ultrasound contrast imaging - aapm.org · pdf filecolor doppler w/o contrast pulse inversion...

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Bruce, Averkiou—AAPM 2004 1

Ultrasound Contrast Imaging

Matthew BruceMike Averkiou

Tony Brock-FisherPatrick RafterJeff Powers

Philips Ultrasound, Bothell, WA, USA


Outline

• History and background

• Basics of Ultrasound Contrast Imaging

• Application to liver lesion characterization

• Quantification

• Upcoming applications


Ultrasound Contrast Agents

• Microbubbles– 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

Contrast and Red Blood Cells


Blood Flow Imaging with Ultrasound

Color Dopplerw/o contrast

Pulse Inversion with contrast

HemangiomaSpleen

lesion

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History of Ultrasound Contrast Agents

• First of microbubbles - Agitated Saline

• Search for stabilization and passage through lungs led to:

– Shelled agents (galactose, albumin, lipid …)

– With Heavy gases (PFC ..)


Clinical Applications of Ultrasound Contrast

• LVO – Left Ventricular Opacification

• Liver tumor detection and characterization

• Myocardial perfusion

• Kidney (transplants), breast, prostate, etc.

• Stroke

• Research for targeted/molecular imaging

– Combined with drug delivery

• Therapy guidance

– RFA

– Biopsy

• Mouse imaging


Contrast Agent Status

YesYesYesYesNoLevovist*

NoNoLVO LVOLVOOptison †

NoNoNoNoPending for MCE

Point Bio

NoIn trialsYes+YesPendingDefinity +

In trialsYESYesPendingIn trialsSonoVue $

JapanChinaEuropeCanadaUSA

$ SonoVue approved for macro / micro flow in heart, liver, renal

* 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.


• Nonlinear oscillators

– generate harmonic components

– f0, 2f0, 3f0 ...

• Transient nature

– slow diffusion (after shell disruption)

– bubble fragmentation into smaller bubbles

(after strong oscillation), and thus faster diffusion

Microbubble Response to Diagnostic Ultrasound Pressures

High MI

Low MI

Courtesy N. deJong, Erasmus UniversityMI – Mechanical Index (High MI > 0.2)

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Contrast Imaging Techniques


Harmonic Imaging

• 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 – Intermittent image acquisitions

• Led to Tissue Harmonic Imaging

Scanhead / beamformerfrequency response

Transmitfrequency Receive

frequency

ffo 2fo

Am

plit

ude

FundamentalImaging

1995 HarmonicImaging

Contrast in ventricle


Harmonic Power Doppler

MI=1.1trig. 1:4

Optison TissueDopplerSignal

BubbleDopplerSignal

RFSpectrum

Higher MI More decorrelated Doppler signals

• Decorrelated Doppler signals – Due to microbubble disruption (pulse to pulse)

– High Frequency Doppler signals

• Triggered at High MI

– Intermittent image acquisitions

– End systole10 2 3 4 5 6

-40

-20

0 RF Spectrum (dB) vs F (MHz)

1 2 3 4 5 6 7 81000

2000

3000

Tissue Doppler Signal

1 2 3 4 5 6 7 8-8000

-4000

0

4000

8000Bubble Doppler Signal


High MI Imaging

• Has highest SNRs

• Majority of microbubbles destroyed MI>0.4– At real time frame rates (>10 Hz)

• 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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Harmonic Power Doppler – High MI


Metastasis (from colorectal) – Levovist, high MI

Courtesy Dr. E. Leen, Royal Infirmary, Glasgow, UK

Harmonic Power Doppler – High MI


Low MI - Real-time Contrast Imaging• 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)

1999 Pulse Inversion

Real Time ImagingMI < 0.10

Frame Rate >15Hz


Pulse Inversion Processing

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∑∞

=1

)(m

mm tpa

NonlinearSystemtj oe ω

)( 2T

o tje +ω

�++++++++++++ tjtjtj ooo eaeaea ωωωωωωωωωωωω 33

221

�+++ tjjtjjtjj ooo eeaeeaeea ωωωωππππωωωωππππωωωωππππ 333

2221

Even Harmonics

Pulse 1

Pulse 2

where To

ππππωωωω 2====

Input Output

Doppler Freq

-40

-20

0

π/2π/2π/2π/2 ππππ

Gai

n (d

B) a1

a3

a2

a4

Phase of the Harmonic Components of Pulse Inversion

�++++−−−−++++++++−−−− tjtjtj ooo eaeaea ωωωωωωωωωωωω 33

221 )1(1)1(


xmit: (0.5, 1)rcv: (2, -1)

Power (Amplitude) Modulation


Clinical Example – Low MICarotid


Clinical Examples – Low MI FNH

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Clinical Examples Liver hemangioma


Liver Lesion CharacterizationUltrasound Contrast Agents


Contrast Quantification

• Contrast destruction provides method for perfusion quantification

• Destroy contrast with high MI frame

• Replenishment rate gives indication of microvascular flow rate


Flash Contrast Imaging

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Parametric Example

Stenosis 1

Stenosis 2


MicroVascular Imaging

• 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• Trace out resulting small-low velocity vessels


MVI Rat Kidney


Mouse Heart Imaging

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Mouse Perfusion Deficit

LAD ligation


Summary

• History

• Basics of Ultrasound Contrast Imaging

• Application to Liver lesion characterization

• Quantification

ultrasound contrast imaging - aapm.org · pdf filecolor doppler w/o contrast pulse inversion...

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