Topic 15: Ultrasound contrast agents

Question 1

Why do bubbles normally dissolve too fast?

Answer 1

the pressure in the bubble is larger than the surrounding fluid

Question 2

what is the extra pressure in bubbles called?

Answer 2

laplace pressure

Question 3

what is the laplace pressure equal to

Answer 3

2*surface tension / Radius of bubble

Question 4

what was the first ultrasound contrast agent to recieve FDA approval?

Answer 4

Albunex with a protein coating

Question 5

What were developed as an attempt to extend the lifetimes of USCAs ?

Answer 5

Phospholipid coatings bubbles filled with air with large molecular weights as they diffuse more slowly than air

Question 6

What is the motion of a bubble in which a sound wave causes it expand and contract referred to as?

Answer 6

Cavitation

Question 7

When does the bubble cavitation (ebbing and flowing) start to act nonlinearly?

Answer 7

when the acoustic pressures are large

Question 8

Why does the bubble start to act nonlinearly when the acoustic pressures are large?

Answer 8

The stiffness provided by the gas is not constant in time but is much greater when the bubble radius is small than when it is large.

Question 9

What happens when you continue to increase the acoustic pressure amplitude? And how can we differentiate between the nonlinearity of the bubble and the nonlinearity of tissue?

Answer 9

The bubble may undergo surface oscillations, this can introduce half-integer harmonics including a sub-harmonic into the scattered spectrum.
The tissue does not have this sub-harmonic.

Question 10

Under certain conditions and at large pressure amplitudes the bubble undergoes inertial cavitation. What does this mean?

Answer 10

In this regime the bubble grows in size very quickly until there comes a moment when the inertia due to the radiation mass is so large that it collapses the bubble which typically breaks up violently.

Question 11

When the bubble radius reaches a minimum during inertial cavitation the pressures and ________ can become very large. And _____can be emitted which is called sonoluminescence

Answer 11

temperatures

light

Question 12

There are a number of ways in which microbubbles provide contrast which can be exploited to enhance ultrasound images

Answer 12

1. Impedance mismatch
2. Compressibility and resonance
3. Nonlinearity

Question 13

Describe how the impedance mismatch of microbubbles can be used to enhance ultrasound images.

Answer 13

The bubbles have a very different acoustic impedance to the surrounding blood, so scatter the ultrasound waves back to the transducer.

Question 14

Describe how the compressibility and resonance of microbubbles can be used to enhance ultrasound images.

Answer 14

The fact that the bubbles oscillate is due to their compressibility. It is convenient that coated bubbles of the right size to fit into capillaries happen to resonate in the 1-15MHz range usually used in ultrasound imaging.

Question 15

It is the ______ response of USCA bubbles to ultrasound waves that give
the most potential for enhancing imaging capabilities.

Answer 15

nonlinear

Question 16

Explain what happens when conventional ultrasound imaging (imaging with the fundamental) uses USCAs. Why is it not a good idea?

Answer 16

It relies on the bulk impedance mismatch between the regions where there are bubbles and the regions where there are not. This does not provide good image enhancement at low amplitudes and at large pressure amplitudes the bubbles are destroyed.

Question 17

In color doppler mode higher pressure ultrasound pulses are sent into the tissue than in conventional B-mode why?

Answer 17

Because of signal-to-noise ratios

Question 18

How can color doppler mode be useful for imaging USCAs?

Answer 18

Color doppler uses high pressure. Imaging USCAs in color doppler mode can therefore have the effect of breaking all the microbubbles so that there is momentarily a large volume of reflecting gas in the region of interest, which shows brightly in the image.

Question 19

What is the advantage of loss of correlation imaging - using color doppler to break up bubbles ?

Answer 19

Its high sensitivity to the presence of USCAs.

Question 20

Describe the process of phase inversion with respect to harmonic imaging with USCAs

Answer 20

Two pulses, one inverted, with one high and one low amplitude pulse. The low keeps the bubbles intact and the second is high. Fewer bubbles are destroyed in this approach. Assumin the response of the former is linear, the difference shows the nonlinear component.

Question 21

Name a major use of USCAs?

Answer 21

In studies of perfusion.

Question 22

Describe two main ways of measuring perfusion using USCAs.

Answer 22

1. Bolus injection - In this approach a ‘lump’ of fluid containing USCA microbubbles is injected into the tissue. The time variation of the image intensity is then observed. The rate with which the USCA washed into and washed out of the different regions can be diagnostically useful.
2. Flash replenishment - An alternative method is to use a higher energy pulse to destroy the USCAs in some region and then to watch as that region is re-perfused with fresh USCA-containing blood.

Question 23

Describe ‘Super-resolution imaging’ as a form of using USCAs to enhance image quality, and one difficulty it poses.

Answer 23

By using the known Point spread function, the blurred individual bubbles can be used to locate the centre of the bubble precisely as it will be the centre of the PSF. The difficulty is it requires SINGLE bubbles which need to be separated.

Question 24

What are two methods that are used to separate bubbles to be used for super-resolution imaging?

Answer 24

1. Low USCA density - So that only a few bubbles appear in the image.
2. High frame rate imaging - Using a large amount of bubbles, and relying on the fact that some - only a few - of the USCA bubbles disintegrate between frames, thereby allowing the positions of those ‘missing’ bubbles to be determined very precisely.

Question 25

What is the future of USCAs?

Answer 25

USCAs are being developed that carry therapeutic drugs and are targeted to ‘stick’ to specific cell receptors.
Also bubbles that are covered in volatile liquids so that when it is insonified the bubble undergoes a phase change to a gas microbubble.