solid tissue, so lies below the displayed
dynamic range
Why Doppler cant assess myocardial perfusion
• Doppler detects large volumes of blood moving
slowly( as in the cavities), and small volumes of
blood moving fast(as in stenotic valvular jets)
• It can visualise the flow at parenchymal level, where
blood vessels lie below the resolvable limit of the
image ( diameter <100 µm and below the
resolution limit of the image)
• as we progress distally in the arterial system, the
blood flows more slowly, producing lower Doppler
shift frequencies.
• weakening the back- scattered echo.
• a point is reached at which the vessel cannot be
visualised and the Doppler signals cannot be detected.
• The myocardial perfusion bed lies beyond this point.
• contrast agent
↓
• enhance the blood echo
↓
• increasing the signal-to-noise ratio
↓
• Increaes success rate of a Doppler examination
• echoes from blood at the arteriolar level exist
in the midst of echoes from the
surrounding solid structures of the organ
parenchyma, echoes which are almost always
stronger than even the contrast-enhanced
blood echo
Why we need UCA
• To increase the blood echo to a level that is
higher than that of the surrounding tissue
OR
• To suppress the echo from noncontrast-
bearing structures
highpass (or ‘wall’) filter VS UCA
• Separates Doppler signals due to blood flow
from those due to the wall itself
• valid for flow in large vessels or across the
cardiac valves
• not valid for the myocardium
MOA
• enhance echo by increasing the back-
scatter of the tissue that bears them while
without increasing the attenuation in the
tissue
b1.Free gas ubbles
• come out of solution either by agitation or by
cavitation during the injection itself
• Agitated solutions of indo- cyanine green and
renografin
• limitation
1. Large Size
2. filtered by the lungs
3. Unstable(go back into solution within a second)
• unsuitable for imaging of left-sided cardiac
chambers, the coronary circulation and the systemic
arterial tree and its organs.
2.Encapsulated air bubbles
• more stable
• comparable size to that of RBC
• can survive passage through the heart and the
pulmonary capillary network
• produced by sonication of a solution of
human serum albumin
• shells’ which stabilise the microbubbles are
extremely thin and allow a gas such as air to
diffuse out and go back into solution
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
3.Low solubility gas bubbles
• increase backscatter enhancement further
• last longer in the bloodstream
• advantage of low solubility gases such as
perfluorocarbons, the consequent lower
diffusion rate increasing the longevity
Revised contraindications
hypersensitivity to the products
products are not for intra-arterial injection.
Revised contraindications
•serious cardiopulmonary reactions during or within
30 minutes following the administration
•high risk patients with PAH or unstable
cardiopulmonary conditions be closely monitored
during and for at least 30 minutes post
administration .
Inadequate bubble concentration, causes less
opacification (MC with first-generation agents
because of excessive bubble destruction when
insonified with ultrasound.)
LVO requires a long duration of the contrast effect
Contrast agents that are easily destroyed will be
useful in myocardial perfusion studies
Preparing for injection
• use of smaller diameter cannula-avoid
• bubbles are subjected to large pressure drop due to the
Bernoulli effect as the fluid exits the tip of the lumen
• faster the injection and the smaller the diameter, the larger
the pressure drop and the greater the likelihood of
damage to the bubbles
• 22 G or larger needle is best
• smaller the needle lumen, the slower the injection should
be
• Bubbles can also be destroyed by pushing the syringe
plunger against a closed line
• total injection volume for some studies can be less than
1ml, So a flush is needed .
• 5–10 ml saline administered through a 3-way stopcock at
the end of a short line which allows free movement of the
syringe for mixing
• saline to traverse the right angle bend of the stopcock, not
the agent
Bolus
• first-pass peak enhancement is followed by a
steady, exponential wash-out phase
• huge enhancement at the peak causes over-
loading of the Doppler receiver, creating
spectral or colour blooming
• wait until the wash-out phase, in which a
more suitable enhancement can be obtained
for a longer period.
Infusion
• bolus injec- tion=short duration, maximum effect
as in LV opacification for the wall motion studies
• slow injection(injection pump/dripping the
diluted agent through an IV line/infusion pump )
• maintain an enhancement comparable to that
of the peak bolus for a period which matches
more closely that of the clinical ultrasound
examination
INFUSION
• the agent must remain stable in the syringe
• Levovist, which is quite viscous after
mixing provides this more easily than
Optison, in which emulsion the bubbles
tend to float.
• Agitating the preparation while it is in the
syringe is in practice difficult
• some perfluorocarbon agents such as
Definity are effective in very high dilution
MOA
• A sound field comprises a train of travelling waves,
much like ripples on a pond.
• The fluid pressure of the medium (tissue) changes
as the sound propagates through it.
• gas bubble is highly compliant and hence is
squashed when the pressure outside it is raised and
expanded when the pressure is lowered.
• bubble undergoes this oscillatory motion two million
times per second.
• bubble becomes a source of sound that radiates
radially
• sound that reaches the transducer from this bubble,
combined with that from all of its neighbours, is what
constitutes the scattered echo
• impedance and hence acts as a strong reflector.
Size for size, a bubble is about one hundred
million million times more effective at scattering
ultrasound. Thus the injection of a relatively
sparse population of bubbles into the
bloodstream results in a substantial enhance-
ment of the blood echo.
Bubble behaviour and incident pressure
• Unlike tissue, a bubble does not scatter in the same
way if it is exposed to weak (that is low amplitude)
sound, than to strong, high ampli tude sound.
LINEAR
• low incident pressures (low transmit power of
the scanner)
↓
• linear backscatter enhancement
↓
• augmentation of the echo from blood.
• E.g. Doppler signal enhancement
• not require any change to ultrasound imaging
and Doppler instrumentation
NON-LINEAR
• pressure incident of about 50–100 kPa(still
below the level used in most diagnostic
scans)
↓
backscatters are nonlinear such as the emission
of harmonics
• E.g=harmonic and pulse inversion imaging
and Doppler
• At peak pressure passes about 1 MPa, near
the maximum emitted by a typical echo
imaging system, many agents exhibit
transient nonlinear scattering
• basis of triggered imaging and most strategies
for detection of myocardial perfusion
(<100 kPa)
(100 kPa–1 Mpa)
The Mechanical Index (MI)
• ultrasound scanners carry an on-screen
label of the estimated peak negative pressure
to which tissue is exposed
• pressure changes according to the tissue
through which the sound travels as well as
the amplitude and geometry of the
ultrasound beam
• higher the attenuation, the less the peak
pressure in tissue will be
• MI=peak rarefactional (that is, negative)
pressure, divided by the square root of the
ultrasound frequency
• related to the amount of mechanical work that
can be per- formed on a bubble during a single
negative half cycle of sound
• lies between 0.1 and 2.0.
• actual MI varies throughout the image.
• In the absence of attenuation, the MI is maximal at
the focus of the beam.
• Attenuation shifts this maximum towards the
transducer.
• controlled by means of the ‘output power’ setting
of the s canner.
Enhancement studies with conventional imaging
• increase success rate of Doppler assessments
of AS, MR & pulmonary venous flow
• enhancement is seen in lumina of ventricles
or large vessels
• Not seen in small vessels within the muscle of
the myocardium
• 10–25 dB of enhancement provided by the
agent still leaves the blood echo some
10–20 dB below that of the echogenic tissue of
the heart wall
• perfusion imaging cannot be effective .
II – Nonlinear backscatter: harmonic imaging
• identifies echo from the contrast agent and
suppress the echo from solid tissue
• means for detection of flow in smaller
vessels
HARMONIC IMAGING
• radial oscillations have a natural – or
resonant – frequency that scatter
ultrasound with a peculiarly high efficiency.
• resonant frequency of radial oscillation of a
bubble of 3 µm diameter, the median
diameter of a typical transpulmonary
microbubble agent is 3 MHz.
NON LINEAR SCATTERING
• if bubbles are ‘driven’ by the ultrasound
field at sufficiently high acoustic pressures,
the oscillatory excursions of the bubble
reach a point where the alternate
expansions and contractions of the
bubble’s size are not equal.
• sound emitted contains harmonics, just as the
resonant strings of a musical instru- ment, if
plucked too vigorously, will produce a
‘harsh’ timbre containing overtones
• this phenomenon of asymmetry which
begins to affect resonant oscillation as the
amplitude becomes large.
• in the rarefaction phase of the ultrasound
pulse, the bubble becomes less stiff, and,
therefore, enlarges much more
• strong echo with respect to the fundamental,
is seen at twice the transmit- ted frequency,
the second harmonic.
• Some Peaks in the echo spectrum at sub- and
ultraharmonics .
• excite them so as to produce harmonics
and detect these in preference to the
fundamental echo from tissue
Echoes from solid tissue, as well as red
blood cells themselves, are suppressed.
Harmonic power Doppler imaging
• Can identify microbubble in the tissue vascu-
lature
• In conventional Doppler, the signal from
blood is larger than the clutter signal from
tissue
• In contrast enhanced Doppler, the signal
from blood is raised
• With harmonic mode, the signal from blood is
raised but that from the tissue reduced, so
reversing the contrast between tissue and
blood.
• greater sensitivity to small quan- tities of agent
• given level of enhancement due to a bolus will
last longer
• cardiac contrast imaging in any mode is
generally more effective with the harmonic
method
• This is the reason that solid tissue is not
completely dark in a typical harmonic image
• detecting per- fusion in the myocardium is
more difficult.
Tissue harmonic imaging
• ultrasound scanner transmits at one frequency
and receives at double this frequency
• any source of a received signal at the
harmonic frequency which does not come
from the bubble, will clearly reduce the
efficacy
• tissue itself can produce harmonics
Pulse inversion imaging
• ordinary tissue, which behaves in a linear
manner, the sum of two inverted pulses is
simply zero.
• For an echo with nonlinear components,
such as that from a bubble, the echoes
produ ced from these two pulses will not be
simple mirror images of each other
III - Transient disruption: intermittent imaging
As the incident pressure to which a resonating bubble is
exposed increases, so its oscillation becomes more wild,
with radius increasing in some bubbles by a factor of five
or more during the rarefaction phase
as a resonating violin string, if bowed over- zealously, will
break, so a microbubble
irreversible disruption of its shell
↓
bubble disappears as an acoustic scatterer
↓
it does so it emits a strong, brief nonlinear echo.
This is the basis of intermittent myocardial perfusion
imaging
• bubble will have a gas content that is
highly diffusible and soluble in blood.
• In this respect, air is perfect.
• Diffusion of air after acoustic dis- ruption is
about 40 times faster than such diffusion
of a perfluorocarbon gas from a simi- lar
bubble, so that air based agents such as
Levovist are easiest to image in this
contraindications removed
worsening or clinically unstable CHF
acute MI or ACS,
serious ventricular arrhythmias or high risk of
arrhythmias due to prolongation of the QT interval,
respiratory failure,
severe emphysema,
PTE or other conditions that cause PAH
Applications of Contrast Echocardiography
Detection of intracardiac shunts: ASD, PFO
Left ventricular opacification for chamber
delineation
Refined definition of LV structural abnormalities
Assessment of myocardial perfusion
Enhancement of doppler signals
Intracardiac shunts
Right vs. Left Heart Contrast
Agitated saline
Bubble diameter is greater
than diameter of pulmonary
capillaries
No transpulmonary passage
(in absence of
intrapulmonary shunt)
PFO/ASD/Persistent LSVC
Microbubble diameter of 1-5
µm
Able to traverse pulmonary
capillary bed
Resonate at frequency of
1.5-7 MHz, corresponding to
clinical transducer
frequencies
NO SHUNT
Shunt detection
 I.v injection of agitated saline
Right to left shunt
 ASD of all types
PFO -- Valsalva and cough
 pulmonary AVMs- 5 to 15 cycles
 Large VSDs may allow some right to left shunting
during diastole when pressure in the two
ventricles is relatively equal
Left SVC
Left-to-right shunt
Negative contrast effect
Intracardiac shunts
The detection of a right to left shunt on contrast
echo is indirect evidence of an ASD or PFO.
Right to left shunt of a large ASD may be nearly
continuous
For smaller ASDs the appearance of contrast in LA
may be phasic, coordinated with respiratory cycle
OS ASD
SINOUS VENOSUS ASD
Intracardiac shunts
•if LA pressure is consistently higher than RA
pressure
↓
exclusively left to right shunt
negative contrast -
•It should be differentiated from noncontrast
enhanced blood flowing from the IVC that could be
confused with a negative jet arising in the LA
PFO
•The shunt is often phasic with the respiratory cycle
•valsalva and cough may allow the occult right to left
shunt to manifest.
STROKE in young;PFO
ATRIAL SEPTAL ANEURYSM
Pulmonary AVMs
•delayed right to left shunt
•contrast appears in the LA after a delay of 5 to 15
cardiac cycles.
•tendency of the contrast to build up persistently
and slowly in the left heart and the lack of phasic
appearance of the contrast in the LA.-more specific
AVM at5sec ,20sec and 40 sec
Abnormal extracardiac comunications
Injection of agitated saline in to lower extremity vein
in an individual with azygos continuation of the IVC
allows detection of contrast in the more superior
portion of RA.
Injecting agitated saline into a left upper extremity
vein resulting in opacification of the dilated coronary
sinus before draining in to RA =persistent LSVC
LSVC
Lv opacification for chamber
delineation
Applications of LV opacification
•patients with reduced image quality
 To improve endocardial visualization
To assess LV structure and function
When two contiguous segments are not seen on
noncontrast images
To reduce variability and increase accuracy in LV
volume and LVEF .
To increase the confidence of the interpreting
physician in LV functional, structure, and volume
assessments
Applications of LV opacification
assessment of LV systolic function
To reduce variability in LV volume measurements
through 2D echo.
To increase the confidence of the interpreting
physician in LV volume measurement
excellent correlation with radionuclide, MR, and CT
measurements of LV volumes and LVEF
Improvement in LVEF Classification
Hundley WG, et al. J Am Coll Cardiol 1998; 32(5): 1426-32.
•Open Bars=Standard
Echocardiography
•Solid Bars=Contrast
Echocardiography
•In subjects with complete
visualization of the
endocardium, contrast agent
administration was of no
benefit.
•If ≥2 endocardial segments
were not visualized at
baseline, contrast
enhancement markedly
improved classification of EF
subsets.
LVO
Contrast Enhancement in Stress Echocardiography
•patients with reduced image quality
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
Exercise stress echocardiogram with contrast enhancement, apical long-axis views at end-
systole .Left view is taken at rest; right view taken after stress. View shows LV cavity dilation
and apical deformity (between yellow arrows) due to RWMA in the mid to apical
anteroseptal region on the post stress image.
ischemia in the LAD
Coronary angiogram (LAO view) =high-grade mid-LAD artery stenosis(white arrow)
Refined definition of LV structural abnormalities
LV structural abnormalities
•To confirm or exclude
Apical variant of hypertrophic cardiomyopathy
Ventricular noncompaction
Apical thrombus
Complications of MI(LV aneurysm,
pseudoaneurysm, and myocardial rupture)
LV structural abnormalities
•To assist in the detection and correct classification
of intracardiac masses, including tumors and thrombi
•For echocardiographic imaging in the ICU when
standard tissue harmonic imaging does not provide
adequate cardiac structural definition
For accurate assessment of LV volumes and LVEF
For exclusion of complications of MI, such as LV
aneurysm, pseudoaneurysm, and myocardial rupture
LV structural abnormalities
structural abnormalities of the LV apical region are
difficult to define clearly.
CEE -enables clear identification of apical endocardial
borders.
LV apical hypertrophy
•characteristic spadelike appearance of the LV cavity,
with marked apical myocardial wall thickening
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
LV apical hypertrophic cardiomyopathy. Four-chamber noncontrast tissue harmonic
image(left)and contrast image (right)at peak systole. Spadelike LV cavity contour is
clearly defined in the contrast image, which is difficult to define on a noncontrast image
LV noncompaction
thickened, hypokinetic segments that consist of 2
layers: a thin, compacted subepicardial myocardium
and a thicker, noncompacted subendocardial
myocardium.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
LV apical thrombus
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
LV apical aneurysm
characterized by thin walls and a dilated apex, which
may be akinetic or dyskinetic
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
Intracardiac masses
•contrast hyperenhancement of the tumor
(compared with the surrounding myocardium)
suggests a highly vascular or malignant tumor.
•stromal tumors (such as myxomas) have a poor
blood supply and appear hypoenhanced.
•Thrombi are avascular and show no enhancement.
Intracardiac Mass in RA vs. Thrombus
(mass hyper-enhanced with echocardiographic contrast
no enhancement of the mass or the adjacent myocardium after a high-mechanical
index impulse destroyed contrast bubbles, ruling out "false-positive perfusion" of
the mass.
follicular thyroid carcinoma.
Kirkpatrick JN, et al. JACC 2004.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
(Ano enhancement
no enhancement of the mass or adjacent myocardium after a high-mechanical index
impulse destroyed the contrast agent.
consistent with thrombus.
Intracardiac Mass vs. Thrombus
Kirkpatrick JN, et al. JACC 2004.
Extracardiac anatomy
Vascular imaging :dissection of the aorta and great
vessels, atherosclerotic plaque, intima-media
thickness, and detection of vasa vasora
Femoral arterial pseudoaneurysms
Myocardial Contrast Echocardiography
Myocardial Contrast Echocardiography
•Newer contrast agents can be used to identify coronary
collateral circulation
•preserved contrast effect in the myocardium was
evidence of microvascular integrity and blood flow to the
area.
•The presence of micorovascular blood flow was shown
to correlate with recovery of function after MI and is an
marker of hibernating myocardium in the chronic setting
•microbubbles will first appear on the right side of the
heart, then in the left heart, and last in the aorta, the
coronary arteries and the myocardial cappilaries.
Myocardial Contrast Echocardiography
Ultrasound with high mechanical index (>1.5)
destroys microbubbles
Myocardium with normal perfusion is enhanced by
microbubbles within 5-7 cardiac cycles
Normal myocardium appears opacified
Areas of decreased perfusion appear dark or patchy
Myocardial Contrast Echocardiography
1. continuous low mechanical index imaging
2. Intermittent triggered imaging
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
Myocardial Contrast Echocardiography
•The intensity of contrast in the myocardium is
directly related to myocardial blood volume but only
indirectly to coronary blood flow.
•A contrast time appearance curve can be generated
and multiple parameters of such a curve can be
correlated with myocardial perfusion.
alpha- intensity at which the contrast effect
plateaus
Beta-time constant of contrast appearance
Myocardial Contrast Echocardiography
•Alpha is directly related to myocardial blood
volume, beta is related to flow rate.
•The product of alpha and beta is directly
proportional to myocardial blood flow.
•By comparing characteristics of the flow curve
including alpha ,beta and their product, a hyperemic
ratio can be calculated by comparison of basal and
vasodilator contrast injections
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
Myocardial Contrast Echocardiography
•used in monitoring trans catheter alcohol septal
ablation (HCM)
•agent is injected directly into the septal perforator
to determining the feasibility of the procedure and
in following its progress.
•Before injection of ethanol, dilute ultrasound
contrast agent is injected into the selected artery in
order to
To ensure no significant reflux of contrast into the
body of the LAD artery or into the blood stream.
There may be a significant amount of contrast that
appears in the RV cavity
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
Doppler enhancement
Doppler enhancement
•Used when signal is weak.
•RR velocities -enhanced by agitated bacteriostatic
saline .
•Peak velocity in AS -enhanced with contrast agents
•transmitral (rarely necessary) and pulmonary
venous flow velocities can be improved .
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
First generation Contrast Agents:
Agitated saline with or without Indocyanine green.
CW Doppler from apical window before (left) and after (right) contrast enhancement.
left panel - only faint visualization of the velocity profile
right panel -shows not only peak transvalvular velocity(white
arrow)but also subvalvular velocity

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Current role of contrast echo recent advances &amp; clinical

  • 1. Current role of contrast echo-recent advances & clinical applications Dr Malleswara Rao
  • 2.
  • 3. blood appears ‘black-Why? • not because blood produces no echo • sound scattered by RBCs is very weak, 1,000–10,000 times weaker than that from solid tissue, so lies below the displayed dynamic range
  • 4. Why Doppler cant assess myocardial perfusion • Doppler detects large volumes of blood moving slowly( as in the cavities), and small volumes of blood moving fast(as in stenotic valvular jets) • It can visualise the flow at parenchymal level, where blood vessels lie below the resolvable limit of the image ( diameter <100 µm and below the resolution limit of the image) • as we progress distally in the arterial system, the blood flows more slowly, producing lower Doppler shift frequencies. • weakening the back- scattered echo. • a point is reached at which the vessel cannot be visualised and the Doppler signals cannot be detected. • The myocardial perfusion bed lies beyond this point.
  • 5.
  • 6. • contrast agent ↓ • enhance the blood echo ↓ • increasing the signal-to-noise ratio ↓ • Increaes success rate of a Doppler examination
  • 7. • echoes from blood at the arteriolar level exist in the midst of echoes from the surrounding solid structures of the organ parenchyma, echoes which are almost always stronger than even the contrast-enhanced blood echo
  • 8. Why we need UCA • To increase the blood echo to a level that is higher than that of the surrounding tissue OR • To suppress the echo from noncontrast- bearing structures
  • 9. highpass (or ‘wall’) filter VS UCA • Separates Doppler signals due to blood flow from those due to the wall itself • valid for flow in large vessels or across the cardiac valves • not valid for the myocardium
  • 10. MOA • enhance echo by increasing the back- scatter of the tissue that bears them while without increasing the attenuation in the tissue
  • 11. b1.Free gas ubbles • come out of solution either by agitation or by cavitation during the injection itself • Agitated solutions of indo- cyanine green and renografin • limitation 1. Large Size 2. filtered by the lungs 3. Unstable(go back into solution within a second) • unsuitable for imaging of left-sided cardiac chambers, the coronary circulation and the systemic arterial tree and its organs.
  • 12. 2.Encapsulated air bubbles • more stable • comparable size to that of RBC • can survive passage through the heart and the pulmonary capillary network • produced by sonication of a solution of human serum albumin • shells’ which stabilise the microbubbles are extremely thin and allow a gas such as air to diffuse out and go back into solution
  • 13. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green.
  • 14. 3.Low solubility gas bubbles • increase backscatter enhancement further • last longer in the bloodstream • advantage of low solubility gases such as perfluorocarbons, the consequent lower diffusion rate increasing the longevity
  • 15.
  • 16. Revised contraindications hypersensitivity to the products products are not for intra-arterial injection.
  • 17. Revised contraindications •serious cardiopulmonary reactions during or within 30 minutes following the administration •high risk patients with PAH or unstable cardiopulmonary conditions be closely monitored during and for at least 30 minutes post administration .
  • 18. Inadequate bubble concentration, causes less opacification (MC with first-generation agents because of excessive bubble destruction when insonified with ultrasound.) LVO requires a long duration of the contrast effect Contrast agents that are easily destroyed will be useful in myocardial perfusion studies
  • 19.
  • 20.
  • 21.
  • 22. Preparing for injection • use of smaller diameter cannula-avoid • bubbles are subjected to large pressure drop due to the Bernoulli effect as the fluid exits the tip of the lumen • faster the injection and the smaller the diameter, the larger the pressure drop and the greater the likelihood of damage to the bubbles • 22 G or larger needle is best • smaller the needle lumen, the slower the injection should be • Bubbles can also be destroyed by pushing the syringe plunger against a closed line • total injection volume for some studies can be less than 1ml, So a flush is needed . • 5–10 ml saline administered through a 3-way stopcock at the end of a short line which allows free movement of the syringe for mixing • saline to traverse the right angle bend of the stopcock, not the agent
  • 23.
  • 24. Bolus • first-pass peak enhancement is followed by a steady, exponential wash-out phase • huge enhancement at the peak causes over- loading of the Doppler receiver, creating spectral or colour blooming • wait until the wash-out phase, in which a more suitable enhancement can be obtained for a longer period.
  • 25. Infusion • bolus injec- tion=short duration, maximum effect as in LV opacification for the wall motion studies • slow injection(injection pump/dripping the diluted agent through an IV line/infusion pump ) • maintain an enhancement comparable to that of the peak bolus for a period which matches more closely that of the clinical ultrasound examination
  • 26. INFUSION • the agent must remain stable in the syringe • Levovist, which is quite viscous after mixing provides this more easily than Optison, in which emulsion the bubbles tend to float. • Agitating the preparation while it is in the syringe is in practice difficult • some perfluorocarbon agents such as Definity are effective in very high dilution
  • 27.
  • 28.
  • 29.
  • 30. MOA • A sound field comprises a train of travelling waves, much like ripples on a pond. • The fluid pressure of the medium (tissue) changes as the sound propagates through it. • gas bubble is highly compliant and hence is squashed when the pressure outside it is raised and expanded when the pressure is lowered. • bubble undergoes this oscillatory motion two million times per second. • bubble becomes a source of sound that radiates radially • sound that reaches the transducer from this bubble, combined with that from all of its neighbours, is what constitutes the scattered echo
  • 31. • impedance and hence acts as a strong reflector. Size for size, a bubble is about one hundred million million times more effective at scattering ultrasound. Thus the injection of a relatively sparse population of bubbles into the bloodstream results in a substantial enhance- ment of the blood echo.
  • 32.
  • 33. Bubble behaviour and incident pressure • Unlike tissue, a bubble does not scatter in the same way if it is exposed to weak (that is low amplitude) sound, than to strong, high ampli tude sound.
  • 34. LINEAR • low incident pressures (low transmit power of the scanner) ↓ • linear backscatter enhancement ↓ • augmentation of the echo from blood. • E.g. Doppler signal enhancement • not require any change to ultrasound imaging and Doppler instrumentation
  • 35. NON-LINEAR • pressure incident of about 50–100 kPa(still below the level used in most diagnostic scans) ↓ backscatters are nonlinear such as the emission of harmonics • E.g=harmonic and pulse inversion imaging and Doppler
  • 36. • At peak pressure passes about 1 MPa, near the maximum emitted by a typical echo imaging system, many agents exhibit transient nonlinear scattering • basis of triggered imaging and most strategies for detection of myocardial perfusion
  • 37.
  • 39. The Mechanical Index (MI) • ultrasound scanners carry an on-screen label of the estimated peak negative pressure to which tissue is exposed • pressure changes according to the tissue through which the sound travels as well as the amplitude and geometry of the ultrasound beam • higher the attenuation, the less the peak pressure in tissue will be • MI=peak rarefactional (that is, negative) pressure, divided by the square root of the ultrasound frequency
  • 40. • related to the amount of mechanical work that can be per- formed on a bubble during a single negative half cycle of sound • lies between 0.1 and 2.0. • actual MI varies throughout the image. • In the absence of attenuation, the MI is maximal at the focus of the beam. • Attenuation shifts this maximum towards the transducer. • controlled by means of the ‘output power’ setting of the s canner.
  • 41.
  • 42. Enhancement studies with conventional imaging • increase success rate of Doppler assessments of AS, MR & pulmonary venous flow • enhancement is seen in lumina of ventricles or large vessels • Not seen in small vessels within the muscle of the myocardium • 10–25 dB of enhancement provided by the agent still leaves the blood echo some 10–20 dB below that of the echogenic tissue of the heart wall • perfusion imaging cannot be effective .
  • 43. II – Nonlinear backscatter: harmonic imaging • identifies echo from the contrast agent and suppress the echo from solid tissue • means for detection of flow in smaller vessels
  • 44. HARMONIC IMAGING • radial oscillations have a natural – or resonant – frequency that scatter ultrasound with a peculiarly high efficiency. • resonant frequency of radial oscillation of a bubble of 3 µm diameter, the median diameter of a typical transpulmonary microbubble agent is 3 MHz.
  • 45.
  • 46. NON LINEAR SCATTERING • if bubbles are ‘driven’ by the ultrasound field at sufficiently high acoustic pressures, the oscillatory excursions of the bubble reach a point where the alternate expansions and contractions of the bubble’s size are not equal.
  • 47.
  • 48. • sound emitted contains harmonics, just as the resonant strings of a musical instru- ment, if plucked too vigorously, will produce a ‘harsh’ timbre containing overtones • this phenomenon of asymmetry which begins to affect resonant oscillation as the amplitude becomes large. • in the rarefaction phase of the ultrasound pulse, the bubble becomes less stiff, and, therefore, enlarges much more
  • 49. • strong echo with respect to the fundamental, is seen at twice the transmit- ted frequency, the second harmonic. • Some Peaks in the echo spectrum at sub- and ultraharmonics . • excite them so as to produce harmonics and detect these in preference to the fundamental echo from tissue Echoes from solid tissue, as well as red blood cells themselves, are suppressed.
  • 50.
  • 51.
  • 52. Harmonic power Doppler imaging • Can identify microbubble in the tissue vascu- lature • In conventional Doppler, the signal from blood is larger than the clutter signal from tissue • In contrast enhanced Doppler, the signal from blood is raised • With harmonic mode, the signal from blood is raised but that from the tissue reduced, so reversing the contrast between tissue and blood.
  • 53. • greater sensitivity to small quan- tities of agent • given level of enhancement due to a bolus will last longer • cardiac contrast imaging in any mode is generally more effective with the harmonic method • This is the reason that solid tissue is not completely dark in a typical harmonic image • detecting per- fusion in the myocardium is more difficult.
  • 54. Tissue harmonic imaging • ultrasound scanner transmits at one frequency and receives at double this frequency • any source of a received signal at the harmonic frequency which does not come from the bubble, will clearly reduce the efficacy • tissue itself can produce harmonics
  • 56. • ordinary tissue, which behaves in a linear manner, the sum of two inverted pulses is simply zero. • For an echo with nonlinear components, such as that from a bubble, the echoes produ ced from these two pulses will not be simple mirror images of each other
  • 57. III - Transient disruption: intermittent imaging As the incident pressure to which a resonating bubble is exposed increases, so its oscillation becomes more wild, with radius increasing in some bubbles by a factor of five or more during the rarefaction phase as a resonating violin string, if bowed over- zealously, will break, so a microbubble irreversible disruption of its shell ↓ bubble disappears as an acoustic scatterer ↓ it does so it emits a strong, brief nonlinear echo. This is the basis of intermittent myocardial perfusion imaging
  • 58. • bubble will have a gas content that is highly diffusible and soluble in blood. • In this respect, air is perfect. • Diffusion of air after acoustic dis- ruption is about 40 times faster than such diffusion of a perfluorocarbon gas from a simi- lar bubble, so that air based agents such as Levovist are easiest to image in this
  • 59. contraindications removed worsening or clinically unstable CHF acute MI or ACS, serious ventricular arrhythmias or high risk of arrhythmias due to prolongation of the QT interval, respiratory failure, severe emphysema, PTE or other conditions that cause PAH
  • 60. Applications of Contrast Echocardiography Detection of intracardiac shunts: ASD, PFO Left ventricular opacification for chamber delineation Refined definition of LV structural abnormalities Assessment of myocardial perfusion Enhancement of doppler signals
  • 62. Right vs. Left Heart Contrast Agitated saline Bubble diameter is greater than diameter of pulmonary capillaries No transpulmonary passage (in absence of intrapulmonary shunt) PFO/ASD/Persistent LSVC Microbubble diameter of 1-5 µm Able to traverse pulmonary capillary bed Resonate at frequency of 1.5-7 MHz, corresponding to clinical transducer frequencies
  • 64. Shunt detection  I.v injection of agitated saline Right to left shunt  ASD of all types PFO -- Valsalva and cough  pulmonary AVMs- 5 to 15 cycles  Large VSDs may allow some right to left shunting during diastole when pressure in the two ventricles is relatively equal Left SVC Left-to-right shunt Negative contrast effect
  • 65. Intracardiac shunts The detection of a right to left shunt on contrast echo is indirect evidence of an ASD or PFO. Right to left shunt of a large ASD may be nearly continuous For smaller ASDs the appearance of contrast in LA may be phasic, coordinated with respiratory cycle
  • 68. Intracardiac shunts •if LA pressure is consistently higher than RA pressure ↓ exclusively left to right shunt negative contrast - •It should be differentiated from noncontrast enhanced blood flowing from the IVC that could be confused with a negative jet arising in the LA
  • 69. PFO •The shunt is often phasic with the respiratory cycle •valsalva and cough may allow the occult right to left shunt to manifest.
  • 72. Pulmonary AVMs •delayed right to left shunt •contrast appears in the LA after a delay of 5 to 15 cardiac cycles. •tendency of the contrast to build up persistently and slowly in the left heart and the lack of phasic appearance of the contrast in the LA.-more specific
  • 73. AVM at5sec ,20sec and 40 sec
  • 74. Abnormal extracardiac comunications Injection of agitated saline in to lower extremity vein in an individual with azygos continuation of the IVC allows detection of contrast in the more superior portion of RA. Injecting agitated saline into a left upper extremity vein resulting in opacification of the dilated coronary sinus before draining in to RA =persistent LSVC
  • 75. LSVC
  • 76. Lv opacification for chamber delineation
  • 77. Applications of LV opacification •patients with reduced image quality  To improve endocardial visualization To assess LV structure and function When two contiguous segments are not seen on noncontrast images To reduce variability and increase accuracy in LV volume and LVEF . To increase the confidence of the interpreting physician in LV functional, structure, and volume assessments
  • 78. Applications of LV opacification assessment of LV systolic function To reduce variability in LV volume measurements through 2D echo. To increase the confidence of the interpreting physician in LV volume measurement excellent correlation with radionuclide, MR, and CT measurements of LV volumes and LVEF
  • 79. Improvement in LVEF Classification Hundley WG, et al. J Am Coll Cardiol 1998; 32(5): 1426-32. •Open Bars=Standard Echocardiography •Solid Bars=Contrast Echocardiography •In subjects with complete visualization of the endocardium, contrast agent administration was of no benefit. •If ≥2 endocardial segments were not visualized at baseline, contrast enhancement markedly improved classification of EF subsets.
  • 80. LVO
  • 81. Contrast Enhancement in Stress Echocardiography •patients with reduced image quality
  • 82. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green.
  • 83. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green. Exercise stress echocardiogram with contrast enhancement, apical long-axis views at end- systole .Left view is taken at rest; right view taken after stress. View shows LV cavity dilation and apical deformity (between yellow arrows) due to RWMA in the mid to apical anteroseptal region on the post stress image. ischemia in the LAD Coronary angiogram (LAO view) =high-grade mid-LAD artery stenosis(white arrow)
  • 84. Refined definition of LV structural abnormalities
  • 85. LV structural abnormalities •To confirm or exclude Apical variant of hypertrophic cardiomyopathy Ventricular noncompaction Apical thrombus Complications of MI(LV aneurysm, pseudoaneurysm, and myocardial rupture)
  • 86. LV structural abnormalities •To assist in the detection and correct classification of intracardiac masses, including tumors and thrombi •For echocardiographic imaging in the ICU when standard tissue harmonic imaging does not provide adequate cardiac structural definition For accurate assessment of LV volumes and LVEF For exclusion of complications of MI, such as LV aneurysm, pseudoaneurysm, and myocardial rupture
  • 87. LV structural abnormalities structural abnormalities of the LV apical region are difficult to define clearly. CEE -enables clear identification of apical endocardial borders.
  • 88. LV apical hypertrophy •characteristic spadelike appearance of the LV cavity, with marked apical myocardial wall thickening
  • 89. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green. LV apical hypertrophic cardiomyopathy. Four-chamber noncontrast tissue harmonic image(left)and contrast image (right)at peak systole. Spadelike LV cavity contour is clearly defined in the contrast image, which is difficult to define on a noncontrast image
  • 90. LV noncompaction thickened, hypokinetic segments that consist of 2 layers: a thin, compacted subepicardial myocardium and a thicker, noncompacted subendocardial myocardium.
  • 91. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green.
  • 93. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green.
  • 94. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green.
  • 95. LV apical aneurysm characterized by thin walls and a dilated apex, which may be akinetic or dyskinetic
  • 96. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green.
  • 97. Intracardiac masses •contrast hyperenhancement of the tumor (compared with the surrounding myocardium) suggests a highly vascular or malignant tumor. •stromal tumors (such as myxomas) have a poor blood supply and appear hypoenhanced. •Thrombi are avascular and show no enhancement.
  • 98. Intracardiac Mass in RA vs. Thrombus (mass hyper-enhanced with echocardiographic contrast no enhancement of the mass or the adjacent myocardium after a high-mechanical index impulse destroyed contrast bubbles, ruling out "false-positive perfusion" of the mass. follicular thyroid carcinoma. Kirkpatrick JN, et al. JACC 2004.
  • 99. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green. (Ano enhancement no enhancement of the mass or adjacent myocardium after a high-mechanical index impulse destroyed the contrast agent. consistent with thrombus. Intracardiac Mass vs. Thrombus Kirkpatrick JN, et al. JACC 2004.
  • 100. Extracardiac anatomy Vascular imaging :dissection of the aorta and great vessels, atherosclerotic plaque, intima-media thickness, and detection of vasa vasora Femoral arterial pseudoaneurysms
  • 102. Myocardial Contrast Echocardiography •Newer contrast agents can be used to identify coronary collateral circulation •preserved contrast effect in the myocardium was evidence of microvascular integrity and blood flow to the area. •The presence of micorovascular blood flow was shown to correlate with recovery of function after MI and is an marker of hibernating myocardium in the chronic setting •microbubbles will first appear on the right side of the heart, then in the left heart, and last in the aorta, the coronary arteries and the myocardial cappilaries.
  • 103. Myocardial Contrast Echocardiography Ultrasound with high mechanical index (>1.5) destroys microbubbles Myocardium with normal perfusion is enhanced by microbubbles within 5-7 cardiac cycles Normal myocardium appears opacified Areas of decreased perfusion appear dark or patchy
  • 104. Myocardial Contrast Echocardiography 1. continuous low mechanical index imaging 2. Intermittent triggered imaging
  • 105. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green.
  • 106. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green.
  • 107. Myocardial Contrast Echocardiography •The intensity of contrast in the myocardium is directly related to myocardial blood volume but only indirectly to coronary blood flow. •A contrast time appearance curve can be generated and multiple parameters of such a curve can be correlated with myocardial perfusion. alpha- intensity at which the contrast effect plateaus Beta-time constant of contrast appearance
  • 108. Myocardial Contrast Echocardiography •Alpha is directly related to myocardial blood volume, beta is related to flow rate. •The product of alpha and beta is directly proportional to myocardial blood flow. •By comparing characteristics of the flow curve including alpha ,beta and their product, a hyperemic ratio can be calculated by comparison of basal and vasodilator contrast injections
  • 109. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green.
  • 110. Myocardial Contrast Echocardiography •used in monitoring trans catheter alcohol septal ablation (HCM) •agent is injected directly into the septal perforator to determining the feasibility of the procedure and in following its progress. •Before injection of ethanol, dilute ultrasound contrast agent is injected into the selected artery in order to To ensure no significant reflux of contrast into the body of the LAD artery or into the blood stream. There may be a significant amount of contrast that appears in the RV cavity
  • 111. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green.
  • 112. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green.
  • 114. Doppler enhancement •Used when signal is weak. •RR velocities -enhanced by agitated bacteriostatic saline . •Peak velocity in AS -enhanced with contrast agents •transmitral (rarely necessary) and pulmonary venous flow velocities can be improved .
  • 115. First generation Contrast Agents: Agitated saline with or without Indocyanine green. First generation Contrast Agents: Agitated saline with or without Indocyanine green. CW Doppler from apical window before (left) and after (right) contrast enhancement. left panel - only faint visualization of the velocity profile right panel -shows not only peak transvalvular velocity(white arrow)but also subvalvular velocity