ultrasonic nonlinear imaging- contrast imaging. history 1968 gramiak et al published observation of...
TRANSCRIPT
History
• 1968 Gramiak et al published observation of echo signal from LV injection of indocyanine dye
• Subsequent research showed this phenomenon occurred with just about any liquid injected through small needle
More History
• First work was with free gas bubbles– bubbles didn’t last very long– size too big to go through lungs, needed intra-arterial
injection
• Late ‘80’s - early ‘90’s - development of numerous agents– more stable– smaller size
Motivation
• X-ray, CT, nuclear, and MR all need it.
• Enhance backscatter signal from blood– Blood signal typically 40dB below tissue
• Provide visualization of low velocity flow normally masked by tissue motion– measure of microvasculature important in many
disease states
Desired Properties
• Non-toxic/easily eliminated
• Able to be injected intravenously
• Small enough to pass through microcirculation
• Physically stable
• Acoustically active
Contrast Imaging
• Contrast agents are used to provide higher contrast. The three commonly seen contrast agents are backscatter, attenuation and sound velocity.
• Contrast agents could be solid particles, emulsion, gas bubbles, encapsulated gas, or liquid.
Contrast Imaging
• Primary clinical benefits:– Enhanced contrast resolution between normal
and diseased tissues.– Outline of vessels or heart chambers.– Tissue characterization by using tissue specific
agents.– Increasing blood flow signals.– Dynamic study using washout curve.
More Examples
Bubbles & Physiology
Parenchymal phase at 90-120 seconds, can be up to 5 min
Arterial phase starts20-45 seconds after injection
Portovenous phaseat 45-90 seconds
Low MI Harmonicusing Sonovue*
* Images with non-approved agents for internal GE training only
Tumor Characterization
Low MI Harmonic - 2using Definity*
* Images with non-approved agents for internal GE training only
Early Phase Late Phase
Tumor Detection
Clinical Values (I)
• Tumor Detection• presence or absence of liver, kidney or pancreatic masses
• Tumor Characterization • avascular- cyst• hypovascular- metastasis, hemangioma• hypervascular- primary carcinoma, hypervascular met
• Others• enhances vessels for RAS, Carotid stenosis, TCD, etc• better visualization of thrombus (IVC, TIPS)• post ablation follow up• trauma assessment
Clinical Values (II)
• Endocardial border detection.
• Left ventricle (LV) function.
• Valvular regurgitation quantification.
• LV flow patterns.
• Perfusion area of coronary artery.
• Assessment of surgery for ventricular septal defect.
Clinical Values (III)
• Liver tumor enhancement.
• Uro-dynamics and kidney functions.
• Tubal function and placenta perfusion.
• Transcranial Doppler enhancement.
• LV pressure measurements.
Current Contrast Agents
• Aerosomes (ImaRx, Tucson, AZ) • Albunex (MBI, San Diego, CA)• BY963 (Byk Gulden, Konstanz, Germany)• Echovist (Schering, Berlin, Germany)• EchoGen (Sonus, Bothell, WA) • DMP115 (DuPont-Merck, N. Billerica, MA) • Imagent US (Alliance, San Diego, CA) • Levovist (Schering, Berlin, Germany)• NC100-100 (Nycomed, Oslo, Norway)
Current Contrast Agents (Cont.)
• Optison (MBI, San Diego, CA) approved in US for cardiac• Oralex (MBI, San Diego, CA)• PESDA (Univ of Nebraska, Omaha, NE)• SonoRx (Bracco, Princeton, NJ) US approved oral agent • Sonovist (Schering, Berlin, Germany)• Sonovue (Bracco, Milan, Italy)• ST68 (Drexel Univ, Philadelphia, PA)• Quantison (Andaris, Nottingham, UK)• Quantison Depot (Andaris, Nottingham, UK)• Many more,…
Contrast Mechanisms
• Strong backscattering produced by air bubbles.
• The backscatter increases roughly linearly with the number of micro-bubbles.
• A bubble in liquid acts as a harmonic oscillator. Acoustic resonance provides the major echo enhancement. In addition, strong harmonics are produced.
Contrast Mechanisms
• Acoustic attenuation of soft tissues is typically represented by a constant (e.g., 0.5dB/cm/MHz).
• Since contrast agents significantly change the scattering properties, attenuation measurements can also be used for contrast enhancement.
Contrast Mechanisms
• Sound velocity is primarily determined by density and compressibility. Apparently, micro-bubble based contrast agents alter sound velocity.
• Contrast enhancement based on sound velocity variations is still academic.
Contrast Mechanisms
• Micro-bubbles produce strong harmonics when insonified near the resonance frequency.
• If such harmonics are stronger than tissue harmonics, contrast can be improved.
• Second harmonic signal is most useful due to limited transducer and system bandwidth.
Bubble Characteristics
• Size
RBC6–8 µm
Microbubble2–8 µm
• Gas– use high molecular weight, less soluble gas
• Shell for stabilization– tune for desired acoustic properties
Ultrasound-Induced Encapsulated Microbubble Phenomena
• Oscillation
• Translation
• Coalescence
• Fragmentation
• Sonic cracking
• Jetting
• ,…
Ultrasound-Induced Oscillation
• Moderate: Alternate expansions and contractions with the same amplitude and duration at low driving pressures (stable cavitation).
• Violent: At higher pressures, greater bubble expansion amplitude than contraction amplitude, and relatively slow expansion followed rapid contraction (inertial or transient cavitation).
• Cavitation threshold: Above which the bubble’s maximum radius is larger than twice the equilibrium radius.
Modeling• Strength of backscatter signal depends on
difference in acoustic properties between two materials...
d2 4 m
m
p m
p m( ) =
c V f
)
2 +
p2
4
23
(cos
p = particle m = surrounding medium
For a particle of volume V in homogenous medium
= compressibility = mass density
Modeling• Now need to include shell effects...
RR + 3
2R
R
RRR - P(t)2
Keff tot0
3
1
For a shell encapsulated gas bubble of instantaneous radius R:
eff ~ elasticity of shell = density of surrounding media
tot = total damping coefficient P(t) = incident acoustic energy
Accurate only at low pressures
Translation
• Resulted from primary radiation force (pressure gradient across the bubble surface).
• Maximal in contraction phase.
• Used for active targeting.
0adrad FFFF
Translation
• Secondary radiation force: The microbubbles translate toward each other (oscillating bubbles generate spatially varying pressure fields).
Coalescence
• Fusion of two or more bubbles.
• As bubbles expand, bubble surfaces flattens and thinning occurs.
• When critical thickness is reached (around 0.1 micron), bubbles rupture and merge with each other.
Fragmentation
• Fission of a bubble into smaller bubbles.
3
2
:fragments ofNumber
3
237
3
1
tension)surface :(
nN
n
RR
Sonic Cracking
• Ultrasound induced formation of a shell defect causing gas to escape from the bubbles.
• Mechanism not yet known.
Non-Linear Response
Contrast agentsTransmit freq.= fo
2fo
fo
Conventional Imaging: Receive freq. = fo
Harmonic Imaging: Receive freq. = 2fo
Various Contrast Modes
• High MI B-Mode, Harmonic - optimized for SAE harmonic imaging
• Low MI B-Mode, Harmonic 1 and 2 - optimized for nondestructive harmonic imaging
• High MI colorflow fundamental - optimized for SAE destruction effect
• High MI colorflow harmonic - optimized for SAE with reduced tissue flash artifact
Step 1:
Xmit2 5
Step 2:
Step 3:
2 5 74Suppress
Rcv2 74 10
Utilizes Encoding Technique
From ‘Coded Harmonics’ To
Suppress Fundamental Signal
Uses decoding techniques similar to B Flow to
separate tissue & contrast signal
Coded Harmonic AngioCoded Harmonic Angio
Step 4:
74SeparateContrastSignal
Contrast Agent
Tissue
Tissue and Contrast
Problem:
Blood echoes are very weak and
sometimes moving too slow for Doppler techniques
Detecting Blood Reflectors
BloodTissue
Noise
Solution: Inject contrast agents to enhance signal
Problem:
Blood echoes are very weak and
sometimes moving too slow for Doppler techniques
Detecting Blood Reflectors
Agent
Noise
Tissue
Solution: Inject contrast agents to enhance signal
Use codes to
1) detect harmonic return signal
Problem:
Blood echoes are very weak and
sometimes moving too slow for Doppler techniques
Detecting Blood Reflectors
AgentTissue
Noise
Solution: Inject contrast agents to enhance signal
Use codes to
1) detect harmonic return signal
2) Suppress tissue signal
Problem:
Blood echoes are very weak and
sometimes moving too slow for Doppler techniques
Detecting Blood Reflectors
AgentTissue
Noise
Harmonic Interference• In contrast imaging, in which the tissue
harmonic signals are un-desirable, the amplitude of the propagating wave needs to minimized.
• Large apertures (smaller f-numbers) may be used.
• It was reported that tissue harmonic signal can be reduced by 3dB by doubling the aperture size.
Reduction of Interference from Tissue
• Harmonic cancellation system.• Sub-harmonic imaging.• Pulse-inversion Doppler (clutter).• Pulse-inversion fundamental imaging.
Sub-Harmonic Imaging
• Tissue propagation does not generate significant sub-harmonic signals.
• Sub-harmonic signals may be generated with microbubbles in proper acoustic fields.
• Sub-harmonic imaging can thus be used for reduction of tissue nonlinear signals.