1. Small Vessel Detection
Diameter
(mm)
Number
vpeak
(cm/s)
Doppler shift
(Hz)
Aorta 10 1
100
5,620
Large Arteries 3 40 18
1,010
Main branches
600
4.5
250
Terminal branches
0.6
1,800
1.5 84
Arterioles
0.02
40,000,000
0.18 12
Capillaries
0.008
1,200,000,000
0.08

2. Microvascular Assessment: Challenges
Low Velocities (velocity resolution and ‘clutter’ issues)
Low Volume (small signals)
Low Flow rate
Small sizes (spatial resolution)
(optional)
Intravital microscopy of
rat cremaster muscle
C Ellis U of Western Ontario
50 microns

3. Microvascular Challenges: Low Velocities
clutter removal issues
velocity resolution issues

4. Low Velocities: Clutter removal
• Kidney tissue velocity: ~ 3 cm/s (30 x capillary velocity)
• Myocardium velocity: ~ 15 cm/s (150 x capillary velocity)

5. Microvascular Challenges: Small signals
hematocrit decreases with vessel size,
results in decreased signal strength

6. Microvascular Challenges: Spatial Resolution

7. Microvascular Assessment: Higher Frequencies
- Improves blood signals
- Improves velocity resolution
- Improves spatial resolution

8. Microvascular Assessment: Higher Frequencies
Problem:
Attenuation
Clutter

9. Microbubble Contrast Agents
Encapsulated gas microbubbles
(e.g. lipids, albumin, polymers)
~ 2-8 m in diameter
Injected intraveneously
into the bloodstream
The illustration at the lower right corner of the scrreen is a cross section of a thin slice of the myocardium. It is composed of a complex network of tiny capillaries which carry the blood supply to the myocardium. They are so small that they are beyond the limits of Doppler to resolve. The same complex network of capillaries is also seen in organs such as the renal cortex and various lesions. Since contrast agent microbubbles are the same size as red blood cells (approx. 3-4 microns) they can easily pass through the circulation system and allow us to image them with advanced techniques such as harmonic imaging.
To understand how contrast agents work, imagine Ella Fitzgerald singing and a glass cracking because of the pitch and frequency of her voice. Microbubbles have similar resonancy properties. They are used as reflectors and intensify acoustic properties during ultrasound.
Bubbles are sized smaller than a blood cell so they can travel with the blood cells when injected intravenously. As they enter the site of interest where the ultrasound beam is directed, their affect is to increase the echo level from blood. In fact, a single bubble gives an echo about a million times stronger than a red blood cell. You only need a small number of bubbles to get an increase in signal.
These bubbles are not toxic, and have a high level of patient acceptance.

10. Scattering from Bubbles
Bubbles: highly compressible, low density relative to plasma

11. Microbubble Contrast Agents
Wavelength of 3 MHz = 0.5 mm ( = v/f, v= 1500 m/s )
Bubble size is mm
Bubble
Radius
Time
Pressure
The illustration at the lower right corner of the scrreen is a cross section of a thin slice of the myocardium. It is composed of a complex network of tiny capillaries which carry the blood supply to the myocardium. They are so small that they are beyond the limits of Doppler to resolve. The same complex network of capillaries is also seen in organs such as the renal cortex and various lesions. Since contrast agent microbubbles are the same size as red blood cells (approx. 3-4 microns) they can easily pass through the circulation system and allow us to image them with advanced techniques such as harmonic imaging.
To understand how contrast agents work, imagine Ella Fitzgerald singing and a glass cracking because of the pitch and frequency of her voice. Microbubbles have similar resonancy properties. They are used as reflectors and intensify acoustic properties during ultrasound.
Bubbles are sized smaller than a blood cell so they can travel with the blood cells when injected intravenously. As they enter the site of interest where the ultrasound beam is directed, their affect is to increase the echo level from blood. In fact, a single bubble gives an echo about a million times stronger than a red blood cell. You only need a small number of bubbles to get an increase in signal.
These bubbles are not toxic, and have a high level of patient acceptance.

12. Mass - Spring System
A mass on a spring has a resonant frequency determined by its
spring constant k and the mass m.
The resonant oscillating frequency (natural) is:

13. Free oscillating bubble: Analogy
With a bubble, the effective mass is provided by the surrounding liquid, and
the spring is due to the gas compressibility. For a ‘free’ bubble the resonant
frequency is…
(the ‘Minnaert’ frequency)
- Assuming adiabatic condition
- Surface tension neglected
For an air bubble in water

14. Acoustically Driven Bubbles
Three regimes can be considered
-Linear (lower pressure)
-Non-linear (intermediate pressure)
-Destruction (higher pressure)
Bubble
Radius
Time

15. Linear regime
Soft-shelled agent
4 micron bubble
US: f=1 MHz, 70 kPa

16. Linear regime US: f=1 MHz, MI=0.05 Diameter vs Time Frequency content2 4 6 8 10 12
6.7
6.8
6.9 7
7.1
7.2
7.3
7.4
7.5
7.6
7.7 1 2 3 4
-50
-40
-30
-20
-10
Diameter [mm] dB
Time
Frequency [MHz]

17. Nonlinear regime US: f=1 MHz, 200 kPa Soft-shelled agent
4 micron bubble

18. Nonlinear regime US: f=1 MHz, 200 kPa
Diameter vs Time Frequency content
2.5 3
3.5 4
4.5 5
-10
-20
Diameter [mm] dB
-30
-40
-50 10 20 30 40 50 60 70 80 1 2 3
Time
Frequency [MHz]

19. Bubble Destruction US: f=1.7MHz, 1.3 MPa hard-shelled agent
3 micron bubble
Hard-shelled agent

20. Microbubble Imaging Methods
Examine the kinetics of Bscan enhancement (earliest approach)
Detect ‘nonlinear’ signals (bubble specific)
- energy: harmonic, subharmonic, differences in transmit band)
- methods: e.g.filtering; phase and/or amplitude modulation
Employ ‘destruction-reperfusion’ approaches
(destroy agent in beam and images kinetics of inflow- ‘negative bolus’)