Harmonic Imaging and Contrast Agents Flashcards
How can the tissue’s nonlinear behaviour be exploited for imaging?
Nonlinear effects require high acoustic pressure, so occur near the focus
When 2nd harmonic is used there is better lateral resolution and reduced side lobes
reduced clutter from near the tissue surface
What must occur in Tissue Harmonic Imaging (THI)?
The harmonic and fundamental components must be separated
What is one approach to separating the nonlinear part?
To ensure harmonic and fundamental components spectra do not overlap
The transmit spectrum must be made narrower to facilitate this but the pulse length becomes longer as a consequence (worsening axial resolution)
How does pulse inversion separate the nonlinear part?
Send two pulses, one inverted and sum the received signals
The fundamental parts sum to zero, leaving only nonlinear components
The sum of the propagated tonebursts is converted to spectrum and harmonic is extracted (frame rate is halved so two pulses are required)
How does amplitude modulation separate the nonlinear part?
Send two pulses, one twice the amplitude of the other: A_1 and A_2 = 2A_1
Subtract the linear part ie. form an image from B_2 – 2B_1
(requires two pulses so halves the frame rate)
What are contrast agents?
Substances injected to enhance image contrast
What type of contrast agent is used in each imaging technique?
Gadolinium in MRI
Iodine and barium in CT
Microbubbles in ultrasound
How are contrast microbubble effective?
Small enough to pass through the lungs(<10 microns, red blood cell size)
Long-lived enough to reach organs
What are the applications of contrast agents?
Imaging small vessels not seen on Doppler
Perfusion studies
What happens to micron-sized gas bubbles?
They improve contrast but dissolve rapidly
Why is the pressure of the gas in the bubble is greater than that in the liquid?
Due to surface tension (Laplace pressure)
What is the pressure of the gas?
P_ gas = P_liquid + P_Laplace = P_liquid + 2σ/R
σ = surface tension
R = bubble radius
What is the effect of higher gas pressure?
The higher gas pressure drives gas diffusion out of the bubbles
What happens to uncoated microbubbles?
They dissolve very rapidly (< 1 second)
What reduces diffusion of gas out of bubbles?
Lowering surface tension reduces Laplace pressure so reduces diffusion
How does microbubble stabilisation work?
Mixing the patient’s blood with the dye before injection
Allows for the formation of a protein coating on the surface of the bubble which stabilised it
What effect does microbubble stabilisation have?
Lowers the surface tension, and forms a physical barrier to gas diffusion
What do the surfactant coatings consist of?
Molecules which are amphiphilic (one end likes water the other doesn’t)
phosopholipid, protein or polymer
What do the current ultrasound contrast agents consist of?
Micron sized bubbles of a non-toxic gas (often of large molecular weight)
Coated with a surfactant or polymer shell for stability
Small enough to be injected into human blood vessels (1 - 8 µm)
How are ultrasound contrast agents administered?
Either freeze dried or in suspension
Prepared by agitating manually or in a mixer
1-5 billion bubbles/ml
Normally injected intravenously in saline as a bolus or infusion (~1-2 ml dose)
When do bubbles oscillate?
In the presence of an acoustic wave (or when hit)
They resonate at frequencies used in medical imaging
What are the responses to bubbles oscillating?
Response is governed by:
–compressibility of the entrapped gas
– stiffness of the coating
– inertia of the surrounding fluid
What happens to bubbles at <0.1 MPa?
Stable cavitation: the bubble oscillations follow the acoustic pressure locally (small linear oscillations)
What happens to bubbles at >0.1 MPa?
Nonlinear behaviour:
Stiffness decreases as bubble expands, and vice-versa
This asymmetric response generates integer harmonics (f, 2f,.. 3f,…), into the scattered ultrasound wave, which can be used for harmonic imaging
What extends the lifetime of ultrasound contrast agents (USCAs)?
Phospholipid coating
When are subharmonics generated?
increase the acoustic pressure amplitude, the bubble may undergo surface oscillations (or bubble missing some driving cycles)
This can introduce half-integer harmonics, including a sub-harmonic (f/2, 3f/2 …)
What can subharmonics be used for?
To separate USCA from tissue nonlinearity, which does not generate a sub-harmonic
What are the effects of increasing the acoustic pressure on the bubble?
The coating on the bubble will start to break up, because when the bubble radius is small its surface area is considerably reduced and there is no room for all the molecules forming the coating
The bubble will collapse violently
How does the bubble response change as peak negative acoustic pressure increases (mechanical index)?
backscatter -> oscillation -> instability/ bubble fission -> destruction (used in colour Doppler)
What is the effect on the USCAs when a higher pressure is applied in Colour Doppler?
The USCAs are destroyed and release gas - strong reflection
Colour Doppler interprets it as large random velocities
What are the advantages and disadvantages of USCA detection in Colour Doppler?
First contrast-specific ultrasound imaging method
Very sensitive means of USCA detection, but low frame rate
What can USCA be used to image?
Usually USCA remains in the vasculature and can be used to image tissue perfusion (volume rate of blood flow)
for kidney and tumour vasculature
What is the Bolus injection method of using USCAs?
A ‘lump’ of fluid containing USCA microbubbles is injected
The Time-Intensity Curve shows the rate with which the USCA washes into and washes out of the different regions which can be diagnostically useful
What is the Flash replenishment method of using USCAs?
Use a higher energy pulse (as for the colour Doppler) to destroy the USCAs in some region and then to watch as that region is re-perfused with fresh USCA-containing blood.
Time-Intensity Curve shows the replenishment time
What happens at high acoustic pressure to the USCAs?
USCA behaviour can be complicated
