Outline
Ultrasound Contrast Imaging
• History and background
• Basics of Ultrasound Contrast Imaging
• Application to liver lesion characterization
Matthew Bruce
Mike Averkiou
Tony Brock-Fisher
Patrick Rafter
Jeff Powers
Philips Ultrasound, Bothell, WA, USA
• Quantification
• Upcoming applications
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Blood Flow Imaging with Ultrasound
Ultrasound Contrast Agents
Color Doppler
w/o contrast
• Microbubbles
Pulse Inversion
with contrast
– Heavy Gas/Air Mixture
• PFC, SF6
– Encapsulated
• Shell ~ lipid, Albumin, polymer
– Diameters 2-10 µm
• Administered
– Intravenous Injection
• Removed
– Dissolve in circulation
– Filtered by liver
– Cleared ~ 15 minutes
lesion
Contrast and Red Blood Cells
Spleen
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Bruce, Averkiou—AAPM 2004
Hemangioma
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Clinical Applications of Ultrasound Contrast
History of Ultrasound Contrast Agents
•
LVO – Left Ventricular Opacification
•
Liver tumor detection and characterization
– Shelled agents (galactose, albumin, lipid …)
•
Myocardial perfusion
– With Heavy gases (PFC ..)
•
Kidney (transplants), breast, prostate, etc.
•
Stroke
•
Research for targeted/molecular imaging
•
Therapy guidance
•
First of microbubbles - Agitated Saline
•
Search for stabilization and passage through lungs led to:
– Combined with drug delivery
– RFA
– Biopsy
•
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Microbubble Response to Diagnostic
Ultrasound Pressures
Contrast Agent Status
SonoVue $
Mouse imaging
USA
Canada
Europe
China
Japan
In trials
Pending
Yes
YES
In trials
•
Nonlinear oscillators
Low MI
– generate harmonic components
Definity +
Pending
Yes
Yes+
In trials
No
Optison †
LVO
LVO
LVO
No
No
Levovist*
No
Yes
Yes
Yes
Yes
Point Bio
Pending for
MCE
No
No
No
No
– f0, 2f0, 3f0 ...
•
Transient nature
– slow diffusion (after shell disruption)
– bubble fragmentation into smaller bubbles
$ SonoVue approved for macro / micro flow in heart, liver, renal
High MI
(after strong oscillation), and thus faster diffusion
* Levovist available in 69 countries, including Latin America and Asia
+ Limited to UK, pending other European countries (LVO and GI)
† Optison and Definity approved for Cardiology applications (LVO) in USA, Canada and Europe. Use in General Imaging
requires “off-label” research agreement and IRB.
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MI – Mechanical Index (High MI > 0.2)
Bruce, Averkiou—AAPM 2004
Courtesy N. deJong, Erasmus University
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Contrast in ventricle
Harmonic Imaging
•
Contrast Imaging Techniques
•
•
•
Designed to extract nonlinear portion of
returned signal
Improved contrast to tissue ratio
Single pulse techniques filter out
fundamental on receive, but this limits
the available bandwidth
Triggered at High MI
Fundamental
Imaging
– Intermittent image acquisitions
Scanhead / beamformer
frequency response
Transmit
Receive
frequency
frequency
Led to Tissue Harmonic Imaging
Amplitude
•
1995 Harmonic
Imaging
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Harmonic Power Doppler
•
Decorrelated Doppler signals
•
Triggered at High MI
Due to microbubble disruption (pulse to pulse)
–
High Frequency Doppler signals
–
–
-40
0
2
3
4
5
6
3000
Tissue
Doppler
Signal
2000
1000
1
8000
4000
0
-4000
-8000
1
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Tissue Doppler Signal
Optison
Higher MI
f
10
2
3
4
5
6
7
Bubble Doppler Signal
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Bubble
Doppler
Signal
2
3
4
5
6
7
• Majority of microbubbles destroyed MI>0.4
– At real time frame rates (>10 Hz)
Intermittent image acquisitions
MI=1.1
trig. 1:4
2fo
• Has highest SNRs
RF
Spectrum
-20
End systole
fo
High MI Imaging
RF Spectrum (dB) vs F (MHz)
0
–
Bruce, Averkiou—AAPM 2004
• Limited visualization times
– Destroy agent being imaged.
– CV – ECG triggered imaging while skipping heart cycles
– GI - Sweep through volume of interest or watch veil as
agent is destroyed
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More decorrelated Doppler signals
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Harmonic Power Doppler – High MI
Harmonic Power Doppler – High MI
Metastasis (from colorectal) – Levovist, high MI
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Low MI - Real-time Contrast Imaging
Bruce, Averkiou—AAPM 2004
Courtesy Dr. E. Leen, Royal Infirmary, Glasgow, UK
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Pulse Inversion Processing
• High MI techniques have high sensitivity but are in
general difficult to use
– Tissue harmonic component competes with bubble signals
• Low MI – harmonics still generated
– Does not destroy microbubbles (extends visualizaton time)
• Does not require interval delay or sweeping
– Low MI reduces harmonic tissue signals (tissue is removed)
Real Time Imaging
MI < 0.10
Frame Rate >15Hz
Bruce, Averkiou—AAPM 2004
1999 Pulse Inversion
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Phase of the Harmonic Components of Pulse Inversion
Nonlinear
System
Pulse 1
e jω o t
∞
m=1
Pulse 2
e
jωo (t +T2 )
ωo =
a1e
jω o t
+ a 2e
j 2ω o t
+ a 3e
j 3ω o t
xmit: (0.5, 1)
rcv: (2, -1)
+
am pm(t)
a1e( −jπ1e)ejωjoωt o+t a+2ae2j 21πeej 2j 2ωωoott ++aa33e( −j 31π)ee jj33ωωoto t++
Even Harmonics
2π
T
Gain (dB)
where
Power (Amplitude) Modulation
Output
Input
a1
0
-20 a 2
-40
a3
a4
Bruce, Averkiou—AAPM 2004
π/2
Doppler Freq
π
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Clinical Example – Low MI
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Clinical Examples – Low MI
FNH
Carotid
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Clinical Examples
Liver hemangioma
Bruce, Averkiou—AAPM 2004
Liver Lesion Characterization
Ultrasound Contrast Agents
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Flash Contrast Imaging
Contrast Quantification
• Contrast destruction
provides method for
perfusion
quantification
• Destroy contrast with
high MI frame
• Replenishment rate
gives indication of
microvascular flow
rate
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MicroVascular Imaging
Parametric Example
• Some lesions have very low flow rates
– bubbles can be seen in real-time, but not enough for good
vessel conspicuity
– Hold on to bubble signals as they traverse vasculature
Stenosis 1
• Trace out resulting small-low velocity vessels
Stenosis 2
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Mouse Heart Imaging
MVI Rat Kidney
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Mouse Perfusion Deficit
Summary
• History
• Basics of Ultrasound Contrast Imaging
• Application to Liver lesion characterization
• Quantification
LAD ligation
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