Harmonic Imaging and Contrast Agents

Question 1

How can the tissue’s nonlinear behaviour be exploited for imaging?

Answer 1

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

Question 2

What must occur in Tissue Harmonic Imaging (THI)?

Answer 2

The harmonic and fundamental components must be separated

Question 3

What is one approach to separating the nonlinear part?

Answer 3

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)

Question 4

How does pulse inversion separate the nonlinear part?

Answer 4

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)

Question 5

How does amplitude modulation separate the nonlinear part?

Answer 5

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)

Question 6

What are contrast agents?

Answer 6

Substances injected to enhance image contrast

Question 7

What type of contrast agent is used in each imaging technique?

Answer 7

Gadolinium in MRI

Iodine and barium in CT

Microbubbles in ultrasound

Question 8

How are contrast microbubble effective?

Answer 8

Small enough to pass through the lungs(<10 microns, red blood cell size)

Long-lived enough to reach organs

Question 9

What are the applications of contrast agents?

Answer 9

Imaging small vessels not seen on Doppler

Perfusion studies

Question 10

What happens to micron-sized gas bubbles?

Answer 10

They improve contrast but dissolve rapidly

Question 11

Why is the pressure of the gas in the bubble is greater than that in the liquid?

Answer 11

Due to surface tension (Laplace pressure)

Question 12

What is the pressure of the gas?

Answer 12

P_ gas = P_liquid + P_Laplace = P_liquid + 2σ/R

σ = surface tension
R = bubble radius

Question 13

What is the effect of higher gas pressure?

Answer 13

The higher gas pressure drives gas diffusion out of the bubbles

Question 14

What happens to uncoated microbubbles?

Answer 14

They dissolve very rapidly (< 1 second)

Question 15

What reduces diffusion of gas out of bubbles?

Answer 15

Lowering surface tension reduces Laplace pressure so reduces diffusion

Question 16

How does microbubble stabilisation work?

Answer 16

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

Question 17

What effect does microbubble stabilisation have?

Answer 17

Lowers the surface tension, and forms a physical barrier to gas diffusion

Question 18

What do the surfactant coatings consist of?

Answer 18

Molecules which are amphiphilic (one end likes water the other doesn’t)

phosopholipid, protein or polymer

Question 19

What do the current ultrasound contrast agents consist of?

Answer 19

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)

Question 20

How are ultrasound contrast agents administered?

Answer 20

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)

Question 21

When do bubbles oscillate?

Answer 21

In the presence of an acoustic wave (or when hit)

They resonate at frequencies used in medical imaging

Question 22

What are the responses to bubbles oscillating?

Answer 22

Response is governed by:

–compressibility of the entrapped gas

– stiffness of the coating

– inertia of the surrounding fluid

Question 23

What happens to bubbles at <0.1 MPa?

Answer 23

Stable cavitation: the bubble oscillations follow the acoustic pressure locally (small linear oscillations)

Question 24

What happens to bubbles at >0.1 MPa?

Answer 24

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

Question 25

What extends the lifetime of ultrasound contrast agents (USCAs)?

Answer 25

Phospholipid coating

Question 26

When are subharmonics generated?

Answer 26

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 …)

Question 27

What can subharmonics be used for?

Answer 27

To separate USCA from tissue nonlinearity, which does not generate a sub-harmonic

Question 28

What are the effects of increasing the acoustic pressure on the bubble?

Answer 28

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

Question 29

How does the bubble response change as peak negative acoustic pressure increases (mechanical index)?

Answer 29

backscatter -> oscillation -> instability/ bubble fission -> destruction (used in colour Doppler)

Question 30

What is the effect on the USCAs when a higher pressure is applied in Colour Doppler?

Answer 30

The USCAs are destroyed and release gas - strong reflection

Colour Doppler interprets it as large random velocities

Question 31

What are the advantages and disadvantages of USCA detection in Colour Doppler?

Answer 31

First contrast-specific ultrasound imaging method

Very sensitive means of USCA detection, but low frame rate

Question 32

What can USCA be used to image?

Answer 32

Usually USCA remains in the vasculature and can be used to image tissue perfusion (volume rate of blood flow)

for kidney and tumour vasculature

Question 33

What is the Bolus injection method of using USCAs?

Answer 33

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

Question 34

What is the Flash replenishment method of using USCAs?

Answer 34

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

Question 35

What happens at high acoustic pressure to the USCAs?

Answer 35

USCA behaviour can be complicated