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Diagnostic ultrasound ( PDFDrive )

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CHAPTER 3 Contrast Agents for Ultrasound 59

Bubble diameter (µm)

10

9

8

7

6

5

4

3

2

1

1

2 3 4 5 6 7 8 9 10

Frequency (MHz)

FIG. 3.4 Microbubbles Resonate in a Diagnostic Ultrasound Field.

This graph shows that the resonant—or natural—frequency of oscillation

of a bubble of air in an ultrasound ield depends on its size. For a 3.5-µm

diameter, the size needed for an intravenously injectable contrast agent,

the resonant frequency is about 3 MHz.

Echo amplitude (dB)

0

–10

–20

–30

–40

–50

–60

–70

–80

Fundamental

Harmonics

0 5 10 15 20 25

US frequency (MHz)

FIG. 3.6 Harmonic Emission From Optison. A sample of a contrast

agent is insonated at 3 MHz and the echo analyzed for its frequency

content. The largest peak of the energy in the echo is at the 3-MHz

fundamental, but there are clear secondary peaks in the spectrum at 6,

9, 12, 15, and 18 MHz, as well as peaks between these harmonics

(known as “ultraharmonics”) and below the fundamental (known as the

“subharmonic”). The second harmonic echo is about 18 dB less than

that of the main, or fundamental, echo. Harmonic imaging and Doppler

aim to separate and process this signal alone. (With permission from

Becher H, Burns P. Handbook of contrast echocardiography: left ventricle

function and myocardial perfusion. New York: Springer; 2000. 63 )

Pressure (kPa)

100

0

–100

Radius (µm)

µm

4

2

0

4

2

0

–2

–4

4

2

0

2

µm –2

0

–2 µm

–4 –4

0 2 4 6 8 10 12

0 2 4 6 8 10 12

Time (µs)

FIG. 3.5 A Microbubble in an Acoustic Field. Bubbles respond

asymmetrically to diagnostic sound waves (top graph), stiffening when

compressed by sound, yielding only small changes in radius (bottom

graph). During the low-pressure portion of the sound wave, the bubble

stiffness decreases and radius changes can be large. This asymmetric

response leads to the production of harmonics in the scattered wave.

4

understanding of sound on which ultrasound imaging is based,

was irst led in 1917 to investigate this by his curiosity over the

creaking noises that his teakettle made as the water came to a

boil. 39 he consequence of such nonlinear motion is that the

sound emitted by the bubble, and detected by the transducer,

contains harmonics, just as the resonant strings of a musical

instrument, depending on how they are bowed or plucked, will

produce a timbre comprising overtones (the musical term for

harmonics), exact octaves above the pitch of the fundamental

note. he origin of this phenomenon is the asymmetry that begins

to afect bubble oscillation as the amplitude becomes large. As

a bubble is compressed by the ultrasound pressure wave, it

becomes stifer and hence resists further reduction in its radius.

Conversely, in the rarefaction phase of the ultrasound pulse, the

bubble becomes less stif, and therefore enlarges much more

(Fig. 3.5). Fig. 3.6 shows the frequency spectrum of an echo

produced by a microbubble contrast agent ater exposure to a

3-MHz burst of sound. he particular agent is Optison, though

most microbubble agents behave in a similar way. Ultrasound

frequency is on the horizontal axis, with the relative amplitude

on the vertical axis. In addition to the fundamental echo at

3 MHz, a series of echoes occur at whole multiples of the transmitted

frequency, known as higher harmonics. Here, then, is one

simple method to distinguish bubbles from tissue: excite them

so as to produce harmonics, and detect these in preference to

the fundamental echo from tissue. Key factors in the harmonic

response of an agent are the incident pressure of the ultrasound

ield, the frequency, the size distribution of the bubbles, and the

mechanical properties of the bubble capsule (a stif capsule, for

example, will dampen the oscillations and attenuate its nonlinear

response).

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